bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis
Authors: LIU Deyu , jian xinchun , XU PU , ZHU Rong , WANG Yuan 
Published: August 2019

Abstract
Background

Mounting studies demonstrate long non-coding RNAs (lncRNAs) play an important role in tumor progression. However, the potential biological functions and clinical importance of linc01234 in oral squamous cell carcinoma (OSCC) still remain unclear.

Methods

Two OSCC cells were transfected with siRNAs targeting linc01234, and RT-qPCR, CCK-8, EDU, wound healing and Transwell and western blot assays were performed to analyze the effect of linc01234 on cell proliferation, migration and invasion. Bioinformatic analysis, luciferase assays and RT-qPCR identified a competitive endogenous RNAs (ceRNAs) among linc01234, miR-433-3p and PAK4.

Results

We found that linc01234 was significantly upregulated in OSCC tissues and cell lines and positively associated with T stage, lymphnode metastasis, differentiation. Kaplan-Meier analysis of OSCC reveals a positive correlation between linc01234 and the overall survival. Following the linc01234 deletion, the cell proliferation and metastasis abilities in CAL27 and SCC25 cells were found to be extremely reduced. Mechanism studies indicated that linc01234 located in cytoplasm and shared microRNA (miRNA) response elements with miR-433-3p. Luciferase assays indicated that miR-433-3p bind to the 3′-UTR of PAK4.

Conclusions

Our results indicated that linc01234 functioned as an oncogene in OSCC and might be a potential therapeutic target for OSCC.
A novel carcinogenic PI3Kα mutation suggesting the role of helical domain in transmitting nSH2 regulatory signals to kinase domain
Authors: Ghalamkari Safoura , Hejazi Sayed Shahryar Alavi , Mianesaz Hamidreza , Khosravian Farinaz , Bahreini Amir , Salehi Mansoor 
Published: August 2019

Abstract
Background Mutations in PIK3CA, which encodes p110 subunit of PI3K class IA enzyme, are highly frequent in breast cancer. Here, we aimed to probe mutations in exon 9 of PIK3CA and computationally simulate their function.
Method PCR/HRM and PCR/sequencing were used for mutation detection in 40 breast cancer specimens. The identified mutations were queried via in silico algorithms to check the pathogenicity. The molecular dynamics (MD) simulations were utilized to assess the function of mutant proteins.
Result Three samples were found to harbor at least one of the E542K, E545K and L551Q mutations of which L511Q has not been reported previously. All mutations were confirmed to be pathogenic and MD simulations revealed their impact on protein function and regulation. The novel L551Q mutant dynamics was similar to that of previously found carcinogenic mutants, E542K and E545K. A functional role for the helical domain was also suggested by which the inhibitory signal of p85α is conducted to kinase domain via helical domain. Helical domain mutations lead to impairment of kinase domain allosteric regulation. Interestingly, our results show that p110α substrate binding pocket of helical domain in mutants may have differential affinity for enzyme substrates, including anit-p110α drugs.
Conclusion The novel p110α L551Q mutation could has carcinogenic feature similar to previously known mutations.
The Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets
Authors: Wang Yuxiu , Wang Xiaolin , Wang Liping , Gu Jianjun , Gong Daohui , Jiang Jixin , Xu Xingxiang , Hu Suwei , Shu Yusheng , Min Lingfeng 
Published: August 2019

Abstract
Background: To explore the mutations expression and prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics.Methods: Mutations expression on chromosome 15q25 of 576 primary LAC patients was selected. And their survival and gene expression data were extracted from TCGA. The cell experiment about Beas-2b, A549 and H1299 cell lines were done to further prove the CHRNA5 and PSMA4 expression difference between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients.Finally, Gene enrichment analysis (GSEA) was used to predict the regulatory genes of CHRNA5 and PSMA4.Results: CHRNA5 and PSMA4 are frequently mutated in the TCGA (CHRNA5, 1.7%; PSMA4, 1.3%).The expression of CHRNA5 and PSMA4 were obviously higher in A549 and H1299 cells. Immunohistochemical staining revealed that the level of CHRNA5 and PSMA4 was considerably higher in LAC group than in normal group. There was a significant association between high expression of CHRNA5 and Smoking History (P=0.011), Smoking History Pack Year Value(P=0.010). Besides, there was a significant correlation between CHRNA5 and PSMA4 expression level and prognosis (P=0.003; P=0.008),and the higher expression, the worse prognosis. GSEA results suggested that CHRNA5 and PSMA4 high expression samples were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, aminoacyl tRNA biosynthesis etc.Conclusions: The expression of CHRNA5 and PSMA4 mRNA has a significant impact on survival of LAC, they may be a potential target for treating patients with lung adenocarcinoma.
Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis
Authors: Qin Kang , Hou Helei , Liang Yu , Zhang Xiaochun 
Published: August 2019

Abstract
Background

The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non–small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments.

Methods

Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Results

In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR=1.88, 95%CI: 1.59-2.23, p<0.001, I2=0.0%, P=0.792) and overall survival (OS) (HR=1.92, 95%CI: 1.55-2.38, p<0.001, I2=0.0%, P=0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P<0.001, I2=0.0%, P=0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P<0.001, I2=0.0%, P=0.484). Begg’s funnel plots and Egger’s tests indicated no significant publication bias in this study.

Conclusions

This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.
Abnormally Expressed Circular RNAs as Novel Non-Invasive Biomarkers for Hepatocellular Carcinoma: A Pair-wise Meta-Analysis
Authors: Jiang Yanlin , Shang Mengmeng , Dong Shizhen , Chen Menglu , Wang Xiaoli , Chang Yongchao 
Published: August 2019

Abstract
Background: In the recent literature, dysregulated circular RNAs (circRNAs) have been extensively investigated in hepatocellular carcinoma (HCC). This study strives to evaluate the diagnostic as well as the predictive value of abnormally expressed circRNAs in HCC.
Methods: Eligible studies were sourced from PubMed, EMBASE, and CNKI online databases. Data on patients’ clinical characteristics, including diagnostic efficacy and overall survival (OS) were extracted. The diagnostic and prognostic parameters were respectively synthesized using the bivariate meta-analysis model and multivariate Cox hazard regression analysis based on STATA 12.0. The trim and fill approach was employed to evaluate the impacts of publication bias.
Results: A sum of 21 eligible types of research was incorporated. The pooled sensitivity, specificity and area under the curve (AUC) of abnormally expressed circRNAs in distinguishing HCC from non-cancer controls were estimated to be 0.78 (95% confidence interval (CI): 0.69–0.85), 0.80 (95% CI: 0.74–0.86) and 0.86, respectively. Survival analyses expressed that the down-regulated circRNA expression signature correlated perfectly with HCC survival (hazard ratio (HR) = 0.42, 95% CI: 0.19–0.91, p = 0.028; I2 = 92.7%; p = 0.000), whereas the HCC cases with high circRNA levels had significantly poorer prognoses than those of patients with low circRNA levels (HR = 2.22, 95% CI: 1.50–3.30, p = 0.000; I2 = 91%; p = 0.000). Moreover, abnormally expressed circRNAs were intimately linked with tumor size, differentiation grade, microvascular invasion, metastasis, TNM stage, and serum AFP level in patients with HCC. Stratified analysis based on sample type, control source, and expression status also yielded robust results.
Conclusions: Abnormally expressed circRNA signatures show immense potential as novel non-invasive biomarker(s) in complementing HCC diagnosis and prognosis.
Serum-to-urine renalase ratio and its differences between healthy adults and chronic kidney disease patients
Authors: Serwin Natalia Maria , Wiśniewska Magda , Cecerska-Heryć Elżbieta , Safranow Krzysztof , Skwirczyńska Edyta , Dołęgowska Barbara 
Published: August 2019

Abstract
Background

Renalase is a flavoprotein involved in pathomechanisms of chronic kidney disease and heart and circulatory system disorders. Secretion and way of action of this protein are still discussed. Aim of our study was to initially estimate the balance between serum and urine renalase in healthy adults and to compare obtained ratio to chronic kidney disease patients.

Methods

Our study involved 28 healthy volunteers and 62 patients with diagnosed chronic kidney disease in stages I to IV. Concentration of renalase in blood serum and urine was measured using enzyme-linked immunosorbent assay (ELISA) kit (Uscn Life Science, Wuhan, China). We analyzed serum-to-urine renalase proportion in both groups and evaluated the differences using Mann Whitney U-test.

Results

Renalase serum-to-urine ratio was significantly higher in chronic kidney disease patients in comparison with control group (1.146 and 0.177, respectively; p<0.05). Also renalase serum-to-urine/mg creatinine ratio was higher in CKD patients than in healthy subjects (0.863 and 0.176, respectively; p<0.05). In both groups, no correlation between renalase concentration or serum-to-urine ratio, and eGFR, was found.

Conclusions

Renalase is involved in chronic kidney disease pathomechanism and is highly secreted and cumulated in blood of subjects with chronic kidney disease, what is accompanied by reduction of urinary renalase excretion. This may occur due to the potential role of renalase as a cytokine, preventing further kidney, and probably heart, dysfunction or injury. Chronic kidney disease causes higher expression of renalase, but its balance between serum and urine depends on more factors and conditions, involved in CKD pathomechanism.
A comparison of immunohistochemistry and mass spectrometry for determining light chain amyloid ﬁbril protein from formalin-ﬁxed renal biopsy tissue in a single Chinese center
Authors: Sun Ying , Sun Jian , Sun Wei , Pang Junyi , Wen Yubing , Zhu Zixuan , Tao Jianling , Chen Limeng , Li Xuemei , Li Mingxi 
Published: August 2019

Abstract
Background Amyloidosis, a disease caused by abnormal protein deposition in tissues, is classiﬁed according to the protein precursor that form amyloid ﬁbrils. Diagnosis of amyloidosis is type-specific as the identification of amyloid protein determines the following treatment. However, around a quarter of amyloidosis cases cannot be accurately subtyped by most commonly used immunohistochemistry (IHC). In order to obtain precise diagnosis, our study is focusing on another protein identification methods, laser microdissection and mass spectrometry (LDMS). Methods 20 cases of Amyloid Light-chain (AL) amyloidosis without further subtype were included. IHC and LDMS were used to detect light chains on formalin-ﬁxed parafﬁn-embedded (FFPE) tissues from renal biopsy. Results 100% consistence between positive IHC and LDMS results were observed, however, chances of subtyping using LDMS is increased to 94% compared to IHC which is only 76%. Conclusion LDMS is a valuable tool in regard to subtyping amyloidosis.
Detection of water-molecular-motion configuration in patients with lupus nephritis: A primary study using diffusion-weighted imaging.
Authors: Zheng Zhenfeng , Wang Yanyan , Yan Tiekun , Jia Junya , Li Dong , Wei Li , Shang Wenya , Shi Huilan 
Published: August 2019

Abstract
Background: Lupus nephritis (LN) is one of most common types of secondary glomerulonephritis, which is characterized by longitudinal pathological changes. Microstructural lesions of LN will impact the motion of water molecules, which can be detected by diffusion-weighted imaging (DWI). There are few reported measurements of water diffusion in patients with LN, and the nature of water diffusion across the entire depth of the renal parenchyma remains largely unknown.
Methods: Twenty adult patients with LN and 11 healthy volunteers underwent DWI inspection. Renal biopsy samples were characterized based on the revised ISN/RPS 2003 classification. The apparent-diffusion coefficient (ADC) was calculated via fitting into a mono-exponential model. To compare the ADC level across the entire renal parenchyma between the two groups, repeated-measures analysis of variance (RM-ANOVA) was performed. ADC data derived from DWI pictures were transformed into tridimensional maps by MATLAB software.
Results: Compared with data from healthy volunteers, lower average ADC values with major undulatory magnitudes were found in patients with LN, especially in the cortical zone. Tridimensional maps of patients with LN displayed geographic terrain-like canyons and/or valleys that were different from the corresponding terrain-like flatlands and/or plateaus in healthy volunteers. A heterogeneity of ADC values was found in bilateral kidneys. Left kidneys predominated higher ADC values in patients with LN. The ADC values across the entire renal parenchyma exhibited statistically significant differences among the three identified pathological subclasses (P<0.001).
Conclusions: Analysis of the motion of water molecules across the entire renal parenchyma may be helpful for better understanding the pathological conditions of LN, for which microstructural and functional heterogeneity may be detected and visualized via DWI.
Utilization of Urban Health Extension Program Services and Associated Factors among Hosanna Dwellers, Hadiya Zone, southern Ethiopia: A Community Based Cross-Sectional Study
Authors: Jikamo Birhannu , Woelamo Temesegen , Samuel Mekonen 
Published: August 2019

Abstract
Abstract
Background: In 2009, in Hadiya zone reported that establishment of Urban Health Extension Program (UHEP) which is subsequent declaration of after the country of Ethiopia. Major contribution of the declared UHEP is to provide accessible service to the potentially vulnerable groups of <5children pregnant women. Therefore, the aim of this study was to assess the utilization and associated factors of the urban health extension program services in Hossana Town, Hadiya Zone, southern Ethiopia, 2018
Methods: we conducted community based cross-sectional study in Hossana town, Hadiya Zone southern Ethiopia. Households were recruited by using systematic random sampling technique and study participants also by using random sampling techniques. A total of 403 study participants were participated in this study. Strength of measure of association between explanatory variables with outcome variable reported using the Odds Ratio (OR) with 95% confidence interval. Bivariate and multivariate binary logistic regression analysis was performed to identify predictors. P-value < 0.05 used to identify factors significantly associated with outcome variable.
Results: Out of 403 households, 397(98.5%) of response rate obtained. The mean score of community knowledge about the utilization of urban health extension program service (UHEP) was 2.352 (SD ±1.156. Regarding knowledge towards UHEP, of 166 (42%) of the respondents had good knowledge towards UHEP service while 231 (58%) had poor knowledge towards UHEP service utilization. The total number of households which graduated as a model family was 79 (19.9%). In the adjusted multivariate model, those respondents in the age group of 36-45 year were 3.73 times(AOR = 3.73; 95% CI:1.04-3.37) more likely to be utilized health extension program services as compared with those respondents in the age group of 18-24year. Those households which graduated as a model family were 2.2 times (AOR = 2.18; 95% CI: 1.36- 3.51) higher odds of utilized health extension program service as compared with those households which didn’t graduated as a model family.
Conclusions: The coverage of utilization of urban health extension program service was low in the study setting compared with previous study. There were also identified predictors that were associated with utilization of urban health extension program service.
The Financial Impact of Genetic Diseases in a Pediatric Accountable Care Organization
Authors: Miller Katherine , Hoyt Richard , Rust Steve , Doerschuk Rachel , Huang Yungui , Lin Simon M. 
Published: August 2019

Abstract
Background

Previous studies revealed patients with genetic disease have more frequent and longer hospitalizations and therefore higher healthcare costs. To understand the financial impact of genetic disease on a pediatric accountable care organization (ACO), we analyzed medical claims from 2014 provided by Partners for Kids, an ACO in partnership with Nationwide Children’s Hospital (Columbus, Ohio, USA).

Methods

Study population included claims from 258,399 children. We assigned patients to four different categories (1-A, 1-B, 2, & 3) based on the strength of genetic basis of disease.

Results

We identified 22.7% patients as category 1A&B- having a disease with a “strong genetic basis” (e.g., single gene diseases, chromosomal abnormalities). Total ACO paid claims for 2014 were $379M, of which $161M (42.5%) was attributed to category 1 patients. Category 1 patients experienced significantly more inpatient admissions (odds ratio = 4.12), emergency room visits, and outpatient visits compared to patients in category 3- those without genetic disease.

Conclusion

Nearly half (42.5%) of healthcare paid claims cost in 2014 for this study population were accounted for by patients with genetic diseases. These findings precede and support a need for an ACO to plan for effective healthcare strategies and capitation models for children with genetic disease.
Prognostic Effect of Preoperative Apolipoprotein B Level in Surgical Patients with Renal Clear Cell Carcinoma
Authors: Wang Kun , Wu Tingchun , Chen Yiming , Song Guanglai , He Xiaozhou , chen zhen 
Published: August 2019

Abstract
Objectives

To assess the prognostic value of preoperative apolipoprotein B level in surgical patients with renal clear cell carcinoma (ccRCC).

Materials and Methods

The study included 308 ccRCC patients receiving radical or partial nephrectomy between 2003 and 2012 in our center. The correlations among the preoperative ApoB, clinico -pathological parameters, and overall survival (OS) were evaluated.

Results

A total of 193 men (62.9%) and 114 women (37.1%) with ccRCC underwent radical or partial nephrectomy were enrolled in the present study. The OS at five years after operation was 90.6% for all patients, 87.4% for the lower ApoB group, and 97.0% for the higher ApoB group. The CSS at 5 years after surgery was 90.2% for all patients, 86.7% for the lower ApoB group, and 97.0% for the higher ApoB group. A higher ApoB level was related to a better OS and CSS in ccRCC patients (P = 0.001 and P < 0.001, respectively). In multivariate analysis, age >60 (P=0.008 and P=0.023), lower Apo B level (P= 0.019 and P= 0.018), were independent prognostic factors for OS and CSS, respectively.

Conclusions

In the Apo apolipoprotein family, the preoperative ApoB level has an important clinical significance for predicting the prognosis survival rate of the ccRCC patients.
A meta-analysis on the curative effect and safety of high-dose flurbiprofen axetil for pain management after general surgery
Authors: Hou Tingting , Cheng Dandan , Nie Huang 
Published: August 2019

Abstract
Background

To compare the curative efficiency or tolerability of flurbiprofen axetil(FA) in a high dose with that in a standard dose for postoperative pain of general surgery.

Methods

Relevant RCTs were retrieved from PubMed, Ovid, EMBASE, the Cochrane library, CBM, and CNKI from their inceptions to July 2019. The included studies were selected according to eligibility criteria. The study design, participant characteristics, interventions, and outcomes were abstracted after assessingmethodological quality of the trials. All data were analyzed by Review Manager 5.3.

Results

10 studies were identified, which compared the curative effect or tolerability of FA between high and standard dose group. 500 patients were involved in this meta-analysis, with 250 patients in high dose group and 250 patients in standard dose group, respectively. Pooled analysis of VAS scores at 1, 2, 4, 6, 8, 12, and 24h showed that VAS scores at 1h(P <0.00001), at 2h (P=0.003), at 4h (P = 0.0007), at 6h (P=0.0002), at 8h (P= 0.0002), at 12h (P = 0.0001), and at 24h (P = 0.0004) in the high dose group were significantly lower than that in the standard group. Pooled analysis of BCS scores at 1, 2, 4, 6, 8, 12, and 24h showed that BCS scores at 1h (P < 0.00001), at 6h (P < 0.00001), at 12h(P=0.03), and at 24h (P=0.01) in the high dose group were significantly higher than that in the standard group. Pooled analysis showed that there was no difference in the incidence of adverse events or administrating rate of analgesics after FA treatment between high and standard dose groups (P>0.05).

Conclusions

In our meta-analysis, we found that FA with high dose (≥1.25 mg/kg or 100 mg) was more effective than that with standard dose in postoperative pain control after general operation,while the incidence of adverse effects with high or standard dose showed no significant difference.