bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a novel human CIC-DUX4 sarcoma cell line, Kitra-SRS, with autocrine IGF-1R activation and metastatic potential to the lungs
Authors: Nakai Sho , Yamada Shutaro , Outani Hidetatsu , Nakai Takaaki , Yasuda Naohiro , Mae Hirokazu , Imura Yoshinori , Wakamatsu Toru , Tamiya Hironari , Tanaka Takaaki , Hamada Kenichiro , Tani Akiyoshi , Myoui Akira , Araki Nobuhito , Ueda Takafumi , Yoshikawa Hideki , Takenaka Satoshi , Naka Norifumi 
Published: November 2019

AbstractApproximately 60–70% of EWSR1-negative small blue round cell sarcomas harbour a rearrangement of CIC, most commonly CIC-DUX4. CIC-DUX4 sarcoma (CDS) is an aggressive and often fatal high-grade sarcoma appearing predominantly in children and young adults. Although cell lines and their xenograft models are essential tools for basic research and development of antitumour drugs, few cell lines currently exist for CDS. We successfully established a novel human CDS cell line designated Kitra-SRS and developed orthotopic tumour xenografts in nude mice. The CIC-DUX4 fusion gene in Kitra-SRS cells was generated by t(12;19) complex chromosomal rearrangements with an insertion of a chromosome segment including a DUX4 pseudogene component. Kitra-SRS xenografts were histologically similar to the original tumour and exhibited metastatic potential to the lungs. Kitra-SRS cells displayed autocrine activation of the insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) pathway. Accordingly, treatment with the IGF-1R inhibitor, linsitinib, attenuated Kitra-SRS cell growth and IGF-1-induced activation of IGF-1R/AKT signalling both in vitro and in vivo. Furthermore, upon screening 1134 FDA-approved drugs, the responses of Kitra-SRS cells to anticancer drugs appeared to reflect those of the primary tumour. Our model will be a useful modality for investigating the molecular pathology and therapy of CDS.
Covalently modified carboxyl side chains on cell surface leads to a novel method toward topology analysis of transmembrane proteins
Authors: Müller Anna , Langó Tamás , Turiák Lilla , Ács András , Várady György , Kucsma Nóra , Drahos László , Tusnády Gábor E. 
Published: October 2019

AbstractThe research on transmembrane proteins (TMPs) is quite widespread due to their biological importance. Unfortunately, only a little amount of structural data is available of TMPs. Since technical difficulties arise during their high-resolution structure determination, bioinformatics and other experimental approaches are widely used to characterize their low-resolution structure, namely topology. Experimental and computational methods alone are still limited to determine TMP topology, but their combination becomes significant for the production of reliable structural data. By applying amino acid specific membrane-impermeable labelling agents, it is possible to identify the accessible surface of TMPs. Depending on the residue-specific modifications, new extracellular topology data is gathered, allowing the identification of more extracellular segments for TMPs. A new method has been developed for the experimental analysis of TMPs: covalent modification of the carboxyl groups on the accessible cell surface, followed by the isolation and digestion of these proteins. The labelled peptide fragments and their exact modification sites are identified by nanoLC-MS/MS. The determined peptides are mapped to the primary sequences of TMPs and the labelled sites are utilised as extracellular constraints in topology predictions that contribute to the refined low-resolution structure data of these proteins.
Heparin and heparan sulfate proteoglycans promote HIV-1 p17 matrix protein oligomerization: computational, biochemical and biological implications
Authors: Bugatti Antonella , Paiardi Giulia , Urbinati Chiara , Chiodelli Paola , Orro Alessandro , Uggeri Matteo , Milanesi Luciano , Caruso Arnaldo , Caccuri Francesca , D’Ursi Pasqualina , Rusnati Marco 
Published: October 2019

Abstractp17 matrix protein released by HIV+ cells interacts with leukocytes heparan sulfate proteoglycans (HSPGs), CXCR1 and CXCR2 exerting different cytokine-like activities that contribute to AIDS pathogenesis. Since the bioactive form of several cytokines is represented by dimers/oligomers and oligomerization is promoted by binding to heparin or HSPGs, here we evaluated if heparin/HSPGs also promote p17 oligomerization. Heparin favours p17 dimer, trimer and tetramer assembly, in a time- and biphasic dose-dependent way. Heparin-induced p17 oligomerization is of electrostatic nature, being it prevented by NaCl, by removing negative sulfated groups of heparin and by neutralizing positive lysine residues in the p17 N-terminus. A new computational protocol has been implemented to study heparin chains up to 24-mer accommodating a p17 dimer. Molecular dynamics show that, in the presence of heparin, two p17 molecules undergo conformational modifications creating a continuous “electropositive channel” in which heparin sulfated groups interact with p17 basic amino acids, promoting its dimerization. At the cell surface, HSPGs induce p17 oligomerization, as demonstrated by using B-lymphoblastoid Namalwa cells overexpressing the HSPG Syndecan-1. Also, HSPGs on the surface of BJAB and Raji human B-lymphoblastoid cells are required to p17 to induce ERK1/2 activation, suggesting that HS-induced oligomerization plays a role in p17-induced lymphoid dysregulation during AIDS.
Spectral slowing is associated with working memory performance in children born very preterm
Authors: Sato Julie , Mossad Sarah I. , Wong Simeon M. , Hunt Benjamin A. E. , Dunkley Benjamin T. , Urbain Charline , Taylor Margot J. 
Published: October 2019

AbstractChildren born very preterm (VPT) often demonstrate selective difficulties in working memory (WM), which may underlie academic difficulties observed in this population. Despite this, few studies have investigated the functional networks underlying WM in young children born VPT, a period when cognitive deficits become apparent. Using magnetoencephalography, we examined the networks underlying the maintenance of visual information in 6-year-old VPT (n = 15) and full-term (FT; n = 20) children. Although task performance was similar, VPT children engaged different oscillatory mechanisms during WM maintenance. Within the FT group, we observed higher mean whole-brain connectivity in the alpha-band during the retention (i.e. maintenance) interval associated with correct compared to incorrect responses. VPT children showed reduced whole-brain alpha synchrony, and a different network organization with fewer connections. In the theta-band, VPT children demonstrated a slight increase in whole-brain connectivity during WM maintenance, and engaged similar network hubs as FT children in the alpha-band, including the left dorsolateral prefrontal cortex and superior temporal gyrus. These findings suggest that VPT children rely on the theta-band to support similar task performance. Altered oscillatory mechanisms may reflect a less mature pattern of functional recruitment underlying WM in VPT children, which may affect the processing in complex ecological situations.
Microplastics induce transcriptional changes, immune response and behavioral alterations in adult zebrafish
Authors: Limonta Giacomo , Mancia Annalaura , Benkhalqui Assja , Bertolucci Cristiano , Abelli Luigi , Fossi Maria Cristina , Panti Cristina 
Published: October 2019

AbstractMicroplastics have become pervasive environmental pollutants in both freshwater and marine ecosystems. The presence of microplastics have been recorded in the tissues of many wild fish species, and laboratory studies have demonstrated that microplastics can exert adverse health effects. To further investigate the biological mechanisms underlying microplastics toxicity we applied an integrated approach, analyzing the effects of microplastics at transcriptomic, histological and behavioral level. Adult zebrafish have been exposed to two concentrations of high-density polyethylene and polystyrene microplastics for twenty days. Transcriptomic results indicate alterations in the expression of immune system genes and the down-regulation of genes correlated with epithelium integrity and lipid metabolism. The transcriptomic findings are supported by tissue alterations and higher occurrence of neutrophils observed in gills and intestinal epithelium. Even the daily rhythm of activity of zebrafish appears to be affected, although the regular pattern of activity is recovered over time. Considering the transcriptomic and histological findings reported, we hypothesize that the effects on mucosal epithelium integrity and immune response could potentially reduce the organism defense against pathogens, and lead to a different utilization of energy stores.
Alleviation of murine osteoarthritis by deletion of the focal adhesion mechanosensitive adapter, Hic-5
Authors: Miyauchi Aya , Kim-Kaneyama Joo-ri , Lei Xiao-Feng , Chang Song Ho , Saito Taku , Haraguchi Shogo , Miyazaki Takuro , Miyazaki Akira 
Published: October 2019

AbstractExcessive mechanical stress is a major cause of knee osteoarthritis. However, the mechanism by which the mechanical stress begets osteoarthritis development remains elusive. Hydrogen peroxide-inducible clone-5 (Hic-5; TGFβ1i1), a TGF-β inducible focal adhesion adaptor, has previously been reported as a mediator of mechanotransduction. In this study, we analyzed the in vivo function of Hic-5 in development of osteoarthritis, and found that mice lacking Hic-5 showed a significant reduction in development of osteoarthritis in the knee. Furthermore, we found reduced expression of catabolic genes, such as metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 in osteoarthritic lesions in mice lacking Hic-5. During osteoarthritis development, Hic-5 is detected in chondrocytes of articular cartilage. To investigate the role of Hic-5 in chondrocytes, we isolated chondrocytes from articular cartilage of wild type and Hic-5-deficient mice. In these primary cultured chondrocytes, Hic-5 deficiency resulted in suppression of catabolic gene expression induced by osteoarthritis-related cytokines such as tumor necrosis factor α and interleukin 1β. Furthermore, Hic-5 deficiency in chondrocytes suppressed catabolic gene expression induced by mechanical stress. Revealing the regulation of chondrocyte catabolism by Hic-5 contributes to understanding the pathophysiology of osteoarthritis induced by mechanical stress.
Reflux finding score is associated with gastroesophageal flap valve status in patients with laryngopharyngeal reflux disease: a retrospective study
Authors: Wu Wei , Li Lianyong , Qu Changmin , Wang Min , Liang Shuwen , Gao Xiaopei , Bao Xinwei , Wang Lei , Liu Hongdan , Han Haolun , Xu Bingxin , Zhou Ying , Li Baowei , Zhang Yiyan , Wang Gang , Zhong Changqing 
Published: October 2019

AbstractEndoscopic grading of gastroesophageal flap valve (GEFV) is simple and reproducible and offers useful information for reflux activity. To investigate the potential correlation between GEFV grading and reflux finding score (RFS) in patients with laryngopharyngeal reflux disease (LPRD), 225 consecutive Patients with suspected LPRD who underwent both routine upper gastrointestinal endoscopy and laryngoscope were enrolled in our study. Patients with a RFS of more than 7 were diagnosed with LPRD. The GEFV was graded as I through IV according to Hill’s classification and was classified into two groups: normal GEFV group (grades I and II) and the abnormal GEFV group (grades III and IV). The percent of GEFV grades I to IV was 39.1%, 39.1%, 12.4%, and 9.3%, respectively. Age was significantly related to an abnormal GEFV (p = 0.002). Gender, BMI, smoke and alcohol were not related to GEFV grade. Fifty-one patients (22.67%) had positive RFS. Reflux finding scores were higher in GEFV grades III and IV than I and II (p < 0.05). Endoscopic grading of GEFV is well correlated with reflux finding score in patients with LPRD. This is a simple and useful technique that provides valuable diagnostic information of LPRD.
Decreasing hill density combined with increasing nitrogen rate led to yield decline in hybrid rice under low-light conditions
Authors: Ao Hejun , Xie Xiaobing , Huang Min , Zou Yingbin 
Published: October 2019

AbstractLow light is a common environmental factor that adversely affects rice yields. This study was conducted to evaluate the combined effect of hill density and nitrogen (N) fertilizer rate on yield attributes in hybrid rice under low-light conditions. Field experiments were conducted in 2014 and 2015. Two hybrid rice cultivars (Y-liangyou 1 and Luoyou 9348) were grown under combinations of three hill density levels (high, 40 × 104 hills ha−1; moderate, 27 × 104 hills ha−1; low, 14 × 104 hills ha−1) and two N rate levels (high, 240 kg ha−1; moderate, 143–148 kg ha−1), and shaded from heading to maturity. Grain yield was highest in the combination of high hill density and moderate N rate and significantly declined with decreasing hill density combined with increasing N rate for both cultivars in both years. Averaged across two cultivars and two years, grain yield declined by about 4% for each 10% decrease in hill density combined with each 10% increase in N rate. A significant reduction in spikelet filling percentage was observed with decreasing hill density combined with increasing N rate in Y-liangyou 1 in 2015 and Luoyou 9348 in 2014. The same trend was observed for grain weight in Y-liangyou 1 in 2014 and Luoyou 9348 in 2015. These results indicate that adopting the practice of decreasing hill density combined with increasing N rate can result in poor grain filling and consequently yield decline in hybrid rice under low-light conditions.
Comprehensive analysis of POLE and POLD1 Gene Variations identifies cancer patients potentially benefit from immunotherapy in Chinese population
Authors: Yao Jianfei , Gong Yuan , Zhao Wei , Han Zhifeng , Guo Shaohua , Liu Hongyi , Peng Xiumei , Xiao Wenhua , Li Yuemin , Dang Shiying , Liu Guifeng , Li Lifeng , Huang Tanxiao , Chen Shifu , Song Lele 
Published: October 2019

AbstractPOLE/POLD1 gene variants have been suggested as potential markers for immunotherapy due to their significant association with the tumor mutational burden (TMB), an effective indicator for response prediction in immunotherapy. However, the correlation of POLE/POLD1 variants with MSI, MMR, TMB, MMR-related and key driver gene mutations needs to be defined to support patient recruitment and therapeutic effect assessment in immunotherapy. 1,392 Chinese cancer patients were recruited, and the correlation of POLE/POLD1 variants with existing immunotherapeutic markers and cancer pathways was investigated. A next-generation sequencing panel including 605 cancer-related genes was used for variant sequencing. It was found that the frequency of POLE variants was not statistically different from that in COSMIC database, while the frequency of POLD1 variants was significantly higher in lung cancer. c.857 C > G and c.2091dupC were potential high frequency variants in Chinese cancer patients. Patients carrying POLE damaging variants were significantly younger than POLE/POLD1 WT patients. Patients carrying POLE/POLD1 damaging variants exhibited significantly higher TMB and frequency of MMR gene variants than POLE/POLD1 WT patients. Patients with POLE damaging variants also exhibited significantly higher frequency of driver gene variants than POLE/POLD1 WT patients. Further analysis showed that POLE damaging variants may affect the cancer development through MMR, TGFβ and RTK/RAS/RAF signaling pathways, and POLD1 through MMR pathways. In conclusion, this study identified key characteristics and regions of POLE/POLD1 genes that correlates with TMB, MMR gene mutations and key driver gene mutations, and provided theoretical and practical basis for patient selection based on POLE/POLD1 gene status in immunotherapy.
Size and distribution of the iron oxide nanoparticles in SBA-15 nanoporous silica via SANS study
Authors: Zeleňáková Adriana , Hrubovčák Pavol , Kapusta Ondrej , Kučerka Norbert , Kuklin Aleksander , Ivankov Oleksandr , Zeleňák Vladimír 
Published: November 2019

AbstractStructural characteristics of nanocomposite series consisting of iron oxide nanoparticles (NPs) embedded in the regular pores of amorphous silica matrix (SBA-15) were investigated by means of small angle neutron scattering (SANS). By virtue of unique neutron properties, insight into the inner structure and matter organization of this kind of systems was facilitated for the first time. Based on rigorous experimental support, fundamental model describing the neutron scattering intensity distribution was proposed by assuming general composite structural features. Model application to SANS data confirmed the presence of iron oxide NPs in the body of examined matrices, providing additional information on their shape, concentration and size distribution. Scattering superposition principle employed in the model conception allows for tailoring its fundamental characteristics, and renders it a potent and versatile tool for a wide range of applications.
In silico re-engineering of a neurotransmitter to activate KCNQ potassium channels in an isoform-specific manner
Authors: Manville Rían W. , Abbott Geoffrey W. 
Published: November 2019

AbstractVoltage-gated potassium (Kv) channel dysfunction causes a variety of inherited disorders, but developing small molecules that activate Kv channels has proven challenging. We recently discovered that the inhibitory neurotransmitter γ-aminobutyric acid (GABA) directly activates Kv channels KCNQ3 and KCNQ5. Here, finding that inhibitory neurotransmitter glycine does not activate KCNQs, we re-engineered it in silico to introduce predicted KCNQ-opening properties, screened by in silico docking, then validated the hits in vitro. Attaching a fluorophenyl ring to glycine optimized its electrostatic potential, converting it to a low-nM affinity KCNQ channel activator. Repositioning the phenyl ring fluorine and/or adding a methylsulfonyl group increased the efficacy of the re-engineered glycines and switched their target KCNQs. Combining KCNQ2- and KCNQ3-specific glycine derivatives synergistically potentiated KCNQ2/3 activation by exploiting heteromeric channel composition. Thus, in silico optimization and docking, combined with functional screening of only three compounds, facilitated re-engineering of glycine to develop several potent KCNQ activators.
Error shaping technique of capacitor mismatch and inter‐stage gain in noise shaping pipelined SAR ADCs
Authors: Shen Changsheng 
Published: October 2019

An error shaping (ES) technique in noise shaping pipelined successive approximation register (SAR) ADC is proposed to deal with capacitor mismatch and inter‐stage gain errors, which is immune from the variation of the process, voltage, and temperature. By adopting data‐weight average logic and delaying the reset of the second stage capacitors, all of the capacitor mismatch and inter‐stage gain errors are shaped. According to the simulation, the signal‐to‐noise and distortion ratio and spurious free dynamic range increase by about 15 and 20 dB after ES.
Intra-Procedural CT/MR-Ultrasound Fusion Imaging Helps to Improve Outcomes of Thermal Ablation for Hepatocellular Carcinoma: Results in 502 Nodules
Authors: Xu Erjiao , Li Kai , Long Yinglin , Luo Liping , Zeng Qingjing , Tan Lei , He Xuqi , Huang Qiannan , Wu Yuxuan , Zheng Rongqin 
Published: October 2019

AbstractPurpose The aim was to assess the value of intra-procedural CT/MR-ultrasound (CT/MR-US) fusion imaging in the management of thermal ablation for hepatocellular carcinoma (HCC).Materials and Methods This retrospective study was approved by the institutional review board. From May 2010 to October 2016, 543 HCC nodules in 440 patients (387 men and 53 women; age range: 25–84 years) that met the Milan Criteria were treated by percutaneous thermal ablation using intra-procedural CT/MR-US fusion imaging. The HCC nodules were divided into subgroups and compared (≤ 3 cm and > 3 cm, or high-risk and low-risk location, or inconspicuous and conspicuous, respectively). Technique efficacy and major complication were calculated. Cumulative local tumor progression (LTP), tumor-free and overall survival rates were estimated with the Kaplan-Meier method.Results CT/MR-US fusion imaging was successfully registered in 419 patients with 502 nodules. The technique efficacy rate of thermal ablation was 99.4 %. The major complication rate was 1.9 %. The cumulative LTP rates were 3.2 %, 5.6 % and 7.2 % at 1, 3, and 5 years, respectively. There were no significant differences for the comparisons of cumulative LTP rates between different subgroups (P = 0.541, 0.314, 0.329). The cumulative tumor-free survival rates were 74.8 %, 54.0 % and 37.5 % at 1, 3, and 5 years, respectively. The cumulative overall survival rates were 97.8 %, 87.1 % and 81.7 % at 1, 3, and 5 years, respectively.Conclusion Intra-procedural CT/MR-ultrasound fusion imaging is a useful technique for percutaneous liver thermal ablation. It could help to achieve satisfying survival outcomes for HCC patients who meet the Milan Criteria.
Postablation Immune Microenvironment: Synergy between Interventional Oncology and Immuno-oncology
Authors: Kim DaeHee , Erinjeri Joseph P. 
Published: October 2019

AbstractCurrent tumor thermal ablation techniques rely on extreme temperatures to induce irreversible cellular injury and coagulative tissue necrosis. Ablation-induced cellular injury or death releases cancer neoantigens and activates the cancer-immunity cycle, potentially generating tumor-specific immune effectors. However, multiple negative regulatory modulators exist at each step of the cycle, mitigating meaningful and therapeutic anticancer effect provided by the immune system. Recent studies have focused on the introduction and testing of adjuvant immunotherapy combined with ablation to synergistically shift the equilibrium out of inhibitory immune modulation. This article reviews the immune microenvironment in relation to image-guided ablation techniques and discusses current and upcoming novel strategies to take advantage of antitumor immunity.
Lipoma arborescente en bursa bicipito-radial del codo: A propósito de un caso
Authors: Pérez Alba Jose Manuel , Gázquez Gázquez Gemma 
Published: October 2019

ResumenEl lipoma arborescente es un tumor infrecuente, a pesar de ello se trata de un tumor que es más frecuente en la rodilla. Entre los diagnósticos diferenciales se encuentra la sinovitis villonodular, y otra serie de enfermedades articulares. El lipoma arborescente se suele presentar con clínica de derrame articular. En el caso que presentamos, la paciente acudía principalmente por tumoración en el antebrazo y síntomas de parestesias y disestesias en 2° y 3er dedos de la mano. Tras una adecuada exploración física y pruebas complementarias, fue diagnosticada de un Lipoma arborescente en la bursa bicipitoradial que generaba una compresión del N mediano a ese nivel. Tras la resección de la tumoración la paciente mejoró de su clínica.