bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azithromycin alleviates the severity of rheumatoid arthritis by targeting the unfolded protein response component of glucose‐regulated protein 78 (GRP78)
Authors: Zhang Yongli , Ge Luna , Song Guanhua , Zhang Ruojia , Li Shufeng , Shi Haojun , Zhang Hongchang , Li Yi , Pan Jihong , Wang Lin , Han Jinxiang 
Published: October 2021

Background and PurposeAzithromycin is a macrolide antibiotic with anti‐inflammatory properties. We aim to substantiate the treatment potential of azithromycin in rheumatoid arthritis.Experimental ApproachGene expression profiles were collected by RNA sequencing and the effects of azithromycin were assessed by in vitro and in vivo assays on the effects of azithromycin‐mediated blockade of glucose‐regulated protein 78 (GRP78). Anti‐inflammatory activity of azithromycin was measured in fibroblast‐like synoviocytes from rheumatoid arthritis patients and in collagen‐induced arthritis in DBA/1 mice. Characterization of the binding of azithromycin to GRP78 was performed using drug affinity responsive target stability, proteomics and cellular thermal shift assays. Azithromycin‐mediated inhibition of GRP78 and its relationship to its anti‐arthritic activity was assessed.Key ResultsAzithromycin reduced proinflammatory factor production, cell migration, invasion and chemoattraction and enhanced apoptosis, reducing the deleterious inflammatory response of rheumatoid arthritis fibroblast‐like synoviocytes in vitro. Azithromycin ameliorated the severity of collagen‐induced arthritis lesions as efficiently as the TNFα inhibitor etanercept. Transcriptional analyses suggested that azithromycin treatment impairs signalling cascades associated with cholesterol and lipid biosynthesis. GRP78 was identified as a novel target of azithromycin. Azithromycin‐mediated activation of the unfolded protein response via the inhibition of GRP78 activity is required not only for inducing the expression of C/EBP‐homologous protein (ChOP) but also for the activating sterol‐regulatory element binding protein (SREBP) and its targeted genes involved in cholesterol and lipid biosynthetic processes. Furthermore, deletion of GRP78 abolished the anti‐arthritic activity of azithromycin.Conclusion and ImplicationsThese findings indicate that azithromycin can used to treat rheumatoid arthritis.
P90 ribosomal S6 kinase confers cancer cell survival by mediating checkpoint kinase 1 degradation in response to glucose stress
Authors: Ma Ying , Cui Danrui , Wang Linchen , Wang Yue , Yang Fei , Pan Hui , Gong Longyuan , Zhang Minrun , Xiong Xiufang , Zhao Yongchao 
Published: October 2021

AbstractIn solid tumors, cancer cells have devised multiple approaches to survival and proliferate in response to glucose starvation that is often observed in solid tumor microenvironments. However, the precise mechanisms are far less known. Herein, we report that glucose deprivation activates 90‐kDa ribosomal S6 kinase (p90 RSK), a highly conserved Ser/Thr kinase, and activated p90 RSK promotes cancer cell survival. Mechanistically, activated p90 RSK by glucose deprivation phosphorylates checkpoint kinase 1 (CHK1), a key transducer in checkpoint signaling pathways, at Ser280 and triggers CHK1 ubiquitination mediated by SCFβ‐TrCP ubiquitin ligase and proteasomal degradation, subsequently suppressing cancer cell apoptosis induced by glucose deprivation. Importantly, we identified an inverse correlation between p90 RSK activity and CHK1 levels within the solid tumor mass, with lower levels of CHK1 and higher activity of p90 RSK in the center of the tumor where low glucose concentrations are often observed. Thus, our study indicates that p90 RSK promotes CHK1 phosphorylation at Ser280 and its subsequent degradation, which allows cancer cells to escape from checkpoint signals under the stress of glucose deprivation, leading to cell survival and thus contributing to tumorigenesis.
The commissioning of infant mental health services in the United Kingdom: A study of stakeholder views
Authors: Homonchuk Olha , Barlow Jane 
Published: October 2021

AbstractContextInfant regulatory disturbances are common and stable over time and can compromise infant outcomes across a range of developmental domains. Many such problems have their origins within the parent–infant relationship and specialized parent–infant relationship teams provide support and intervention that is explicitly aimed at addressing such relationship difficulties. However, there are currently only around 27 such teams across the United Kingdom, and just under half of CAMHS do not accept referrals of children under 2 years of age.AimThe current research aimed to examine the views of commissioners of children's services regarding the reasons for commissioning (or not) infant mental health services.MethodFourteen in‐depth interviews were conducted with a range of stakeholders involved in commissioning children's services across 14 areas of England, half of which were commissioning specialized infant mental health services. A thematic analysis was undertaken.ResultsA total of five themes emerged from the data as being key factors in the commissioning of infant mental health services: pressure from local practitioners, policy transfer through policy networks, opportunity for long‐term cost reduction, potential to embed the service model within existing services and perinatal mental health funding.ConclusionAs with commissioning more widely, the commissioning of infant mental health services is a complex process, with a range of factors influencing whether such services are commissioned or not, and data to suggest that the process is currently driven by informal and contingent factors, as much as by the evidence regarding what works.
The prevalence of CFTR mutations in patients with chronic rhinosinusitis: A systematic review and meta‐analysis
Authors: Yong Michael , Hernaiz‐Leonardo Juan Carlos , Alqunaee Marwan , Quon Bradley S , Javer Amin 
Published: October 2021

AbstractObjectivesUndetected cystic fibrosis transmembrane regulator (CFTR) mutations may predispose individuals to develop CRS independent of formal CF diagnosis. The objective of this study was to determine the prevalence of CFTR mutations among individuals with CRS.DesignA systematic search following PRISMA guidelines was performed. A meta‐analysis was performed to calculate pooled estimates for the prevalence of any CFTR mutation and for the DF508 mutation.Setting and participantsThe systematic search included all studies identifying adults diagnosed with CRS, with no limitation to region or publication date. Studies had to identify a sample of patients previously diagnosed with CRS but not with CF and reporting testing for the prevalence of CF or the CFTR gene mutation.Main outcome measuresPrevalence of CFTR mutations among the general CRS population, with subgroup analysis of individuals with the dF508 mutation.Results and conclusionsThe 6 included studies represented five countries: the United States, the UK, France, Poland and Finland. The pooled prevalence of CFTR mutations of any kind in CRS subjects without CF was 5.65% (RE 95% CI 2.99 – 10.41). The overall prevalence for the dF508 mutation was 4.22% (RE 95% CI 1.71 – 10.07). These estimates were significantly higher than the baseline estimated prevalence of CFTR carrier status of 3%–4% in the general population. However, the clinical relevance of the presence of CFTR mutations in CRS patients who have not been diagnosed with CF is currently unclear. Future studies should include sweat chloride testing as a measure of CFTR function.
Translating habitat class to land cover to map area of habitat of terrestrial vertebrates
Authors: Lumbierres Maria , Dahal Prabhat Raj , Di Marco Moreno , Butchart Stuart H. M. , Donald Paul F. , Rondinini Carlo 
Published: October 2021

AbstractArea of habitat (AOH) is defined as the “habitat available to a species, that is, habitat within its range” and is calculated by subtracting areas of unsuitable land cover and elevation from the range. The International Union for the Conservation of Nature (IUCN) Habitats Classification Scheme provides information on species habitat associations, and typically unvalidated expert opinion is used to match habitat to land‐cover classes, which generates a source of uncertainty in AOH maps. We developed a data‐driven method to translate IUCN habitat classes to land cover based on point locality data for 6986 species of terrestrial mammals, birds, amphibians, and reptiles. We extracted the land‐cover class at each point locality and matched it to the IUCN habitat class or classes assigned to each species occurring there. Then, we modeled each land‐cover class as a function of IUCN habitat with (SSG, using) logistic regression models. The resulting odds ratios were used to assess the strength of the association between each habitat and land‐cover class. We then compared the performance of our data‐driven model with those from a published translation table based on expert knowledge. We calculated the association between habitat classes and land‐cover classes as a continuous variable, but to map AOH as binary presence or absence, it was necessary to apply a threshold of association. This threshold can be chosen by the user according to the required balance between omission and commission errors. Some habitats (e.g., forest and desert) were assigned to land‐cover classes with more confidence than others (e.g., wetlands and artificial). The data‐driven translation model and expert knowledge performed equally well, but the model provided greater standardization, objectivity, and repeatability. Furthermore, our approach allowed greater flexibility in the use of the results and uncertainty to be quantified. Our model can be modified for regional examinations and different taxonomic groups.
Cardiovascular risk profiles: A cross‐sectional study evaluating the generalizability of the glucagon‐like peptide‐1 receptor agonist cardiovascular outcome trials REWIND, LEADER and SUSTAIN‐6 to the real‐world type 2 diabetes population in the United Kingdom
Authors: Webb Joanne , Mount Julie , von Arx Lill‐Brith , Rachman Jonathan , Spanopoulos Dionysis , Wood Robert , Tritton Theo , Massey Olivia , Idris Iskandar 
Published: October 2021

AbstractAimsTo determine the proportion of UK patients with type 2 diabetes (T2D) who meet the cardiovascular (CV) or combined CV/core eligibility criteria used for the CV outcome trials (CVOTs) of UK‐marketed glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) showing CV benefit (dulaglutide in REWIND, liraglutide in LEADER and injectable semaglutide in SUSTAIN‐6).Materials and MethodsAdults with T2D on/before June 2018 were identified from the UK Clinical Practice Research Datalink GOLD primary care database and linked to Hospital Episode Statistics data (Protocol 19_262). Patient CV and clinical data were evaluated against the CVOT eligibility criteria. Data were analysed descriptively.ResultsThe study cohort (N = 33 118 patients with T2D) had a mean (standard deviation) age of 66.0 (13.3) years and 56.6% were male. Almost two‐thirds (64.5%) of the study cohort met the CV criteria for REWIND, versus 43.0% for both LEADER and SUSTAIN‐6. The proportions of the study cohort who met the CVOT criteria of “established CV disease” and “CV risk factors only” for REWIND were 22.4% and 42.1%, respectively, versus 38.7% and 4.3%, respectively, for both LEADER and SUSTAIN‐6. The proportions of patients satisfying both CV and core criteria were 44.4% for REWIND, 13.3% for LEADER and 13.5% for SUSTAIN‐6. Study findings remained consistent when restricted to GLP‐1RA users.ConclusionsREWIND captured a trial population more representative of the real‐world T2D population in the United Kingdom than LEADER or SUSTAIN‐6 with regard to both CV and combined CV/core eligibility criteria.
Early inventory management practices in the foreign exchange market: Insights from sixteenth‐century Lyon
Authors: Matringe Nadia 
Published: October 2021

AbstractStudies of the early modern exchange market have usually focused on the strategies of traders who made profits from differences in exchange rates. This article instead focuses on the inventory management practices of exchange dealers, who traded almost exclusively on behalf of third parties while acting as market makers in the Lyon fairs in the sixteenth century. Using evidence from 1 937 transactions performed by one of the major Lyon banks (Salviati), it uncovers a specific rebalancing technique based on the use of the bill of exchange as a netting instrument. Thanks to a system of limit orders, the Lyon exchange dealers were able to offset order flows, thus minimizing their credit risk while remaining exposed to reputational risk. Such a rebalancing mechanism involved multiple clients and markets and contributed to the clearing of international payments once bills reached maturity. Double‐entry bookkeeping both facilitated and limited the use of the bill of exchange as a multilateral netting instrument.
Stay home and be unfair: The amplification of inequalities among families with young children during COVID‐19
Authors: Pitzalis Marco , Spanò Emanuela 
Published: October 2021

AbstractThis article focuses on the educational practices and strategies mobilised by Italian families with children aged six years and younger, during the health crisis caused by the COVID‐19 pandemic in Italy, in 2020. Specifically, we analyse practices and strategies mobilised by families from different social milieus living in rural or urban contexts. We argue that the shift in childcare practices and needs during the pandemic promoted the reaffirmation of traditional gender stereotypes and patterns of gendered labour division through the blurring of temporal and spatial boundaries between paid work, domestic labour and childcare. Our findings shed light on how differences in household circumstances, such as the availability of space in the home, have impacted disparities in childcare. Specifically, how different housing conditions have profoundly influenced the coping mechanisms of both children and parents during school closures. We conclude by discussing teachers' attempts to realise educational activities for supporting continuity in the pedagogical relationship, in a context of different family conditions and educational patterns.
Steady‐state visual evoked potential responses predict visual discomfort judgements
Authors: O'Hare Louise , Hird Emily , Whybrow Mercedes 
Published: October 2021

AbstractIt has been suggested that aesthetically pleasing stimuli are processed efficiently by the visual system, whereas uncomfortable stimuli are processed inefficiently. This study consists of a series of three experiments investigating this idea using a range of images of abstract artworks, photographs of natural scenes, and computer‐generated stimuli previously shown to be uncomfortable. Subjective judgements and neural correlates were measured using electroencephalogram (EEG) (steady‐state visual evoked potentials, SSVEPs). In addition, global image statistics (contrast, Fourier amplitude spectral slope and fractal dimension) were taken into account. When effects of physical image contrast were controlled, fractal dimension predicted discomfort judgements, suggesting the SSVEP response is more likely to be influenced by distribution of edges than the spectral slope. Importantly, when effects of physical contrast and fractal dimension were accounted for using linear mixed effects modelling, SSVEP responses predicted subjective judgements of images. Specifically, when stimuli were not matched for perceived contrast, there was a positive relationship between SSVEP responses and how pleasing a stimulus was judged to be, and conversely a negative relationship between discomfort and SSVEP response. This is significant as it shows that the neural responses in early visual areas contribute to the subjective (un)pleasantness of images, although the results of this study do not provide clear support for the theory of efficient coding as the cause of perceived pleasantness or discomfort of images, and so other explanations need to be considered.
Doing family: Nicaraguan transnational families’ narratives on motherhood
Authors: DePalma Renée , Pérez‐Caramés Antía , Verdía Varela Verónica 
Published: October 2021

AbstractThis article explores transnational motherhood from the perspective of Nicaraguan migrant workers in Spain and Nicaraguan family members caring for migrant women's children. Our sample included families with children who have special needs, to explore how economically disadvantaged families draw upon migration as a strategy to address educational and physical needs not provided by a weak ‘exclusionary’ social policy regime. Applying the notion of the family display to migrant mothers and their families, our research reveals how gendered expectations of parenting shape their experience and the ways in which they explain and justify the migratory project. Migrants and family members, with certain reservations and limitations, actively reinvent motherhood by (re)constructing financial contribution as a type of caring. Our research also unsettles the classic notion of the ‘other mother’, as respondents describe caring as distributed over extended kin networks.
Analysis of water distribution in delipidated human hair by small‐angle neutron scattering (SANS)
Authors: Ishihara Aya , Tsukamoto Yoshiaki , Inoue Hiroyuki , Noda Yohei , Koizumi Satoshi , Joko Kyohei 
Published: October 2021

AbstractObjectiveIt is known that damaged hair has a part of its internal structure damaged, and its water absorption and desorption behavior are different. In recent years, it has been reported that internal lipids play an important role in the adsorption and desorption of water to the hair. Therefore, we investigate whether the water distribution in hair and the amount of internal lipids are related.MethodsTo investigate the effect of internal lipid on water distribution, we prepare human hair samples with and without a partial lack of internal lipids. Internal lipids have been removed using formic acid. The distribution of D2O in the hair is investigated using small angle neutron scattering (SANS) under the wet and dry conditions of each hair sample.ResultsIt is found from the obtained SANS data that formic acid‐treated hairs tended to have fewer 40Å‐sized water clusters that were periodically present along the fibre axis in the wet condition. On the other hand, in the dry condition, there were no differences in water distribution between samples.ConclusionThese observations are believed to have been caused by the reduction of 40Å‐sized water clusters existing on the constituents removed by formic acid treatment, especially the hydrophobic (lipid) constituent tissues. Consequently, it is clarified that internal lipids are deeply involved in the state of water distribution on hair in wet conditions.
Application of Raman spectroscopy in a correlation study between protein oxidation/denaturation and conformational changes in beef after repeated freeze–thaw
Authors: Chen Qingmin , Xie Yunfei , Yu Hang , Guo Yahui , Cheng Yuliang , Yao Weirong 
Published: October 2021

AbstractKnowledge of protein properties is vital for quality assessment in meat systems. This study applied Raman spectroscopy to investigate the relationship between protein oxidation/denaturation and conformational changes in beef during repeated freeze–thaw (RFT). A lower α‐helix and higher β‐sheet content was observed after RFT. The I850 cm−1/I830 cm−1 intensity ratio of tyrosine indicates that tyrosine residues were exposed to the polar environment during RFT. Further, RFT led to increased carbonyl content and surface hydrophobicity, with decreased total sulphydryl content, Ca2+‐ATPase activity and enthalpy of myosin (ΔH1). Subsequently, correlation analysis showed that carbonyl content, Ca2+‐ATPase activity and ΔH1 in beef protein have good correlations with secondary protein structure data, especially ΔH1, which has a strong negative correlation (r = −0.906) with the β‐sheet/α‐helix ratio. Therefore, protein secondary conformation information during RFT has the potential to be used as a parameter for studying the thermal properties of myosin.
Improving moisture barrier and functional properties of active film from genipin‐crosslinked chitosan/astaxanthin film by heat curing
Authors: Inthamat Patthrare , Lee Youn Suk , Boonsiriwit Athip , Siripatrawan Ubonrat 
Published: October 2021

SummaryThis research aimed to improve moisture barrier and functional properties of genipin‐crosslinked chitosan/astaxanthin film by heat curing. The effect of heat curing (25, 80 and 105 °C) on film properties was investigated by measuring water vapour permeability (WVP), contact angle, tensile strength (TS), elongation at break (EAB), Young’s modulus (YM), opacity, chemical structure and antioxidant activity. Results showed that genipin‐crosslinked chitosan/astaxanthin film and heat cured at 105 °C (CAG‐105) have the lowest (P < 0.05) WVP value which decreased by 55% while a contact angle increased from 50.2° to 74.6°, when compared to CAG‐25 film. Heat curing affected the chemical‐crosslinked interaction between chitosan and genipin with the establishment of new chemical bonds, leading to the improvement of TS and YM by 55% and 42%, respectively, for CAG‐105 film. However, EAB and antioxidant activity of the CAG‐105 slightly decreased. Moreover, heat curing changed the colour of genipin‐crosslinked chitosan/astaxanthin film from light brown to reddish brown and increased the film opacity which can lower light transmission through the film. The developed film not only had better water barrier, TS and YM but, due to its opacity, could also provide light protection, and thus would be appropriate for packaging material of foods that degrade when exposed to moisture or light.
Effect of wheat pearling process on composition and nutritional profile of flour and its bread‐making performance
Authors: Navarro José L. , Biglione Camila , Paesani Candela , Moiraghi Malena , León Alberto E. , Steffolani María Eugenia 
Published: October 2021

SummaryPearling process on wheat grains was evaluated as a strategy to reduce their adverse effect on whole‐wheat bread (WWB) quality and simultaneously preserve part of the nutrients of the whole grain. The grains were pearled applying different times (25, 125, 225 and 250 s) before milling. Characteristic, nutritional composition and rheology of the pearled wheat flour (P), and their bread‐making performance, were analysed. Whole‐wheat flour and refined flour (RF) were used as control. P125s, P225s and P250s exhibited a superior nutritional profile concerning RF. P had lower water absorption and led to higher volume bread with lighter crust and crumb compared to WWB. P125s, P225s and P250s bread showed characteristics similar to those of white bread, but their hardness was lower. The improvement resulted from the extraction of the outermost bran layers, a decrease in insoluble dietary fibre, an increase in the proportion of water‐soluble pentosans and a lower protein weakening.