bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syntaxin 6: A novel predictive and prognostic biomarker in papillary renal cell carcinoma
Authors: Peak Taylor C. , Su Yixin , Chapple Andrew G. , Chyr Jacqueline , Deep Gagan 
Published: February 2019

AbstractSyntaxin 6 is a SNARE family protein known to play an important role in intracellular trafficking. Here, we examined the tumorogenic role of syntaxin 6 in renal cell carcinoma (RCC). The Cancer Genome Atlas (TCGA) was queried for clinicopathologic data and syntaxin 6 expression. We found a significant difference in overall survival (OS) between groups, with high syntaxin 6 expression correlating with decreased survival. When stratifying the data based on histological subtype, the papillary RCC subtype exhibited a significant correlation between syntaxin 6 expression and survival. Using ROC curve, we calculated the area under the curve (AUC) to determine the ability of syntaxin 6 to predict 3-year overall survival. The AUC for syntaxin 6 was 0.73, significantly higher compared to 0.52 for T stage. Next, syntaxin 6 expression was evaluated in clear cell (786-O and Caki-1) and papillary (Caki-2 and ACHN) RCC cells. Syntaxin 6 expression was higher in Caki-1 and ACHN RCC cells. Silencing of syntaxin 6 in ACHN cells significantly decreased the cell viability (p < 0.001). Overall, syntaxin 6 could be a prognostic biomarker for patients with papillary RCC and syntaxin 6 inhibitors hold promise as a novel therapy against RCC.
Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice
Authors: Xing Xiaoliang , Zhang Jing , Wu Kunyang , Cao Beibei , Li Xianfeng , Jiang Fang , Hu Zhengmao , Xia Kun , Li Jia-Da 
Published: February 2019

AbstractAutism spectrum disorders (ASD) form a heterogeneous, neurodevelopmental syndrome characterized by deficits in social interactions and repetitive behavior/restricted interests. Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/−, Tsc2+/−, Pten−/− mice and valproic acid-induced ASD animal models. However, it is still unknown if dysregulation of mTOR signaling is responsible for the ASD-related deficit caused by other genes mutations. Contactin associated protein-like 2 (CNTNAP2) is the first widely replicated autism-predisposition gene. Mice deficient in Cntnap2 (Cntnap2−/− mice) show core ASD-like phenotypes, and have been demonstrated as a validated model for ASD-relevant drug discovery. In this study, we found hyperactive Akt-mTOR signaling in the hippocampus of Cntnap2−/− mice with RNA sequencing followed with biochemical analysis. Treatment with Akt inhibitor LY294002 or mTOR inhibitor rapamycin rescued the social deficit, but had no effect on hyperactivity and repetitive behavior/restricted behavior in Cntnap2−/− mice. We further showed that the effect of LY294002 and rapamycin on social behaviors is reversible. Our results thus identified hyperactive Akt-mTOR signaling pathway as a therapeutic target for abnormal social behavior in patients with dysfunction of CNTNAP2.
Overexpression of Aiolos promotes epithelial-mesenchymal transition and cancer stem cell-like properties in lung cancer cells
Authors: Hung Jung-Jyh , Kao Ying-Shiun , Huang Chi-Hung , Hsu Wen-Hu 
Published: February 2019

AbstractAiolos/Ikaros family zinc finger 3 (IKZF3), a member of the Ikaros family of lymphocyte maturation-driving transcription factors, is highly expressed in hematopoietic malignancies. However, its role in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties in lung cancer remains unknown. Human lung cancer cell lines H1299 with overexpressing Aiolos (H1299-Aiolos) and A549 with overexpressing Aiolos (A549-Aiolos) were generated by stable transfection. Cell migration and invasion assays were done to demonstrate their invasion and migration ability. Sphere formation assay was used to determine their tumor-initiating capability. Aiolos overexpression induced EMT and increased migration/invasiveness in H1299 and A549 cells. Aiolos overexpression also increased metastatic ability in vivo. Aiolos overexpression upregulated the expression of Twist and matrix metalloproteinase 16 (MMP16). By using knockdown of Twist or an inhibitor of phosphatidylinositol (PI) 3-kinase, EMT, migration/invasiveness ability, and MMP16 expression were reversed in H1299-Aiolos and A549-Aiolos cells. Overexpression of Aiolos upregulated the CSC-like properties in lung cancer cells, and were also reversed by an inhibitor of PI 3-kinase. For lung cancer cells, Aiolos overexpression promotes EMT and CSC-like properties through upregulating the PI 3-kinase/Akt pathway. The information is helpful for developing therapeutic strategies targeting Aiolos expression for lung cancer treatment.
Prognostic significance of preoperative MRI findings in young patients with breast cancer
Authors: Bitencourt Almir G. V. , Eugênio Deise S. G. , Souza Juliana A. , Souza Juliana O. , Makdissi Fabiana B. A. , Marques Elvira F. , Chojniak Rubens 
Published: February 2019

AbstractThe objective is to evaluate the prognostic value of preoperative magnetic resonance imaging (MRI) findings in breast cancer patients aged less than 40 years. This retrospective, single-center study evaluated 92 women aged <40 years who received a diagnosis of invasive breast carcinoma between 2008 and 2012. These patients underwent a breast MRI before treatment and follow-up at the same institution. Kaplan-Meier survival curves were used to analyze overall survival, with the log-rank test used to compare different groups. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence interval (95% CI) values. The mean age of the patients was 34 years (range: 25–39 years) and the mean tumor size was 3.9 cm in maximal dimension (range: 0.7–10.5 cm). Recurrence was observed in 21 (22.8%) patients and 15 (16.3%) patients did not survive during a mean follow-up period of 5.4 ± 1.9 years. MRI findings associated with worse overall survival included tumor size >5 cm (HR:5.404; 95% CI:1.922–15.198; p = 0.017), presence of non-mass enhancement (HR:3.730; 95% CI:1.274–10.922; p = 0.016) and multifocal tumor (HR:3.618; 95% CI:1.151–11.369; p = 0.028). Inconclusion, MRI findings that are suggestive of more extensive disease were associated with worse overall survival in young breast cancer patients.
GPDPLQ1237—A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro
Authors: Löfvall Henrik , Katri Anna , Dąbrowska Aneta , Karsdal Morten A. , Luo Yunyun , He Yi , Manon-Jensen Tina , Dziegiel Morten H. , Bay-Jensen Anne-Christine , Thudium Christian S. , Henriksen Kim 
Published: February 2019

AbstractC-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe the GPDPLQ1237 ELISA which targets the EKGPDPLQ↓ neo-epitope, an elongated version of the CTX-II neo-epitope (EKGPDP↓), speculated to be a blood-precursor of CTX-II generated by the cysteine protease cathepsin K. Human osteoclast cartilage resorption cultures as well as oncostatin M and tumour necrosis factor α-stimulated bovine cartilage explant cultures were used to validate GPDPLQ1237 biologically by treating the cultures with the cysteine protease inhibitor E-64 and/or the matrix metalloproteinase (MMP) inhibitor GM6001 to assess the potential contributions of these two protease classes to GPDPLQ1237 release. Cartilage resorption-derived GPDPLQ1237 release was inhibited by E-64 (72.1% inhibition), GM6001 (75.5%), and E-64/GM6001 (91.5%), whereas CTX-II release was inhibited by GM6001 (87.0%) but not by E-64 (5.5%). Cartilage explant GPDPLQ1237 and CTX-II release were both fully inhibited by GM6001 but were not inhibited by E-64. No clinically relevant GPDPLQ1237 reactivity was identified in human serum, plasma, or urine from healthy donors or arthritis patients. In conclusion, the GPDPLQ1237 biomarker is released during osteoclast-derived cysteine protease- and MMP-mediated cartilage degradation in vitro, whereas CTX-II release is mediated by MMPs and not by cysteine proteases, as well as from MMP-mediated cartilage degradation under a pro-inflammatory stimulus. These findings suggest that GPDPLQ1237 may be relevant in diseases with pathological osteoclast activity and cartilage degradation. Further studies are required to validate the neo-epitope in human samples.
Neural representations of Groups and Stereotypes using fMRI repetition suppression
Authors: Delplanque Jeroen , Heleven Elien , Van Overwalle Frank 
Published: February 2019

AbstractCategorizing people in groups and associating them with stereotypical behavior is an integral part of human social understanding and interaction. This study investigates where knowledge on social groups and their stereotypes is represented in the brain. We presented participants with two sentences describing a group member (e.g. the police officer) performing a behavior believed to be stereotypical of the group (e.g. makes an arrest, i.e. authoritative), and asked them to rate the degree to which the behavior was typical of the group. Our critical manipulation was the repetition of this information across the two sentences: Either both the group and the stereotype implied by the behavior was repeated, only the group was repeated, only the stereotype implied by the behavior, or neither. Results showed robust suppression of hemodynamic activation from the first to second sentence in the medial prefrontal cortex in response to the repetition of the stereotype implied in the behavior, but only when groups were different. This finding suggests that the neural representation of stereotypes is located in this area, and this is in line with similar repetition suppression research showing trait representation in this area. A suppression effect for the repetition of groups was observed in the posterior cingulate cortex, regardless of whether stereotypes were repeated or not. This finding suggests that the neural representation of groups is located in this area. Because this location is unexpected, we discuss several suggestions for future research to confirm this finding.
CRISPR-mediated activation of endogenous BST-2/tetherin expression inhibits wild-type HIV-1 production
Authors: Zhang Yanzhao , Ozono Seiya , Yao Weitong , Tobiume Minoru , Yamaoka Shoji , Kishigami Satoshi , Fujita Hideaki , Tokunaga Kenzo 
Published: February 2019

AbstractThe CRISPR technology not only can knock out target genes by using the RNA-guided Cas9 nuclease but also can activate their expression when a nuclease-deficient Cas9 (dCas9) is employed. Using the latter function, we here show the effect of the CRISPR-mediated pinpoint activation of endogenous expression of BST-2 (also known as tetherin), a virus restriction factor with a broad antiviral spectrum. Single-guide RNA (sgRNA) sequences targeting the BST-2 promoter were selected by promoter assays. Potential sgRNAs and dCas9 fused to the VP64 transactivation domain, along with an accessory transcriptional activator complex, were introduced into cells by lentiviral transduction. Increased expression of BST-2 mRNA in transduced cells was confirmed by real-time RT-PCR. Cells in which BST-2 expression was highly enhanced showed the effective inhibition of HIV-1 production and replication even in the presence of the viral antagonist Vpu against BST-2. These findings confirm that the physiological stoichiometry between host restriction factors and viral antagonists may determine the outcome of the battle with viruses.
Elevated red cell distribution width to platelet count ratio predicts poor prognosis in patients with breast cancer
Authors: Takeuchi Hideya , Abe Miyuki , Takumi Yohei , Hashimoto Takafumi , Miyawaki Michiyo , Okamoto Tatsuro , Sugio Kenji 
Published: February 2019

AbstractRed cell distribution width (RDW) to platelet ratio (RPR) is a prognosticator in acute pancreatitis and myocardial infarction; however, the prognostic values of RDW and RPR in breast cancer have not been studied. This retrospective analysis of 299 breast cancer patients investigated the association between RDW and RPR and clinicopathological characteristics and prognosis, compared to platelet distribution width to platelet count ratio (PDW/P) which is a known independent prognostic factor in patients with breast cancer. We found a significant correlation between RPR, and age and HER2 status. An elevated RPR significantly correlated with age and HER2 status. After a median follow-up duration of 48 months, tumour size, nuclear grade, PDW/P, and RPR were recgnized to be significantly associated with lower disease-free survival rates (tumour size: p < 0.01; nuclear grade, PDW/P, and RPR: p < 0.05) in univariate analysis. Tumour size and RPR were significant prognostic factors for lower disease-free survival rates, with hazard ratios of 4.31 (95% confidence interval: 1.76–10.53) (p < 0.01)] and 2.79 [95% confidence interval: 1.01–87.69) (p < 0.05)], respectively, in a multivariate analysis using the Cox proportional hazards model. This is the first study showing that an elevated RPR could independently predict poor prognosis in patients with breast carcinoma. Thus, RPR could be a novel biomarker for prognostic estimation.
Interplay of arene radical cations with anions and fluorinated alcohols in hole catalysis
Authors: Shida Naoki , Imada Yasushi , Nagahara Shingo , Okada Yohei , Chiba Kazuhiro 
Published: February 2019

AbstractChemical reactions via radical cation intermediates are of great interest in photoredox catalysis and electrosynthesis, while their reactivities are not clearly understood. For example, how the counter anions correlate with the reactivity of radical cations is still ambiguous. Here we report the effect of anions and fluorinated alcohols on the reactivity of organic radical cations in hole catalysis. The addition of salts in a radical cation Diels–Alder reaction under photoredox catalysis demonstrates that common anions significantly decease the efficiency of hole catalysis. The use of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) restores the reaction efficiency in the presence of salts, presumably due to solvation of the anions by HFIP to reduce their nucleophilicity. These findings enable hole catalysis under electrolytic conditions with greatly improved efficiency. The effect of anions and fluorinated alcohol described in this paper gives important insights on the fundamental understanding for the reactivity of arene radical cations.
Efficacy and Prognostic Factors of Combined Hyperbaric Oxygen Therapy in Patients With Idiopathic Sudden Sensorineural Hearing Loss
Authors: Wang Yong , Gao Yali , Wang Boxuan , Chen Liyan , Zhang Xiaoxiao 
Published: February 2019

Purpose
Idiopathic sudden sensorineural hearing loss is a clinical emergency with an increased incidence of occurrence in recent years. Hyperbaric oxygen has been widely used in the clinical treatment of sudden hearing loss. However, prognostic factors related to its curative effects are still not clear, which hinders its clinical application. The aim of this study was to investigate the efficacy and prognostic factors of hyperbaric oxygen therapy (HBOT) plus drug therapies in the treatment of sudden hearing loss.

Method
Patients with sudden hearing loss who were treated with hyperbaric oxygen from April to October 2017 were retrospectively included. Clinical information was collected, including pure-tone audiometry data before and after hyperbaric oxygen treatment, age, gender, hearing curve classification, concomitant symptoms, history of diseases (diabetes and hypertension), history of hormone therapy, start time of hyperbaric oxygen treatment, and total number of hyperbaric oxygen treatments. The prognostic factors were analyzed with univariate and multivariate analyses.

Results

Sixty-four patients with sudden hearing loss were enrolled, including 7 cases of low-frequency loss, 4 cases of high-frequency loss, 32 cases of flat loss, and 21 cases of complete hearing loss. After HBOT, there were 16 cases (25%) of complete recovery, 15 cases (23.43%) of partial recovery, 7 cases (10.93%) of slight improvement, and 26 cases (40.63%) of no improvement. The total effective rate was 59.37%. Twelve of 21 cases (57.14%) of complete hearing loss showed recovery. Multivariate logistic regression analysis showed that the start time of HBOT ≤ 7 days from disease onset was independently associated with hearing recovery (
OR
= 27.763, 95% CI [4.209, 183.115],
p
= .001).

Conclusion
Combined HBOT can improve the hearing impairment of sudden hearing loss. The early HBOT showed the most promising therapeutic effects, especially among patients with complete hearing loss.
Studies on metallurgical contamination accumulation characteristics on ceramic insulator of 500 kV AC transmission line
Authors: Lan Lei , Mu Lin , Yuan Xiaoqing , Yan Jing , Wang Yu , Wang Wei , Shen Yang , Hao Lu 
Published: February 2019

The composition of metallurgical contamination is rather special, which has a great influence on the contamination accumulation and flashover characteristics of the insulators. In this study, the 500 kV AC line insulators in metallurgical industry area of central China were sampled. The ion composition, element composition, micromorphology and particle size distribution of contamination at high and low end of insulator string were tested, respectively. The equivalent salt deposit density (ESDD) and non‐soluble deposit density (NSDD) of high‐voltage end, low‐voltage end and middle segment of three‐phase insulator strings were tested. The results indicate that the contamination particles are irregular in shape and dispersed with each other. The contamination particle size of high‐voltage end is larger than that of low‐voltage end. The main components of the contamination are Fe2O3 and CaSO4. The ESDD and NSDD of upper surface of upper phase is lower than that of middle phase and lower phase with the cleaning of rainwater. Due to the subsidence of metallurgical contamination from high altitude, the ESDD and NSDD of lower surface of the upper phase is higher than that of middle phase and lower phase. The ESDD and NSDD of lower surface of three phases reduce with the decrease of height.
Effects of composition and heat treatment on manganese–bismuth magnets
Authors: Sirisathitkul Chitnarong , Charoensuk Thanida 
Published: February 2019

Synchrotron X‐ray absorption near‐edge structure (XANES) spectra are used to complement X‐ray diffractometry (XRD) in the phase identification of pressed manganese–bismuth (MnBi) pellets. The heat treatment at 1000°C for 10 min after the synthesis improves the ferromagnetic properties. The magnetisation and coercive field are further enhanced when the Mn:Bi ratio is raised to 2:1. The obtained magnetic properties are related to the MnBi peaks in XRD patterns as well as the Mn‐edge XANES spectra. Although the spectra in the case of Mn:Bi ratio of 2:1 and 3:1 resemble that of MnO reference, the pre‐edge is shifted by the contribution of zero valent Mn and the peak intensity is reduced. A variety of phases in MnBi alloys dictate their magnetic properties required for permanent magnets and desirable ferromagnetic properties are governed by the increase of MnBi phase at the expense of MnO.
Co2 P/reduced graphene oxide nanocomposites and their multifunctional performances
Authors: Liu Shuling , Chen Yuanru , Wang Xiaojian , Wang Yueyan 
Published: February 2019

Cobalt phosphide/reduced graphene oxide (Co2 P/RGO) nanocomposites were synthesised successfully via a facile in‐situ solvothermal method. Co2 P nanoparticles with a mean size of 80 nm anchor uniformly and firmly on the surface of RGO nanosheets, which not only avoid the aggregation of Co2 P nanoparticles, but also prevent the restacking of RGO nanosheets. Used as a degradation agent, the as‐prepared composites exhibit superior adsorption degradation activity for various organic dyes. As an anode material for Li‐ion battery, the Co2 P/RGO composites also show good electrochemical properties and its initial discharge specific capacity of the as‐prepared composites can achieve to 900 mAh/g. The reason might be attributed to the interfacial interaction and the effective combination of Co2 P nanoparticles with RGO nanosheets.
CO2 vs. air insufflation in endoscopic ultrasonography: a prospective study
Authors: Serrani Marta , Lisotti Andrea , Spada Alessia , Sferrazza Sandro , Calvanese Claudio , Fusaroli Pietro 
Published: February 2019

Abstract
Background and study aims Carbon dioxide (CO2) is being increasingly used for insufflation during endoscopy for safety and better tolerance. The role of CO2 during endoscopic ultrasonography (EUS) has not been studied yet. Our main aim was to compare the effects of CO2 vs. air insufflation on abdominal discomfort in patients undergoing EUS. Our secondary outcomes were to ascertain the effects of CO2 insufflation on image quality/visual artifacts and on the amount of sedation.
Patients and methods This was a prospective, controlled, single-blind, observational study. Abdominal discomfort was assessed before diagnostic EUS, and 1 and 3 hours post-procedure and recorded as a visual analogue scale. Image quality was also recorded as a 4-point scale from optimal to poor at four different scanning sites (esophagus, stomach, duodenal bulb and second portion).
Results A total of 198 patients were enrolled. We observed that CO2 resulted in less abdominal discomfort than air insufflation that was statistically significant at 3 hours (P = 0.048) but not at 1 hour after EUS (P = 0.112), probably due to the ongoing effects of sedation at the latter stage. On the other hand, no differences were found in the dose of sedation administered in the two groups. Image quality was significantly better in the CO2 group compared to the air group at all four different scanning sites (P < 0.01). Similarly, CO2 correlated with less visual artifacts and need of suction (P < 0.01).
Conclusions Similarly to previous findings with other endoscopic procedures, EUS was associated with improved scores for abdominal discomfort with CO2 rather than air insufflation. Moreover, overall EUS image quality was improved using CO2 insufflation. Future studies are warranted to ascertain whether CO2 insufflation should be regarded as the standard of care for diagnostic EUS.