bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells
Authors: Mazor Gal , Levin Liron , Picard Daniel , Ahmadov Ulvi , Carén Helena , Borkhardt Arndt , Reifenberger Guido , Leprivier Gabriel , Remke Marc , Rotblat Barak 
Published: March 2019

AbstractGlioblastoma multiform (GBM) is the most common brain tumor characterized by a dismal prognosis. GBM cancer stem cells (gCSC) or tumor-initiating cells are the cell population within the tumor-driving therapy resistance and recurrence. While temozolomide (TMZ), an alkylating agent, constitutes the first-line chemotherapeutic significantly improving survival in GBM patients, resistance against this compound commonly leads to GBM recurrence and treatment failure. Although the roles of protein-coding transcripts, proteins and microRNA in gCSC, and therapy resistance have been comprehensively investigated, very little is known about the role of long noncoding RNAs (lncRNAs) in this context. Using nonoverlapping, independent RNA sequencing and gene expression profiling datasets, we reveal that TP73-AS1 constitutes a clinically relevant lncRNA in GBM. Specifically, we demonstrate significant overexpression of TP73-AS1 in primary GBM samples, which is particularly increased in the gCSC. More importantly, we demonstrate that TP73-AS1 comprises a prognostic biomarker in glioma and in GBM with high expression identifying patients with particularly poor prognosis. Using CRISPRi to downregulate our candidate lncRNA in gCSC, we demonstrate that TP73-AS1 promotes TMZ resistance in gCSC and is linked to regulation of the expression of metabolism- related genes and ALDH1A1, a protein known to be expressed in cancer stem cell markers and protects gCSC from TMZ treatment. Taken together, our results reveal that high TP73-AS1 predicts poor prognosis in primary GBM cohorts and that this lncRNA promotes tumor aggressiveness and TMZ resistance in gCSC.
Amyloid β oligomers suppress excitatory transmitter release via presynaptic depletion of phosphatidylinositol-4,5-bisphosphate
Authors: He Yang , Wei Mengdi , Wu Yan , Qin Huaping , Li Weinan , Ma Xiaolin , Cheng Jingjing , Ren Jinshuai , Shen Ye , Chen Zhong , Sun Binggui , Huang Fu-De , Shen Yi , Zhou Yu-Dong 
Published: March 2019

AbstractAmyloid β (Aβ) oligomer-induced aberrant neurotransmitter release is proposed to be a crucial early event leading to synapse dysfunction in Alzheimer’s disease (AD). In the present study, we report that the release probability (Pr) at the synapse between the Schaffer collateral (SC) and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Aβ production. High nanomolar synthetic oligomeric Aβ42 also suppresses Pr at the SC-CA1 synapse in wild-type mice. This Aβ-induced suppression of Pr is mainly due to an mGluR5-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PIP2) in axons. Selectively inhibiting Aβ-induced PIP2 hydrolysis in the CA3 region of the hippocampus strongly prevents oligomeric Aβ-induced suppression of Pr at the SC-CA1 synapse and rescues synaptic and spatial learning and memory deficits in APP/PS1 mice. These results first reveal the presynaptic mGluR5-PIP2 pathway whereby oligomeric Aβ induces early synaptic deficits in AD.
AKF-PD alleviates diabetic nephropathy via blocking the RAGE/AGEs/NOX and PKC/NOX Pathways
Authors: Qin Jiao , Peng Zhangzhe , Yuan QiongJing , Li Qian , Peng Yu , Wen Rui , Hu Zhaolan , Liu Jun , Xia Xiongfang , Deng Hong , Xiong Xuan , Hu Jinyue , Tao Lijian 
Published: March 2019

AbstractDiabetic nephropathy (DN) is a major complication of diabetes. Currently, drugs are not available to effectively control the disease. Fluorofenidone (AKF-PD) is a recently developed drug; it possesses activities in reducing DN progression in preclinical research. Nonetheless, its renal protection and the underlying mechanisms have not been thoroughly investigated. We report here that AKF-PD significantly alleviatesrenal oxidative stress (OS) in db/dbmice through downregulation of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase and upregulation of glutathione peroxidase and superoxide dismutase, thereby protecting kidney from DN pathogenesis. AKF-PD likely reduces OS through the advanced glycation end products (AGE) and protein kinase C (PKC) pathways. While renal AGEs, PKCα, PKCβ, and NADPH oxidase 4 (NOX4) were all substantially upregulated in db/db mice compared to db/m animals, AKF-PD robustly downregulated all these events to the basal levelsdetected in db/m mice. In primary human renal mesangial cells (HMCs), high glucose (HG) elevated receptor for advanced glycation endproducts (RAGE), PKCα, PKCβ and NOX4 activity, and induced the production of reactive oxygen species (ROS); these events were all inhibited by AKF-PD. Furthermore, HG led to mitochondrial damagein HMCs;AKF-PD conferred protection on the damage. Knockdown of either PKCα or PKCβ reduced HG-induced ROS production and mitochondrial damage in HMCs. The knockdown significantly enhanced AKF-PD-mediated inhibition of ROS production and mitochondrial damage in HG-treated HMCs. Collectively, our study demonstrates that AKF-PD protects renal function under diabetes conditions in part through inhibition of OS during DN pathogenesis. AKF-PD can be explored for clinical applications in DN therapy.
The immunosuppressant drug azathioprine restrains adipogenesis of muscle Fibro/Adipogenic Progenitors from dystrophic mice by affecting AKT signaling
Authors: Reggio Alessio , Spada Filomena , Rosina Marco , Massacci Giorgia , Zuccotti Alessandro , Fuoco Claudia , Gargioli Cesare , Castagnoli Luisa , Cesareni Gianni 
Published: March 2019

AbstractFibro/Adipogenic Progenitors (FAPs) define a stem cell population playing a pro-regenerative role after muscle damage. When removed from their natural niche, FAPs readily differentiate into adipocytes or fibroblasts. This digressive differentiation potential, which is kept under tight control in the healthy muscle niche, contributes to fat and scar infiltrations in degenerative myopathies, such as in Duchenne Muscular Dystrophy (DMD). Controlling FAP differentiation by means of small molecules may contribute to delay the adverse consequences of the progressive pathological degeneration while offering, at the same time, a wider temporal window for gene therapy and cell-based strategies. In a high content phenotypic screening, we identified the immunosuppressant, azathioprine (AZA) as a negative modulator of FAP adipogenesis. We show here that AZA negatively affects the adipogenic propensity of FAPs purified from wild type and mdx mice by impairing the expression of the master adipogenic regulator, peroxisome proliferator-activated receptor γ (PPARγ). We show that this inhibition correlates with a decline in the activation of the AKT-mTOR axis, the main pathway that transduces the pro-adipogenic stimulus triggered by insulin. In addition, AZA exerts a cytostatic effect that has a negative impact on the mitotic clonal process that is required for the terminal differentiation of the preadipocyte-committed cells.
Effects of Black Raspberries and Their Ellagic Acid and Anthocyanin Constituents on Taxane Chemotherapy of Castration-Resistant Prostate Cancer Cells
Authors: Eskra Jillian N. , Schlicht Michael J. , Bosland Maarten C. 
Published: March 2019

AbstractCancer patients often use dietary supplements while on therapy, but little is known about interactions of supplements with cancer chemotherapy. Black raspberries (BRB) have anti-cancer effects, but have not been evaluated for interference with chemotherapy for castrate-resistant prostate cancer (CRPC). Here we studied whether BRB and some of their constituents interact with docetaxel and cabazitaxel on CRPC cells in culture and implanted into nude mice. Ellagic acid increased, but BRB extract inhibited, microtubule assembly. Ellagic acid decreased tubulin polymerization by cabazitaxel and bound to tubulin. Ellagic acid, its metabolite urolithin A, BRB extract, and the anthocyanin metabolite protocatechuic acid (PCA) did not alter cytotoxicity of taxanes. Ellagic acid inhibited drug efflux in CRPC cells, but BRB extract and PCA did not. None of these compounds altered CYP3A4 activity. Although dietary ellagic acid did not alter the tumor growth inhibition by docetaxel of xenografted 22Rv1 cells, ellagic acid has the potential to interfere with taxane chemotherapy by reducing tubulin polymerization while inhibiting P-glycoprotein drug efflux. These data are cause for concern of consuming ellagic acid during treatment for CRPC and indicate need for further research, but BRB consumption appears safe.
Early Detection of Tomato Spotted Wilt Virus by Hyperspectral Imaging and Outlier Removal Auxiliary Classifier Generative Adversarial Nets (OR-AC-GAN)
Authors: Wang Dongyi , Vinson Robert , Holmes Maxwell , Seibel Gary , Bechar Avital , Nof Shimon , Tao Yang 
Published: March 2019

AbstractTomato spotted wilt virus is a wide-spread plant disease in the world. It can threaten thousands of plants with a persistent and propagative manner. Early disease detection is expected to be able to control the disease spread, to facilitate management practice, and further to guarantee accompanying economic benefits. Hyperspectral imaging, a powerful remote sensing tool, has been widely applied in different science fields, especially in plant science domain. Rich spectral information makes disease detection possible before visible disease symptoms showing up. In the paper, a new hyperspectral analysis proximal sensing method based on generative adversarial nets (GAN) is proposed, named as outlier removal auxiliary classifier generative adversarial nets (OR-AC-GAN). It is an all-in-one method, which integrates the tasks of plant segmentation, spectrum classification and image classification. The model focuses on image pixels, which can effectively visualize potential plant disease positions, and keep experts’ attention on these diseased pixels. Meanwhile, this new model can improve the performances of classic spectrum band selection methods, including the maximum variance principle component analysis (MVPCA), fast density-peak-based clustering, and similarity-based unsupervised band selection. Selecting spectrum wavebands reasonably is an important preprocessing step in spectroscopy/hyperspectral analysis applications, which can reduce the computation time for potential in-field applications, affect the prediction results and make the hyperspectral analysis results explainable. In the experiment, the hyperspectral reflectance imaging system covers the spectral range from 395 nm to 1005 nm. The proprosed model makes use of 83 bands to do the analysis. The plant level classification accuracy gets 96.25% before visible symptoms shows up. The pixel prediction false positive rate in healthy plants gets as low as 1.47%. Combining the OR-AC-GAN with three existing band selection algorithms, the performance of these band selection models can be significantly improved. Among them, MVPCA can leverage only 8 spectrum bands to get the same plant level classification accuracy as OR-AC-GAN, and the pixel prediction false positive rate in healthy plants is 1.57%, which is also comparable to OR-AC-GAN. This new model can be potentially transferred to other plant diseases detection applications. Its property to boost the performance of existing band selection methods can also accelerate the in-field applications of hyperspectral imaging technology.
Community-Based Event Detection in Temporal Networks
Authors: Moriano Pablo , Finke Jorge , Ahn Yong-Yeol 
Published: March 2019

AbstractWe propose a method for detecting large events based on the structure of temporal communication networks. Our method is motivated by findings that viral information spreading has distinct diffusion patterns with respect to community structure. Namely, we hypothesize that global events trigger viral information cascades that easily cross community boundaries and can thus be detected by monitoring intra- and inter-community communications. By comparing the amount of communication within and across communities, we show that it is possible to detect events, even when they do not trigger a significantly larger communication volume. We demonstrate the effectiveness of our method using two examples—the email communication network of Enron and the Twitter communication network during the Boston Marathon bombing.
Earthquake segmentation in northern Chile correlates with curved plate geometry
Authors: Shrivastava Mahesh N. , González Gabriel , Moreno Marcos , Soto Hugo , Schurr Bernd , Salazar Pablo , Báez Juan Carlos 
Published: March 2019

AbstractWe performed an integrated analysis of the coseismic slip, afterslip and aftershock activity of the 2014 Mw8.1 Pisagua earthquake. This earthquake seems to be spatially located between two major historical earthquakes, the 1868 Mw8.8 earthquake in southern Peru and the 1877 Mw8.5 earthquake in northern Chile. Continuous GPS data were used to model the coseismic slip of the mainshock and the largest aftershock (Mw7.6). The afterslip was modeled for 273 days (end of year 2014) after the largest aftershock, revealing two patches of afterslip: a southern patch between the mainshock and the largest aftershock and a patch to the north of the mainshock. Observations from the seismic network indicate that aftershocks were concentrated near the southern patch. Conversely, the northern patch contained hardly any aftershocks, indicating a dominant aseismic slip. The Pisagua earthquake occurred within a prominent, curved section of the Andean subduction zone. This section may have acted as a barrier for the largest historical earthquakes and as an isolated segment during the Pisagua earthquake.
Prognostic Impact of Carboxylesterase 2 in Cholangiocarcinoma
Authors: Goeppert Benjamin , Renner Marcus , Singer Stephan , Albrecht Thomas , Zhang Qiangnu , Mehrabi Arianeb , Pathil Anita , Springfeld Christoph , Köhler Bruno , Rupp Christian , Weiss Karl Heinz , Kühl Anja A. , Arsenic Ruza , Pape Ulrich Frank , Vogel Arndt , Schirmacher Peter , Roessler Stephanie , Utku Nalân 
Published: March 2019

AbstractCarboxylesterase 2 (CES2) is instrumental for conversion of ester-containing prodrugs in cancer treatment. Novel treatment strategies are exceedingly needed for cholangiocarcinoma (CCA) patients. Here, we assessed CES2 expression by immunohistochemistry in a CCA cohort comprising 171 non-liver fluke associated, intrahepatic (n = 72) and extrahepatic (perihilar: n = 56; distal: n = 43) CCAs. Additionally, 80 samples of high-grade biliary intraepithelial neoplastic tissues and 158 corresponding samples of histological normal, non-neoplastic biliary tract tissues were included. CES2 expression was highest in non-neoplastic biliary tissue and significantly decreased in CCA. Patients showing any CES2 expression in tumor cells had a significantly better overall survival compared to negative cases (p = 0.008). This survival benefit was also maintained after stratification of CES2-positive cases, by comparing low, medium and high CES2 expression levels (p-trend = 0.0006). Evaluation of CCA subtypes showed the survival difference to be restricted to extrahepatic tumors. Correlation of CES2 expression with data of tumor-infiltrating immune cells showed that particularly CD8+ T cells were more frequently detected in CES2-positive CCAs. Furthermore, treatment of CCA cell lines with the prodrug Irinotecan reduced cell viability, increased cytotoxicity and modulated inflammatory gene expression. In conclusion, reduced CES2 expression is associated with poor outcome and low CD8+ T cell infiltration in CCA patients. Further clinical studies could show, whether CES2 expression may serve as a predictive marker in patients treated with prodrugs converted by CES2.
Sustained response to symmetry in extrastriate areas after stimulus offset: An EEG study
Authors: Bertamini Marco , Rampone Giulia , Oulton Jennifer , Tatlidil Semir , Makin Alexis D. J. 
Published: March 2019

AbstractElectrophysiological (EEG) studies of human perception have found that amplitude at posterior electrodes is more negative for symmetrical patterns compared to asymmetrical patterns. This negativity lasts for hundreds of milliseconds and it has been called sustained posterior negativity (SPN). Symmetry activates a network of visual areas, including the lateral occipital complex (LOC). The SPN is a response to presence of symmetry in the image. Given the sustained nature of this activation, in this study we tested the persistence of the SPN after stimulus offset. Two shapes were presented (for 0.5 s each) with a 1 s blank interval in between. We observed a sustained response after stimulus offset, irrespective of whether the task required processing of shape information. This supports the idea that the response to symmetry is generated by information in the image, independently of task, and that it is sustained over approximately one second post stimulus onset.
Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
Authors: Thiem Kathrin , Hoeke Geerte , van den Berg Susan , Hijmans Anneke , Jacobs Cor W. M. , Zhou Enchen , Mol Isabel M. , Mouktaroudi Maria , Bussink Johan , Kanneganti Thirumala D. , Lutgens Esther , Stienstra Rinke , Tack Cees J. , Netea Mihai G. , Rensen Patrick C. N. , Berbée Jimmy F. P. , van Diepen Janna A. 
Published: March 2019

AbstractInflammatory reactions activated by pattern recognition receptors (PRRs) on the membrane of innate immune cells play an important role in atherosclerosis. Whether the PRRs of the C-type lectin receptor (CLR) family including Dectin-2 may be involved in the pathogenesis of atherosclerosis remains largely unknown. Recently, the CLR-adaptor molecule caspase recruitment domain family member 9 (CARD9) has been suggested to play a role in cardiovascular pathologies as it provides the link between CLR activation and transcription of inflammatory cytokines as well as immune cell recruitment. We therefore evaluated whether hematopoietic deletion of Dectin-2 or CARD9 reduces inflammation and atherosclerosis development. Low-density lipoprotein receptor (Ldlr)-knockout mice were transplanted with bone marrow from wild-type, Dectin-2- or Card9-knockout mice and fed a Western-type diet containing 0.1% (w/w) cholesterol. After 10 weeks, lipid and inflammatory parameters were measured and atherosclerosis development was determined. Deletion of hematopoietic Dectin-2 or CARD9 did not influence plasma triglyceride and cholesterol levels. Deletion of hematopoietic Dectin-2 did not affect atherosclerotic lesion area, immune cell composition, ex vivo cytokine secretion by peritoneal cells or bone marrow derived macrophages. Unexpectedly, deletion of hematopoietic CARD9 increased atherosclerotic lesion formation and lesion severity. Deletion of hematopoietic CARD9 did also not influence circulating immune cell composition and peripheral cytokine secretion. Besides a tendency to a reduced macrophage content within these lesions, plasma MCP-1 levels decreased upon WTD feeding. Deletion of hematopoietic Dectin-2 did not influence atherosclerosis development in hyperlipidemic mice. The absence of CARD9 unexpectedly increased atherosclerotic lesion size and severity, suggesting that the presence of CARD9 may protect against initiation of atherosclerosis development.
Tsunamigenic potential of crustal faults and subduction zones in the Mediterranean
Authors: Petricca Patrizio , Babeyko Andrey Y. 
Published: March 2019

AbstractWe compiled a database and systematically evaluated tsunamigenic potential of all up-to-date known crustal fault systems and subduction zones in the entire Mediterranean region that has experienced several catastrophic tsunamis in historical times. The task is accomplished by means of numerical modeling of tsunami generation and propagation. We have systematically simulated all representative ruptures populating known crustal faults and subduction interfaces with magnitudes ranging from 6.1 up to expected Mwmax. Maximum tsunami heights calculated everywhere along the coasts allowed us to classify the sources in terms of their tsunamigenic potential and to estimate their minimum tsunamigenic magnitude. Almost every source in the Mediterranean, starting from Mw = 6.5, is capable to produce local tsunami at the advisory level (wave height >20 cm and ≤50 cm). In respect to the watch level (wave height >50 cm) larger magnitudes are needed (Mw ≥ 6.9). Faults behave more heterogeneously in the context of far field early warning. De-aggregation of the database at any selected coastal location can reveal relevant sources of tsunami hazard for this location. Our compilation blueprints methodology that, if completed with source recurrence rates and site-specific amplification factors, can be considered as a backbone for development of optimal early warning strategies by Mediterranean tsunami warning providers.
A comparison study of radiation effective dose in ECG-Gated Coronary CT Angiography and calcium scoring examinations performed with a dual-source CT scanner
Authors: Sabarudin Akmal , Siong Tiong Wei , Chin Ang Wee , Hoong Ng Kwan , Karim Muhammad Khalis Abdul 
Published: March 2019

AbstractIn this report we have evaluated radiation effective dose received by patients during ECG-gated CCTA examinations based on gender, heart rate, tube voltage protocol and body mass index (BMI). A total of 1,824 patients were retrospectively recruited (1,139 men and 685 women) and they were divided into Group 1 (CCTA with calcium scoring), Group 2 (CCTA without calcium scoring) and Group 3 (only calcium scoring), where the association between gender, heart rate, tube voltage protocol and body mass index (BMI) were analysed. Examinations were performed using a retrospective ECG-gated CCTA protocol and the effective doses were calculated from the dose length product with a conversion coefficient of 0.026 mSv.mGy−1cm−1. No significant differences were observed in the mean effective dose between gender in all groups. The mean estimated dose was significantly higher when the heart rate was lower in Group 1 (p < 0.001) and Group 2 (p = 0.002). There were also significant differences between the mean effective dose in tube voltage protocol and BMI among the three groups. The mean effective dose was positively correlated with BMI (p < 0.001), but inversely related to the heart rate. This study supported the theory that a high heart rate, low tube voltage and low BMI could significantly reduce radiation dose exposure.