bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic characteristics and prognosis of m6A RNAmethylation regulator in acute myeloid leukemia
Authors: Xu Jiasheng , Liao Kaili , Fu Zhonghua , Xiong Zhenfang 
Published: July 2020

Abstract
Background: To identify the genetic characteristics of m6A RNA methylation regulators in AML and explore their potential value as prognostic markers.Methods: RNA-seq transcriptome data and clinical survival data of acute myeloid leukemia (AML) were downloaded from ICGC and TCGA, gene annotation files were downloaded from GENECODE (1). 13 widely reported m6A RNA alphas were obtained from the literature. The expression of m6A RNA methylation regulators were collected and analized using gene annotation files. The samples were subjected to consistent clustering to obtain two subgroups RM1 and RM2, and the pathological characteristics and survival between the two subgroups were analyzed. Comparative analysis and functional analysis of m6A RNA methylation regulators between subgroups were completed. The STRING database analyzed the interactions between m6A RNA methylation regulators, and Spearman analyzed the correlation of expression of m6A RNA methylation regulators. COX regression analysis and risk scores were used to predict prognosis and pathological characteristics, and risk scores calculated using features were used to predict the prognosis and clinicopathological characteristics of tumor patients.Results: According to the morphological characteristics of AML, the samples were divided into 8 categories (M0 Undifferentiated, M1, M2, M3, M4, M5, M6, M7), and among them, the expression profile and expression heat map of 13 m6A RNA methylation regulators were constructed. Using m6A RNA methylation regulator as a feature vector, consistent clustering of 151 samples yielded two subgroups RM1 and RM2. Among them, the expression of the regulator in RM1 was higher than RM2,and RM2 patients had a longer survival time than RM1. Gene set enrichment analysis found that functional processes such as endothelial-hematopoietic transformation through the Notch pathway were significantly enriched in RM1. The analysis of the KM curve indicates that when the expression of FTO or ALKBH5 or of ZC3H13 was low, the survival time of patients was significantly higher than that with high expression.Conclusion: m6A RNA methylase regulator is not only an independent prognostic marker of AML, but also can predict its clinicopathological characteristics, which has potential value for stratifying prognosis and improving treatment strategies.
The distribution and abundance of multiple chalazia in pediatrics receiving surgery in Zhejiang province, China: a hospital-based cross-sectional study.
Authors: Zheng Xiaoyu , Dorazio Robert M. , Wang Tingyan , Zhao Sujuan , Zhao Zhengyan 
Published: July 2020

Abstract
Background: To investigate the distribution and abundance of multiple chalazia in pediatric patients that need surgical treatments.Methods: Patients with multiple chalazia treated in a tertiary Children's Hospital were reviewed between June and December 2016. Demographic data, locations and numbers of chalazia were recorded. Data were analyzed using generalized linear models of the counts and the occurrences of chalazia. Hypotheses were tested using likelihood ratio tests appropriate for each type of data.Results: The study included 128 subjects, most of which were 1-3 years of age. The majority of patients had bilateral chalazia (95.3%), and the proportions of patients with internal, external and marginal chalazion differed significantly (99.2%, 61.7% and 2.3% respectively). The total number of internal chalazia had a negative binomial distribution, whereas the total number of external chalazia followed a Poisson distribution. The number of internal and external chalazia did not differ significantly with gender, age, or residence of patients. Internal chalazia were located more frequently on the upper lids (P < 0.01). External chalazia showed no preference of localization. The average abundance of internal chalazia on each eyelid did not relate to the presence of external chalazia.Conclusions: In Zhejiang province, China, multiple chalazia that require surgery are more common among younger children (aged 1-3 years) than older ones. The anatomical distribution varies depending on the chalazion’s types. Multiple chalazia often occur bilaterally and internally. Doctors should pay more attention to the anatomical distribution to achieve a higher success rate in chalazion surgery.
Calcination Temperatures, Compositions and Antimicrobial Properties of Heterostructural ZnO–CuO Nanocomposites from Calotropis Gigantea Targeted for Skin Ulcer Pathogens
Authors: Govindasamy G Ambarasan , Mydin Rabiatul Basria S.M.N. , Harun Nor Hazliana , Sreekan Srimala 
Published: July 2020

Abstract
An eco-friendly green route is employed for the successful synthesis of heterostructured ZnO-CuO nanocomposites using Calotropis gigantea plant and the investigation of their antimicrobial properties against skin ulcer pathogens. Binary ZnO-CuO nanocomposites prepared at calcination temperature of 300 °C exhibited superior antimicrobial effect on S. aureus, whereas the negative control sample did not show any antibacterial activities. High ZnO nanoparticles of 75 wt.% ZnO-CuO nanocomposites showed zero count of Staphylococcus aureus at a minimum inhibitory concentration of 0.625 mg/mL and minimum bactericidal concentration (MBC) of 2.5 mg/mL. Interestingly, the 75 wt.% ZnO-CuO nanocomposites exhibited strong antimicrobial activity against multi-drug resistant pathogens, with MBC ranging from 0.3125 mg/mL to 1.25 mg/mL. A time-kill assay captured a reduction in viable count from 4.3 log 10 to 1.3 log 10 after 12 h of incubation for S. aureus . Elucidating the antimicrobial activities could be useful for identifying novel ways to incorporate ZnO-CuO nanocomposites in polymers for applications in biocide materials, such as for wound dressing. Further, molecular studies are needed to explain the underlying biocidal mechanism of ZnO-CuO nanocomposites especially in the presence of Cu 2+ and Zn 2+.
Dependence of heme biosynthesis on iron-sulfur cluster biogenesis: human ALAD is an unrecognized iron-sulfur protein
Authors: Liu Gang , Sil Debangsu , Tong Wing-Hang , Maio Nunziata , Bollinger J. Martin , Krebs Carsten , Rouault Tracey Ann 
Published: July 2020

Abstract
Heme biosynthesis and iron-sulfur cluster (ISC) biogenesis are two major mammalian metabolic pathways that require iron. It has long been known that these two pathways interconnect, but the previously described interactions do not fully explain why heme biosynthesis depends on intact ISC biogenesis. Herein we have identified a previously unrecognized connection between these two pathways through our discovery that human aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme biosynthesis, is an Fe-S protein. We found that several highly conserved cysteines and an Ala306-Phe307-Arg308 motif of human ALAD are important for [Fe4S4] cluster acquisition and coordination. The enzymatic activity of human ALAD was greatly reduced upon loss of its Fe-S cluster, which resulted in reduced heme biosynthesis in human cells. Our findings explain why heme biosynthesis depends on intact ISC biogenesis, as ALAD provides an early Fe-S-dependent checkpoint in the heme biosynthetic pathway.
The proportion and effect of corticosteroid therapy for patients with COVID-19 infection: a systematic review and meta-analysis
Authors: Wang Jun-ning , Yang Wei-xia , Chen Pu-wen , Guo Jian-bin , Liu Rui , Wen Peng-fei , Li Kun , Lu Yao , Ma Tao , Song Wei , Qin Si-qing , Zhang Yu-Min , Wang Yakang 
Published: July 2020

Abstract
Objectives: COVID-19 remains a global challenge. Corticosteroids are a group of anti-inflammatory and suppressive immune response drugs that are widely used in the treatment of COVID-19, especially when it presents with viral pneumonia. Comprehensive reviews investigating the comparative proportion and efficacy of corticosteroid use are scarce. Therefore, we conducted a systematic review and meta-analysis of clinical trials to evaluate the proportion and efficacy of corticosteroid use for the treatment of COVID-19.Methods: We conducted a comprehensive literature review of PubMed, EMBASE, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Database for relevant trials on glucocorticoid therapy in COVID-19 patients. Outcome measures were the proportion of patients administered corticosteroids, viral clearance and mortality. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with associated 95% confidence intervals (CIs).Results: Forty-three trials involving 6603 patients were included. The meta-analysis demonstrated that the proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. In addition, our meta-analysis demonstrated no significant difference in the proportions of severe and nonsevere patients who were administered corticosteroids. We also performed subgroup analyses stratified by severity, indicating that the proportion of patients administered corticosteroids was significantly higher among intensive care unit (ICU) patients than among non-ICU patients. The results of our meta-analysis indicated that corticosteroid treatment significantly delayed the viral clearance time. Finally, our meta-analysis demonstrated no significant difference between the use of corticosteroids for COVID-19 patients who died and those who survived. This result indicated that mortality was not correlated with corticosteroid therapy.Conclusion: The proportion of COVID-19 patients who received corticosteroids was significantly lower than that of patients who did not receive corticosteroids. Corticosteroid use in subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections delayed virus clearance and did not convincingly improve survival;therefore, corticosteroids should be used with caution in the treatment of COVID-19.
Macromolecule Biomaterials Promote the Osteogenic Differentiation Capacity of Equine Adipose -Derived Mesenchymal Stem Cells
Authors: Elashry Mohamed I. , Baulig Nadine , Wagner Alena-Svenja , Klymiuk Michele C. , Kruppke Benjamin , Hanke Thomas , Wenisch Sabine , Arnhold Stefan 
Published: July 2020

Abstract
Background: Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. In the present study, the effect of biomaterial bone substitutes on equine adipose derived MSCs morphology, viability, adherence, migration and osteogenic differentiation were investigated. Methods: MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and B30Str biomaterials in osteogenic differentiate medium either under static or mechanical fluid shear stress (FSS) culture conditions. The data were generated by histological means, life cell imaging, cell viability, adherence and migration assays. Osteogenic differentiation was detected by semi-quantification of alkaline phosphatase (ALP) activity, matrix mineralization using Alizarin Red S (ARS) staining and quantification of the osteogenic markers; runt related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) expression using RT-qPCR. All data were statistically analyzed using ANOVA. Results: The data revealed that combined mechanical stress with MC but not B30 enhanced MSCs viability and promoted their migration. Combined osteogenic medium with MC, B30 and B30Str increased ALP activity compared to cultivation in basal medium. Osteogenic induction with MC, B30 and B30Str resulted in diffused matrix mineralization by means of ARS. FSS increased the viability in the presence of the osteogenic medium with MC but not B30 or B30Str. FSS enhanced osteogenic differentiation in the presence of B30Str. Upregulation of Runx2 and ALP expression was detected with osteogenic differentiation together with B30 and B30Str regardless of static or FSS culture. Conclusions: Taken together, the data revealed that FSS in conjunction with biomaterials promoted osteogenic differentiation of MSCs. This combination may be considered as a marked improvement for clinical applications to cure bone defects.
TRIM16 Positively Regulates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating the Ubiquitination and Degradation of RUNX2
Authors: Zhao Yi , Zhai Qiaoli , Liu Hong , Xi Xun , Chen Shuai , Liu Dongxu 
Published: July 2020

Abstract
BackgroundPeriodontal disease is a common disease that compromises the integrity of tooth-supporting tissues. Bone regeneration is the ultimate goal of periodontal therapies, in which osteogenic differentiation of human periodontal ligament stem cells plays a critical role. The tripartite motif (TRIM)16 is downregulated in periodontal tissues of patients with periodontitis and involved in osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs).However, the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown.MethodshPDLSCs were isolated and identified by immunophenotype assays using flow cytometry. Overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS) and enzyme‐linked immunosorbent assays (ELISA) were used to evaluate osteogenic potential capacity. Reverse transcription quantitative PCR (RT-qPCR) and Western blot analysis were performed to determine the expression of osteogenic-related markers and activation of relevant signaling pathways. Co-immunoprecipitation assays were performed to confirm the interactions between proteins and the ubiquitination of RUNX2. A LC-MS/MS analysis was performed to explore the different expression proteins in present of TRIM16.ResultsTRIM16 significantly promoted alkaline phosphatase activity and mineralized nodule formation, and positively regulated the osteogenic differentiation of hPDLSCs by enhancing protein expression of RUNX2, COL1A1 and OCN. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. Besides, TRIM16 significantly increased expression of COL1A1 via activation of p38MAPK/RUNX2.ConclusionThis study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which may promote the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.
Differentially expressed genes in cotyledon of ewes fed mycotoxins
Authors: Britt Jessica L , Noorai Rooksana , Duckett Susan 
Published: July 2020

Abstract
Background
Ergot alkaloids (E+) are mycotoxins produced by the endophytic fungus, Epichloë coenophiala, in tall fescue that are associated with ergotism in animals. Exposure to ergot alkaloids during gestation reduces fetal weight and placental mass in sheep. These reductions are related to vasoconstrictive effects of ergot alkaloids and potential alterations in nutrient transport to the fetus. Cotyledon samples were obtained from eight ewes that were fed E+ (n = 4; E+/E+) or E- (endophyte-free without ergot alkaloids; n = 4; E-/E-) seed during both mid (d 35 to 85) and late (d 85–133) gestation to assess differentially expressed genes associated with ergot alkaloid induced reductions in placental mass and fetal weight, and discover potential adaptive mechanisms to alter nutrient supply to fetus.
Results
Ewes fed E+/E + fescue seed during both mid and late gestation had 20% reduction in fetal body weight and 33% reduction in cotyledon mass compared to controls (E-/E-). Over 13,000 genes were identified with 110 upregulated and 33 downregulated. Four genes had a |log2FC|>5 for ewes consuming E+/E + treatment compared to controls: LECT2, SLC22A9, APOC3, and MBL2. REViGO revealed clusters of upregulated genes associated glucose, carbohydrates, lipid, protein, macromolecular and cellular metabolism, regulation of wound healing and response to starvation. For downregulated genes, no clusters were present, but all enriched GO terms were associated with anion and monocarboxylic acid transport. The complement and coagulation cascade and the peroxisome proliferator-activated receptor signaling pathway were found to be enriched for ewes consuming E+/E + treatment.
Conclusions
Consumption of ergot alkaloids during gestation altered the cotyledonary transcriptome specifically related to macronutrient metabolism, wound healing and starvation. These results show that ergot alkaloid exposure upregulates genes involved in nutrient metabolism to supply the fetus with additional substrates in attempts to rescue fetal growth.
A genome-wide screening for RNAi pathway genes in Acari
Authors: Soroker Victoria , Nganso Beatrice T , Sela Noa 
Published: July 2020

Abstract
BackgroundRNA interference (RNAi) is a highly conserved, sequence-specific gene silencing mechanism present in Eukaryotes. Three RNAi pathways critical for organismal development and survival are known, namely micro-RNA (miRNA), Piwi-interacting RNA (piRNA) and short interfering RNA (siRNA) pathways. Little knowledge exist about the genes involved in these pathways in Acari. Moreover, variable successes has been obtained in gene knockdown via siRNA pathway in functional genomics and management of Acari species. We hypothesized that the clue may be in the variability in the composition and the efficacy of siRNAi machinery among Acari. ResultsBoth comparative genomic analyses and domain annotation suggest that all the analyzed species have orthologs of genes that mediate gene silencing via the three RNAi pathways though gene duplication and/or loss have occurred in the different species. We also identified orthologs of Caenorhabditis elegans RNA-dependent RNA polymerase (RdRP) gene in all Acari species though no secondary Argonaute homologs that operate with this gene in siRNA amplification mechanism were found. This finding suggests that the siRNA amplification mechanism present in Acari may be distinct from that described in C. elegans. Moreover, the genomes of these Acari species encode no ortholog of C. elegans systemic RNAi defective 1 (Sid-1) that mediate systemic RNAi, suggesting that the phenomena of systemic and parental RNAi that has been reported in some Acari species probably occur through a different mechanism. Orthologs of RNAi spreading defective-3 (Rsd-3) gene and scavenger receptors namely Eater and SR-CI that mediate endocytosis cellular update of dsRNA in C. elegans and Drosophila melanogaster were found in Acari genomes. This result suggests that cellular dsRNA uptake in Acari is endocytosis-dependent. Detailed phylogenetic analyses of core RNAi pathway genes in the studied Acari species revealed that their evolution is compatible with the proposed monophyletic evolution of this group.ConclusionsTaken together, our in silico comparative analyses have revealed the potential activity of all three pathways in Acari. However, much experimental work remains to be done in elucidating the operating mechanisms behind these pathways in particular those that govern systemic/parental RNAi and siRNA amplification in Acari.
The Role of Age Distribution, Time Lag Between Reporting and Death and Healthcare System Capacity in Case Fatality Estimates of COVID-19
Authors: Vanella Patrizio , Wiessner Christian , Holz Anja , Krause Gérard , Möhl Annika , Wiegel Sarah , Lange Berit , Becher Heiko 
Published: July 2020

Abstract
Background: European countries report large differences in coronavirus disease (COVID-19) case fatality risk (CFR). CFR estimates depend on demographic characteristics of the cases, time lags between reporting of infections and deaths and infrastructural characteristics, such as healthcare and surveillance capacities. Methods: We used publicly available data from official reports of the national health authorities of Germany, Italy, France, and Spain on COVID-19. These include age-specific numbers of cases and deaths for different dates, which we used to compute age-standardized CFR ratios using a standard European population for standardization. Moreover, we investigated the impact of different potential time lags on the estimation of the CFR using data published by the European Centre for Disease Prevention and Control (ECDC). Finally, we described the association between case fatality and the intensive care bed capacity.Results: We found that age-standardized CFR estimates increased from the beginning of March to mid-May 2020 in all included European countries. In Germany, CFRs are lower than in other countries. However, the differences are much larger when comparing the crude risks rather than the age-adjusted risks. Thus, the different age distribution of the cases account for a major proportion of the reported differences. Case fatality estimates using time lags of 1-10 days converged in all countries over time, however, there is no optimal time lag to assess the CFR during the pandemic. Time lags that provided the most constant estimates and approach best the observed CFR after the pandemic ranged from 5-10 days in different countries and at different time points during the pandemic. For the association between intensive care bed capacity and fatality we found that days with a high need for intensive care beds were positively correlated with daily hospitalization fatality in France, Italy, and Spain, but not in Germany. Conclusions: Our results highlight that cross-country comparisons of crude CFR estimates can be misleading and should be avoided. However, to adjust for potential sources of bias more disaggregated data and information on surveillance and health care capacities are needed. Filling these gaps and harmonizing data across European countries will facilitate further analysis.
Serum miR-218 is a Potential Biomarker in the Diagnosis of Colorectal Cancer
Authors: Zhang Keqian , Mao Tianqi , He Zhicheng , Wu Xiaojiao , Peng Yu , Chen Yanrong , Dong Yan , Ruan Zhihua , Wang Zhe 
Published: July 2020

Abstract
Background: Our study was designed to explore the diagnostic role of serum microRNA-218 (miR-218) in colorectal cancer (CRC).Methods: Serum level of miR-218 was measured in 117 CRC samples and 88 normal controls using quantitative reverse transcription (qRT-PCR). Chi-square test was performed to assess the relationships between miR-218 expression and clinical characteristics of CRC patients. The receiver operating characteristic (ROC) analysis was established to investigate the diagnostic significance of miR-218 in CRC with the area under ROC curve (AUC).Results: MiR-218 was found to be weekly expressed in CRC serum samples compared with healthy controls (P < 0.001). And the down-regulation of miR-218 shared close relationships with lymph node metastasis (P = 0.013), vascular invasion (P = 0.020) and TNM stage (P = 0.031). However, age, tumor size and gender had no significant influence on miR-218 expression (P > 0.05). According to the ROC curve, miR-218 yielded an AUC value of 0.897 and an optimal cutoff point value of 0.021, providing a 83.8% sensitivity and a 78.4% specificity. Conclusion: In summary, decreased expression of serum miR-218 was detected in CRC patients and the expression of miR-218 was a diagnostic marker in CRC.