bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early toll‐like receptor 4 blockade reduces ROS and inflammation triggered by microglial pro‐inflammatory phenotype in rodent and human brain ischaemia models
Authors: Parada Esther , Casas Ana I. , Palomino‐Antolin Alejandra , Gómez‐Rangel Vanessa , Rubio‐Navarro Alfonso , Farré‐Alins Victor , Narros‐Fernandez Paloma , Guerrero‐Hue Melania , Moreno Juan Antonio , Rosa Juliana M. , Roda José M. , Hernández‐García Borja J. , Egea Javier 
Published: May 2019

Background and PurposeIschaemic stroke is a leading cause of death, disability, and a high unmet medical need. Post‐reperfusion inflammation and an up‐regulation of toll‐like receptor 4 (TLR4), an upstream sensor of innate immunity, are associated with poor outcome in stroke patients. Here, we identified the therapeutic effect of targeting the LPS/TLR4 signal transduction pathway.Experimental ApproachWe tested the effect of the TLR4 inhibitor, eritoran (E5564) in different in vitro ischaemia‐related models: human organotypic cortex culture, rat organotypic hippocampal cultures, and primary mixed glia cultures. We explored the therapeutic window of E5564 in the transient middle cerebral artery occlusion model of cerebral ischaemia in mice.Key ResultsIn vivo, administration of E5564 1 and 4 hr post‐ischaemia reduced the expression of different pro‐inflammatory chemokines and cytokines, infarct volume, blood–brain barrier breakdown, and improved neuromotor function, an important clinically relevant outcome. In the human organotypic cortex culture, E5564 reduced the activation of microglia and ROS production evoked by LPS.Conclusion and ImplicationsTLR4 signalling has a causal role in the inflammation associated with a poor post‐stroke outcome. Importantly, its inhibition by eritoran (E5564) provides neuroprotection both in vitro and in vivo, including in human tissue, suggesting a promising new therapeutic approach for ischaemic stroke.
The detection of DNA methylation of tumour suppressor genes in cervical high‐grade squamous intraepithelial lesion: A prospective cytological‐histological correlation study of 70 cases
Authors: Ondič Ondrej , Němcová Jana , Alaghehbandan Reza , Černá Kateřina , Gomolčáková Barbora , Kinkorová‐Luňáčková Iva , Chytra Jan , Šidlová Henrieta , Májek Ondřej , Bouda Jiří 
Published: May 2019

AbstractBackgroundDNA methylation has been suggested as one of the epigenetic changes promoting carcinogenesis. The aim of this study was to prospectively evaluate the methylation status of CADM 1, MAL and hsa‐miR‐124 genes in high‐grade squamous intraepithelial lesion (HSIL) liquid‐based cytology (LBC) samples with a histological correlation.MethodsSeventy histologically confirmed cases of HSIL paired with prior screening LBC diagnosis of HSIL within a 3‐month interval were selected. Histologically, the lesions were reviewed and assessed including: (a) number of blocks harbouring dysplastic squamous epithelium; (b) number of blocks containing glandular extension of dysplastic epithelium; and (c) the depth of glandular extension (which was assessed semi‐quantitatively as graded 1‐3). Human papillomavirus (HPV) subtyping was performed from residual LBC materials using the LINEAR ARRAY HPV Genotyping Test and in‐house polymerase chain reaction targeting the HPV E1 gene. The detection of methylation silencing of tumour suppressor genes CADM1, MAL and hsa‐miR‐124 was performed by multiplex methylation‐specific real‐time polymerase chain reaction.ResultsA positive methylation status was detected in 41 cases (58.6%). The number of blocks with HSIL varied from one to 13. Glandular extension was seen in 44 cases with the number of blocks involved ranging from one to 10. The depth of HSIL glandular extension varied.ConclusionThe DNA methylation test allows HSIL lesions to be divided into two distinct groups of methylated HSIL in significantly older patients and unmethylated HSIL in younger patients. This study was not able to prove that methylation status in cervical HSIL correlates with the size of the lesion (measured by the number of blocks involved) or with HSIL propensity for endocervical glandular extension, nor with HPV type or multi‐infection.
Communication in Angelman syndrome: a scoping review
Authors: Pearson Effie , Wilde Lucy , Heald Mary , Royston Rachel , Oliver Chris 
Published: May 2019

AimA scoping review was conducted to examine and evaluate empirical data on the communication profile of Angelman syndrome beyond the described dissociation between receptive language and speech.MethodThree databases (PsycINFO, Embase, and Web of Science) were searched to retrieve articles investigating communication in Angelman syndrome. Seventeen articles investigating the broader communication profile were found; their methodology was evaluated against quality criteria.ResultsDespite the absence of speech, individuals with Angelman syndrome have a wide repertoire of non‐verbal communicative behaviours, mainly characterized by gestures, although advanced forms such as symbolic communication are used by some individuals. The use of communicative forms differs between the genetic aetiologies of Angelman syndrome; individuals with non‐deletion aetiologies typically have greater communicative abilities.InterpretationThe broader communication profile of Angelman syndrome is characterized by diverse and multimodal abilities, including some use of symbolic forms of communication that appears atypical given the absence of speech. This is suggestive of a probable dissociation between speech and other expressive forms of communication, indicating an isolated speech production impairment. This highlights a need in this population for alternative communication and specific input from services tailored to support the nuances of the communication profile of Angelman syndrome.What this paper adds

Although absent speech is near universal, a diverse profile of other communicative abilities has been reported.

Parental reporting has been predominantly used to assess the communication profile of Angelman syndrome.

Literature that investigates the specificities and possible dissociations in such a communication profile is limited.
Autonomy, Cognitive Offloading, and Education
Authors: Carter J. Adam 
Published: May 2019

AbstractIf we want our intellectual lives to go as well as possible, should we be “delegating” as many information‐gobbling tasks to our gadgets as we can? If not, then how much cognitive outsourcing is too much and, relatedly, what kinds of considerations are relevant to determining this? In this article, J. Adam Carter submits that one particular dimension of intellectual flourishing that will be helpful for the purpose of exploring such questions is that of intellectual autonomy, in particular what he describes as the value of one's freedom to achieve. Several related conclusions are drawn and then applied to recent discussions in the philosophy of education concerning education's epistemic aims.
Might Knowledge Be Insertable?
Authors: Tillson John 
Published: May 2019

AbstractCan we coherently conceive of our having knowledge inserted into our minds, bypassing forms of knowledge acquisition hitherto relied on? In this article, John Tillson contends that there is value in giving serious consideration to this question. First, insofar as technology develops apace, it is wise to start thinking about how we would use it before its uses are available to us lest we should unreflectively abuse it. Second, even though having knowledge inserted might turn out to be physically impossible, its metaphysical possibility would still make reflecting on its desirability fruitful, since evaluating this will help us to better understand what it is that we value about education and about knowledge. While handling practical knowledge and theoretical knowledge (or “knowledge how” and “knowledge that”) somewhat separately, Tillson argues that, for each, insertion is conceivable. He contends that if (a) we seem to be able to imagine inserting knowledge, (b) our seeming to be able to imagine it survives extended critical reflection, and (c) we can elaborate what it would consist of with plausible detail, then we have defeasible reason for thinking that inserting knowledge is in fact metaphysically possible. In the first section, Tillson begins by motivating the question, next briefly considers an imaginary scenario presented in the film The Matrix as an example of what is meant by implanting or inserting knowledge, and then fleshes out the scenario with some more plausible details to help make the case for its coherent conceivability. In the second section, he discusses five objections to the thesis, so as to subject the case to extended critical reflection. These include arguments that inserting knowledge requires inserting justification, but that justification cannot be inserted; that the possibility of inserting false beliefs undermines the possibility of self‐trust, which is crucial to knowledge; that inserted content has the wrong causal history to count as knowledge; and that inserted knowledge would lack the appropriate connections to other mental items in order to count as knowledge. Upon answering each of these objections, Tillson concludes that the notion of knowledge insertion as coherently conceivable can survive extended critical reflection.
Cheating Education and the Insertion of Knowledge
Authors: Aldridge David 
Published: May 2019

AbstractThis article by David Aldridge concerns the promise of knowledge “insertion.” The promise can be elucidated as follows: knowledge could be inserted by a less time‐consuming (and possibly in many senses less expensive) technological process than traditional learning, whereby, for example, some relatively swift procedure of implanting or more radically transforming the structure of the brain could save its subject the trouble of spending several years studying for a university degree. Such a promise, if coherent and realizable, would certainly count as an instance of “cheating education” in that it would appear to circumvent or evade the learning process. Here, Aldridge develops a phenomenological account of knowing that emphasizes a background of practical understanding, which he then contrasts with an account of knowing as the possession of an internal representation that he understands as underpinning claims for the promise of knowledge insertion. The incoherence of “knowledge insertion” is not, however, the end of the story, according to Aldridge. He closes by exploring how a flawed concept of “information insertion” already pervades contemporary educational thinking and practice. It is not, that is to say, merely an impossible science fiction dream, but an example of how technological modes of thought do indeed threaten to “cheat” education — not by helping us to “cheat” in our learning, but by cheating us of an experience that might properly be called educational.
Incentive effect of joint and several liability in fishery cooperatives on regulatory compliance
Authors: Bellanger Manuel , Holland Daniel S. , Anderson Christopher M. , Guyader Olivier 
Published: May 2019

AbstractCooperative‐based catch share systems can be implemented such that the members of the same fishery cooperative are jointly and severally liable for not exceeding collectively assigned fishing rights. In practice, this means that a regulator can take away catch privileges from an entire cooperative that overruns its collective quota, effectively creating a penalty much larger than what could be recovered with an individual fine. Fishery cooperatives then typically implement their own internal compliance regime that includes monitoring and penalties. This article first reviews compliance practice in cooperative‐based catch share systems by examining the commonalities and differences in the way compliance regimes are structured (observation and reporting requirements, penalty scheme, internal enforcement authority and indemnification mechanisms) in a number of internal agreements from fishery cooperatives in North America and in Europe. Based on our review of cooperatives and the literature on compliance, we discuss how incentives to comply may be different for an individual fisherman operating in a fishery cooperative where joint and several liability applies as compared to an individual fishing quota baseline situation without fishery cooperative. Our review suggests that, from the regulators’ point of view, joint and several liability can increase the level of compliance for a given enforcement expenditure. However, the regulator cannot rely solely on cooperatives to carry out controls and must ensure that the cooperatives themselves have an interest in setting up an effective monitoring system and will enforce sanctions within the cooperative.
Effects of historic and projected climate change on the range and impacts of an emerging wildlife disease
Authors: Price Stephen J. , Leung William T. M. , Owen Christopher J. , Puschendorf Robert , Sergeant Chris , Cunningham Andrew A. , Balloux Francois , Garner Trenton W. J. , Nichols Richard A. 
Published: May 2019

AbstractThe global trend of increasing environmental temperatures is often predicted to result in more severe disease epidemics. However, unambiguous evidence that temperature is a driver of epidemics is largely lacking, because it is demanding to demonstrate its role among the complex interactions between hosts, pathogens, and their shared environment. Here, we apply a three‐pronged approach to understand the effects of temperature on ranavirus epidemics in UK common frogs, combining in vitro, in vivo, and field studies. Each approach suggests that higher temperatures drive increasing severity of epidemics. In wild populations, ranavirosis incidents were more frequent and more severe at higher temperatures, and their frequency increased through a period of historic warming in the 1990s. Laboratory experiments using cell culture and whole animal models showed that higher temperature increased ranavirus propagation, disease incidence, and mortality rate. These results, combined with climate projections, predict severe ranavirosis outbreaks will occur over wider areas and an extended season, possibly affecting larval recruitment. Since ranaviruses affect a variety of ectothermic hosts (amphibians, reptiles, and fish), wider ecological damage could occur. Our three complementary lines of evidence present a clear case for direct environmental modulation of these epidemics and suggest management options to protect species from disease.
Citizen perspectives on the use of publicly reported primary care performance information: Results from citizen‐patient dialogues in three Canadian provinces
Authors: Johnston Sharon , Abelson Julia , Wong Sabrina T. , Langton Julia , Hogel Mathew , Burge Fred , Hogg William 
Published: May 2019

AbstractObjectivePerformance measurement and reporting is proliferating in all sectors of the healthcare system, including primary care, despite a dearth of evidence on how the public uses reports on primary care performance. We explored how the public might use this information, to guide the development of effective reporting systems for primary care.MethodsWe conducted six full‐day deliberative dialogue sessions with a purposive sample of 56 citizen‐patients across three Canadian provinces (British Columbia, Ontario and Nova Scotia). Participants identified how they would use publicly reported performance data. We conducted a thematic analysis of the data by region.ResultsCommon uses for primary care performance information emerged across all sessions. Participants most often discussed the utility of this information for community advocacy and participation in health system decision making. Similar barriers for using performance information to choose a primary care provider were identified in each region including the perceived lack of choice of providers and the high value placed on relationships with current providers. Finally, the value of public performance reporting in enhancing trust that people would receive good care was also a common theme.ConclusionsCitizen‐patient perspectives highlight that public reporting on primary care performance could promote the health system's responsiveness by enabling public engagement in decision making at the community level. The role of public reporting in promoting trust rather than empowering patient choice may reflect unique elements of the Canadian health system's context.
The impact of motivational interviewing on communication of patients undergoing periodontal therapy
Authors: Kitzmann Julia , Ratka‐Krueger Petra , Vach Kirstin , Woelber Johan P. 
Published: May 2019

AbstractAimThere has been growing interest in motivational interviewing (MI) as a structured method for supporting health behaviour change in periodontal therapy. The aim of this study was to investigate the influence of communication techniques used in MI on statements of patients undergoing periodontal therapy.Materials and MethodsThirty audio‐recorded sessions between dental MI providers and their patients undergoing periodontal therapy were coded using the German version of the Motivational Interviewing Sequential Code for Observing Process Exchanges (MISCOPE; D). Sequential analyses were performed to access transition probabilities among certain counsellor and patient statements.ResultsMI‐consistent counsellor statements were statistically significantly positive correlated with patients’ language in favour of change (change talk) (OR = 1.31; p = 0.027). MI‐inconsistent statements were statistically significantly more likely to be followed by patients’ language against change (sustain talk) (OR = 2.27, p = 0.002). An additional sequential analysis revealed significant correlations between certain evocative counsellor behaviours and the language of their patients.ConclusionSpecific verbal expressions described in the theory of MI significantly influence the subsequent statements of the patient in periodontal therapy. Accordingly, the periodontist can guide patient communication in a desired direction, evoke motivational statements and reduce expressions of resistance.
Distribution, body size and biology of the megamouth shark Megachasma pelagios
Authors: Watanabe Yuuki Y. , Papastamatiou Yannis P. 
Published: May 2019

AbstractWe compiled historical reports of megamouth sharks Megachasma pelagios (mostly fishery by‐catch and strandings) from 1976 to 2018 (n = 117) and found that they are distributed globally (highest latitude, 36°) with three hotspots: Japan, Taiwan and the Philippines. Despite possible biases due to variability in fishing effort, more individuals were reported at higher latitudes in the summer, suggesting seasonal, latitudinal migrations. Sex ratios were female‐biased in Japan, but more even in Taiwan and the Philippines, suggesting some sexual segregation. Females (total length, LT = 3.41–7.10 m) were larger than males (LT = 1.77–5.39 m) and matured at a larger LT (5.17 m) than males (4.26 m). Also, we reviewed the systematics, feeding ecology and swimming behaviour of Megachasma pelagios based on the literature. Our review shows that, compared with their morphology, anatomy and genetics, behavioural ecology of this species remains largely unknown and electronic tagging studies are warranted.
Transcriptional response of USP18 predicts treatment outcomes of interferon‐alpha in HBeAg‐positive chronic hepatitis B patientsefere
Authors: Liu Wei , Liang Huiqing , Wang Shaojuan , Wu Chuncheng , Liu Yang , Liu Yongliang , Zhang Manying , Xiong Lixia , Zhong Zhouyue , Chen Yue , Mao Qianguo , Ge Shengxiang , Xia Ningshao 
Published: May 2019

AbstractUbiquitin‐specific protease 18 (USP18) is an important inhibitor of interferon (IFN) antiviral activity, and the aim of this study was to investigate the association between the USP18 mRNA level change in peripheral blood mononuclear cells (PBMCs) when stimulated with IFN in vitro before initiating treatment and the treatment outcomes in HBeAg‐positive chronic hepatitis B (CHB) patients treated with IFN. A total of 44 patients who received standard IFN‐based anti‐HBV therapy and follow‐up were enrolled in the study. The in vitro IFN‐induced USP18 mRNA change (USP18IFN‐N) was measured via comparison of quantitative PCR‐determined USP18 transcription levels of BPMCs cultured with and without IFN stimulation. Either for virological (VR) or serological response (SR), the baseline USP18IFN‐N was significantly higher (P = 0.018 for VR, P = 0.008 for SR) among nonresponders (n = 23 for VR, n = 33 for SR) than that of responders (n = 21 for VR, n = 11 for SR). Multivariate analyses revealed baseline USP18IFN‐N was a novel independent predictor for either VR (OR = 0.292, 95% CI = 0.102‐0.835, P = 0.022) or SR (OR = 0.173, 95% CI = 0.035‐0.849, P = 0.031) in our cohort. In addition, baseline USP18IFN‐N in combination with HBV DNA loads or HBeAg levels showed improved accuracy of pretreatment prediction for VR or SR responders, respectively. Baseline USP18IFN‐N levels are associated with both virological and serological response, and have the potential to become a clinical predictor for treatment outcomes in HBeAg‐positive CHB patients before initiating IFN‐α therapy.
A systematic review of supervisory relationships in general practitioner training
Authors: Jackson Dawn , Davison Ian , Adams Rachel , Edordu Adaeze , Picton Aled 
Published: May 2019

ObjectivesThe educational alliance is argued to be at the heart of supervision in medical education. This review aims to map the research field and develop a conceptualisation of the nature of such educational alliances within postgraduate supervision for general practitioners.MethodsAn integrative review of the international literature on supervision from 2011 to 2018 was undertaken, and papers assessed for relevance and quality. Data analysis incorporated framework analysis techniques. Bordin's working alliance‐based model of supervision was used as a springboard for synthesis, as well as allowing for the emergence of new ideas, theories and concepts from the literature.ResultsA total of 49 full texts were included for analysis. There was evidence of the importance of trust, agreement and bond in accordance with Bordin's model. The results also highlighted the importance of greater clarity on supervisory goals, and the tasks to support these goals, to effectively address competing priorities and roles within supervision. Non‐hierarchical relationships were advocated, although supervisors must remain impartial in their assessment and monitoring roles. The influence of the wider practice community and situated learning through legitimate peripheral participation are documented. A model of General practice (GP) supervision is proposed that integrates the findings.ConclusionsGP supervision requires a greater emphasis than is suggested by the working alliance model, both on the clarity of expectations and the appreciation of the multiple roles and competing priorities of both trainee and supervisor. Furthermore, as GP supervision develops within the rising workload of contemporary general practice, the role of the wider community of practice may become more prominent. We have adapted the working alliance model for postgraduate General practice (GP) supervision, emphasising the explicit sharing of expectations relating to goals, tasks and roles to facilitate negotiation and agreement.