Follow-up study of neuropsychological scores of infant patients with cobalamin C defects and influencing factors of cerebral magnetic resonance imaging characteristics

PurposeThe purpose of this study was to investigate whether baseline cerebral magnetic resonance imaging (MRI) characteristics could predict therapeutic responsiveness in patients with cobalamin C (cblC) defects.Materials and methodsThe cerebral MRI results of 40 patients with cblC defects were evaluated by a neuroradiologist. Neuropsychological scores and imaging data were collected. Neuropsychological tests were performed before and after standardized treatment.ResultsThirty-eight patients initially underwent neuropsychological testing [developmental quotient (DQ)]. CblC defects with cerebellar atrophy, corpus callosum thinning and ventricular dilation had significantly lower DQs than those without (P < 0.05). Through a multivariate linear stepwise regression equation after univariate analysis, ventricular dilation was the most valuable predictor of lower DQs. Thirty-six patients (94.7%) underwent follow-up neuropsychological testing. The pre- and post-treatment DQ values were not significantly different (Z = −1.611, P = 0.107). The post-treatment DQ classification (normal, moderately low, or extremely low) showed nearly no change compared to the pretreatment DQ classification (k = 0.790, P < 0.001).ConclusionVentricular dilation, cerebral atrophy and corpus callosum thinning are the main MRI abnormalities of cblC defects, and these manifestations are significantly correlated with delayed development in children. MRI findings can be considered an important tool for determining the severity of cblC defects

Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

© 2017 The Author(s). Background: Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined. Methods: We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo. Results: During in vitro culture period, the percentages and absolute numbers of T cells expressing the CARs containing a hinge domain continuously increased, mainly through the promotion of CD4+ CAR T cell expansion, regardless of the single-chain variable fragment (scFv). In vitro migration assay showed that the hinges enhanced CAR T cells migratory capacity. The T cells expressing anti-CD19 CARs with or without a hinge had similar antitumor capacities in vivo, whereas the T cells expressing anti-mesothelin CARs containing a hinge domain showed enhanced antitumor activities. Conclusions: Hence, our results demonstrate that a hinge contributes to CAR T cell expansion and is capable of increasing the antitumor efficacy of some specific CAR T cells. Our results suggest potential novel strategies in CAR vector design.Link_to_subscribed_fulltex

Accounting for taste? Analysing diverging public support for energy sources in Great Britain

Public acceptance of energy technologies is an important area of energy and social science research. However, few studies utilise large datasets which include spatial and temporal dimensions, as well as the demographic and attitudinal characteristics of survey respondents. In this paper, we analyse twenty-five waves of the UK Government's Energy and Climate Change Public Attitudes Tracker: a large, nationally representative dataset spanning six years (2012 - 2018). This enables unique insights into trends in public acceptance across time, space and social groups, covering eight energy sources. We find differing profiles in terms of who supports which types of energy, with a key division between support for renewable technologies on the one hand, and nuclear and fracking on the other. We also identify a growing gap between public and policymakers’ attitudes to energy technologies which we argue must be bridged to ensure a smooth rapid transition that is acceptable to all

Quantitative evaluation of the immunodeficiency of a mouse strain by tumor engraftments

© 2015 Ye et al. Background: The mouse is an organism that is widely used as a mammalian model for studying human physiology or disease, and the development of immunodeficient mice has provided a valuable tool for basic and applied human disease research. Following the development of large-scale mouse knockout programs and genome-editing tools, it has become increasingly efficient to generate genetically modified mouse strains with immunodeficiency. However, due to the lack of a standardized system for evaluating the immuno-capacity that prevents tumor progression in mice, an objective choice of the appropriate immunodeficient mouse strains to be used for tumor engrafting experiments is difficult. Methods: In this study, we developed a tumor engraftment index (TEI) to quantify the immunodeficiency response to hematologic malignant cells and solid tumor cells of six immunodeficient mouse strains and C57BL/6 wild-type mouse (WT). Results: Mice with a more severely impaired immune system attained a higher TEI score. We then validated that the NOD-scid-IL2Rg-/- (NSI) mice, which had the highest TEI score, were more suitable for xenograft and allograft experiments using multiple functional assays. Conclusions: The TEI score was effectively able to reflect the immunodeficiency of a mouse strain.Link_to_subscribed_fulltex

Deep joint optimized clustering model for life cycle identification of enterprise electricity consumption

Motivation analysis is significant in inspecting illegal power consumption behavior. Based on enterprise life cycle theory, this study proposes enterprise electricity consumption life cycle to conceptually aid the analysis of motives for enterprise illegal power consumption behavior. The identification of the aforementioned life cycle is achieved by clustering. We propose a deep clustering model based on the joint optimization of Gated Recurrent Unit (GRU) autoencoder and an improved K-prototypes algorithm. The proposed model utilizes GRU autoencoder to learn the latent features of high-dimensional enterprise electricity data and dynamically adjust the distance metric in K-prototypes algorithm based on the reconstruction error of GRU autoencoder. By jointly optimizing the two components, the proposed model can effectively cluster the enterprise electricity consumers and enterprises’ electricity consumption life cycle is identified based on the features and patterns of enterprises in each cluster. Experiment demonstrates that the proposed model can effectively capture the non-linear transformation from electricity data to its latent space and yield superior clustering results, and can provide data support for the identification of enterprise electricity consumption life cycle

Data_Sheet_1_Follow-up study of neuropsychological scores of infant patients with cobalamin C defects and influencing factors of cerebral magnetic resonance imaging characteristics.XLSX

PurposeThe purpose of this study was to investigate whether baseline cerebral magnetic resonance imaging (MRI) characteristics could predict therapeutic responsiveness in patients with cobalamin C (cblC) defects.Materials and methodsThe cerebral MRI results of 40 patients with cblC defects were evaluated by a neuroradiologist. Neuropsychological scores and imaging data were collected. Neuropsychological tests were performed before and after standardized treatment.ResultsThirty-eight patients initially underwent neuropsychological testing [developmental quotient (DQ)]. CblC defects with cerebellar atrophy, corpus callosum thinning and ventricular dilation had significantly lower DQs than those without (P ConclusionVentricular dilation, cerebral atrophy and corpus callosum thinning are the main MRI abnormalities of cblC defects, and these manifestations are significantly correlated with delayed development in children. MRI findings can be considered an important tool for determining the severity of cblC defects.</p

Data_Sheet_2_Follow-up study of neuropsychological scores of infant patients with cobalamin C defects and influencing factors of cerebral magnetic resonance imaging characteristics.DOCX

PurposeThe purpose of this study was to investigate whether baseline cerebral magnetic resonance imaging (MRI) characteristics could predict therapeutic responsiveness in patients with cobalamin C (cblC) defects.Materials and methodsThe cerebral MRI results of 40 patients with cblC defects were evaluated by a neuroradiologist. Neuropsychological scores and imaging data were collected. Neuropsychological tests were performed before and after standardized treatment.ResultsThirty-eight patients initially underwent neuropsychological testing [developmental quotient (DQ)]. CblC defects with cerebellar atrophy, corpus callosum thinning and ventricular dilation had significantly lower DQs than those without (P ConclusionVentricular dilation, cerebral atrophy and corpus callosum thinning are the main MRI abnormalities of cblC defects, and these manifestations are significantly correlated with delayed development in children. MRI findings can be considered an important tool for determining the severity of cblC defects.</p

3,5-Dimethyaminophenol is not Mutagenic in Ames Test and HPRT Test and may have Anti-Carcinogenic Potential Against Lung Cancer Cells

Exposure to 3,5-dimethylaminophenol (3,5-DMAP), the metabolite of the 3-5-dimethylaniline, was shown to cause high levels of oxidative stress in different cells. However, we have shown that this alkylaniline metabolite was non-mutagenic to different strains of Salmonella typhimurium in Ames test and also was found to be not mutagenic to CHO cells in HPRT test. Concerning all the available data, we aimed to observe whether this metabolite may have anti-carcinogenic potential in human non-small cell lung cancer line (A549 cells). 3,5-DMAP caused a dose-dependent increase in cytotoxicity and generation of superoxide (O2-.) and reactive oxygen species (ROS). 3,5-DMAP did not produce significant cytotoxicity to human lung fibroblasts even at very high concentrations; however showed higher cytotoxic effect on A549 lung cancer cells at the same concentrations. 3,5-DMAP also led to molecular events, like increases in apoptotic markers (i.e., p53, Bad, Bax and cytochrome and decreases anti-apoptotic proteins (Bcl-2). Furthermore, 3,5-DMAP provided significant decreases in cell viability of A549 cells and eventually inhibited growth of A549 cells in an in vivo mouse model. Tumor sections showed that 3,5-DMAP down-regulated c-Myc expression but up-regulated p53 and cytochrome c, all of which might result in tumor growth arrest. In conclusion, our findings demonstrate 3,5-DMAP is not mutagenic to Salmonella typhimurium and CHO cells; toxic to A549 cells and therefore may have anti-cancer properties, the importance of which should be elucidated with further mechanistic studies