bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report
Authors: Zhang Wen-ying , Wang Yao , Guo Ye-lei , Dai Han-ren , Yang Qing-ming , Zhang Ya-jing , Zhang Yan , Chen Mei-xia , Wang Chun-meng , Feng Kai-chao , Li Su-xia , Liu Yang , Shi Feng-xia , Luo Can , Han Wei-dong 
Published: March 2016

AbstractPatients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis. Chimeric Antigen Receptor (CAR)-modified T cells (CART cells) that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas. We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART (CART-20) cells to patients with refractory or relapsed CD20+ B-cell lymphoma. Eleven patients were enrolled, and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions. The overall objective response rate was 9 of 11 (81.8%), with 6 complete remissions (CRs) and 3 partial remissions; no severe toxicity was observed. The median progression-free survival lasted for >6 months, and 1 patient had a 27-month continuous CR. A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed. Clinically, the lesions in special sites, specifically the spleen and testicle, were refractory to CART-20 treatment. Collectively, these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study. This study was registered at www.clinicaltrials.org as NCT01735604.
Precession and nutation dynamics of nonlinearly coupled non-coaxial three-dimensional matter wave vortices
Authors: Driben R. , Konotop V. V. , Meier T. 
Published: March 2016

AbstractNonlinearity is the driving force for numerous important effects in nature typically showing transitions between different regimes, regular, chaotic or catastrophic behavior. Localized nonlinear modes have been the focus of intense research in areas such as fluid and gas dynamics, photonics, atomic and solid state physics etc. Due to the richness of the behavior of nonlinear systems and due to the severe numerical demands of accurate three-dimensional (3D) numerical simulations presently only little knowledge is available on the dynamics of complex nonlinear modes in 3D. Here, we investigate the dynamics of 3D non-coaxial matter wave vortices that are trapped in a parabolic potential and interact via a repulsive nonlinearity. Our numerical simulations demonstrate the existence of an unexpected and fascinating nonlinear regime that starts immediately when the nonlinearity is switched-on and is characterized by a smooth dynamics representing torque-free precession with nutations. The reported motion is proven to be robust regarding various effects such as the number of particles, dissipation and trap deformations and thus should be observable in suitably designed experiments. Since our theoretical approach, i.e., coupled nonlinear Schrödinger equations, is quite generic, we expect that the obtained novel dynamical behavior should also exist in other nonlinear systems.
An implantable compound-releasing capsule triggered on demand by ultrasound
Authors: Ordeig Olga , Chin Sau Yin , Kim Sohyun , Chitnis Parag V. , Sia Samuel K. 
Published: March 2016

AbstractImplantable devices have a large potential to improve human health, but they are often made of biofouling materials that necessitate special coatings, rely on electrical connections for external communication, and require a continuous power source. This paper demonstrates an alternative platform, which we call iTAG (implantable thermally actuated gel), where an implanted capsule can be wirelessly controlled by ultrasound to trigger the release of compounds. We constructed a millimeter-sized capsule containing a co-polymer gel (NiPAAm-co-AAm) that contracts above body temperature (i.e. at 45 °C) to release compounds through an opening. This gel-containing capsule is biocompatible and free of toxic electronic or battery components. An ultrasound hardware, with a focused ultrasound (FUS) transducer and a co-axial A-mode imaging transducer, was used to image the capsule (to monitor in real time its position, temperature, and effectiveness of dose delivery), as well as to trigger a rapid local rise in temperature, contraction of gel, and release of compounds in vitro and in vivo. The combination of this gel-based capsule and compact ultrasound hardware can serve as a platform for triggering local release of compounds, including potentially in deep tissue, to achieve tailored personalized therapy.
Determination of cyanidin 3-glucoside in rat brain, liver and kidneys by UPLC/MS-MS and its application to a short-term pharmacokinetic study
Authors: Fornasaro Stefano , Ziberna Lovro , Gasperotti Mattia , Tramer Federica , Vrhovšek Urška , Mattivi Fulvio , Passamonti Sabina 
Published: March 2016

AbstractAnthocyanins exert neuroprotection in various in vitro and in vivo experimental models. However, no details regarding their brain-related pharmacokinetics are so far available to support claims about their direct neuronal bioactivity as well as to design proper formulations of anthocyanin-based products. To gather this missing piece of knowledge, we intravenously administered a bolus of 668 nmol cyanidin 3-glucoside (C3G) in anaesthetized Wistar rats and shortly after (15 s to 20 min) we collected blood, brain, liver, kidneys and urine samples. Extracts thereof were analysed for C3G and its expected metabolites using UPLC/MS-MS. The data enabled to calculate a set of pharmacokinetics parameters. The main finding was the distinctive, rapid distribution of C3G in the brain, with an apparently constant plasma/brain ratio in the physiologically relevant plasma concentration range (19–355 nM). This is the first report that accurately determines the distribution pattern of C3G in the brain, paving the way to the rational design of future tests of neuroprotection by C3G in animal models and humans.
Reusable nanosilver-coated magnetic particles for ultrasensitive SERS-based detection of malachite green in water samples
Authors: Song Dan , Yang Rong , Wang Chongwen , Xiao Rui , Long Feng 
Published: March 2016

AbstractA novel nanosilver-deposited silica-coated Fe3O4 magnetic particle (Fe3O4@SiO2@Ag) with uniform size, good SERS activity and magnetic responsiveness was synthesized using amination polymer. The Fe3O4@SiO2@Ag magnetic particles have been successfully applied for ultrasensitive SERS detection of malachite green (MG) in water samples. The mechanism is that MG can be adsorbed on the silver surface of nanosilver-coated magnetic particles via one nitrogen atom and the Raman signal intensity of MG is significantly enhanced by the nanosilver layer formed on the magnetic particles. The developed sensing system exhibited a sensitive response to MG in the range of 10 fM to 100 μM with a low limit of detection (LOD) 2 fM under optimal conditions. The LOD was several orders of magnitude lower than those of other methods. This SERS-based sensor showed good reproducibility and stability for MG detection. The silver-coated magnetic particles could easily be regenerated as SERS substrates only using low pH solution for multiple sensing events. The recovery of MG added to several water samples at different concentrations ranged from 90% to 110%. The proposed method facilitates the ultrasensitive analysis of dyes to satisfy the high demand for ensuring the safety of water sources.
Superconductivity of novel tin hydrides (SnnHm) under pressure
Authors: Mahdi Davari Esfahani M. , Wang Zhenhai , Oganov Artem R. , Dong Huafeng , Zhu Qiang , Wang Shengnan , Rakitin Maksim S. , Zhou Xiang-Feng 
Published: March 2016

AbstractWith the motivation of discovering high-temperature superconductors, evolutionary algorithm USPEX is employed to search for all stable compounds in the Sn-H system. In addition to the traditional SnH4, new hydrides SnH8, SnH12and SnH14are found to be thermodynamically stable at high pressure. Dynamical stability and superconductivity of tin hydrides are systematically investigated. I"Equation missing"m2-SnH8, C2/m-SnH12and C2/m-SnH14exhibit higher superconducting transition temperatures of 81, 93 and 97 K compared to the traditional compound SnH4 with Tcof 52 K at 200 GPa. An interesting bent H3–group in I"Equation missing"m2-SnH8and novel linear H"Equation missing"in C2/m-SnH12are observed. All the new tin hydrides remain metallic over their predicted range of stability. The intermediate-frequency wagging and bending vibrations have more contribution to electron-phonon coupling parameter than high-frequency stretching vibrations of H2 and H3.
In silico assessment of primers for eDNA studies using PrimerTree and application to characterize the biodiversity surrounding the Cuyahoga River
Authors: Cannon M. V. , Hester J. , Shalkhauser A. , Chan E. R. , Logue K. , Small S. T. , Serre D. 
Published: March 2016

AbstractAnalysis of environmental DNA (eDNA) enables the detection of species of interest from water and soil samples, typically using species-specific PCR. Here, we describe a method to characterize the biodiversity of a given environment by amplifying eDNA using primer pairs targeting a wide range of taxa and high-throughput sequencing for species identification. We tested this approach on 91 water samples of 40 mL collected along the Cuyahoga River (Ohio, USA). We amplified eDNA using 12 primer pairs targeting mammals, fish, amphibians, birds, bryophytes, arthropods, copepods, plants and several microorganism taxa and sequenced all PCR products simultaneously by high-throughput sequencing. Overall, we identified DNA sequences from 15 species of fish, 17 species of mammals, 8 species of birds, 15 species of arthropods, one turtle and one salamander. Interestingly, in addition to aquatic and semi-aquatic animals, we identified DNA from terrestrial species that live near the Cuyahoga River. We also identified DNA from one Asian carp species invasive to the Great Lakes but that had not been previously reported in the Cuyahoga River. Our study shows that analysis of eDNA extracted from small water samples using wide-range PCR amplification combined with high-throughput sequencing can provide a broad perspective on biological diversity.
Pathways for Modulating Exosome Lipids Identified By High-Density Lipoprotein-Like Nanoparticle Binding to Scavenger Receptor Type B-1
Authors: Angeloni Nicholas L. , McMahon Kaylin M. , Swaminathan Suchitra , Plebanek Michael P. , Osman Iman , Volpert Olga V. , Thaxton C. Shad 
Published: March 2016

AbstractExosomes are produced by cells to mediate intercellular communication and have been shown to perpetuate diseases, including cancer. New tools are needed to understand exosome biology, detect exosomes from specific cell types in complex biological media and to modify exosomes. Our data demonstrate a cellular pathway whereby membrane-bound scavenger receptor type B-1 (SR-B1) in parent cells becomes incorporated into exosomes. We tailored synthetic HDL-like nanoparticles (HDL NP), high-affinity ligands for SR-B1, to carry a fluorescently labeled phospholipid. Data show SR-B1-dependent transfer of the fluorescent phospholipid from HDL NPs to exosomes. Modified exosomes are stable in serum and can be directly detected using flow cytometry. As proof-of-concept, human serum exosomes were found to express SR-B1 and HDL NPs can be used to label and isolate them. Ultimately, we discovered a natural cellular pathway and nanoparticle-receptor pair that enables exosome modulation, detection and isolation.
Chloroquine enhances TRAIL-mediated apoptosis through up-regulation of DR5 by stabilization of mRNA and protein in cancer cells
Authors: Park Eun Jung , Min Kyoung-jin , Choi Kyeong Sook , Kubatka Peter , Kruzliak Peter , Kim Dong Eun , Kwon Taeg Kyu 
Published: March 2016

AbstractChloroquine (CQ), an anti-malarial drug, has immune-modulating activity and lysosomotropic activity. In this study, we investigated CQ sensitizes TRAIL-mediated apoptosis in human renal cancer Caki cells. Combination of CQ and TRAIL significantly induces apoptosis in human renal cancer Caki cells and various human cancer cells, but not in normal mouse kidney cells (TMCK-1) and human mesangial cells (MC). CQ up-regulates DR5 mRNA and protein expression in a dose- and time- dependent manner. Interestingly, CQ regulates DR5 expression through the increased stability in the mRNA and protein of DR5, rather than through the increased transcriptional activity of DR5. Moreover, we found that CQ decreased the expression of Cbl, an E3 ligase of DR5, and knock-down of Cbl markedly enhanced DR5 up-regulation. Other lysosomal inhibitors, including monensin and nigericin, also up-regulated DR5 and sensitized TRAIL-mediated apoptosis. Therefore, this study demonstrates that lysosomal inhibition by CQ may sensitize TRAIL-mediated apoptosis in human renal cancer Caki cells via DR5 up-regulation.
Study of individual erythrocyte deformability susceptibility to INFeD and ethanol using a microfluidic chip
Authors: Liu Lihong , Huang Sha , Xu Xiaoying , Han Jongyoon 
Published: March 2016

AbstractHuman red blood cells (RBCs) deformability in vitro was assessed during iron dextran (INFeD) loading and/or ethanol co-administration using microfluidic deformability screening. The results showed donor-specific variations in dose dependent deformability shift were revealed below 500 μg/mL iron dextran. Two out of nine blood samples exhibited significant cell stiffening at 500 μg/mL iron dextran loading concentration (p < 0.05, Tukey test). More interestingly, co-administration of moderate amount of ethanol was identified to have significant protective effects on RBC deformability. We also noted that ethanol can reverse the deformability of impaired RBCs. Meanwhile obvious donor dependent response to ethanol administration on RBC deformability was noted using our biomimetic microfluidic chip.
Association between secondary thrombocytosis and viral respiratory tract infections in children
Authors: Zheng Shou-Yan , Xiao Qiu-Yan , Xie Xiao-Hong , Deng Yu , Ren Luo , Tian Dai-Yin , Luo Zheng-Xiu , Luo Jian , Fu Zhou , Huang Ai-Long , Liu En-Mei 
Published: March 2016

AbstractSecondary thrombocytosis (ST) is frequently observed in children with a variety of clinical conditions. The leading cause of ST is respiratory tract infection (RTI) in children. Nasopharyngeal aspirate samples were collected and assessed for common respiratory viruses. The relationships between virus infections and secondary thrombocytosis were analyzed retrospectively. The blood platelet count and the presence of respiratory viruses were determined for 3156 RTI patients and 817 (25.9%) cases with platelet ≥500 × 109/L were considered as the thrombocytosis group. Compared with the normal group, the detection rates of respiratory syncytial virus (RSV) and human rhinovirus (HRV) were significantly higher in the thrombocytosis group (P = 0.017 and 0.042, respectively). HRV single infection was a risk factor associated with thrombocytosis [odds ratio (OR) = 1.560, 95% confidence interval (CI) = 1.108–2.197]. Furthermore, ST was more likely to occur in younger patients who had clinical manifestations of wheezing and dyspnea and who had been diagnosed with bronchiolitis. Furthermore, the course of disease lasted longer in these patients. ST is associated with viral respiratory tract infections, especially RSV and HRV infections. HRV single infection is a risk factor associated with thrombocytosis.
The Wnt/β-catenin signaling/Id2 cascade mediates the effects of hypoxia on the hierarchy of colorectal-cancer stem cells
Authors: Dong Hye-Jin , Jang Gyu-Beom , Lee Hwa-Yong , Park Se-Ra , Kim Ji-Young , Nam Jeong-Seok , Hong In-Sun 
Published: March 2016

AbstractHypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have not been examined in detail. In the present study, we showed that hypoxia specifically promoted the self-renewal potential of CSCs. Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44+ subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression.
Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content
Authors: Ruiz-Zapata Alejandra M. , Kerkhof Manon H. , Ghazanfari Samaneh , Zandieh-Doulabi Behrouz , Stoop Reinout , Smit Theo H. , Helder Marco N. 
Published: March 2016

AbstractPelvic organ prolapse (POP) is characterised by the weakening of the pelvic floor support tissues, and often by subsequent prolapse of the bladder outside the body, i.e. cystocele. The bladder is kept in place by the anterior vaginal wall which consists of a dense extracellular matrix rich in collagen content that is maintained and remodelled by fibroblastic cells, i.e. fibroblasts and myofibroblasts. Since altered matrix production influences tissue quality, and myofibroblasts are involved in normal and pathological soft tissue repair processes, we evaluated matrix production of cells derived from pre- and post-menopausal POP and non-POP control anterior vaginal wall tissues. Results showed that cells from postmenopausal POP women deposited matrices with high percentage of collagen fibres with less anisotropic orientation and increased stiffness than those produced by controls. There was a transient increase in myofibroblastic phenotype that was lost after the peak of tissue remodelling. In conclusion, affected fibroblasts from postmenopausal prolapsed tissues produced altered matrices in vitro compared to controls. Such aberrant altered matrix production does not appear to be a consequence of abnormal phenotypical changes towards the myofibroblastic lineage.
Extensible Multiplex Real-time PCR of MicroRNA Using Microparticles
Authors: Jung Seungwon , Kim Junsun , Lee Dong Jin , Oh Eun Hae , Lim Hwasup , Kim Kwang Pyo , Choi Nakwon , Kim Tae Song , Kim Sang Kyung 
Published: March 2016

AbstractMultiplex quantitative real-time PCR (qPCR), which measures multiple DNAs in a given sample, has received significant attention as a mean of verifying the rapidly increasing genetic targets of interest in single phenotype. Here we suggest a readily extensible qPCR for the expression analysis of multiple microRNA (miRNA) targets using microparticles of primer-immobilized networks as discrete reactors. Individual particles, 200~500 μm in diameter, are identified by two-dimensional codes engraved into the particles and the non-fluorescent encoding allows high-fidelity acquisition of signal in real-time PCR. During the course of PCR, the amplicons accumulate in the volume of the particles with high reliability and amplification efficiency over 95%. In a quick assay comprising of tens of particles holding different primers, each particle brings the independent real-time amplification curve representing the quantitative information of each target. Limited amount of sample was analyzed simultaneously in single chamber through this highly multiplexed qPCR; 10 kinds of miRNAs from purified extracellular vesicles (EVs).
Activation of c-Jun predicts a poor response to sorafenib in hepatocellular carcinoma: Preliminary Clinical Evidence
Authors: Chen Wei , Xiao Weikai , Zhang Kunsong , Yin Xiaoyu , Lai Jiaming , Liang Lijian , Chen Dong 
Published: March 2016

AbstractWe determined the mitogen-activated protein kinase (MAPK) gene expression profile of acquired resistance in sorafenib-sensitive hepatocellular carcinoma (HCC) cells and aimed to identify c-Jun as an important molecule mediating the efficacy of sorafenib. Differences in gene expression of the MAPK signaling between untreated and sorafenib-treated HCC cell lines were investigated using real-time polymerase chain reaction array. Western blot and real-time PCR further evaluated the expression of c-Jun. Pathological specimens from 50 patients with advanced HCC were collected to measure p-c-Jun expression. Sorafenib-resistant HCC cells demonstrated greater levels of basal c-Jun mRNA and protein compared with sorafenib-sensitive HCC cells. Sorafenib activated p-c-Jun in a dose- and time-dependent manner in PLC/PRF/5 and MHCC97H cell lines. Decreased expression levels of 6 genes after sorafenib treatment suggested a robust inhibitory impact of sorafenib on MAPK signaling in HCC cells. c-Jun and p-c-Jun expression levels were inversely correlated with the efficacy of sorafenib; a high expression level of p-c-Jun was associated with resistance to sorafenib and poor overall survival in patients with clinical HCC. p-c-Jun may act as a biomarker for predicting responses of sorafenib treatment, thus advocating targeting of JNK/c-Jun signaling as an optimal therapeutic strategy in a subset of HCC.
Hierarchical TiO2 spheres as highly efficient polysulfide host for lithium-sulfur batteries
Authors: Yang Zhi-Zheng , Wang Hui-Yuan , Lu Lun , Wang Cheng , Zhong Xiao-Bin , Wang Jin-Guo , Jiang Qi-Chuan 
Published: March 2016

AbstractHierarchical TiO2 micron spheres assembled by nano-plates were prepared through a facile hydrothermal route. Chemical tuning of the TiO2 through hydrogen reduction (H-TiO2) is shown to increase oxygen-vacancy density and thereby modifies the electronic properties. H-TiO2 spheres with a polar surface serve as the surface-bound intermediates for strong polysulfides binding. Under the restricting and recapturing effect, the sulfur cathode could deliver a high reversible capacity of 928.1 mA h g−1 after 50 charge-discharge cycles at a current density of 200 mA g−1. The H-TiO2 additive developed here is practical for restricting and recapturing the polysulfide from the electrolyte.
Evolution of conditional cooperation under multilevel selection
Authors: Zhang Huanren , Perc Matjaž 
Published: March 2016

AbstractWe study the emergence of conditional cooperation in the presence of both intra-group and inter-group selection. Individuals play public goods games within their groups using conditional strategies, which are represented as piecewise linear response functions. Accordingly, groups engage in conflicts with a certain probability. In contrast to previous studies, we consider continuous contribution levels and a rich set of conditional strategies, allowing for a wide range of possible interactions between strategies. We find that the existence of conditional strategies enables the stabilization of cooperation even under strong intra-group selection. The strategy that eventually dominates in the population has two key properties: (i) It is unexploitable with strong intra-group selection; (ii) It can achieve full contribution to outperform other strategies in the inter-group selection. The success of this strategy is robust to initial conditions as well as changes to important parameters. We also investigate the influence of different factors on cooperation levels, including group conflicts, group size and migration rate. Their effect on cooperation can be attributed to and explained by their influence on the relative strength of intra-group and inter-group selection.