bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of Virion-Associated σ1 Fibers on Oncolytic Reovirus Variants Promotes Adaptation toward Tumorigenic Cells
Authors: Mohamed Adil , Teicher Carmit , Haefliger Sarah , Shmulevitz Maya 
Published: February 2015

ABSTRACT

Wild-type mammalian orthoreovirus serotype 3 Dearing (T3wt) is nonpathogenic in humans but preferentially infects and kills cancer cells in culture and demonstrates promising antitumor activity
in vivo
. Using forward genetics, we previously isolated two variants of reovirus, T3v1 and T3v2, with increased infectivity toward a panel of cancer cell lines and improved
in vivo
oncolysis in a murine melanoma model relative to that of T3wt. Our current study explored how mutations in T3v1 and T3v2 promote infectivity. Reovirions contain trimers of σ1, the reovirus cell attachment protein, at icosahedral capsid vertices. Quantitative Western blot analysis showed that purified T3v1 and T3v2 virions had ∼2- and 4-fold-lower levels of σ1 fiber than did T3wt virions. Importantly, using RNA interference to reduce σ1 levels during T3wt production, we were able to generate wild-type reovirus with reduced levels of σ1 per virion. As σ1 levels were reduced, virion infectivity increased by 2- to 5-fold per cell-bound particle, demonstrating a causal relationship between virion σ1 levels and the infectivity of incoming virions. During infection of tumorigenic L929 cells, T3wt, T3v1, and T3v2 uncoated the outer capsid proteins σ3 and μ1C at similar rates. However, having started with fewer σ1 molecules, a complete loss of σ1 was achieved sooner for T3v1 and T3v2. Distinct from intracellular uncoating, chymotrypsin digestion, as a mimic of natural enteric infection, resulted in more rapid σ3 and μ1C removal, unique disassembly intermediates, and a rapid loss of infectivity for T3v1 and T3v2 compared to T3wt. Optimal infectivity toward natural versus therapeutic niches may therefore require distinct reovirus structures and σ1 levels.

IMPORTANCE
Wild-type reovirus is currently in clinical trials as a potential cancer therapy. Our molecular studies on variants of reovirus with enhanced oncolytic activity
in vitro
and
in vivo
now show that distinct reovirus structures promote adaptation toward cancer cells and away from conditions that mimic natural routes of infection. Specifically, we found that reovirus particles with fewer molecules of the cell attachment protein σ1 became more infectious toward transformed cells. Reduced σ1 levels conferred a benefit to incoming particles only, resulting in an earlier depletion of σ1 and a higher probability of establishing productive infection. Conversely, reovirus variants with fewer σ1 molecules showed reduced stability and infectivity and distinct disassembly when exposed to conditions that mimic natural intestinal proteolysis. These findings support a model where the mode of infection dictates the precise optimum of reovirus structure and provide a molecular rationale for considering alternative reovirus structures during oncolytic therapy.
Origin and Proliferation of Multiple-Drug Resistance in Bacterial Pathogens
Authors: Chang Hsiao-Han , Cohen Ted , Grad Yonatan H. , Hanage William P. , O'Brien Thomas F. , Lipsitch Marc 
Published: February 2015

SUMMARY
Many studies report the high prevalence of multiply drug-resistant (MDR) strains. Because MDR infections are often significantly harder and more expensive to treat, they represent a growing public health threat. However, for different pathogens, different underlying mechanisms are traditionally used to explain these observations, and it is unclear whether each bacterial taxon has its own mechanism(s) for multidrug resistance or whether there are common mechanisms between distantly related pathogens. In this review, we provide a systematic overview of the causes of the excess of MDR infections and define testable predictions made by each hypothetical mechanism, including experimental, epidemiological, population genomic, and other tests of these hypotheses. Better understanding the cause(s) of the excess of MDR is the first step to rational design of more effective interventions to prevent the origin and/or proliferation of MDR.
The effect of Chinese herbal medicine Jian Ling Decoction for the treatment of essential hypertension: a systematic review
Authors: Xiong Xingjiang , Wang Pengqian , Li Xiaoke , Zhang Yuqing 
Published: February 2015

ObjectivesJian Ling Decoction (JLD) is often prescribed to improve hypertension-related symptoms in China. However, this treatment has not been systematically reviewed for its efficacy against essential hypertension (EH). This review aims to assess the current clinical evidence of JLD in the treatment of EH.DesignSeven electronic databases, including the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM) and the Wanfang Database, were searched up to March 2014. Randomised control trials (RCTs) comparing JLD or combined with antihypertensive drugs versus antihypertensive drugs were included. We assessed the methodological quality, extracted the valid data and conducted the meta-analysis according to criteria from the Cochrane group. The primary outcome was categorical or continuous blood pressure (BP), and the secondary outcome was quality of life (QOL).ResultsTen trials (655 patients) with unclear-to-high risk of bias were identified. Meta-analysis showed that JLD used alone showed no BP reduction effect; however, improvement on QOL was found in the JLD group compared to antihypertensive drugs. A significant reduction in systolic and diastolic BP was observed for JLD plus antihypertensive drugs when compared with antihypertensive drugs alone. No serious adverse effects were reported.ConclusionsOwing to insufficient clinical data, it is difficult to draw a definite conclusion regarding the effectiveness and safety of JLD for EH, and better trials are needed.
Can certified health professionals treat obesity in a community-based programme? A quasi-experimental study
Authors: Miedema Baukje , Reading Stacey A , Hamilton Ryan A , Morrison Katherine S , Thompson Ashley E 
Published: February 2015

ObjectiveTo test the effectiveness of a non-pharmaceutical programme for obese participants in a rural Eastern Canadian Province using certified health professionals.DesignA prospective quasi-experimental design with repeated premeasure and postmeasure.Participants146 participants with obesity (body mass index >30 kg/m2) from rural and urban communities in an Eastern Canadian Province were divided into four groups.InterventionA 6-month intensive active community-based lifestyle intervention (InI) delivered by Certified Exercise Physiologists, Certified Personal Trainers and Registered Dietitians, followed by 6 months of self-management. A second intervention (InII) was nested in InI and consisted of group-mediated cognitive–behavioral intervention (GMCBI) delivered by an exercise psychologist to two of the four InI groups.Outcomes(1) Improving health outcomes among the participants’ preactive and postactive 6-month intervention and self-management period, (2) Documenting the impact of InII (GMCBI) and location of the intervention (urban vs rural).ResultsThe 6-month active InI significantly improved cardiovascular health for participants who completed the intervention. InII (GMCBI) significantly lowered the attrition rate among the participants. The self-management period was challenging for the participants and they did not make further gains; however, most were able to maintain the gains achieved during the active intervention. The location of the intervention, urban or rural, had little impact on outcomes.ConclusionsA community-based programme utilising healthcare professionals other than physicians to treat obese patients was effective based on premeasure and postmeasure. During the self-management phase, the participants were able to maintain the gains. Psychological support is essential to participant retention.
Over-reassurance and undersupport after a ‘false alarm’: a systematic review of the impact on subsequent cancer symptom attribution and help seeking
Authors: Renzi Cristina , Whitaker Katriina L , Wardle Jane 
Published: February 2015

ObjectivesThis literature review examined research into the impact of a previous ‘all-clear’ or non-cancer diagnosis following symptomatic presentation (‘false alarm’) on symptom attribution and delays in help seeking for subsequent possible cancer symptoms.Design and settingThe comprehensive literature review included original research based on quantitative, qualitative and mixed data collection methods. We used a combination of search strategies, including in-depth searches of electronic databases (PubMed, EMBASE, PsychInfo), searching key authors and articles listed as ‘related’ in PubMed, and reference lists. We performed a narrative synthesis of key themes shared across studies.ParticipantsThe review included studies published after 1990 and before February 2014 reporting information on adult patients having experienced a false alarm following symptomatic presentation. We excluded false alarms in the context of screening.Primary and secondary outcome measuresWe evaluated the effect of a ‘false alarm’ on symptom attribution and help seeking for new or recurrent possible cancer symptoms.ResultsOverall, 1442 papers were screened and 121 retrieved for full-text evaluation. Among them, 19 reported on false alarms and subsequent symptom attribution or help seeking. They used qualitative (n=14), quantitative (n=3) and mixed methods (n=2). Breast (n=7), gynaecological (n=3), colorectal (n=2), testicular (n=2), and head and neck cancers (n=2) were the most studied. Two broad themes emerged underlying delays in help seeking: (1) over-reassurance from the previous ‘all-clear’ diagnosis leading to subsequent symptoms being interpreted as benign, and (2) unsupportive healthcare experiences in which symptoms were dismissed, leaving patients concerned about appearing hypochondriacal or uncertain about the appropriate next actions. The evidence suggested that the effect of a false alarm can persist for months and even years.ConclusionsIn conclusion, over-reassurance and undersupport of patients after a false alarm can undermine help seeking in the case of new or recurrent potential cancer symptoms, highlighting the need for appropriate patient information when investigations rule out cancer.
Ear for recovery: protocol for a prospective study on parent–child communication and psychological recovery after paediatric injury
Authors: Alisic Eva , Barrett Anna , Bowles Peter , Babl Franz E , Conroy Rowena , McClure Roderick J , Anderson Vicki , Mehl Matthias R 
Published: February 2015

IntroductionOne in six children who have been admitted to hospital with an injury develop persistent stress symptoms that put their development at risk. Parents play a crucial role in children's psychological recovery, however, it is unknown how specific parenting behaviours can help or hinder. We aim to describe the nature and quantity of parent–child communication after a child has been injured, and to examine how these interactions are related to children's psychological recovery.Methods and analysisWe are conducting a prospective observational study among children aged 3–16 years, who have been admitted to a tertiary children's hospital with a serious injury. Data collection involves a naturalistic observation of spontaneous, everyday parent–child communication at home, shortly after discharge, and an assessment of children's psychological recovery at 6 weeks and 3 months post-injury. Main analyses comprise descriptive statistics, cluster analysis and analyses of variance.Ethics and disseminationThis study has been approved by the Human Research Ethics Committee of the Royal Children's Hospital Melbourne (33103) and Monash University Human Research Ethics Committee (CF13/2515—2013001322). We aim to disseminate the findings through international peer-reviewed journals, international conferences and social media. Participants will be sent a summary of the overall study findings.
Positive and negative behaviours in workplace relationships: a scoping review protocol
Authors: Almost Joan , Wolff Angela , Mildon Barbara , Price Sheri , Godfrey Christina , Robinson Sandra , Ross-White Amanda , Mercado-Mallari Sheile 
Published: February 2015

IntroductionEngaging in teamwork requires a clear understanding of positive and negative behaviours that act as facilitators and barriers to collegial workplace relationships. Identifying and correcting underlying barriers, while promoting facilitators, is fundamental to improving care delivery and, ultimately, clinical outcomes. Despite a considerable amount of literature in this area, there is a lack of clarity of the different behaviours as several parallel literatures address similar questions about antecedents, processes and outcomes. The purpose of this study is to synthesise the current state of literature reporting on behaviours in workplace relationships. Using a scoping review methodology, the following research question will be addressed: “What is known about positive and negative behaviours in workplace relationships?”Methods and analysisWe will employ the methodological frameworks used by Arksey and O'Malley and Levacet al. The search strategy will include numerous electronic databases, grey literature sources and hand-searching of reference lists from 1990 to present with a limit to English language. Search strategies will be developed using controlled vocabulary and keyword terms related to various components of workplace relationships. Two reviewers will independently screen titles and abstracts for inclusion, followed by screening of the full text of potential articles to determine final inclusion. A descriptive numerical analysis will describe characteristics of included studies. A thematic analysis will provide an overview of the literature, including definitions, conceptual frameworks, antecedents, outcomes and interventions.DisseminationIn reviewing a wide range of positive and negative behaviours, then integrating into a manageable, meaningful whole, this study is a critical step in helping policymakers, leaders and healthcare professionals effectively use what is known thus far. Knowledge translation activities will occur throughout the study with dissemination of findings to local, national, and international stakeholders, including a wide range of clinicians, leaders and administrators in all sectors.
Hemodynamics in growing and stable cerebral aneurysms
Authors: Sforza Daniel M , Kono Kenichi , Tateshima Satoshi , Viñuela Fernando , Putman Christopher , Cebral Juan R 
Published: February 2015

ObjectiveThe detailed mechanisms of cerebral aneurysm evolution are poorly understood but are important for objective aneurysm evaluation and improved patient management. The purpose of this study was to identify hemodynamic conditions that may predispose aneurysms to growth.MethodsA total of 33 intracranial unruptured aneurysms longitudinally followed with three-dimensional imaging were studied. Patient-specific computational fluid dynamics models were constructed and used to quantitatively characterize the hemodynamic environments of these aneurysms. Hemodynamic characteristics of growing (n=16) and stable (n=17) aneurysms were compared. Logistic regression statistical models were constructed to test the predictability of aneurysm growth by hemodynamic features.ResultsGrowing aneurysms had significantly smaller shear rate ratios (p=0.01), higher concentration of wall shear stress (p=0.03), smaller vorticity ratios (p=0.01), and smaller viscous dissipation ratios (p=0.01) than stable aneurysms. They also tended to have larger areas under low wall shear stress (p=0.06) and larger aspect ratios (p=0.18), but these trends were not significant. Mean wall shear stress was not significantly different between growing and stable aneurysms. Logistic regression models based on hemodynamic variables were able to discriminate between growing and stable aneurysms with a high degree of accuracy (94–100%).ConclusionsGrowing aneurysms tend to have complex intrasaccular flow patterns that induce non-uniform wall shear stress distributions with areas of concentrated high wall shear stress and large areas of low wall shear stress. Statistical models based on hemodynamic features seem capable of discriminating between growing and stable aneurysms.
Hemodynamic characteristics of large unruptured internal carotid artery aneurysms prior to rupture: a case control study
Authors: Liu Jian , Fan Jixing , Xiang Jianping , Zhang Ying , Yang Xinjian 
Published: February 2015

ObjectivePost-ruptured intracranial aneurysm geometry models have been widely used in computational fluid dynamic studies to assess hemodynamic parameters associated with aneurysm rupture. However, their results may not be valid due to the morphological changes of the aneurysm after rupture. Our aim was to identify the hemodynamic features of aneurysms prior to rupture in comparison with unruptured aneurysms.Materials and methodsWe retrospectively identified three large unruptured internal carotid artery (ICA) aneurysms (pre-ruptured group) with adequate image quality just before rupture. Matched with the same location and similar size, eight unruptured aneurysms (unruptured group) were selected as controls during the same time period. Flow simulations for these aneurysms were performed to compare differences in hemodynamics.ResultsCompared with unruptured aneurysms, pre-ruptured aneurysms had a significantly more irregular aneurysm shape, a higher aspect ratio, and lower aneurysm averaged wall shear stress (WSS) (p=0.024, p=0.048, and p=0.048, respectively). Although pre-ruptured aneurysms had a lower low WSS area and higher Oscillatory Shear Index, these were not statistically significant.ConclusionsFor large unruptured ICA aneurysms, low WSS, higher aspect ratio, and irregular shape were indicators of fatal rupture. Early treatment for such lesions with flow diverter and coils may be the best therapeutic option.
Republished: Non-alcoholic fatty liver disease: a practical approach to treatment
Authors: Dyson J K , Anstee Q M , McPherson S 
Published: February 2015

ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population in many developed countries. Between 10% and 30% of patients with NAFLD have non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis. There are metabolic risk factors common to both NAFLD and cardiovascular disease, so patients with NASH have an increased risk of liver-related and cardiovascular death. Management of patients with NAFLD depends largely on the stage of disease, emphasising the importance of careful risk stratification. There are four main areas to focus on when thinking about management strategies in NAFLD: lifestyle modification, targeting the components of the metabolic syndrome, liver-directed pharmacotherapy for high risk patients and managing the complications of cirrhosis.
Republished: Key characteristics of successful quality improvement curricula in physician education: a realist review
Authors: Jones Anne C , Shipman Scott A , Ogrinc Greg 
Published: February 2015

ABSTRACT

Purpose
Quality improvement (QI) is a common competency that must be taught in all physician training programmes, yet, there is no clear best approach to teach this content in clinical settings. We conducted a realist systematic review of the existing literature in QI curricula within the clinical setting, highlighting examples of trainees learning QI by doing QI.

Method
Candidate theories describing successful QI curricula were articulated a priori. We searched MEDLINE (1 January 2000 to 12 March 2013), the Cochrane Library (2013) and Web of Science (15 March 2013) and reviewed references of prior systematic reviews. Inclusion criteria included study design, setting, population, interventions, clinical and educational outcomes. The data abstraction tool included categories for setting, population, intervention, outcomes and qualitative comments. Themes were iteratively developed and synthesised using realist review methodology. A methodological quality tool assessed the biases, confounders, secular trends, reporting and study quality.

Results
Among 39 studies, most were before–after design with resident physicians as the primary population. Twenty-one described clinical interventions and 18 described educational interventions with a mean intervention length of 6.58 (SD=9.16) months. Twenty-eight reported successful clinical improvements; no studies reported clinical outcomes that worsened. Characteristics of successful clinical QI curricula include attention to the interface of educational and clinical systems, careful choice of QI work for the trainees and appropriately trained local faculty.

Conclusions
This realist review identified success characteristics to guide training programmes, medical schools, faculty, trainees, accrediting organisations and funders to further develop educational and improvement resources in QI educational programmes.
Should single layer centrifugation of dog semen be done before or after the semen is cooled?
Authors: Gálvez M. J. , Ortiz I. , Hidalgo M. , Morrell J. M. , Dorado J. 
Published: February 2015

The aim of this study was to assess the effectiveness of sperm selection by single layer centrifugation (SLC) on canine sperm quality when SLC was performed before or after the cooling process, or when double SLC (before and after cooling) was performed. Twenty ejaculates from four dogs were divided into four aliquots as follows: unselected: no SLC was performed; SLC prior to cooling (SLC‐PC): sperm selection was carried out before cooling; SLC after cooling (SLC‐AC): sperm selection was performed after cooling; and double SLC: sperm selection was carried out before and after cooling. Sperm motility (by computer‐assisted semen analysis), morphology (Diff‐Quick staining), sperm membrane integrity (Vital‐Test kit) and acrosome integrity (double fluorescent stain) were assessed in re‐warmed semen samples. Four sperm subpopulations (sP) were detected using a pattern analysis technique (sP1: highly active, non‐progressive; sP2: low velocity, highly progressive; sP3: less vigorous, poorly progressive; sP4: highly progressive motility). A higher proportion of sperm were classified as sP4 in SLC‐AC samples. Most of the sperm parameters assessed showed higher values in the SLC‐AC group. We conclude that SLC‐AC is the best protocol to improve sperm quality in chilled canine semen in comparison to the other procedures tested.