bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer
Authors: Zhou Xiaoxiao , Liu Kun , Cui Jing , Xiong Jiongxin , Wu Heshui , Peng Tao , Guo Yao 
Published: April 2021

Abstract
Background
Pancreatic cancer is a malignant tumor and ranks the sixth in incidence among cancers. Circular RNA (circRNA) has been reported to regulate the progression of pancreatic cancer. However, the effects of circ-membrane bound O-acyltransferase domain containing 2 (circ-MBOAT2) on regulating pancreatic cancer process were unclear.

Methods
The expression levels of circ-MBOAT2, microRNA-433-3p (miR-433-3p) and glutamic-oxaloacetic transaminase 1 (GOT1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). GOT1 protein expression was determined by western blot analysis. Cell proliferation was illustrated by 3-(4,5)-dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide (MTT) and cell colony formation assay. Cell apoptosis was demonstrated by flow cytometry analysis. Cell invasion and migration were investigated by transwell invasion and wound-healing assays. Glutamine catabolism was explained by detecting glutamine consumption, alpha ketoglutarate (α-KG) production and glutamate production. In vivo assay was performed to illustrate the impacts of circ-MBOAT2 silencing on tumor formation in vivo. The binding relationship between miR-433-3p and circ-MBOAT2 or GOT1 was predicted by circinteractome or starbase online databases, and identified by dual-luciferase reporter assay.

Results
Circ-MBOAT2 and GOT1 expression were significantly upregulated, while miR-433-3p expression was downregulated in pancreatic cancer tissues and cells compared with normal pancreatic tissues or cells. Circ-MBOAT2 silencing repressed cell proliferation, migration, invasion and glutamine catabolism, whereas promoted cell apoptosis in pancreatic cancer. Additionally, circ-MBOAT2 acted as a sponge of miR-433-3p, which was found to be associate with GOT1. MiR-433-3p inhibitors hindered circ-MBOAT2 silencing-mediated impacts on pancreatic cancer progression and glutamine catabolism. Furthermore, circ-MBOAT2 silencing repressed tumor formation in vivo.

Conclusion
Circ-MBOAT2 modulated tumor development and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. This finding suggests that circ-MBOAT2 may be a therapeutic target for pancreatic cancer.
Hypoxia-dependent expression of MAP17 coordinates the Warburg effect to tumor growth in hepatocellular carcinoma
Authors: Dong Fangyuan , Li Rongkun , Wang Jiaofeng , Zhang Yan , Yao Jianfeng , Jiang Shu-Heng , Hu Xiaona , Feng Mingxuan , Bao Zhijun 
Published: April 2021

Abstract
Background
Reprogrammed glucose metabolism, also known as the Warburg effect, which is essential for tumor progression, is regarded as a hallmark of cancer. MAP17, a small 17-kDa non-glycosylated membrane protein, is frequently dysregulated in human cancers. However, its role in hepatocellular carcinoma (HCC) remains largely unknown.

Methods
Immunohistochemistry was used to analyze the expression pattern of MAP17 in HCC. Loss-of-function and gain-of-function studies were performed to investigate the oncogenic roles of MAP17 in vitro and in vivo. RNA sequencing, co-immunoprecipitation, immunofluorescence and western blotting were used to study the molecular mechanism of MAP17 affecting the tumor growth and glycolytic phenotype of HCC.

Results
An integrative analysis showed that MAP17, a small 17-kDa non-glycosylated membrane protein, is significantly related to the glycolytic phenotype of hepatocellular carcinoma (HCC). Firstly, we found that MAP17 expression is hypoxia-dependent and predicts a poor prognosis in HCC. Genetic silencing of MAP17 reduced the rate of glucose uptake, lactate release, extracellular acidification rate, and expression of glycolytic genes. Ectopic expression of wild type MAP17 but not its PDZ binding domain mutant MAP17-PDZm increased tumor glycolysis. Further research showed that MAP17 knockdown markedly retarded in vivo tumor growth in HCC. Importantly, attenuation of tumor glycolysis by galactose largely hijacked the growth-promoting role of MAP17 in HCC cells. RNA sequencing analysis revealed that MAP17 knockdown leads to transcriptional changes in the ROS metabolic process, cell surface receptor signaling, cell communication, mitotic cell cycle progression, and regulation of cell differentiation. Mechanistically, MAP17 exerted an increased tumoral phenotype associated with an increase in reactive oxygen species (ROS), which activates downstream effectors AKT and HIF1α to enhance the Warburg effect. In HCC clinical samples, there is a close correlation between MAP17 expression and HIF1α or phosphorated level of AKT.

Conclusions
Our results show that MAP17 is a novel glycolytic regulator, and targeting MAP17/ROS pathway may be an alternative approach for the prevention and treatment of HCC.
Extinction and persistence of a stochastic SIRV epidemic model with nonlinear incidence rate
Authors: Rifhat Ramziya , Teng Zhidong , Wang Chunxia 
Published: April 2021

AbstractIn this paper, a stochastic SIRV epidemic model with general nonlinear incidence and vaccination is investigated. The value of our study lies in two aspects. Mathematically, with the help of Lyapunov function method and stochastic analysis theory, we obtain a stochastic threshold of the model that completely determines the extinction and persistence of the epidemic. Epidemiologically, we find that random fluctuations can suppress disease outbreak, which can provide us some useful control strategies to regulate disease dynamics. In other words, neglecting random perturbations overestimates the ability of the disease to spread. The numerical simulations are given to illustrate the main theoretical results.
Combining self-reported and objectively measured survey data to improve hypertension prevalence estimates: Portuguese experience
Authors: Kislaya Irina , Leite Andreia , Perelman Julian , Machado Ausenda , Torres Ana Rita , Tolonen Hanna , Nunes Baltazar 
Published: April 2021

Abstract
Background
Accurate data on hypertension is essential to inform decision-making. Hypertension prevalence may be underestimated by population-based surveys due to misclassification of health status by participants. Therefore, adjustment for misclassification bias is required when relying on self-reports. This study aims to quantify misclassification bias in self-reported hypertension prevalence and prevalence ratios in the Portuguese component of the European Health Interview Survey (INS2014), and illustrate application of multiple imputation (MIME) for bias correction using measured high blood pressure data from the first Portuguese health examination survey (INSEF).

Methods
We assumed that objectively measured hypertension status was missing for INS2014 participants (n = 13,937) and imputed it using INSEF (n = 4910) as auxiliary data. Self-reported, objectively measured and MIME-corrected hypertension prevalence and prevalence ratios (PR) by sex, age group and education were estimated. Bias in self-reported and MIME-corrected estimates were computed using objectively measured INSEF data as a gold-standard.

Results
Self-reported INS2014 data underestimated hypertension prevalence in all population subgroups, with misclassification bias ranging from 5.2 to 18.6 percentage points (pp). After MIME-correction, prevalence estimates increased and became closer to objectively measured ones, with bias reduction to 0 pp - 5.7 pp. Compared to objectively measured INSEF, self-reported INS2014 data considerably underestimated prevalence ratio by sex (PR = 0.8, 95CI = [0.7, 0.9] vs. PR = 1.2, 95CI = [1.1, 1.4]). MIME successfully corrected direction of association with sex in bivariate (PR = 1.1, 95CI = [1.0, 1.3]) and multivariate analyses (PR = 1.2, 95CI = [1.0, 1.3]). Misclassification bias in hypertension prevalence ratios by education and age group were less pronounced and did not require correction in multivariate analyses.

Conclusions
Our results highlight the importance of misclassification bias analysis in self-reported hypertension. Multiple imputation is a feasible approach to adjust for misclassification bias in prevalence estimates and exposure-outcomes associations in survey data.
Youth sport participation and physical activity in rural communities
Authors: Kellstedt Debra K. , Schenkelberg Michaela A. , Essay Ann M. , Von Seggern Mary J. , Rosenkranz Richard R. , Welk Gregory J. , High Robin , Dzewaltowski David A. 
Published: April 2021

Abstract
Background
Physical activity, a high-frequency health behavior, varies by where children live, learn, and play. Children accumulate physical activity in adult-led in-school and out-of-school settings. Youth sport is a potential setting for physical activity, but there are differences in youth sport participation based on age, sex, and socioeconomic status. There is a gap in understanding demographic influences on youth sport participation and how these factors interact to influence physical activity. This study examines influences of grade, sex, and family income on youth sport participation and these factors and youth sport participation on moderate-to-vigorous physical activity of children in rural communities.

Methods
Children (n = 418 3rd–6th graders) living in two rural communities completed the online Youth Activity Profile as part of Wellscapes, a type 3 hybrid implementation-effectiveness community randomized trial. Mixed models with community as a random effect examined main effects and interactions of grade, sex, and family income on youth sport participation and these factors and youth sport participation on moderate-to-vigorous physical activity.

Results
About 80% of children engaged in youth sport, and full-pay lunch students were almost four times more likely to have youth sport participation than students with free/reduced lunch (OR = 3.91, 95% CI = 1.95, 7.8). Females and 6th graders (p < 0.05) had lower physical activity than comparison groups. Males with higher family income had greater physical activity; females with higher family income had less physical activity. For 6th graders, high family income had less effect on physical activity than similar 3rd-5th graders (p < 0.01).

Conclusions
While a fairly high percentage of children participate in youth sports, there are disparities in rural communities on youth sport participation and physical activity outcomes based on age, sex, and family income.
Echinacea reduces antibiotic usage in children through respiratory tract infection prevention: a randomized, blinded, controlled clinical trial
Authors: Ogal Mercedes , Johnston Sebastian L. , Klein Peter , Schoop Roland 
Published: April 2021

Abstract
Background
In children, up to 30% of viral respiratory tract infections (RTIs) develop into bacterial complications associated with pneumonia, sinusitis or otitis media to trigger a tremendous need for antibiotics. This study investigated the efficacy of Echinacea for the prevention of viral RTIs, for the prevention of secondary bacterial complications and for reducing rates of antibiotic prescriptions in children.

Methods
Echinaforce® Junior tablets [400 mg freshly harvested Echinacea purpurea alcoholic extract] or vitamin C [50 mg] as control were given three times daily for prevention to children 4–12 years. Two × 2 months of prevention were separated by a 1-week treatment break. Parents assessed respiratory symptoms in children via e-diaries and collected nasopharyngeal secretions for screening of respiratory pathogens (Allplex® RT-PCR).

Results
Overall, 429 cold days occurred in NITT = 103 children with Echinacea in comparison to 602 days in NITT = 98 children with vitamin C (p < 0.001, Chi-square test). Echinacea prevented 32.5% of RTI episodes resulting in an odds ratio of OR = 0.52 [95% CI 0.30–0.91, p = 0.021]. Six children (5.8%) with Echinacea and 15 children (15.3%) with vitamin C required 6 and 24 courses of antibiotic treatment, respectively (reduction of 76.3%, p < 0.001). A total of 45 and 216 days of antibiotic therapy were reported in the two groups, respectively (reduction of 80.2% (p < 0.001). Eleven and 30 events of RTI complications (e.g., otitis media, sinusitis or pneumonia) occurred with Echinacea and vitamin C, respectively (p = 0.0030). Echinacea significantly prevented influenza (3 vs. 20 detections, p = 0.012) and enveloped virus infections (29 vs. 47 detections, p = 0.0038). Finally, 76 adverse events occurred with Echinacea and 105 events with vitamin C (p = 0.016), only three events were reported possibly related with Echinacea.

Conclusions
Our results support the use of Echinacea for the prevention of RTIs and reduction of associated antibiotic usage in children.
Trial registration clinicaltrials.gov, NCT02971384, 23th Nov 2016.
Pre-implantation exogenous progesterone and pregnancy in sheep. II. Effects on fetal-placental development and nutrient transporters in late pregnancy
Authors: Halloran Katherine M. , Hoskins Emily C. , Stenhouse Claire , Moses Robyn M. , Dunlap Kathrin A. , Satterfield M. Carey , Seo Heewon , Johnson Gregory A. , Wu Guoyao , Bazer Fuller W. 
Published: April 2021

Abstract
Background
Administration of progesterone (P4) to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy, likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen. This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy. Suffolk ewes (n = 35) were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle (CO, n = 18) or 25 mg progesterone in CO (P4, n = 17) for the first 8 days of pregnancy. All ewes were hysterectomized on day 125 of pregnancy and: 1) fetal and placental weights and measurements were recorded; 2) endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism; and 3) maternal plasma, fetal plasma, allantoic fluid, and amniotic fluid were analyzed for amino acids, agmatine, polyamines, glucose, and fructose.

Results
Treatment of ewes with exogenous P4 did not alter fetal or placental growth, but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid, respectively. Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1, SLC7A2, SLC2A1, AGMAT, and ODC1 in endometria, as well as SLC1A4, SLC2A5, SLC2A8 and ODC1 in placentomes. In addition, AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes, whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.

Conclusions
This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy, suggesting a ‘programming’ effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.
Hsp90 co-chaperones, FKBP52 and Aha1, promote tau pathogenesis in aged wild-type mice
Authors: Criado-Marrero Marangelie , Gebru Niat T. , Blazier Danielle M. , Gould Lauren A. , Baker Jeremy D. , Beaulieu-Abdelahad David , Blair Laura J. 
Published: April 2021

AbstractThe microtubule associated protein tau is an intrinsically disordered phosphoprotein that accumulates under pathological conditions leading to formation of neurofibrillary tangles, a hallmark of Alzheimer’s disease (AD). The mechanisms that initiate the accumulation of phospho-tau aggregates and filamentous deposits are largely unknown. In the past, our work and others’ have shown that molecular chaperones play a crucial role in maintaining protein homeostasis and that imbalance in their levels or activity can drive tau pathogenesis. We have found two co-chaperones of the 90 kDa heat shock protein (Hsp90), FK506-binding protein 52 (FKBP52) and the activator of Hsp90 ATPase homolog 1 (Aha1), promote tau aggregation in vitro and in the brains of tau transgenic mice. Based on this, we hypothesized that increased levels of these chaperones could promote tau misfolding and accumulation in the brains of aged wild-type mice. We tested this hypothesis by overexpressing Aha1, FKBP52, or mCherry (control) proteins in the hippocampus of 9-month-old wild-type mice. After 7 months of expression, mice were evaluated for cognitive and pathological changes. Our results show that FKBP52 overexpression impaired spatial reversal learning, while Aha1 overexpression impaired associative learning in aged wild-type mice. FKBP52 and Aha1 overexpression promoted phosphorylation of distinct AD-relevant tau species. Furthermore, FKBP52 activated gliosis and promoted neuronal loss leading to a reduction in hippocampal volume. Glial activation and phospho-tau accumulation were also detected in areas adjacent to the hippocampus, including the entorhinal cortex, suggesting that after initiation these pathologies can propagate through other brain regions. Overall, our findings suggest a role for chaperone imbalance in the initiation of tau accumulation in the aging brain.
Correlation-aided method for identification and gradation of periodicities in hydrologic time series
Authors: Xie Ping , Wu Linqian , Sang Yan-Fang , Chan Faith Ka Shun , Chen Jie , Wu Ziyi , Li Yaqing 
Published: April 2021

AbstractIdentification of periodicities in hydrological time series and evaluation of their statistical significance are not only important for water-related studies, but also challenging issues due to the complex variability of hydrological processes. In this article, we develop a “Moving Correlation Coefficient Analysis” (MCCA) method for identifying periodicities of a time series. In the method, the correlation between the original time series and the periodic fluctuation is used as a criterion, aiming to seek out the periodic fluctuation that fits the original time series best, and to evaluate its statistical significance. Consequently, we take periodic components consisting of simple sinusoidal variation as an example, and do statistical experiments to verify the applicability and reliability of the developed method by considering various parameters changing. Three other methods commonly used, harmonic analysis method (HAM), power spectrum method (PSM) and maximum entropy method (MEM) are also applied for comparison. The results indicate that the efficiency of each method is positively connected to the length and amplitude of samples, but negatively correlated with the mean value, variation coefficient and length of periodicity, without relationship with the initial phase of periodicity. For those time series with higher noise component, the developed MCCA method performs best among the four methods. Results from the hydrological case studies in the Yangtze River basin further verify the better performances of the MCCA method compared to other three methods for the identification of periodicities in hydrologic time series.
French Translation and Validation of the Rating-of-Fatigue Scale
Authors: Brownstein Callum G. , Rimaud Diana , Singh Benjamin , Fruleux-Santos Laurie-Anne , Sorg Marine , Micklewright Dominic , Millet Guillaume Y. 
Published: April 2021

Abstract
Background
The Rating of Fatigue (ROF) scale can measure changes in perceived fatigue in a variety of contexts.

Objective
The aim of the present study was to translate and subsequently validate the ROF scale in the French language.

Methods
The study was composed of three phases. Phase 1 involved a comprehensive translation, back-translation, and consolidation process in order to produce the French ROF scale. During phase 2, the face validity of the French ROF scale was assessed. A cohort of 60 native French speaking participants responded to a range of Likert scale items which probed the purposes of the ROF scale and what it is intended to measure. During phase 3, the convergent and divergent validity of the ROF scale was assessed during ramped cycling to exhaustion and 10 min of resting recovery.

Results
The results from phase 1 demonstrated comparability and interpretability between the original and back-translated ROF scale. In phase 2, participants reported a high face validity, with a score of 3.48 ± 0.70 out of 4 when given the item probing whether the scale “measures fatigue”. This score further improved (3.67 ± 0.57, P = 0.01) after participants read the accompanying instructions. Participants were able to distinguish the purposes of the scale for measuring fatigue rather than exertion. In phase 3, strong correlations were found between ROF and heart rate (HR) both during exercise (r = 0.91, P < 0.01) and recovery (r = 0.92, P < 0.01), while discriminant validity between ROF and rating of perceived exertion (RPE) was found during recovery.

Conclusion
The present study permits the applications of the ROF scale in the French language.
CSR reporting by Chinese and Western MNEs: patterns combining formal homogenization and substantive differences
Authors: Ervits Irina 
Published: April 2021

AbstractIn light of the growing economic might and intensification of global activities of Chinese multinational enterprises (MNE), this paper looks into the nature of their corporate social responsibility (CSR) reporting. CSR communications of the largest Chinese companies and their counterparts from advanced economies have been compared based on quantitative and qualitative content analysis of CSR reports. A mixed method approach has been rarely utilized in the analysis of CSR reporting. To analyze CSR reports the paper uses a two-dimensional conceptual framework based on Wood (Acad Manag Rev 16:691–717, 1991); Jamali and Mirshak (J Bus Ethics 72:243–262, 2007) and Lockett, Moon and Visser (J Manag Stud 43:115–136, 2006); Moon and Shen (J Bus Ethics 94:613–629, 2010). The findings indicate that quantitatively Chinese MNEs display patterns of CSR reporting comparable to major MNEs in developed economies. This paper argues that just like MNEs from developed economies Chinese MNEs use a global CSR reporting template as a convenient tool to align and harmonize various isomorphic pressures. However, qualitatively substantive discrepancies in content have been also identified due to national or other contextual characteristics. The analysis reveals a complex picture of national and international isomorphic forces at play. The paper addresses the lack of consensus concerning convergence/divergence of CSR reporting across the globe and, more specifically, between developed economies and emerging markets. In this respect this paper responds to the general call for research looking into various aspects of business operations, including CSR reporting, of MNEs from emerging markets.