bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRT1 Expression and BRAF V600E Mutation in Papillary Thyroid Cancer: Implications for Diagnosis and Prognosis
Authors: Li Tong , Wang Guangzhi , Li Zhenlu , Zhang Ning , Li Yuguo , Zhao Yongfu , Tian Xiaofeng 
Published: May 2020

Abstract
Background

The BRAF V600E mutation is closely associated with aggressive clinicopathologic features and increased recurrence and disease-specific mortality of papillary thyroid cancer (PTC). Silent mating type information regulation 2 homolog-1 (SIRT1) has long been suggested to have tumor promotor activity and is strongly associated with the presence of BRAF mutations and higher grades of malignancy in many cancer types. However, no evidence or mechanism have been identified in PTC.
Methods

PTC tissue samples and their adjacent normal tissues from 42 PTC patients were collected; qRT-PCR, western blotting, T1799A BRAF mutation testing were utilized and the association with clinicopathologic features were assessed. Three different thyroid cell lines, Nthy-ori 3 − 1, TPC-1 and BCPAP, were used in in vitro studies. Cell counting kits and cell cycle analyses were utilized to investigate the level of cell proliferation and cell cycle progression. Transwell and Matrigel invasion assays were used to investigate the level of cell migration and invasion.
Results

SIRT1 is significantly upregulated in PTC, especially in lymph node metastatic and BRAF V600E-mutated patients. Cell counting kits and cell cycle analyses demonstrated that SIRT1 significantly promoted cell proliferation and cell cycle progression in BRAF V600E-mutated cells. Transwell and Matrigel invasion assays confirmed that SIRT1 promoted the migration and invasion ability of BRAF V600E-mutated cells. Additionally, the results of western blotting showed that the aberrant activation of the mitogen-activated protein kinase (MAPK) pathway played a crucial role in the tumor-promoting role of SIRT1 in BRAF V600E-mutated PTC biology.
Conclusions

SIRT1 expression with a BRAF V600E mutation may serve as new candidate targets for the diagnosis and treatment of papillary thyroid carcinomas.
A practical nomogram predicting the prognosis of hepatocellular carcinoma patients with lymph node metastasis: A population-based analysis
Authors: Zhang Kai , Tao Changcheng , Wu Jianxiong , Rong Weiqi 
Published: May 2020

Abstract
Background: Lymph node (LN) metastasis is associated with poor survival outcomes in patients with hepatocellular carcinoma (HCC) patients and because of the reported low probability of lymph node metastasis, research into the Anchorprognoses of such patients is difficult to conduct. In this study, we aimed to develop a nomogram model to predict the prognosis of HCC patients with lymph node metastasis.

Methods: HCC patients diagnosed with LN metastasis from 2010 to 2015 were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate Cox regression and lasso regression were used to screen prognostic factors. Cox multiple-factor analysis was used to investigate the independent risk factors for survival. We developed a prognostic nomograms using these independent risk factors. The predictive performance of our nomogram model was evaluated according to the concordance index (C-index) and calibration curve. The net clinical benefit was assessed via decision curve analysis (DCA). Patients were divided into different risk groups according to the model. A survival curve was drawn using the Kaplan-Meier method and the difference was compared by the log-rank test.

Results: There were 944 patients in the training cohort and 402 patients in the validation cohort. Grade, T stage, surgery to the liver, chemotherapy, radiation recode, AFP, fibrosis score, tumor size group, M stage were selected as independent prognostic factors, and we developed nomograms using these variables. The calibration curves for probability of survival showed good agreement between the prediction by our model and actual observation in both the training and validation groups. DCA indicated that the nomogram had positive net benefits.

Conclusions: The nomogram can accurately predict the prognosis of HCC patients with lymph nodes metastasis and provide a reasonable basis for treatment.

Keywords: Hepatocellular carcinoma, prognosis, lymph nodes metastasis, prediction model, nomogram
The Mechanism of Ischemic Preconditioning Up-Regulation the Expression of Tissue Kallikrein Protects Neurons from Cerebral Ischemia/Reperfusion Injury
Authors: Su Lu , Liang Dan , Kuang Shenyi , Dong Qiang , Han Xiang , Wang Zheng 
Published: May 2020

Abstract
Ischemic stroke is an important clinical problem with few effective treatments. Many studies have shown that exogenous tissue kallikrein (TK) can protect neurons against hypoxia/reoxygenation injury. In the present study, we explored the possible molecular mechanisms underlying the regulation and function of endogenous TK. Western blot, chromatin immunoprecipitation (ChIP) and real-time PCR (RT-PCR) revealed that cerebral ischemic preconditioning (IP) upregulated the expression of endogenous TK by regulating the acetylation of histone H3. Cresyl violet staining was used to assess the neuroprotective role of endogenous TK on rat hippocampal CA1 neurons against cerebral ischemia/reperfusion (I/R) injury. Western blot results showed that IP activated the expression of p-Raf, p-MEK1/2 and p-ERK1/2 by Western blot. Moreover, Western blotfurther determined that endogenous TK upregulated the expression of p-Bad, depressed the release of cytochrome c and Bax from mitochondria to the cytosol and inhibited caspase-3 activation. In conclusion, endogenous TK can play a neuroprotective role and its upregulation induced by IP treatment can activate the phosphorylation of Raf, MEK1/2 and p-ERK1/2, depress the release of cytochrome c and Bax from mitochondria to the cytosol and inhibit caspase-3 activation.
Mine TCGA Database for Tumor Microenvironment-Related Genes of Prognostic value in lung squamous cell carcinoma
Authors: Chen Xiao , Li Rui , Yin Yun-Hong , Liu Xiao , Zhou Xi-Jia , Qu Yi Qing 
Published: May 2020

Abstract
Background: Tumor microenvironment (TME) plays a significant role in the development of cancer. However, the roles of TME in lung squamous cell carcinoma (LUSC) are not well studied. In our study, we aimed to identify differentially expressed tumor microenvironment-related genes as biomarker for predicting the prognosis of LUSC.Methods: We combined The Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissue using Expression data (ESTIMATE) datasets to identified differentially expressed genes in lung squamous cell carcinoma microenvironment. Then, functional enrichment analysis and protein-protein interaction (PPI) network were conducted. The top six genes in the PPI network were regarded as tumor microenvironment-related hub genes. Finally, the relationship between hub genes and tumor-infiltrating immune cells was deciphered using TIMER.Results: Our study revealed that immune and stromal scores are associated with specific clinicopathologic variables in LUSC. These variables include gender, age, distant metastasis and prognosis. In addition, a total of 874 upregulated and 72 downregulated genes were identified. Functional enrichment analysis demonstrated a correlation between DEGs and the tumor microenvironment, tumor immune cells differentiation and activation. C3AR1, CSF1R, CCL2, CCR1, TYROBP, CD14were selected as the hub genes. A positive correlation was obtained between the expression of hub genes and the abundance of six immune cells.Conclusions: The results of the present study showed that ESTIMATE algorithm-based stromal and immune scores may be a reference indicator of cancer prognosis. We identified five TME-related genes, which could be used to predict the prognosis of LUSC patients.
Distribution of Serum Adiponectin Isoforms in Pediatric Patients with Steroid-Sensitive Nephrotic Syndrome
Authors: Tamai Tetsuro , Kamijo Kaori , Abe Yoshifusa , Hibino Satoshi , Sakurai Shunsuke , Watanabe Shuichiro , Watanabe Yoshitaka , Shiratori Atsutoshi , Nimura Satomi , Takayanagi Takaaki , Watanabe Tsuneki , Nakano Yuya , Ikeda Hirokazu , Dobashi Kazushige , Nakano Yasuko , Mizuno Katsumi , Itabashi Kazuo 
Published: May 2020

Abstract
Background Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. Therefore, this study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS.Methods We measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 patient with NS. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin and all values in 31 with those of 51 control subjects.Results The mean total serum adiponectin levels in patients were 40.6 ± 16.0 µg/mL, 41.1 ± 18.5 µg/mL, and 25.5 ± 16.6 µg/mL at the onset of NS, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects (12.6 ± 8.5 µg/mL). The mean values of %HMW, %MMW, and %LMW values were 57.0/28.0/14.2 at the onset of NS, 61.6/23.8/14.0 at the initial remission, and 58.1/21.7/17.7 at during the remission period, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset of NS were high, and the %LMW values at the onset of NS and at initial remission were low.Conclusions In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms.
Evaluation of Circulating microRNAs as Non-Invasive Biomarkers in the Diagnosis of Ovarian Cancer – A Case-Control Study
Authors: Berner Kai , Hirschfeld Marc , Weiß Daniela , Rücker Gerta , Asberger Jasmin , Ritter Andrea , Nöthling Claudia , Jäger Markus , Juhasz-Böss Ingolf , Erbes Thalia 
Published: May 2020

Abstract
Background Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide and over 150.000 women die from it every year. More than 70 percent of all ovarian cancer patients are diagnosed at a late stage disease with poor prognosis necessitating the development of sufficient screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo.Methods Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a, miR-15a, miR-15b, miR-19b, miR-20a, miR-21, miR-100, miR-125b, miR-155, miR-222) were quantified performing quantitative real-time-PCR. Therefore, the three ovarian cancer cell lines SK-OV-3, OAW-42, EFO-27 as well as urine samples of ovarian cancer patients and healthy controls were analyzed.Results MiR-15a, miR-20a and miR-222 showed expression level alterations extracellularly, whereas miR-125b did intracellularly across the analyzed cell lines. MicroRNA expression alterations in single cell lines suggest subtype specificity in both compartments. Hypoxia and acidosis showed scarce effects on single miRNA expression levels only. Furthermore, we were able to demonstrate the feasibility to clearly detect the 12 miRNAs in urine samples. In urine, miR-15a was upregulated whereas let-7a was down-regulated in ovarian cancer patients.Conclusion Intracellular, extracellular and urinary micoRNA expression alterations emphasize their great potential as biomarkers in liquid biopsies. Especially miR-15a and let-7a qualify for possible circulating biomarkers in liquid biopsies of ovarian cancer patients.
Interactome of SARS-CoV-2 / nCoV19 modulated host proteins with computationally predicted PPIs
Authors: Karunakaran Kalyani B. , Balakrishnan N. , Ganapathiraju Madhavi K. 
Published: May 2020

Abstract
World over, people are looking for solutions to tackle the pandemic coronavirus disease (COVID-19) caused by the virus SARS-CoV-2/nCoV-19. Notable contributions in biomedical field have been characterizing viral genomes, host transcriptomes and proteomes, repurposable drugs and vaccines. In one such study, 332 human proteins targeted by nCoV19 were identified. We expanded this set of host proteins by constructing their protein interactome, including in it not only the known protein-protein interactions (PPIs) but also novel, hitherto unknown PPIs predicted with our High-precision Protein-Protein Interaction Prediction (HiPPIP) model that was shown to be highly accurate. In fact, one of the earliest discoveries made possible by HiPPIP is related to activation of immunity upon viral infection. We found that several interactors of the host proteins are differentially expressed upon viral infection, are related to highly relevant pathways, and that the novel interaction of NUP98 with CHMP5 may activate an antiviral mechanism leading to disruption of viral budding. We are making the interactions available as downloadable files to facilitate future systems biology studies and also on a web-server at http://hagrid.dbmi.pitt.edu/corona that allows not only keyword search but also queries such as “PPIs where one protein is associated with ‘virus’ and the interactors with 'pulmonary'”.
Clemastine Improves Hypomyelination in Rats with Hypoxic–Ischemic Brain Injury by Reducing Astroglia-Derived IL-1β via Autophagy
Authors: Xie Di , Niu Lei , Gao Chengjin , Ge Xiaoli , Wang Yang , Zhu Yajie , Tang Jialong , Fei Aihua , Pan Shuming 
Published: May 2020

Abstract
Background Cardiac arrest can lead to a poor prognosis of the nervous system. Neuroinflammation plays an important role in hypoxic ischemic brain injury (HIBI). Regulation of inflammation via autophagy might be a suitable therapeutic target in HIBI. This study aims to determine whether clemastine can improve hypomyelination by suppressing the activated astrocytes via autophagy and improving axonal hypomyelination in HIBI.Methods A bilateral common carotid artery occlusion (BCCAO) rat model that received continuous intraperitoneal injection (1 mg/kg) for 14 days was employed to elaborate the neuroprotection effects of clemastine. interleukin-1β (IL-1β), nod-like receptor protein 3 (NLRP3), histamine H1 receptor, autophagy related protein and OPCs differentiation levels in the corpus callosum were measured. Primary cultured OPCs and co-culture of astrocytes and OPCs were used to explore the link between astrocytes activation and hypomyelination. Data were evaluated by one-way ANOVA with Fisher’s protected least significant difference test.Results Clemastine treatment could reverse hypomyelination and restrain the upregulation of IL-1β and NLRP3 in the corpus callosum of BCCAO rats. Primary cultured OPCs treated with IL-1β showed failed maturation. Expression of LC3Ⅱ/Ⅰdecreased after astrocytic activation. Co-culture of astrocytes and OPCs with oxygen glucose deprivation treatment exhibited NLRP3/1β upregulation and PLP downregulation. Clemastine could downregulate NLRP3/1β and reverse hypomyelination by promoting the autophagy.Conclusions Clemastine could improve axonal hypomyelination by inhibiting astrocytes activation via promoting the autophagy in BCCAO rats, thus might be a viable strategy to inhibit hypomyelination in the corpus callosum of patients with HIBI.
Why Nigerian Secondary School Geography students perform poorly in external examinations: synthesis of WAEC Chief Examiners’ Reports of a decade
Authors: Eze Emmanuel 
Published: May 2020

Abstract
The perpetual decline of students’ performance in WASSCE Geography is an utmost concern, given the present advantages and prospects of the study of Geography. This study undertakes a qualitative analysis of all WAEC Chief examiners’ report from 2008 to 2018 to extract vital information on why Nigerian students perform poorly in Geography, using the grounded theory methodology. RQDA was used for data analyses. Poor map work, inadequate preparation and scanty explanation of points were identified. Ideal Geography teachers ought to be multiplied in schools, with provision of relevant and current instructional resources, and the application of student-centered teaching strategies.
Rotavirus contamination of surface waters from the northwest of Argentina
Authors: Prez Verónica Emilse , Poma Hugo Ramiro , Giordano Georgina Gisela , Victoria Matías , Nates Silvia Viviana , Rajal Verónica Beatriz , Barril Patricia Angélica 
Published: May 2020

Abstract
Fecal pollution of water is a serious concern because it is associated with the transmission of pathogens. The aim of this study was to analyze the occurrence of group A rotavirus (RVA) in surface waters from the Arias–Arenales River in Salta, a northern city in Argentina, and to define possible sources of fecal viral pollution. A total of 116 water samples were analyzed and RVA was detected in 3.4% (95% CI: 0.1–7.0%), with concentrations ranging from 1.9 × 105 to 3.8 × 106 genome copies per liter. RVA strains were characterized as G1P[8], G4P[8] and G9P[8], which are common genotypes circulating in the local population. The Arias–Arenales River presented unusual and sporadic contamination by RVA, originated from stormwater discharges and a variety of non-identified sources, and support the essential need of viral indicators for enhanced monitoring of water quality.
Improving and upgrading an existing activated sludge with a compact MBBR – disc filters parallel line for municipal wastewater treatment in touristic alpine areas
Authors: Desa L. , Kängsepp P. , Quadri L. , Bellotti G. , Sørensen K. , Pellicer-Nàcher C. 
Published: May 2020

Abstract
Many wastewater treatment plants (WWTP) in touristic areas struggle to achieve the effluent requirements due to seasonal variations in population. In alpine areas, the climate also determines a low wastewater temperature, which implies long sludge retention time (SRT) needed for the growth of nitrifying biomass in conventional activated sludge (CAS). Moreover, combined sewers generate high flow and dilution. The present study shows how the treatment efficiency of an existing CAS plant with tertiary treatment can be upgraded by adding a compact line in parallel, consisting of a Moving Bed Biofilm Reactor (MBBR)-coagulation-flocculation-disc filtration. This allows the treatment of influent variations in the MBBR and a constant flow supply to the activated sludge. The performance of the new 2-step process was comparable to that of the improved existing one. Regardless significant variations in flow (10,000–25,000 m3/d) and total suspended solids (TSS) (50–300 mg/L after primary treatment) the effluent quality fulfilled the discharge requirements. Based on yearly average effluent data, TSS were 11 mg/L, chemical oxygen demand (COD) 27 mg/L and total phosphorus (TP) 0.8 mg/L. After the upgrade, ammonium nitrogen (NH4-N) dropped from 4.9 mg/L to 1.3 mg/L and the chemical consumption for phosphorus removal was reduced.
Quantifying the energy consumption and greenhouse gas emissions of changing wastewater quality standards
Authors: Cardenes Iliana , Hall Jim W. , Eyre Nick , Majid Aman , Jarvis Simon 
Published: May 2020

Abstract
Regulations to ensure adequate wastewater treatment are becoming more stringent as the negative effects of different pollutants on human health and the environment are understood. However, treatment of wastewater to remove pollutants is energy intensive, so has added significantly to the operation costs of wastewater treatment plants. Analysis from six of the largest wastewater treatment works in South East England reveals that the energy consumption of these treatment works has doubled in the last five years due to expansions to meet increasingly stringent effluent standards and population growth. This study quantifies the relationship between energy use for wastewater treatment and four measures of pollution in effluents from UK wastewater treatment works (biochemical oxygen demand, ammoniacal nitrogen, chemical oxygen demand and suspended solids). The linear regression results show that indicators of these pollutants in effluents, together with the extension of plants to improve wastewater treatment, can predict over 95% of energy consumption. Secondly, using scenarios, the energy consumption and greenhouse gas emissions of effluent quality standards are estimated. The study finds that tightening effluent standards to increase water quality could result in a doubling of electricity consumption and an increase of between 1.29 and 2.30 additional MTCO2 per year from treating wastewater in large works in the UK.
Application of response surface methodology for optimization of oxytetracycline hydrochloride degradation using hydrogen peroxide/polystyrene-supported iron phthalocyanine oxidation process
Authors: Sun Yue , Feng Xinlei , Fu Shun 
Published: May 2020

Abstract
Inspired by metalloporphyrin-based enzymes, a biomimetic catalyst, R-N-Fe, was prepared by grafting iron phthalocyanine (FePc) covalently onto a macroporous chloromethylated polystyrene-divinylbenzene resin (R), which was pre-functionalized using 4-aminopyridine (4-ampy) as an axial ligand. The novel catalyst was used for the degradation of oxytetracycline hydrochloride (OTCH). The response surface methodology was employed to optimize the independent operating parameters, including temperature, catalyst amount, H2O2 dosage, and initial pH value. The results displayed that the initial pH and temperature had the most significant effect on the removal efficiency. Under optimum conditions, the OTCH removal efficiency was 93.98%. Additionally, the classical quenching experiment and electron paramagnetic resonance (EPR) test indicated that R-N-Fe could generate hydroxyl radicals by decomposing H2O2, which was the main active species for eliminating OTCH. Furthermore, R-N-Fe can be easily recycled and can maintain high stability in the reusability test, rendering it a good potential for practical application.