bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heritability estimation of dichotomous phenotypes using a liability threshold model on ascertained family‐based samples
Authors: Kim Wonji , Kwak Soo Heon , Won Sungho 
Published: July 2019

AbstractNumerous methods for estimating heritability have been proposed; however, unlike quantitative phenotypes, heritability estimation for dichotomous phenotypes is computationally and statistically complex, and the use of heritability is infrequent. In this study, we developed a statistical method to estimate heritability of dichotomous phenotypes using a liability threshold model in the context of ascertained family‐based samples. This model assumes that dichotomous phenotypes are determined by unobserved latent variables that are normally distributed and can be applied to general pedigree data. The proposed methods were applied to simulated data and Korean type‐2 diabetes family‐based samples, and the accuracy of the estimates provided by the experimental methods was compared with that of the established methods.
Early signal from the hippocampus for memory encoding
Authors: Raynal Elsa , Schnider Armin , Manuel Aurélie L. 
Published: July 2019

AbstractThe mediotemporal lobe (MTL), including the hippocampus, is involved in all stages of episodic memory including memory encoding, consolidation, and retrieval. However, the exact timing of the hippocampus' involvement immediately after stimulus encounter remains unclear. In this study, we used high‐density 156‐channel electroencephalography to study the processing of entirely new stimuli, which had to be encoded, in comparison to highly overlearned stimuli. Sixteen healthy subjects performed a continuous recognition task with meaningful pictures repeated up to four consecutive times. Waveform and topographic cluster analyses of event‐related potentials revealed that new items, in comparison to repetitions, were processed significantly differently at 220–300 ms. Source estimation localized activation for processing new stimuli in the right MTL. Our study demonstrates the occurrence of a transient signal from the MTL in response to new information already at 200–300 ms poststimulus onset, which presumably reflects encoding as an initial step toward memory consolidation.
Visualizing the knowledge structure of medication‐adherence research: A bibliometric analysis (1997‐2016)
Authors: Ye Liping , Zhang Xinping 
Published: July 2019

SummaryThis study involves a bibliometric analysis of the medication‐adherence research and covers publications from 1997 to 2016. A database of 19 621 publications and 335 208 references from the Web of Science was investigated using the CiteSpace software. Some interesting findings were obtained. First, the most significant developments and progress in the medication‐adherence research have occurred in North America and Europe. Second, Osterberg L. and the Journal of the American Medical Association (JAMA) are the most cited author and journal, respectively, with the strongest academic influence. Third, the existing studies on medication adherence primarily focus on pharmacology/pharmacy, psychiatry, public environmental occupational health, and general internal medicine. Fourth, research hotspots showed a diversifying trend and increasingly covered chronic diseases. Moreover, the topic of integrating formal outcome evaluations into adherence interventions is one long‐term research hotspot. In addition, the research frontiers mainly focus on medication adherence for HIV/AIDS patients, especially active antiretroviral therapy. Finally, the evolution of the medication‐adherence research has occurred in approximately three stages: The first stage involved the introduction of the term “compliance” into medicine, then the primary focus shifted to patient adherence to HIV/AIDS medication, and the final stage has involved a diversifying trend with more diseases and methods for measuring adherence being researched in the current stage. Furthermore, because of an aging population and a disease spectrum change in the current phase, the focus of medication‐adherence research has gradually shifted from infectious diseases to chronic diseases.
Influences of Drought and Microbial Water‐Retention Fertilizer on Leaf Area Index and Photosynthetic Characteristics of Flue‐Cured Tobacco
Authors: Yang Xu , Shao Xiaohou , Mao Xinyu , Li Minhui , Zhao Tingchao , Wang Feng , Chang Tingting , Guang Jianfang 
Published: July 2019

AbstractDrought has become a severe and frequently happening issue in the Guizhou province of China due to unevenly distributed rainfall and long‐term continuous cropping. Since drought and continuous cropping could be significant in causing the soil environment to deteriorate, measures which are beneficial for improving the growth of crops need are of great concern. In this study, drought conditions and a microbial water‐retention fertilizer (MWF) were applied as influencing factors for the leaf area index (LAI) and photosynthetic characteristics of flue‐cured tobacco. Under different drought conditions, the largest leaf area was obtained in normal conditions combined with 45 g basin−1 MWF (T13), which significantly increased by 32.0% when compared to normal conditions combined with 0 g basin−1 MWF (T1). An index model was further used to validate the above‐mentioned results and the correlation coefficients of LAI among different treatments were precisely simulated (0.981–0.993). The MWF had remarkable effects on tobacco's net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci) and transpiration rate (Tr). Furthermore, normal conditions (550 mm irrigation) combined with MWF (45 g basin−1) proved to be the preferable strategy for improving water use efficiency as well as the tobacco plantation. The results might provide theoretical and practical guidance for the growth of crops in areas with water shortage. © 2019 John Wiley & Sons, Ltd.
Highly hydrophilic cationic gold nanorods stabilized by novel quaternary ammonium surfactant with negligible cytotoxicity
Authors: Salajkova Sarka , Sramek Michal , Malinak David , Havel Filip , Musilek Kamil , Benkova Marketa , Soukup Ondrej , Vasicova Pavla , Prchal Lukas , Dolezal Rafael , Hodny Zdenek , Bartek Jiri , Zarska Monika , Kuca Kamil 
Published: July 2019

AbstractThe photothermal cancer therapy using cationic gold nanorods (GNRs) stabilized by quaternary ammonium salts (QAS) have a great potential to enhance conventional cancer treatment as it promises the effective eradication of cancer cells including cells resistant to radio‐ and chemo‐therapy and the stimulation of anti‐tumor immune response. However, as the cytotoxicity of the conventional alkanethiol‐QAS compounds limits their utility in medicine, here we developed GNRs modified by novel highly hydrophilic cationic surfactant composed of the quaternary ammonium group and ethylene glycol chain N,N,N‐trimethyl‐3,6,9,12,15‐pentaoxaheptadecyl‐17‐sulfanyl‐1‐ammonium bromide (POSAB) showing insignificant cytotoxicity in the free state. Surface modification of GNRs by POSAB allowed to prepare nanoparticles with good stability in water, high cellular uptake and localization in lysosomes that are a promising alternative to alkanethiol‐stabilized GNRs especially for biomedical applications.
Methotrexate anticancer drug delivery to breast cancer cell lines by iron oxide magnetic based nanocarrier
Authors: Attari Elahe , Nosrati Hamed , Danafar Hossein , Kheiri Manjili Hamidreza 
Published: July 2019

AbstractIn this study, we have achieved to provide an efficient method for production of iron oxide magnetic nanoparticles (MNPs) with arginine capping using in situ and one‐pot co‐precipitation method. As a novel drug delivery system, methotrexate (MTX) was conjugated to the obtained nanoparticles. These MNPs conjugate can potentially use in controlled drug delivery as carrier, and in magnetic resonance imaging as a contrast agent. Also, these nanoparticles can serve as a target in cancer therapy and diagnosis. These MNPs were covalently bond with MTX and can target the majority of cancer cells that their surfaces overexpressed by folate receptors. These conjugated nanoparticles were obtained through amide bond between the amine groups on their surface and the carboxylic acid end groups on MTX due to being functionalized with arginine. MTX was cleaved from nanoparticles according to drug release experiments in the presence of protease‐like lysosomal conditions. Fe‐Arg‐MTX was characterized by transmission electron microscopes, dynamic light scattering, thermogravimetric analysis, differential scanning calorimetry, X‐ray diffraction, and Fourier transform infrared spectroscopy. Furthermore, vibrating sample magnetometry analysis showed excellent magnetic properties of them. The average particle size of Fe‐Arg‐MTX was approximately 27 nm. The result revealed that the bare nanoparticles have no cytotoxicity against MCF‐7, 4T1, and HFF‐2 cell lines. Hemolysis assay showed that these nanoparticles are biocompatible. Regarding the research success, an efficient technique can be presented for drug delivery and controlled release and for studying cancer‐fighting in alive creature's bodies.
Identification of a 4‐miRNA signature as a potential prognostic biomarker for pancreatic adenocarcinoma
Authors: Wang Zhi‐Xin , Deng Tong‐Xing , Ma Zhao 
Published: July 2019

AbstractAn microRNA (miRNA) signature to predict the clinical outcome of pancreatic adenocarcinoma (PAAD) is still lacking. In the current study, we aimed at identifying and evaluating a prognostic miRNA signature for patients with PAAD. The miRNA expression profile and the clinical information regarding patients with PAAD were recruited from The Cancer Genome Atlas database. Differentially expressed miRNAs were identified between normal and tumor samples. By means of survival analysis, a 4‐miRNA signature for predicting patients' with PAAD overall survival (OS) was constructed. Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of survival prediction. Furthermore, the biological function of the predicted miRNAs was evaluated using a bioinformatics approach. Four (hsa‐mir‐126, hsa‐mir‐3613, hsa‐mir‐424, and hsa‐mir‐4772) out of 17 differentially expressed miRNAs were associated to the OS of patients with PAAD. Moreover, the area under the curve (AUC) of the constructed 4‐miRNA signature associated to patients' with PAAD 2‐year survival was 0.789. The multivariate Cox's proportional hazards regression model suggested that this 4‐miRNA signature was an independent prognostic factor of other clinical parameters in patients with PAAD. Further pathway enrichment analyses revealed that the miRNAs in the 4‐miRNA signature might regulate genes that affect focal adhesion, Wnt signaling pathway, and PI3K‐Akt signaling pathway. Thus, these findings indicated that the 4‐miRNA signature might be an effective independent prognostic biomarker in the prediction of PAAD patients' survival.
Neurexophilin and PC‐esterase domain family member 4 (NXPE4) and prostate androgen‐regulated mucin‐like protein 1 (PARM1) as prognostic biomarkers for colorectal cancer
Authors: Liu Ya‐Rui , Hu Yang , Zeng Ying , Li Zhi‐Xing , Zhang Hai‐Bo , Deng Jun‐Li , Wang Guo 
Published: July 2019

AbstractOwing to the high morbidity and mortality, novel biomarkers in the occurrence and development of colorectal cancer (CRC) are needed nowadays. In this study, the CRC‐related datasets were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. After screening the differentially expressed genes (DEGs) in R software, a total of 238 upregulated and 199 downregulated DEGs were revealed simultaneously. Then the Kaplan‐Meier survival analysis and Cox regression analysis were used to reveal the prognostic function of these DEGs. Neurexophilin and PC‐esterase domain family member 4 (NXPE4) and prostate androgen‐regulated mucin‐like protein 1 (PARM1) were two outstanding independent overall survival (OS) and relapse‐free survival (RFS) prognostic genes of CRC in TCGA database. We next verified the expression of NXPE4 and PARM1 messenger RNA (mRNA) levels were significantly lower in CRC tumor tissue than in the adjacent noncancerous tissue in our clinical samples, and NXPE4 mRNA expression level was related to the tumor location and tumor size, while PARM1 was related to tumor location, lymph nodes metastasis, and tumor size. This study demonstrated that NXPE4 and PARM1 might be two potential novel prognostic biomarkers for CRC.
Protective effect of RNA interference targeting Ikkβ on hepatic fibrosis in rats
Authors: Wei Shi‐Fang , Sun Jian‐Jun , Zhou Ning , Li Xiang‐Lin , Lin Yan , Zhang Yao‐Di , Zhang Yue‐Rong , Wu Li‐Yang 
Published: July 2019

AbstractNuclear factor‐κB (NF‐κB) is an important regulatory factor in cells. NF‐κB has a wide range of biological activities. After activation, it participates in the transcription and regulation of many genes and plays a role in infection, inflammatory response, oxidative stress, cell multiplication, and apoptosis. The activation of the NF‐κB signal pathway is dependent on the degradation of the IκB kinase β (IKKβ) complex. IKK β is the key kinase in the NF‐κB activation pathway. After inhibition, it can block the activation of NF‐κB. IKKβ is a key regulator of NF‐κB activation, also an early regulator of inflammation in all stages of the immune response. This study aimed to investigate the effect of IKKβ‐siRNA lentivirus vector treatment for hepatic fibrosis of rats. An IKKβ‐siRNA expression plasmid was constructed and injected in the tail vein of rats. Then, IKKβ‐siRNA distribution in the liver was observed by immunofluorescence, and the quantitative polymerase chain reaction was used to detect inflammation‐related and fibrosis‐related factors. IKKβ‐siRNA lentiviruses could be delivered to the liver and significantly decrease carbon tetrachloride‐induced hepatic fibrosis. Furthermore, serum transaminase levels significantly decreased, and inflammation‐related and fibrosis‐related factors decreased. IKKβ‐siRNA can be an effective method of anti‐fibrosis gene therapy for liver fibrosis.
hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma
Authors: Zhu Xiaoqin , Shao Peng , Tang Yanchi , Shu Mingyang , Hu Wei‐Wei , Zhang Yong 
Published: July 2019

AbstractOral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real‐time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa‐miR‐933 overexpression. hsa_circRNA_100533 binds to hsa‐miR‐933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533‐miR‐933‐GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.
ITE promotes hypoxia‐induced transdifferentiation of human pulmonary arterial endothelial cells possibly by activating transforming growth factor‐β/Smads and MAPK/ERK pathways
Authors: Wang Jinxia , Yan Guosen , Guo Haixu , Zhu Ying , Shui Xiaorong , He Yuan , Chen Can , Lei Wei 
Published: July 2019

AbstractThis study aimed to investigate the transdifferentiation of human pulmonary arterial endothelial cells (HPAECs) into smooth muscle like (SM‐like) cells under hypoxic conditions and reveal the role of endogenous small molecular compound 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylicacid methyl ester (ITE) in this process. HPAECs were treated by hypoxia and hypoxia + ITE with different durations. The endothelial markers (CD31 and VE‐cad) and smooth muscle markers (α‐SMA, SM22α, and OPN) were investigated by immunofluorescence double staining, and their expressions, along with the differentiation regulators transforming growth factor‐β (TGF‐β) ligands and downstream signals including TGF‐β1, bone morphogenetic protein (BMP2), BMP9, Samd2/3, ERK, and p38 MAPK, were determined by Western blot analysis. The viability and proliferation of HPAECs were detected by Cell Counting Kit‐8 (CCK‐8) method and bromodeoxyuridine (BrdU) assays. As a result, hypoxia induced HPAECs transdifferentiation from paving‐stone‐like into polygonal or spindle cells, whose number increased greatly after additional ITE stimulation for 7 days. Compared with the normoxic HPAECs, the expression of endothelial markers reduced and smooth muscle markers were enhanced with the extension of hypoxia + ITE treatment, and meanwhile the cell viability increased significantly. Hypoxia could promote expression of TGF‐β1 protein rather than BMP2 and BMP9, and regulate phosphorylation levels of Samd2/3, ERK and p38 MAPK in different manners. In conclusion, ITE can promote the hypoxia‐induced transdifferentiation of HPAECs into SM‐like cells via TGF‐β/Smads and MAPK/ERK pathways.
YAP1 regulates PPARG and RXR alpha expression to affect the proliferation and differentiation of ovine preadipocyte
Authors: Deng Kaiping , Ren Caifang , Fan Yixuan , Pang Jing , Zhang Guomin , Zhang Yanli , You Peihua , Wang Feng 
Published: July 2019

AbstractAdipose tissue development is regulated by a serial of developmental signaling pathways. The Hippo pathway is a novel signaling cascade closely associated with adipogenesis. While most of Hippo pathway components had been verified that have a vital role in preadipocytes proliferation and differentiation, little is known about the function of Yes‐associated protein 1 (YAP1) in mammalian adipose tissue development. Therefore, we investigated the role of YAP1 in ovine adipose tissue development by in vitro and in vivo experiments. We observed that the adipocyte size in subcutaneous adipose tissue increased with development. YAP1 expression increased during adipose tissue development, while decreased during the differentiation of ovine preadipocytes in vitro. YAP1 knockdown notably promoted lipid accumulation and suppressed ovine preadipocyte proliferation. In addition, we observed that YAP1 deficiency significantly upregulated peroxisome proliferator‐activated receptor gamma (PPARG) and retinoid X receptor alpha (RXR alpha) expression. By contrast, overexpression of YAP1 led to the suppression of preadipocyte differentiation, lipid droplets formation, and PPARG expression. In brief, our findings demonstrated that YAP1 regulates the proliferation and differentiation of ovine preadipocyte via altering PPARG and RXR alpha expression.
Retracted: Notoginsenoside R1 protects WI‐38 cells against lipopolysaccharide‐triggered injury via adjusting the miR‐181a/TLR4 axis
Authors: Qian Daolin , Shao Xiankun , Li Yingchun , Sun Xinyan 
Published: July 2019

AbstractNotoginsenoside R1 (NGR1) is a neoteric phytoestrogen extracted from Panax notoginseng, and possesses comprehensive pharmacological functions in multitudinous ailments. But, whether NGR1 is utilized in neonatal pneumonia is not clear. This research study aspired to disclose the protective activity of NGR1 in neonatal pneumonia. WI‐38 cells were co‐stimulated with NGR1 and lipopolysaccharide (LPS, 10 ng/mL), CCK‐8 and flow cytometry assays were implemented for cell viability and apoptosis assessment. Real‐time quantitative plymerase chain reaction (RT‐qPCR), enzyme‐linked immunosorbent assay (ELISA), and Western blot analysis were executed for inflammatory cytokine determination. MicroRNA‐181a (miR‐181a) expression was evaluated through RT‐qPCR, simultaneously, the impact of miR‐181a was estimated in NGR1 and LPS co‐managed cells. Dual luciferase report assay was performed to disclose the relation between miR‐181a and Toll‐like receptor 4 (TLR4). The nuclear factor‐κB (NF‐κB) and TAK1/JNK pathways were ultimately appraised. We found that NGR1 decreased cell viability, evoked apoptosis and impeded interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) expression and secretions in LPS‐managed WI‐38 cells. MiR‐181a expression was enhanced by NGR1, and miR‐181a inhibition inverted the impacts of NGR1 in LPS‐managed WI‐38 cells. Besides, TLR4 was predicted to be a firsthand direct target of miR‐181a. Furthermore, NGR1 hindered NF‐κB and TAK1/JNK pathways through modulating TLR4. These discoveries disclosed the fact that NGR1 protected WI‐38 cells against LPS‐triggered injury via adjusting the miR‐181a/TLR4 and NF‐κB and TAK1/JNK pathways.
Overexpression of CDKN2B is involved in poor gastric cancer prognosis
Authors: Chen Xi , Yu Xingtong , Shen Enjian 
Published: July 2019

AbstractThe objective of this investigation is to elucidate the clinical significance of cyclin‐dependent kinase inhibitor 2B (CDKN2B) expression regarding gastric cancer (GC), as well as to detect the involvement of CDKN2B expression in the clinicopathological indexes and prognosis of GC. Immunohistochemical analysis was used for identification of CDKN2B expression in GC specimens. Chi‐square (χ2) test was applied to detect the association of CDKN2B expression and clinicopathological parameters of GC. The involvement of CDKN2B expression in the prognosis was analyzed via univariate and multivariate analysis. It was indicated that relative to the corresponding para‐carcinoma tissues, CDKN2B expression was notably upregulated in GC specimens. Moreover, the expression of CDKN2B was strongly correlated with the differentiation (r = −0.182; P = .015), invasion (r = −0.157; P = .038), distant metastases (r = −0.196; P = .004), and TNM stage (r = −0.204; P = .005). Nevertheless, no remarkable variance was related to age, tumor loci, or sex. Kaplan‐Meier survival curve and univariate analysis showed that CDKN2B overexpression predicted poorer disease‐free survival (P = .007) and overall survival (P = .005) in those with GC. In addition, Cox proportional hazards regression model revealed that CDKN2B was an isolated biomarker of disease‐free survival and overall survival in patients with GC. Taken together, our data demonstrated that the overexpression of CDKN2B could be an isolated factor for GC prognostic in patients. CDKN2B gene may be a useful target and new treatment for improving the prognosis of GC.