bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐based discovery of CZL80, a caspase‐1 inhibitor with therapeutic potential for febrile seizures and later enhanced epileptogenic susceptibility
Authors: Tang Yangshun , Feng Bo , Wang Yi , Sun Huiyong , You Yi , Yu Jie , Chen Bin , Xu Cenglin , Ruan Yeping , Cui Sunliang , Hu Gang , Hou Tingjun , Chen Zhong 
Published: April 2020

Background and PurposeFebrile seizures (FS), the most common seizures in childhood and often accompanied by later epileptogenesis, are not well controlled. Inflammatory processes have been implicated in the pathophysiology of epilepsy. However, whether caspase‐1 is involved in FS generation and could be a target for the treatment of FS is still unclear.Experimental ApproachBy using pharmacological and gene intervention methods in C57BL/6J mice, we assessed the role of caspase‐1 in FS generation. We used structural virtual screening against the active site of caspase‐1, to screen compounds for druggable and safe low MW inhibitors of caspase‐1 in vitro. One compound was chosen to test in vivo for therapeutic potential, using FS models in neonatal mice and epileptogenesis in adult mice.Key ResultsIn mice, levels of cleaved caspase‐1 increased prior to FS onset.Caspase‐1−/−mice were resistant to FS and showed lower neuronal excitability than wild‐type littermates. Conversely, overexpression of caspase‐1 usingin uteroelectroporation increased neuronal excitability and enhanced susceptibility to FS. The structural virtual screening, using molecular docking approaches for the active site of caspase‐1 of over 1 million compounds yielded CZL80, a brain‐penetrable, low MW inhibitor of caspase‐1. In neonatal mice, CZL80 markedly reduced neuronal excitability and incidence of FS generation, and, in adult mice, relieved later enhanced epileptogenic susceptibility. CZL80 was devoid of acute diazepam‐like respiratory depression and chronic liver toxicity.Conclusion and ImplicationsCaspase‐1 is essential for FS generation. CZL80 is a promising low MW inhibitor of FS and later enhanced epileptogenic susceptibility.
Performance of the unilateral AV/IVC index in primary hyperaldosteronism subtype prediction: A validation study in a single tertiary centre
Authors: Suntornlohanakul Onnicha , Soonthornpun Supamai , Srisintorn Wisarut , Murray Robert D. , Kietsiriroje Noppadol 
Published: April 2020

AbstractBackgroundFailure of cannulation of the right adrenal vein is frequent during AVS for investigation of primary aldosteronism (PA). The aldosterone:cortisol ratio of either adrenal vein compared with the inferior vena cava (AV/IVC index) has been proposed to differentiate between unilateral and bilateral disease, and aid in lateralization of unilateral disease.MethodsSixty‐two patients with unilateral or bilateral PA identified by either successful bilateral (45 patients) or unilateral (17 patients) adrenal vein cannulation, and with biochemical remission following surgery were enrolled into the analysis. The diagnostic performances of the previously identified AV/IVC index cut‐offs of ≥5.5 to predict ipsilateral disease and ≤0.5 to predict contralateral disease were validated using data from the entire cohort.ResultsFifty‐three patients had unilateral PA and 9 patients bilateral PA. The area under ROC curve (AUROC) of the AV/IVC cut‐off ≤0.5 for identifying unilateral aldosterone secretion from the contralateral adrenal was 0.95 (95% CI; 0.88‐0.99), whereas the AUROC of the AV/IVC cut‐off ≥5.5 for identifying unilateral aldosterone secretion from ipsilateral adrenal was 0.96 (95% CI; 0.92‐0.99). The AV/IVC index cut‐off value of 0.5 had 93% sensitivity and 91% specificity, and the AV/IVC index cut‐off value of 5.5 had 21% sensitivity and 100% specificity. The optimal AV/IVC cut‐offs to achieve 100% specificity for our cohort were >2.4 and <0.1 to predict ipsilateral and contralateral disease.ConclusionOur data confirm that the AV/IVC index is a potential tool for subtype classification and lateralization in patients with PA in the setting of failed bilateral, but successful unilateral, adrenal vein cannulation during AVS.
Clinical characteristics of familial hypocalciuric hypercalcaemia type 1: A multicentre study of 77 adult patients
Authors: Mouly Céline , Vargas‐Poussou Rosa , Lienhardt Anne , Silve Caroline , Hureaux Marguerite , Magdelaine Corinne , Buffet Alexandre , Grunenwald Solange , Kuhn Jean-Marc , Brue Thierry , Reznik Yves , Tabarin Antoine , Martin‐Coignard Dominique , Haymann Jean‐Philippe , Tack Ivan , Bennet Antoine , Caron Philippe , Linglart Agnès , Vezzosi Delphine ,   for the Reference Centre for Rare Diseases of Calcium, Phosphate Metabolism
Published: April 2020

AbstractObjectiveFamilial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss‐of‐function mutations of the calcium‐sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1.Design and patientsThis observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.ResultsHypercalcaemia was diagnosed at a median age of 53 years [IQR: 38‐61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63‐2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1‐7.1], and the median 24‐hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9‐4.0]. Osteoporosis (dual X‐ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established.ConclusionThis large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.
Socioeconomic deprivation and social capital in kinship carers using a helpline service
Authors: Taylor Emily P. , Di Folco Simona , Dupin Melanie , Mithen Heather , Wen Luis , Rose Lilian , Nisbet Kirsty 
Published: April 2020

AbstractKinship care is the preferred alternative for children who cannot remain with their birth family, maintaining birth family links and continuity in other parts of their life. However, kinship care has also been associated with risk factors including lack of support, difficult contact with biological parents, adverse childhood experiences for the child, carer stress and financial difficulties. Using routine data from a kinship care helpline service, this study employed a mixed‐method analysis of the association between socioeconomic deprivation and risk factors reported by kinship carers and explored social capital in kinship families. Findings indicated common risk factors experienced by kinship families regardless of deprivation level. However, certain risk factors were reported more in areas of high or low socioeconomic deprivation. Mapping the social capital of kinship families indicated that kinship families connect more with relatives than other types of informal, semi‐formal or formal support services. However, these relationships are often problematic. The most prominent obstacle to social capital growth in kinship carers was financial difficulties. Our findings suggest that kinship carers may use support services differentially according to deprivation level, and socioeconomic deprivation may influence building social capital in kinship families.
Predicting bone and soft tissue alterations of immediate implant sites in the esthetic zone using clinical parameters
Authors: Lee Chun‐Teh , Sanz‐Miralles Elena , Zhu Liang , Glick Jaclyn , Heath Andrew , Stoupel Janet 
Published: April 2020

AbstractBackgroundImmediate implantation is generally a predictable treatment, but sometimes there are significant tissue alterations at the surgical site which compromise clinical outcomes.PurposeThis study aimed to investigate the association between tissue alterations and different clinical parameters in esthetic areas following immediate implant placement and provisionalization.Materials and MethodsClinical parameters were measured at 36 non‐grafted immediate implant sites enrolled in a randomized controlled trial. Alterations of bone and soft tissue were measured at 12 months after the treatment. Stepwise linear regression analysis was performed to analyze the association between different clinical parameters and outcomes of interest.ResultsGingival thickness 3 mm apical to the gingival margin (GT3) was positively associated with recession of mid‐buccal gingival margin, while vertical distance between the buccal gingival margin and the crest (GM‐bone) was negatively associated (P = .03, .01). Flap elevation and older age were positively associated with recession of the interproximal gingival margin (P = .04, .01). Horizontal defect dimension was positively associated with buccal ridge dimensional reduction while gingival thickness at free gingival margin (GT1) was negatively associated (P = .01, .04). Regarding interproximal bone level change, none of the clinical parameters was significantly associated.ConclusionsGingival phenotype was the only parameter significantly associated with both buccal gingival recession and buccal ridge dimensional reduction. It is important to assess clinical parameters before and during immediate implant procedure.
A comparative evaluation of dexmedetomidine and midazolam in pediatric sedation: A meta‐analysis of randomized controlled trials with trial sequential analysis
Authors: Lang Bingchen , Zhang Lingli , Zhang Wensheng , Lin Yunzhu , Fu Yuzhi , Chen Shouming 
Published: April 2020

AbstractBackgroundThe present study with trial sequential analysis (TSA) was conducted to evaluate comprehensively the efficacy and safety of dexmedetomidine and midazolam in pediatric sedation, and to investigate whether the outcomes achieved the required information size to draw the conclusions.MethodsPubMed, Embase, and Cochrane Library were searched from inception to October 2019. All randomized controlled trials used dexmedetomidine and midazolam in pediatric sedation were enrolled. Sedative efficacy, postoperative analgesic effect, and incidence of emergence agitation were considered as the co‐primary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to rate the quality of evidences.ResultsWe acquired data from 34 studies involving 2281 pediatric patients. The results indicated that administration of dexmedetomidine was associated with less incidence of emergence agitation (RR = 0.78, with 95% CI [0.65, 0.92]) and more satisfactory sedation at parental separation (RR = 0.31, with 95% CI [0.24, 0.41]) compared to midazolam, and the current sample sizes were sufficient with unnecessary further trials. Two groups did not differ significantly in sedation level at mask induction (RR = 0.86, with 95% CI [0.74, 1.00]). And using of dexmedetomidine was associated with less incidence of postoperative analgesic rescue (RR = 0.57, with 95% CI [0.35, 0.93]), but the number of patients was too few to achieve the required information size and to draw reliable conclusions. Premedication of dexmedetomidine was associated with significant less value of SBP, heart rate, increased incidence of bradycardia, and a lower rate of shivering. And there were no differences about onset of sedation and recovery time between two groups.ConclusionsGiven that more satisfactory sedation at separation from parents and less incidence of emergence agitation, dexmedetomidine is preferred for pediatric sedation. However, compared with midazolam, the superiority of dexmedetomidine in providing adequate sedation at mask induction and postoperative analgesic effects has not yet been defined.
Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p
Authors: Cao Lihua , Liu Wei , Zhong Yancheng , Zhang Yanru , Gao Dan , He Tiantian , Liu Ying , Zou Zi , Mo Yuqing , Peng Shuping , Shuai Cijun 
Published: April 2020

AbstractObjectivesIncreasing evidences suggest that inducing mesenchymal stem cells to differentiate into osteoblasts has been as an especially important component in the prevention and therapy for degenerative bone disease. Here, we identify a novel lncRNA, linc02349, which increases significantly during osteogenic differentiation.Materials and methodsHuman umbilical cord‐derived stem cells (hUC‐MSCs) and dental pulp mesenchymal stem cells were used. Overexpression and knockdown of linc02349 in cell lines were generated using lentiviral‐mediated gene delivery method. Bioinformatics prediction, Ago2‐RIP assay and dual‐luciferase reporter system were employed to examine miRNA which interacts with linc02349. The RNA FISH assay was performed to identify the subcelluar location of linc02349. Alizarin Red S staining, ALP staining and qPCR were applied to identify the osteogenic differentiation. The potential linc02349‐regulated genes, miR‐25‐3p and miR‐33b‐5p, were explored by ChIP, RIP and Western blotting assays. Micro‐CT was used to measure the osteogenic content in bone formation assay in vivo.ResultsLinc02349 overexpression improves osteogenic differentiation by in vitro and in vivo analysis. Mechanistically, linc02349 acts as a molecular sponge for miR‐25‐3p and miR‐33b‐5p to control expression abundance of SMAD5 and Wnt10b, respectively, which eventually activated Dlx5/OSX pathway and hence promoted osteogenic differentiation. In addition, we revealed that STAT3 interacts with linc02349 promoter region and positively regulates the linc02349 transcriptional activity.ConclusionThese findings identify that linc02349 modulates the osteogenic differentiation through acting as a sponge RNA of miR‐25‐3p and miR‐33b‐5p and regulating SMAD5 and Wnt10b, and proposed a new interaction between STAT3 and linc02349, which could be a potential target in the process the osteogenesis of hUC‐MSCs for future clinical application.
Left ventricular geometry as a predictor of carotid artery stenosis severity in patients undergoing carotid artery stenting
Authors: Duran Karaduman Bilge , Ayhan Hüseyin , Keleş Telat , Bozkurt Engin 
Published: April 2020

AbstractBackground and AimCerebrovascular diseases are the second most common cause of death worldwide. Moderate and severe carotid artery stenosis causes nearly 10% of all strokes. LV geometry is a familiar prognostic and diagnostic factor in several populations; yet, data on its role in carotid artery stenosis are unknown. In our study, we investigated the prognostic value of LV geometry in predicting carotid artery stenosis severity in patients undergoing carotid artery stenting.MethodsPatients who underwent carotid artery stenting between January 2012 and January 2016 at our tertiary care center were evaluated retrospectively. Two hundred fifty‐five patients who underwent carotid artery stenting were included in the study. Accessible echocardiographic documentation of ninety‐eight patients was accessed and evaluated.ResultsLV normal geometry was detected in 37 (37.7%) of the 98 carotid artery stenting (CAS) patients, concentric hypertrophy in 13 (13.2%), eccentric hypertrophy in 9 (9.1%), and concentric remodeling in 39 (39.7%). By a majority, distal filter was used in normal geometry and eccentric hypertrophy groups (82.9% vs 100%, P: .017). Considering the relationship between carotid artery stenosis severity and LV geometry, we determined that the stenosis severity was statistically significantly higher in the concentric hypertrophy group (p:0.012). However, although no complications were detected in the concentric hypertrophy group, it did not reach statistical significance between the groups (P: .058). LVMi and as expected, Doppler velocity showed a significant correlation with stenosis severity (r = .23 vs .54; P: .021, <.001, respectively).ConclusionEchocardiographic evaluation of LV geometry provided prognostic information in the development of carotid artery stenosis. Abnormal LV geometry is an independent predictor in detecting the severity of carotid artery stenosis undergoing carotid artery stenting.
Implications of size‐selective fisheries on sexual selection
Authors: Uusi‐Heikkilä Silva 
Published: April 2020

AbstractFisheries often combine high mortality with intensive size selectivity and can, thus, be expected to reduce body size and size variability in exploited populations. In many fish species, body size is a sexually selected trait and plays an important role in mate choice and mate competition. Large individuals are often preferred as mates due to the high fecundity and resources they can provide to developing offspring. Large fish are also successful in competition for mates. Fisheries‐induced reductions in size and size variability can potentially disrupt mating systems and lower average reproductive success by decreasing opportunities for sexual selection. By reducing population sizes, fisheries can also lead to an increased level of inbreeding. Some fish species avoid reproducing with kin, and a high level of relatedness in a population can further disrupt mating systems. Reduced body size and size variability can force fish to change their mate preferences or reduce their choosiness. If mate preference is genetically determined, the adaptive response to fisheries‐induced changes in size and size variability might not occur rapidly. However, much evidence exists for plastic adjustments of mate choice, suggesting that fish might respond flexibly to changes in their social environment. Here, I first discuss how reduced average body size and size variability in exploited populations might affect mate choice and mate competition. I then consider the effects of sex‐biased fisheries on mating systems. Finally, I contemplate the possible effects of inbreeding on mate choice and reproductive success and discuss how mate choice might evolve in exploited populations. Currently, little is known about the mating systems of nonmodel species and about the interplay between size‐selective fisheries and sexual selection. Future studies should focus on how reduced size and size variability and increased inbreeding affect fish mating systems, how persistent these effects are, and how this might in turn affect population demography.
The time‐varying performance of UK analyst recommendation revisions: Do market conditions matter?
Authors: Su Chen , Zhang Hanxiong , Hudson Robert S. 
Published: April 2020

AbstractThis study examines the time‐varying performance of investment strategies following analyst recommendation revisions in the UK stock market, with specific emphasis on the impact of changing market conditions. We find a negative relationship between the recommendation performance and market conditions as measured in terms of past market return and market volatility. In particular, the upgrade (downgrade) portfolio generates significantly positive (negative) net abnormal returns in bad market conditions (e.g., the dot‐com bubble burst in 2000 and the credit crisis in 2007), but not in other periods of time. Moreover, our non‐temporal threshold regression analysis shows that the reported negative relationship disappears when market conditions become better, i.e., when the past market return (market volatility) is higher (lower) than a certain level, indicating the importance of taking non‐linearity into account in the long sample period as examined in this study. Our time‐series bootstrap simulations further confirm that the superior recommendation performance in bad market conditions is not due to random chance; analysts have certain skills in making valuable up/downward revisions in bad markets.
Evidence for intraspecific phenotypic variation in songbirds along elevation gradients in central Europe
Authors: Sander Martha Maria , Chamberlain Dan 
Published: April 2020

Studying phenotypic variations along gradients may provide insights into mechanisms that drive species distributions and thus can be useful indicators of environmental change. In mountains, the study of phenotypic variation along elevation gradients is of increasing relevance due to the impacts of climate change. We analysed European ringing data to measure the direction of phenotypic variation along elevation gradients in six common, resident songbird species occurring along a wide elevational range. We modelled intraspecific change in wing length, body mass and their ratio with elevation and found a significant increase in wing length and a decrease in body mass at high elevations. The results of our exploratory analysis show the potential that continent‐wide ringing databases offer to describe patterns of phenotypic variation along environmental gradients.
Effects of oral health promotion programmes on adolescents’ oral health‐related quality of life: A systematic review
Authors: Lattanzi Aretuza Pires dos Santos , Silveira Flávia Maia , Guimarães Ludmila , Antunes Lívia Azeredo Alves , dos Santos Antunes Leonardos , Assaf Andrea Videira 
Published: April 2020

AbstractObjectiveTo evaluate the effects of oral health promotion programmes (OHPP) on adolescents' oral health‐related quality of life (OHRQoL).MethodsAn electronic search was performed in five databases (MEDLINE via PubMed, Scopus, Virtual Health Library, Web of Science, Cochrane, Grey Literature databases), and specific indexers were used in the manual search. Clinical/community trials, cross‐sectional or cohort studies, published in any language, were included. Studies meeting the inclusion criteria were analysed for quality and bias risk. ResultsFrom a total of 2343 abstracts, 4 articles were selected for quality evaluation including 2 studies classified with low, 1 with moderate and 1 with high methodological quality. The qualitative synthesis showed some methodological biases and heterogeneous interventions. Effective OHPP improve OHRQoL. The association of educational and dental care strategies generated greater positive effects on OHRQoL than those related only to treatment or isolated educational practices.ConclusionAlthough studies showed positive effects of OHPP on adolescents’ OHRQoL, both their shortage and low methodological quality indicates the need for developing other well‐designed studies to investigate the present question. Record number in PROSPERO database (CRD42018084434).
Milk lipid in vitro digestibility in wheat, corn and rice starch hydrogels
Authors: Huang Zhiguang , Brennan Charles S. , Mohan Maneesha S. , Stipkovits Letitia , Zheng Haotian , Kulasiri Don , Guan Wenqiang , Zhao Hui , Liu Jianfu 
Published: April 2020

SummaryStarch‐based hydrogels or nanoemulsions have been used to regulate lipid digestibility. However, there is a paucity of reports on how starch gels affect milk lipid in vitro digestion. This study compared the pancreatic‐lipase‐catalysed digestibility of milk lipids in two matrices: milk fat dispersion and milk fat‐loaded starch gels. Optical microscopy analysis illustrated that lipid droplets were distributed evenly in starch gels. The peak viscosities of lipid‐containing starch gels were higher than those of samples without filled‐lipids, whereas final viscosities were reduced with the addition of lipid. Free fatty acid release measurement showed that milk fat embedded in starch gels were two to three times more digestible than dispersed milk fat globules in aqueous phase, as confirmed by a multistep hydrolysis reaction model. This study offers a feasible way to manipulate milk lipid digestibility by stabilisation with starch gels.