bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nordic screening guideline for juvenile idiopathic arthritis‐related uveitis
Authors: Leinonen Sanna 
Published: December 2022

AbstractPurposeThe purpose of this perspective was to shed light on screening of uveitis among Nordic children with juvenile idiopathic arthritis (JIA).MethodsA literature search was conducted to review predictors of JIA‐uveitis and previous JIA‐uveitis screening recommendations.ResultsPredictors of uveitis in JIA are younger age and positive antinuclear antibody titre at onset of JIA, specific subtypes of JIA (extended and persistent oligoarthritis, rheumatoid factor negative polyarthritis and psoriatic arthritis) and short duration of JIA. Methotrexate and monoclonal tumour necrosis factor (TNF) inhibitor treatment reduce the risk JIA‐uveitis.ConclusionChildren with all of the above risk factors should be screened frequently but if they receive TNF inhibitor or methotrexate therapy, they may be screened less frequently. Children with none of the risk factors do not benefit from long‐term screening for uveitis. A guideline for intervals and overall length of screening was prepared considering currently known risk factors for JIA‐uveitis, the Nordic population and previous guidelines.
Effect of a strong CYP3A4 inhibitor and inducer on the pharmacokinetics of senaparib (IMP4297) in healthy volunteers: A drug–drug interaction study
Authors: Hu Xiaolei , Hsieh Chih‐Yi , Zhang Yanxin , Liu Wanli , Xu Sumei , Cai Sui Xiong , Liu Lan , Zhang Ming , Shi Huiyan , Zhang Hongxia , Liu Ping , Li Xiaomin , Xu Pingsheng 
Published: December 2022

AimsA phase I open‐label study assessed the effect of multiple oral doses of a potent CYP3A4 inhibitor (itraconazole) and inducer (rifampicin) on the pharmacokinetic profile of a single oral dose of senaparib, a novel, highly potent poly‐(ADP‐ribose) polymerase 1/2 inhibitor and CYP3A4 substrate, in Chinese healthy male volunteers (HMV).MethodsAdult HMV were enrolled to the itraconazole or rifampicin group (n = 16 each). In Period 1, all participants received a single oral dose of senaparib 40 mg (itraconazole group) or 100 mg (rifampicin group). In Period 2, the same dose was coadministered with itraconazole (200 mg) and rifampicin (600 mg), respectively. The primary endpoints were senaparib exposure parameters.ResultsCoadministration with itraconazole significantly increased exposure of senaparib and decreased that of its major metabolites M9 and M14. Maximum plasma senaparib concentration (Cmax) was increased by ~79% and area under the concentration–time curve (AUC) increased by ~2.8‐fold. Coadministration with rifampicin significantly reduced the Cmax and AUC of senaparib by ~59 and 83%, respectively. The Cmax for both M9 and M14 was slightly increased, although AUC was decreased. All treatment‐emergent adverse events were grade ≤2, regardless of the treatment administered.ConclusionIn Chinese HMV, the exposure of senaparib was significantly increased when coadministered with itraconazole and significantly decreased when coadministered with rifampicin. It is recommended to avoid concomitant use of senaparib and strong inhibitors or inducers of CYP3A4.
Which method delivers greater signal‐to‐noise ratio: Structural equation modelling or regression analysis with weighted composites?
Authors: Yuan Ke‐Hai , Fang Yongfei 
Published: December 2022

AbstractObservational data typically contain measurement errors. Covariance‐based structural equation modelling (CB‐SEM) is capable of modelling measurement errors and yields consistent parameter estimates. In contrast, methods of regression analysis using weighted composites as well as a partial least squares approach to SEM facilitate the prediction and diagnosis of individuals/participants. But regression analysis with weighted composites has been known to yield attenuated regression coefficients when predictors contain errors. Contrary to the common belief that CB‐SEM is the preferred method for the analysis of observational data, this article shows that regression analysis via weighted composites yields parameter estimates with much smaller standard errors, and thus corresponds to greater values of the signal‐to‐noise ratio (SNR). In particular, the SNR for the regression coefficient via the least squares (LS) method with equally weighted composites is mathematically greater than that by CB‐SEM if the items for each factor are parallel, even when the SEM model is correctly specified and estimated by an efficient method. Analytical, numerical and empirical results also show that LS regression using weighted composites performs as well as or better than the normal maximum likelihood method for CB‐SEM under many conditions even when the population distribution is multivariate normal. Results also show that the LS regression coefficients become more efficient when considering the sampling errors in the weights of composites than those that are conditional on weights.
Improved PIEZO1 agonism through 4‐benzoic acid modification of Yoda1
Authors: Parsonage Gregory , Cuthbertson Kevin , Endesh Naima , Murciano Nicoletta , Hyman Adam J. , Revill Charlotte H. , Povstyan Oleksandr V. , Chuntharpursat‐Bon Eulashini , Debant Marjolaine , Ludlow Melanie J. , Futers Timothy Simon , Lichtenstein Laeticia , Kinsella Jacob A. , Bartoli Fiona , Rotordam Maria Giustina , Becker Nadine , Brüggemann Andrea , Foster Richard , Beech David J. 
Published: December 2022

Background and PurposeThe protein PIEZO1 forms mechanically activated, calcium‐permeable, non‐selective cation channels in numerous cell types from several species. Options for pharmacological modulation are limited and so we modified a small‐molecule agonist at PIEZO1 channels (Yoda1) to increase the ability to modulate these channels.Experimental ApproachMedicinal chemistry generated Yoda1 analogues that were tested in intracellular calcium and patch‐clamp assays on cultured cells exogenously expressing human or mouse PIEZO1 or mouse PIEZO2. Physicochemical assays and wire myography assays on veins from mice with genetic disruption of PIEZO1.Key ResultsA Yoda1 analogue (KC159) containing 4‐benzoic acid instead of the pyrazine of Yoda1 and its potassium salt (KC289) have equivalent or improved reliability, efficacy and potency, compared with Yoda1 in functional assays. Tested against overexpressed mouse PIEZO1 in calcium assays, the order of potency (as EC50 values, nM) was KC289, 150 > KC159 280 > Yoda1, 600). These compounds were selective for PIEZO1 over other membrane proteins, and the physicochemical properties were more suited to physiological conditions than those of Yoda1. The vasorelaxant effects were consistent with PIEZO1 agonism. In contrast, substitution with 2‐benzoic acid failed to generate a modulator.Conclusion and Implications4‐Benzoic acid modification of Yoda1 improves PIEZO1 agonist activity at PIEZO1 channels. We suggest naming this new modulator Yoda2. It should be a useful tool compound in physiological assays and facilitate efforts to identify a binding site. Such compounds may have therapeutic potential, for example, in diseases linked genetically to PIEZO1 such as lymphatic dysplasia.
The flavonoid GL‐V9 alleviates liver fibrosis by triggering senescence by regulating the transcription factor GATA4 in activated hepatic stellate cells
Authors: Zhao Jiawei , Bai Dongsheng , Qi Lei , Cao Wangjia , Du Jiaying , Gu Chunyang , Zhou Chen , Gao Yuan , Zhang Lulu , Zhao Yue , Lu Na 
Published: December 2022

Background and purposeLiver fibrosis is a critical risk factor for the progression from chronic liver injury to hepatocellular carcinoma. Clinically, there is a lack of therapeutic drugs for liver fibrosis. Previous studies have confirmed that GL‐V9, a newly synthesized flavonoid derivative, exhibits anti‐inflammatory activity, but whether it has anti‐hepatic fibrosis actions remains unclear. This study aimed to investigate the anti‐fibrotic activities and potential mechanisms of GL‐V9.Experimental approachBile duct ligation (BDL) and carbon tetrachloride (CCl4) challenges were used to assess the anti‐fibrotic effects of GL‐V9 in vivo. Mouse primary hepatic stellate cells (pHSCs) and the human HSC line LX2 also served as a liver fibrosis model in vitro. Cellular functions and molecular mechanism were analysed using senescence‐associated beta‐galactosidase staining, real‐time PCR, western blotting, immunofluorescence, and co‐immunoprecipitation.Key resultsGL‐V9 attenuated hepatic histopathological injury and collagen accumulation, as well as decreasing the expression of fibrotic genes in vivo. GL‐V9 promoted senescence and inhibited the expression of fibrogenic genes in HSCs in vitro. Mechanistic studies revealed that GL‐V9 induced senescence by upregulating GATA4 expression in HSCs. Further studies confirmed that GL‐V9 stabilized GATA4 by promoting autophagic degradation of P62.Conclusion and implicationsGL‐V9 exerted potent anti‐fibrotic effects both in vivo and in vitro by stabilizing GATA4, thereby promoting the senescence of HSCs, and by avoiding its activation and ultimately inhibiting liver fibrosis. This action indicated that the flavonoid GL‐V9 is a potential therapeutic candidate for the treatment of liver fibrosis.
Histone deacetylase activity is a novel target for epithelial barrier defects in patients with eosinophilic chronic rhinosinusitis with nasal polyps
Authors: Duan Su , Han Xinling , Jiao Jian , Wang Ming , Li Ying , Wang Yang , Zhang Luo 
Published: December 2022

AbstractBackgroundStudies have independently indicated that eosinophils and histone deacetylases (HDACs) may compromise the integrity of the epithelial barrier in nasal polyps; however, the underlying mechanisms are not clear. In this study, we aimed to investigate the role of eosinophilia and HDACs in regulation of tight junctions (TJs) and nasal epithelial barrier integrity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients.MethodsExpression of mRNAs and proteins of TJs and HDACs of biopsy specimens and air‐liquid interface (ALI) human nasal epithelial cell cultures (HNECs) from eosinophilic and noneosinophilic CRSwNP patients and healthy controls was assessed. The ALI HNECs were also assessed for changes in transepithelial electrical resistance (TER) and paracellular flux of fluorescein isothiocyanate (FITC)‐labelled dextran. Meanwhile, the assessments for the effect of HDAC inhibitor in eosinophilic nasal polyps were also conducted.ResultsDecreased TER and increased paracellular flux of FITC‐labelled dextran in the ALI cultures were found in both eosinophilic and noneosinophilic CRSwNP, along with irregular, patchy and reduced expression of claudin‐1, 4, 7, occludin, zonula occludens (ZO)‐1 and ZO‐2 and increased expression of HDAC1, 9 and SIRT7 for both ALI culture cells and biopsy specimens, especially for the eosinophilic CRSwNP group. Treatment of eosinophilic CRSwNP ALI‐HNECs with an HDAC inhibitor improved the TJs expression and epithelial barrier integrity.ConclusionsOur data suggest that eosinophilia and HDACs influence epithelial barrier function in CRSwNP patients by regulating TJ protein expression. Targeting HDACs with specific inhibitors may be a potential treatment option for patients with eosinophilic CRSwNP.
Gradual Route to Productivity: Evidence from Turkish Morphological Causatives
Authors: Ger Ebru , You Guanghao , Küntay Aylin C. , Göksun Tilbe , Stoll Sabine , Daum Moritz M. 
Published: December 2022

AbstractBecoming productive with grammatical categories is a gradual process in children's language development. Here, we investigated this transition process by focusing on Turkish causatives. Previous research examining spontaneous and elicited production of Turkish causatives with familiar verbs attested the onset and early stages of productivity at ages 2 to 3 (Aksu‐Koç & Slobin, 1985; Nakipoğlu, Uzundag, & Sarıgül, 2021). So far, however, we know very little about children's understanding of causatives with novel verbs. In the present study, we asked: (a) When does the generalization of causative morphology in a novel context emerge? and (b) What role does child‐directed input play in this development? To answer the first question, we conducted comprehension‐judgment experiments with children aged 2;6–6;11 using pseudo‐verbs (Study 1 & 2). Results showed that children preferred the Turkish causative suffix ‐DIr over an unrelated or no suffix to denote caused events earliest at age 4;10. To answer the second question, we analyzed child‐directed speech from a longitudinal corpus of Turkish language acquisition (Study 3). Results showed that when addressing children younger than age 3, caregivers used the ‐DIr suffix with little variation considering the overall variability of verbs they could utter. Overall, these findings suggest that productivity with morphological causatives in a novel context emerges in a later stage of acquisition. This later development might partly be accounted for by the insufficient variation of morphological causatives in the early input.
Prediction of pine mistletoe infection using remote sensing imaging: A comparison of the artificial neural network model and logistic regression model
Authors: Usta Ayhan , Yilmaz Murat 
Published: December 2022

AbstractIn this study, the prediction of pine mistletoe distribution in Scots pine ecosystems was explored using remote sensing variables to compare the multilayer perceptron (MLP) artificial neural network (ANN) and logistic regression (LR) model performances. For this purpose, 109 sample plots were distinguished in pure Scots pine forests (natural) in the Eastern Black Sea Region of Turkey. Distinguishing mistletoe‐infected stands (69) and uninfected stands (40) was performed with field observations. The variables acquired from Landsat 8 (Level 1) images were used as independent variables for independent‐sample t‐test, MLP ANN and LR models. Remote sensing variables indicated that mistletoe‐infected stands were in drier areas with a lower vegetation‐leaf area index. Based on the performance results of both models, the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV) and accuracy of the MLP ANN model were superior to those of the LR model. The prediction percentages (SEN, SPE, PPV and NPV) of mistletoe‐infected stands were better than the prediction percentages of uninfected stands. The prediction accuracies of LR and MLP ANN models were 74.3% and 89.6%, respectively. However, all remote sensing variables were included in the prediction equation of the MLP ANN model, while the thermal infrared 1 (TIRS1) variable was included in the LR model. In the MLP ANN model, the TIRS1 variable also had the highest normalized importance (100%). The area under the curve (AUC) value for identifying the mistletoe‐infected stands of Scots pine forests used by the MLP ANN model (0.892 ± 0.034) was higher than in the LR model (0.838 ± 0.039), explaining the more accurate predictions obtained from the MLP ANN model. The MLP ANN model showed much better performance than the LR model. The results of this study are expected to make important contributions to the identification of potential mistletoe‐infected areas.
CCL6 promotes M2 polarization and inhibits macrophage autophagy by activating PI3‐kinase/Akt signalling pathway during skin wound healing
Authors: Feng Xiao , Ji Yu , Zhang Ce , Jin Tingting , Li Jingyu , Guo Jincai 
Published: December 2022

AbstractThe transition of macrophages from the proinflammatory M1 to the anti‐inflammatory M2 phenotype is crucial during the wound healing process. In this study, we assess the role of chemokine (C‐C motif) ligand 6 (CCL6) in modulating macrophage polarization and wound healing. Initially, we observed significantly upregulated CCL6 expression in the skin tissue on the edge of the wound during the inflammation and proliferation phases. Furthermore, we discovered that the mice treated with rCCL6 had significantly accelerated wound healing and increased levels of M2‐type macrophages. Using in vitro models, we found that CCL6 promotes the M2 polarization of macrophages by activating the PI3‐kinase/Akt signalling pathway. Additionally, our results showed that CCL6 inhibited macrophage autophagy and accelerated wound healing, whereas the autophagy inducer rapamycin delayed wound healing. Finally, we determined that the PI3‐kinase inhibitor LY294002 promoted macrophage autophagy and decreased M2 macrophages, indicating the importance of PI3‐kinase in M2 polarization, and this process was reversed by CCL6. Taken together, our study demonstrates that CCL6 promotes M2 polarization, inhibits macrophage autophagy, and accelerates skin wound healing by activating the PI3‐kinase/Akt signalling pathway.
c‐Src activation as a potential marker of chemical‐induced skin irritation using tissue‐engineered skin equivalents
Authors: Harding Amy L. , Colley Helen E. , Vazquez Inmaculada Barragan , Danby Simon , Hasan Md Zobaer , Nakanishi Hirofumi , Furuno Tetsuo , Murdoch Craig 
Published: December 2022

AbstractSkin irritancy to topically applied chemicals is a significant problem that affects millions of people worldwide. New or modified chemical entities must be tested for potential skin irritancy by industry as part of the safety and toxicity profiling process. Many of these tests have now moved to a non‐animal‐based format to reduce experiments on animals. However, these tests for irritancy potential often rely on monolayer cultures of keratinocytes that are not representative of the skin architecture or tissue‐engineered human skin equivalents (HSE) using complex multi‐gene expression panels that are often cumbersome and not amenable for high throughput. Here, we show that human skin equivalents increase abundance of several phosphorylated kinases (c‐Src, c‐Jun, p53, GSK3α/β) in response to irritant chemical stimulation by phosphokinase array analysis. Specific phosphorylation of c‐SrcY419 was confirmed by immunoblotting and was plasma membrane‐associated in basal/spinous cells by phospho‐specific immunohistochemistry. Moreover, c‐SrcY419 phosphorylation in response to the irritants lactic acid and capsaicin was inhibited by the c‐Src inhibitors KB‐SRC and betaine trimethylglycine. These data provide the first evidence for c‐Src specific activation in response to chemical irritants and point to the development of new modes of rapid testing by immunodetection for first‐pass screening of potential irritants.
Impact of Covid‐19 pandemic on the transnationalization of LGBT* activism in Japan and beyond
Authors: Yamamura Sakura 
Published: December 2022

AbstractThe global Covid‐19 pandemic has strongly impacted social practices, relocating communications and social networks into the digital space. Contextualized in such impact of the Covid‐19 pandemic, the local LGBT* activism in Japan achieved a special momentum: both the acceleration of the socio‐spatial relocation of LGBT* activism to the digital space and the postponement of the Tokyo Olympics 2020 by 1 year enabled activists to mobilize people domestically and globally. The pandemic was not the actual cause or driver of the local LGBT* activism, yet it has been an important catalyst for the transnationalization of the local movement in Japan, pushing evidently the spatial boundaries to achieve broader public outreach but in turn also receiving stronger support from the global community through transnational networks. This study explores novel dynamics of spatiality and temporality of social transformations through the Covid‐19‐induced increase in global digital connectedness as well as transnationalization of local actions.
‘We want it all’:ARTpreferences assessed byDesirability ofOutcomeRanking
Authors: Homerova Ivana , Patel Avani , Macallan Derek C. 
Published: December 2022

AbstractObjectivesUnderstanding how people living with HIV (PLWH) view antiretroviral therapy (ART) prescribing choices is fundamental to patient‐centred care. We used the Desirability of Outcome Ranking (DOOR) approach to explore patient ART preferences.MethodsSeventy‐four PLWH entered the study, 20 into the ‘pilot study’, and 54 in the ‘comparative study’. Participants ranked five different hypothetical patient stories by desirability. Each story comprised five narrative lines, each line addressing one treatment characteristic drawn from one of five pre‐selected domains (treatment failure, treatment difficulty, adverse effects, long‐term complications, life events). Narrative lines could be favourable or adverse. In the pilot study the number of adverse domains varied from one to five. Comparative study stories were fixed at two adverse versus three favourable domains, to test the relative ranking of different domains.ResultsThe pilot study identified a relationship between the number of adverse domains and rank (R2 = 0.54;p < 0.0001, Friedman test), however pairwise differences in ranking were not significant beyond three adverse domains. In the comparative study, all domains were ranked equally across the cohort (p = 0.88; Friedman test). In pre‐defined demographic subgroup analyses, women ranked the ‘treatment failure’ domain significantly less desirable than men (p = 0.0014, Mann–Whitney test).ConclusionsPeople living with HIV appear to care equally about all aspects of ART. The observation that male and female PLWH have different treatment priorities merits further investigation in larger studies. Interindividual differences highlight the importance of individualized shared decision‐making and treatment personalization. DOOR may have a role as a pre‐treatment assessment tool as well as a research technique.
Effect of recombinant buckwheat trypsin inhibitor on gel properties of chicken meat emulsion
Authors: Li Chen , Liu Xin , Li Anzhi , Li Fang 
Published: December 2022

SummaryThe aim of this study was to investigate the effects of purified recombinant buckwheat trypsin inhibitor (rBTI) on gelling properties of chicken meat emulsion. Recombinant BTI was obtained by culturing and inducing an M15 strain containing pQE30‐BTI plasmid, and then purified by Ni2+ affinity chromatography. rBTI exhibited good thermal stability and retained 67.7% ± 4.0% of its initial activity even after heating in a boiling water bath for 100 min. Results showed that the breaking force, deformation, penetration force and water‐holding capacity of chicken meat gels increased with the increase of rBTI (0‰–0.10‰), indicating that rBTI could improve the gel‐forming ability of chicken meat. Meanwhile, trichloroacetic acid (TCA)‐soluble peptide content decreased with rBTI addition and more myosin heavy chain (MHC) was retained on SDS‐PAGE. Compared with the group without rBTI, the content of TCA‐soluble peptide in the group with rBTI (0.10‰) decreased by 52.4%. rBTI is a specific inhibitor for trypsin, one of the dominant proteases resulting in myosin degradation. Thus, we concluded that rBTI improved the gel properties by deducing the degradation of myosin by endogenous enzymes. Furthermore, the addition of rBTI had no significant influence on the whiteness of the gels. With the advantages of good thermal stability, no unpleasant smell and the function of improving gel properties of meat emulsion, rBTI could be used as a potential candidate for food additives in food processing.