bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Ambient Temperature, Particulate Air Pollution and Emergency Room Visits for Conjunctivitis
Authors: khalaila soltan , Coreanu Tara , Vodonos Alina , Kloog Itai , Shtein Alexandra , Novack Victor , Tsumi Erez
Published: August 2019

Background

Numerous studies have confirmed that ambient temperature and air pollution are associated with higher risk of morbidities to different systems of the human body, yet few have addressed their effect on the ocular system. The purpose of this study is to determine the association between temperature, air pollution and emergency room visits for non-specific conjunctivitis

Methods

In this retrospective cohort study, the records of all emergency room visits to Soroka University Medical Center (SUMC) from 2009 to 2014 were reviewed for patients with conjunctivitis. Exposure to fine and coarse particulate matter and temperature were assessed by a hybrid model that incorporated daily satellite remote sensing.

Results

The records of the 6001 patients who visited the SUMC emergency room with conjunctivitis, together with the meteorological data, revealed a positive association between temperature increment and incidence of conjunctivitis. The strongest effect was found during summer and autumn: the incidence increased 8.1% for each 1oC rise in temperature between 24oC and 28oC in the summer, and 7.2% for each 1oC rise in temperature between 13oC and 23oC in autumn. The association between fine and coarse particulate matter and incidence of conjunctivitis was not statistically significant.

Conclusion

High ambient temperature is significantly associated with an increased risk of nonspecific conjunctivitis in summer and autumn and not in spring and winter. Conjunctivitis is not associated with air pollution. The findings can assist community clinics and hospital emergency rooms prepare for the upticks in the condition during certain seasons and acute rises in temperatures, lowering the financial costs to both the individual and the public.
Change in Angle of Eyes with Primary Angle Closure Suspects One Year after Laser Peripheral Iridotomy : a randomised study
Authors: Mou Dapeng , Liang Yuan Bo , Fan Su Jie , Peng Yi , Wang Ning Li , Thomas Ravi
Published: August 2019

Background: To report the changes in anterior chamber angle and progression rate to PAC(primary angle closure) following laser peripheral iridotomy (LPI) in primary angle closure suspects(PACS). Methods: Prospective, randomized controlled interventional clinical trial conducted at the Handan Eye Hospital, China. 134 bilateral PACS, defined as non-visibility of the posterior trabecular meshwork for ≥ 180 degrees on gonioscopy were randomly assigned to undergo LPI in one eye. Gonioscopy and Goldmann applanation tonometry were performed prior to, on day 7 and 12 months’ post LPI. Results: 80 of 134 patients (59.7%) could be followed up at one year. The mean IOP in treated eyes was 15.9±2.7 mmHg at baseline, 15.4±3.0 mmHg on day 7; 16.5±2.9 mmHg at one month and 15.5±2.9 mmHg at 12 months; the IOP in untreated eyes was similar (p=0.834). One or more quadrants of the angle opened in 93.7% of the LPI treated eyes, but 67.0% (53/79) remained closed in two or more quadrants. The progression rate to PAC in untreated eyes was 3.75% and one developed acute angle closure glaucoma(AACG), the progression rate to PAC(primary angle closure) in treated eyes 2.5% in treated eyes, none had developed PAS or AACG. Conclusion: LPI can open some of the occludable angle in the majority of eyes with PACS, but 67% continue to have non-visibility of the trabecular meshwork for over 180 degrees. IOP remained similar in treated and untreated eyes. Further research is needed to determine the full implications of residual closure as well as the need for follow up and treatment in PACS. The cumulative incidence for PAC/AACG in treated eyes were not significantly different from untreated eyes. Trial registration: Current Controlled Trials Chinese Clinical Trial Registry ChiCTR-TCH-10000820, as well as the date of registration(retrospectively registered).
Investigating Associated Factors with Glomerular Filtration Rate : Structural Equation Modeling
Authors: Jamshidi Parastoo , Najafi Farid , Mostafaee Shayan , Shakiba Ebrahem , pasdar yahya , Hamzeh Behrooz , Moradinazar Mahdi
Published: August 2019

Background: Glomerular Filtration Rate (GFR) is a valid indicator for kidney function, both in healthy and diseased people. Different factors can affect GFR. The purpose of this study is to assess a causal model to show direct and indirect effects of GFR-related factors using structural equation modeling.
Patients and methods : We analyzed data from recruitment phase of Ravansar Non-Communicable Disease cohort study. Data on socio-behavioral, nutritional, cardiovascular, and metabolic risk factors were entered in a conceptual model in order to test direct and indirect effects of the associated factors on GFR, separately in male and female, using the structural equation modeling.
Results : Of 8927 individuals participated in this study, 4212 subjects were male (47.2%) and 4715 subjects were female (52.8%). The obtained standard deviation of GFR was 76.05 (±14.3) per 1.73 . Filtration rate for 11.52%, 72.96% and 15.50% of people were <60, and , respectively. Hypertension in both gender and atherogenic factor in male directly, and in female directly and indirectly had a decreasing effect on GFR. Blood Urea Nitrogen (BUN) and smoking in male and female, directly or indirectly through other variables, was associated with a decrease in GFR. In female, diabetes had a decreasing direct and indirect effect on GFR. Obesity in female was directly associated with increasing and indirectly associated with decreasing filtration.
Conclusion : According to our results, increasing age, hypertension, diabetes, obesity and high blood lipids, and BUN had a decreasing direct and indirect effects on GFR. Although low GFR might have different reasons and it is not a consistent sign of CKD, our findings, in line with other reports, provide more detailed informations about important risk factors of low GFR. Public awareness about such factors can improve public practice of positive health behaviours.
Adaptation and psychometric evaluation of the simplified Chinese version of the Identification of Functional Ankle Instability questionnaire in Chinese-speaking patients with chronic ankle instability disorders
Authors: Wang Wei , Sheng Jun , Tang Yinchao , Xie Qingyun , Wei Meng , Li Zhiqiang , Zheng Wei
Published: August 2019

Background: This study aimed to adapt the Identification of Functional Ankle Instability (IdFAI) questionnaire into simplified Chinese version and assess its reliability, validity, and responsiveness in Chinese-speaking patients with chronic ankle instability (CAI) disorders.
Methods: The simplified Chinese version of the IdFAI (SC-IdFAI) questionnaire was developed in a five-step procedure of cross-cultural translation and adaptation. Three questionnaires, including the SC-IdFAI, Medical Outcomes Study Short-Form 36 (SF-36), and Foot and Ankle Ability Measure (FAAM), were administered to the recruited patients. Then, the Cronbach’s alpha, intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimal detectable change (MDC), Spearman’s correlation coefficient (rs), effect size (ES), and standardized response mean (SRM) were calculated to evaluate the reliability, validity, and responsiveness of the SC-IdFAI questionnaire.
Results: A total of 131, 119, and 86 patients with CAI successfully completed the first, second, and third rounds of the questionnaires, respectively. Good or excellent internal consistency and test–retest reliability were found in the overall scale and subscales of the SC-IdFAI questionnaire. Low values for SEM (1.346) and MDC (3.73) indicated that small clinical changes could be detected by the SC-IdFAI questionnaire. The correlations of SC-IdFAI with FAAM and SF-36 were generally in agreement with a priori hypotheses (85%, 34/40), suggesting good construct validity of the SC-IdFAI questionnaire. Moreover, good responsiveness was observed in the overall scale and subscales of the SC-IdFAI questionnaire.
Conclusion: The SC-IdFAI questionnaire was reliable, valid, and responsive for evaluating Chinese-speaking patients with CAI and might prove to be an effective instrument.
Risk factors for extended length of stay following hip fracture surgery: A retrospective cohort study of patients aged 90 years and over in China
Authors: Lan Ling , Pei Li-jian , Zhai Feifei , Zhang Yuelun , Jing Jun , Huang Yuguang
Published: August 2019

Background

Hip fractures are typical fractures in geriatric patients and are associated with a high risk of postoperative complications and extended length of stay (LOS) compared with other osteoporotic fractures, particularly among patients over age 90. We aimed to identify the risk factors for extended LOS (more than 14 days) in patients older than 90 years.

Methods

A single-centre retrospective cohort study was performed in 50 patients (over age 90) who experienced hip fracture between June 1, 2013, and August 31, 2017. Their medical records were retrospectively reviewed from the hospital’s electronic database. The baseline characteristics of the patients, intraoperative data and postoperative complications were collected for the assessment of potential risk factors. Univariate analysis and multivariate binary logistic regression analysis were performed to determine potential risk factors for extended LOS.

Results

The age of the patients in the cohort ranged from 90 to 101 years, and the analysis demonstrated that 70% (n = 35) of the patients experienced a complicated course of treatment with an in-hospital mortality rate of 4% (n = 2). The most common complication was the occurrence of postoperative pneumonia (38%). The median duration of hospital stay was 18 (IQR 11, 21) days. Multivariate binary logistic regression analysis showed that a LOS of more than 14 days was significantly associated with a lower mean diastolic blood pressure during surgery [odds ratio (OR) =0.86, 95% confidence interval (CI)=0.76-0.98, P = 0.018] and the occurrence of postoperative pneumonia (OR=8.95, 95% CI=1.45-55.3, P = 0.018). The occurrence of postoperative pneumonia was significantly associated with the neutrophil-to-lymphocyte ratio (NLR) at admission (D0) [odds ratio (OR) =1.20, 95% confidence interval (CI)=1.02-1.41, P = 0.029]. Neither the LOS nor postoperative pneumonia was found to be associated with the anaesthesia technique.

Conclusions

A lower mean diastolic blood pressure during surgery and the occurrence of postoperative pneumonia may extend the LOS in patients aged 90 years and over who undergo hip fracture surgery. The use of regional anaesthesia was not associated with a shorter LOS.
Reduced strength, poor balance and concern about falls mediate the relationship between knee pain and fall risk in older people
Authors: Hicks Cameron J , Levinger Pazit , Menant Jasmine C , Lord Stephen R , Sachdev Perminder S , Brodaty Henry , Sturnieks Daina L
Published: August 2019

Aims

Pain is an independent risk factor for falling. One in two older community-dwelling people with musculoskeletal pain fall each year. This study examined physical, psychological and medical factors as potential mediators to explain the relationship between knee pain and falls.

Methods

Three hundred and thirty-three community-dwelling people aged 70+ years (52% women) participated in this cohort study with a 1-year follow-up for falls. Participants completed questionnaires (medical history, general health and concern about falls) and underwent physical performance tests. Participants were classified into ‘pain’ and ‘no pain’ groups based on self-reported knee pain. Poisson Regression models were computed to determine the Relative Risk (RR) of having multiple falls and potential mediators for increased fall risk.

Results

One hundred and eighteen (35.5%) participants were categorised as having knee pain. This group took more medications and had more medical conditions (P <0.01) compared to the no pain group. The pain group had poorer balance, physical function and strength and reported increased concern about falls. Sixty one participants (19.5%) reported ≥ 2 falls, with the pain group twice as likely to experience multiple falls over the 12 month follow up (RR = 2.0, 95% confidence interval (CI) = 1.27 – 3.13). Concern about falls, knee extension torque and postural sway with eyes closed were identified as significant and independent mediators of fall risk, and when combined explained 23% of the relationship between knee pain and falls.

Conclusion

This study has identified several medical, medication, psychological, sensorimotor, balance and mobility factors to be associated with knee pain, and found the presence of knee pain doubles the risk of multiple falls in older community living people. Alleviating knee pain, as well as addressing associated risk factors may assist in preventing falls in older people with knee pain.
Old subjects with sepsis: trend analysis of case fatality rate in the Emergency Department
Authors: Fabbri Andrea , Marchesini Giulio , Benazzi Barbara , Morelli Alice , Montesi Danilo , Bini Cesare , Rizzo Stefano Giovanni
Published: August 2019

Background

The burden of sepsis represents a global health care problem. We aimed to assess the case fatality rate (CFR) and its predictors in subjects with sepsis admitted to a general Italian hospital from 2009 to 2016, stratified by risk score.

Methods

We performed a retrospective analysis of all sepsis-related hospitalizations after Emergency Department (ED) visit in a public Italian hospital in an 8-year period. A risk score to predict CFR was computed by logistic regression analysis of selected variables in a training set (2009-2012), and then confirmed in the whole study population. A trend analysis of CFR during the study period was performed dividing patient as high-risk (upper tertile of risk score) or low-risk .

Results

2,492 subjects were included. Over time the incidental admission rate (no. of sepsis-related admissions per 100 total admissions) increased from 4.1% (2009-2010) to 5.4% (2015-2016); P<0.001, accompanied by a reduced CFR (from 38.0% to 18.4%; P<0.001). A group of 10 variables (admission in intensive care unit, cardio-vascular dysfunction, HIV infection, diabetes, age ≥80 years, respiratory diseases, number of organ dysfunction, digestive diseases, dementia and cancer) were selected by the logistic model to predict CFR with good accuracy: AUC 0.873 [0.009]. Along the years CFR decreased from 31.8% (2009-2010) to 25.0% (2015-2016); P = 0.007. The relative proportion of subjects ≥80 years (overall, 52.9% of cases) and classified as high-risk did not change along the years. CFR decreased only in low-risk subjects (from 13.3% to 5.2%; P<0.001), and particularly in those aged ≥80 (from 18.2% to 6.6%; P=0.003), but not in high-risk individuals (from 69.9% to 64.2%; P=0.713).

Conclusion

Between 2009 and 2016 the incidence of sepsis-related hospitalization increased in a general Italian hospital, with a downward trend in CFR, only limited to low-risk patients and particularly to subjects ≥80 years.
The prognostic values of m6A RNA methylation regulators in Uveal melanoma
Authors: Wan Qi , Tang Jing , Lu Jianqun
Published: August 2019

Purpose

The aim of this study were to identify gene signatures and prognostic values of m6A methylation regulators in uveal melanoma (UM).

Methods

The RNA sequencing dataset and corresponding clinical information were downloaded from TCGA and GEO database. Based on the expression of m6A RNA methylation regulators, the patients were further clustered into different groups by applying the “ClassDiscovery” algorithm. Survival analysis was performed using log-rank tests and LASSO regression model. The association between mutations and m6A regulators was assessed by student t tests and clinical characteristics was examined by using chi-square test.

Result

Totally, we identified two molecular subtypes of UM (C1/2) by applying consensus clustering to m6A RNA methylation regulators. Contrasted to the C1 subtype, the C2 subtype associates with a better prognosis, longer survival time and lower percentage of Monosomy 3. The malignant hallmarks of mTORC1 signaling, oxidative phosphorylation, interferon-a response and apoptosis signaling are also significantly enriched in the C1 subtype. Moreover, a 2-m6A regulators signature was screened out by LASSO method, which can robustly predict UM patients survival.

Conclusions

m6A RNA methylation regulators take a crucial role in the potential malignant progression and prognostic value of UM and might be regarded as a new promising biomarker for UM prognosis and treatment strategy development.
A genomic-clinicopathologic nomogram predict survival for patients with laryngeal squamous cell carcinoma
Authors: Cui Jie , Wen Qingquan , Tan Xiaojun , Piao Jinsong , Zhang Qiong , Wang Qian , He Lizhen , Wang Yan , Chen Zhen , Liu Genglong
Published: August 2019

Long non-coding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. We aimed to establish a lncRNAs signature and a nomogram incorporating the genomic and clinicopathologic factors to improve the accuracy of survival prediction for laryngeal squamous cell carcinoma (LSCC). LSCC RNA sequencing (RNA-seq) data set and the matched clinicopathologic information were downloaded from the Cancer Genome Atlas (TCGA). Using univariable Cox regression and Least absolute shrinkage and selection operator (LASSO) analysis, we developed a thirteen lncRNAs signature related to prognosis. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to assess clinical value of our nomogram. Consequently, thirteen overall survival (OS) -related lncRNAs were identified, and the signature consisting of the selected thirteen lncRNAs could effectively divide patients into high-risk and low-risk subgroup, with the area under curve (AUC) of 0.89 (3-year OS) and AUC of 0.885(5-year OS). Independent factors derived from multivariable analysis to predict survival were margin status, tumor status and lncRNAs signature, which were all assembled into the nomogram. The calibration curve for the survival probability showed that the predictions based on the nomogram were in good coincide with actual observations. The C-index of the nomogram was 0.82 (0.77-0.87), and the area under curve (AUC) of nomogram in predicting overall survival (OS) was 0.938, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage. In summary, an inclusive nomogram for patients with LSCC, comprising genomic and clinicopathologic variables, generates more accurate estimations of the survival probability when compared TNM stage alone, but more additional data remains needed before being used in clinical practice.
HPV E6/E7 mRNA test for the detection of high grade cervical intraepithelial neoplasia (CIN2+): A systematic review
Authors: Derbie Awoke , Mekonnen Daniel , Woldeamanuel Yimtubeznash , Ostade Xaveer Van , Abebe Tamrat
Published: August 2019

Background: Genital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences are coming out on the usefulness of HPV E6/E7 mRNA test as a potential tool compared with cytology and HPV DNA testing. Taking into account shortage of compiled data on this field, the aim of this systematic review was to describe the latest diagnostic performance of HPV E6/E7 mRNA testing to detect high grade cervical lesions (CIN2+) where by histology as was taken as a ‘gold standard’.

Methods: Articles published in English were systematically searched using key words from PubMed/Medline and SCOPUS. In addition, Google Scholar and the Google database were searched manually for grey literature. Two reviewers independently assessed study eligibility, risk of bias and extracted the data. We performed a descriptive presentation of the performance of E6/E7 mRNA testings (interims of sensitivity, specificity, negative and positive predictive values) for the detection of CIN2+.

Results: Out of 231 applicable citations, we have included 29 articles with a total of 23,576 study participants (age range, 15-84) who had different cervical pathologies. Among the participants who had cervical histology, the proportion of CIN2+ was between 10.6% and 90.6%. Using histology as a gold standard, 11 studies evaluated the PreTect HPV Proofer, 7 studies evaluated the APTIMA HPV assay (Gen-Probe) and 6 studies evaluated the Quantivirus® HPV assay. The diagnostic performance of those three most common mRNA testing tools to detect CIN2+ was; 1) PreTect Proofer; median sensitivity 83%, median specificity 73%, median PPV 70 and median NPV 88.9%. 2) APTIMA assay; median sensitivity 91.4%, median specificity 46.2%, median PPV 34.3% and median NPV 96.3%. 3) Quantivirus®: median sensitivity 86.1%, median specificity 54.6%, median PPV 54.3%, median NPV 89.3%. Further, the area under the receiver operating characteristics (AU-ROC) curve varied between 63.8% and 90.9%.

Conclusions: The reported diagnostic accuracy implies that mRNA tests possess diagnostic relevance to detect CIN2+ and could potentially be considered in areas where there is no histology facility. Further studies including its cost should be considered.
Comprehensive Gene Expression Analysis Reveals Factors that Influence the Progression, Occurrence and Development of AML-M4
Authors: Qu Ying , Zhang Shuying , Qu Yanzhang , Guo Heng , Wang Suling , Wang Xuemei , Huang Tianjiao , Zhou Hong
Published: August 2019

Background Acute myelomonocytic leukemia (M4), a special type of acute myeloid leukemia (AML), is a clonal malignant disease with poor prognosis and a low overall survival rate. Here, we aim to explore the molecular mechanism of AML-M4 development and progression using integrative bioinformatic analysis. Methods We used an integrative method to identify potential driven genes in AML-M4. We firstly identify DEGs using limma packages and annotated them by GO and KEGG. To avoid individual bias, GSEA was adopted to certify the results. Furthermore, we constructed the PPI network using WGCNA which was superimposed onto STRING database. We also assessed the correlation and mutation among hub genes to deeply explore the biological mechanism in AML-M4. Finally, we confirmed our results by experiments. Results The results show that FLT3, WT1 and TP53, which are involved in transcriptional misregulation were upregulated, while PPBP and CCR7, which regulate cytokine-cytokine receptor interaction, as well as CD24, which acts as a protein marker of AML, were downregulated. 12 hub genes were found through the TCGA an Oncomain analysis, and the results also show that FLT3, CCR7 and MMP-9 can be potential targets for the detection and treatment of AML-M4. Conclusion The overall aim of this study was to identify critical pathways and genes associated with AML-M4, and to also provide potential therapeutic targets and new research ideas for the treatment and early detection of AML-M4.
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

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

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

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

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

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

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

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

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
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

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

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

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.