bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of β-arrestin1 and p53-MDM2 signaling in the development of missed abortion
Authors: Liu Ting , Ma Yuyan , Yin Qihui , Zhou Huanyu , Fang Yan 
Published: October 2020

Abstract
BackgroundMissed abortion is a nonviable pregnancy before the 20th week of gestation with retained products of conception. The definite etiology and pathogenesis are not fully understood. β-arrestin1, the important dynamic multitask scaffold protein, it play an important regulatory role in interacting with G protein-coupled receptor (GPCR) to mediate its homologous desensitization and internalization. Recent studies have demonstrated that p53/Mdm2-mediated ubiquitination of the IGF-1R maybe closely related to G protein-coupled receptor kinases (GRK)/β-arrestin1 system. Our previous studies have confirmed that the elevated expression of p53 and Mdm2 may be responsible for apoptosis during missed abortion. However, there was no information surrounding β-arrestin1 in missed abortion.MethodsThe mRNA levels of β-arrestin1 in villous samples of 31 missed abortion patients and 31 healthy controls were determined by real-time quantitative PCR. Immunohistochemistry was used to explore the expression and location of β-arrestin1, p53, Mdm2, VEGF, HIF-lα in trophoblasts. We up-regulated and silenced the expression of β-arrestin1 by lentiviral transfection, transwell assays were performed to examine the influences of β-arrestin1 expression on cell invasion. Furthermore, we explored the expression of several important proteins which may be related to β-arrestin1.Resultsβ-arrestin1 mRNA levels in the villous samples from women with missed abortion were found to be dramatically lower than in women who had normal pregnancies. The immunohistochemistry results showed that β-arrestin1 positive staining was significantly lower in missed abortion group than that in normal pregnancies group. Furthermore, the patients with missed abortion showed significantly higher levels of p53, Mdm2 and HIF-lα, lower level of VEGF than healthy controls by immunohistochemistry. The protein expressions of p-ERK、p-AKT、p-p53 in HRT-8 cells were significantly downregulated by reducing β-arrestin1 expression, while the expression of p-NF-ΚB、p-Mdm2 were enhanced. Overexpression of β-arrestin1 exhibited the adverse effect. The loss expression of β-arrestin1 expression was significantly related with decreased cell invasion ability.ConclusionOur data indicated that β-arrestin1 could play an important role in maintaining the maternal-fetal tolerance, the decreased β-arrestin1 expression in the villous samples may be related to the development of missed abortion.
Widespread Mitochondrial DNA&nbsp;Methylation Drift Contributes to Postoperative Delirium in Young and Old Mice
Authors: Liu Yue , Yang Shuai , Zhang Wei , Yang Yan , Jiang Ming , Ma Zhengliang , Gu Xiaoping 
Published: October 2020

Abstract
Background: Mitochondrial dysfunction is linked to the etiopathogenesis of postoperative delirium (POD), which severely affects the prognosis of elderly patients undergoing surgery. The methylation of mitochondrial DNA (mtDNA), a new and incompletely described phenomenon that regulates the structure and function of mitochondria, is associated with aging. However, the relationship between mtDNA methylation and POD has not been established. Methods: 5-methylcytosine (5-mC) at 5 CpG sites of the displacement loop (D-loop) and at 60 CpG sites of coding gene loci in the mitochondrial genome after surgery of the hippocampus, prefrontal cortex, amygdala, and anterior cingulate cortex in 6- and 18-month-old mice were detected using bisulfite pyrosequencing. Mitochondrial structure, mitochondrial gene expression and mtDNA copy number were also examined using Electron microscopy and real time PCR to find the association with mtDNA methylationResults: The mtDNA methylation drift manifested as a decrease in the methylation levels at the D-loop and an increase or decrease in the methylation levels at several coding gene loci, ultimately resulting in reduced mtDNA copy numbers, altered mitochondrial gene expression, and damaged mitochondrial structures in the hippocampus and prefrontal cortex after surgery. The activation of Silent information regulator-1 (SIRT1) ameliorated anesthesia- and surgery-induced mitochondrial dysfunction and delirium-like behaviors by regulating mtDNA methyltransferase-mediated mtDNA methylation. Conclusions: These data support the existence of epigenetic mtDNA regulation in POD; however, further studies are required to explore the specific mechanisms.
The Aberrant Expression Levels of miR-423-5p and&nbsp;miR-664b-5p in Peripheral Blood of Patients With Familial and Sporadic Ovarian Carcinoma
Authors: KURT BUSRA , TUNCER Seref Bugra , ODEMIS Demet AKDENIZ , GHAFOUR Arash ADAMNEJAD , Sarali Mukaddes Avsar , KILIC Seda , Erdogan Ozge Sukruoglu , Celik Betul , Saip Pınar , Yazici Hulya 
Published: October 2020

Abstract
MicroRNAs (miRNAs), are endogenous noncoding single strand RNA molecules with approximate length of 22 nucleotides. Ovarian cancer is a heterogenous disease which includes different biologic behaviors in the clinical, and molecular level. miRNAs have roles in the early diagnosis, prognosis, and chemotherapy sensitivity for ovarian cancer, and in the regulation of reproduction by being expressed in the ovaries. The expression level of two miRNAs of miR-423-5p, and miR-664b-5p selected from the miRNAs which were detected to be important for the ovarian cancer etiology in our previous studies were investigated in the peripheral blood of familial and sporadic ovarian cancer patients, and in healthy individuals. The expression analyses were statistically evaluated with SPSS v21.0 program using the Quantitative Real-Time PCR technique. A statistically significant difference was detected for both miRNAs between the healthy controls and ovarian cancer patient groups (p:0.000). The miR-423-5p expression was detected to increase 2.35 fold, and miR-664b-5p was detected to increase 2.47 fold in ovarian cancer patients compared with the levels in the control group. miR-423-5p was reported to be overexpressed in various cancer types, and in different disease stages in previous study, and miR-423-5p was demonstrated to have increased in the lymphocytes in the peripheral circulation of ovarian cancer patients first in our literature. The miR-664b-5p expression level was detected in high levels in ovarian cancer patient group, however was detected to have decreased in 64% of ovarian cancer patients with BRCA mutation carrier. The expressions of both miRNA molecules were detected to have decreased in the ovarian cancer subgroups in patients with ovarian cancer with addition of a second primary cancer of endometrium cancer, however, were detected in the highest level in ovarian cancer patients in addition to another secondary cancer except breast and endometrium cancer. The results obtained from the study showed that the increased expression of both miRNA molecules were suggested to be associated with ovarian cancer, and decrease was suggested to be associated with endometrium cancer. In summary, the miRNA molecules in the present study might be the non-invasive biological indicator in ovarian cancer, and the demonstration of these molecules on the tumor tissue, and their change during treatment in future studies will be beneficial.
Exercise capacity, Cardiovascular- and Metabolic Risk of German Police officers in an international comparison
Authors: Strauß Markus , Foshag Peter , Jehn Ulrich , Vollenberg Richard , Littwitz Henning , Leischik Roman 
Published: October 2020

Abstract
Background: The police force has a mandate to protect citizens and enforce law for public safety. Employment in the police force is recognized as a dangerous occupation and characterized by job-related physical hazards. Therefore, good health and adequate physical condition are necessary. The aim of this study was to determine cardiovascular, cardiorespiratory and metabolic risk parameters of German police officer (POs) in comparison to POs from other nations. Methods: 55 male police officers from Germany participated in the survey. Anthropometric measurements, cardiovascular and metabolic risk factors and blood parameters were taken. 10-year cardiovascular risk was calculated by using the Framingham Risk Score. The diagnosis of metabolic syndrome was based on the criteria of the International Diabetes Federation. Cardiorespiratory status was assessed by exercise spirometry. Results: The analyzed group of POs demonstrated a high prevalence of preobesity (BMI: 28.0±3.2, waist circumference: 97.8±12.4 cm). 61.8 % of POs showed an increased waist circumference. POs shows elevated cholesterol and triglyceride values and high prevalence of abnormal systolic and diastolic blood pressure. 10-year cardiovascular system risk of examined POs were 9.6 ± 7.4 %. The cardiovascular risk profile of our examined German cohort seems to be in the higher range in comparison to international data. 32 % of POs in our study group were diagnosed with metabolic syndrome. Maximal relative oxygen uptake of POs was 34.1 ± 8.0 ml/kg-1 ·min-1. Conclusions: To our knowledge this study was one of the first to assess data on cardiovascular health, metabolic syndrome and cardiorespiratory status of police officers in Germany. The results of our study population demonstrated the high cardiovascular and metabolic risk of German police officers and displaying a decreased cardiorespiratory fitness. The present study results demonstrated the need for implementation of interventions and creating health-promoting concepts like corporate sports activities and nutrition courses to counteract cardiovascular and metabolic risk factors and the subsequent development of cardiovascular and metabolic disease in this occupational group.
The appearance and increase in the quantity and proportion of the clinical research coordinator's service fee in drug clinical trial research fund and its impact on trial quality
Authors: Chen Liran , Chen Zhimin , Chen Huafang 
Published: October 2020

Abstract
Objective: The changes of absolute value and relative value of clinical research coordinator service fee and its influence on the quality of drug clinical trial were analyzed.Methods: This study compared the amount and structural changes of drug clinical trial costs in before 3 years and after 3 years of self-examination and inspection initiated by the China Food and Drug Administration, identified the increase number and composition of each individual cost of a clinical trial research funds which including clinical research coordinator service fee, investigator labor fee, subjects examination fee, subjects traffic subsidy, documents management fee, drug management fee, etc.Result: The most significant appearance and increase in volume and proportion were the clinical research coordinator service fee. From the initial few to the global multicenter tumor drug clinical trials RMB31,624 or 34.92% of the proportion and domestic multicenter tumor drug clinical trials RMB16,500,accounted for 33.74%.Discussion: It has become common for more money to be spent on clinical trials to be accompanied by improved quality, but the occurrence and continuous increase of clinical research coordinator service fee were divided into two aspects, On the one hand, the quality of clinical trials was promoted by the large amount of low-skill trivial work undertaken by clinical research coordinator; on the other hand, the quality of clinical trials was undermined by the fact that clinical research coordinator did too much treatment evaluation work that should have been done by the investigator.
Dietary Dihydroartemisinin Supplementation Alleviates Intestinal Inflammatory Injury Through TLR4/NODs/NF-κB Signaling Pathway in Weaned Piglets with Intrauterine Growth Retardation
Authors: Niu Yu , Zhao Yongwei , He Jintian , Yun Yang , Shen Mingming , Gan Zhending , Zhang Lili , Wang Tian 
Published: October 2020

Abstract
Background: Intrauterine growth retardation (IUGR) leads to impaired intestinal morphology and function. IUGR infants are at a risk for intestinal inflammatory diseases. Dihydroartemisinin (DHA) is a derivative of artemisinin, which possesses anti-inflammatory activity and immunomodulatory effect. However, little is known about the effects of DHA on IUGR piglets. Therefore, the present study was conducted to investigate whether dietary DHA supplementation could attenuate intestinal injury in IUGR weaned piglets. Methods: Piglets with normal birth weight or IUGR were fed the basal diet or basal diet supplemented with 80 mg/kg DHA from 21 d to 49 days of age. At 49 days of age, eight piglets from each group with nearly similar body weight were sacrificed. The jejunal and ileal samples were collected for further analysis.Results: IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated TLR4/NODs/NF-κB signaling pathway. DHA supplementation improved intestinal morphology, indicated by higher villus height, villus height to crypt depth ratio, villus surface area and lower villus width of IUGR piglets (P < 0.05). DHA inclusion exhibited higher apoptosis index and the expression of caspase-3, and lower proliferation index and the expression of proliferating cell nuclear antigen in the intestine of IUGR piglets (P < 0.05). Diet supplemented with DHA could attenuate intesitnal inflammation, indicated by higher concentrations of intestinal inflammatory cytokines and lipopolysaccharides in IUGR piglets (P < 0.05). In addition, DHA down-regulated the related mRNA expressions of TLR4/NODs/NF-κB signaling pathway and up-regulated mRNA expressions of TLR4 and NODs signaling negative regulators in the intestine of IUGR piglets (P < 0.05). Dietary DHA supplementation decreased the protein expressions of toll-like receptors 4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and increased the protein expression of cytoplasmic pNF-κB in the intestine of IUGR piglets (P < 0.05). Conclusions: Dietary DHA supplementation may have beneficial effects in improving intestinal morphology, regulating enterocyte proliferation and apoptosis, and alleviating intestinal inflammation through TLR4/NODs/NF-κB signaling pathway in IUGR weaned piglets.
Deletion of an Enhancer in FGF5 is Associated With Ectopic Expression in Goat Hair Follicles and the Cashmere Growth Phenotype
Authors: Li Yefang , Song Shen , Liu Xuexue , Zhang Yanli , Wang Dandan , He Xiaohong , Zhao Qianjun , Pu Yabin , Guan Weijun , Ma Yuehui , Jiang Lin 
Published: October 2020

Abstract
BackgroundResearch on cashmere growth has a significant effect on the production of cashmere and a profound influence on cashmere goat breeding. Whole-genome sequencing is a powerful platform to rapidly gain novel insights into the identification of genetic mechanisms underlying cashmere fiber growth. ResultsIn this study, we generated whole-genome sequences of 115 domestic goats from China, Nepal and Pakistan, including 51 cashmere goats and 64 non-cashmere goats. We found genetically distinct clusters according to their geographic locations but genetic admixture or introgression may have occurred between the Chinese and Nepalese goats. We identified that the fibroblast growth factor 5 gene (FGF5) shows a strong signature for positive selection in the cashmere goat. The 505-bp indel variant at the FGF5 gene locus appeared to be strongly associated with cashmere growth. Functional validation showed that the insertion variant may serve as an enhancer for transcription factor binding, resulting in increased transcription of the upstream FGF5 gene in non-cashmere goats. ConclusionsOur study provides useful information for the sustainable utilization and improved conservation of goat genetic resources and demonstrates that the indel mutation in the FGF5 gene could potentially serve as a molecular marker of cashmere growth in cashmere goat breeding.
Association of Pericardial Adipose Tissue With Left Ventricular Structure and Function: A Region-specific Effect?
Authors: Kim Jin-Seok , Kim Seon Won , Lee Jong Seok , Lee Seung Ku , Abbott Robert , Lee Ki Yeol , Lim Hong Euy , Sung Ki-Chul , Cho Goo-Yeong , Koh Kwang Kon , Kim Sun H. , Shin Chol , Kim Seong Hwan 
Published: October 2020

Abstract
Background: The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity.Methods: We studied 2,471 participants (50.9% women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT.Results: Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P <0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P <0.001) and decreased systolic (P = 0.015) and early diastolic (P <0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was the only obesity index independently associated with systolic TDI velocity (P <0.001).Conclusions: PAT was associated with subclinical LV structural and functional changes, and these associations were independent of and stronger than with general and abdominal obesity measures.
Best Practices for Human Milk Collection for COVID-19 Research
Authors: McGuire Michelle K , Seppo Antti , Goga Ameena , Buonsenso Danilo , Collado Maria Carmen , Donovan Sharon M. , Muller Janis A. , Ofman Gaston , Monroy-Valle Michele , O'Connor Deborah L. , Pace Ryan M. , Perre Philippe Van de 
Published: October 2020

Abstract
In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs – particularly when it is associated with a novel pathogen – the question will naturally arise as to whether the pathogen can be transmitted via breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens via milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from pre-analytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. Here we provide “best practices” for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.
Association Between Pyrethrum Knockdown Time and Sodium Channel Genotypes in California Aedes Aegypti
Authors: Mack Lindsey K , Kelly Erin Taylor , Lee Yoosook , Brisco Katherine K , Shen Kaiyuan Victoria , Zahid Aamina , Schoor Tess van , Cornel Anthony J. , Attardo Geoffrey M 
Published: October 2020

Abstract
Background: Since their detection in 2013, Aedes aegypti has become a widespread urban pest in California. The availability of cryptic larval breeding sites in residential areas and resistance to insecticides pose significant challenges to control efforts. Resistance to pyrethroids is largely attributed to mutations in the voltage gated sodium channels (VGSC), the pyrethroid site of action. However, past studies have indicated that VGSC mutations may not be entirely predictive of the observed resistance phenotype. Methods: To investigate the frequencies of VGSC mutations and the relationship with pyrethroid insecticide resistance in California, we sampled Ae. aegypti from four locations in the Central Valley, and the Greater Los Angeles area. Mosquitoes from each location were subjected to an individual pyrethrum bottle bioassay to determine knockdown times. A subset of assayed mosquitoes from each location was then analyzed to determine the composition of 8 single nucleotide polymorphism (SNP) loci within the VGSC gene. Results: The distribution of knockdown times for each of the five Californian populations sampled was non-parametric with bimodal distributions. One group succumbs to insecticidal effects around 35-45 minutes and the second group lasts up to and beyond the termination of the assay (120+ minutes). We detected 5 SNPs polymorphic within California populations. One is potentially new and alternatively spliced (I915K), and four are known and associated with resistance: F1534C, V1016I, V410L and S723T. The Central Valley populations (Clovis, Dinuba, Sanger and Kingsburg) are fairly homogenous with only 5% of the mosquitoes showing heterozygosity at any given position. In the Greater LA mosquitoes 55% had at least one susceptible allele at any of the five SNPs. The known resistance allele F1534C was detected in almost all sampled mosquitoes (99.4%). We observe significant heterogeneity in individuals with the same genotypes, confirming that the resistance SNPs alone cannot. Conclusions: Resistance associated VGSC SNPs are prevalent, particularly in the Central Valley. Interestingly, among mosquitoes with all 4 resistance associated SNPs, we observe heterogeneity in bottle bioassay profiles suggesting that other mechanisms are important to the individual resistance of Ae. aegypti in California.
The Effectiveness of Synchronous Online Flipped Learning in College EFL Reading Course During the COVID-19 Epidemic
Authors: Ma Guihua 
Published: October 2020

Abstract
The purpose of this study was to examine the effectiveness of synchronous online flipped learning (SOFL) when no one can go to school and merely rely on online learning during the COVID-19 epidemic. According to community of inquiry (CoI), put forward by Garrison et al (2001), only when the three key elements of blended teaching, social presence, teaching presence and cognitive presence reach a high level, can effective learning occur, which were used as the framework of this study. Mixed methods were used to evaluate the effectiveness of SOFL teaching. A total of 60 undergraduates from pre-service English teacher training program participated in an online questionnaire survey and 25 of them voluntarily joined online in-depth interviews. Results showed that the learning effect was improved in SOFL context. Anonymity was found to improve learning in asynchronous online learning while distraction and lack of sustainable attention were found in synchronous online learning session. The findings suggest that instructors may need to have a careful design, strict organization and scientific implementation of synchronous online teaching and learning in order to achieve distinctive teaching effects, and that they may also consider the complex influence factors of synchronous and asynchronous online learning to arouse students’ interest and attention, and meet their learning needs (Wong 2020).