bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Hybrid Secretion System Facilitates Bacterial Sporulation: A Structural Perspective
Authors: Zeytuni Natalie , Strynadka Natalie C.J. 
Published: January 2019

ABSTRACT

Bacteria employ a number of dedicated secretion systems to export proteins to the extracellular environment. Several of these comprise large complexes that assemble in and around the bacterial membrane(s) to form specialized channels through which only selected proteins are actively delivered. Although typically associated with bacterial pathogenicity, a specialized variant of these secretion systems has been proposed to play a central part in bacterial sporulation, a primitive protective process that allows starving cells to form spores that survive in extreme environments. Following asymmetric division, the mother cell engulfs the forespore, leaving it surrounded by two bilayer membranes. During the engulfment process an essential channel apparatus is thought to cross both membranes to create a direct conduit between the mother cell and forespore. At least nine proteins are essential for channel formation, including SpoIIQ under forespore control and the eight SpoIIIA proteins (SpoIIIAA to -AH) under mother cell control. Presumed to form a core channel complex, several of these proteins share similarity with components of Gram-negative bacterial secretion systems, including the type II, III, and IV secretion systems and the flagellum. Based on these similarities it has been suggested that the sporulation channel represents a hybrid, secretion-like transport machinery. Recently, in-depth biochemical and structural characterization of the individual channel components accompanied by
in vivo
studies has further reinforced this model. Here we review and discuss these recent studies and suggest an updated model for the unique sporulation channel apparatus architecture.
Evaluation of the combined effect of factors influencing bowel preparation and adenoma detection rates in patients undergoing colonoscopy
Authors: Tariq Hassan , Kamal Muhammad Umar , Sapkota Binita , ElShikh Fady , Pirzada Usman Ali , Pullela Nanda , Azam Sara , Zhang Aiyi , Baiomi Ahmed , Abbas Hafsa , Makker Jasbir , Balar Bhavna , Ihimoyan Ariyo , Daniel Myrta , Dev Anil 
Published: January 2019

BackgroundColonoscopy is a commonly used modality for screening and surveillance of colorectal cancer (CRC). Therefore, it is essential to have adequate bowel preparation (prep) for the procedure which depends on type of bowel regimens, diet before colonoscopy and timing of the procedure.AimsThe purpose of this study is to analyse the effect of multiple factors on adenoma detection rate (ADR) and prep quality of colonoscopy. This is the also the first study determining outcomes based on various combinations of diet, timing of the procedure and bowel prep regimens.MethodsThis is a retrospective single-centre observational study. Data about diet before procedure, bowel prepprep regimen and timing of the procedure was collected for patients coming for screening colonoscopy.ResultsPatients with split prep had higher good prep rates (73.8% vs 56.2%) and higher ADRs (34.2 % vs 29.9%) as compared with non-split prep. The good prep quality (65.8% vs 62.1%) and ADRs (31.9% vs 31.5%) were comparable in patients who received clear liquid diet as compared with low residue diet. The good results of bowel prep were obtained with split prep with either clear liquids or low residue diet irrespective of the timing of procedure. The poor prep was noticed in patients who underwent procedure in afternoon, with a low restrictive diet and non-split bowel regimen.ConclusionsThe current study adds to our knowledge about the combined effect of multiple variables affecting the bowel prep quality and ADR. It is imperative to opt for the best combination required for colonoscopy, as this will influence the effectiveness of colonoscopies regarding timely cancer detection and prevention.
Is a government-regulated rehabilitation guideline more effective than general practitioner education or preferred-provider rehabilitation in promoting recovery from acute whiplash-associated disorders? A pragmatic randomised controlled trial
Authors: Côté Pierre , Boyle Eleanor , Shearer Heather M , Stupar Maja , Jacobs Craig , Cassidy John David , Carette Simon , van der Velde Gabrielle , Wong Jessica J , Hogg-Johnson Sheilah , Ammendolia Carlo , Hayden Jill Alison , van Tulder Maurits , Frank John W 
Published: January 2019

ObjectiveTo evaluate the effectiveness of a government-regulated rehabilitation guideline compared with education and activation by general practitioners, and to a preferred-provider insurance-based rehabilitation programme on self-reported global recovery from acute whiplash-associated disorders (WAD) grade I–II.DesignPragmatic randomised clinical trial with blinded outcome assessment.SettingMultidisciplinary rehabilitation clinics and general practitioners in Ontario, Canada.Participants340 participants with acute WAD grade I and II. Potential participants were sampled from a large automobile insurer when reporting a traffic injury.InterventionsParticipants were randomised to receive one of three protocols: government-regulated rehabilitation guideline, education and activation by general practitioners or a preferred-provider insurance-based rehabilitation.Primary and secondary outcome measuresOur primary outcome was time to self-reported global recovery. Secondary outcomes included time on insurance benefits, neck pain intensity, whiplash-related disability, health-related quality of life and depressive symptomatology at 6 weeks and 3, 6, 9 and 12 months postinjury.ResultsThe median time to self-reported global recovery was 59 days (95% CI 55 to 68) for the government-regulated guideline group, 105 days (95% CI 61 to 126) for the preferred-provider group and 108 days (95% CI 93 to 206) for the general practitioner group; the difference was not statistically significant (Χ2=3.96; 2 df: p=0.138). We found no clinically important differences between groups in secondary outcomes. Post hoc analysis suggests that the general practitioner (hazard rate ratio (HRR)=0.51, 95% CI 0.34 to 0.77) and preferred-provider groups (HRR=0.67, 95% CI 0.46 to 0.96) had slower recovery than the government-regulated guideline group during the first 80 days postinjury. No major adverse events were reported.ConclusionsTime-to-recovery did not significantly differ across intervention groups. We found no differences between groups with regard to neck-specific outcomes, depression and health-related quality of life.Trial registration numberNCT00546806.
Adapting health interventions for local fit when scaling-up: a realist review protocol
Authors: Power Jessica , Gilmore Brynne , Vallières Frédérique , Toomey Elaine , Mannan Hasheem , McAuliffe Eilish 
Published: January 2019

IntroductionScaling-up is essential to ensure universal access of effective health interventions. Scaling-up is a complex process, which occurs across diverse systems and contexts with no one-size-fits-all approach. To date, little attention has been paid to the process of scaling-up in how to make adaptations for local fit. The aim of this research is to develop theory on what actions can be used to make adaptations to health interventions for local fit when scaling-up across diverse contexts that will have practical application for implementers involved in scaling-up.Methods and analysisGiven the complexity of this subject, a realist review methodology was selected. Specifically, realist review emphasises an iterative, non-linear process, whereby the review is refined as it progresses. The identification of how the context may activate mechanisms to achieve outcomes is used to generate theories on what works for whom in what circumstances. This protocol will describe the first completed stage of development of an initial programme theory framework, which identified potential actions, contexts, mechanisms and outcomes that could be used to make adaptations when scaling-up. It will then outline the methods for future stages of the review which will focus on identifying case examples of scale-up and adaptation in practice. This realist review consists of six stages: (i) clarifying scope and development of a theoretical framework, (ii) developing a search strategy, (iii) selection and appraisal, (iv) data extraction, (v) data synthesis and analysis and (vi) further theory refinement with stakeholders.Ethics and disseminationThis review will develop theory on how adaptations can be made when scaling-up. Findings will be disseminated in a peer-reviewed journal and through stakeholder engagement as part of the research process. Ethical approval has been received through Health Policy and Management/Centre for Global Health Research Ethics Committee of Trinity College Dublin.
Levetiracetam optimal dose-finding as first-line treatment for neonatal seizures occurring in the context of hypoxic-ischaemic encephalopathy (LEVNEONAT-1): study protocol of a phase II trial
Authors: Favrais Geraldine , Ursino Moreno , Mouchel Catherine , Boivin Estelle , Jullien Vincent , Zohar Sarah , Saliba Elie 
Published: January 2019

IntroductionTherapeutic schedules for treating neonatal seizures remain elusive. First-line treatment with phenobarbital is widely supported but without strong scientific evidence. Levetiracetam (LEV) is an emerging and promising antiepileptic drug (AED). The aim of this phase II trial is to determine the benefits of LEV by applying a strict methodology and to estimate the optimal dose of LEV as a first-line AED to treat seizures in newborns suffering from hypoxic-ischaemic encephalopathy.Methods and analysisLEVNEONAT-1 is an open and sequential LEV dose-finding study. The optimal dose is that which is estimated to be associated with a toxicity not exceeding 10% and an efficacy higher than 60%. Efficacy is defined by a seizure burden reduction of 80% after the loading dose. Four increasing dose regimens will be assessed including one loading dose of 30, 40, 50 or 60 mg/kg followed by eight maintenance doses (ie, a quarter of the loading dose) injected every 8 hours. A two-patient cohort will be necessary at each dose level to consider an upper dose level assignment. The maximal sample size expected is 50 participants with a minimum of 24 patients or fewer in the case of a high rate of toxicity. Patients will be recruited in five neonatal intensive care units beginning in October 2017 and continuing for 2 years. In parallel, the LEV pharmacokinetics will be measured five times (ie, 30 min; 4 and 7 hours after the loading dose; 1–3 hours and 12–18 hours after the last maintenance dose).Ethics and disseminationEthics approval has been obtained from the regional ethical committee (2016-R25) and the French Drug Safety Agency (160652A-31). The results will be published in a peer-reviewed journal. The results will also be presented at medical meetings.Trial registration numberNCT02229123; Pre-results.
Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis
Authors: Peters Ruth , Booth Andrew , Rockwood Kenneth , Peters Jean , D’Este Catherine , Anstey Kaarin J 
Published: January 2019

ObjectiveTo systematically review the literature relating to the impact of multiple co-occurring modifiable risk factors for cognitive decline and dementia.DesignA systematic review and meta-analysis of the literature relating to the impact of co-occurring key risk factors for incident cognitive decline and dementia. All abstracts and full text were screened independently by two reviewers and each article assessed for bias using a standard checklist. A fixed effects meta-analysis was undertaken.Data sourcesDatabases Medline, Embase and PsycINFO were searched from 1999 to 2017.Eligibility criteriaFor inclusion articles were required to report longitudinal data from participants free of cognitive decline at baseline, with formal assessment of cognitive function or dementia during follow-up, and an aim to examine the impact of additive or clustered comorbid risk factor burden in with two or more core modifiable risk factors.ResultsSeventy-nine full-text articles were examined. Twenty-two articles (18 studies) were included reporting data on >40 000 participants. Included studies consistently reported an increased risk associated with greater numbers of intraindividual risk factors or unhealthy behaviours and the opposite for healthy or protective behaviours. A meta-analysis of studies with dementia outcomes resulted in a pooled relative risk for dementia of 1.20 (95% CI 1.04 to 1.39) for one risk factor, 1.65 (95% CI 1.40 to 1.94) for two and 2.21 (95% CI 1.78 to 2.73) for three or more, relative to no risk factors. Limitations include dependence on published results and variations in study outcome, cognitive assessment, length of follow-up and definition of risk factor exposure.ConclusionsThe strength of the reported associations, the consistency across studies and the suggestion of a dose response supports a need to keep modifiable risk factor exposure to a minimum and to avoid exposure to additional modifiable risks. Further research is needed to establish whether particular combinations of risk factors confer greater risk than others.PROSPERO registration number42016052914.
Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis: interaction effect with disease severity—a retrospective study
Authors: Shen Yanfei , Huang Xinmei , Zhang Weimin 
Published: January 2019

ObjectiveThe role of platelet-to-lymphocyte ratio (PLR) as an indicator of inflammation has been the focus of research recently. We aimed to investigate theprognosticvalue of PLR for sepsis.DesignA retrospective cohort study.Setting and participantsData were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. Data on 5537 sepsis patients were analysed.MethodsLogistic regression was used to explore the association between PLR and hospital mortality. Subgroup analyses were performed based on vasopressor use, acute kidney injury (AKI) and a Sequential Organ Failure Assessment (SOFA) score >10.ResultsIn the logistic model with linear spline function, a PLR >200 was significantly (OR 1.0002; 95% CI 1.0001 to 1.0004) associated with mortality; the association wasnon-significantfor PLRs ≤200 (OR 0.997; 95% CI 1.19 to 1.67). In the logistic model using the PLR as a design variable, only high PLRs were significantly associated with mortality (OR 1.29; 95% CI 1.09 to 1.53); the association with low PLRs wasnon-significant(OR 1.15; 95% CI 0.96 to 1.38). In the subgroups with vasopressor use, AKI and a SOFA score >10, the association between high PLR and mortality wasnon-significant; this remained significant in the subgroups without vasopressor use (OR 1.39; 95% CI 1.08 to 1.77) and AKI (OR 1.54; 95% CI 1.20 to 1.99) and with a SOFA score ≤10 (OR 1.51; 95% CI 1.17 to 1.94).ConclusionsHigh PLRs at admission were associated with an increased risk of mortality. In patients with vasopressor use, AKI or a SOFA score >10, this association wasnon-significant.
Five-year standardised mortality ratios in a cohort of homeless people in Dublin
Authors: Ivers Jo-Hanna , Zgaga Lina , O’Donoghue-Hynes Bernie , Heary Aisling , Gallwey Brian , Barry Joe 
Published: January 2019

ObjectiveTo calculate standardised mortality ratios (SMRs) for a cohort of homeless people in the Dublin region over a 5-year period and to examine leading causes of death.SettingHomeless services reporting deaths from homeless persons in their care across the Dublin Homeless Region.MethodsDeath data among people who experience homelessness was acquired from the Dublin Region Homeless Executive (2011–2015) and validated from both death certificates and records from the Dublin Coroner’s Office.ParticipantsTwo hundred and nine deaths were recorded; of these 201 were verified (n=156 males, 77.6%). Deaths that could not be verified by certificate or coroners record were excluded from the study.ResultsSMRs were 3–10 times higher in homeless men and 6–10 times higher in homeless women compared with the general population. Drug and alcohol-related deaths were the leading cause of death, accounting for 38.4% of deaths in homeless individuals. These were followed by circulatory (20%) and respiratory causes (13%).ConclusionMortality rates among homeless persons are exceptionally high. Services and programmes, particularly housing and those targeting overdose and alcoholism, are urgently needed to prevent premature mortality in this vulnerable population.
How do primary healthcare workers in low-income and middle-income countries obtain information during consultations to aid safe prescribing? A systematic review protocol
Authors: Smith Chris , van Velthoven Michelle Helena , Pakenham-Walsh Neil 
Published: January 2019

IntroductionThere is a wide variety in prescribing by primary healthcare workers in low-income and middle-income countries. While there is much information available, both online and offline, there is variation in quality and relevance to different settings. Acting on incorrect or out-of-date information can lead to inappropriate prescribing and impact on patient safety. The aim of this review is to systematically review the evidence on how primary healthcare workers obtain information during consultations to prescribe safely and appropriately.Methods and analysisWe will identify relevant articles by searching electronic databases: Medline (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials, CABI Global Health (Ovid), WHO global health library, POPLINE, Africa-Wide Information (Ebsco), Library, Information Science & Technology Abstracts (Ebsco), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. Also, the Health Information For All network will be consulted and evidence databases (TRIP database, Epistemonikos, PDQ Evidence) will be searched. We will hand-search reference lists, run citation searches of included studies and email authors of identified papers. Observational and intervention studies involving primary healthcare workers in low-income and middle-income countries who prescribe and/or dispense medication will be included. The primary outcome is the proportion of healthcare workers obtaining information relevant to consultations from different sources. Secondary outcomes are the change in healthcare provider and patient knowledge or behaviour, adverse outcomes and use of resources. We will exclude studies focusing on secondary care. We anticipate a limited scope for meta-analysis and will provide a narrative overview of findings and tabular summaries of extracted data.Ethics and disseminationNo ethics approval is required. Findings will be disseminated through the Healthcare Information For All network.PROSPERO registration numberCRD42018091088.
Does price regulation affect atorvastatin sales in India? An impact assessment through interrupted time series analysis
Authors: Selvaraj Sakthivel , Farooqui Habib Hasan , Mehta Aashna 
Published: January 2019

ObjectiveThe objective of this study was to examine the impact of medicines price regulation (Drug Price Control Order, 2013) on the market share of atorvastatin in the Indian retail market for statins.SettingAll Indian states, January 2012 to December 2015.DesignQuasi-experimental—interrupted time series analysis.DataPharmaceutical sales audit data set from IMS Health (now IQVIA) for the 48-month period from January 2012 to December 2015.Outcome measureShare of atorvastatin (in percentage) in the Indian market for statins in terms of sales volumes.ResultsWe observed that the price regulation notification (Drug Price Control Orders, 2013) was associated with 0.12% (p<0.001; 95% CI 0.06 to 0.18) increase in the trend of the average monthly market share of atorvastatin (5 mg and 10 mg). After 31 months of price ceilings notification, the average market share of atorvastatin was 3.41% higher than would have been expected had the price ceilings not been notified. In sensitivity analysis, with a control, our findings remain robust, we observed a 0.16% (p<0.001; 95% CI 0.08 to 0.24) rise in the trend of average monthly market share of atorvastatin (5 mg and 10 mg) as compared with the change in the control.ConclusionsPrice control as a public intervention did improve the relative sales of atorvastatin in the statin market in India.
Efficacy of biological drugs in short-duration versus long-duration inflammatory bowel disease: a protocol for a systematic review and an individual-patient level meta-analysis of randomised controlled trials
Authors: Ben-Horin Shomron , Zhao Yue , Guo Jing , Mao Ren , Novack Lena , Sergienko Ruslan , Zhang Jian , Kobayashi Taku , Hibi Toshifumi , Chowers Yehuda , Colombel Jean Frederic , Peyrin-Biroulet Laurent , Kaplan Gilaad , Chen Min-hu 
Published: January 2019

IntroductionCrohn’s disease (CD) and ulcerative colitis (UC) are remitting–relapsing inflammatory diseases often culminating in disease complications and/or need for surgery. Biologic monoclonal antibody drugs (‘Biologics’) are efficacious for both diseases, but there are no systematic assessments of their efficacy if administered early after disease onset (‘top-down’ strategy) vis-à-vis later in the course of disease (‘step-up’ approach).Methods and analysisElectronic databases (MEDLINE, EMBASE/EMBASE classic Cochrane CENTRAL register of controlled trials, the Cochrane IBD Group Specialised Trials Register and Clinicaltrials.gov registry) will be searched to identify all randomised placebo-controlled clinical trials of food and drug administration (FDA)-approved biologics for CD and UC (by March 2016). Two independent reviewers will screen identified papers, extract data and assess the risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. Individual-patient-level data (IPD) will be extracted from the identified trials through data-sharing platforms for pharmaceutical companies’ sponsored trials and by contacting principal investigators of independent investigator-initiated trials. We will analyse induction of remission in patients with early-disease (<18 months since disease onset) versus patients with longer disease duration, using a generalised linear mixed effect model and by a two-stage approach using coefficient for the treatment-by-subgroup interaction within each trial. We will perform receiver operator curve analysis of optimal disease duration for response. Analyses will be separate for CD and UC. This first-of-its-kind meta-analysis at IPD level of interaction of disease duration with the response to biologics in UC and CD may elucidate the impact of early initiation of biologics, which is of paramount importance for clinical practice and management strategies of inflammatory bowel disease.Ethics and disseminationThis meta-analysis was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. Findings will be published in peer-reviewed journal and disseminated via scientific meetings and links with organisations.PROSPERO registration numberCRD42018041961.