bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and preliminary validation of the patient-reported Chronic Itch Burden Scale assessing health-related quality of life in chronic pruritus
Authors: Theunis J. , Nordon C. , Falissard B. , Orri M. , Mengeaud V. , Misery L. 
Published: June 2021

SummaryBackgroundChronic pruritus (CP) significantly affects patients’ health-related quality of life (HRQoL). Very few self-reported HRQoL questionnaires exploring CP have been developed according to international guidelines, thus limiting their use in preauthorization trials.ObjectivesTo develop a self-reported HRQoL questionnaire in patients with CP owing to psoriasis, atopic dermatitis, seborrhoeic dermatitis of the scalp or idiopathic dermatitis, and to explore the preliminary psychometric properties of the questionnaire.MethodsThe study was performed in France. A conceptual framework was developed based on a structured literature review and expert insight, and was improved using three focus groups involving 19 participants. A 50-item questionnaire was created and tested with 21 participants using cognitive debriefings; 11 items were removed. A cross-sectional study including 251 participants was performed to explore the preliminary psychometric properties of the 39-item questionnaire. Dimensionality was explored using principal component analysis. Cronbach’s alpha and correlation coefficients (interitem, item-total score and item-dimension score) were measured. The number of items was reduced through expert consensus.ResultsIn the 39-item version, three main dimensions were identified (Cronbach’s alpha = 0·94) and all correlation coefficients were &gt; 0·34. Upon review, 13 items were deleted owing to poor quality and six items were deleted by the team, generating a 20-item version. The questionnaire’s factorial structure was best reflected with a two-dimension solution, i.e. (i) social and emotional repercussions and (ii) relation to others, fear of judgement.ConclusionsThe Chronic Itch Burden Scale patient-reported questionnaire explores broad aspects of HRQoL that are relevant for patients with various skin diseases. Its good cross-sectional validity makes it useful for trials and practitioners.
ICT self‐efficacy mediates most effects of university ICT support on preservice teachers' TPACK: Evidence from three normal universities in China
Authors: Wang Qiong , Zhao Guoqing 
Published: June 2021

AbstractA thorough understanding of how ICT support provided by teacher preparation programmes influences preservice teachers' technological pedagogical content knowledge (TPACK) has become increasingly essential. This study aimed at exploring the mediating role of ICT perception, perceived ICT competence and ICT self‐efficacy between university ICT support and preservice teachers' TPACK. Data were collected through an online self‐assessment questionnaire translated and adapted from existing studies and verified with confirmatory factor analysis (CFA). A total of 298 preservice teachers, who were senior students studying at three different normal universities in China, participated in this study. Structural equation modelling revealed the following: (a) university ICT support significantly predicted preservice teachers' ICT perception, perceived ICT competence and ICT self‐efficacy, but had no significant direct effects on their TPACK; (b) ICT self‐efficacy was a strong predictor of preservice teachers' TPACK and ICT perception was a weak one, while perceived ICT competence did not predict TPACK at all; and (c) among three potential mediators, ICT self‐efficacy mediated the most effects of university ICT support on preservice teachers' TPACK. These findings demonstrate strong positive effects of institutional support on preservice teachers' TPACK development, which was strongly underestimated in previous studies. Findings suggest normal universities should create practical opportunities for preservice teachers to perceive the power of technology, especially opportunities that could improve preservice teachers' self‐efficacy while applying technology into instruction.
Practitioner notesWhat is already known about this topic

ICT support from schools is an essential precondition while enhancing in‐service teachers' motivation to apply ICT into instruction.

Research revealing how ICT support provided by teacher preparation programmes affects preservice teachers' TPACK is absent.

What the paper adds

This study adds to the previous literature by exploring the mediating role of ICT perception, perceived ICT competence and ICT self‐efficacy in the relationship between university ICT support and preservice teachers' TPACK.

This study found that university ICT support significantly predicted preservice teachers' ICT perception, perceived ICT competence and ICT self‐efficacy, but had no significant direct effects on their TPACK.

Among the three potential mediators, ICT self‐efficacy mediated the most effects of university ICT support on preservice teachers' TPACK.

Implications for practice and/or policy

Normal universities need to provide effective and professionally targeted ICT support to meet preservice teachers' needs.

The mediating role of ICT self‐efficacy should be highlighted on the path from university ICT support to TPACK.
Insights into the mechanisms underlying opioid use disorder and potential treatment strategies
Authors: Cao Dan‐Ni , Li Fei , Wu Ning , Li Jin 
Published: June 2021

Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non‐opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development.LINKED ARTICLESThis article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc
Why aren't warning signals everywhere? On the prevalence of aposematism and mimicry in communities
Authors: Kikuchi David W. , Herberstein Marie E. , Barfield Michael , Holt Robert D. , Mappes Johanna 
Published: June 2021

ABSTRACTWarning signals are a striking example of natural selection present in almost every ecological community – from Nordic meadows to tropical rainforests, defended prey species and their mimics ward off potential predators before they attack. Yet despite the wide distribution of warning signals, they are relatively scarce as a proportion of the total prey available, and more so in some biomes than others. Classically, warning signals are thought to be governed by positive density‐dependent selection, i.e. they succeed better when they are more common. Therefore, after surmounting this initial barrier to their evolution, it is puzzling that they remain uncommon on the scale of the community. Here, we explore factors likely to determine the prevalence of warning signals in prey assemblages. These factors include the nature of prey defences and any constraints upon them, the behavioural interactions of predators with different prey defences, the numerical responses of predators governed by movement and reproduction, the diversity and abundance of undefended alternative prey and Batesian mimics in the community, and variability in other ecological circumstances. We also discuss the macroevolution of warning signals. Our review finds that we have a basic understanding of how many species in some taxonomic groups have warning signals, but very little information on the interrelationships among population abundances across prey communities, the diversity of signal phenotypes, and prey defences. We also have detailed knowledge of how a few generalist predator species forage in artificial laboratory environments, but we know much less about how predators forage in complex natural communities with variable prey defences. We describe how empirical work to address each of these knowledge gaps can test specific hypotheses for why warning signals exhibit their particular patterns of distribution. This will help us to understand how behavioural interactions shape ecological communities.
Nonchalant neighbors: Space use and overlap of the critically endangered Elongated Tortoise
Authors: Ward Matthew , Marshall Benjamin Michael , Hodges Cameron Wesley , Montano Ysabella , Artchawakom Taksin , Waengsothorn Surachit , Strine Colin Thomas 
Published: June 2021

AbstractTo prevent population extirpations, we need to understand a species’ requirements, especially for critically endangered species inhabiting biodiversity hotspots. Studying animal movement provides necessary insights and gauges protected area effectiveness. Southeast Asian protected areas are becoming isolated, stressing the need for maintaining population viability. We used radio‐telemetry with the critically endangered Elongated Tortoise (Indotestudo elongata) to assess: movements, space use, and conspecific overlap in a small protected area—Sakaerat Biosphere Reserve, Thailand. Movements were weakly seasonal, higher in hot and wet seasons than the dry season, and annual space use varied (4.24–55.57 ha), with conspecifics frequently overlapping. Conspecific comparisons revealed males (n = 5) moved similarly to females (n = 12) but used larger areas. Despite more instances of conspecific attraction over avoidance (20:8), avoidance/attraction behavior appeared disconnected from individual size; therefore, interaction patterns may result from resources locations (mates or food) rather than competition (i.e., no evidence of smaller individuals avoiding larger individuals). Female–female attraction suggests no resource exclusion tactics at our temporal resolution. Male–female attraction may indicate seasonal reproductive movements, but we could not detect significant interactive effects linking conspecific attraction or step length to breeding activity. Our observations of annual space use and overlap present critical components when designing robust population assessments underlining any successfulI.elongataconservation effort. In the context of previous work connecting space overlap with population viability, our results suggest the biosphere population ofI.elongatato be reproductive, with enough resources to be viable, emphasizing the importance of relatively small protected natural areas.
ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta‐analysis
Authors: Karimi Leila , Vijverberg Susanne J. , Engelkes Marjolein , Hernandez‐Pacheco Natalia , Farzan Niloufar , Soares Patricia , Pino‐Yanes Maria , Jorgensen Andrea L. , Eng Celeste , Mukhopadhyay Somnath , Schieck Maximilian , Kabesch Michael , Burchard Esteban G. , Chew Fook Tim , Sio Yang Yie , Potočnik Uroš , Gorenjak Mario , Hawcutt Daniel B. , Palmer Colin N. , Turner Steve , Janssens Hettie M. , Maitland‐van der Zee Anke H. , Verhamme Katia M. C. ,   the PiCA and SysPharmPedia consortia
Published: June 2021

AbstractBackgroundThe polymorphism Arg16 in β2‐adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long‐acting β2‐agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymorphisms at codons 16 and 27.ObjectiveWe assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA.MethodsThe study was undertaken using data from 10 independent studies (n = 5903) participating in the multi‐ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma‐related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12 months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta‐analysed using the inverse variance weighting method assuming random‐effects.ResultsIn subjects treated with ICS and LABA (n = 832, age: 3–21 years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05–1.87, I2 = 0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05–1.94, I2 = 0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71–1.39, I2 = 0.0%), were significantly associated with an increased risk of asthma exacerbations. The sensitivity analyses indicated no significant association between the ADRB2 haplotypes and asthma exacerbations in the other treatment categories, namely as‐required short‐acting β2‐agonists (n = 973), ICS monotherapy (n = 2623), ICS plus leukotriene receptor antagonists (LTRA; n = 338), or ICS plus LABA plus LTRA (n = 686).Conclusion and clinical relevanceThe ADRB2 Arg16 haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2 genotype‐guided treatment which might improve clinical outcomes in asthmatic patients.
A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects
Authors: Erol Seyit Ahmet , Tanacan Atakan , Firat Oguz Esra , Anuk Ali Taner , Goncu Ayhan Sule , Neselioglu Salim , Sahin Dilek 
Published: June 2021

AbstractIt was aimed to evaluate the levels of maternal serum proprotein convertase subtilisin/kexin type 9 (PCSK9) in pregnant women with a fetus diagnosed with open neural tube defects (NTDs). This case‐control study included 38 pregnant women carrying fetuses with open NTDs and 44 age‐matched, pregnant women with no specified risk factors. Comparisons were made of the groups in respect of demographic and clinical data and PCSK9 levels. To examine the performance of PCSK9 levels in the prediction of fetal open NTDs, receiver operating characteristic (ROC) curve analysis was used. In the first and second trimesters, PCSK9 levels were determined to be lower in the NTD group than in the control group (p = 0.010 and p = 0.015, respectively). In the first trimester, the lower PCSK9 levels in the NTD group were not statistically significant (p = 0.575). In the second trimester, the ROC curve value with the best balance of sensitivity/specificity for PCSK9 was 71.9 ng/ml (84.6% sensitivity, 51.7% specificity) and in the first and second trimester combined, 74.4 ng/ml (81.6% sensitivity, 45.5% specificity) (p = 0.015, p = 0.036, respectively). PCSK9 may be involved in the etiopathogenesis of open NTDs at the critical steps of fetal neuronal differentiation. Although it has limitations, PCSK9 may be used as an additional biomarker for the screening of NTDs.
Long‐term effectiveness of 6 mm micro‐rough implants in various indications: A 4.6‐ to 18.2‐year retrospective study
Authors: Raabe Clemens , Monje Alberto , Abou‐Ayash Samir , Buser Daniel , von Arx Thomas , Chappuis Vivianne 
Published: June 2021

AbstractObjectivesTo evaluate the long‐term effectiveness of 6 mm implants in various indications with a micro‐rough surface after 4.6–18.2 years in function and to assess key factors associated with implant survival, success, and biologic/technical complications.Materials and methodsFifty‐five patients with seventy‐four 6 mm implants placed from 2000 to 2013 attended the re‐examination assessing well‐established clinical and radiographic parameters, biologic and prosthetic complications, and patient‐reported outcome measures.ResultsFive implants were lost after a mean follow‐up period of 9.1 years resulting in a survival rate of 93.2%. All losses occurred in free‐end situations in the mandible. Smoking habit significantly reduced implant survival (hazard ratio 36.25). Two implants exhibited a history of peri‐implantitis, and one implant showed progressive marginal bone loss (MBL) resulting in a success rate of 89.2%. The mean MBL amounted to 0.029 mm. Increased MBL was found for implants placed in the maxilla (0.057 mm) and for implants with a diameter of 4.1 mm (0.043 mm). Soft tissue thickness (1.39 mm) and width of keratinized mucosa (1.91 mm) had no effect on MBL. Patient‐reported outcome measures showed high satisfaction (mean VAS scores 88%) and high quality of life (mean OHIP‐G14 score 2.2).ConclusionThe present study demonstrated survival and success rates of 93.2% and 89.2% for 6 mm implants used in various indications. A factor leading to higher implant failure was smoking, whereas modulating factors increasing annual MBL included implants placed in the maxilla and implants with a diameter of 4.1 mm compared to 4.8 mm.
Cyclic nucleotide‐dependent ionic currents in olfactory receptor neurons of the hawkmoth Manduca sexta suggest pull–push sensitivity modulation
Authors: Dolzer Jan , Schröder Katrin , Stengl Monika 
Published: June 2021

AbstractOlfactory receptor neurons (ORNs) of the hawkmoth Manduca sexta sensitize via cAMP‐ and adapt via cGMP‐dependent mechanisms. Perforated patch clamp recordings distinguished 11 currents in these ORNs. Derivatives of cAMP and/or cGMP antagonistically affected three of five K+ currents and two non‐specific cation currents. The Ca2+‐dependent K+ current IK(Ca2+) and the sensitive pheromone‐dependent K+ current IK(cGMP−), which both express fast kinetics, were inhibited by 8bcGMP, while a slow K+ current, IK(cGMP+), was activated by 8bcGMP. Furthermore, application of 8bcAMP blocked slowly activating, zero mV‐reversing, non‐specific cation currents, ILL and Icat(PKC?), which remained activated in the presence of 8bcGMP. Their activations pull the membrane potential towards their 0‐mV reversal potentials, in addition to increasing intracellular Ca2+ levels voltage‐ and ILL‐dependently. Twenty minutes after application, 8bcGMP blocked a TEA‐independent K+ current, IK(noTEA), and a fast cation current, Icat(nRP), which both shift the membrane potential to negative values. We conclude that conditions of sensitization are maintained at high levels of cAMP, via specific opening/closure of ion channels that allow for fast kinetics, hyperpolarized membrane potentials, and low intracellular Ca2+ levels. In contrast, adaptation is supported via cGMP, which antagonizes cAMP, opening Ca2+‐permeable channels with slow kinetics that stabilize depolarized resting potentials. The antagonistic modulation of peripheral sensory neurons by cAMP or cGMP is reminiscent of pull–push mechanisms of neuromodulation at central synapses underlying metaplasticity.
Microglia proliferation plays distinct roles in acquired epilepsy depending on disease stages
Authors: Di Nunzio Martina , Di Sapia Rossella , Sorrentino Diletta , Kebede Valentina , Cerovic Milica , Gullotta Giorgia S. , Bacigaluppi Marco , Audinat Etienne , Marchi Nicola , Ravizza Teresa , Vezzani Annamaria 
Published: June 2021

AbstractObjectiveMicrogliosis occurs in animal models of acquired epilepsy and in patients. It includes cell proliferation that is associated with seizure frequency and decreased neuronal cells in human epilepsy. The role of microglia proliferation in the development of acquired epilepsy is unknown; thus, we examined its contribution to spontaneous seizure, neurodegeneration, and cognitive deficits in different disease phases.MethodsWe used a model of acquired epilepsy triggered by intra‐amygdala kainic acid in C57BL6N adult male mice. Mice were electroencephalographically (EEG) monitored (24/7) during status epilepticus and in early and chronic disease. Microglia proliferation was blocked by GW2580, a selective CSF1 receptor inhibitor, supplemented in the diet for 21 days from status epilepticus onset. Then, mice were returned to placebo diet until experiment completion. Control mice were exposed to status epilepticus and fed with placebo diet. Experimental mice were tested in the novel object recognition test (NORT) and in Barnes maze, and compared to control and sham mice. At the end of the behavioral test, mice were killed for brain histopathological analysis. Additionally, seizure baseline was monitored in chronic epileptic mice, then mice were fed for 14 days with GW2580 or placebo diet under 24/7 EEG recording.ResultsGW2580 prevented microglia proliferation in mice undergoing epilepsy, whereas it did not affect microglia or basal excitatory neurotransmission in the hippocampus of naive mice. Mice with occluded microglia proliferation during early disease development underwent status epilepticus and subsequent epilepsy similar to placebo diet mice, and were similarly impaired in NORT, with improvement in Barnes maze. GW2580‐treated mice displayed neuroprotection in the hippocampus. In contrast, blockade of microglia proliferation in chronic epileptic mice resulted in spontaneous seizure reduction versus placebo mice.SignificanceMicroglia proliferation during early disease contributes to neurodegeneration, whereas in late chronic disease it contributes to seizures. Timely pharmacological interference with microglia proliferation may offer a potential target for improving disease outcomes.
Rapid evolution of knockdown resistance haplotypes in response to pyrethroid selection in Aedes aegypti
Authors: Baltzegar Jennifer , Vella Michael , Gunning Christian , Vasquez Gissella , Astete Helvio , Stell Fred , Fisher Michael , Scott Thomas W. , Lenhart Audrey , Lloyd Alun L. , Morrison Amy , Gould Fred 
Published: June 2021

AbstractThis study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific kdr haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasize how quickly Ae. aegypti populations can evolve. In our examination of the literature on mosquitoes and other insect pests, we could find no cases where a pest evolved so quickly to so few exposures to low or nonresidual insecticide applications. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance‐conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.