bluuebunny/crossref_metadata_2025_split huggingface dataset:
How new technology is addressed by researchers in Educational Studies: Approaches from high‐performing universities in China and the UK
Authors: Crook Charles , Gu Xiaoqing 
Published: February 2019

AbstractThere is a crisis of expectation in relation to educational technology. This is sometimes interpreted as a failure of academic researchers to disseminate their work to educational practitioners. However, another interpretation dwells on the lack of vision characterising such research. Because teachers often encounter research most intensely during their own pre‐service and in‐service education, we review academic research here through a snapshot of output from 10 leading university Education departments sampled in the UK and China. Empirical papers with a central interest in new technology were scarce, representing only around 10% of the sample. Research was strongly situated in “classroom” contexts, although, as critics have suggested, with limited attention to the wider ecology of those places, and with teachers being the focal interest as much as students. A “learning outcomes” research orientation was less common than an interest in process and practice. Although this was approached with different methodologies in China and the UK. Discussion addresses the challenge of effective and authoritative dissemination and those constraints from the political economy of research practice.
Difficulty and self‐efficacy: An exploratory study
Authors: Power Jason , Lynch Raymond , McGarr Oliver 
Published: February 2019

AbstractSerious games are becoming increasingly popular due to their association with increased learning outcomes when compared to traditional self‐regulated learning activities. However, the majority of research examining the outcomes of serious games has focused almost exclusively on learning outcomes. This has resulted in a lack of research examining why these types of games result in increased positive outcomes, such as engagement or performance. This study seeks to address this gap in existing research by examining the relationship between game difficulty and participants’ engagement, performance and self‐efficacy in a Pacman style maze navigation game. This required the use of hidden difficulty variations which participants were randomly assigned. Participants engaged with the game over a 5‐days practice period. Results from this study suggest that difficulty plays a considerable role in influencing participants’ self‐efficacy for the task. Self‐efficacy has been consistently linked to positive outcomes such as increased engagement and performance. This highlights the importance of difficulty as a game design factor as well as providing an insight into the manner in which serious games could be further refined in order to increase user’s self‐efficacy and associated positive outcomes. Implications for future serious games and self‐efficacy research are discussed.
Pathological downstaging as a novel endpoint for the development of neoadjuvant chemotherapy for upper tract urothelial carcinoma
Authors: Martini Alberto , Daza Jorge , Poltiyelova Elona , Gul Zeynep , Heard John R. , Ferket Bart S. , Waingankar Nikhil , Galsky Matthew D. , Sfakianos John P. 
Published: February 2019

ObjectivesTo evaluate whether pathological downstaging (pDS) was more informative in predicting overall survival (OS) than pathological complete response (pCR) in patients treated with neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC).Patients and MethodsThe National Cancer Database was queried for patients with high‐grade cN0M0 disease who had received NAC. pDS was defined as a decrease of at least one stage from cT to pT stage along with pN0, including pCR. A multivariable Cox model predicting OS was generated by fitting alternatively either pDS or pCR, and adjusted for potential confounders. The discrimination of the Cox models for predicting OS was evaluated using Harrell's C‐index. The analyses were repeated in patients diagnosed as having cT2–4N0M0 disease.ResultsAmong 264 patients meeting the inclusion criteria, 72 (27%) and 39 (15%) achieved pDS and pCR, respectively. On multivariable analysis, both pDS (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.13, 0.45; P < 0.001) and pCR (HR 0.37, 95% CI 0.18, 0.79; P = 0.01) were associated with OS. The model including pDS achieved better discrimination with respect to the model including pCR: C‐index 76.4 vs 72.7, respectively.In the 128 patients diagnosed with cT2–4 disease, both pDS (HR 0.19, 95% CI 0.09, 0.40; P < 0.001) and pCR (HR 0.31, 95% CI 0.11, 0.85; P = 0.023) were confirmed as predictors of OS. The model including pDS was confirmed to discriminate better than the model including pCR: C‐index 75 vs 68.9, respectively.ConclusionThe study showed that pDS after NAC for UTUC was more informative than pCR when predicting OS. These findings, although requiring prospective validation, can aid in the design of clinical trials seeking to refine the use of chemotherapy and other systemic therapies in this setting.
The relationship between the morphological subtypes of microglia and Alzheimer’s disease neuropathology
Authors: Paasila Patrick Jarmo , Davies Danielle Suzanne , Kril Jillian June , Goldsbury Claire , Sutherland Greg Trevor 
Published: February 2019

AbstractMicroglial associations with both the major Alzheimer’s disease (AD) pathognomonic entities, β‐amyloid‐positive plaques and tau‐positive neurofibrillary tangles, have been noted in previous investigations of both human tissue and mouse models. However, the precise nature of their role in the pathogenesis of AD is debated; the major working hypothesis is that pro‐inflammatory activities of activated microglia contribute to disease progression. In contrast, others have proposed that microglial dystrophy with a loss of physiological and neuroprotective activities promotes neurodegeneration. This immunohistochemical study sought to gain clarity in this area by quantifying the morphological subtypes of microglia in the mildly‐affected primary visual cortex (PVC), the moderately affected superior frontal cortex (SFC) and the severely affected inferior temporal cortex (ITC) of 8 AD cases and 15 age and gender‐matched, non‐demented controls with ranging AD‐type pathology. AD cases had increased β‐amyloid and tau levels compared to controls in all regions. Neuronal loss was observed in the SFC and ITC, and was associated with atrophy in the latter. A major feature of the ITC in AD was a decrease in ramified (healthy) microglia with image analysis confirming reductions in arborized area and skeletal complexity. Activated microglia were not associated with AD but were increased in non‐demented controls with greater AD‐type pathology. Microglial clusters were occasionally associated with β‐amyloid‐ and tau‐positive plaques but represented less than 2% of the total microglial population. Dystrophic microglia were not associated with AD, but were inversely correlated with brain pH suggesting that agonal events were responsible for this morphological subtype. Overall these novel findings suggest that there is an early microglial reaction to AD‐type pathology but a loss of healthy microglia is the prominent feature in severely affected regions of the AD brain.
Adrenoceptors in white, brown, and brite adipocytes
Authors: Evans Bronwyn A. , Merlin Jon , Bengtsson Tore , Hutchinson Dana S. 
Published: February 2019

Adrenoceptors play an important role in adipose tissue biology and physiology that includes regulating the synthesis and storage of triglycerides (lipogenesis), the breakdown of stored triglycerides (lipolysis), thermogenesis (heat production), glucose metabolism, and the secretion of adipocyte‐derived hormones that can control whole‐body energy homeostasis. These processes are regulated by the sympathetic nervous system through actions at different adrenoceptor subtypes expressed in adipose tissue depots. In this review, we have highlighted the role of adrenoceptor subtypes in white, brown, and brite adipocytes in both rodents and humans and have included detailed analysis of adrenoceptor expression in human adipose tissue and clonally derived adipocytes. We discuss important considerations when investigating adrenoceptor function in adipose tissue or adipocytes.Linked ArticlesThis article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc
Signalling in response to sub‐picomolar concentrations of active compounds: Pushing the boundaries of GPCR sensitivity
Authors: Civciristov Srgjan , Halls Michelle L. 
Published: February 2019

There is evidence for ultra‐sensitive responses to active compounds at concentrations below picomolar levels by proteins and receptors found in species ranging from bacteria to mammals. We have recently shown that such ultra‐sensitivity is also demonstrated by a wide range of prototypical GPCRs, and we have determined the molecular mechanisms behind these responses for three family A GPCRs: the relaxin receptor, RXFP1; the β2‐adrenoceptor; and the M3 muscarinic ACh receptor. Interestingly, there are reports of similar ultra‐sensitivity by more than 15 human GPCR families, in addition to other human receptors and channels. These occur through a diverse range of signalling pathways and produce modulation of important physiological processes, including neuronal transmission, chemotaxis, gene transcription, protein/ion uptake and secretion, muscle contraction and relaxation, and phagocytosis. Here, we summarise the accumulating evidence of ultra‐sensitive receptor signalling to show that this is a common, though currently underappreciated, property of GPCRs.Linked ArticlesThis article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc
Evidence for metabotropic function of epithelial nicotinic cholinergic receptors in rat colon
Authors: Lottig Lena , Bader Sandra , Jimenez Marcel , Diener Martin 
Published: February 2019

Background and PurposeACh exerts its actions via nicotinic (nAChR) and muscarinic receptors. In the peripheral nervous system, ionotropic nAChR mediate responses in excitable cells. However, recent studies demonstrate the expression of nAChR in the colonic epithelium, which are coupled to an induction of Cl− secretion via activation of the Na+‐K+‐pump.Experimental ApproachIn order to find out whether these epithelial nAChR function as ionotropic receptors, intracellular microelectrode and imaging experiments were performed in isolated crypts from rat colon. Apically permeabilized epithelia were used to measure pump current across the basolateral membrane.Key ResultsImaging experiments with the Na+‐sensitive dye SBFI revealed that nicotine induced a decrease in the cytosolic Na+ concentration concomitant with a fall in the cytosolic Ca2+ concentration in about 50% of the cells. as shown in fura‐2 experiments. Nicotine hyperpolarized the membrane by 6.4 ± 2.1 mV. These observations contradict the assumption that epithelial nAChR function as ligand‐gated non‐selective cation channels. The decrease in the cytosolic Na+ concentration was strongly delayed, when the Na+‐K+‐pump was inhibited by scilliroside. Ussing chamber experiments revealed a strong dependence of the nicotine‐induced pump current on the presence of Ca2+, and chelation of cytosolic Ca2+ with BAPTA prevented the fall in the cytosolic Na+ concentration in SBFI‐loaded crypts. Inhibition of PKC with GF 109203X or Goe 6983 significantly reduced the nicotine‐induced pump current.Conclusions and ImplicationsThese results suggest that epithelial nAChR activate the Na+‐K+‐pump via a PKC dependent on a sufficient cytosolic Ca2+ concentration.
Synthesis and biological activity of Ub2 derived peptides as potential host‐directed antitubercular therapy
Authors: Singh Shalini , Yabaji Shivraj M. , Ali Rafat , Srivastava Kishore K. , Haq Wahajul 
Published: February 2019

AbstractThe correlation of mycobactericidal property of macrophages with its potential to deliver bacteria to hydrolytic lysosomes, augmented with ubiquitin‐derived peptides (Ub2), activates the process of autophagy. This leads to the formation of phagolysosomes supported by factor involving increased cationic charges which regulate the acidic pH causing elimination of Mycobacterium. To better understand this interaction of cationic‐rich ubiquitin‐derived peptides with mycobacteria and to identify putative mycobacterial intrinsic resistance mechanisms for phagolysosome formation, we have synthesized a new series of Ub2 peptides, wherein the Gly residues are replaced with azaGly with the aim to improve metabolic stability. In addition to that a new methodology is reported for the synthesis of heteroaryl tethered peptides using azaGly as a linker. We have demonstrated that positive puncta (directly proportional to the acidification of lysosome) in cytosol was significantly increased after 6 hours on the treatment of macrophage with Ub2 peptide derivatives (1, 6, 10, and 11) causing the higher intensity of lysosome observed through LysoTracker Red Dye. The circular dichroism spectral studies are carried out in water and water:TFE mixture and demonstrated that the Ub2 peptides have helix‐forming tendency in the presence of TFE. The recognizable intracellular killing of Mycobacterium tuberculosis by Ub2 peptides provides a new approach for host‐directed therapy.
Synthesis of new bis‐pyrazole linked hydrazides and their in vitro evaluation as antimicrobial and anti‐biofilm agents: A mechanistic role on ergosterol biosynthesis inhibition in Candida albicans
Authors: Khan Irfan , Kanugala Sirisha , Shareef Mohd. Adil , Ganapathi Thipparapu , Shaik Anver Basha , Shekar Kunta Chandra , Kamal Ahmed , Kumar Chityal Ganesh 
Published: February 2019

AbstractLiterature reports suggest that pyrazoles and hydrazides are potential antimicrobial pharmocophores. Considering this fact, a series of nineteen conjugates containing hybrids of bis‐pyrazole scaffolds joined through a hydrazide linker were synthesized and further evaluated for their antimicrobial activity against a panel of Gram‐positive and Gram‐negative bacteria along with Candida albicansMTCC 3017 strain. Although the derivatives exhibited good antibacterial activity, some of the derivatives (13d, 13j, 13l, 13p, and 13r) showed excellent anti‐Candida activity with MICs values of 3.9 μg/ml, which was equipotent to that of the standard Miconazole (3.9 μg/ml), which has inspired us to further explore their anti‐Candida activity. The same compounds were also tested for anti‐biofilm studies against various Candida strains and among them, compounds 13l and 13r efficiently inhibited the formation of fungal biofilms. Field emission scanning electron micrographs revealed that one of the promising compound 13r showed cell damage and in turn cell death of the Candida strain. These potential conjugates (13l and 13r) also demonstrated promising ergosterol biosynthesis inhibition against some of the strains C. albicans, which were further validated through molecular docking studies. In silico computational studies were carried out to predict the binding modes and pharmacokinetic parameters of these conjugates.
Changes in alveolar process dimensions following extraction of molars with advanced periodontal disease: A clinical pilot study
Authors: Zhao Liping , Wei Yiping , Xu Tao , Zhang Bo , Hu Wenjie , Chung Kwok‐Hung 
Published: February 2019

AbstractObjectiveTo use cone beam computed tomography (CBCT) to assess the alterations of socket dimensions after a 6‐month healing period following molar extraction.Materials and methodsSeventeen molars were extracted due to advanced periodontitis. CBCT scans were taken immediately after extraction and once more 6 months later. Superimposition of CBCT images was used to measure the following: horizontal changes at extraction sites at three corono‐apical levels (−1, −3, and −5 mm) below the bone crest, three mesio‐distal levels (mesial, central, and distal), vertical changes at nine regions of the alveolar crest, and alveolar bone volume.ResultsThe width of the central crests at −1 mm decreased by 0.59 and 0.72 mm in the buccal and 0.27 and 0.02 mm in the lingual, in the maxilla and mandible, respectively. No statistically significant decreases in the ridge height were observed except in the disto‐palatal region with a 1.11 mm decrease in the maxilla (p < 0.05). Heights of the buccal and lingual bone plates decreased significantly and ranged from 0.56 to 1.38 mm in the mandible after 6 months of healing (p < 0.05). Overall, ridge height changes were not significantly different between the maxilla and mandible (p > 0.05) and no significant volumetric bone loss occurred in either maxillary or mandibular sockets after 6 months of healing.ConclusionsSocket dimensions of molars with advanced periodontal disease showed a significant increase at the middle‐central portion, although there were no significant changes of horizontal width 6 months following the procedures.
Quality of life and disease severity in dermatitis patients with fragrance allergy—A cross‐sectional European questionnaire study
Authors: Bennike Niels H. , Heisterberg Maria S. , White Ian R. , Mahler Vera , Silvestre‐Salvador Juan F. , Giménez‐Arnau Ana , Johansen Jeanne D. 
Published: February 2019

BackgroundFragrance contact allergy is common, but few studies on quality of life (QoL) in affected patients exist. Recently, the disease‐specific Fragrance Quality of Life Index (FQLI) was developed.ObjectivesTo characterize QoL in European dermatitis patients with fragrance contact allergy at the time of diagnosis.MethodsThis was a cross‐sectional study, in which 2011 Danish, British, Spanish and German adult consecutive dermatitis patients were invited to complete a questionnaire on self‐reported disease severity, the Dermatology Life Quality Index (DLQI), and the FQLI immediately prior to being patch tested.ResultsOne thousand seven hundred and fifty‐eight patients responded, and 259 (14.7%; country range 11.7%‐18.5%) were fragrance‐positive. Among these, the total (SD) DLQI score was 6.2 (5.6) and the total (SD) FQLI score was 60 (25), with both estimates being comparable to those in fragrance‐negative patients. Adjusting the total FQLI score for age, sex and self‐rated disease severity showed a higher (ie, worse) score in fragrance‐positive patients (3.6‐point increase; 95% confidence interval: 0.30‐6.8 points; P = 0.03). Specifically, contact allergy to oxidized linalool was associated with greater impairment in QoL.ConclusionsQoL in patients with fragrance contact allergy is impaired at a level comparable to that in other patch tested dermatitis patients, at the time of diagnosis, across several European countries.
Antireflux covered metal stent for nonresectable distal malignant biliary obstruction: Multicenter randomized controlled trial
Authors: Hamada Tsuyoshi , Isayama Hiroyuki , Nakai Yousuke , Iwashita Takuji , Ito Yukiko , Mukai Tsuyoshi , Yagioka Hiroshi , Saito Tomotaka , Togawa Osamu , Ryozawa Shomei , Hirano Kenji , Mizuno Suguru , Yamamoto Natsuyo , Kogure Hirofumi , Yasuda Ichiro , Koike Kazuhiko 
Published: February 2019

Background and AimAn antireflux metal stent (ARMS) for nonresectable distal malignant biliary obstruction (MBO) may prevent recurrent biliary obstruction (RBO) as a result of duodenobiliary reflux and prolong time to RBO (TRBO). Superiority of ARMS over conventional covered self‐expandable metal stents (SEMS) has not been fully examined.MethodsWe conducted a multicenter randomized controlled trial to examine whether TRBO of an ARMS with a funnel‐shaped valve was longer than that of a covered SEMS in SEMS‐naïve patients. We enrolled 104 patients (52 patients per arm) at 11 hospitals in Japan. Secondary outcomes included causes of RBO, adverse events, and patient survival.ResultsTRBO did not differ significantly between the ARMS and covered SEMS groups (median, 251 vs 351 days, respectively; P = 0.11). RBO as a result of biliary sludge or food impaction was observed in 13% and 9.8% of patients who received an ARMS and covered SEMS, respectively (P = 0.83). ARMS was associated with a higher rate of stent migration compared with the covered SEMS (31% vs 12%, P = 0.038). Overall rates of adverse events were 20% and 18% in the ARMS and covered SEMS groups, respectively (P = 0.97). No significant between‐group difference in patient survival was observed (P = 0.26).ConclusionsThe current ARMS was not associated with longer TRBO compared with the covered SEMS. Modifications including addition of an anti‐migration system are required to use the current ARMS as first‐line palliative treatment of distal MBO (UMIN‐CTR clinical trial registration number: UMIN000014784).
Monitoring the SDGs: Digital and social technologies to ensure citizen participation, inclusiveness and transparency
Authors: Saner Raymond , Yiu Lichia , Nguyen Melanie 
Published: February 2019

AbstractMotivationThe article shows that the measurement of SDG attainment remains vague and incomplete and argues that participation‐based and inclusive monitoring must be an integral part of managing the SDG implementation process.PurposeCountries are supposed to review their progress of SDG implementation every four years, but the method of reviewing is left open. In addition, and even more urgent is the need to improve on the inadequate definition of monitoring methods that countries are supposed to deploy.Approach and methodsThe article reviews the various options currently available to conduct the four‐year review and the methods of on‐going SDG monitoring.FindingsThe analysis shows that the SDG monitoring methods have not yet been defined, leaving stakeholders (governments, business and civil society) without appropriate guidance.Policy implicationsThe authors propose two types of monitoring: micro‐monitoring and macro‐monitoring, both of which are necessary to ensure effective and efficient monitoring in achieving process accountability, institutional learning, and innovation.
Comparison of chloral hydrate and pentobarbital sedation for pediatric echocardiography
Authors: Ganigara Madhusudan , Srivastava Shubhika , Malik Preeti , Fong Sherman , Ko Helen , Parness Ira , Shenoy Rajesh 
Published: February 2019

BackgroundIn 2013, outpatient use of chloral hydrate (CH) was limited and other alternatives such as oral pentobarbital (PB) were explored to achieve conscious sedation in young children for transthoracic echocardiography (TTE). We aimed to assess efficacy and safety of the two medications.MethodsClinical information, from a computerized database, about children who received sedation with either CH or PB for TTE at our center (2008–2015) was reviewed, and the two groups were compared for sedation effectiveness and complications.ResultsThree thousand eight hundred fifty one pediatric patients (median age 8 months) underwent conscious sedation during TTE (mean doses CH 50 mg/kg, PB 4 mg/kg). Demographic characteristics of the two groups were similar. Sedation failure rate (CH 2.4%, PB 2.9%, P = NS), need for supplemental doses (CH 17.9%, PB 16.2%, P = NS), and overall adverse event rate (PB 1.4%, CH 1.9%; P = NS) were similar in the two groups. There were fewer episodes of respiratory depression with PB (0.3% vs 1.6%, P < 0.05). The rate of paradoxical reactions was higher with PB (1% vs 0.03%, P < 0.05). Increasing age predicted the need for supplemental doses and for sedation failure in both groups. Neonates (7.5% vs 0%) and infants (2% vs 0.6%) given CH were more likely to develop adverse reactions.ConclusionChloral hydrate and PB are equally effective. However, CH is associated with an increased incidence of transient desaturation, while PB is associated with an increased incidence of a paradoxical reaction. Increasing age is predictive of the need for supplemental doses and for failure of sedation in both groups.