bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of Graves’ hyperthyroidism with very long-term methimazole treatment: A clinical trial
Authors: Azizi Fereidoun , Abdi Hengameh , Amouzegar Atieh 
Published: January 2021

Abstract
Background: Long-term antithyroid drugs therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years.Methods: Fifty nine patients with Graves’ disease on long-term MMI for 14.2±2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years.Results: Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8±1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study.Conclusions: Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research.Trial registration: IRCT201009224794N1, 2010-10-25. Retrospectively registered.www. IRCT.IR/Trial/5143.
Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer
Authors: Wu Lei , Quan Wen , Yue Guojun , Luo Qiong , Peng Dongxu , Pan Ying , Zhang Guihai 
Published: January 2021

Abstract
Background: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear.Methods: An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2-3). Based on STRING analysis results, we found that the NKX2-3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2-3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2-3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa.Results: We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2-3). Further analysis demonstrated that NKX2-3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa.Conclusions: The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa.
Long non-coding RNA FAM83H-AS1 acts as a potential oncogenic driver in human ovarian cancer
Authors: Yuan Xiaolei , Huang Ying , Guo Man , Hu Xiaowei , Li Peiling 
Published: January 2021

Abstract
Objective

Ovarian cancer (OC) is one of the most aggressive women cancers with increasing incidence and mortality rates worldwide. Long non-coding RNAs (lncRNAs) could as major players in OC process. Although FAM83H antisense RNA1 (FAM83H-AS1) is demonstrated play an important roles in a many cancers, the detailed function and mechanism has not been reported in OC.

Results

We integrated multiple kinds of bioinformatics approaches and experiments validated method to evaluate functions of FAM83H-AS1 in OC. Some differential expressed lncRNAs were identified between OC and normal control tissues. FAM83H-AS1 was one of most differentially expressed lncRNAs and up-regulated in multiple cancer types. Specially, expression of FAM83H-AS1 was higher in OC and showed difference in diverse stages. High FAM83H-AS1 expression is associated with worse pan-cancer and OC outcomes. FAM83H-AS1-centric network including lncRNA-miRNA, lncRNA-protein and lncRNA-mRNA ceRNA network were constructed to infer the function and mechanism of FAM83H-AS1. There were two methylation sites including cg01399317 and cg20519035 located at FAM83H-AS1. The methylation level of cg01399317 was correlated with gene expression of FAM83H-AS1. The expression level of FAM83H-AS1 was correlated with infiltration level of immune cell including macrophage, neutrphil and dendritic cell in OC patients. Lastly, qRT-PCR showed that the expression of FAM83H-AS1 was higher in OC tissues than normal control tissues.

Conclusion

Collectively, these results indicated that FAM83H-AS1 may act as an oncogenic driver and it may be a potential therapy target in OC.
An efficient computational Method for Predicting Drug-Target Interactions using Weighted Extreme Learning Machine and Speed Up Robot Features
Authors: Yong An Ji , Fan-Rong Meng , Zi-Ji Yan 
Published: January 2021

Abstract
Background: Prediction of novel Drug–Target interactions (DTIs) plays an important role in discovering new drug candidates and finding new proteins to target. In consideration of the time-consuming and expensive of experimental methods. Therefore, it is a challenging task that how to develop efficient computational approaches for the accurate predicting potential associations between drug and target. Results: In the paper, we proposed a novel computational method called WELM-SURF based on drug fingerprints and protein evolutionary information for identifying DTIs. More specifically, for exploiting protein sequence feature, Position Specific Scoring Matrix (PSSM) is applied to capturing protein evolutionary information and Speed up robot features (SURF) is employed to extract sequence key feature from PSSM. For drug fingerprints, the chemical structure of molecular substructure fingerprints was used to represent drug as feature vector. Take account of the advantage that the Weighted Extreme Learning Machine (WELM) has short training time, good generalization ability, and most importantly ability to efficiently execute classification by optimizing the loss function of weight matrix. Therefore, the WELM classifier is used to carry out classification based on extracted features for predicting DTIs. The performance of the WELM-SURF model was evaluated by experimental validations on enzyme, ion channel, GPCRs and nuclear receptor datasets by using fivefold cross-validation test. The WELM-SURF obtained average accuracies of 93.54%, 90.58%, 85.43% and 77.45% on enzyme, ion channels, GPCRs and nuclear receptor dataset respectively. We also compared our performance with the Extreme Learning Machine (ELM), the state-of-the-art Support Vector Machine (SVM) on enzyme and ion channels dataset and other exiting methods on four datasets. By comparing with experimental results, the performance of WELM-SURF is significantly better than that of ELM, SVM and other previous methods in the domain.Conclusion: The results demonstrated that the proposed WELM-SURF model is competent for predicting DTIs with high accuracy and robustness. It is anticipated that the WELM-SURF method is a useful computational tool to facilitate widely bioinformatics studies related to DTIs prediction.
Integrated Transcriptomic and Metabolomic Analysis Reveals a Transcriptional Regulation Network for the Biosynthesis of Carotenoids and Flavonoids in ‘Cara cara’ Navel Orange
Authors: Zhang Haipeng , Chen Jiajing , Peng Zhaoxin , Shi Meiyan , Liu Xiao , Wen Huan , Jiang Youwu , Cheng Yunjiang , Xu Juan , Zhang Hongyan 
Published: January 2021

Abstract
Background: Carotenoids and flavonoids are important secondary metabolites in plants, which exert multiple bioactivities and benefits to human health. Although the genes that encode carotenogenesis and flavonoid biosynthetic enzymes are well characterized, the transcriptional regulatory mechanisms that are related to the pathway genes remain to be investigated. In this study, ‘Cara cara’ navel orange (CNO) fruit at four development stages were used to identify the key genes and TFs for carotenoids and flavonoids accumulation.Results: In this study, CNO was used to investigate the profiles of carotenoids and flavonoids by a combination of metabolomic and transcriptomic analyses. The important stage for the accumulation of the major carotenoid, lycopene was found to be at 120 days after florescence (DAF). The transcripts of five carotenogenesis genes were highly correlated with lycopene contents, and 16, 40, 48, 24 and 18 transcription factors (TFs) were predicted to potentially bind 1-deoxy-D-xylulose-5-phosphate synthase (DXS1), deoxyxylulose 5-phosphate reductoisomerase (DXR), geranylgeranyl diphosphate synthase (GGPPS2), phytoene synthase (PSY1) and lycopene β-cyclase (LCYB) promoters, respectively. Narirutin was the most abundant flavonoid in the flesh at the early stages, 60 DAF was the most important stage for the accumulation of flavonoids, and 17, 22, 14, 25, 24 and 16 TFs could potentially bind phenylalanine ammonia-lyase (PAL-1 and PAL-4), 4-Coumarate-CoA ligase (4CL-2 and 4CL-5), chalcone synthase (CHS-1) and chalcone isomerase (CHI) promoters, respectively. Furthermore, both sets of fifteen candidate TFs might regulate at least three key genes and contribute to carotenoids/flavonoids accumulation in CNO fruit. Finally, a hierarchical model for the regulatory network among the pathway genes and TFs was proposed.Conclusions: Collectively, our results suggest that DXS1, DXR, GGPPS2, PSY1 and LCYB genes were the most important genes for carotenoids accumulation, while PAL-1, PAL-4, 4CL-2, 4CL-5, CHS-1 and CHI for flavonoids biosynthesis. A total of 24 TFs were postulated as co-regulators in both pathways directly, which might play important roles in carotenoids and flavonoids accumulation in CNO fruit.
Single Nucleotide Polymorphisms Associated with Methotrexate-induced Nausea in Juvenile Idiopathic Arthritis
Authors: Kyvsgaard Nini , Mikkelsen Torben Stamm , Als Thomas D. , Christensen Anne Estmann , Corydon Thomas J. , Herlin Troels 
Published: January 2021

Abstract
BackgroundContext: Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). MTX treatment is commonly associated with nausea. Large inter-individual variation exists in the level of MTX-induced nausea, possibly due to genetic factors. Purpose: To investigate whether MTX-induced nausea was associated with single nucleotide polymorphisms (SNPs) in genes encoding MTX-transporter proteins, a MTX metabolizing enzyme and a nausea receptor.FindingsMethods: Children aged ≥9 years treated with MTX for JIA were eligible. MTX-induced nausea was registered by the children’s completion of a nausea diary (min. 7 days) and the parents’ completion of the MTX intolerance severity score (MISS). The selected SNPs were: SLCO1B1 (rs4149056; rs4149081), SLCO1B3 (rs2117032), SLC19A1 (rs1051266), ABCC2 (rs2273697; rs3740066; rs717620), ABCB1 (rs2032582; rs1045642), MTHFR (rs1801131, rs1801133), HTR3A (rs1062613; rs1985242; rs1176713) and HTR3B (rs1176744). Results: Enrolled were 121 JIA patients (82 girls: 39 boys) with a median age of 13.3 years (IQR: 11.3-15.1). The median MTX dose was 9.7 mg/m2/week (IQR: 9.0-10.9). The median MTX treatment duration prior to enrolment was 340 days (IQR: 142-766). The SNP analysis was available for 119 patients. MTX intolerance was associated with the genotype distribution of rs1801133 (MTHFR) (p= 0.02). There was no additive effect of the minor alleles for any of the selected SNPs, nor any significant haplotype associations. Conclusion Summary: MTX-induced nausea may be influenced by genetic polymorphisms in a MTX metabolizing enzyme (rs1801133; MTHFR). Implications: Further analyses involving inclusion of larger cohorts are needed to understand the impact of SNPs on MTX-induced nausea in JIA.
Evaluation Of Cardiovascular Risk Factors In Patients With Familial Hypercholesterolemia From The North-Eastern Area Of Romania
Authors: Vlad Cristiana-Elena , Foia Liliana , Florea Laura , Costache Irina-Iuliana , Covic Andreea , Popescu Roxana , Reurean-Pintilei Delia , Covic Adrian 
Published: January 2021

Abstract
Background. Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were:(a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents. Methods. This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included.Results. 980 patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them. Conclusions. In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.
Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway
Authors: Zhao Xiuhao , Zhou Jin , Liang Wenhua , Sheng Qingfeng , Lu Li , Chen Tong , Chen Jianglong , Tan Kezhe , lv Zhibao 
Published: January 2021

Abstract
Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated.Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components.Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.
Post-treatment work patterns amongst survivors of lymphoma treated with high-dose chemotherapy with autologous stem-cell transplantation
Authors: Hernaes Kjersti Helene , Smeland Knut Halvor Bjøro , Fagerli Unn Merete , Kiserud Cecilie Essholt 
Published: January 2021

Abstract
Background This study describes post-treatment work patterns in lymphoma survivors treated with high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). It aims to identify determinants for labour force participation and exclusion after HDT-ASCT.Methods All survivors treated with HDT-ASCT for lymphoma in Norway between 1995 and 2008, aged ≥ 18 years at HDT-ASCT and alive at survey in 2012-2013 were eligible. We divide survivors by current employment status (full-time, part-time and unemployed). Main outcomes are current employment status, work hours and work ability. Withdrawals are patients employed when diagnosed but not before HDT-ASCT. Results Of the 274 who completed the survey, 82% (N=225) were included in the final analyses. Mean age at survey was 52 years, 39% were female, 85% were employed when diagnosed, 77% before HDT-ASCT and 69% at survey. Employment before HDT-ASCT corresponds with a higher probability of employment at survey for a given symptom burden. In the most extensive statistical model, it increases with 37.3 percentage points. Work hours amongst withdrawals plummet after HDT-ASCT while work ability shows a rebound effect. The potential economic gain from their re-enter into the work force equals 70% of the average annual wage in Norway in 2012.Conclusions For a given symptom burden, staying employed throughout diagnosis and treatment is associated with a higher probability of future employment. These results favour policies for labour force inclusion past diagnosis and treatment increasing cancer survivors’ probability of future employment. However, we need more research on withdrawal mechanisms, and on policy measures that promote inclusion.
The Association of Quality of Life and Personality Characteristics with Adolescent Metabolic Syndrome: a Cohort Study
Authors: liang xiaohua , Zhang Peng , Luo Shunqing , Zhang Guifang , Tang Xian , Liu Lingjuan 
Published: January 2021

Abstract
Background: An increased prevalence of adolescent metabolic syndrome (MS) is associated with adulthood cardiovascular diseases. This study aimed to explore the potential relationship of quality of life (QoL) and personality traits with adolescent MS. Methods：A total of 1961 participants from Chongqing with an average age of 11.68 years from a cohort study established in 2014 and followed through 2019 were included. QoL information, Eysenck’s personality questionnaire and MS components were collected.Results: The prevalence of adolescent MS was 4.69% (95% confidence interval, 3.84%-5.72%). A higher QoL domain score of physical activity ability (PAA) was a protective factor for both MS and MS score (all P<0.01), which was mainly negatively correlated with central obesity, diastolic blood pressure (DBP) and triglycerides levels, as well as positively correlated with high density lipoprotein cholesterol (HDL-C) level. The total QoL score was negatively correlated with triglycerides level and positively correlated with DBP (all P<0.01). High extraversion personality score was a protective factor against adolescent MS (P=0.04) and MS score (P<0.05), which was mainly negatively correlated with waist circumference, systolic blood pressure and TGs, and positively correlated with HDL-C (all P≤0.01).Conclusions: QoL score and extraversion personality score were independent protective factors against both MS prevalence and MS score, suggesting that community intervention to improve the QoL and psychological health of children is essential.
Recombinant Expression of Cec-B Peptide in Escherichia coli with a Significant Anticancer Effect on Hepatocellular Carcinoma
Authors: Okasha Hend , Nasr Sami Mohamed , Samir Safia 
Published: January 2021

Background:
Cecropin-B (Cec-B) is an Antimicrobial Peptide (AMP) found in insects.

Objectives:
Recombinant production of Cec-B peptide in Escherichia coli (Rosetta™ DE3), and studying its anticancer
effect on hepatocellular carcinoma cell line (HCC).

Methods:
The Cec-B gene of Drosophila melanogaster was synthesized by PCR assembly using the simplified gene
synthesis (SGS) method. To express the recombinant peptide in E. coli (Rosetta™ DE3); the synthesized gene was cloned
into pET-15b expression vector. The recombinant peptide was expressed as insoluble aggregates called inclusion bodies
(IBs) using 2mM lactose inducer. IBs were solubilized in a denatured form using 8 M urea followed by in-vitro protein
refolding using rapid dilution method. The refolded Cec-B was purified using cation-exchange SP-FF column. Cytotoxicity
of recombinant Cec-B (rCec-B) was reported on normal human lung cell line (WI-38), and hepatocellular carcinoma cell
line (HepG2).

Results:
The Cec-B gene was expressed and purified at concentration 1.212±0.1 mg/ml which represents 48.49±4% of the
total proteins injected to the column (2.5±0.2 mg/ml). The safe dose of purified rCec-B on normal WI-38 cells was
calculated to be 1.57 mg/ml. The half-maximal inhibitory concentration (IC50) of rCec-B on HepG2 cell line was
calculated to be 25 µg/ml. Scanning electron microscope (SEM) showed that untreated and treated HepG2 cells had cell
diameters from 11-12.92 μm and 14.18-21.58 μm, respectively.

Conclusion:
The results of this study revealed a successful expression of the rCec-B peptide using a pET-based expression
system with a simple purification step. The purified peptide could be considered as a hopeful anticancer drug against HCC.
Increased Level of Interleukin-8 in Female Genital Tract After HP Eradication Lines
Authors: Kravtsov Viacheslav , Surovtceva Tatiana , Taame Maria , Grukhin Yuriy , Kalinina Natalia 
Published: January 2021

Background:
Antibiotics are known to be effective in treating bacterial infectious disease.
Changes in microflora and mucosal dysbiosis may take place after antibiotic treatment. We investigated
in this research the effect of anti-Helicobacter pylori treatment (AHT) on local immunity of the
female genital tract.

Methods:
The study identified the levels of cytokines IL-8 and TNF-α in vaginal secretion in a group
of female patients with Helicobacter-associated acid-related diseases who were or were not treated
with antibiotics against Helicobacter Pylori.

Results:
Research outcomes turned out that the secretory cytokine (chemokine) IL-8 is dramatically increased
in the vaginal mucosa in patients treated with antibiotics, specifically in post-menopause women.

Conclusion:
Helicobacter pylori eradication treatment affects the immune status of the female genital
tract.