bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Transcription Factor Ap1 in The Activation of Nrf2/ARE Pathway Through TET1 in Diabetic Nephropathy
Authors: Tan Yongshun , Cao Huaimin , Li Qingfei , Sun Jianjun 
Published: August 2020

Abstract
Background: TET1 abnormal expression is related to tumorigenesis, but its role in diabetic nephropathy (DN), the most common diabetic complication, is unclear. We attempted to probe the possible mechanism of TET1 in DN.Methods: The DN rat model was established and verified by marker detection and histopathological observation. The in vitro model was established in human mesangial cells (HMCs) induced by high glucose (HG), and levels of IL-6, TNF-α, IV-C and FN were examined. The differentially expressed mRNAs were screened out by microarray analysis. The most differentially expressed mRNA (TET1) was overexpressed in DN rats and HMCs to evaluate inflammation, cell viability and apoptosis, biochemical indexes and renal injury. The upstream transcription factor of TET1 was verified, and overexpressed with/without TETE1 to access its role in inflammation and renal injury. The downstream gene and pathway were also verified.Results: TET1 was poorly expressed in DN rats and HG-HMCs. High expression of TET1 decreased biochemical indexes, and renal injury of DN rats, decreased the activity, fibrosis and inflammation of HG-HMCs. Ap1 inhibited TET1 expression, and enhanced secretion of inflammatory factors in HG-HMCs and renal injury in DN rats. TET1 overexpression inhibited the effect of Ap1 on DN. TET1 promoted the transcription of Nrf2. The Ap1/Tet1 axis mediated the Nrf2/ARE pathway activity.Conclusion: Ap1 inhibits TET1 expression and activates the Nrf2/ARE pathway in DN, thus aggravating inflammation and renal injury.
Comparison Between 200 μg and 800 μg of Misoprostol for Cervical Ripening Prior to Operative Hysteroscopy: A Study Protocol for A Randomized Controlled Trial.
Authors: Maior Maria da Conceição Farias Souto , Costa Aurélio Antônio Ribeiro , Souza Alex Sandro Rolland 
Published: August 2020

Abstract
Background: Hysteroscopy, a minimally invasive procedure, has been increasingly used to treat disorders of the cervical canal and uterine cavity. However, difficulties related to the insertion of the hysteroscope through the cervical canal still remain. Although there are reported advantages in reducing cervical resistance with the use of misoprostol for cervical ripening, systematic reviews highlight the need to determine the optimal dose. This study was designed to compare two groups of patients submitted to cervical dilatation prior to operative hysteroscopy and pre-treated with either 200 µg or 800 µg of misoprostol for cervical ripening. Methods: A randomized, quadruple-blind clinical trial with patients submitted to cervical dilatation prior to operative hysteroscopy at university teaching hospitals in Recife, Pernambuco, Brazil. After the internal review boards of the participating institutes had approved the study protocol, data collection began on November 7, 2019, with expected completion on November 1, 2020. Patients included in the study following the informed consent process are randomly allocated to one of two groups, the first allocated to use 200 μg misoprostol and the second to use an 800-μg dose. In both groups, misoprostol will be administered vaginally 10-12 hours prior to operative hysteroscopy. The groups will be compared in relation to intraoperative and postoperative outcomes based on the following endpoints: baseline cervical dilatation, cervical length, degree of difficulty, duration of cervical dilatation, failure to dilate, adverse events and surgical complications. The chi-square test of association, Fisher's exact test and the Mann-Whitney test will be used to compare the groups, with an alpha error of <5% being considered significant. Discussion: The findings of this study will contribute towards establishing the optimal misoprostol dose for cervical ripening prior to operative hysteroscopy, ultimately facilitating hysteroscope insertion through the cervical canal. A gap will be filled in the currently available literature, providing future preoperative guidance. The 800-μg dose of misoprostol is expected to reduce resistance in the cervix and shorten the time until achieving cervical dilatation, delivering a less traumatic procedure for the patient. Therefore, the study is relevant for surgeons in this field, for the scientific community and, particularly, for patients. Trial registration: Clinical Trials Register: NCT04152317. Registered on November 5, 2019. URL https://clinicaltrials.gov/ct2/show/study/NCT04152317.
Novel immune-related genes in the tumor microenvironment with prognostic value in breast cancer
Authors: Tan Wen , Liu Maomao , Wang Liangshan , Guo Yang , Wei Changsheng , Zhang Shuqi , Luo Chengyu , Liu Nan 
Published: August 2020

Abstract
Background: Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical. Results: The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas were employed to comprehensively evaluate the TME. Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on Gene Ontology (GO) functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. We further analyzed and screened the overlapping genes of the top 3 GO terms and upregulated differentially expressed genes (DEGs). Overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network analyses revealed that the genes of the top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.Conclusions: High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.
A Comparison Between Different Anti-retroviral Therapy Regimes on Soluble Infammation Markers: a Pilot Study
Authors: Maritati Martina , Alessandro Trentini , Zanotta Nunzia , Comar Manola , Bellini Tiziana , Sighinolfi Laura , Contini Carlo 
Published: August 2020

Abstract
Background: Although HIV-related deaths have decreased dramatically following the introduction of antiretroviral therapy (ART), HIV infection itself causes increased morbidity and mortality for both non-AIDS-related events or chronic inflammation and immune activation. The use of certain antiretroviral drugs can contribute to this process.Methods: We investigated 26 potential biomarkers in serum samples from HIV-1 infected patients virologically suppressed under ART. The main objective of our study was to evaluate if virological suppression achieved with a triple drug regimen containing tenofovir disoproxil fumarate co-formulated with emtricitabine (TDF/FTC) as backbone, could correlate with a better immunological and inflammatory profile in relation to the third class of antiretroviral drug administered. The eligible patients were then divided into 3 groups in relation to the third drug associated with TDF/FTC: nucleoside reverse transcriptase inhibitors (NNRTI) (Group 1, n=16), protease inhibitors (PI) (Group 2, n=17) and integrase inhibitors (INI) (Group 3, n=16).Results: Inflammatory cytokines and chemokines were more represented in Group 2 than in Group 3 (IL-1Ra, p=0.013; IL-12p70 p=0.039; TNF-α p=0.041; IL-8, p=0.027; MIP1 β, p=0.033). Eotaxin showed lower levels in Group 1 compared to Group 2 (p=0.010), while IP-10 was significantly lower in Group 1 compared to both Group 2 and Group 3 (p=0.003 and p=0.007, respectively).Conclusions: our results seem to discourage the administration of PI as a third drug in a virologically effective antiretroviral regimen, as its use is linked to the detection of higher levels of pro-inflammatory mediators in comparison with INI and NNRTI.
Development of a novel nomogram for the prediction of cause specific survival for patients with non-metastatic Chromophobe Cell Renal Carcinoma, following radical nephrectomy
Authors: Liu Feng , Cai Meng Hui , Ge Tian yu , Feng Zi Hao , Huang Kung Ping , Ge Bo 
Published: August 2020

Abstract
Background:The applicability of the nomogram approach to the prognosis of CCRC patients following radical nephrectomy has yet been established or tested. In this study, we utilized data from a large publicly available US cancer database to obtain a large sample size of data on CCRC patients, and used this dataset to evaluate the independent prognostic risk factors for cause-specific survival (CSS) in patients with non-metastatic CCRC. The data were used to construct a new novel prognostic nomogram for CCRC following radical nephrectomy in order to provide a clinically useful predictive tool for estimating a patient's survival probability.This study aimed to establish a novel prognostic nomogram for patients with non-metastatic Chromophobe Cell Renal Carcinoma (CCRC) after radical nephrectomy.Methods:A total of 1040 CCRC patients with non-metastatic cancer who had undergone radical nephrectomy, were identified in SEER (2004 through 2014). A novel nomogram was constructed based on the data and variables associated with cause specific survival time were included in the model using the Cox Proportional-Hazards Model. The nomogram was cross-validated against a subset of the data (n = 520 patients) from 9 randomly selected cancer registries in SEER, by calculation of Harell’s Concordance index (C-index) and the calibration curve for the time-related probability of survival. Results:Multivariate analysis of the training dataset (n = 1040 patients) revealed age at diagnosis, tumor size and tumor grade as independent factors associated with cause specific survival (CSS), and these were selected for inclusion in the nomogram. The calibration curve for the time-limited probability of survival showed good agreement between the predictions of the nomogram and actual observation. The C-index of the nomogram for predicting survival was 0.81 (95% CI 0.75 - 0.87), which was statistically higher than the C-index values produced by the 6/7th AJCC systems (0.75, 95% CI 0.67 - 0.83). The nomogram prediction of survival based on the validation dataset was also superior to that of the 6/7th AJCC staging systems (C-index 0.83 vs. 0.71; P = 0.038 ). Conclusion：The nomogram prediction model we built has a higher C index value, and has better sensitivity and predictive value. A prospective study with a larger sample is needed to verify our findings.
Pathways Leading to Prevention of Fatal and Non-Fatal Cardiovascular Disease: An Interaction Model on 15 years Population-Based Cohort study
Authors: Shakibaei Najmeh , Hassannejad Razieh , Mohammadifard Noushin , Marateb Hamid Reza , Mansourian Marjan , Mañanas Miguel Angel , Sarrafzadegan Nizal 
Published: August 2020

Abstract
Background: A comprehensive study on the interaction of cardiovascular disease (CVD) risk factors is critical to prevent cardiovascular events. The main focus of this study is thus to understand direct and indirect relationships between different CVD risk factors. Methods: A longitudinal data on adults aged ≥35 years, who were free of CVD at baseline, were used in this study. The endpoints were CVD events, whereas their measurements were demographic, lifestyle components, socio-economics, anthropometric measures, laboratory findings, quality of life status, and psychological factors. A Bayesian structural equation modelling was used to determine the relationships among 21 relevant factors associated with total CVD, stroke, acute coronary syndrome (ACS), and fatal CVDs. Results: In this study, a total of 3161 individuals with complete information were involved in the study. A total of 407 CVD events, with an average age of 54.77(10.66) years, occurred during follow-up. The causal associations between six latent variables were identified in the causal network for fatal and non-fatal CVDs. Lipid profile, with the coefficient of 0.26 (0.01), influenced the occurrence of CVD events as the most critical factor, while it was indirectly mediated through risky behaviours and comorbidities. Lipid profile at baseline was influenced by a wide range of other protective factors, such as quality of life and healthy lifestyle components. Conclusions: Analysing a causal network of risk factors revealed the flow of information in direct and indirect paths. It also determined predictors and demonstrated the utility of integrating multi-factor data in a complex framework to identify novel preventable pathways to reduce the risk of CVDs.
The Latest Research Trends of Teaching &amp; Learning in Higher Education by Leveraging Advanced technology and Big data
Authors: Park Young-Eun 
Published: August 2020

Abstract
Digital transformation in higher education has had a transformative effect on modern education. It means transforming an institutional core value of education to better meet students’ needs by leveraging digital technology and big data. Accordingly, this study aims to catch the principal directions, trends, or new paradigms as predictors with a linkage of each topic by identifying the latest research agendas of teaching and learning in higher education through semantic network analysis. For this, 285 research articles from four international ‘top-tier’ journals ranked as ISI/SCOPUS Q1 were gathered in the area of teaching and learning in higher education for two years in 2018 ~ 2019, and then it was analyzed using a text mining technique that processes natural language. Consequently, the study of researches on teaching and learning shows a relatively high connection with ‘student’ or ‘student-centered/led’ rather than ‘teacher-led’. Moreover, it is observed that the practice and assessment of learning can be achieved through various activities including community activities. Besides that, experience-based classes, research in academic contexts, the effect of group activities, how students’ perceptions or feelings and relationships affect learning outcomes were mentioned as the main topics through topic modeling of LDA, a machine learning algorithm. This study proposes that educators, researchers, and academic leaders can exert the remarkable power to reshape the educational programs for future quality education properly and a timely fashion based on recognizable trends or topics in teaching and learning of higher education.
Silver Nanoparticles Protects Streptozotocin-induced Hepatotoxicity: a Biochemical and Histopathological Approach
Authors: BEGUM QUDSIA , Mahboob Tabassum 
Published: August 2020

Abstract
Recently in many industries biologically synthesized silver nanoparticles are used as an alternative for their biomedicinal applications predominantly demonstrated as an effective agent in the diabetes treatment. On the other hand, oxidative stress crucially associated with the pathogenesis of diabetic comorbidities like diabetic hepatopathy, which is less common. Thus, the existing study explored the protective role of biologically synthesized silver nanoparticles (AV-AgNPs) against hepatic toxicity persuaded by streptozotocin (STZ) in rats. Wistar male albino rats (200 ± 20 g) were segregated into five groups (n=10) and designated as, Group I-Control (no treatment); Group II-Diabetic control (35 mg/kg single dose of streptozotocin, IP); Group III-Diabetic treated with AV-AgNPs (10 mg/kg); Group IV-Diabetic treated with aloe vera leaves extract (AVLE) (100 mg/kg); Group V-Diabetic treated with glibenclamide (GLB) (600 μg/kg) orally. After treatment of 28 days, animals were euthanized and collected blood and liver specimens for investigations of biochemical, oxidative stress, antioxidant, and histological parameters. Outcomes of the study exhibited that STZ persuades diabetes and hepatic impairments indicated by significant raised (p<0.05) in the levels of blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, (ALP), and malondialdehyde (MDA) with decreased catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GSH) enzymes activities. AV-AgNPs treatment reverted and reestablished the liver enzymes levels, antioxidant enzymes, and histological damages of the liver persuaded by STZ near to normal. In general, these results suggested that AV-AgNPs may have antioxidant potentials and proved to be hepatoprotective therefore, they could be used for the treatment of diabetic hepatopathy and other liver injuries.
A qualitative investigation of influencing factors for anxiety and depression in patients with advanced cancer after multiline treatment failure
Authors: Yang Xujing , Xie Qingqing , Sun Caixia , Fei Zhenghua 
Published: August 2020

Abstract
Background: To investigate the anxiety and depression of patients with advanced cancer who received immunotherapy using programmed death-1 or programmed death-ligand 1 after multiline treatment failure, to explore the influencing factors, and to provide reference for clinical medical staff and psychological support for patients.Methods: The Hospital Anxiety and Depression Scale was used to calculate the anxiety and depression scores before and after 1, 2 and 3 courses of treatment, respectively. The patients with anxiety and depression were counted. Purposive sampling was used to conduct face-to-face semi-structured interviews with 21 patients to find out the reasons. The obtained data were analyzed and collated using the Colaizzi's phenomenological method.Results: Before and after 1, 2 and 3 courses of treatment, 18.26%, 23.0%, 50% and 54% of patients suffered from anxiety and depression, respectively. Four related factors, i.e. low expectations for immunotherapy, lack of timely information after treatment, lack of awareness of treatment and drugs, and lack of family and social support, were extracted with the sampling survey. The proportion of patients with anxiety and depression during immunotherapy kept increasing.Conclusion: The anxiety and depression of patients with advanced cancer who receive immunotherapy after multiline treatment failure are aggravated along with treatment. Patients need to be given humane care and emotional support from their families, society and medical staff. Nursing staff should adopt personalized measures to meet the psychological needs of patients, and a targeted and complete nursing system should be established to extend the life span and to improve the quality of life.Trial registration: ChiCTR, ChiCTR1800015942. Registered 1 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=26476
Transcriptome survey and expression analysis reveals effects and metabolic pathways of Yuluxiang Pear in response to drought stress
Authors: Yang Sheng , Bai Mudan , Hao Guowei , Zhang Xiaowei , Wang Yanping , Guo Huangping , Fu Baochun 
Published: August 2020

Abstract
Background: Pear is one of the most important economic fruits worldwide. The quality and productivity is frequently threatened by drought disaster, but the effects mechanism of drought stress on pear has not been well understood, especially in respond to drought stress at the gene transcription levels. Results: That showed that drought stress weakened antioxidant systematization and the synthesis of photosynthetic pigment of Yuluxiang Pear leaves, and the reduced light utilization and photosynthetic productivity finally resulted in the inhibited fruit development. The transcriptome from leaves were sequenced and analyzed using Illumina HiSeq 2500 to evaluate the effects of drought stress on the expression of genes in different biosynthetic pathways. Deferentially expressed genes analysis showed that the enzyme genes involved in lignin biosynthesis were up-regulated by drought stress, and the promoted lignification process may be beneficial to decrease the transpiration rate and increase water use efficiency of Yuluxiang Pear leaves. The up-regulated malate dehydrogenase and adenosylmethionine decarboxylase were also observed in drought stress groups, and the activated soluble sugar biosynthesis could be helpful to promote osmotic regulation and increase antioxidant capacity to enhance drought resistance of leaves. Drought stress increased the expression of enzyme genes related with hormones biosynthesis including ethylene, abscisic acid, and gibberellin, suggesting promoted cell proliferation and slowed young leaves growth. Conclusions: Present study reveals that drought stress severely decrease photosynthetic productivity to negatively affect fruit development, and the inhibited photosynthesis could be closely related with drought-induced lignification and hormones promoting leaf abscission.
Clinical profiles of subclinical disease among pulmonary tuberculosis patients: a prospective cohort study in South Korea
Authors: Min Jinsoo , Chung Chaeuk , Jung Sung Soo , Park Hye Kyeong , Lee Sung-Soon , Lee Ki Man 
Published: August 2020

Abstract
Background: Subclinical tuberculosis (TB) is a potential target for public health intervention because its early identification may reduce TB transmission. Here, we have described clinical and laboratory findings of subclinical disease among pulmonary TB patients.Methods: In this prospective cohort study, we enrolled adult patients with pulmonary TB between 2016 and 2018. Subclinical TB was defined as the presence of radiographic or microbiologic test results consistent with TB without clinical symptoms. We implemented two-stage symptom assessment using a predefined TB symptom checklist. Demographic, clinical, and laboratory data were compared between subclinical and active disease using the multivariate binary logistic regression analysis. We evaluated treatment outcomes in the drug-susceptible cohort. Results: Among 420 enrolled patients, 81 (19.3%) had subclinical TB. Multivariate analysis showed that age <65 years was the only significant variable associated with subclinical disease. Subclinical disease had a significantly lower proportion of acid-fast bacilli smear and culture positivity and multiple lobe involvement compared to active disease. Among 319 patients with treatment success in the drug-susceptible cohort, six (1.9%) recurrent cases were identified, and all were active disease. Patients with subclinical disease had a higher proportion of favorable outcomes; however, its odds ratio was insignificant.Conclusions: Nearly one-fifth of tuberculosis cases were subclinical under the universal health coverage in South Korea. Despite its milder clinical presentation, the treatment outcomes of subclinical TB were not significantly different from that of active disease.