bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multiorganism pipeline for antiseizure drug discovery: Identification of chlorothymol as a novel γ‐aminobutyric acidergic anticonvulsant
Authors: Jones Alistair , Barker‐Haliski Melissa , Ilie Andrei S. , Herd Murray B. , Baxendale Sarah , Holdsworth Celia J. , Ashton John‐Paul , Placzek Marysia , Jayasekera Bodiabaduge A. P. , Cowie Christopher J. A. , Lambert Jeremy J. , Trevelyan Andrew J. , White H. Steve , Marson Anthony G. , Cunliffe Vincent T. , Sills Graeme J. , Morgan Alan 
Published: August 2020

AbstractObjectiveCurrent medicines are ineffective in approximately one‐third of people with epilepsy. Therefore, new antiseizure drugs are urgently needed to address this problem of pharmacoresistance. However, traditional rodent seizure and epilepsy models are poorly suited to high‐throughput compound screening. Furthermore, testing in a single species increases the chance that therapeutic compounds act on molecular targets that may not be conserved in humans. To address these issues, we developed a pipeline approach using four different organisms.MethodsWe sequentially employed compound library screening in the zebrafish, Danio rerio, chemical genetics in the worm, Caenorhabditis elegans, electrophysiological analysis in mouse and human brain slices, and preclinical validation in mouse seizure models to identify novel antiseizure drugs and their molecular mechanism of action.ResultsInitially, a library of 1690 compounds was screened in an acute pentylenetetrazol seizure model using D rerio. From this screen, the compound chlorothymol was identified as an effective anticonvulsant not only in fish, but also in worms. A subsequent genetic screen in C elegans revealed the molecular target of chlorothymol to be LGC‐37, a worm γ‐aminobutyric acid type A (GABAA) receptor subunit. This GABAergic effect was confirmed using in vitro brain slice preparations from both mice and humans, as chlorothymol was shown to enhance tonic and phasic inhibition and this action was reversed by the GABAA receptor antagonist, bicuculline. Finally, chlorothymol exhibited in vivo anticonvulsant efficacy in several mouse seizure assays, including the 6‐Hz 44‐mA model of pharmacoresistant seizures.SignificanceThese findings establish a multiorganism approach that can identify compounds with evolutionarily conserved molecular targets and translational potential, and so may be useful in drug discovery for epilepsy and possibly other conditions.
Inflection point in climatic suitability of insect pest species in Europe suggests non‐linear responses to climate change
Authors: Grünig Marc , Calanca Pierluigi , Mazzi Dominique , Pellissier Loïc 
Published: August 2020

AbstractClimate change and globalization affect the suitable conditions for agricultural crops and insect pests, threatening future food security. It remains unknown whether shifts in species’ climatic suitability will be linear or rather non‐linear, with crop exposure to pests suddenly increasing when a critical temperature threshold is crossed. Moreover, uncertainty of forecasts can arise because of the modelling approach based either on species distribution data or on physiological measurements. Here, we compared the predictions of two modelling approaches (physiological models and species distribution models) for forecasting the potential distribution of agricultural insect pests in Europe. Despite conceptual differences, we found good agreement overall between the two approaches. We further identified a potential regime change in pest pressure along a temperature gradient. With both modelling approaches, we found an inflection point in the number of pest species with suitable climatic conditions around a minimum temperature of the coldest month of −3°C. Our results could help decision‐makers anticipate the onset of rising pest pressure and provide support for intensifying surveillance measures, particularly in regions where temperatures are already beyond the inflection point.
Asymmetric response of soil methane uptake rate to land degradation and restoration: Data synthesis
Authors: Wu Junjun , Chen Qiong , Jia Wei , Long Chunyan , Liu Wenzhi , Liu Guihua , Cheng Xiaoli 
Published: August 2020

AbstractLand degradation and restoration profoundly affect soil CH4 uptake capacity in terrestrial ecosystems. However, a comprehensive assessment of the response of soil CH4 uptake to land degradation and restoration at global scale is not available. Here, we present a global meta‐analysis with a database of 228 observations from 83 studies to investigate the effects of land degradation and restoration on the capacity of soil CH4 uptake. We found that land degradation significantly decreased the capacity of soil CH4 uptake, except the conversion of pasture to cropland where the soil CH4 uptake rate showed no response. In contrast, all types of land restoration significantly increased the capacity of soil CH4 uptake. Interestingly, the response of soil CH4 uptake rate to land degradation and restoration was asymmetric: the increased soil CH4 uptake rate in response to the land restoration was smaller compared to the decrease in CH4 uptake rate induced by the land degradation. The effect of land degradation on soil CH4 uptake rate was not dependent on the time since land use change, but the CH4 sink strength increased with the time since land restoration. The response of soil CH4 uptake rate to both land degradation and restoration was predominantly regulated by changes in the soil water‐filled pore space, soil bulk density, and pH, whereas alterations in the substrate quantity and quality had negligible effect. Additionally, the effects of land degradation and restoration on soil CH4 uptake were strongly related to the mean annual precipitation and soil texture. Overall, our results provide novel insights for understanding of how land degradation and restoration can affect the CH4 sink strength of upland soils, and more importantly, our findings are beneficial to take measures to enhance the potential of soil CH4 uptake in response to global land use change.
Wear‐Off of OnabotulinumtoxinA Effect Over the Treatment Interval in Chronic Migraine: A Retrospective Chart Review With Analysis of Headache Diaries
Authors: Ruscheweyh Ruth , Athwal Bal , Gryglas‐Dworak Anna , Frattale Ilaria , Latysheva Nina , Ornello Raffaele , Pozo‐Rosich Patricia , Sacco Simona , Torres Ferrus Marta , Stark Catherine D. 
Published: August 2020

ObjectiveTo quantify wear‐off of the response to OnabotulinumtoxinA (OnabotA) treatment over the treatment cycle in chronic migraine at group and individual level.BackgroundOnabotA administered quarterly is an effective treatment for chronic migraine. However, some patients report that headache recurs before the scheduled follow‐up injection.MethodsIn this retrospective chart review performed in 6 university outpatient centers or private practices specialized in headache treatment, 112 patients with a ≥30% response to OnabotA who completed headache diaries over 13 weeks after OnabotA treatment were included (age [mean ± SD] 45 ± 12 years, 82% female, headache days/month at baseline 24 ± 6).ResultsCompared to weeks 5 to 8 after injection, headache days/week increased significantly in weeks 12 (+0.52 ± 1.96, 95% CI [0.15, 0.88], P < .009) and 13 (+1.15 ± 1.95, CI[0.79, 1.52], P < .001), demonstrating significant wear‐off of the OnabotA effect. Similarly, acute medication days/week significantly increased in weeks 12 (0.38±1.67, CI [0.06, 0.69], P ≤ .027) and 13 (+0.83 ± 1.76, CI [0.49, 1.16], P < .001). At an individual level, 57 patients (51%) showed ≥30% wear‐off by weeks 12 and 13, and 28 patients (25%) showed ≥30% wear‐off already by weeks 10 and 11. Age, gender, OnabotA dose or cycle number, or headache center did not predict individual wear‐off.ConclusionsThese data show that in clinical practice, on average the response of chronic migraine patients to OnabotA injection shows a clinically significant wear‐off from week 12 after treatment. About 25% of the patients experience wear‐off even by weeks 10 and 11. It must be noted that wear‐off detected in a real‐world study on OnabotA responders can be due to wear‐off of a pharmacological OnabotA effect or a placebo effect, or to regression to the mean effects. This wear‐off phenomenon may negatively affect quality of life of chronic migraine patients under OnabotA treatment. The best way to counteract wear‐off remains to be determined.
Emollient structure and chemical functionality effects on the biomechanical function of human stratum corneum
Authors: Berkey C. , Kanno D. , Mehling A. , Koch J. P. , Eisfeld W. , Dierker M. , Bhattacharya S. , Dauskardt R. H. 
Published: August 2020

AbstractObjectiveCosmetic emollients are widely used in skincare formulations due to their ability to 'soften' the skin and modulate formulation spreadability. Though emollients are commonly used, little is known about their effects on the biomechanical barrier properties of human stratum corneum (SC), which play a critical role in consumer perception of formulation efficacy. Accordingly, our objective was to provide new insights with a study involving fourteen cosmetic emollient molecules with widely varying structures, molecular weights, SC diffusivities, topological polar surface areas (TPSAs), viscosities and chemical functionalities.MethodsMechanical stress in the SC was measured in vitro using a substrate curvature measurement technique. Stress development due to SC drying was measured before and after topical treatment with cosmetic emollients. Emollient diffusivity and alterations to lipid content in SC after treatment were measured via ATR‐FTIR spectroscopy. The maximum penetration volume of emollient in SC was characterized to elucidate mechanisms underlying emollient effects on stress.ResultsThe application of all cosmetic emollients caused a reduction in SC mechanical stress under dehydrating conditions, and a linear correlation was discovered between emollient penetration volume and the degree of stress reduction. These molecules also induced increases in stress equilibration rate, signalling changes to SC transport kinetics. Stress equilibration rate increases linearly correlated with decreasing intensity of the νCH2 band, indicating a previously unknown interaction between cosmetic emollients and SC lipids. Stress and penetration volume results were rationalized in terms of a multi‐parameter model including emollient molecular weight, diffusivity, TPSA and viscosity.ConclusionWe provide a new rational basis for understanding the effects of cosmetic emollient choice on biomechanical properties affecting SC barrier function and consumer perception. We demonstrate for the first time that emollients very likely reduce SC mechanical stress through their ability to take up volume when penetrating the SC, and how molecular weight, SC diffusivity, TPSA and viscosity are predictive of this ability. As cosmetic formulations continue to evolve to meet the needs of customers, emollient molecules can be selected that not only contribute to formulation texture and/or spreadability but that also leverage this novel connection between emollient penetration and SC biomechanics.
The cellular origins of cancer with particular reference to the gastrointestinal tract
Authors: Alison Malcolm R. 
Published: August 2020

SummaryStem cells or their closely related committed progenitor cells are the likely founder cells of most neoplasms. In the continually renewing and hierarchically organized epithelia of the oesophagus, stomach and intestine, homeostatic stem cells are located at the beginning of the cell flux, in the basal layer of the oesophagus, the isthmic region of gastric oxyntic glands and at the bottom of gastric pyloric‐antral glands and colonic crypts. The introduction of mutant oncogenes such as KrasG12D or loss of Tp53 or Apc to specific cell types expressing the likes of Lgr5 and Mist1 can be readily accomplished in genetically engineered mouse models to initiate tumorigenesis. Other origins of cancer are discussed including ‘reserve’ stem cells that may be activated by damage or through disruption of morphogen gradients along the crypt axis. In the liver and pancreas, with little cell turnover and no obvious stem cell markers, the importance of regenerative hyperplasia associated with chronic inflammation to tumour initiation is vividly apparent, though inflammatory conditions in the renewing populations are also permissive for tumour induction. In the liver, hepatocytes, biliary epithelial cells and hepatic progenitor cells are embryologically related, and all can give rise to hepatocellular carcinoma and cholangiocarcinoma. In the exocrine pancreas, both acinar and ductal cells can give rise to pancreatic ductal adenocarcinoma (PDAC), although the preceding preneoplastic states are quite different: acinar‐ductal metaplasia gives rise to pancreatic intraepithelial neoplasia culminating in PDAC, while ducts give rise to PDAC via. mucinous cell metaplasia that may have a polyclonal origin.
Porous chitosan/ZnO‐doped bioglass composites as carriers of bioactive peptides
Authors: Biernat Monika , Ciołek Lidia , Dzierżyńska Maria , Oziębło Artur , Sawicka Justyna , Deptuła Milena , Bauer Marta , Kamysz Wojciech , Pikuła Michał , Jaegermann Zbigniew , Rodziewicz‐Motowidło Sylwia 
Published: August 2020

AbstractIn this study, we aimed to assess whether the composite of chitosan/ZnO‐doped bioglass can be applied as a suitable scaffold for the incorporation of bioactive peptides. Material of a porous composite with 1:1 ratio of bioglass:polymer was produced and used as a matrix for delivery of peptide. A peptide with the PEPTIDES sequence (Pro‐Glu‐Pro‐Thr‐Ile‐Asp‐Glu‐Ser) was chosen as a model peptide. Microstructure and pore sizes of chitosan/ZnO‐doped bioglass were assessed. Open porosity and pore sizes of the composite were suitable for enabling the migration of cells and ensuring the easy delivery of nutrients within the implant. In addition, composite showed bioactivity and bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa strains. Peptide alone did not have any cytotoxic activity on human fibroblasts and keratinocytes. Also it did not show any antibacterial properties and did not cause hemolysis of red blood cells. The peptide incorporated in composite showed a rapid release in the kinetics profile. The obtained results indicate that there is the technological possibility to incorporate peptides in chitosan/ZnO‐doped bioglass scaffolds. Such biomaterials have potential application in bone tissue engineering.
Ocular manifestations of dermatological diseases part I: infectious and inflammatory disorders
Authors: Al Akrash Lamia S. , Al Semari Mohammad A. , Al Harithy Ruaa 
Published: August 2020

AbstractSkin and eyes share a common embryological origin from the embryonic surface ectoderm. Ocular manifestations are one of the most important and common associations of dermatological diseases. Currently, there are few comprehensive reviews of the ocular manifestations of dermatological diseases. We have reviewed more than 40 published articles related to the ocular manifestations of the most important dermatological diseases. The search included Pubmed, Google Scholar, and Cochrane databases from 2014 to 2019. This review was divided into three parts including infections, inflammatory, genetics, connective tissue, autoimmune, neoplasms, and drug‐related disorders. We excluded metabolic, endocrine, and nutrition‐related dermatological diseases. The relationship of ocular manifestations and dermatological diseases is important to recognize for appropriate management since many dermatological diseases can manifest initially with ocular findings. In this part, we summarized the most common and significant ocular findings in infectious and inflammatory dermatological disorders with appropriate referral recommendations to ophthalmology.
Trichoscopic features of tinea capitis among primary school children in north central Nigeria
Authors: Olarinoye Gboyega M. , Katibi Oludolapo S. , Ilesanmi Omotoyosi N. , Fayemiwo Samuel A. , Ogunbiyi Adebola O. , George Adekunle O. 
Published: August 2020

AbstractBackgroundThe myriad of coexisting risk factors for tinea capitis (TC) in parts of Africa makes it common among schoolchildren from this region. Diagnosis ideally involves microscopy and culture of scalp scrapings, which is not always feasible in resource‐poor settings. Small‐scale reports have identified trichoscopy (dermoscopy of hair and surrounding skin) as a cheap, quick, and simple tool for evaluating TC. We sought to describe the trichoscopic features of TC among Nigerian children.MethodsA total of 204 children with clinically diagnosed TC had trichoscopy of their scalp lesions and culture of scalp scrapings. Trichoscopic features and culture results were noted.ResultsPerifollicular scaling (78.4%), interfollicular scaling (69.1%), and black dots (44.1%) were the commonest trichoscopic features. Others include regrowing hairs (18.6%), comma hairs (14.7%), broken hairs (13.2%), corkscrew hairs (3.4%), zigzag hairs (2.5%), and peripilar casts (2.0%). All children with comma, corkscrew, and zigzag hairs, as well as most with black dots (88.9%), broken hairs (88.9%), and regrowing hairs (77.5%) had positive cultures, irrespective of the isolated dermatophyte. Comma hairs were specific for Tinea infection with positive culture of dermatophytes. The presence of black dots in combination with individual features like broken hairs, regrowing hairs, perifollicular scaling, or interfollicular scaling also had a high specificity for positive cultures.ConclusionIn the management of children with TC, trichoscopy is useful as a diagnostic tool, especially where access to laboratory evaluation is either not instant or unavailable.
Prevalence of dental anxiety in children and adolescents globally: A systematic review with meta‐analyses
Authors: Grisolia Barbara Monteiro , dos Santos Ana Paula Pires , Dhyppolito Izabel Monteiro , Buchanan Heather , Hill Kirsty , Oliveira Branca Heloisa 
Published: August 2020

AbstractBackgroundDental anxiety (DA) negatively impacts oral health–related quality of life, and patients with DA usually require more dental treatment time.AimTo describe the global prevalence of DA in children and adolescents and to examine the influence of individual factors (age, sex, and caries experience) and variables related to DA measurement on pooled prevalence.DesignSystematic review with meta‐analyses of observational studies published between 1985 and 2020 (PROSPERO CRD42014013879).ResultsSearches yielded 1207 unique records; 224 full‐text articles were screened, and 50 studies were used in the qualitative and quantitative synthesis. No study was considered as having high methodological quality according to ‘The Joanna Briggs Institute assessment tool’. Overall pooled DA prevalence was 23.9% (95% CI 20.4, 27.3). Pooled prevalence in preschoolers, schoolchildren, and adolescents was as follows: 36.5% (95% CI 23.8, 49.2), 25.8% (95% CI 19.5, 32.1), and 13.3% (95% CI 9.5, 17.0), respectively. DA was significantly more prevalent in preschool children (one study) and schoolchildren (two studies) with caries experience and in female adolescents (one study). The scale used for DA assessment was shown to influence pooled prevalence in preschoolers and adolescents.ConclusionDA is a frequent problem in 3‐ to 18‐year‐olds worldwide, more prevalent in schoolchildren and preschool children than in adolescents.
Self‐activated persistent luminescence from Ba2Zr2Si3O12for information storage
Authors: Xiong Puxian , Zheng Chibin , Peng Mingying , Zhou Zhihao , Xu Feifei , Qin Kexin , Hong Yiyu , Ma Zhijun 
Published: August 2020

AbstractTill now, many doped persistent luminescence (PersL) phosphors have been investigated and found various applications in such as bioimaging, photocatalysis and information storage, but introducing PersL emitters into a proper host is mostly complex. In this research, a self‐activated PersL phosphor Ba2Zr2Si3O12(BZSO) is prepared by solid state reaction. By adding NH4Cl, the self‐activated PersL intensity is evidently enhanced. The trap depths and concentrations are examined by thermoluminescence spectra. Meanwhile, Bi3+ions are introduced into BZSO and show wide band photoluminescence (PL) from 300 to 600 nm. Moreover, the PL of Bi3+is tunable under excitation by 265‐350 nm lights. Furthermore, as a proof‐of‐concept design, we designed a patterned quick response (QR) code based on the self‐activated PersL of BZSO, and the information of “South China University of Technology (SCUT)” can be read out by the code scanning technology. Bi3+‐doped BZSO phosphors are suggested to provide potential applications in information storage by its self‐activated PersL, and to excite researchers to study the tunable PL in Bi3+‐doped phosphor.
Enhanced energy storage density in Ca and Ta co‐doped AgNbO3 antiferroelectric ceramics
Authors: Chao Wenna , Yang Tongqing , Li Yongxiang , Liu Zhifu 
Published: August 2020

AbstractCa and Ta co‐doped AgNbO3 antiferroelectric lead‐free ceramics were fabricated by rolling process technique, and improved energy storage properties were obtained. X‐ray diffraction and Raman spectra indicate a single perovskite structure for (Ag1‐2xCax)(Nb1‐xTax)O3 ceramics. The dielectric performances were also investigated, showing that increasing the content of Ca and Ta from 0.1 to 5 mol% gradually decreased the temperatures of the phase transition of monoclinic M1‐M2 and M2‐M3. This proved the enhanced antiferroelectricity stability associated with the enlarged low temperature phase transition region. The obtained (Ag0.90Ca0.05)(Nb0.95Ta0.05)O3 ceramics exhibit an enhanced recoverable energy storage density (3.36 J/cm3) and efficiency (58.3%) with good temperature and frequency stability. The same composition shows excellent charge and discharge properties with a discharge current as high as 91.5 A and fast discharge speed (150 ns discharge period). All these merits demonstrate that AgNbO3‐based antiferroelectric ceramics are competitive with other lead‐based and lead‐free dielectric capacitors, which are promising candidates for dielectric energy storage applications.