bluuebunny/crossref_metadata_2025_split huggingface dataset:
WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress
Authors: Yang Bo , Liu Xi-Juan , Yao Yongxuan , Jiang Xuan , Wang Xian-Zhang , Yang Hong , Sun Jin-Yan , Miao Yun , Wang Wei , Huang Zhen-Li , Wang Yanyi , Tang Qiyi , Rayner Simon , Britt William J. , McVoy Michael A. , Luo Min-Hua , Zhao Fei 
Published: February 2018

ABSTRACT
WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target.

IMPORTANCE
Human cytomegalovirus (HCMV) has a large (∼235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
Mobile stroke unit triage of patients with a suspected stroke: a novel solution to reducing suspected stroke admissions in busy emergency departments
Authors: Shuaib Ashfaq , Amlani Shy , Kalashyan Hayrapet , Morrison Laurel , Khan Khurshid , Jickling Glen , Buck Brian , Butcher Kenneth , Saqqur Maher , Jeerakathil Thomas 
Published: February 2018

BackgroundEvaluation of patients with a suspected stroke is one of the most common neurological emergencies requiring rapid, comprehensive assessment by the stroke service to determine patient eligibility for timely reperfusion therapies. Prehospital evaluation may help to improve patient selection and reduce avoidable admissions to overcapacity emergency departments.Methods and resultsWe report on our early experience of prehospital triage of patients with a suspected stroke using a mobile stroke unit (MSU) equipped with CT scanner in rural Alberta. During the initial 4 months of operation, 28 patients were evaluated by the team in the MSU. Eight patients were within the time window of thrombolysis and were treated with intravenous tissue plasminogen activator in the MSU. No patients suffered haemorrhage or any other complications. Fourteen patients with multiple aetiologies (stroke mimics 6, transient ischaemic attacks 2, subacute stroke outside thrombolysis window 2, intracranial haemorrhage 3 and cerebral contusion 1) were assessed in the field and transferred to the tertiary hospital. Six patients after assessment and imaging were repatriated back to the local hospital as they were deemed stroke mimics or were outside of the reperfusion window.ConclusionsThe MSU offers a novel approach to performing timely evaluation and treatment of patients with a suspected stroke in rural settings and may help reduce admissions to overcapacity tertiary care facilities.
Protocol for a prospective, school-based standardisation study of a digital social skills assessment tool for children: The Paediatric Evaluation of Emotions, Relationships, and Socialisation (PEERS) study
Authors: Thompson Emma J , Beauchamp Miriam H , Darling Simone J , Hearps Stephen J C , Brown Amy , Charalambous George , Crossley Louise , Darby David , Dooley Julian J , Greenham Mardee , Jaimangal Mohinder , McDonald Skye , Muscara Frank , Turkstra Lyn , Anderson Vicki A 
Published: February 2018

BackgroundHumans are by nature a social species, with much of human experience spent in social interaction. Unsurprisingly, social functioning is crucial to well-being and quality of life across the lifespan. While early intervention for social problems appears promising, our ability to identify the specific impairments underlying their social problems (eg, social communication) is restricted by a dearth of accurate, ecologically valid and comprehensive child-direct assessment tools. Current tools are largely limited to parent and teacher ratings scales, which may identify social dysfunction, but not its underlying cause, or adult-based experimental tools, which lack age-appropriate norms. The present study describes the development and standardisation of Paediatric Evaluation of Emotions, Relationships, and Socialisation(PEERS®), an iPad-based social skills assessment tool.MethodsThe PEERS project is a cross-sectional study involving two groups: (1) a normative group, recruited from early childhood, primary and secondary schools across metropolitan and regional Victoria, Australia; and (2) a clinical group, ascertained from outpatient services at The Royal Children’s Hospital Melbourne (RCH). The project aims to establish normative data for PEERS®, a novel and comprehensive app-delivered child-direct measure of social skills for children and youth. The project involves recruiting and assessing 1000 children aged 4.0–17.11 years. Assessments consist of an intellectual screen, PEERS® subtests, and PEERS-Q, a self-report questionnaire of social skills. Parents and teachers also complete questionnaires relating to participants’ social skills. Main analyses will comprise regression-based continuous norming, factor analysis and psychometric analysis of PEERS® and PEERS-Q.Ethics and disseminationEthics approval has been obtained through the RCH Human Research Ethics Committee (34046), the Victorian Government Department of Education and Early Childhood Development (002318), and Catholic Education Melbourne (2166). Findings will be disseminated through international conferences and peer-reviewed journals. Following standardisation of PEERS®, the tool will be made commercially available.
Major determinant of the occurrence of pacing-induced cardiomyopathy in complete atrioventricular block: a multicentre, retrospective analysis over a 15-year period in South Korea
Authors: Kim Jun Hyung , Kang Ki-Woon , Chin Jung Yeon , Kim Tae-Seok , Park Jae-Hyeong , Choi Yu Jeong 
Published: February 2018

ObjectivesThe predictors of pacing-induced cardiomyopathy (PICM) for complete atrioventricular block (CAVB) have not yet been defined. The aim of this study was to investigate the major determinant of the occurrence of PICM.SettingThis is a multicentre, retrospective analysis of CAVB from tertiary referral centres in Daejeon, South Korea.ParticipantsA cohort of 900 consecutive patients with an implanted pacemaker was collected from December 2001 to August 2015. Of these, a total of 130 patients with CAVB with pacing-dependent rhythm who underwent ECG and echocardiogram before and after implantation were analysed for the occurrence of PICM.Outcome measuresCox proportional hazards models evaluated the determinant of PICM by ECG, device parameters and echocardiogram over a mean of 4.5 years.ResultsPICM was observed in 16.1% (n=21) of all patients with CAVB (age, 64±11 years; male, 36.2%). The preimplant left ventricular (LV) ejection fraction (66%±9% vs 66%±8%) and non-apical pacing (40.4% vs 33.3%) were similar; however, the native QRS duration (124±34 ms vs 149±32 ms) and the paced QRS duration (pQRSd) (139±29 ms vs 167±28 ms) were significantly different between the two groups. The postimplant LV ejection fraction (61%±7% vs 31%±8%) was also significantly different at the end of follow-up. A pQRSd significantly correlated with PICM (HR 1.05, 95% CI 1.02 to 1.09, P=0.001). A pQRSd with a cut-off value of above 140 ms had a sensitivity of 95% while a pQRSd with a cut-off value of above 167 ms had a specificity of 90% for PICM.ConclusionIn patients with CAVB with pacing-dependent rhythm, regardless of the pacing site, the pQRSd is a major determinant of the occurrence of PICM.
Osteochondral defects of the talus with a focus on platelet-rich plasma as a potential treatment option: a review
Authors: Elghawy Ahmed Aly , Sesin Carlos , Rosselli Michael 
Published: February 2018

ObjectiveTo provide a review of osteochondral lesions of the talus, to discuss the evidence of the risks and benefits of platelet-rich plasma (PRP) as a viable treatment option, and to measure the efficacy of PRP using MRI evidence of cartilage regeneration, as well as scales that measure improvement in ‘pain’ and ‘functionality’.Eligibility criteriaStudies that use PRP in either conservative or intraoperative settings to treat osteochondral defects of the talus.ResultsThere are seven studies that compare hyaluronic acid or standard surgical options against PRP in treating osteochondral lesions of the talus. Five studies use PRP as supplemental treatment in intraoperative settings, while two studies use PRP conservatively as intra-articular injections. There were minimal adverse effects. Pain and functionality scores consistently improved in those who underwent PRP treatments over the course of 4 years. MRI showed significant but inconsistent results in chondral regeneration.ConclusionPRP may show clinical benefit in those with osteochondral lesions of the talus in terms of pain and functionality, although chondral regeneration via MRI is inconsistent. Limitations include the small sample sizes in these seven studies, as well as no standardised formula for PRP preparation.Clinical relevanceTo serve as an overview of the literature regarding PRP treatment for osteochondral lesions of the talus and how this modality may improve patient outcomes in pain, functionality and chondral regeneration. A case is reported to complement the subject review.
Run Clever – No difference in risk of injury when comparing progression in running volume and running intensity in recreational runners: A randomised trial
Authors: Ramskov Daniel , Rasmussen Sten , Sørensen Henrik , Parner Erik Thorlund , Lind Martin , Nielsen Rasmus Oestergaard 
Published: February 2018

Background/aimThe Run Clever trial investigated if there was a difference in injury occurrence across two running schedules, focusing on progression in volume of running intensity (Sch-I) or in total running volume (Sch-V). It was hypothesised that 15% more runners with a focus on progression in volume of running intensity would sustain an injury compared with runners with a focus on progression in total running volume.MethodsHealthy recreational runners were included and randomly allocated to Sch-I or Sch-V. In the first eight weeks of the 24-week follow-up, all participants (n=839) followed the same running schedule (preconditioning). Participants (n=447) not censored during the first eight weeks entered the 16-week training period with a focus on either progression in intensity (Sch-I) or volume (Sch-V). A global positioning system collected all data on running. During running, all participants received real-time, individualised feedback on running intensity and running volume. The primary outcome was running-related injury (RRI).ResultsAfter preconditioning a total of 80 runners sustained an RRI (Sch-I n=36/Sch-V n=44). The cumulative incidence proportion (CIP) in Sch-V (reference group) were CIP2 weeks4.6%; CIP4 weeks8.2%; CIP8 weeks13.2%; CIP16 weeks28.0%. The risk differences (RD) and 95% CI between the two schedules were RD2 weeks=2.9%(−5.7% to 11.6%); RD4 weeks=1.8%(−9.1% to 12.8%); RD8 weeks=−4.7%(−17.5% to 8.1%); RD16 weeks=−14.0% (−36.9% to 8.9%).ConclusionA similar proportion of runners sustained injuries in the two running schedules.
How consistent are associations between maternal and paternal education and child growth and development outcomes across 39 low-income and middle-income countries?
Authors: Jeong Joshua , Kim Rockli , Subramanian S V 
Published: February 2018

BackgroundMaternal and paternal education are associated with improved early child outcomes. However, less is known about how these relative associations compare for preschool children’s growth versus development outcomes; and across country contexts.MethodsWe analysed data from 89 663 children aged 36 to 59 months in 39 low-income and middle-income countries (LMICs). We used linear regression models with country fixed effects to estimate the joint associations between maternal and paternal education and children’s growth and development outcomes. Additionally, we examined the variability in these relationships by each country and within subgroups of countries.ResultsIn the pooled sample, maternal and paternal education were independently associated with 0.37 (95% CI 0.33 to 0.41) and 0.20 (95% CI 0.16 to 0.24) higher height-for-age z-scores, and 0.31 (95% CI 0.29 to 0.34) and 0.16 (95% CI 0.14 to 0.18) higher Early Childhood Development Index z-scores, respectively (comparing secondary or higher to no education). Associations were stronger for maternal education than paternal education but comparable between child outcomes. In country-specific regressions, we found the most heterogeneity in the associations between maternal education and children’s growth; and between paternal education and children’s development. Subgroup analyses suggested that these associations may be systematically patterned by country-level adult illiteracy, infant mortality and food insecurity.ConclusionOur findings highlight variability in the statistical significance and magnitude of the associations between caregivers’ education and children’s outcomes. Further research is needed to understand the sources of variation that may promote or constrain the benefits of caregivers’ education for children’s early health and development in LMICs.
Combat-related foot injuries: impact on gait and functional outcome
Authors: de Kruijff Loes G M , Prins M , van der Krans A , Hoencamp R , van der Wurff P 
Published: February 2018

IntroductionPrior to deployment of the Netherlands Army Task Force Urozgan in Afghanistan, the Dutch Military and civilian healthcare systems had limited experience in treating blast injuries and their long-term consequences. This meant that guidelines for treatment and rehabilitation were lacking. The aim of this cohort study was to quantify kinematic and kinetic abnormalities in service members with foot injuries in relation to functional outcome using gait analysis.MethodIn nine service members with combat-related talus, calcaneus and/or navicular bone (TCN) fractures and nine controls, gait parameters were measured using Gait Real-Time Analysis Interactive Lab system. High-level mobility was evaluated by the Comprehensive High-Level Activity Mobility Predictor (CHAMP), and functional ability was assessed by Lower Extremity Functional Scale (LEFS) questionnaire.ResultsSignificant differences were found for LEFS and CHAMP scores (P<0.01), comfortable walking speed and ankle joint range of motion (ROM) (P<0.05), all lower in the group with TCN fractures. For this group, a trend (0.1>P>0.05) for higher step width and lower stride duration and peak power was found. A strong correlation (0.6>r>0.79) is shown between LEFS and comfortable walking speed and CHAMP and ankle joint ROM. The correlations between LEFS and stride duration, step width, ankle joint ROM and peak power, and between CHAMP and comfortable walking speed and stride duration, were moderate (0.4>r>0.59).ConclusionsThis study demonstrated that service members with TCN fractures, compared with healthy controls, have altered gait characteristics, specifically lower walking speed and ankle joint ROM, both related to lower physical functioning. Patients with bilateral depressed Böhler’s angle had the worse functional performance, and further research is recommended to evaluate the relationship between Böhler’s angle and physical performance.Clinical TrialThe Dutch Ministry of Defence (MOD) and the Institutional Review Board and Medical Ethics Review Committee Brabant, The Netherlands, approved this study (P1550).
The Barrel vascular reconstruction device for endovascular coiling of wide-necked intracranial aneurysms: a multicenter, prospective, post-marketing study
Authors: Gory Benjamin , Blanc Raphaël , Turjman Francis , Berge Jérôme , Piotin Michel 
Published: February 2018

Background and purposeThe Barrel vascular reconstruction device (Barrel VRD) is a novel stent with design features that allow endovascular coiling of wide-necked bifurcation aneurysms while preserving adjacent branches, without necessitating dual stent implantation. This study aimed to assess the safety and effectiveness of the Barrel VRD at 12-month follow-up.Materials and methodsThe Barrel VRD trial is a prospective, multicenter, observational post-marketing registry evaluating the use of the Barrel VRD for treatment of wide-necked bifurcation aneurysms. The primary effectiveness endpoint was successful aneurysm treatment measured by digital subtraction angiography with a Raymond–Roy occlusion grade of 1 or 2 in the absence of retreatment, parent artery stenosis (>50%), or target aneurysm rupture at 12 months. The primary safety endpoint was the absence of neurological death or major stroke at 12 months.ResultsTwenty patients were enrolled from December 2013 to December 2014. The device was implanted in 19 patients with 19 aneurysms (8 middle cerebral artery, 4 anterior communicating artery, 1 internal carotid artery terminus, 4 basilar artery aneurysms; mean dome height 5.7±1.91 mm; mean neck length 4.8±1.35 mm, mean dome-to-neck ratio 1.6±2.0). Coiling was performed in all cases. The primary effectiveness endpoint was achieved in 78.9% of subjects (15/19; 12 complete occlusions, 3 neck remnants), and the primary safety endpoint was 5.3% (1/19).ConclusionsThis prospective study demonstrates that the Barrel VRD device resulted in ~80% occlusion rates and ~5% rates of neurological complications at 1 year after endovascular treatment of wide-necked bifurcation intracranial aneurysms.Registered clinical trialNCT02125097;Results.
‘Drip-and-drive’: shipping the neurointerventionalist to provide mechanical thrombectomy in primary stroke centers
Authors: Brekenfeld Caspar , Goebell Einar , Schmidt Holger , Henningsen Henning , Kraemer Christoffer , Tebben Jörg , Flottmann Fabian , Thomalla Götz , Fiehler Jens 
Published: February 2018

BackgroundTo satisfy the increasing demand of mechanical thrombectomy (MT) for acute ischemic stroke treatment, new organizational concepts for patient care are required. This study evaluates time intervals of acute stroke management in two stroke care models, including one based on transportation of the interventionalist from a comprehensive stroke center (CSC) to treat patients in two primary stroke centers (PSC). We hypothesized that time intervals were not inferior for the ‘drip-and-drive’ concept compared with the traditional ‘drip-and-ship’ concept.MethodsPatients treated with MT at the PSC (‘drip-and-drive’, ‘D+D group’) were compared with patients transferred from PSC to CSC for MT (‘drip-and-ship’, ‘D+S group’) with regard to time delays. Time intervals assessed were: symptom onset to initial CT, to angiography, and to recanalization; time from initial CT to telephone call activation, to arrival, and to angiography; and time from telephone call activation to arrival and from arrival to angiography.Results42 patients were treated at the PSC after transfer of the interventionalist, and 32 patients were transferred to the CSC for MT. The groups did not differ with regard to median Onset–CT and CT–Phone times. Significant differences between the groups were found for the primary outcome measure CT–Arrival time (‘D+D group’: median 121 (IQR 108–134) min vs 181 (157–219) min for the ‘D+S group’; P<0.001). Time difference between the groups increased to more than 2 hours for median CT–Angio times (median 123 (IQR 93–147) min vs 252 (228–275) min; P<0.001).ConclusionTime intervals for the ‘D+D group’ were not inferior to those of the ‘D+S group’. Moreover, under certain conditions, the ‘drip-and-drive’ concept might even be superior.
A Casino goes smoke free: a longitudinal study of secondhand and thirdhand smoke pollution and exposure
Authors: Matt Georg E , Quintana Penelope J E , Hoh Eunha , Zakarian Joy M , Chowdhury Zohir , Hovell Melbourne F , Jacob Peyton , Watanabe Kayo , Theweny Teaba S , Flores Victoria , Nguyen Anh , Dhaliwal Narinder , Hayward Gary 
Published: February 2018

BackgroundSecondhand smoke (SHS) in US casinos is common, but little is known about the residue of tobacco smoke pollutants left behind in dust and on surfaces, commonly referred to as thirdhand smoke (THS). We examined SHS and THS pollution and exposure before and during a casino smoking ban and after smoking resumed.MethodsA casino was visited nine times over a 15-month period to collect dust, surface and air samples in eight locations. Finger wipe and urine samples were collected from non-smoking confederates before and after a 4-hour casino visit. Samples were analysed for markers of SHS and THS pollution and exposure.ResultsExceptionally high levels of THS were found in dust and on surfaces. Although the smoking ban led to immediate improvements in air quality, surface nicotine levels were unchanged and remained very high for the first month of the smoking ban. Surface nicotine decreased by 90% after 1 month (P<0.01), but nicotine and tobacco-specific nitrosamines in dust decreased more slowly, declining by 90% only after 3 months (P<0.01). Exposure was significantly reduced after the ban, but the benefits of the ban were reversed after smoking resumed.ConclusionsLong-term smoking in a casino creates deep THS reservoirs that persist for months after a smoking ban. A complete smoking ban immediately improves air quality and significantly reduces exposure to SHS and THS. However, THS reservoirs contribute to continued low-level exposure to toxicants. To accelerate the effect of smoking bans, remediation efforts should address specific THS reservoirs, which may require intensive cleaning as well as replacement of carpets, furniture and building materials.