bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts of Recurrent Hitchhiking on Divergence and Demographic Inference inDrosophila
Authors: Lange Jeremy D. , Pool John E. 
Published: September 2017

AbstractIn species with large population sizes such asDrosophila, natural selection may have substantial effects on genetic diversity and divergence. However, the implications of this widespread nonneutrality for standard population genetic assumptions and practices remain poorly resolved. Here, we assess the consequences of recurrent hitchhiking (RHH), in which selective sweeps occur at a given rate randomly across the genome. We use forward simulations to examine two published RHH models forD. melanogaster, reflecting relatively common/weak and rare/strong selection. We find that unlike the rare/strong RHH model, the common/weak model entails a slight degree of Hill-Robertson interference in high recombination regions. We also find that the common/weak RHH model is more consistent with our genome-wide estimate of the proportion of substitutions fixed by natural selection betweenD. melanogasterandD. simulans(19%). Finally, we examine how these models of RHH might bias demographic inference. We find that these RHH scenarios can bias demographic parameter estimation, but such biases are weaker for parameters relating recently-diverged populations, and for the common/weak RHH model in general. Thus, even for species with important genome-wide impacts of selective sweeps, neutralist demographic inference can have some utility in understanding the histories of recently-diverged populations.
Crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage
Authors: Kulcsér Péter István , Tálas András , Huszár Krisztina , Ligeti Zoltán , Tóth Eszter , Weinhardt Nóra , Fodor Elfrieda , Welker Ervin 
Published: September 2017

AbstractBackgroundThe propensity for off-target activity of Streptococcus pyogenes Cas9 (SpCas9) has been considerably decreased by rationally engineered variants with increased fidelity (eSpCas9; SpCas9-HF1). However, a subset of targets still generate considerable off-target effects. To deal specifically with these targets, we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1 and examined these improved nuclease variants side-by-side, to decipher the factors that affect their specificities and to determine the optimal nuclease for applications sensitive to off-target effects.ResultsThese three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers; a matching 5' G extension being more detrimental to their activities than a mismatching one. HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity. There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases. Furthermore, we show that the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s.ConclusionsNo single nuclease variant shows generally superior fidelity; instead, for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease. We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools.
Strategic organizational discourse and framing in hypermodal spaces
Authors: Ravazzani Silvia , Maier Carmen Daniela 
Published: September 2017

Purpose
The purpose of this paper is to explore how organizations can strategically frame their legitimate perspective on a specific issue in order to gain salience and public support in a social media context.

Design/methodology/approach
By means of framing theory and a critical perspective on strategic discourse in hypermodal spaces, the study examines in detail the discursive strategies and framing processes employed by a non-profit organization that faces local and global contestation of its corporate operations.

Findings
Through a critical discourse analysis of the organization’s 385 Facebook posts during two periods of time, the results not only show how the corporate perspective is strategically framed and legitimized, but also challenged and consequently adapted in this hypermodal issue sub-arena. In addition to legitimizing the organizational perspective by providing evidence-based facts and external expert views as reliable and neutral sources, and echoing supporters’ voices and actions as further endorsements, the organization also strategically manages the Facebook dialogue by delegitimizing counterarguments.

Originality/value
This study contributes to the corporate communication field by revealing how framing can be materialized in specific discursive strategies aimed to legitimize and delegitimize. It shows how such strategies are interrelated in hypermodal clusters in ways that sustain the organizational discourse, and can evolve across time and within the same actor’s strategy. Methodologically, this study expands the research toolkit by introducing hypermodality in exploring framing and strategic organizational discourse.
Secrecy and communication: towards a research agenda
Authors: Fan Ziyun , Costas Jana , Grey Chris 
Published: September 2017

Purpose
The purpose of this paper is to identify possible lines of research relating to communication and secrecy.

Design/methodology/approach
This paper is a conceptual essay drawing on recent research on secrecy.

Findings
The findings suggest that secrecy entails the communication of rules about communication, and that secrecy can play a role in the communicative constitution of organizations.

Originality/value
The paper is innovative in configuring secrecy as a form of communication rather than being the opposite of communication, and in showing the linkages between what are normally two separate domains of research.
You can lead a horse to water but you can’t make it drink: how effective is staff training in the prevention of abuse of adults?
Authors: Moore Steve 
Published: September 2017

Purpose
The purpose of this paper is to present findings from a research project designed to determine the qualifications held by those staff who had perpetrated abuse in private sector care and nursing homes for older people during a 12-month period.

Design/methodology/approach
A self-completion, postal questionnaire was issued to the safeguarding teams of all local authorities in England with adult social care responsibilities to determine the qualifications held by staff who were proven to have perpetrated abuse in these facilities.

Findings
Though findings with respect to qualified nurses who had perpetrated abuse when considered in isolation were inconclusive in numerical terms, the proportion of all nursing and care staff who had perpetrated abuse, and who held either a professional or vocational qualification was high.

Research limitations/implications
Responses to the postal questionnaire represented 21.8 per cent of local authorities with social services responsibilities, yet the data secured suggests that care providing staff who have received recognised training are disproportionately represented among those proven to have perpetrated abuse.

Originality/value
Findings indicate that recognised training for those who provide care in care and nursing homes is of limited efficacy in the prevention of abuse.
Alamandine reverses hyperhomocysteinemia‐induced vascular dysfunction via PKA‐dependent mechanisms
Authors: Qaradakhi Tawar , Matsoukas Minos Timotheos , Hayes Alan , Rybalka Emma , Caprnda Martin , Rimarova Kvetoslava , Sepsi Milan , Büsselberg Dietrich , Kruzliak Peter , Matsoukas John , Apostolopoulos Vasso , Zulli Anthony 
Published: September 2017

SummaryIntroductionHyperhomocysteinemia (HHcy) impairs nitric oxide endothelium‐dependent vasodilation, consequently leading to atherosclerosis, a risk factor for cardiovascular disease. Novel treatments for HHcy are necessary.AimWe tested the hypothesis that alamandine, a vasoactive peptide of the renin‐angiotensin system (RAS), could reverse HHcy‐induced vascular dysfunction through the MrgD receptor and that this is mediated by the protein kinase A (PKA) pathway. Furthermore, we sought to determine a putative binding model of alamandine to the MrgD receptor through docking and molecular dynamics simulations.MethodThe abdominal aorta was excised from New Zealand white rabbits (n = 15) and incubated with 3 mmol/L Hcy (to mimic HHcy) to induce vascular dysfunction in vitro. Vascular function was assessed by vasodilatory responses to cumulative doses of acetylcholine.ResultVasodilation was significantly impaired in HHcy‐incubated aortic rings while alamandine reversed this effect (control, 74.2 ± 5.0%; Hcy, 30.3 ± 9.8%; alamandine + Hcy, 59.7 ± 4.8%, P < .0001). KT5720 (PKA inhibitor) significantly inhibited the ability of alamandine to attenuate the impaired vasodilation caused by HHcy (KT5720 + Hcy + alamandine, 27.1 ± 24.1, P < .01). Following immunohistochemistry analysis, the MrgD receptor was highly expressed within the media and endothelial layer of aortic rings in HHcy compared to control (media: 0.23 ± 0.003 vs control 0.16 ± 0.01, P < .05 and endothelium: 0.68 ± 0.07 vs control 0.13 ± 0.02, P < .01, in PA/I (A.U) units). Computational studies also propose certain interactions of alamandine within the MrgD transmembrane domain.ConclusionThis study shows that alamandine is effective in reversing HHcy‐induced vascular dysfunction, possibly through the PKA signaling pathway via MrgD. Our results indicate a therapeutic potential of alamandine in reversing the detrimental effects of HHcy.
Effects of red blood cell storage time on transfused patients in the ICU—protocol for a systematic review
Authors: Rygård S. L. , Jonsson A. B. , Madsen M. B. , Perner A. , Holst L. B. , Johansson P. I. , Wetterslev J. 
Published: September 2017

BackgroundPatients in the intensive care unit (ICU) are often anaemic due to blood loss, impaired red blood cell (RBC) production and increased RBC destruction. In some studies, more than half of the patients were treated with RBC transfusion. During storage, the RBC and the storage medium undergo changes, which lead to impaired transportation and delivery of oxygen and may also promote an inflammatory response. Divergent results on the clinical consequences of storage have been reported in both observational studies and randomised trials. Therefore, we aim to gather and review the present evidence to assess the effects of shorter vs. longer storage time of transfused RBCs for ICU patients.MethodsWe will conduct a systematic review with meta‐analyses and trial sequential analyses of randomised clinical trials, and also include results of severe adverse events from large observational studies. Participants will be adult patients admitted to an ICU and treated with shorter vs. longer stored RBC units. We will systematically search the Cochrane Library, MEDLINE, Embase, BIOSIS, CINAHL and Science Citation Index for relevant literature, and we will follow the recommendation by the Cochrane Collaboration and the Preferred Reporting Items for Systemtic Review and Meta‐Analysis (PRISMA)‐statement. We will assess the risk of bias and random errors, and we will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the overall quality of evidence.ConclusionWe need a high‐quality systematic review to summarise the clinical consequences of RBC storage time among ICU patients.
Return of spontaneous circulation and long‐term survival according to feedback provided by automated external defibrillators
Authors: Agerskov M. , Hansen M. B. , Nielsen A. M. , Møller T. P. , Wissenberg M. , Rasmussen L. S. 
Published: September 2017

BackgroundWe aimed to investigate the effect of automated external defibrillator (AED) feedback mechanisms on survival in out‐of‐hospital cardiac arrest (OHCA) victims. In addition, we investigated converting rates in patients with shockable rhythms according to AED shock waveforms and energy levels.MethodsWe collected data on OHCA occurring between 2011 and 2014 in the Capital Region of Denmark where an AED was applied prior to ambulance arrival. Patient data were obtained from the Danish Cardiac Arrest Registry and medical records. AED data were retrieved from the Emergency Medical Dispatch Centre (EMDC) and information on feedback mechanisms, energy waveform and energy level was downloaded from the applied AEDs.ResultsA total of 196 OHCAs had an AED applied prior to ambulance arrival; 62 of these (32%) provided audio visual (AV) feedback while no feedback was provided in 134 (68%). We found no difference in return of spontaneous circulation (ROSC) at hospital arrival according to AV‐feedback; 34 (55%, 95% confidence interval (CI) [13–67]) vs. 72 (54%, 95% CI [45–62]), P = 1 (odds ratio (OR) 1.1, 95% CI [0.6–1.9]) or 30‐day survival; 24 (39%, 95% CI [28–51]) vs. 53 (40%, 95% CI [32–49]), P = 0.88 (OR 1.1 (95% CI [0.6–2.0])). Moreover, we found no difference in converting rates among patients with initial shockable rhythm receiving one or more shocks according to AED energy waveform and energy level.ConclusionsNo difference in survival after OHCA according to AED feedback mechanisms, nor any difference in converting rates according to AED waveform or energy levels was detected.
Sudden cardiac death in isolated right ventricular hypertrabeculation/noncompaction cardiomyopathy
Authors: Bekheit Soad , Karam Boutros , Daneshvar Farshid , Zaidan Julie , Tabet Rabih , Spagnola Jonathan , Lafferty James 
Published: September 2017

AbstractHypertrabeculation/noncompaction of the myocardium is a rare disorder that involves most commonly the left ventricle of the heart and it has been recognized as a distinct cardiomyopathy by the World Health Organization. However, it is extremely rare for this condition to involve exclusively the right ventricle. We report the cases of three patients who presented with ventricular tachyarrhythmia and sudden cardiac death. They were found to have isolated right ventricular hypertrabeculation/noncompaction on echocardiography. This supports the hypothesis that this condition is highly arrhythmogenic and is associated with high mortality similarly to the left ventricular hypertrabeculation/noncompaction cardiomyopathy.
Specificity of wide QRS complex tachycardia criteria and algorithms in patients with ventricular preexcitation
Authors: Jastrzębski Marek , Moskal Paweł , Kukla Piotr , Fijorek Kamil , Kisiel Roksana , Czarnecka Danuta 
Published: September 2017

BackgroundDespite substantial progress in the field of differentiation between ventricular tachycardia (VT) and supraventricular tachycardia (SVT) with wide QRS complexes, differentiation between VT and preexcited SVT remains largely unresolved due to significant overlap in QRS morphology. Our aim was to assess the specificities of various single ECG criteria and sets of criteria (Brugada algorithm, aVR algorithm, Steurer algorithm, and the VT score) for diagnosis of VT in a sizable cohort of patients with preexcitation.MethodsWe performed a retrospective study of consecutive accessory pathway ablation procedures to identify preexcited tachycardias. Among 670 accessory pathway ablation procedures, 329 cases with good quality ECG with either bona fide preexcited SVT (n = 30) or a surrogate preexcited SVT (fast paced atrial rhythm with full preexcitation, n = 299) were identified. ECGs were analyzed with the use of wide QRS complex algorithms/criteria to determine specificities of these methods.ResultsThe Steurer algorithm and VT score (≥3 points), with specificities of 97.6% and 96.1%, respectively, were significantly (p < .01) more specific for the diagnosis of VT than Brugada algorithm, aVR algorithm, and Pava criterion with specificities of 31%, 11.6%, and 57.1%, respectively. The first step of the Brugada algorithm and the first step of the aVR algorithm had also high specificities of 93.3% and 96.0%, respectively.ConclusionThere are sufficient electrocardiographical differences between VT and preexcited SVT to allow electrocardiographic differentiation. VT score, Steurer algorithm, and some single criteria do not overdiagnose VT in patients with preexcitation.
Total cosine R‐to‐T for predicting ventricular arrhythmic and mortality outcomes: A systematic review and meta‐analysis
Authors: Tse Gary , Gong Mengqi , Wong Cheuk Wai , Chan Cynthia , Georgopoulos Stamatis , Chan Yat Sun , Yan Bryan P. , Li Guangping , Whittaker Paula , Ciobanu Ana , Ali‐Hasan‐Al‐Saegh Sadeq , Wong Sunny H. , Wu William K. K. , Bazoukis George , Lampropoulos Konstantinos , Wong Wing Tak , Tse Lap Ah , Baranchuk Adrian M. , Letsas Konstantinos P. , Liu Tong ,   International Health Informatics Study (IHIS) Network
Published: September 2017

BackgroundThe total cosine R‐to‐T (TCRT), a vectorcardiographic marker reflecting the spatial difference between the depolarization and repolarization wavefronts, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD) in different clinical settings. However, its prognostic value has been controversial.ObjectiveThis systematic review and meta‐analysis evaluated the significance of TRCT in predicting arrhythmic and/or mortality endpoints.MethodsPubMed and Embase databases were searched through December 31, 2016.ResultsOf the 890 studies identified initially, 13 observational studies were included in our meta‐analysis. A total of 11,528 patients, mean age 47 years old, 72% male, were followed for 43 ± 6 months. Data from five studies demonstrated lower TCRT values in myocardial infarction patients with adverse events (syncope, ventricular arrhythmias, or sudden cardiac death) compared to those without these events (mean difference = −0.36 ± 0.05, p < .001; I2 = 48%). By contrast, only two studies analyzed outcomes in heart failure, and pooled meta‐analysis did not demonstrate significant difference in TCRT between event‐positive and event‐negative patients (mean difference = −0.01 ± 0.10, p > .05; I2 = 80%).ConclusionTCRT is lower in MI patients at high risk of adverse events when compared to those free from such events. It can provide additional risk stratification beyond the use of clinical parameters and traditional electrocardiogram markers. Its value in other diseases such as heart failure requires further studies.
Women's experiences of continuous fetal monitoring – a mixed‐methods systematic review
Authors: Crawford Alexandra , Hayes Dexter , Johnstone Edward D , Heazell Alexander E.P. 
Published: September 2017

AbstractIntroductionAntepartum stillbirth is often preceded by detectable signs of fetal compromise, including changes in fetal heart rate and movement. It is hypothesized that continuous fetal monitoring could detect these signs more accurately and objectively than current forms of fetal monitoring and allow for timely intervention. This systematic review aimed to explore available evidence on women's experiences of continuous fetal monitoring to investigate its acceptability before clinical implementation and to inform clinical studies.Material and methodsSystematic searching of four electronic databases (Embase, PsycINFO, MEDLINE and CINAHL), using key terms defined by initial scoping searches, identified a total of 35 studies. Following title and abstract screening by two independent researchers, five studies met the inclusion criteria. Studies were not excluded based on language, methodology or quality assessment. An integrative methodology was used to synthesize qualitative and quantitative data together.ResultsForms of continuous fetal monitoring used included Monica AN24 monitors (n = 4) and phonocardiography (n = 1). Four main themes were identified: practical limitations of the device, negative emotions, positive perceptions, and device implementation. Continuous fetal monitoring was reported to have high levels of participant satisfaction and was preferred by women to intermittent cardiotocography.ConclusionThis review suggests that continuous fetal monitoring is accepted by women. However, it has also highlighted both the paucity and heterogeneity of current studies and suggests that further research should be conducted into women's experiences of continuous fetal monitoring before such devices can be used clinically.
Review article: next‐generation transformative advances in the pathogenesis and management of autoimmune hepatitis
Authors: Czaja A. J. 
Published: September 2017

SummaryBackgroundAdvances in autoimmune hepatitis that transform current concepts of pathogenesis and management can be anticipated as products of ongoing investigations driven by unmet clinical needs and an evolving biotechnology.AimTo describe the advances that are likely to become transformative in autoimmune hepatitis, based on the direction of current investigations.MethodsPertinent abstracts were identified in PubMed by multiple search terms. Full‐length articles were selected for review, and a secondary bibliography was developed. The discovery process was repeated, and a tertiary bibliography was identified. The number of abstracts reviewed was 2830, and the number of full‐length articles reviewed exceeded 150.ResultsRisk‐laden allelic variants outside the major histocompatibility complex (rs3184504, r36000782) are being identified by genome‐wide association studies, and their gene products are potential therapeutic targets. Epigenetic changes associated with environmental cues can enhance the transcriptional activity of genes, and chromatin re‐structuring and antagonists of noncoding molecules of ribonucleic acid are feasible interventions. The intestinal microbiome is a discovery field for microbial products and activated immune cells that may translocate to the periphery and respond to manipulation. Epidemiological studies and controlled interview‐based surveys may implicate environmental and xenobiotic factors that warrant evidence‐based changes in lifestyle, and site‐directed molecular and cellular interventions promise to change the paradigm of treatment from one of blanket immunosuppression.ConclusionsAdvances in genetics, epigenetics, pathophysiology, epidemiology, and site‐directed molecular and cellular interventions constitute the next generation of transformative advances in autoimmune hepatitis.