bluuebunny/crossref_metadata_2025_split huggingface dataset:
CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling
Authors: Lin Xian , Wang Feng , Liu Jing , Lin Yibin , Li Li , Li Zirong , Pan Junping , Song Yanwen , Chen Chuanben , Xu Qin 
Published: May 2021

Abstract
Background

Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. It is meaningful to develop alternative targets for eliminating cancer stem cells (CSCs) properties, suppressing metastasis, and alleviating chemoresistance in cervical cancer. This study clarifies the role of CENPK in cervical cancer stemness and chemoresistance and its clinical significance in cancer progression.
Methods

Human cervical cancer cell lines, xenografts, and clinical samples were used for expression and functional analysis. CENPK expression in cervical cancer was analyzed by bioinformatics based on a microarray and TCGA database and immunohistochemistry based on 119 paraffin-embedded cervical cancer specimens and 35 paraffin-embedded adjacent normal tissues in a tissue chip.
Results

CENPK served as an oncogene by promoting CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication, thus inducing cisplatin/carboplatin resistance, cell metastasis and proliferation in cervical cancer. Intriguingly, targeting CENPK markedly prolonged the survival time of cervical cancer-bearing mice, and improved chemotherapy sensitivity of cervical cancer cells in vivo. CENPK also interacted with tumor suppressor gene SOX6 to activate Wnt signaling and inactivate p53 signaling. CENPK modulated expression of key regulators in CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication by disrupting SOX6-β-catenin interaction, promoting β-catenin expression and nuclear translocation, and facilitating SOX6-mediated p53 ubiquitination and nuclear export, thus stimulating cervical cancer stemness, chemoresistance, metastasis and proliferation by. Interestingly, the RAD21/SMC3 complex, downstream targets of β-catenin, enhanced CENPK transcription to form a positive regulatory circuit through Wnt signaling. Facilitation of Wnt signaling by iRhom2 further activated the CENPK/SOX6-β-catenin-RAD21/SMC3 loop and conferred cervical cancer progression, suggesting a Wnt-p53 pathway crosstalk. Importantly, CENPK was upregulated in cervical cancer, correlated with cancer recurrence, and independently predicted poor patient prognosis.
Conclusions

This work identifies CENPK as a prognostic indicator and highlights targeting of CENPK as a novel strategy in the treatment of cervical cancer.
Prevalence, Correlations, and Impact of Sleep Disturbance in Chinese Meningioma Patients
Authors: Zhang Dandan , Wang Jing , Gu Xixi , Gu Zhifeng , Li Liren , Dong Chen , Zhang Xiaomei , Zhao Rui 
Published: May 2021

Abstract
Purpose

Sleep disturbance is common in meningioma patients and may lead to disease aggravation and decreases health-related quality of life (HRQoL). However, the sleep quality of meningioma patients newly diagnosed and ready for surgery has not been well clarified in China. This study aims to evaluate the prevalence, correlates, and impact of sleep disturbance among Chinese meningioma patients.
Methods

In this cross-sectional study, meningioma patients were recruited from the Affiliated Hospital of Nantong University from January 2020 to November 2020. A series of questionnaires were applied: the 0–10 Numerical Rating Scale (NRS), the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Inventory (MFI-20), the Epworth Sleepiness Scale (ESS), the Short-Form 36 (SF-36), the Pittsburgh Sleep Quality Index (PSQI). Independent samples t test, Mann-Whitney U test, chi-square analysis, Pearson/Spearman correlation, and binary logistic regression were used to analyze the data.
Results

100 meningioma patients completed the questionnaires. Sleep disturbance affected 43% of the meningioma patients and was linked to many concomitant symptoms, such as headache, fatigue, anxiety and depression. Binary logistic regression indicated that fatigue and headache were predictors of sleep disturbance in meningioma patients. Meanwhile, severe sleep disturbance led to lower quality of life.
Conclusions

These findings demonstrated that a considerable number of meningioma patients newly diagnosed and ready for surgery suffered from sleep disturbance, potentially contributing to impair HRQoL. Medical personnel should pay more attention to meningioma patients with sleep disturbance and take effective measures to improve sleep quality, with the ultimate goal to improve their HRQoL.
Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation
Authors: Lv Xuyang , Sun Jiangchuan , Hu Linfeng , Qian Ying , Fan Chunlei , Tian Nan 
Published: May 2021

Abstract
Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.
Daurisoline Suppresses Growth of Esophageal Squamous Cell Carcinoma by Inhibiting MEK1/2 In Vitro and In Vivo
Authors: Wang Donghao , Yang Ning , Zhang Xiaofan , Li Mingzhu , Li Xin , Zhao Lili , Yuan Qiang , Yu Yin , Lu Jing , Zhao Jimin , Jiang Yanan , Dong Zigang , Liu Kangdong 
Published: May 2021

Abstract
Background

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancer and has a high mortality rate worldwide. The clinical treatment of ESCC is mainly surgical resection. The five-year survival rate of ESCC patients in developing countries is less than 20%. Therefore, identifying new and effective drugs that can prevent the occurrence and recurrence of ESCC is clinically significant. Here, daurisoline, a bis-benzylisoquinoline alkaloid, was found to have an anticancer effect on ESCC.
Methods

We investigated the effects of daurisoline on ESCC cell growth and proliferation using ESCC cell lines (KYSE150 and KYSE450 cells) and tumor growth in an ESCC patient-derived xenograft model. Phosphoproteomics was used to identify changes in protein phosphorylation after daurisoline treatment. Molecular docking simulation, pull down assay and amino acid mutation experiments were conducted to determine the target proteins and specific amino acid binding sites of daurisoline. In vitro kinase assay was used to determine the effect of daurisoline on protein phosphorylation. The correlation between MEK1/2 and ERK1/2 expression levels in ESCC was analyzed using TCGA database.
Results

In vitro experiments showed that daurisoline inhibited the proliferation and anchorage-independent growth of ESCC cells. In vivo experiments indicated that daurisoline significantly inhibited tumor growth. Phosphoproteomics analysis revealed that daurisoline reduced ERK1/2 phosphorylation. A pull down assay showed that daurisoline could bind to MEK1/2. In vitro kinase assay confirmed that daurisoline inhibited the biological functions of MEK1/2. We observed a significant correlation between MEK1 and ERK2 in ESCC from the TCGA database.
Conclusion

Daurisoline is a MEK1/2 inhibitor that suppressed ESCC growth in vitro and in vivo.
Evaluation of hierarchical model of trait and disorder- specific intolerance of uncertainty in anxiety disorder symptoms
Authors: Moloodi Reza , Mohebban Fatemeh , Taremian Farhad , Poursharifi hamid 
Published: May 2021

Abstract
Background: Research suggests that Intolerance of Uncertainty is a transdiagnostic risk and maintaining factor in anxiety disorders. The aim of this study was to evaluate the hierarchical model of trait Intolerance of Uncertainty and disorder-specific Intolerance of Uncertainty in symptoms of anxiety disorders in Iranian university students.Methods: Participants (N = 561) completed a battery of questionnaires which assess intolerance of uncertainty, disorder-specific intolerance of uncertainty, metacognition beliefs, fear of negative evaluation, obsessive cognitions, agoraphobic cognitions, obsessive compulsive symptoms, generalized anxiety disorder symptoms, social phobia symptoms, and panic disorder symptoms. Results: Results showed hierarchical model of trait Intolerance of Uncertainty and disorder-specific Intolerance of Uncertainty fit with data. Trait intolerance of uncertainty and disorder-specific intolerance of uncertainty had significant direct and indirect association with various cognitive vulnerabilities and symptoms of anxiety disorders. Conclusion: The findings showed trait intolerance of uncertainty and disorder-specific intolerance of uncertainty have significant contribution to various anxiety disorders. These findings have important implications in conceptualization, prevention and treatment of anxiety disorders.
KCTD1 Downregulation Suppresses Hepatocellular Carcinoma by Regulating Angiogenesis and Influencing the HIF-1α/VEGF Pathway
Authors: Zhu Xinyu , Li Zhiwei , Li Limin , Chen Li , Ouyang Mi , Zhou Hao , Xiao Kai , Lin Ling , Chu Paul K. , Zhou Chang , Xun Chengfeng , Yang Liu , Huang Wenhuan , Ding Xiaofeng 
Published: May 2021

Abstract
Background: Potassium channel tetramerization domain-containing 1 (KCTD1) plays a critical role in transcriptional regulation and adipogenesis, but the significance of KCTD1 in hepatocellular cancer (HCC) has not been reported. Methods: KCTD1 expression was detected by immunohistochemistry, Western blotting, and quantitative RT-PCR. Malignant behaviors of cells were analyzed by MTT assays, liquid colony formation, scratch, transwell assays and FACS analysis. The in vivo functional assays were examined by mouse models using subcutaneous, tail vein, intrahepatic injection combined with sorafenib or exosome treatment. The angiogenesis was analyzed by tube formation and Matrigel plug model. The protein-protein interaction was demonstrated by Co-immunoprecipitation. The protein-DNA binding was confirmed by luciferase assays and chromatin immunoprecipitation.Results: KCTD1 expression is increased in human HCC tissues and closely associated with advanced tumor stages. KCTD1 overexpression enhances HCC growth, migration, and invasion both in vitro and in vivo, while KCTD1 knockdown reverses these effects. Moreover, KCTD1 overexpression promotes the in vitro growth, migration, and tube formation of human umbilical-vein endothelial cells (HUVECs) and induces in vivo angiogenesis. Mechanistically, KCTD1 interacts with HIF-1α to activate the VEGF pathway in HCC cells, which is concurrent with increased M2 macrophage infiltration. Sorafenib blocks the expression of KCTD1 protein and synergistically inhibits subcutaneous and intrahepatic tumor growth. miR-129-5p downregulates KCTD1 expression by binding with KCTD1 3′ UTR and abrogates the oncogenic role of KCTD1 in vitro. Finally, exosomes derived from miR-129-5p-overexpressing HCC cells combine with sorafenib to decrease HCC tumor size. Conclusions: These results suggest that KCTD1 expression activates the VEGF signaling cascade to enhance HCC progression, and angiogenesis. Therefore, KCTD1 may serve as a novel target of sorafenib and pave the way for an efficient therapy for advanced human HCC.
GPBAR1 Promotes Proliferation and Is Related to Poor Prognosis of High-Grade Glioma via Inducing MAFB Expression
Authors: Sun Suohui , Guo Hui , Liang Nan , Wu Tao , Zhang Chunpu , Li Huaqing 
Published: May 2021

Abstract
Background

Glioma is the most prevalent brain tumors with extremely poor prognosis, but the prognostic biomarkers of high-grade (grade III and IV) gliomas (HGG) are still insufficient.
Methods

In our study, we investigated the expression of GPBAR1 in HGG by qRT-PCR and immunohistochemistry (IHC), and evaluated the clinical significance of GPBAR1 with univariate and multivariate analyses. By retrieving the data from TCGA, we screened the genes significantly associated with GPBAR1, and identified the correlation between GPBAR1 and MAFB. By experiments in vitro, we showed the pivotal role of MAFB in GPBAR1-induced proliferation of HGG.
Results

GPBAR1 expression in HGGs was significantly higher than that in normal brain tissues. GPBAR1 was an independent prognostic biomarker of HGG. GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. MAFB was also a prognostic biomarker of HGG, and patients with co-expression of MAFB and GPBAR1 had worse prognosis.
Conclusions

GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. Both GPBAR1 and MAFB were prognostic biomarkers of HGG, and patients with co-expression of MAFB and GPBAR1 had worse prognosis than those with only GPBAR1 or MAFB expression.
A Formal Outpatient Parenteral Antimicrobial Therapy Program for Patients with Solid Tumors
Authors: Robins Alison , Dishner Emma , McDaneld Patrick , Rowan Meagan , Bartek Jalen , Jiang Ying , Adachi Javier , Garnes Natalie J.M. Dailey 
Published: May 2021

Abstract
Background and Objectives: Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. Methods: We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the quality of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. Results: Completeness of ID provider notes improved from a baseline of 77% to 100% (p<.0001) for antimicrobial recommendations, 75% to 97% (p<.0001) for follow-up recommendations, and 19% to 98% (p<.0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24% to 56% (p=.027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. Conclusions: Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.
Suboptimal birth spacing practice and associated factors among women of reproductive age in West Badwacho district, Hadyia zone, South Ethiopia, 2020: Cross-sectional study design
Authors: Wassihun Alemu Workineh , Hunegnaw Yilkal Simachew , Abebo Teshome Abuka , Bekele Alex Yeshaneh 
Published: May 2021

Abstract
Introduction: Birth spacing is the time gaps between two consecutive life births. One of the key strategies to reduce fertility and promote the health status of mothers and their children is optimal birth spacing. Recent evidences showed that the health of mothers and children with the birth interval of 3 to 5 years is safer than 2 years or less. However, women still have shorter birth intervals and studies addressing their associated factors were scarce. Objectives: To assess prevalence of suboptimal birth spacing practice and its associated factors among women of reproductive age in West Badwacho district, Hadyia Zone, South Ethiopia, 2020.Method and materials: Community based cross sectional study was conducted from February to March, 2020. Multi stage sampling technique was used to select samples of 626 women. Structured and pretested interview based questionnaire was used to collect the data. Data was checked for completeness and entered using EPI data version 3.1 and analyzed using SPSS version 25. Bivariable logistic regression was done and variables with a p-value of < 0.25 in bi-variable logistic regression were recruited as candidate variable for the final multivariable logistic regression model and P value less than 0.05 at 95 % confidence level was taken as statistically significant. Result: The prevalence of suboptimal birth interval in this study was 60.4 %. Independent predictors of suboptimal birth spacing were: age at first marriage less than 18 years (AOR: 2.18, 95% CI=1.34,3.53), HEWs education about birth sapcing (AOR: 1.89, 95% CI=1.02,3.48), non -formal maternal education (A0R: 2.25, 95%CI=1.31,3.87), non -formal husband education (AOR: 2.64, 95%CI=1.74,4.01), sex of index child being female (AOR:1.58, 95%CI=1.06, 2.38),, having poor knowledge on optimal birth interval (AOR: 2.96, 95%CI=1.64,5.37), duration of breast feeding for less than 24 months (AOR: 4.64, 95%CI=2.32,9.29), and modern contraceptive non users (AOR: 6.31, 95%CI=3.99,9.96),Conclusion and recommendation: More than half of the study respondents were practicing suboptimal birth interval. Educational status, age at first marriage, HEWs education about birth sapacing, short duration of breastfeeding was some of the factors associated with the outcome variable. Thus, to optimize birth spacing, strategies of providing information using HEWs, education and communication targeting associated variables should be improved.
Uptake, Translocation and Subcellular Distribution of Three Triazole Pesticides in Rice
Authors: Li Haocong , Li Yong , Wang Wenfeng , Wan Qun , Yu Xiang-Yang , Sun Wenjing 
Published: May 2021

Abstract
Triazole pesticide is a widely-used pesticide for the control of pathogenic fungi in crops and its extensive use has caused food safety issues due to its uptake byedible crops. The residue of triazole pesticides has caused many toxicity risks and food safety problems. In this study, the uptake, translocation, and subcellular distribution of three triazole pesticides (triadimefon, tebuconazole, and epoxiconazole) in rice were investigated. The results showed that the three selected triazole pesticides could be taken up by rice roots, but their distribution in plant tissues was different. The accumulation of the three pesticides in rice root followed the order of epoxiconazole > tebuconazole > triadimefon, while a reversed order was observed in rice shoots. The movement of triazole pesticides within rice tissues involved both symplast and apoplast pathways, with triadimefon preferentially through the symplast pathway and epoxiconazole throughby the symplast pathway. The subcellular distribution reveals that all pesticides have a higher proportion in cell walls than in cell organelles and soluble components. Epoxiconazole has the highest accumulated capacity in the cell wall (45%-67%) and triadimefon was more concentrated in the soluble components (24%-29%). However, there exists no significant difference in the amount of three pesticides in cell organelles. The pesticide uptake, the movement of pesticides in symplast and apoplast, and the subcellular distribution of the three pesticides are related to the hydrophobicity of the three pesticides.
Neutrophil Extracellular Traps and Macrophage Polarization Formation In The Inner And Outer Area of Carotid Plaque Arteries
Authors: Saberianpour Shirin , Modaghegh Mohammad hadi saeed , Kamyar Mohammad Mahdi 
Published: May 2021

Abstract
Introduction: It is noteworthy that vast data exists which links NETs to arterial and venous thrombosis in both animal models and humans. In the current study, the level of extracellular neutrophil networks and macrophage polarization in the area outside and inside the carotid plaque of patients with carotid stenosis were assessed.Material and Methods: Ten patients were included in this pilot study. Confirmed cases of carotid stenosis were selected to participate in the study using the simple sampling method. Samples of carotid plaques of each patient were divided into two halves with a transverse incision; the terms inner part and outer part were used for the plaque’s inner part and the adjacent area, respectively. Carotid plaque was excised, and half of them were sorted in 10% formalin for CD163,CD11c ,MPO and histone H3 immunohistochemistry assessment while the other halves were stored at -80 ° C for western blotting assay with PDA4 marker. For statistical analysis, we used independent samples T-test or its non-parametric equivalents.Results: Results of this study showed that the extracellular neutrophil chicks in the inner part of the carotid plaque were significantly increased (P <0.0001), while the number of M1 and M2 macrophages was higher in the inner part compared with the outer part of the carotid plaque (P <0.0001).Conclusion: NETs and Macrophages have great potential for further investigation to find a better treatment for carotid plaque.