bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA and transcriptomic analysis of fetal membrane reveal potential targets involved in oligohydramnios
Authors: Ou Yu-hua , Liu Yu-kun , Zhu Li-qiong , Chen Man-qi , Yi Xiao-chun , Chen Hui , Zhang Jian-ping 
Published: September 2020

Abstract
Background: The multiple causes of oligohydramnios make it challenging to study. Long noncoding RNAs (lncRNAs) are sets of RNAs that have been proven to function in multiple biological processes. The purpose of this study is to study expression level and possible role of lncRNAs in oligohydramnios.Methods: In this study, total RNA was isolated from fetal membranes resected from oligohydramnios pregnant women (OP) and normal amount of amniotic fluid pregnant women (Normal). LncRNA microarray was used to analyze the differentially expressed lncRNAs and mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to analyze the main enrichment pathways of differentially expressed mRNAs. Real-time quantitative PCR (qPCR) was used to validate the lncRNA expression level.Results: LncRNA microarray analysis revealed that a total of 801 lncRNAs and 367 mRNAs were differentially expressed in OP; in these results, 638 lncRNAs and 189 mRNAs were upregulated, and 163 lncRNAs and 178 mRNAs were downregulated. Of the lncRNAs, 566 were intergenic lncRNAs, 351 were intronic antisense lncRNAs, and 300 were natural antisense lncRNAs. The differentially expressed lncRNAs were primarily located in chromosomes 2, 1, and 11. KEGG enrichment pathways revealed that the differentially expressed mRNAs were enriched in focal adhesion as well as in the signaling pathways of Ras, tumor necrosis factor (TNF), estrogen, and chemokine. The qPCR results confirmed that LINC00515 and RP11-388P9.2 were upregulated in OP. Furthermore, the constructed lncRNA–miRNA–mRNA regulatory network revealed tenascin R (TNR), cystic fibrosis transmembrane conductance regulator (CFTR), ATP-binding cassette sub-family A member 12 (ABCA12), and collagen 9A2 (COL9A2) as the candidate targets of LINC00515 and RP11-388P9.2.Conclusions: In summary, we revealed the profiles of lncRNA and mRNA in OP. These results might offer potential targets for biological prevention for pregnant women with oligohydramnios detected before delivery and provided a reliable basis for clinical biological treatment in OP.
p.Arg72Pro polymorphism of P53 and Breast Cancer Risk: A meta-analysis of case-control studies
Authors: Diakite Brehima , Kassogue Yaya , Dolo Guimogo , Wang Jun , Neuschler Erin , Kassogue Oumar , Keita Mamadou L , Traore Cheick Bougari , Kamate Bakarou , Dembele Etienne , Sellama Nadifi , Murphy Robert L , Doumbia Seydou , Hou Lifang , Maiga Mamoudou 
Published: September 2020

Abstract
Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results : Twenty-one publications with cases age-matched controls including7841disease cases and 8876controls were evaluated in this meta-analysis. Overall, our results suggested that p.Arg72ProP53 was associated with a risk for breast cancer for the dominant model (OR= 1.09, 95% CI = 1.02-1.16; P= 0.01) and the additive model (OR= 1.09, 95% CI = 1.01-1.17; P= 0.03), but not in the recessive model (OR = 1.07, 95% CI = 0.97-1.16; P= 0.19). According to the ethnic group, allele Pro has been associated with breast cancer risk in Europeans for the dominant and additive models. Conclusions : This meta-analysis found a significant association between p.Arg72Pro in the P53 gene and the risk of breast cancer. Individuals carrying at least one Pro allele of the P53 gene are more likely to have breast cancer with dominant and additive models than individualsharboringthe Arg allele.
Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma
Authors: Kim Min-Young , Shin Jung-Young , Kim Jeong-Oh , Son Kyoung-Hwa , Kim Yeon Sil , Jung Chan Kwon , Kang Jin-Hyoung 
Published: September 2020

Abstract
Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in massive apoptotic tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.Methods: A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516+IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516+IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).Conclusions: Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.
Financial risk protection of Thailand’s Universal Health Coverage: results from series of national household surveys between 1996 and 2015
Authors: Tangcharoensathien Viroj , Tisayaticom Kanjana , Suphanchaimat Rapeepong , Vongmongkol Vuthiphan , Viriyathorn Shaheda , Limwattananon Supon 
Published: September 2020

Abstract
Background: Thailand, an upper-middle income country, has demonstrated exemplary outcomes of Universal Health Coverage (UHC). The country achieved full population coverage and a high level of financial risk protection since 2002, through implementing three public health insurance schemes. UHC has two explicit goals of improved access to health services and financial protection where use of these services does not create financial hardship. Prior studies in Thailand do not however provide evidence of long-term UHC financial risk protection. This study assessed financial risk protection as measured by the incidence of catastrophic health spending and impoverishment in Thai households prior to and after UHC in 2002.Methods: We used data from a fifteen-year series of annual national household socioeconomic surveys between 1996 and 2015, which were conducted by the National Statistical Office. The survey covered about 52,000 nationally representative households in each round. Descriptive statistics were used to assess the incidence of catastrophic payment as measured by the share of out-of-pocket payments for health by households exceeding 10% and 25% of household total consumption expenditure, and the incidence of impoverishment as determined by the additional number of non-poor households falling below the national and international poverty lines after making health payments. Results: Using the 10% threshold, the incidence of catastrophic spending dropped from 6.0% in 1996 to 2% in 2015. This incidence reduced more significantly when the 25% threshold was applied from 1.8% to 0.4% during the same period. The incidence of impoverishment against the national poverty line reduced considerably from 2.2% in 1996 to approximately 0.3% in 2015. When the international poverty line of US$ 3.1 per capita per day was applied, the incidence of impoverishment was 1.4% and 0.4% in 1996 and 2015 respectively; and when US$ 1.9 per day was applied, the incidence was negligibly low. Conclusion: The significant decline in the incidence of catastrophic health spending and impoverishment was attributed to the deliberate design of Thailand’s UHC, which provides a comprehensive benefits package and zero co-payment at point of services. The well-founded healthcare delivery system and favourable benefit package concertedly support the achievement of UHC goals of access and financial risk protection.
The impact of occupational and personal factors on musculoskeletal pain - A cohort study of female nurses, sonographers and teachers.
Authors: Arvidsson Inger , Simonsen Jenny Gremark , Andersson Agneta Lindegård , Björk Jonas , Nordander Catarina 
Published: September 2020

Abstract
Background: Musculoskeletal pain is common in the general population and constitutes a major public health problem. A large proportion of these conditions may be work related. The aim of this study was to explore the relative importance of physical, psychosocial and personal factors, in number of pain sites and in five specific pain sites, among women in common professions with a broad variety of occupational exposures. Methods: A cohort of 1115 women responded to a questionnaire on ergonomic, psychosocial, personal and life-style factors, and the outcome measure of musculoskeletal pain (based on frequency and intensity of complaints at nine anatomical sites), at baseline and at follow-up. Sum scores of ergonomic and psychosocial factors were created. The importance of exposure at baseline for the number of pain sites at follow-up were estimated using ordinal regression. The importance of exposure at baseline for pain in the neck, shoulders, hands, lower back and feet at follow-up were estimated using multi-exposure Poisson regression models. Results: High sum scores for ergonomic and psychosocial factors were of importance for a high number of pain sites, although the strongest risk factor was a high number of pain sites already at baseline. On the individual level, there was a large fluctuation in number of pain sites between the two time points. Eighteen percent reported persistent (or recurrent) ≥four pain sites, while only eleven percent did not report any pain at baseline or at follow-up. Among the specific pain sites, a high sum score of ergonomic factors was associated with pain in the neck, hands and feet. A high sum score of psychosocial factors was associated with neck and shoulder pain. The strongest risk factor was, however, pain at that specific anatomical site at baseline. Only a few of the personal and life-style factors were associated with pain. Conclusions: An overwhelming majority of the women in common occupations were affected by musculoskeletal pain. Both ergonomic and psychosocial factors were predictive of a high number of pain sites and of specific pain sites. These findings indicate the need for preventive measures on the individual, organizational and societal level.
A phase I study of a dual PI3-Kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia
Authors: Lang Fabian , Wunderle Lydia , Badura Susanne , Schleyer Eberhard , Brüggemann Monika , Serve Hubert , Schnittger Susanne , Gökbuget Nicola , Pfeifer Heike , Wagner Sebastian , Ashelford Kevin , Bug Gesine , Ottmann Oliver 
Published: September 2020

Abstract
Background: Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. The primary objective of this phase I single center open label study was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the dual pan-class I PI3K and mTOR inhibitor BEZ235 in patients with advanced leukemia.Methods: Herein patients > 18 years of age who had relapsed or showed refractory leukemia were treated with BEZ235 (orally at 300-400 mg BID (cohort -1/1)) to assess safety, tolerability, preliminary efficacy and pharmacokinetic (PK). Adverse events data and serious adverse events were analyzed and haematological and clinical biochemistry toxicities were assessed from laboratory test parameters. Response was assessed for the first time at the end of cycle 1 (day 29) and after every subsequent cycle. Pharmacokinetic and pharmacodynamic analyses of BEZ235 were also included (BEZ235 plasma levels, phosphorylation of AKT, S6 and 4EBP1). On statistics this trial is a multiple ascending dose study in which a following variant of the 3+3 rule (“Rolling Six”), a minimum of 6 and a maximum of 12 patients was recruited for the dose escalation and another 5 were planned for the expansion phase.Results: Twenty-four patients with ALL (n=11) or AML (n=12) or CML-BP (n=1) were enrolled. All patients had failed one (n=5) or more lines of therapy (n=5) and 14 patients were in refractory / refractory relapse. No formal MTD was defined, stomatitis and gastrointestinal toxicity at 400 mg BID dose was considered incompatible with prolonged treatment. The RP2D of BEZ235 was defined as 300 mg BID. Four of 24 patients showed clinical benefit. Twenty-two of 24 patients discontinued because of progression, (median time to progression 27 days (4d-112d). There was no association between PK parameters and efficacy or tolerability.Conclusions: Combined inhibition of PI3K and mTOR inhibits a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML.Trial registration: ClinicalTrials.gov, identifier NCT01756118. retrospectively registered 19th December 2012, https://clinicaltrials.gov/ct2/show/NCT01756118.
RNA-seq analysis of galaninergic neurons from ventrolateral preoptic nucleus identifies expression changes between sleep and wake
Authors: Guo Xiaofeng , Gao Xiaoling , Keenan Brendan T. , Zhu Jingxu , Sarantopoulou Dimitra , Lian Jie , Galante Raymond J. , Grant Gregory R. , Pack Allan I. 
Published: September 2020

Abstract
Background: Previous studies show that galanin neurons in ventrolateral preoptic nucleus (VLPO-Gal) are essential for sleep regulation. Here, we explored the transcriptional regulation of the VLPO-Gal neurons in sleep by comparing their transcriptional responses between sleeping mice and those kept awake, sacrificed at the same diurnal time. Results: RNA-sequencing (RNA-seq) analysis was performed on eGFP(+) galanin neurons isolated using laser captured microdissection (LCM) from VLPO. Expression of Gal was assessed in our LCM eGFP(+) neurons via real time qPCR and showed marked enrichment when compared to LCM eGFP(-) cells and to bulk VLPO samples. Gene set enrichment analysis utilizing data from a recent single-cell RNA-seq study of the preoptic area demonstrated that our VLPO-Gal samples were highly enriched with galanin-expressing inhibitory neurons, but not galanin-expressing excitatory neurons. A total of 263 genes were differentially expressed between sleep and wake in VLPO-Gal neurons. When comparing differentially expressed genes in VLPO-Gal neurons to differentially expressed genes in a wake-active neuronal region (the medial prefrontal cortex), evidence indicates that both systemic and cell-specific mechanisms contribute to the transcriptional regulation in VLPO-Gal neurons. In both wake-active and sleep-active neurons, ER stress pathways are activated by wake and cold-inducible RNA-binding proteins are activated by sleep. In contrast, expression of DNA repair genes is increased in VLPO-Gal during wakefulness, but increased in wake-active cells during sleep. Conclusion: Our study identified transcriptomic responses of the galanin neurons in the ventrolateral preoptic nucleus during sleep and sleep deprivation. Data indicate that VLPO contains mainly sleep-active inhibitory galaninergic neurons. The VLPO galanin neurons show responses to sleep and wake similar to wake-active regions, indicating these responses, such as ER stress and cold-inducible RNA-binding proteins, are systemic affecting all neuronal populations. Region-specific differences in sleep/wake responses were also identified, in particular DNA repair. Our study expands knowledge about the transcriptional response of a distinct group of neurons essential for sleep.
An immunochemistry-based screen for chemical inhibitors of DNA-protein interactions and its application to human CGGBP1
Authors: Patel Manthan , Patel Divyesh , Datta Subhamoy , Singh Umashankar 
Published: September 2020

Abstract
Background: Inhibition of DNA-binding of proteins by small-molecule chemicals holds immense potential in manipulating the activities of DNA-binding proteins. Such a chemical inhibition of DNA-binding of proteins can be used to modulate processes such as replication, transcription, DNA repair and maintenance of epigenetic states. This prospect is currently challenged with the absence of robust and generic protocols to identify DNA-protein interactions. Additionally, much of the current approaches to designing inhibitors requires structural information of the target proteins.Methods: We have developed a simple dot blot and immunodetection-based assay to screen chemical libraries for inhibitors of DNA-protein interactions. The assay has been applied to a library of 1685 FDA-approved chemicals to discover inhibitors of CGGBP1, a multifunctional DNA-binding protein with no known structure. Additional in vitro and in cellulo assays have been performed to verify and supplement the findings of the screen.Results: Our primary screen has identified multiple inhibitors of direct or indirect interactions between CGGBP1 and genomic DNA. Of these, one inhibitor, Givinostat, was found to inhibit direct DNA-binding of CGGBP1 in the secondary screen using purified recombinant protein as the target. DNA and chromatin immunoprecipitation assays reinforced the findings of the screen that Givinostat inhibits CGGBP1-DNA binding.Conclusions: The assay we have described successfully identifies verifiable inhibitors of DNA-binding of protein; in this example, the human CGGBP1. This assay is customizable for a wide range of targets for which primary antibodies are available. It works with different sources of the target protein, cell lysates or purified recombinant preparations and does not require special equipment, DNA modifications or protein structural data. This assay is scalable and highly adaptable with the potential to discover inhibitors of transcription factors with implications in cancer biology.
A hybrid cost-sensitive ensemble for heart disease prediction
Authors: Qi Zhenya , Zhang Zuoru 
Published: September 2020

Abstract
Background: Heart disease is the primary cause of morbidity and mortality in the world. It includes numerous problems and symptoms. The diagnosis of heart disease is difficult because there are too many factors to analyze. What’s more, the misclassification cost could be very high.

Methods: A cost-sensitive ensemble model was proposed to improve the efficiency of diagnosis and reduce the misclassification cost. The proposed model contains five heterogeneous classifiers: random forest, logistic regression, support vector machine, extreme learning machine and k-nearest neighbor. T-test was used to investigate if the performance of the ensemble model was better than individual classifiers and the contribution of Relief algorithm.

Results: The best performance was achieved by the proposed model according to ten-fold cross validation. The statistical tests demonstrated that the performance of the proposed model was significantly superior to individual classifiers, and the efficiency of classification was distinctively improved by Relief algorithm.

Conclusions: The proposed ensemble model gained significantly better results compared with individual classifiers and previous studies, which implies that it can be used as a promising alternative tool in medical decision making for heart disease diagnosis.
Three-dimensional versus two-dimensional derived strain echocardiography for assessing right ventricular myocardial deformation in patients with chronic left ventricular heart failure: A proof-of-concept study
Authors: Gao Fei , Liu Chong , Guo Qiang , Jiang Shuang-quan , Wang Zhen-zhen , Liu Li , Li Hai-Ru , Du Guo-Qing , Tian Jia-wei 
Published: September 2020

Abstract
Background: A novel three-dimensional echocardiography (3DE)-derived strain analysis software specialized for right ventricular (RV) monitoring is emerging that could definitely evaluate RV free wall and interventricular septum longitudinal strain. The aim of this study was to compare the diagnostic performance in evaluating RV function between 3DE and two-dimensional echocardiography (2DE)-derived longitudinal strain.Methods: Echocardiographic examinations were performed in 82 patients with RV dysfunction associated with chronic left-sided heart failure and 40 control subjects. RV dysfunction was defined as a 3DE-derived RV ejection fraction (EF) <45%. Both 2DE and 3DE-derived strain analyses were performed in all the patients to measure the longitudinal strain of RV.Results: 3DE-derived peak systolic longitudinal strain of RV free wall (RV-fwLS) was significantly lower in patients with RV dysfunction compared to control subjects (-14.0±4.1 vs. -26.7±4.7%; p<0.001), and it correlated well with cardiac magnetic resonance-derived RVEF (r=0.74, p<0.001). On receiver operator characteristic analysis, a 3DE-derived RV-fwLS cutoff value of >-21.1% was most useful in identifying patients at higher risk of RV dysfunction (sensitivity: 90% and specificity: 85%), also higher than 2DE-derived strain parameters. Additionally, RV dysfunctional patients with pulmonary hypertension (PH) had significantly reduced 3DE-derived RV-fwLS value than the subgroup without PH (-13.1±3.8 vs. -15.0±4.2; p<0.05).Conclusion：Assessment of impaired RV systolic function by 3DE-derived longitudinal strain is better than 2DE in chronic left-sided heart failure patients with left ventricular EF <45%. 3DE-derived strain analysis specialized for RV should be considered as a complementary tool for assessing RV function.