bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an Autophagy-Related Gene Signature that Can Improve Prognosis of Hepatocellular Carcinoma Patients
Authors: Huo Xingxing , Qi Jian , Huang Kaiquan , Bu Su , Yao Wei , Chen Ying , Nie Jinfu 
Published: March 2020

Abstract
Background: Autophagy is a programmed cell degradation mechanism that has been associated with several physiological and pathophysiological processes, including malignancy. Improper induction of autophagy has been proposed to play a pivotal role in the progression of hepatocellular carcinoma (HCC).Methods: Univariate Cox regression analysis of overall survival (OS) was performed to identify risk-associated autophagy-related genes (ARGs) in HCC data set from The Cancer Genome Atlas (TCGA). Multivariate cox regression was then performed to develop a risk prediction model for the prognosis of 370 HCC patients. The multi-target receiver operating characteristic (ROC) curve was used to determine the model’s accuracy. Besides, the relationship between drug sensitivity and ARGs expression was also examined. Results: A total of 62 differentially expressed ARGs were identified in HCC patients. Univariate and multivariate regression identified five risk-associated ARGs ( HDAC1, RHEB , ATIC, SPNS1 and SQSTM1 ) that were correlated with OS in HCC patients. Of importance, the risk-associated ARGs were independent risk factor s in the multivariate risk model including clinical parameters such as malignant stage (HR=1.433, 95% CI=1.293-1.589, P<0.001). In addition, the area under curve for the prognostic risk model was 0.747, which indicates the high accuracy of the model in prediction of HCC outcomes. Interestingly, the risk-associated ARGs were also correlated with drug sensitivity in HCC cell lines.Conclusions: We developed a novel prognostic risk model by integrating the molecular signature and clinical parameters of HCC, which can effectively predict the outcomes of HCC patients.
lncRNA CRNDE promotes the proliferation and metastasis by acting as sponge miR-539-5p to regulate POU2F1 expression in HCC
Authors: Li Zhixi , Wu Gang , Li Jie , Wang Youyu , Ju Xueming , Jiang Wenjun 
Published: March 2020

Abstract
Background This article focuses on the roles and mechanism of lncRNA CRNDE on the progression of HCC. Methods We used qRT-PCR to detect the expression of lncRNA CRNDE in HCC cells, normal cells and clinical tissues. MTT assay, FCM analysis, Transwell migration and invasion assay were used to detect the effects of lncRNA CRNDE on cell viability, apoptosis, migration and invasion of HCC cells. The expression of apoptosis-related proteins Bcl-2, Bax, Cleaved Caspase 3, Cleaved Caspase 9, EMT epithelial marker E-cadherin and mesothelial marker Vimentin were analyzed by Western blot. Online prediction software was used to predict the binding sites between lncRNA CRNDE and miR-539-5p, or miR-539-5p and POU2F1 3’UTR. Dual luciferase reporter assay, qRT-PCR and RNA pulldown were used to detect target-relationship between lncRNA CRNDE and miR-539-5p. Dual luciferase reporter assay, qRT-PCR, Western blot and Immunofluorescence were used to detect target-relationship between miR-539-5p and POU2F1. qRT-PCR was used to detect the expression of miR-539-5p and POU2F1 in clinical tissues. Rescue experiments was used to evaluate the association among lncRNA CRNDE, miR-539-5p and POU2F1. Finally, we used Western blot to detect the effects of lncRNA CRNDE, miR-539-5p and POU2F1 on NF-κB and AKT pathway. Results lncRNA CRNDE was highly expressed in HCC cells and HCC tissues compared with normal cells and the corresponding adjacent normal tissues. lncRNA CRNDE promoted the cell viability, migration and invasion of HCC cells, while inhibited the apoptosis and promoted the EMT process of HCC cells. lncRNA CRNDE adsorbed miR-539-5p acts as a competitive endogenous RNA to regulate POU2F1 expression indirectly. In HCC clinical tissues, miR-539-5p expression decreased and POU2F1 increased compared with the corresponding adjacent normal tissues. lncRNA CRNDE/miR-539-5p/POU2-F1 participated the NF-κB and AKT pathway in HCC. Conclusion lncRNA CRNDE promotes the expression of POU2F1 by adsorbing miR-539-5p, thus promoting the progression of HCC.﻿Keywords: liver cancer, lncRNA CRNDE, miR-539-5p, POU2F1, ceRNA
KIAA0101 and UbcH10 interact to regulate non-small cell lung cancer cell proliferation by disrupting the function of the spindle assembly checkpoint
Authors: Lei Han , Wang Kun , Jiang Tongying , Lu Jingjing , Dong Xue , Wang Feilong , Li Qiang , Zhao Liming 
Published: March 2020

Abstract
Background Chromosome mis-segregation caused by spindle assembly checkpoint (SAC) dysfunction during mitosis is an important pathogenic factor in cancer, and modulating SAC function has emerged as a potential novel therapy for non-small cell lung cancer (NSCLC). UbcH10 is considered to be associated with SAC function and the pathological types and clinical grades of NSCLC. KIAA0101, which contains a highly conserved proliferating cell nuclear antigen (PCNA)-binding motif that is involved in DNA repair in cancer cells, plays an important role in the regulation of SAC function in NSCLC cells, and bioinformatics predictions showed that this regulatory role is related to UbcH10. We hypothesized KIAA0101 and UbcH10 interact to mediate SAC dysfunction and neoplastic transformation during the development of USCLC. Methods NSCLC cell lines were used to investigate the spatial-temporal correlation between UbcH10 and KIAA0101 expression and the downstream effects of modulating their expression were evaluated. Further immunoprecipitation assays were used to investigate the possible mechanism underlying the correlation between UbcH10 and KIAA0101. Eventually, the effect of modulating UbcH10 and KIAA010 on tumor growth and its possible mechanisms were explored through in vivo tumor-bearing models. Results In this study, we demonstrated that both UbcH10 and KIAA0101 were upregulated in NSCLC tissues and cells and that their expression levels were correlated in a spatial and temporal manner. Importantly, UbcH10 and KIAA0101 coordinated to mediate the premature degradation of various SAC components to cause further SAC dysfunction and neoplastic proliferation. Moreover, tumor growth in vivo was significantly inhibited by silencing UbcH10 and KIAA0101 expression. Conclusions KIAA0101 and UbcH10 interact to cause SAC dysfunction, chromosomal instability and malignant proliferation in NSCLC, suggesting that UbcH10 and KIAA0101 are potential therapeutic targets for the treatment of NSCLC by ameliorating SAC function.
Examining the quality of record linkage process using nationwide Brazilian administrative databases to build a large birth cohort
Authors: Almeida Daniela , Gorender David , Ichihara Maria Yury , Sena Samila , Menezes Luan , Barbosa George C. G. , Fiaccone Rosimeire L. , Paixao Enny , Pita Robespierre , Barreto Mauricio L. 
Published: March 2020

Abstract
Introduction Research using linked routine population-based data collected for non-research purposes has increased in recent years because they are a rich and detailed source of information. The objective of this study is to present an approach to prepare and link data from administrative sources in a middle-income country, to estimate its accuracy and to identify potential sources of bias by comparing linked and no-linked case. Methods We linked two administrative datasets with data covering the period 2001 to 2015, using maternal attributes (maternal name, age, date of birth, and municipally of residence) from Brazil: live birth information system and the baseline of the 100 Million Brazilian Cohort (created using administrative records from over 114 million individuals whose families applied for social assistance via the National Register for Social Programmes) implementing an in house developed linkage tool CIDACS-RL. We then estimated the accuracy of the linkage and examined the characteristics of missed-matches to identify any potential source of bias. Results A total of 27,699,891 live births were recorded of those, 16,447,414 (59.4%) were linked with SINASC. The sensitivity of the linkage ranged from 39.3% in 2001 to 82.1% in 2014. A substantial improvement in the linkage sensitivity after the introduction of maternal date of birth attribute, in 2011, was observed. Our analyses indicated a slightly higher proportion of missing data among missed matches and a higher proportion of people living in an urban area and self-declared as Caucasian among linked pairs when compared with non-linked sets. Discussion We demonstrated that CIDACS-RL is capable of performing high quality and accurate linkage even with a limited number of common attributes, using indexation as a blocking strategy in large routine databases from a middle-income country. However, residual records occurred more among people under worse living conditions. The results presented in this study reinforce the need of evaluating linkage quality and when necessary to take linkage error into account for the analyses of any generated dataset.
Geoconservação e geodiversidade na área de proteção ambiental da Bica do Ipu – Ceará: desafios para a sustentabilidade
Authors: Sousa Lopes Francisca Lusimara , Claudino Sales Vanda Carneiro de 
Published: March 2020

Este artigo tem como objetivo apresentar uma análise sobre geodiversidade e geoconservação na Área de Proteção Ambiental da Bica do Ipu- Ceará. A metodologia envolveu levantamento bibliográfico, pesquisa in locu e produção cartográfica. Observa-se que, de maneira geral a geodiversidade na área é representada por uma variedade de paisagens, rochas, minerais, fósseis e solos, os quais constituem a base da vida na Terra. Para fundamentar a análise da área foi possível identificar seu principal curso d’água, o Riacho Ipuçaba, que disseca as rochas sedimentares (arenitos) da Formação Jaicós, Formação Ipu e Formação Tianguá, de idade paleozoica. Como valores da geodiversidade foram identificados o econômico, o cultural, o funcional, o educativo e o científico. Por conta do valor econômico, muitas são as ameaças à geodiversidade, onde a sociedade é o principal agente modificador e degradador. As ameaças consistem em desmatamento, queimadas, retirada/desvio da água de seu curso da água.
Abstract
This article aims to present an analysis on geodiversity and geoconservation in the Environmental Protection Area of Bica do Ipu-Ceará. The methodology involved bibliographical research, in situ research and cartographic production. It is observed that in general geodiversity in the area is represented by a variety of landscapes, rocks, minerals, fossils and soils, which form the basis of life on Earth. In order to support the analysis of the area it was possible to identify its main watercourse, Riacho Ipuçaba, which dissects the sedimentary rocks (sandstones) of the Formation Ipu, Formation Jaicos and Formation Tianguá, of paleozoic age. As geodiversity values were identified the economic, the cultural, the functional, the educational and the scientific. Because of the economic value, many are the threats to geodiversity, where society is the main modifying and degrading agent. Threats consist of deforestation, burnt out, water withdrawal / diversion from the water course.
An Investigation of the Mechanism of Rapid Relief of Ulcerative Colitis Induced by Five-flavor Sophora Flavescens Enteric-coated Capsules Based on Network Pharmacology
Authors: Gu Sizhen , Xue Yan , Zhang Yuli , Chen Kanjun , Xue Shigui , Pan Ji , Tang Yini , Zhu Hui , Wu Huan , Dou Danbo 
Published: March 2020

Aim and Objective:
Five-Flavor Sophora flavescens Enteric-Coated Capsules (FSEC)
are the only proprietary Chinese medicine approved for the treatment of ulcerative colitis (UC) in
China. Phase II and III clinical trials have shown that the curative effect of FSEC in relieving UC
was not inferior to that of mesalazine granules and enteric-coated tablets, but its pharmacological
mechanism is unclear. Therefore, the network pharmacology is used to reveal the more
comprehensive effective components and targets of FSEC in the treatment of UC.

Methods:
We screened the components of FSEC based on the TCMSP database, determined the
action targets of these compounds through target fishing, and integrated the UC disease targets of
several disease gene databases. The FSEC-UC composite targets were obtained by matching the
two results, and then a PPI network was constructed to analyze the relationship between these
targets, and the core targets were selected by topological correlation parameters. Finally, GO-BP
and KEGG enrichment analyses were carried out using the clusterProfiler software package.

Results:
One hundred and sixty active components of FSEC were identified and 77 targets were
obtained. Of these, 30 core targets were the main targets of FESC in the treatment of UC. And
quercetin, kaempferol, luteolin and mangiferin were regarded as the core active components of
FSEC. The results screened by GO and KEGG enrichment analysis showed that FSEC played a
comprehensive therapeutic role in immune recognition, anti-inflammation and antioxidation
mainly through IL-17, TNF, Toll-like receptor, NF-kappa B, and Th17 cell differentiation.

Conclusion:
The molecular mechanism of UC remission induced by FSEC was predicted by
network pharmacology. These findings provide an important theoretical basis for further study of
the effective substances and mechanism of FSEC in the treatment of UC.
TNF Receptor: Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis
Authors: Zhang Peiyi , Zhou Shufen , Chen Zhe , Tian Ye , Wang Qianqian , Li Hui , Zhang Tiantian , Guo Qin , Wang Meiying , Guo Chengshan 
Published: March 2020

Background:
Clinical studies indicate that recombinant tumor necrosis factor receptor:Fc
fusion protein (rhTNFR:Fc) quickly alleviates symptoms and physical signs of active Ankylosing
Spondylitis (AS), improving the manifestation of spinal inflammation on radiological imaging. However,
the regulatory mechanism of rhTNFR:Fc in the chemokine pathway is unclear. Thus we study the
mechanism of phlogogenic activity of CXCL16/CXCR6 in AS and the related mechanism of rhTNFR:
Fc treatment.

Methods:
Thirty-two cases of active AS were treated with rhTNFR:Fc for 3 consecutive months. Clinical
response was evaluated at baseline and after treatment. CXCL16/CXCR6 expression as well as
Receptor Activator Of Nuclear Factor-Κb Ligand (RANKL)/Osteoprotegerin (OPG), essential molecules
for osteoclast differentiation, were studied in AS before and after treatment. Further, the proliferation
of lymphocytes and the RANKL level stimulated by recombinant human CXCL16 (rhCXCL16)
were measured in vitro.

Results:
Thirty cases responded to rhTNFR:Fc treatment. The RANKL level, RANKL/OPG ratio,
CXCLl6 level in serum, and CXCLl6 and CXCR6 mRNA levels in active AS were higher than those
in controls and treated patients (P<0.001). rhCXCL16 treatment increased lymphocyte proliferation
and RANKL level in active AS (P<0.001), but not in controls or treated patients (P>0.05). A positive
linear correlation was noted between CXCL16 serum levels and RANKL/OPG ratio and between
CXCL16 levels and C-reactive protein results (P<0.001).

Conclusions:
Our findings suggest that rhTNFR:Fc suppresses inflammation and bone destruction of
AS by reducing the RANKL/OPG ratio through inhibition of the CXCL16/CXCR6 pathway.
The e-Psychonauts’ ‘Spiced’ World; Assessment of the Synthetic Cannabinoids’ Information Available Online
Authors: Zangani Caroline , Schifano Fabrizio , Napoletano Flavia , Arillotta Davide , Gilgar Liam , Guirguis Amira , Corkery John M. , Gambini Orsola , Vento Alessandro 
Published: March 2020

Background:
A wide range of novel psychoactive substances (NPS) is regularly
searched and discussed online by web-based drug enthusiasts (i.e. the e-psychonauts). Among NPS,
the range of synthetic cannabinoids (SC; ‘Spice’) currently represents a challenge for governments
and clinicians.

Methods:
Using a web crawler (i.e. the NPS.Finder®), the present study aimed at assessing psychonauts’
fora/platforms to better understand the online mentions of SC.

Results:
The open-web crawling/navigating software identified here some 1,103 synthetic cannabinoids.
Of these, 863 molecules were not listed in either the international or the European NPS databases.

Conclusions:
A web crawling approach helped here in identifying a large range of unknown SC
likely to possess a misuse potential. Most of these novel/emerging molecules are still relatively
unknown. This is a reason for concern; each of these analogues potentially presents different toxicodynamic
profiles and there is a lack of docking, preclinical, and clinical observations. Strengthening
multidisciplinary collaboration between clinicians and bioinformatics may prove useful in better
assessing SC-associated public health risks.
Biological Activities of Saussurea lappa Antioxidants Recovered by Solid–liquid, Ultrasound and Ired-Irrad®
Authors: Rajha Hiba N. , El Khoury Gisèle , El Darra Nada , Raafat Karim , Debs Espérance , Maroun Richard G. , Louka Nicolas 
Published: March 2020

Background:Saussurea lappa is a traditionally well-known plant appreciated for its biological activities and medicinal uses.Objective:In the present study, the recovery of antioxidants from Saussurea lappa was optimized using Response Surface Methodology (RSM). The efficiency of a newly-patented Infrared (IR) technology, Ired-Irrad®, was compared to that of the emerging ultrasound method (US) and the conventional solid liquid Water Bath (WB) extraction.Methods:The effects of time (t) and Temperature (T), mostly known to affect the extraction process, were tested on maximizing the Total Phenolic compounds Concentration (TPC) and the radical scavenging activity (AA). Response surface methodology was used for the optimization process.Results:A multiple response optimization of both time (t) and Temperature (T) was conducted, showing the best extraction conditions to be for WB: t= 43.86 min, T=33.79°C, for US: t= 65.47 min, T= 57.97°C and for IR: t= 42.5 min, T=34.19°C. The quantity of the optimally extracted polyphenols by WB, US and IR; as well as many of their bioactivities were compared. IR extraction gave the highest yield of TPC (15.3 mg GAE/g DM) followed by US (14.8 mg GAE/g DM) and lastly WB (13.9 mg GAE/g DM). The highest antioxidant and antiradical activities were also obtained by the IR treatment. The optimal IR extract inhibited the growth of Staphylococcus aureus and Escherichia coli up to 65 and 35%, respectively. Moreover, all Saussurea lappa extracts (WB, US and IR) inhibited up to 96% the production of Aflatoxin B1 (AFB1) by Aspergillus flavus.Conclusion:Our findings on the extraction of antioxidants from Saussurea lappa demonstrated that IR technology is an efficient novel method that can be used to extract the maximum yield of polyphenols, with the highest antioxidant, antiradical and antibacterial activities.
Withdrawal Notice: Cryptotanshinone Suppresses Liver Fibrosis by Attenuating Epithelial-Mesenchymal Transition through Targeting Hedgehog Pathway
Authors: Ren Shurong , Yue Qizhen , Wang Qiubo , Zhang Yanli , Zhang Bei 
Published: March 2020

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Leveraging Providers’ Preferences to Customize Instructional Content in Information and Communications Technology–Based Training Interventions: Retrospective Analysis of a Mobile Phone–Based Intervention in India
Authors: Tyagi Hanu , Sabharwal Manisha , Dixit Nishi , Pal Arnab , Deo Sarang 
Published: March 2020

BackgroundMany public health programs and interventions across the world increasingly rely on using information and communications technology (ICT) tools to train and sensitize health professionals. However, the effects of such programs on provider knowledge, practice, and patient health outcomes have been inconsistent. One of the reasons for the varied effectiveness of these programs is the low and varying levels of provider engagement, which, in turn, could be because of the form and mode of content used. Tailoring instructional content could improve engagement, but it is expensive and logistically demanding to do so with traditional trainingObjectiveThis study aimed to discover preferences among providers on the form (articles or videos), mode (featuring peers or experts), and length (short or long) of the instructional content; to quantify the extent to which differences in these preferences can explain variation in provider engagement with ICT-based training interventions; and to compare the power of content preferences to explain provider engagement against that of demographic variables.MethodsWe used data from a mobile phone–based intervention focused on improving tuberculosis diagnostic practices among 24,949 private providers from 5 specialties and 1734 cities over 1 year. Engagement time was used as the primary outcome to assess provider engagement. K-means clustering was used to segment providers based on the proportion of engagement time spent on content formats, modes, and lengths to discover their content preferences. The identified clusters were used to predict engagement time using a linear regression model. Subsequently, we compared the accuracy of the cluster-based prediction model with one based on demographic variables of providers (eg, specialty and geographic location).ResultsThe average engagement time across all providers was 7.5 min (median 0, IQR 0-1.58). A total of 69.75% (17,401/24,949) of providers did not consume any content. The average engagement time for providers with nonzero engagement time was 24.8 min (median 4.9, IQR 2.2-10.1). We identified 4 clusters of providers with distinct preferences for form, mode, and length of content. These clusters explained a substantially higher proportion of the variation in engagement time compared with demographic variables (32.9% vs 1.0%) and yielded a more accurate prediction for the engagement time (root mean square error: 4.29 vs 5.21 and mean absolute error: 3.30 vs 4.26).ConclusionsProviders participating in a mobile phone–based digital campaign have inherent preferences for instructional content. Targeting providers based on individual content preferences could result in higher provider engagement as compared to targeting providers based on demographic variables.