bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Localization of PTTG1&nbsp;Promotes Migration and Invasion of Seminoma Tumor Through Activation of MMP-2.
Authors: Teveroni Emanuela , Nicuolo Fiorella Di , Bianchetti Giada , Epstein Alan L. , Grande Giuseppe , Maulucci Giuseppe , De Spirito Marco , Pontecorvi Alfredo , Milardi Domenico , Mancini Francesca 
Published: December 2020

Abstract

Background: Seminoma is the most common subtype of testicular germ cell tumors (TGCTs) and its molecular patterns have not been fully clarified. The pituitary tumor-transforming gene 1 (PTTG1) is a securin, inhibitor of premature sister chromatid segregation during mitosis and is overexpressed in many cancers. PTTG1 shows the ability to sustain the invasiveness of several cancer types through its transcriptional activity. In the present study, we investigate the PTTG1 role on the invasive properties of seminoma.Methods: Three seminoma cell lines showing different proliferation rates and marker expression features were used as an in vitro model. Biochemical and immunofluorescence analyses were performed to evaluate PTTG1 levels and subcellular localization. Functional analyses, including wound healing, matrigel invasion assays and zymography were applied to study migratory and invasive capability of the cell lines. RNA interference studies and overexpression experiments were performed to address the PTTG1 role in seminoma cell lines invasiveness. Finally, the Atlas database was interrogated to study PTTG1 subcellular localization in seminoma and non-seminomas testicular tumors in order to analyze the PTTG1 and matrix metalloproteinase-2 (MMP-2) levels in these groups.Results: We found that PTTG1 was highly and differentially expressed in the seminoma cell lines. PTTG1 nuclear localization was positively correlated to the aggressive phenotype. Modulation of PTTG1 expression uncovered a direct causal link between PTTG1 and seminoma cell line invasiveness. Importantly, analysis of the human Atlas database revealed that PTTG1 was localized in the nucleus exclusively in seminoma compared with non-seminoma tumors and showed that MMP-2 levels was significant higher in seminomas.Conclusions: The results of the present research elucidate the role of nuclear PTTG1 in promoting invasiveness and metastatic process of seminoma cell lines. Analysis from the Atlas database strongly supported these results, revealing an exclusive PTTG1 nuclear localization and an increase of MMP-2 levels in seminoma versus non-seminoma tumors. Overall, these data lead to the hypothesis that nuclear PTTG1 is an eligible prognostic factor in seminomas.
CircMETTL3, Upregulated in a m6A-dependent Manner, Promotes Breast Cancer Progression through&nbsp;circMETTL3/miR-31-5p/CDK1 axis
Authors: Li Zhi , Yang HaiYan , Dai XinYuan , Zhang Xu , Huang YuZhou , Shi Liang , Wei Jifu , Ding Qiang 
Published: December 2020

Abstract
Background: Growing evidence indicates N6-methyladenosine (m6A) has biological function in oncogenesis. METTL3, the catalytic component, is the most important part of methyltransferase complex and plays a crucial role in cancers. However, the biological function of circRNAs derived from METTL3 and the underlying molecular mechanism remains unclear.Methods: Quantitative real-time PCR was used to determine the circMETTL3 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circMETTL3 on tumor growth and metastasis in breast cancer. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between circMETTL3 and miR-31-5p in breast cancer. Furthermore, we explored regulatory effects of m6A modification on circMETTL3 expression with m6A RNA immunoprecipitation.Results: We found that circMETTL3 was significantly upregulated in breast cancer. The results indicated that circMETTL3 could promote breast cancer cell proliferation, migration and invasion as well as tumorigenesis in vivo. Mechanistic analysis showed that circMETTL3 might act as a ceRNA (competing endogenous RNA) of miR-31-5p to relieve the repressive effect of miR-31-5p on its target cyclin-dependent kinases (CDK1). Moreover, m6A modification of circMETTL3 might affect its expression.Conclusion: Our findings suggest that circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/CDK1 axis. Moreover, METTL3, the host gene of circMETTL3, may regulates circMETTL3 expression in a m6A-dependent manner, while circMETTL3 has no effect on METTL3 expression, providing a new relationship between the circRNA and the corresponding host gene. Thus, it may serve as a new diagnostic marker or therapeutic target for breast cancer patients.
Proteomic Analysis of Capacitated and Non-Capacitated Spermatozoa of Yanbian Yellow Cattle
Authors: Chen Xuan , Li Zuochen , Lv Yanqiu , Xu Yichao , Cheng Mimi , Qu Xinglin , Zhang Yuyang , Jin Yi 
Published: December 2020

Abstract
Background: Sperm capacitation is a process which occurs prior to fertilization, and is essential for producing high-quality living embryos. The main purpose of this study was to explore the difference of proteomics between capacitated and non-capacitated sperm of Yanbian yellow cattle. Bioinformatic analyses of LC-MS/MS data included GO enrichment, KEGG pathway enrichment, and protein-protein interaction (PPI) analysis. Results: The results revealed 23 specific proteins in the capacitated group and 345 in the non-capacitated group. Compared with non-capacitated sperm, capacitated sperm exhibited 89 upregulated proteins and 509 downregulated proteins. Western blotting was used to confirm our proteomics data. The expression level of PSMD1 in the capacitated sperm group was significantly lower than that in the non-capacitated sperm group, and the expression level of HSPA5 was significantly higher than in the non-capacitated sperm group. Conclusions: Our results revealed that many proteins were differentially expressed between capacitated and non-capacitated sperm, particularly those involved in the proteasome signaling and protein transport signaling pathways. This work enhances our understanding of molecular processes involved in sperm viability in Yanbian yellow cattle, and provides a framework for future studies.
Depression and Adherence to Healthy Lifestyle Among Patients with Coronary Artery Diseases
Authors: Al-Zaru Ibtisam M. , Masha'al Dina , Shahrour Ghada , Hayajneh Audai A. 
Published: December 2020

Abstract
Background: It is well-established in the literature that coronary artery disease (CAD) is a risk factor for depression and that depressive symptoms inversely affect the development and progression of CAD. No published studies have examined the relationship between depression and adherence to healthy lifestyle behaviors among patients with CAD in Jordan. Therefore, the purpose of this study is to investigate the impact of depression on adherence to healthy lifestyle behaviors among CAD patients in Jordan. Methods: A convenience sample of 130 patients with CAD was recruited from out-patient cardiac clinics in a university-affiliated hospital and government-operated hospital in Northern Jordan. Data were collected using self-administered questionnaires on depression and adherence to healthy lifestyle behaviors among CAD patients. Results: Our data showed that 41% of the participants were non-adherent to healthy lifestyle behaviors, especially in the areas of physical activity (6.2%), maintaining a healthy diet (24.6%), and weight loss (26.15%). Gender, smoking status, and number of cardiac catheterization procedures were found to be significant predictors of patient adherence to healthy lifestyle behaviors. Although depressive symptoms were present in 56.9 % of the participants, depression was not found to be a significant predictor of adherence to healthy lifestyle behaviors among our sample. Conclusion: Our study provides valuable data regarding the levels and predictors of adherence to healthy lifestyle behaviors among CAD patients with CADs. Implications for future research and practice are addressed.
Efficacy of a Comprehensive Binary Classification Model Using a Deep Convolutional Neural Network for Wireless Capsule Endoscopy
Authors: Kim Sang Hoon , Hwang Youngbae , Oh Dong Jun , Nam Ji Hyung , Kim Ki Bae , Park Junseok , Song Hyun Joo , Lim Yun Jeong 
Published: December 2020

Abstract
Manual reading of capsule endoscopy (CE) video is a time-consuming process in diagnosing small bowel diseases. Although many algorithms have been introduced, multi-diagnosis has not been sufficiently validated. They are promising but still premature to be used in clinical practice. Therefore, we developed a practical binary classification model and tested it with unseen cases.400,000 CE images were randomly selected from 84 cases. Among them, 240,000 were used to train an algorithm to categorize images binarily. The remaining images were utilized for validation and internal testing. The algorithm was externally tested with 256,591 unseen images.Diagnostic accuracy was 98.067% when the trained model was applied to the validation set. It was 97.946% when applied to images for internal testing. When the model was applied to a dataset provided by an independent hospital not participated during training, its accuracy was 85.470%. The area under the curve was 0.922.Our binary classification model showed excellent internal test results, and when tested in unseen external cases, misreadings were slightly increased while judging ‘insignificant’ images containing ambiguous substances. When we can get over this problem, CNN-based binary classification will become the most promising candidates for developing clinically ready computer-aided reading methods.
Role of Robotic Natural Orifice Specimen Extraction Surgery in Colorectal Neoplasms
Authors: Yao Hongliang , Li Tiegang , Chen Weidong , Lei Sanlin , Liu Kuijie , Liu Bo , Zhou Jiangjiao 
Published: December 2020

Abstract
To explore the safety and feasibility of robotic natural orifice specimen extraction surgery(NOSES) for colorectal neoplasms. All patients underwent robotic NOSES from March 2016 to October 2019 in our hospital were enrolled for retrospective analysis. Clinicopathological data were collected and analyzed. A total of 180 patients were enrolled. The average distance from the lower edge of the tumor to the anus was (8.64 ± 3.64) cm and Maximum circumferential diameter (CDmax) of specimen was (3.5 ± 1.6) cm. In terms of safety, the average operation time, intraoperative blood loss, and postoperative hospital stay were (187.5 ± 78.3) min, (47.4 ± 34) mL, and (11.3 ± 7.5) days, respectively. In terms of feasibility, the average number of lymph node harvested was (14.8 ± 5). Notably, a close distance from the lower edge of the tumor to the anus with long operation time and postoperative hospital stay indicates high incidence of anastomotic leakage. In addition, either received nRCT has no effect on perioperative safety. Robotic NOSES shows advantages in terms of safety and feasibility compared with laparoscopic NOSES. This procedure could not only be a safe procedure but also could achieve good oncological outcomes.
Metformin Reduces Histone H3K4me3&nbsp;at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells
Authors: Kim Dongho , Kim Yujin , Lee Bo Bin , Cho Eun Yoon , Han Joungho , Shim Young Mog , Kim Duk-Hwan 
Published: December 2020

Abstract

BackgroundThis study aimed at understanding the effect of metformin on histone H3 modifications at the promoters of cell cycle regulatory genes in lung cancer cells. MethodsHistone H3 modifications were analyzed using ChIP-seq, and changes in DNA methylation and chromatin accessibility were evaluated using the SureSelect Methyl-Seq Target Enrichment System and ATAC-seq, respectively. MLL2 overexpression was analyzed in tumor and matched normal tissues from 42 non-small cell lung cancer (NSCLC) patients. ResultsMetformin showed little effect on DNA methylation or chromatin accessibility at the promoter regions of cell cycle regulatory genes in lung cancer cells but significantly downregulated histone H3K4 methyltransferase MLL2 and reduced H3K4me3 levels at the promoters of positive cell cycle regulatory genes such as CDK1, CDK6, and E2F8. Eighty-eight genes involved in cell cycle showed reduced H3K4me3 levels in response to metformin, and 27% of them showed mRNA downregulation. The siRNA-mediated knockdown of MLL2 significantly reduced the H3K4me3 levels at the promoters of positive cell cycle regulatory genes. MLL2 overexpression was found in 14 (33%) of 42 NSCLC patients, with a higher prevalence in females (P = 0.04). A Cox proportional hazards analysis showed that recurrence-free survival of adenocarcinoma patients with MLL2 overexpression was approximately 1.32 (95% CI = 1.08–4.72; p = 0.02) times poorer than in those without it after adjusting for sex and pathologic stage. ConclusionsThe present study suggests that metformin might reduce H3K4me3 levels at the promoters of positive cell cycle regulatory genes through MLL2 downregulation in lung cancer cells. And, MLL2 may be a potential therapeutic target for reducing the recurrence of lung adenocarcinoma.
The Effect of Kuchala (Arum Korolkowii Regel, 1873) Tuber Tincture to Increase of the Serum Testosterone in the Adult Male Guinea Pigs (Cavia Porcellus Linnaeus, 1758)
Authors: ALDAYROV NURBEK SAIDILLAEVICH , JUMABEKOVA JARKINAY , KURMANBEKOVA GULBUBU , OMURZAKOVA NURJAMAL , KIDIRALIEVA BERMET , BORKOEV BAKIT , SALIEVA KALIPA , TULOBAEV ASKARBEK , SALYKOV RUSLAN , SHARSHENALIEVA GULNARA , CHEKIROV KADYRBAY 
Published: December 2020

Abstract
BackgroundKuchala (Arum korolkowii Regel) is one of the medicinal plants often used in folk medicine in the Kyrgyz Republic. As a medicinal raw material, tubers tincture used in small doses to increase human sexual potency. However, there is no scientific evidence proving the medicinal effects of kuchala. For these reasons, we decided to study the effect of kuchala tuber tincture on the sexual potency of adult male guinea pigs.MethodsWe analyzed the effect of kuchala at age ±48-month-old, in 12 male guinea pigs. Prepared 10% tuber tincture of kuchala in 70% ethanol was administered perorally a once-daily dose of 150 µl for 30 days for the male guinea pigs. These study data were obtained by the ethological, hematological and serum biochemistry, gross anatomical, histological and statistical methods.ResultsThe hematological and serum biochemistry parameters were significantly different between control and experimental group. Neutrophils’ percentage in experimental group was significantly lower (dР < 0.001) than in control group. Lymphocyte counts on the contrary were significantly higher in experimental group (dР < 0.001). RBC counts, Hgb, Hct, MCH and MCHC were significantly higher in the experimental group (dР < 0.001; dР < 0.001; cР < 0.01; dР < 0.001; dР < 0.001 respectively) than control group. The color indicator and mean platelet volume contrary was higher (bР < 0.05) and significantly higher (dР < 0.001) in control animals than in the experimental. ALT and AST levels were lower in experimental than control group (both dР < 0,001). The testosterone concentration in serum was much higher (dР < 0,001) in the experimental group. Microscopically was found minor structural damage in the liver tissue that indicates a metabolic disorder. However, the testes showed an improvement in spermatogenesis in the experimental if compared with the control group.Conclusion﻿The 10% kuchala tuber tincture in 70% ethanol has a positive effect to improve the sexual potency of old guinea pigs by increasing the production of testosterone and increasing spermatogenesis.
A Novel Spleen Tyrosine Kinase Inhibitor Suppresses Invasiveness of Rheumatoid Arthritis Fibroblast Like Synoviocytes and Improves Collagen Induced Arthritis
Authors: Kim Seon Uk , Yoo Hyun Jung , Kim Jung Ho , Hwang Hae Jun , Park Jin Kyun , Lee Eun Young , Song Yeong-Wook 
Published: December 2020

Abstract
Background/PurposeRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by bone and cartilage destruction with leukocyte infiltration and activation at synovial tissue. The fibroblast-like synoviocytes (FLS) have a central role in disease pathogenesis and their invasiveness correlates with articular damage in RA patients. Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase known to have a crucial role in immune receptor signaling. This study aimed to evaluate the inhibitory effect of a novel small-molecule SYK inhibitor, SKI-O-592, on the invasiveness of RA FLS and inflammation of monocytes in vitro and in a mouse collagen-induced arthritis (CIA) model in vivo.MethodsFLS were isolated from synovial tissues of RA patients. FLS were treated with SKI-O-592 for 1 hr and then stimulated with tumor necrosis factor-alpha (TNF-α) for 48 hr. After stimulation, cell viability was measured using cell counting kit-8 (CCK-8) assay. The levels of IL-6, IL-8, CXCL10, MMP-3, and TNF-α were measured in culture supernatant of RA FLS and the monocytic cell line THP-1 cells by ELISA. Wound healing assay transwell migration and invasion assay using RA FLS was performed to evaluate cell migration ability. The adhesion ability of FLS was evaluated by co-culture with calcein-AM labeled THP-1 cells, and the expression of VCAM-1, ICAM-1, α-tubulin, β-actin, total and phosphorylated SYK, c-Jun N-terminal kinase (JNK), p38, ERK, phosphorylated c-Jun, mitogen-activated protein kinase kinase 4 (MKK4), and MKK3/6 was determined by Western blotting. CIA was developed in DBA/1J mice. Clinical arthritis score and histological scores were evaluated after treatment with SKI-O-592.ResultsSKI-O-592 reduced the secretion of chemokine, CXCL10 in RA FLS. Migration of cells to the wound region and through membrane pores and matrigel were decreased by SKI-O-592. Phosphorylation of JNK and p38 was reduced by SKI-O-592 after TNF-α stimulation. SKI-O-592 decreased secretion of TNF-α levels dose-dependently in THP-1 cells with IgG stimulation. The viability and proliferation of FLS and THP-1 were not affected by SKI-O-592. In the CIA model, scores for clinical arthritis and histology were decreased following SKI-O-592 treatment.ConclusionSKI-O-592 inhibited the invasiveness of RA FLS and had an anti-inflammatory effect on monocytes. SKI-O-592 exhibited therapeutic effects in the mouse CIA model by improving clinical and histological scores with amelioration of joint destruction. In conclusion, a novel SYK inhibitor, SKI-O-592, may provide a new therapeutic option for RA patients.
Determinants of Market Participation of Smallholder Sorghum Farmers and Strategies for Improving Their Participation; the Case of Moretna Jiru District, Ethiopia
Authors: Belete Atinkugn Assefa 
Published: December 2020

Abstract
The purpose of this study is to identify market participation of smallholder’s Sorghum producers in Moretna jiru district, central Ethiopia. Primary data was collected from 355 randomly selected smallholder farm households from three randomly selected kebeles in the district. The survey data was analyzed using descriptive statistics and econometrics model with probit and Tobit censored model. Results of the probit model analysis showed that output, farm size, extension contact and ownership of transport positive and significant role in households’ decision to participate in sorghum output sales at 1% level of significance; whereas, household income, off-farm income, access to credit and lack of information negatively at 1% and 10% level of significance. Results of Tobit censored analysis showed; extension contact, farm size, output and membership of farmer group have positive and significant role in the value of sorghum at 1% level of significance; while access to credit was found to have negative significant role at 5% level of significance. Farm size, output, extension contact and membership of farmer group was found to affect both households’ decisions to participate and intensity of participation in sorghum sales at 1% level of significance. Based on the findings there is a need to enhance the interaction between extension export and farmers and distribute trained extension exports in all kebeles by giving different trainings. ; and help the farmers improve land productivity, where possible, by intensifying farm practices through provision of sustainable and timely availability of inputs and management practices so as to generate surplus sorghum output and boost sales.
Linezolid-containing Regimen Lowers Mortality of Rifampicin/multidrug-resistant Tuberculous Meningitis in Shenzhen, China
Authors: Fang Mu-tong , Su You-feng , Deng Guo-fang , Zhang Pei-ze , Liu Hou-ming , Mao Zhi , Zeng Jian-feng , Li Guo-bao , Yang Qian-ting , Wang Zhong-yuan 
Published: December 2020

Abstract
Background: The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) is increasing in many countries and regions in the world. Its mortality is significantly higher than non rifampicin/multidrug-resistant ones (NRR/MDR-TBM ). This article aims to explore the RR/MDR-TBM related risk factors, and compare the different therapeutic effects to the RR/MDR-TBM patients between linezolid-containing anti-tuberculosis regimen and non linezolid regimen in Shenzhen city. Furthermore, we want to find a better therapy for pathogen negative TBM with RR/MDR-TBM related risk factors. Methods: 137 cases with confirmed TBM (pathogen positive), who were hospitalized in the Third People’s Hospital of Shenzhen from June 2014 to March 2020, were enrolled in this study, all patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) according to the GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test of CSF (cerebral spinal fluid). The risk factors related to RR/MDR-TBM were investigated through comparing the clinical and examination features between the two groups.The mortality of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects to the RR/MDR-TBM . P<0.05 differences is considered statistically significant. Results: Most of the patients(111/137, 81%) were from southern or southwestern China, and a large proportion(72/137, 52.55%) is migrant workers. 12 cases were RR/MDR-TBM (12/137,8.8%) in all TBM patients while 125 cases were NRR/MDR-TBM(125/137,91.2%). The proportion of previously treated cases in RR/MDR-TBM group was significantly higher than that in NRR/MDR-TBM group (6/12vs12/125, 50%vs10.5%,P<0.01), while there was no significant difference in other clinical and examination features between the two groups. The mortality of RR/MDR-TBM treated with the linezolid-containing regimen was significantly lower than that treated with non linezolid regimen (P=0.045). Conclusions: The main related high-risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid -containing regimen appears to lower the mortality of RR/MDR-TBM significantly. Therefore, it is recommended that linezolid-containing regimen can be used as a better empirical anti-tuberculosis therapy for pathogen negative TBM previously treated in China.