bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dynamic effect of macroeconomic news on the euro/US dollar exchange rate
Authors: Ben Omrane Walid , Welch Robert , Zhou Xinyao 
Published: May 2019

AbstractThis study investigates the impact of 70 US and EU macroeconomic news announcements on euro/dollar returns and volatility from November 2004 to April 2014. We use regime smooth transition regression to endogenously define recession and expansion. Our sample period includes the US mortgage crisis and EU sovereign debt crisis. Most news is unstable as its effect varies between these economic states. There are asymmetrical effects between recession and expansion states for both US and EU news, with most US news having a larger impact and nearly double the number of significant EU announcements. Volatility increases for over 85% of news coefficients, with more than half still being significantly different between states.
Experimental design modulates variance in BOLD activation: The variance design general linear model
Authors: Gaut Garren , Li Xiangrui , Lu Zhong‐Lin , Steyvers Mark 
Published: May 2019

AbstractTypical fMRI studies have focused on either the mean trend in the blood‐oxygen‐level‐dependent (BOLD) time course or functional connectivity (FC). However, other statistics of the neuroimaging data may contain important information. Despite studies showing links between the variance in the BOLD time series (BV) and age and cognitive performance, a formal framework for testing these effects has not yet been developed. We introduce the variance design general linear model (VDGLM), a novel framework that facilitates the detection of variance effects. We designed the framework for general use in any fMRI study by modeling both mean and variance in BOLD activation as a function of experimental design. The flexibility of this approach allows the VDGLM to (a) simultaneously make inferences about a mean or variance effect while controlling for the other and (b) test for variance effects that could be associated with multiple conditions and/or noise regressors. We demonstrate the use of the VDGLM in a working memory application and show that engagement in a working memory task is associated with whole‐brain decreases in BOLD variance.
Evaluation of the Potential of Cobalamin Derivatives Bearing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy
Authors: Jakubaszek Marta , Rossier Jeremie , Karges Johannes , Delasoie Joachim , Goud Bruno , Gasser Gilles , Zobi Fabio 
Published: May 2019

AbstractThe current photosensitizers (PSs) for photodynamic therapy (PDT) lack selectivity for cancer cells. To tackle this drawback, in view of selective cancer delivery, we envisioned conjugating two ruthenium polypyridyl complexes to vitamin B12(Cobalamin, Cbl) to take advantage of the solubility and active uptake of the latter. Ultimately, our results showed that the transcobalamin pathway is unlikely involved for the delivery of these ruthenium‐based PDT PSs, emphasizing the difficulty in successfully delivering metal complexes to cancer cells.
Rs531564 polymorphism in microRNA‐214 regulates interleukin‐6R expression in anal fissure patients to affect the risk of anal abscess formation
Authors: Liu Jiangang , Li Changlu , Yin Peiwei , Guo Xiuli , Liu Zhichao 
Published: May 2019

AbstractBackgroundAnal abscess is an important complication of anal fissure (AF), whereas interleukin‐6R (IL‐6R) has been implicated in the development of abscess. In this study, we aimed to explore the possible molecular mechanisms underlying the regulatory effects of miRNAs on IL‐6R and other inflammatory factors related to the induction of anal abscess in AF.MethodsBioinformatics analysis, luciferase assay, real‐time polymerase chain reaction, and Western blot analysis were performed to identify the possible regulatory relationships between IL‐6R and miR‐124/miR‐125a by comparing the differentiated expression of miR‐125a, miR‐124, tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), and IL‐4 among different groups of AF patients.ResultsIL‐6R messenger RNA (mRNA) was identified as a target gene of miR‐124 because the luciferase activity in cells cotransfected with wild‐type IL‐6R and miR‐124 mimics was significantly reduced. In addition, the expression of IL‐6R mRNA and protein was significantly inhibited in the presence of miR‐124 or an IL‐6R inhibitor, confirming the presence of a negative regulatory relationship between miR‐124 and IL‐6R. Moreover, miR‐124 and inflammatory factors were differentially expressed in AF patients carrying different genotypes of rs531564 polymorphism.ConclusionsmiR‐124 and inflammatory factors TNF‐α, IFN‐γ, and IL‐4 may be used as indicators of anal abscess development in AF patients. In addition, miR‐124 polymorphism rs531564 is involved with the pathogenesis of anal abscess in AF patients, and the presence of rs531564 may increase the incidence of anal abscess via upregulating the expression of IL‐6R, TNF‐α, IFN‐γ, and IL‐4.
miR‐4319 inhibited the development of thyroid cancer by modulating FUS‐stabilized SMURF1
Authors: Bian Shuquan 
Published: May 2019

AbstractThyroid cancer, a common type of endocrine system cancer, has witnessed rising incidence and deaths over the past few years. The role of microRNAs is being increasingly discovered in a variety of cancers, including thyroid cancer. miR‐4319 has been elucidated in several studies to exert an antitumor function in multiple cancers but has never been explored in thyroid cancer. Our study proposed to explore the function and modulatory mechanism of miR‐4319 in thyroid cancer. First, we confirmed the downregulation of miR‐4319 in thyroid cancer tissues and cells, and revealed the correlation of miR‐4319 expression and clinical features in thyroid cancer. Functional assays illustrated that miR‐4319 attenuated proliferation, migration, and epithelial‐to‐mesenchymal transition (EMT) in thyroid cancer. Mechanistically, we identified through the miRDB database and proved that miR‐4319 targeted SMAD specific E3 ubiquitin protein ligase 1 (SMURF1). Furthermore, we discovered that miR‐4319 competed with fused in sarcoma (FUS) to bind to SMURF1, inhibiting the stabilization of SMURF1 messenger RNA. Rescue assays suggested that miR‐4319 retarded proliferation, migration, and EMT through SMURF1. Collectively, the results of this study showed that miR‐4319 inhibited the development of thyroid cancer by modulating FUS‐stabilized SMURF1, indicating miR‐4319 as a potent biological target for thyroid cancer.
Clinical diagnostic performance of light‐initiated chemiluminescent assay compared with the Architect chemiluminescence immunoassay for detection of HCV antibody
Authors: Yang Shuo , Yang Ruifeng , Zhang Siyu , Liu Di , Zhou Jiansuo , Wang Tiancheng , Cui Liyan 
Published: May 2019

AbstractBackgroundHepatitis C virus antibody (anti‐HCV) test had been approved as a preliminary screening test for HCV infection. Light‐initiated chemiluminescent assay (LiCA) was a homogenous method. We aimed to assess the clinical diagnostic performance of LiCA and compare it with that of chemiluminescence immunoassay (CLIA) which was widely used in clinical laboratories.MethodsA total of 10 772 patients from the Peking University Third Hospital were enrolled. The serum samples were detected on the ChIVD LiCA500 and Abbott Architect i2000SR platforms. Recombinant immunoblot assay (RIBA) and HCV RNA assay were used for confirmation.ResultsThe negative agreement rate between ChIVD LiCA anti‐HCV assay and Abbott Architect anti‐HCV assay was 99.91%, the positive agreement rate was 37.31%, the total agreement rate was 98.74%, and the kappa coefficient (κ) was 0.519. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ChIVD LiCA anti‐HCV assay were 96.39%, 99.95%, 89.58%, and 99.97%, respectively, which were superior to those of Abbott Architect anti‐HCV assay (93.98%, 99.25%, 51.90%, and 99.95%, respectively).ConclusionChIVD LiCA anti‐HCV assay was a highly sensitive, specific homogenous method with good diagnostic performance, and was applicable for the routine screening of HCV infection in clinical laboratories.
GNAS knockdown suppresses osteogenic differentiation of mesenchymal stem cells via activation of Hippo signaling pathway
Authors: An Jiangdong , Li Guangjie , Zhang Jin , Zhou Haiyu , Jiang Jin , Wang Xingwen , Feng Xiaofei , Wang Shuanke 
Published: May 2019

AbstractBone marrow‐derived mesenchymal stem cells (BMSCs) are a suitable option for cell‐based tissue engineering therapies due to their ability to renew and differentiate into multiple different tissue types, such as bone. Over the last decade, the effect of GNAS on the regulation of osteoblast differentiation has attracted great attention. Herein, this study aimed to explore the role of GNAS in osteogenic differentiation of MSCs. A total of 85 GNASf/f male mice were selected for animal experiments and 10 GNASf/f male mice for BMSC isolation to conduct cell experiments. The mice and BMSCs were treated with Verteporfin (a Hippo signaling pathway inhibitor) to inhibit the Hippo signaling pathway or recombinant adenovirus‐expressing Cre to knockout the GNAS expression. Next, computed tomography scan, Von Kossa staining, and alizarin red staining were performed to detect osteogenic differentiation ability. Moreover, immunohistochemistry and alkaline phosphatase (ALP) staining were used to assess the expression of Oc and Osx in femur tissues and ALP activity. At last, the expression of GNAS, osteogenic markers, and factors related to the Hippo signaling pathway was evaluated. Initially, the results displayed successful knockout of the GNAS gene from mice and BMSCs. Moreover, the data indicated that GNAS knockout inhibits expression of Oc, Osx, ALP, BMP‐2, and Runx2, and ALP activity. Additionally, GNAS knockout promotes activation of the Hippo signaling pathway, so as to repress osteogenic differentiation. Collectively, depleted GNAS exerts an inhibitory role in osteogenic differentiation of MSCs by activating Hippo signaling pathway, providing a candidate mediator for osteoporosis.
KPC1 alleviates hypoxia/reoxygenation‐induced apoptosis in rat cardiomyocyte cells though BAX degradation
Authors: Yuan Ye , Wang Yong‐yi , Liu Xin , Luo Bin , Zhang Lei , Zheng Fei , Li Xing‐Yuan , Guo Ling‐Yun , Wang Lu , Jiang Miao , Pan Ya‐mu , Yan Yu‐wen , Yang Jian‐ye , Chen Shi‐You , Wang Jia‐Ning , Tang Jun‐Ming 
Published: May 2019

AbstractBax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia‐reperfusion (I/R)‐induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R‐myocardium in vivo and in hypoxia and reoxygenation (H/R)‐induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short‐hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress‐induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R‐induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1.
Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in RAW264.7 cells
Authors: Li Qi‐Zhang , Chang Yu‐Zhou , He Zhu‐Mei , Chen Lei , Zhou Xuan‐Wei 
Published: May 2019

AbstractGanoderma lucidum immunomodulatory protein (FIP‐glu) is an active ingredient with potential immunoregulatory functions. The study was conducted to explore the immunomodulatory activities of recombinant FIP‐glu (rFIP‐glu) and its possible mechanism in macrophage RAW264.7 cells. In vitro assays of biological activity indicated that rFIP‐glu significantly activated RAW264.7 cells and possessed proinflammatory and anti‐inflammatory abilities. RNA sequencing analysis and Western blot analysis showed that macrophage activation involved PI3K/Akt and MAPK pathways. Furthermore, real‐time quantitative polymerase chain reaction indicated that the PI3K inhibitor LY294002 blocked the messenger RNA (mRNA) levels of MCP‐1 (CCL‐2), the MEK1/2 inhibitor U0126 reduced the mRNA levels of TNF‐α and MCP‐1 (CCL‐2), and the JNK1/2/3 inhibitor SP600125 prevented the upregulation of inducible nitric oxide synthase mRNA in rFIP‐glu‐induced cells. rFIP‐glu did not mediate these inflammatory effects through a general pathway but rather through a different pathway for a different inflammatory mediator. These data imply that rFIP‐glu possessed immunomodulatory activity in macrophages, which was mediated through PI3K/Akt and MAPK pathways.
Validation of a self‐report adherence measurement tool among a multinational cohort of children living with HIV in Kenya, South Africa and Thailand
Authors: Vreeman Rachel C , Scanlon Michael L , Tu Wanzhu , Slaven James E , McAteer Carole I , Kerr Stephen J , Bunupuradah Torsak , Chanthaburanum Sararut , Technau Karl‐Günter , Nyandiko Winstone M 
Published: May 2019

AbstractIntroductionThere are few data on adherence and low‐cost measurement tools for children living with HIV. We collected prospective data on adherence to antiretroviral therapy (ART) among a multinational cohort of children to evaluate an adherence questionnaire.MethodsWe enrolled 319 children ages 0 to 16 years on ART in Kenya (n = 110), South Africa (n = 109) or Thailand (n = 100). Children were followed up for six months of adherence monitoring between March 2015 and August 2016 using Medication Event Monitoring Systems (MEMS®) with at least one viral load measure. At month 3 and 6, children or their caregivers were administered a 10‐item adherence questionnaire. Repeated measures analyses were used to compare responses on questionnaire items to external adherence criteria: MEMS® dichotomized adherence (≥90% of doses taken vs. <90%), 48‐hour MEMS® treatment interruptions and viral suppression (<1000 copies/mL). Items associated with outcomes (p < 0.10) were coefficient‐weighted to calculate a total adherence score, which was tested in multivariate regression against MEMS® and viral suppression outcomes. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated.ResultsMean child age was 11 years and 54% were female. Children from Thailand (median age 14 years) were significantly older compared to Kenya (10 years) and South Africa (10 years). Prevalence of viral suppression was 97% in Thailand, 81% in South Africa and 69% in Kenya, while the prevalence of MEMS® adherence ≥90% was 57% in Thailand, 58% in South Africa and 40% in Kenya. Across sites, child‐reported adherence using the questionnaire was significantly associated with dichotomized MEMS® adherence (OR 1.8, 95% CI 1.4 to 2.4), 48‐hour treatment interruptions (OR 0.41, 95% CI 0.3 to 0.6), and viral suppression (OR 3.4, 95% CI 1.7 to 6.7). We did find, however, that different cut‐points for the adherence score may be context‐specific. For example, MEMS® non‐adherent children in Kenya had a lower adherence score (0.98) compared to South Africa (1.77) or Thailand (1.58).ConclusionsWe found suboptimal adherence to ART was common by multiple measures in this multi‐country cohort of children. The short‐form questionnaire demonstrated reasonable validity to screen for non‐adherence in these diverse settings.
Evaluation of the serum metabolome of patients with alkaptonuria before and after two years of treatment with nitisinone using LC‐QTOF‐MS
Authors: Davison Andrew S. , Norman Brendan P. , Ross Gordon A. , Hughes Andrew T. , Khedr Milad , Milan Anna M. , Gallagher James A. , Ranganath Lakshminarayan R. 
Published: May 2019

AbstractBackgroundThe homogentisic acid‐lowering therapy nitisinone is being evaluated for the treatment of alkaptonuria (AKU) at the National Centre for AKU. Beyond hypertyrosinemia, the wider metabolic consequences of its use are largely unknown. The aim of this work was to evaluate the impact of nitisinone on the serum metabolome of patients with AKU after 12 and 24 months of treatment.MethodsDeproteinized serum from 25 patients with AKU (mean age[±SD] 51.1 ± 14.9 years, 12 male) was analyzed using the 1290 Infinity II liquid chromatography system coupled to a 6550 quadrupole time‐of‐flight mass spectrometry (Agilent, UK). Raw data were processed using a batch targeted feature extraction algorithm and an accurate mass retention time database containing 469 intermediary metabolites (MW 72‐785). Matched entities (±10 ppm theoretical accurate mass and ±0.3 minutes retention time window) were filtered based on their frequency and variability (<25% CV) in group quality control samples, and repeated measures statistical significance analysis with Benjamini‐Hochberg false discovery rate adjustment was used to assess changes in metabolite abundance.ResultsEight metabolites increased in abundance (log2 fold change [FC] 2.1‐15.2, P < .05); 7 of 8 entities were related to tyrosine metabolism, and 13 decreased in abundance (log2 FC 1.5‐15.5, P < .05); including entities related to tyrosine (n = 2), tryptophan (n = 3), xanthine (n = 2), and citric acid cycle metabolism (n = 2).ConclusionsEvaluation of the serum metabolome of patients with AKU showed a significant difference in the abundance of several metabolites following treatment with nitisinone, including a number that have not been previously reported; several of these were not related to the tyrosine metabolic pathway.SynopsisNitisinone therapy has a significant impact on several metabolites beyond the tyrosine metabolic pathway, several of which appear to be related to the redox state of the cell.
Increasing body mass index in an elderly cohort: Effects on the quantitative MR parameters of the brain
Authors: Schall Melissa , Iordanishvili Elene , Mauler Jörg , Oros‐Peusquens Ana‐Maria , Shah N. Jon 
Published: May 2019

BackgroundBody mass index (BMI) is increasing in a large number of elderly persons. This increase in BMI is known to put one at risk for many "diseases of aging," although less is known about how a change in BMI may affect the brains of the elderly.PurposeTo investigate the relationship between BMI and quantitative water content, T1, T2*, and the semi‐quantitative magnetization transfer ratio (MTR) of various structures in elderly brains.Study TypeCross‐sectional.SubjectsForty‐two adults (BMI range: 19.1–33.5 kg/m2, age range: 58–80 years).Field Strength3T MRI (two multi‐echo gradient echoes, actual flip angle imaging, magnetization prepared rapid gradient echo, fluid attenuated inversion recovery).AssessmentThe 3D two‐point method was used to derive (semi‐)quantitative parameters in global white (WM) and gray matter (GM) and their regions as defined by the Johns Hopkins University and the Montreal Neurological Institute atlases.Statistical TestsMultivariate linear regression with BMI as principal regressor, corrected for the additional regressors age, gender, and glycated hemoglobin. Spearman correlation between quantitative parameters of the regions showing significant changes and the lipid spectra / C‐reactive protein (CRP). Voxel‐based morphometry and analysis of covariance (ANCOVA) to explore changes in the GM volume.ResultsT1increased significantly (P < 0.05) in the frontal, temporal, and parietal cortices, while the bilateral corona radiata, right superior longitudinal fasciculus, as well as the corpus callosum showed significant changes in the WM regions. T2* increased significantly in the global WM and left corona radiata. Changes in MTR and the free water content did not reach significance. No significant correlation between any quantitative parameter and the lipid spectra or CRP could be identified.Data ConclusionThese results suggest that an elevated BMI predominantly affects T1in WM as well as GM structures in the elderly human brain.Level of Evidence:3Technical Efficacy:Stage 3J. Magn. Reson. Imaging 2020;51:514–523.
Rationale for and Design of the Study of Early Enteral Dextrose in Sepsis: A Pilot Placebo‐Controlled Randomized Clinical Trial
Authors: Shah Faraaz Ali , Kitsios Georgios D. , Zhang Yingze , Morris Alison , Yende Sachin , Huang David T. , O'Donnell Christopher P. , McVerry Bryan J. 
Published: May 2019

AbstractBackgroundSepsis is characterized by life‐threatening organ dysfunction caused by a dysregulated host response to infection and affects over 1 million Americans annually. Loss of glycemic control in sepsis is associated with increased morbidity and mortality, and novel approaches are needed to promote euglycemia and improve outcomes in sepsis. Recent studies from our laboratory demonstrate that early low‐level enteral dextrose infusion in septic mice attenuates the systemic inflammatory response and improves glycemic control by inducing intestine‐derived incretin hormone secretion.AimThe aim of the Study of Early Enteral Dextrose in Sepsis (SEEDS) is to test the effect of a 24‐hour enteral dextrose infusion in critically ill septic patients as a therapeutic agent to decrease systemic inflammation and promote euglycemia.MethodsSEEDS is a single‐center, double‐blind, randomized, controlled trial that will enroll 60 septic patients admitted to the intensive care units at the University of Pittsburgh Medical Center Health System in Pittsburgh. Participants will be randomized 1:1 to receive enteral dextrose (n = 30) or water (placebo, n = 30) infusion for 24 hours. The primary outcome is the circulating interleukin‐6 level measured after the 24‐hour infusion compared between dextrose and placebo groups. Secondary outcomes include postinfusion circulating insulin, incretin, and other proinflammatory cytokine levels, as well as incidence of hyperglycemia and hypoglycemia during the infusion period.DiscussionThis trial will characterize the effects of early enteral dextrose on endogenous endocrine pathways and the systemic inflammatory response in sepsis. The results of this trial will inform future larger interventional studies of early enteral nutrients in critically ill patients with sepsis.