bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial and temporal responses of metastatic renal cell carcinoma lesions to sequential treatments over a 10‐year period
Authors: Kobayashi Hirohito , Takagi Toshio , Iizuka Junpei , Yoshida Kazuhiko , Kondo Tsunenori , Tanabe Kazunari 
Published: December 2018

IntroductionSurvival among patients with metastatic renal cell carcinoma has been prolonged with advancements in treatment; however, its cure remains challenging. We describe three patients with metastatic renal cell carcinoma who showed long‐term survival and discuss their response to sequential therapy.Case presentationThree patients underwent radical nephrectomy and subsequent treatment for metastatic renal cell carcinoma. They received cytokine therapy, target therapy, and an immuno‐oncology drug. Metastatic growth patterns based on computed tomography scans were plotted using a line or bar graph to visualize the response to sequential therapy, and the numbers of International Metastatic renal cell carcinoma Database Consortium risk score were also calculated.ConclusionThe metastatic lesions responded differently to the administered drugs, and the sum of the axis of measurable metastasis is valuable to get an overview of treatment. Furthermore, having the same or lower International Metastatic renal cell carcinoma Database Consortium risk score during sequential therapy, and long duration of each target therapy contributed to prolonged survival.
Photofunctionalizing effects of hydroxyapatite combined with TiO2 on bone regeneration in rabbit calvarial defects
Authors: Kim Shin‐Young , Bark Chung Wung , Van Quy Hoang , Seo Seung‐Jun , Lim Jae‐Hong , Lee Jae‐Mok , Suh Jo‐Young , Lee Youngkyun , Um Heung‐Sik , Kim Yong‐Gun 
Published: December 2018

AbstractThe hydrophilicity of bone graft material generally used as a carrier can play an important role in regulating bone morphogenetic protein (BMP) expression at the bone graft site. The hydrophilicity, altering physicochemical properties, and enhancing biological capabilities, can be increased via surface modification through ultraviolet (UV) photofunctionalization and the effect on de novo osteogenesis could be further improved. Therefore, this study aimed to assess the effects of UV‐irradiated TiO2‐coated hydroxyapatite (HA) in combination with rhBMP‐2 on bone regeneration in rabbit calvarial defects.The hydrophilicity of HA and TiO2‐coated HA pellets was evaluated by measuring the contact angle of water droplets with UV irradiation. To compare de novo osteogenesis in rabbit calvarial defects, the rabbits were segregated into four different groups: negative control, HA, TiO2‐coated HA, and TiO2‐coated HA with UV; histomorphometric analysis and micro‐computed tomography (μCT) imaging were performed after 4 and 8 weeks.
In vivo analysis revealed that de novo osteogenesis occurred on the critical size defects in all groups and was significantly increased in the TiO2‐coated HA with UV group than in other groups (p < 0.05). The present results indicate that UV photofunctionalization promotes de novo osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1953–1959, 2019.
A four‐gene signature predicts the efficacy of paclitaxel‐based neoadjuvant therapy in human epidermal growth factor receptor 2–negative breast cancer
Authors: Li Zhi , Zhang Ye , Zhang Zhe , Zhao Zhenkun , Lv Qingjie 
Published: December 2018

AbstractNeoadjuvant chemotherapy (NAC) is the major preoperative treatment of breast cancer (BC) with negative human epidermal growth factor receptor 2 (HER2), and the efficacy of NAC and the optimization of regimen are under intensive research. The current study aimed to define the predictive biomarkers for paclitaxel (PTX) response in NAC of HER2‐negative BC. Data from GSE25065, GSE26065, GSE41998, as well as drug sensitivity data of breast and ovarian cancer cell line from NCI60, were used. Through logistic regression, COX regression, and correlation analysis with bootstrapping, we found that four genes (CDK8, FAM64A, MARC2, and OCEL1) were associated with drug sensitivity of PTX. The four gene “≥3” model had the best classification accuracy. Subgroup analysis found that the model performed well in the hormone receptor positive, HER2‐negative subgroup and did not perform well in the triple‐negative subgroup. Decision curve analysis showed that the model could enhance the predictive effect of clinical features. Subsequent gene set enrichment analysis, network analysis showed that these genes may be related to the cell cycle, mitosis and other pathways. The current study demonstrated the promising potential of the novel four‐gene signature as a predictive biomarker for pathological complete response of HER2‐negative BC patients and indicated the drug sensitivity of PTX.
Yak OXGR1 promotes fibroblast proliferation via the PI3K/AKT pathways
Authors: Wang Qi , Zhang Quanwei , Zhang Yong , Zhao Xingxu 
Published: December 2018

AbstractOxoglutarate receptor 1 (OXGR1), as one of the intermediates in G protein‐coupled receptors (GPCRs), plays a crucial role in the citric acid cycle receptor of α‐ketoglutarate and metabolism. GPCR can control the cell proliferation by regulating the downstream signaling of G protein signaling pathways. The PI3K/AKT pathway transmits the downstream signals of GPCRs and receptor tyrosine kinases. However, the speciﬁc role of
OXGR1 promoting cell proliferation and differentiation are still unknown. In current study, the over‐expression vector and knockdown sequence of yak
OXGR1 were transfected into yak fibroblasts, and the effects were detected by a series of assays. The results revealed that
OXGR1 expression in yak lung parenchyma tissue was significantly higher than that of other tissues. In yak fibroblasts, the upregulated expression of
OXGR1 resulted in activating the
PIK3CG (downstream signal) of the PI3K/AKT1 pathway that can upregulated the expression of proliferation genes (
CDK1, PCNA, and
CyclinD1) and promote cell proliferation. Conversely, the downregulated expression of
OXGR1 inhibited cell proliferation via PI3K/AKT1 pathway. Cell cycle and cell proliferation assays demonstrated that over‐expression of
OXGR1 can enhanced the DNA synthesis and promoted yak fibroblasts proliferation. While the conversely, knockdown of
OXGR1 can decreased DNA synthesis and inhibited cell proliferation. These results illustrated that changes of
OXGR1 expression can trigger the fibroblasts proliferation via PI3K/AKT signaling pathway, which indicating that
OXGR1 is a novel regulator for cell proliferation and differentiation. Furthermore, these results provide evidence supporting the functional role of GPCRs‐PI3K‐AKT1 and
OXGR1 in cell proliferation.
RETRACTED: Downregulation of fibroblast growth factor 5 inhibits cell growth and invasion of human nonsmall‐cell lung cancer cells
Authors: Zhou Yanjuan , Yu Qiuhua , Chu Ying , Zhu Xiaobo , Deng Jianzhong , Liu Qian , Wang Qiang 
Published: December 2018

AbstractThe morbidity and mortality rates of nonsmall‐cell lung cancer (NSCLC) have increased in recent years. We aimed to explore the biological role of fibroblast growth factor 5 (FGF5) in NSCLC. We first established that the expression of FGF5 was increased in NSCLC tissues compared with the normal adjacent tissues. The expression of FGF5 was also increased in NSCLC cell lines. The effect of FGF5 silencing on cell proliferation, cell cycle, apoptosis, migration, and invasion of H661 and CALU1 cells was then examined. Downregulation of FGF5 significantly inhibited cell proliferation and induced G1 phase cell cycle arrest compared with the negative control small interfering (siNC) groups. Cell apoptosis was promoted by siFGF5 treatment. Cell migration and invasion of H661 and CALU1 cells with siFGF5 transfection were markedly diminished compared with the siNC groups. In addition, migration and invasion‐associated proteins (E‐cadherin, matrix metalloproteinase‐2 [MMP‐2], and MMP‐9) and epithelial mesenchymal transition markers (N‐cadherin, vimentin, snail, and slug) were also regulated by FGF5 siRNA treatment. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) cell cycle and vascular endothelial growth factor (VEGF) pathways were correlated with FGF5 expression, which was further confirmed in NSCLC cells by Western blot analysis. Our results indicated that FGF5 silencing suppressed cell growth and invasion via regulation of the cell cycle and VEGF pathways. Therefore, FGF5 may serve as a promising therapeutic strategy for NSCLC.
alpha1A‐adrenoceptor is involved in norepinephrine‐induced proliferation of pulmonary artery smooth muscle cells via CaMKII signaling
Authors: Luo Qian , Wang Xiaoyan , Liu Ruxia , Qiao Hui , Wang Peng , Jiang Chao , Zhang Qianlong , Cao Yonggang , Yu Hang , Qu Lihui 
Published: December 2018

AbstractPulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Some studies have demonstrated the sympathetic nervous system is activated in PAH and norepinephrine (NE) released is closely linked with its activation. However, the subtypes of adrenoreceptor (AR) and the downstream molecular cascades which are involved in the proliferation of PASMCs are still unclear. In this study, adult male Wistar rats were exposed to chronic hypoxia and PASMCs were cultured in hypoxic condition. Significant upregulation of α1A‐AR was identified by Western blot analysis or immunofluorescence in all of the pulmonary arteries, lung tissues, and cell hypoxic models. Western blot analysis, flow cytometry, and immunofluorescence were applied to detect the roles of α1A‐AR in NE mediated proliferation of PASMCs. We revealed 5‐methylurapidil (5‐MU) reversed NE‐induced upregulation of PCNA, CyclinA and CyclinE, more cells from G0/G1 phase to G2/M+S phase, enhancement of the microtubule formation. In addition, we found calcium/calmodulin(CaM)‐dependent protein kinase type II (CaMKII) pathway was involved in α1A‐AR‐mediated cell proliferation. [Ca2+]i measurements showed that an increase of [Ca2+]i caused by NE or/and hypoxia could be blocked by 5‐MU in PASMCs. Western blot analysis results demonstrated the augmentation of CaMKII phosphorylation level was caused by hypoxia or NE in pulmonary arteries, lung tissues, and PASMCs. KN62 attenuated NE‐induced proliferation of PASMCs under normoxia and hypoxia. In conclusion, those results suggested NE which stimulated α1A‐AR‐mediated the proliferation of PASMCs, which may be via the CaMKII pathway, and it could be used as a novel treatment strategy in PAH.
Long noncoding RNA HAND2‐AS1 inhibits cancer cell proliferation, migration, and invasion in esophagus squamous cell carcinoma by regulating microRNA‐21
Authors: Yan Yusheng , Li Shaobin , Wang Suihai , Rubegni Pietro , Tognetti Linda , Zhang Jiaqing , Yan Lu 
Published: December 2018

AbstractLong noncoding RNA (lncRNA) HAND2‐AS1 is a well‐characterized tumor suppressor in several types of malignancies, while its role in esophagus squamous cell carcinoma (ESCC) is unknown. In this study, we found that lncRNA
HAND2‐AS1 was downregulated, while
microRNA‐21 (
miRNA‐21) was upregulated in tumor tissues than in adjacent healthy tissues of ESCC patients. Expression levels of lncRNA
HAND2‐AS1 and
miRNA‐21 were significantly and inversely correlated in tumor tissues but not in healthy tissues. Plasma levels of lncRNA
HAND2‐AS1 were lower in ESCC patients than in healthy controls, and downregulation of plasma lncRNA HAND2‐AS1 distinguished early stage ESCC patients from healthy controls. lncRNA
HAND2‐AS1 overexpression resulted in downregulation of
miRNA‐21 in cells of ESCC cell lines and inhibited cell proliferation, migration, and invasion.
miRNA‐21 overexpression failed to affect lncRNA
HAND2‐AS1 expression but significantly attenuated the inhibitory effect of lncRNA
HAND2‐AS1 overexpression on cancer cell proliferation, migration, and invasion. Therefore, lncRNA
HAND2‐AS1 may inhibit cancer cell proliferation, migration, and invasion in ESCC by regulating
miRNA‐21.
Twelve‐year Follow‐up of A Large Italian Family with Atypical Phenotypes of DYT1‐dystonia
Authors: Magrinelli Francesca , Bacchin Ruggero , Tinazzi Michele , Gambarin Mattia 
Published: December 2018

AbstractBackgroundA heterozygous mutation in the TOR1A gene (DYT1) accounts for isolated dystonia typically presenting during childhood or adolescence, with initial involvement of one limb, spreading rapidly to other limbs and the trunk, sparing craniocervical muscles. However, atypical phenotypes, regarding age at onset, site of presentation, and spreading have been reported.Methods and FindingsIn 2006, we described a large Italian family showing atypical phenotypes and intrafamilial clinical variability of DYT1‐dystonia. The current article reports on a 12‐year follow‐up of this family, focusing on disease onset in three previously asymptomatic DYT1 mutation carriers, and the reassessment of initially affected individuals.ConclusionsThe new cases confirm the intrafamilial phenotypic heterogeneity of DYT1‐dystonia. Moreover, this case series highlights that symptoms in atypical phenotypes seem not to spread significantly and in the long term, rarely worsen. Prolonged follow‐up of DYT1‐positive pedigrees may expand the clinical spectrum of DYT1‐dystonia.
Differentially fed CP antenna with quasi‐self‐complementary semicircular‐ring structure
Authors: Lee Ching‐Her , Hong Wan‐Chu , Chen Wen‐Jie , Hsu Chung‐I G. 
Published: December 2018

AbstractThis article presents a new design of a common‐mode suppressed differentially fed circularly polarized (CP) antenna using a quasi‐self‐complementary (QSC) structure. The antenna radiating element consists of a semicircular‐ring radiating patch and its complementary radiating slot counterpart. The design idea for producing CP radiation is based on field orthogonality of the QSC structure. For better impedance matching, a fan‐shaped notch (stub) around the feeding position was cut from (implemented in) the semicircular radiating patch (slot). In addition, to improve the axial ratio, a QSC semielliptical structure is embedded in the central area of the antenna. For the designed differentially fed CP antenna, measurement shows that the differential‐mode (DM) operating band with return loss >10 dB covers 4.76‐6.38 GHz. The measured DM 3‐dB axial‐ratio band is 4.95‐5.43 GHz. Also, very good common‐mode (CM) suppression is observed with the measured CM reflection coefficient >−1.21 dB in 4.50‐6.5 GHz.
PPICurator: A Tool for Extracting Comprehensive Protein–Protein Interaction Information
Authors: Li Mansheng , He Qiang , Ma Jie , He Fuchu , Zhu Yunping , Chang Cheng , Chen Tao 
Published: December 2018

AbstractProtein–protein interaction extraction through biological literature curation is widely employed for proteome analysis. There is a strong need for a tool that can assist researchers in extracting comprehensive PPI information through literature curation, which is critical in research on protein, for example, construction of protein interaction network, identification of protein signaling pathway, and discovery of meaningful protein interaction. However, most of current tools can only extract PPI relations. None of them are capable of extracting other important PPI information, such as interaction directions, effects, and functional annotations. To address these issues, this paper proposes PPICurator, a novel tool for extracting comprehensive PPI information with a variety of logic and syntax features based on a new support vector machine classifier. PPICurator provides a friendly web‐based user interface. It is a platform that automates the extraction of comprehensive PPI information through literature, including PPI relations, as well as their confidential scores, interaction directions, effects, and functional annotations. Thus, PPICurator is more comprehensive than state‐of‐the‐art tools. Moreover, it outperforms state‐of‐the‐art tools in the accuracy of PPI relation extraction measured by F‐score and recall on the widely used open datasets. PPICurator is available at https://ppicurator.hupo.org.cn.
Photochemical generation of 9‐Fluorenyl radicals
Authors: Duffy Ian R. , Leigh William J. , Afifi Hanan , Ebead Abdelaziz , Fournier René , Lee‐Ruff Edward 
Published: December 2018

AbstractA series of 9H‐fluorenols and 9H, 9′H‐bifluorenyls were irradiated in less polar solvents giving photoproducts derived from their corresponding 9H‐fluorenyl radicals. These transient species were directly observed by laser flash photolysis and their UV/visible spectra compared with those of their corresponding cations. Theoretical calculations (density functional theory [DFT]) of these intermediates indicate their destabilizing nature in similar fashion to the antiaromatic character of the corresponding cations.
The influence of intrinsic folding mechanism of an unfolded protein on the coupled folding‐binding process during target recognition
Authors: Xiong Junwen , Gao Meng , Zhou Jingjing , Liu Sen , Su Zhengding , Liu Zhirong , Huang Yongqi 
Published: December 2018

AbstractIntrinsically disordered proteins (IDPs) are extensively involved in dynamic signaling processes which require a high association rate and a high dissociation rate for rapid binding/unbinding events and at the same time a sufficient high affinity for specific recognition. Although the coupled folding‐binding processes of IDPs have been extensively studied, it is still impossible to predict whether an unfolded protein is suitable for molecular signaling via coupled folding‐binding. In this work, we studied the interplay between intrinsic folding mechanisms and coupled folding‐binding process for unfolded proteins through molecular dynamics simulations. We first studied the folding process of three representative IDPs with different folded structures, that is, c‐Myb, AF9, and E3 rRNase. We found the folding free energy landscapes of IDPs are downhill or show low barriers. To further study the influence of intrinsic folding mechanism on the binding process, we modulated the folding mechanism of barnase via circular permutation and simulated the coupled folding‐binding process between unfolded barnase permutant and folded barstar. Although folding of barnase was coupled to target binding, the binding kinetics was significantly affected by the intrinsic folding free energy barrier, where reducing the folding free energy barrier enhances binding rate up to two orders of magnitude. This accelerating effect is different from previous results which reflect the effect of structure flexibility on binding kinetics. Our results suggest that coupling the folding of an unfolded protein with no/low folding free energy barrier with its target binding may provide a way to achieve high specificity and rapid binding/unbinding kinetics simultaneously.
Co‐occurrence of V1016I and F1534C mutations in the voltage‐gated sodium channel and resistance to pyrethroids in Aedes aegypti (L.) from the Colombian Caribbean region
Authors: Maestre‐Serrano Ronald , Pareja‐Loaiza Paula , Gomez Camargo Doris , Ponce‐García Gustavo , Flores Adriana E 
Published: December 2018

AbstractBACKGROUNDKnockdown resistance is conferred primarily by non‐synonymous mutations that reduce pyrethroids binding to voltage‐gated sodium channels. In 2014, kdr mutation V1016I in Aedes aegypti populations resistant to pyrethroids was reported for the first time in Colombiα, in 2016 another kdr mutation, F1534C, and in 2018 the mutation V419L. Nine populations of A. aegypti, previously characterized as being resistant to λ‐cyhalothrin, deltamethrin, cyfluthrin and permethrin, were used for this study. Genomic DNA was used to determine genotypes by allele‐specific PCR for mutations V1016I and F1534C, and to determine their association with pyrethroid resistance.RESULTSAll the populations analyzed showed both mutations, with allelic frequencies of 0.07–0.35 for I1016 and 0.47–0.88 for C1534. A percentage of co‐occurrence of mutant homozygotes I1016/C1534 of 5.3% was detected. A significant positive correlation was found between the frequency of the genotype I1016 and the resistance to permethrin, λ‐cyhalothrin and cyfluthrin, but not to deltamethrin; on the other hand, the correlation was not significant for the C1534 genotype and the four pyrethroids evaluated. No significant correlation was found between the frequencies of the mutations V1016I and F1534C.CONCLUSIONSBoth mutations V1016I and F1534C are present in A. aegypti populations of the Colombian Caribbean, and although the frequency of F1534C exceeds V1016I, the latter was correlated to resistance to pyrethroid insecticides. © 2018 Society of Chemical Industry
Relativistic effects on the ring current strengths of the substituted borazine: B3N3H6 (X=H, F, Cl, Br, I, At)
Authors: Rabanal‐León Walter A. , Tiznado William , Alvarez‐Thon Luis 
Published: December 2018

AbstractIn this study, we report about the relativistic effects on the aromaticity of borazine, B3N3H6, and their halogenated derivatives (B3N3F6, B3N3Cl6, B3N3Br6, B3N3I6, and B3N3At6), via the magnetically‐induced current density method. All‐electron density functional theory calculations were carried out using the four‐component Dirac‐Coulomb hamiltonian, including scalar and spin‐orbit relativistic effects. Ring current strengths were obtained by numerical integration over the current flow. These values were compared to the spin‐free (scalar relativistic) and nonrelativistic values, to assess the corresponding contributions to aromaticity. It was found that in B3N3I6 and B3N3At6 there exists a significant spin‐orbit influence, in line with the expected relativistic effects associated to the heavy elements, iodine, and astatine.Borazine, B3N3H6, is known to be slightly aromatic, but much less aromatic than benzene. The application of an external magnetic field induces a current density, that accounts for the delocalization and mobility of electrons in a molecule. Using this theoretical method, the aromaticity of the derivatives B3N3X6(X = H, F, Cl, Br, I, At) was investigated. The inclusion of heavy elements requires a relativistic treatment where the spin‐orbit coupling must be included. The figure shows the three‐dimensional pathways of the current density flow in B3N3At6.
Pattern formation using polystyrene benzaldimine self‐assembled monolayer by soft X‐ray
Authors: Channapura Halappa Chandrashekhar , Park So‐Jin 
Published: December 2018

A nanopatterning fabrication by soft X‐ray generated chemical construction of a polystyrene benzaldehydeimine monolayer has been carried out from the polystyrenebezaldehyde resin with (3‐aminopropyl) triethoxysilane for the first time. The molecular layer was exposed to soft X‐rays; the involved chemical modification on the monolayer was analyzed by using Fourier transform infrared spectroscopy‐attenuated total internal reflectance and contact angle measurement. As a result, we could confirm that the imine monolayer was cleaved upon the soft X‐ray irradiation, leaving the hydrophobic part, the imine functionality was changed into a new nonhydrolysable, and the hydrophilic amine functionality was established from the unexposed imine monolayer through acid hydrolysis. This above phenomenon is used for the patterning of self‐assembled monolayers. The microscope images revealed patterns as small as ≤52.4 nm with regular height and phase variations.