bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a brief alcohol intervention addressing the full spectrum of drinking in an adult general population sample: a randomized controlled trial
Authors: Baumann Sophie , Staudt Andreas , Freyer‐Adam Jennis , Bischof Gallus , Meyer Christian , John Ulrich 
Published: January 2021

AbstractBackground and aimsEvidence for efficacy of brief alcohol interventions (BAIs) is mainly limited to primary care and at‐risk drinkers. The aim was to test the efficacy of a BAI addressing the full spectrum of alcohol use in a general population sample and across alcohol risk groups.DesignTwo‐parallel‐group randomized controlled trial (allocation ratio 1:1) with post‐baseline assessments at months 3, 6 and 12.SettingOne municipal registry office in Germany responsible for registration, passport and vehicle admission issues.ParticipantsA total of 1646 proactively recruited 18–64‐year‐old adults with past year alcohol use (56% women, 66% low‐risk drinkers) were randomized to intervention (n = 815) or control (n = 831).Intervention and comparatorThe intervention consisted of assessment plus computer‐generated individualized feedback letters at baseline and months 3 and 6. Comparator was assessment only.MeasurementsPrimary outcome was change in the self‐reported number of drinks/week from baseline to 12 months. Changes at 3 and 6 months were secondary outcomes. Moderator was alcohol risk group (low‐risk versus at‐risk drinking) according to the Alcohol Use Disorders Identification Test–Consumption, with scores from 1‐3 (women) and from 1‐4 (men) indicating low‐risk drinking.FindingsFor the whole sample, significant group differences were observed neither at 12‐month follow‐up [incidence rate ratio (IRR) = 1.01, 95% confidence interval (CI) = 0.87–1.17, Bayes factor (BE) = 0.52] nor at previous assessments (month 3: IRR = 1.01, 95% CI = 0.92–1.12, BE = 0.41; month 6: IRR = 0.93, 95% CI = 0.81–1.07, BE = 1.10). Moderator analyses revealed that low‐risk drinkers were more likely to benefit from BAI only at month 6 than at‐risk drinkers (IRR = 0.77, 95% CI = 0.70–0.86).ConclusionsIn a randomized controlled trial, there was no clear evidence for efficacy of a computer‐based brief alcohol intervention in a general population sample, but there was some evidence of medium‐term benefits in the large but understudied group of low‐risk drinkers.
Acidity, fluoride and silver ion concentrations in silver diamine fluoride solutions: a pilot study
Authors: Patel J , Foster D , Smirk M , Turton B , Anthonappa R 
Published: January 2021

AbstractBackgroundThere has been renewed interest in the use of silver diamine fluoride (SDF) for the management of carious lesions in high‐risk groups. Previous studies have found a difference in clinical efficacy among different concentrations of SDF and discrepancies between ionic concentrations of fluoride (F) and silver (Ag) in SDF preparations. The aim of this study was to measure the free F, Ag ion concentrations and pH of a variety of commercially available SDF preparations.MethodsSeven SDF products used globally were evaluated for F and Ag ion concentrations using a calibrated ion‐selective electrode and optical emission spectrometry respectively. Acidity was determined with a pH electrode.ResultsThe 30% SDF solution contained almost half the F concentration and a much higher Ag concentration than expected (16 343 ppmF and 246 000 ppmAg). Comparatively, the mean F concentration of the remaining six 38% solutions was 74 802 ppm (expected mean 44 800 ppm) ranging from 36 457 ppm to 120 760 ppm. The mean Ag concentration was 326 000 ppm (expected mean 253 870 ppm) and ranged from 246 000 ppm to 425 451 ppm. All solutions were found to be neutral or mildly alkaline in nature (pH 7–10.3).ConclusionsWide variations between claimed and measured F and Ag ion concentrations exist among the different brands of commercially available SDF products.
Are high elevation crag lizards sensitive to climate change?
Authors: Perold Vonica , Ferguson Jan Willem H. , Verburgt Luke , Malherbe Johan B. 
Published: January 2021

AbstractCrag lizards are restricted to montane areas where biota are strongly exposed to the effects of climate change. We investigated the factors shaping the distribution of Drakensberg crag lizards (Pseudocordylus melanotus melanotus; Cordylidae) by quantifying their elevational ranges, availability of shelter and prey as well as the thermal environment at three elevations. We recorded expected body temperatures using copper models of the lizards at each elevation in the field and in the laboratory, estimating the duration for which lizards must shelter from high temperatures. This correlated strongly with field observations of lizard activity during winter, spring and summer. Our models predicted that at lower elevations, lizards would shelter for longer periods each day, resulting in a marked reduction in time available for essential activities such as feeding and breeding, possibly explaining why these animals do not occur at lower elevations. The distribution and survival of these animals therefore appear to be impacted by the degree to which daytime temperatures limit their activity. Modelling future climate change scenarios at the high elevation site indicates that crag lizards would be resilient against small to moderate warming reflected by RCP4.5 climate change predictions, but populations are unlikely to persist under conditions predicted in the RCP8.5 scenario. This study is important as, unlike broader‐scope studies that cannot quantify climate change impacts on individual species, we combine detailed field data with laboratory measurements and modelling of a single species to assess the ecological constraints to which crag lizards are exposed.
Molecular markers of type 2 airway inflammation are similar between eosinophilic severe asthma and eosinophilic chronic obstructive pulmonary disease
Authors: Fricker Michael , McDonald Vanessa M. , Winter Natasha A. , Baines Katherine J. , Wark Peter A. B. , Simpson Jodie L. , Gibson Peter G. 
Published: January 2021

AbstractBackgroundAirway and systemic eosinophilia are important treatable traits in both severe asthma and COPD. The molecular basis of eosinophilia in COPD is poorly understood but could involve type 2 cytokines (IL5, IL13) and prostaglandin D2 (PGD2).MethodsThis study included non‐obstructive airways disease (OAD) controls (n = 19), a COPD cohort (n = 96) and a severe asthma cohort (n = 84). Demographics, exacerbation history, disease impact (SGRQ) and spirometry were assessed. Participants were categorized as eosinophilic using either sputum eosinophil proportion (≥3%) or blood eosinophil count (≥300/μL). Sputum type 2 inflammatory measures included PGD2 by ELISA and gene expression (qPCR) of IL5, IL13 and the haematopoietic PGD2 synthase (HPGDS).ResultsType 2 markers did not differ across groups except HPGDS mRNA which was highest in non‐OAD controls and lowest in COPD. IL5 and IL13 mRNA and PGD2 levels were significantly increased in eosinophilic vs non‐eosinophilic severe asthma but did not differ between eosinophilic COPD and eosinophilic severe asthma or non‐eosinophilic COPD. HPGDS expression was higher in eosinophilic severe asthma compared with eosinophilic COPD. Results were similar using sputum or blood eosinophil cut‐offs. Sputum IL5 and IL13 were highly intercorrelated in severe asthma (r = 0.907, p < 0.001) and COPD (r = 0.824, p < 0.001), were moderately correlated with sputum eosinophils in severe asthma (IL5 r = 0.440, p < 0.001; IL13 r = 0.428, p < 0.001) and were weakly correlated in COPD (IL5 r = 0.245, p < 0.05; IL13 r = 0.317, p < 0.05).ConclusionsMolecular markers of type 2 airway inflammation do not differ between eosinophilic asthma and eosinophilic COPD; however, the relationship between eosinophilia and type 2 airway markers appears weaker in COPD than in severe asthma.
Banking crises and economic growth in developing countries: Why privileging foreign direct investment over external debt?
Authors: Gaies Brahim , Nabi Mahmoud‐Sami 
Published: January 2021

AbstractThe impact of external financing on the economies of developing countries is still a subject of debate among economists and policy makers. The objective of this paper is to contribute to this debate by shedding light on the interaction between foreign direct investment (FDI) and external debt. To this end, we begin by formulating an overlapping generation growth model that integrates a banking sector and find two complementary results. First, we show that external financing boosts investment projects and accelerates the dynamic of capital accumulation and economic growth. The second one mitigates this channel by showing two opposite indirect effects of external debt and FDI. Indeed, while external debt financing increases the vulnerability to a bank run that generates a recessionary impact on economic growth, FDI attenuates this recessionary impact and plays the role of a shock absorber. We empirically confirm these results for 67 developing countries over the period 1972–2015 using the GMM estimation of growth models and panel‐logit models to predict the determinants of banking crises. Hence, this study provides a comprehensive assessment of developing countries’ involvement in financial globalization and offers recommendations for their future international economic policies.
Combining mesenchymal stem cells with serelaxin provides enhanced renoprotection against 1K/DOCA/salt‐induced hypertension
Authors: Li Yifang , Shen Matthew , Ferens Dorota , Broughton Brad R.S. , Murthi Padma , Saini Sheetal , Widdop Robert E. , Ricardo Sharon D. , Pinar Anita A. , Samuel Chrishan S. 
Published: January 2021

Background and PurposeFibrosis is a hallmark of chronic kidney disease (CKD) that significantly contributes to renal dysfunction, and impairs the efficacy of stem cell‐based therapies. This study determined whether combining bone marrow‐derived mesenchymal stem cells (BM‐MSCs) with the renoprotective effects of recombinant human relaxin (serelaxin) could therapeutically reduce renal fibrosis in mice with one kidney/deoxycorticosterone acetate/salt (1K/DOCA/salt)‐induced hypertension, compared with the effects of the ACE inhibitor, perindopril.Experimental ApproachAdult male C57BL/6 mice were uni‐nephrectomised and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt) for 21 days. Control mice were uni‐nephrectomised but received water over the same time period. Sub‐groups of 1K/DOCA/salt‐injured mice (n = 5–8 per group) were treated with either serelaxin (0.5 mg·kg−1·day−1) or BM‐MSCs (1 × 106 per mouse) alone; both treatments combined (with 0.5 × 106 or 1 × 106 BM‐MSCs per mouse); or perindopril (2 mg·kg−1·day−1) from days 14–21.Key Results1K/DOCA/salt‐injured mice developed elevated BP and hypertension‐induced renal damage, inflammation and fibrosis. BM‐MSCs alone reduced the injury‐induced fibrosis and attenuated BP to a similar extent as perindopril. Serelaxin alone modestly reduced renal fibrosis and effectively reduced tubular injury. Strikingly, the combined effects of BM‐MSCs (at both doses) with serelaxin significantly inhibited renal fibrosis and proximal tubular epithelial injury while restoring renal architecture, to a greater extent than either therapy alone, and over the effects of perindopril.Conclusion and ImplicationsCombining BM‐MSCs and serelaxin provided broader renoprotection over either therapy alone or perindopril and might represent a novel treatment for hypertensive CKD.
Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis
Authors: Li Danyu , Liu Bing , Fan Yumei , Liu Ming , Han Bihui , Meng Yanxiu , Xu Xiao , Song Zhiyuan , Liu Xiaopeng , Hao Qiang , Duan Xianglin , Nakai Akira , Chang Yanzhong , Cao Pengxiu , Tan Ke 
Published: January 2021

Background and PurposeAcute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid‐induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury.Experimental ApproachThe effects of nuciferine on folic acid‐induced acute kidney injury in mice were investigated. HK‐2 human proximal tubular epithelial cells and HEK293T HEK cells were used to evaluate the protective effect of nuciferine on RSL3‐induced ferroptosis.Key ResultsNuciferine treatment mitigated the pathological alterations, ameliorated inflammatory cell infiltration and improved kidney dysfunction in mice with folic acid‐induced acute kidney injury. In HK‐2 and HEK293T cells, nuciferine significantly prevented RSL3‐induced ferroptotic cell death. Mechanistically, nuciferine significantly inhibited ferroptosis by preventing iron accumulation and lipid peroxidation in vitro and in vivo. Moreover, knockdown of glutathione (GSH) peroxidase 4 (GPX4) abolished the protective effect of nuciferine against ferroptosis.Conclusion and ImplicationsNuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis.
The ratio of ursodeoxycholyltaurine to 7‐oxolithocholyltaurine serves as a biomarker of decreased 11β‐hydroxysteroid dehydrogenase 1 activity in mouse
Authors: Weingartner Michael , Stücheli Simon , Kratschmar Denise V. , Birk Julia , Klusonova Petra , Chapman Karen E. , Lavery Gareth G. , Odermatt Alex 
Published: January 2021

Background and Purpose11β‐Hydroxysteroid dehydrogenase 1 (11β‐HSD1) regulates tissue‐specific glucocorticoid metabolism and its impaired expression and activity are associated with major diseases. Pharmacological inhibition of 11β‐HSD1 is considered a promising therapeutic strategy. This study investigated whether alternative 7‐oxo bile acid substrates of 11β‐HSD1 or the ratios to their 7‐hydroxy products can serve as biomarkers for decreased enzymatic activity.Experimental ApproachBile acid profiles were measured by ultra‐HPLC tandem‐MS in plasma and liver tissue samples of four different mouse models with decreased 11β‐HSD1 activity: global (11KO) and liver‐specific 11β‐HSD1 knockout mice (11LKO), mice lacking hexose‐6‐phosphate dehydrogenase (H6pdKO) that provides cofactor NADPH for 11β‐HSD1 and mice treated with the pharmacological inhibitor carbenoxolone. Additionally, 11β‐HSD1 expression and activity were assessed in H6pdKO‐ and carbenoxolone‐treated mice.Key ResultsThe enzyme product to substrate ratios were more reliable markers of 11β‐HSD1 activity than absolute levels due to large inter‐individual variations in bile acid concentrations. The ratio of the 7β‐hydroxylated ursodeoxycholyltaurine (UDC‐Tau) to 7‐oxolithocholyltaurine (7oxoLC‐Tau) was diminished in plasma and liver tissue of all four mouse models and decreased in H6pdKO‐ and carbenoxolone‐treated mice with moderately reduced 11β‐HSD1 activity. The persistence of 11β‐HSD1 oxoreduction activity in the face of H6PD loss indicates the existence of an alternative NADPH source in the endoplasmic reticulum.Conclusions and ImplicationsThe plasma UDC‐Tau/7oxo‐LC‐Tau ratio detects decreased 11β‐HSD1 oxoreduction activity in different mouse models. This ratio may be a useful biomarker of decreased 11β‐HSD1 activity in pathophysiological situations or upon pharmacological inhibition.LINKED ARTICLESThis article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
The anti‐parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice
Authors: Knuplez Eva , Kienzl Melanie , Trakaki Athina , Schicho Rudolf , Heinemann Akos , Sturm Eva M. , Marsche Gunther 
Published: January 2021

Background and PurposeMiltefosine is an alkylphosphocholine drug with proven effectiveness against various types of parasites and cancer cells. Miltefosine is not only able to induce direct parasite killing but also modulates host immunity, for example by reducing the severity of allergies in patients. To date, there are no reports on the effect of miltefosine on eosinophils, central effector cells involved in allergic inflammation.Experimental ApproachWe tested the effect of miltefosine on the activation of human eosinophils and their effector responsesin vitroand in mouse models of eosinophilic migration and ovalbumin‐induced allergic lung inflammation.Key ResultsThe addition of miltefosine suppressed several eosinophilic effector reactions such as CD11b up‐regulation, degranulation, chemotaxis and downstream signalling. Miltefosine significantly reduced the infiltration of immune cells into the respiratory tract of mice in an allergic cell recruitment model. Finally, in a model of allergic inflammation, treatment with miltefosine resulted in an improvement of lung function parameters.Conclusion and ImplicationsOur observations suggest a strong modulatory activity of miltefosine in the regulation of eosinophilic inflammationin vitroandin vivo. Our data underline the potential efficacy of miltefosine in the treatment of allergic diseases and other eosinophil‐associated disorders and may raise important questions regarding the immunomodulatory effect of miltefosine in patients treated for leishmania infections.
CircPVT1 promotes progression in clear cell renal cell carcinoma by sponging miR‐145‐5p and regulating TBX15 expression
Authors: Zheng Zaosong , Chen Zhiliang , Zhong Qiyu , Zhu Dingjun , Xie Yingwei , Shangguan Wentai , Xie Wenlian 
Published: January 2021

AbstractEmerging evidence revealed that circular RNAs (circRNAs) play significant roles in regulating tumorigenesis and cancer progression. However, few circRNAs were well characterized in clear cell renal cell carcinoma (ccRCC). We found that circPVT1 was significantly upregulated in ccRCC tissues and positively associated with the clinical stage. The Area Under Curve of tissue and serum circPVT1 expression in ccRCC were 0.93 and 0.86, respectively. Importantly, we demonstrated that circPVT1 promoted ccRCC growth and metastasis in vitro and in vivo. We also found that circPVT1 directly binds to miRNA‐145‐5p via the Biotin‐labelled miRNA pulldown assay and dual‐luciferase reporter assay, and miR‐145‐5p inhibitor significantly attenuated the effect of circPVT1 knockdown on ccRCC cells. Moreover, through RNA sequencing and bioinformatics analysis, we demonstrated that TBX15 was regulated by the circPVT1/miR‐145‐5p axis and predicted poor prognosis in ccRCC. These findings suggest that circPVT1 promotes ccRCC growth and metastasis through sponging miR‐145‐5p and regulating downstream target TBX15 expression. The circPVT1/miR‐145‐5p/TBX15 axis might be a potential diagnostic marker and therapeutic target in ccRCC.
Selective inhibition of prostaglandin D2 biosynthesis in human mast cells to overcome need for multiple receptor antagonists: Biochemical consequences
Authors: Johnsson Anna‐Karin , Choi Jeong‐Hee , Rönnberg Elin , Fuchs David , Kolmert Johan , Hamberg Mats , Dahlén Barbro , Wheelock Craig E. , Dahlén Sven‐Erik , Nilsson Gunnar 
Published: January 2021

AbstractBackgroundThe major mast cell prostanoid PGD2 is targeted for therapy of asthma and other diseases, because the biological actions include bronchoconstriction, vasodilation and regulation of immune cells mediated by three different receptors. It is not known if the alternative to selectively inhibit the biosynthesis of PGD2 affects release of other prostanoids in human mast cells.ObjectivesTo determine the biochemical consequences of inhibition of the hematopoietic prostaglandin D synthase (hPGDS) PGD2 in human mast cells.MethodsFour human mast cell models, LAD2, cord blood derived mast cells (CBMC), peripheral blood derived mast cells (PBMC) and human lung mast cells (HLMC), were activated by anti‐IgE or ionophore A23187. Prostanoids were measured by UPLC‐MS/MS.ResultsAll mast cells almost exclusively released PGD2 when activated by anti‐IgE or A23187. The biosynthesis was in all four cell types entirely initiated by COX‐1. When pharmacologic inhibition of hPGDS abolished formation of PGD2, PGE2 was detected and release of TXA2 increased. Conversely, when the thromboxane synthase was inhibited, levels of PGD2 increased. Adding exogenous PGH2 confirmed predominant conversion to PGD2 under control conditions, and increased levels of TXB2 and PGE2 when hPGDS was inhibited. However, PGE2 was formed by non‐enzymatic degradation.ConclusionsInhibition of hPGDS effectively blocks mast cell dependent PGD2 formation. The inhibition was associated with redirected use of the intermediate PGH2 and shunting into biosynthesis of TXA2. However, the levels of TXA2 did not reach those of PGD2 in naïve cells. It remains to determine if this diversion occurs in vivo and has clinical relevance.
Evaluation of interleukin‐29 in autoimmune and inflammatory thyroid diseases
Authors: Falkowski Bogusz , Szczepanek‐Parulska Ewelina , Krygier Aleksandra , Wrotkowska Elzbieta , Ruchala Marek 
Published: January 2021

AbstractObjectiveInterleukins play an important role in the development of autoimmune disorders. The aim of this study was to compare the concentration of interleukin‐29 (IL‐29) between healthy controls (CS) and patients with selected thyroid disorders: Graves’ disease (GD), Hashimoto's thyroiditis (HT) and subacute thyroiditis (SAT).Design and methodsThe following parameters were examined in the group of 95 individuals (45 with GD, 22 with HT, 28 with SAT) and 72 CS: thyroid hormones and autoantibodies, inflammatory markers and the concentration of IL‐29 in serum.ResultsThe concentration of IL‐29 in the GD subgroup was higher than that in the CS subgroup [264.0 (62.5‐1018.0) vs. 62.5 (62.5‐217.0) pg/mL, P = .001]. We found no differences in IL‐29 concentrations between the CS and HT or SAT subgroups. Multivariable linear regression analysis indicated that IL‐29 was a statistically significant independent predictor of GD presence (r = 0.24; P = .003) after adjustment for TRAb (R2 = 0.45; P < .001). The ROC analysis of IL‐29 at GD diagnosis revealed an IL‐29 cut‐off of 123 pg/mL (sensitivity: 0.689 and specificity: 0.625) as the best value, which significantly indicated the presence of GD [area under the ROC curve (AUC): 0.676; 95% confidence interval (CI): 0.574‐0.778, P < .001].ConclusionThis is the first study to demonstrate elevated IL‐29 serum levels in patients with GD. Our results suggest that IL‐29 might be engaged in one of the pathogenetic pathways of GD, but no HT and SAT. Future studies are required to evaluate the potential of the protein as a therapeutic target in GD.