bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and follow‐up of postmarketing studies of conditionally authorized medicines in the EU
Authors: Hoekman Jarno , Klamer Thea T. , Mantel‐Teeuwisse Aukje K. , Leufkens Hubert G. M. , De Bruin Marie L. 
Published: March 2016

AimThe aim of the present study was to provide an insight into the characteristics and follow‐up of postmarketing studies of medicines that were conditionally authorized in the European Union (EU).MethodsWe compiled a list of all postmarketing studies attached as specific obligations to the licence of medicines that were granted conditional marketing authorization from January 2006 to April 2014. Studies were characterized based on their objective, design, status upon marketing authorization (MA) and due data set by authorities. They were linked to online study registrations (Clinicaltrials.gov, ENCePP) to determine completion date. We described and associated characteristics of studies and medicines, and determined whether studies were completed on time.ResultsA total of 59 postmarketing studies were requested for 21 conditionally authorized medicines. Most studies had an interventional study design (73%), were ongoing upon MA (61%) and aimed to provide additional data on efficacy (45%). Interventional studies were more often ongoing and providing efficacy data, while observational and other studies were more often new and providing safety data. Frequent grounds for requesting postmarketing studies were ‘long‐term follow‐up’ and ‘increase data on subpopulations’. Of the 34 studies eligible for follow‐up analysis, 26 (76%) were completed and 17 (50%) completed on time. Actual completion time took a median (interquartile range) of 274 (−121 to 556) days longer than expected.ConclusionsOur results indicated that most postmarketing studies attached to a conditional marketing authorization were eventually completed but that half were completed with a substantial delay. The observations suggest caution when broadening the use of postmarketing studies for resolving uncertainties about benefits and risks after MA.
Unintentional Pharmaceutical‐Related Medication Errors Caused by Laypersons Reported to the Toxicological Information Centre in the Czech Republic
Authors: Urban Michal , Leššo Roman , Pelclová Daniela 
Published: March 2016

AbstractThe purpose of the article was to study unintentional pharmaceutical‐related poisonings committed by laypersons that were reported to the Toxicological Information Centre in the Czech Republic. Identifying frequency, sources, reasons and consequences of the medication errors in laypersons could help to reduce the overall rate of medication errors. Records of medication error enquiries from 2013 to 2014 were extracted from the electronic database, and the following variables were reviewed: drug class, dosage form, dose, age of the subject, cause of the error, time interval from ingestion to the call, symptoms, prognosis at the time of the call and first aid recommended. Of the calls, 1354 met the inclusion criteria. Among them, central nervous system‐affecting drugs (23.6%), respiratory drugs (18.5%) and alimentary drugs (16.2%) were the most common drug classes involved in the medication errors. The highest proportion of the patients was in the youngest age subgroup 0–5 year‐old (46%). The reasons for the medication errors involved the leaflet misinterpretation and mistaken dose (53.6%), mixing up medications (19.2%), attempting to reduce pain with repeated doses (6.4%), erroneous routes of administration (2.2%), psychiatric/elderly patients (2.7%), others (9.0%) or unknown (6.9%). A high proportion of children among the patients may be due to the fact that children's dosages for many drugs vary by their weight, and more medications come in a variety of concentrations. Most overdoses could be prevented by safer labelling, proper cap closure systems for liquid products and medication reconciliation by both physicians and pharmacists.
Integrating socio‐cultural contexts and location‐based systems for ubiquitous language learning in museums: A state of the art review of 2009–2014
Authors: Wang Hong‐You , Liu Gi‐Zen , Hwang Gwo‐Jen 
Published: March 2016

AbstractContext‐dependent learning systems are now becoming more common in museums, as most students are equipped with mobile devices. As there has been little research into context‐aware mobile applications in museums, the present study aims to investigate ubiquitous language learning in socio‐cultural contexts, as well as recent trends in using location‐based systems. Therefore, the following three issues are reviewed in related articles published between 2009 and 2014: system usefulness, activity usefulness and activity playfulness in museum learning. The researchers used keywords to search for relevant articles from the ISI (Institute for Scientific Information) Web of Science and other databases. The abstracts and content of the searched articles were then analyzed. The results show that the location‐aware features (GPS or Google App‐based) embedded in mobile phones, adaptive language learning and socio‐cultural interaction in museums are intertwined in the literature. The literature also shows that in recent years students have transformed from being passive receivers to active learners. Specifically, students tended to rely on system guidance in 2009–2011, and activities were more focused on individual learning with less real‐life social interaction, and this thus reduced the level of playfulness. An important finding in the literature from 2012 to 14 is that many museums adopted ubiquitous location‐based systems using mobile devices, which help to strengthen social ties when students work collaboratively to perform language learning activities. This has also allowed museums to evolve from mobile‐learning to ubiquitous‐learning environments, in various socio‐cultural contexts. The results of this review study have implications for language teachers and museum educators, to help them implement appropriate ubiquitous learning systems in various socio‐cultural contexts.
Introducing electronic textbooks as daily‐use technology in schools: A top‐down adoption process
Authors: Chiu Thomas K. F. 
Published: March 2016

AbstractThis study took frequency of use and the adoption process into account to define the participants and external variables of the research model. School electronic textbooks are a daily‐use technology and they are adopted in a compulsory, top‐down way. Their introduction can evoke feelings of anxiety among teachers because of a possible increase in workload. This compulsory adoption process contrasts with that for most other technologies, which are voluntary and less disruptive. In a school context, instructional designs of electronic textbooks that help explain user acceptance are sufficient in a bottom‐up, but not a top‐down, approach. To address this, individual, organizational, and social factors were included in our research model. A survey questionnaire to collect data from 306 in‐service teachers from eight secondary schools was used. The results showed that anxiety and positive attitude were the main barrier and catalyst, respectively, to the acceptance of such technology. One suggestion for researchers and two suggestions for school leaders on the adoption process were made.
Interaction pattern analysis in cMOOCs based on the connectivist interaction and engagement framework
Authors: Wang Zhijun , Anderson Terry , Chen Li , Barbera Elena 
Published: March 2016

AbstractConnectivist learning is interaction‐centered learning. A framework describing interaction and cognitive engagement in connectivist learning was constructed using logical reasoning techniques. The framework and analysis was designed to help researchers and learning designers understand and adapt the characteristics and principles of interaction in connectivist learning contexts. In this study empirical evidence to support and further develop this framework is presented. This study analyzed 6 weeks of data harvested from the daily newsletter, Twitter, and a Facebook group in a well‐known cMOOC led by George Siemens and Stephen Downes. These text transcripts were analyzed using a deductive approach of qualitative content analysis. This study revealed the main activity patterns of participants as they engage in four levels of interaction (operation interaction, wayfinding interaction, sensemaking interaction, and innovation interaction) during the MOOC. Generally the framework serves as a conceptual model to understand and to analyze the interaction in this cMOOC, although some implied interaction is hard to recognize and categorize. The relationship of the four levels of interaction and the role of each element in the framework were explored with the intent of offering the framework as a conceptual and analytic tool to guide both researchers and practitioners in designing and studying connectivist learning.
Design possibilities for the e‐Schoolbag: Addressing the 1:1 challenge within China
Authors: Gu Xiaoqing , Xu Xiaojuan , Wang Huawen , Crook Charles 
Published: March 2016

AbstractThere is widespread enthusiasm for 1:1 computing in education. Recognizing that secure innovation of educational practice should be built upon contextual sensitivity, this article reported two case studies anticipating the potential development of 1:1 classes in the particular cultural context of China. The first case described how the new technology of e‐Textbooks could align with a tradition where the textbook is central to teaching practice. A science teacher used the e‐Textbook to design his pedagogy to accommodate the contextual learning needs of the classroom. Students reported a positive reaction. They understood that new learning possibilities were crafted through this engagement with diversified media formats that content fitted their class, and this gave them increased confidence in relation to both student–computer and interpersonal interaction. The second case study described how a social app could align with the local tradition of practice whereby a student's performance in front of class is an important part of instructional practice. In this case, students who were learning native Chinese were offered the opportunity for performing within a novel “digital stage”: revealing high levels of engagement and a strengthening confidence with language performance.
The effect of the flipped classroom approach to OpenCourseWare instruction on students’ self‐regulation
Authors: Sun Jerry Chih‐Yuan , Wu Yu‐Ting , Lee Wei‐I 
Published: March 2016

AbstractThe purpose of this study was to investigate the effect of the flipped classroom approach to OpenCourseWare instruction on students’ self‐regulation. OpenCourseWare was integrated into the flipped classroom model (experimental group) and distance learning (control group). Overall, 181 freshmen taking a physics course were allowed to choose their own class based on their preferred teaching method (experimental or control group). The findings indicated that there was no significant between‐group difference in terms of self‐regulation. However, when comparing the means for the six categories of self‐regulation, the results showed that the experimental group learners had significantly higher scores for the category of help‐seeking. The use of the flipped classroom model created a learning environment which prompted its learners to proactively seek external help. These learners were more aware of their need for external help in their studies and were able to identify the person/people who could solve their academic problems, while they were able to find the appropriate means to do so and actually obtain help. The results of this study can serve as a reference for future studies on the flipped classroom model and OpenCourseWare, as well as for teachers and researchers in related fields.
Single versus tandem high‐dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long‐term results from the phase III GMMG‐HD2 trial
Authors: Mai Elias K. , Benner Axel , Bertsch Uta , Brossart Peter , Hänel Annette , Kunzmann Volker , Naumann Ralph , Neben Kai , Egerer Gerlinde , Ho Anthony D. , Hillengass Jens , Raab Marc S. , Neubauer Andreas , Peyn Astrid , Ko Yon‐Dschun , Peter Norma , Scheid Christof , Goldschmidt Hartmut 
Published: March 2016

SummaryThe prospective, randomized phase III trial GMMG‐HD2 aimed at demonstrating non‐inferiority of single (Arm A) versus tandem (Arm B) high‐dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2‐year event‐free survival (EFS) in newly‐diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention‐to‐treat population, (ITT), single/tandem HDM/ASCT: n = 177/181].After a median follow‐up of more than 11 years, non‐inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non‐inferiority threshold of 15% of the 2‐year EFS rate. Neither EFS (P = 0·53) nor overall survival (OS) (P = 0·33) differences were observed in the ITT population. In the tandem arm, 26% (n = 47/181) of patients refused a second HDM/ASCT due to non‐medical reasons. A per‐protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n = 156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n = 22/181), did not yield differences in EFS (P = 0·61) or OS (P = 0·16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P = 0·04). Ten‐year OS for the entire ITT was 34% (95% confidence interval: 29–40%). OS after first relapse was significantly shortened in the tandem arm (P = 0·04). In this study single HDM/ASCT was non‐inferior to tandem HDM/ASCT in MM.
Current status and future directions of T‐lymphoblastic lymphoma in children and adolescents
Authors: Burkhardt Birgit , Mueller Stephanie , Khanam Tasneem , Perkins Sherrie L. 
Published: March 2016

SummaryThe main challenges in the treatment of T‐cell lymphoblastic lymphoma (T‐LBL) in children and adolescents are twofold: to increase survival rates in concert with reduction of acute and long‐term toxicities including the rate of secondary malignancies. The need for molecular and prognostic markers in T‐LBL is crucial to allow for systematic treatment optimization and may serve as targets for new treatment approaches.
Mature T‐ and NK‐cell non‐Hodgkin lymphoma in children and young adolescents
Authors: Pillai Vinodh , Tallarico Michael , Bishop Michael R. , Lim Megan S. 
Published: March 2016

SummaryMature T/Natural killer (NK)‐cell neoplasms of children and the young adolescent population exhibit higher prevalence in Central and South American and Asian populations and many are associated with Epstein‐Barr virus (EBV). They are represented in large part by extranodal T/NK cell lymphomas‐ nasal‐type or extra nasal‐type, chronic lymphoproliferative disorders of T/NK cells or chronic active EBV disease, systemic EBV‐positive lymphoproliferative disorders of childhood, hydroa vacciniforme‐like lymphoma, hepatosplenic T‐cell lymphoma and primary cutaneous gamma/delta T‐cell lymphoma among others. Many T/NK cell neoplasms in this age group are derived from cells of the innate immune system, in contrast to adults where they are predominantly from the adaptive immune system. The genetic basis of T/NK cell lymphomas in children and young adolescents remains largely unknown. Anthracycline‐based regimens and haematopoietic stem cell transplants (allogeneic and autologous) are current treatment modalities, however it is anticipated that novel targeted therapeutic agents will be available in the near future.
Investigating peer attitudes towards the use of key word signing by children with Down syndrome in mainstream schools
Authors: Bowles Caoimhe , Frizelle Pauline 
Published: March 2016

Accessible Summary

This research looked at young children's attitudes towards the use of a signing system by children with Down syndrome, in mainstream school.

These attitudes can help to reveal factors which support the successful use of signing as well as those that make it difficult to use signs effectively in a mainstream setting.

The results show that although children expressed a number of difficulties in relation to signing, overall they have a positive attitude towards signing on which we should capitalise, to enhance the communicative experiences of both the children with Down syndrome and their peers in mainstream school.

AbstractBackground: Lámh is a key word signing approach used in Ireland, which can support the communication needs of children with Down syndrome. However, the success of this approach in mainstream schools relies heavily on the attitudes of those within the school environment. To date, two studies have explored the attitudes of teaching staff towards the use of keyword signing in schools; however, no previous research has investigated peer attitudes towards this method of communication. This study aimed to explore the attitudes of peers towards the use of Lámh by children with Down syndrome in mainstream schools.Materials and Methods: The study was qualitative, using interpretative phenomenological analysis procedures to analyse eight interviews with children, ranging in age from 6 to 8 years.Results and Conclusion: Overall, mainstream school peers demonstrated an understanding and an appreciation of the use of key word signing. However, the success of this approach within the school was limited by a number of challenges evinced by the school peers, including making the signs accurately and remembering their meanings. Given the important interactive role of the peers of a child with Down syndrome in a mainstream school setting, these challenges need to be addressed to optimise the use of key word signing and increase the likelihood of successful communication between children with Down syndrome and their peers.
New insights into the yin and yang of the endocannabinoid system in health and disease
Authors: Wainwright Cherry L 
Published: March 2016

Linked ArticlesThis article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.
Effects of glucagon‐like peptide‐1 on the differentiation and metabolism of human adipocytes
Authors: El Bekay Rajaa , Coín‐Aragüez Leticia , Fernández‐García Diego , Oliva‐Olivera Wilfredo , Bernal‐López Rosa , Clemente‐Postigo Mercedes , Delgado‐Lista Javier , Diaz‐Ruiz Alberto , Guzman‐Ruiz Rocío , Vázquez‐Martínez Rafael , Lhamyani Said , Roca‐Rodríguez María Mar , Veledo Sonia Fernandez , Vendrell Joan , Malagón María M. , Tinahones Francisco José 
Published: March 2016

Background and PurposeGlucagon‐like peptide‐1 (GLP‐1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP‐1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up‐regulated in AT of insulin‐resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP‐1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects.Experimental ApproachWe analysed the effects of GLP‐1 on human AT and isolated adipocytes in vitro and the effects of GLP‐1 mimetics on AT of morbidly obese T2D subjects in vivo.Key ResultsGLP‐1 down‐regulated the expression of lipogenic genes when administered during in vitro differentiation of human adipocytes from morbidly obese patients. GLP‐1 also decreased the expression of adipogenic/lipogenic genes in AT explants and mature adipocytes, while increasing that of lipolytic markers and adiponectin. In 3T3‐L1 adipocytes, GLP‐1 decreased free cytosolic Ca2+ concentration ([Ca2+]i). GLP‐1‐induced responses were only partially blocked by GLP‐1 receptor antagonist exendin (9–39). Moreover, administration of exenatide or liraglutide reduced adipogenic and inflammatory marker mRNA in AT of T2D obese subjects.Conclusions and ImplicationsOur data suggest that the beneficial effects of GLP‐1 are associated with changes in the adipogenic potential and ability of AT to expand, via activation of the canonical GLP‐1 receptor and an additional, as yet unknown, receptor.
Sputum interleukin‐13 as a biomarker for the evaluation of asthma control
Authors: Tsilogianni Z. , Hillas G. , Bakakos P. , Aggelakis L. , Konstantellou E. , Papaioannou A. I. , Papaporfyriou A. , Papiris S. , Koulouris N. , Loukides S. , Kostikas K. 
Published: March 2016

SummaryBackgroundAsthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin‐13 (IL‐13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control.ObjectiveTo assess the diagnostic performance of sputum IL‐13 for the evaluation of asthma control and furthermore to investigate the performance of sputum eosinophils and FeNO.MethodsOne hundred and seventy patients with asthma were studied. All subjects underwent assessment of asthma control by asthma control test (ACT), lung function tests, FeNO measurement and sputum induction for cell count identification and IL‐13 measurement in supernatants.ResultsIL‐13 (pg/mL) levels in sputum supernatant differed significantly among patients with well‐controlled asthma and those with not well‐controlled asthma [median IQR 78 (66–102) vs. 213 (180–265), P < 0.001]. Receiver operating characteristic (ROC) analysis showed that, for the whole study population, the diagnostic performance of IL‐13 was superior to both sputum eosinophils and FeNO levels [area under the curve (AUC) 0.92, 95% CI 0.87 to 0.95 vs. AUC 0.65, 95% CI 0.58 to 0.72 vs. AUC 0.65, 95% CI 0.55 to 0.72, respectively].ConclusionThe diagnostic performance of sputum IL‐13 was superior to both sputum eosinophils and FeNO levels for the identification of well‐controlled asthma. Sputum IL‐13 levels could serve as a useful biomarker for asthma control assessment.
The differential effects of 1,25-dihydroxyvitamin D3 on Salmonella-induced interleukin-8 and human beta-defensin-2 in intestinal epithelial cells
Authors: Huang F-C 
Published: March 2016

Summary
Salmonellosis or Salmonella, one of the most common food-borne diseases, remains a major public health problem worldwide. Intestinal epithelial cells (IECs) play an essential role in the mucosal innate immunity of the host to defend against the invasion of Salmonella by interleukin (IL)−8 and human β-defensin-2 (hBD-2). Accumulated research has unravelled important roles of vitamin D in the regulation of innate immunity. Therefore, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25D3) on Salmonella-induced innate immunity in IECs. We demonstrate that pretreatment of 1,25D3 results in suppression of Salmonella-induced IL-8 but enhancement of hBD-2, either protein secretion and mRNA expression, in IECs. Furthermore, 1,25D3 enhanced Salmonella-induced membranous recruitment of nucleotide oligomerization domain (NOD2) and its mRNA expression and activation of protein kinase B (Akt), a downstream effector of phosphoinositide 3-kinase (PI3K). Inhibition of the PI3K/Akt signal counteracted the suppressive effect of 1,25D3 on Salmonella-induced IL-8 expression, while knock-down of NOD2 by siRNA diminished the enhanced hBD-2 expression. These data suggest differential regulation of 1,25D3 on Salmonella-induced IL-8 and hBD-2 expression in IECs via PI3K/Akt signal and NOD2 protein expression, respectively. Active vitamin D-enhanced anti-microbial peptide in Salmonella-infected IECs protected the host against infection, while modulation of proinflammatory responses by active vitamin D prevented the host from the detrimental effects of overwhelming inflammation. Thus, active vitamin D-induced innate immunity in IECs enhances the host's protective mechanism, which may provide an alternative therapy for invasive Salmonella infection.