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Mesenchymal stem cells and the neuronal microenvironment in the area of spinal cord injury

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Neural Regeneration Research 2019年第2期14卷 227-237页

作者： Yana O.Mukhamedshina Olga A.Gracheva Dina M.Mukhutdinova Yurii A.Chelyshev albert a.rizvanov OpenLab Gene and Cell Technologies Institute of Fundamental Medicine and Biology Kazan (Volga Region)Federal University Department of Histology Cytology and Embryology Kazan State Medical University Department of Therapy and Clinical Diagnostics with radiology Faculty of Veterinary Medicine Bauman Kazan State Academy of Veterinary Medicine OpenLab Gene and Cell Technologies Institute of Fundamental Medicine and Biology Kazan (Volga Region) Federal University

Cell-based technologies are used as a therapeutic strategy in spinal cord injury(SCI). Mesenchymal stem cells(MSCs), which secrete various neurotrophic factors and cytokines, have immunomodulatory, anti-apoptotic and anti-inflammatory effects, modulate reactivity/phenotype of astrocytes and the microglia, thereby promoting neuroregeneration seem to be the most promising. The therapeutic effect of MSCs is due to a paracrine mechanism of their action, therefore the survival of MSCs and their secretory phenotype is of particular importance. Nevertheless, these data are not always reported in efficacy studies of MSC therapy in SCI. Here, we provide a review with summaries of preclinical trials data evaluating the efficacy of MSCs in animal models of SCI. Based on the data collected, we have tried(1) to establish the behavior of MSCs after transplantation in SCI with an evaluation of cell survival, migration potential, distribution in the area of injured and intact tissue and possible differentiation;(2) to determine the effects MSCs on neuronal microenvironment and correlate them with the efficacy of functional recovery in SCI;(3) to ascertain the conditions under which MSCs demonstrate their best survival and greatest efficacy.

关键词： spinal cord injury mesenchymal stem cells survival migration Rho/ROCK/PTEN astrocytes microglia myelin-forming cells axon growth tissue integrity

Functionality of a bicistronic construction containing HEXA and HEXB genes encoding β-hexosaminidase A for cell-mediated therapy of GM2 gangliosidoses

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Neural Regeneration Research 2022年第1期17卷 122-129页

作者： Alisa A.Shaimardanova Daria S.Chulpanova Valeriya V.Solovyeva Aleksandr M.Aimaletdinov albert a.rizvanov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia

Tay-Sachs disease and Sandhoff disease are severe hereditary neurodegenerative disorders caused by a deficiency ofβ-hexosaminidase A(HexA)enzyme,which results in the accumulation of GM2 gangliosides in the nervous system *** this work,we analyzed the efficacy and safety of cell-mediated gene therapy for Sandhoff disease and Sandhoff disease using a bicistronic lentiviral vector encoding cDNA of HexAα-andβ-subunit genes separated by the nucleotide sequence of a P2A peptide(HEXA-HEXB).The functionality of the bicistronic construct containing the HEXA-HEXB genetic cassette was analyzed in a culture of HEK293T cells and human umbilical cord blood mononuclear cells(hUCBMCs).Our results showed that the enzymatic activity of HexA in the conditioned medium harvested from genetically modified HEK293T-HEXA-HEXB and hUCBMCs-HEXA-HEXB was increased by 23 and 8 times,respectively,compared with the conditioned medium of native *** blot analysis showed that hUCBMCs-HEXA-HEXB secreted both completely separated HEXA and HEXB proteins,and an uncleaved protein containing HEXA+HEXB linked by the P2A *** injection of genetically modified hUCBMCs-HEXA-HEXB to laboratory Wistar rats was carried out,and the HexA enzymatic activity in the blood plasma of experimental animals,as well as the number of live cells of immune system organs(spleen,thymus,bone marrow,lymph nodes)were determined.A significant increase in the enzymatic activity of HexA in the blood plasma of laboratory rats on days 6 and 9(by 2.5 and 3 times,respectively)after the administration of hUCBMCsHEXA-HEXB was *** the same time,the number of live cells in the studied organs remained ***,the functionality of the bicistronic genetic construct encoding cDNA of the HEXA and HEXB genes separated by the nucleotide sequence of the P2A peptide was shown in vitro and in *** hypothesize that due to the natural ability of hUCBMCs to overcome biological barriers,such a strategy can rest

关键词： bicistronic vector cell-mediated gene therapy GM2 gangliosidosis P2A peptide Sandhoff disease Tay-Sachs disease umbilical cord blood mononuclear cells β-hexosaminidase

Extracellular vesicles in the diagnosis and treatment of central nervous system diseases

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Neural Regeneration Research 2020年第4期15卷 586-596页

作者： Alisa A.Shaimardanova Valeriya V.Solovyeva Daria S.Chulpanova Victoria James Kristina V.Kitaeva albert a.rizvanov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry The Russian Academy of SciencesMoscowRussia School of Veterinary Medicine and Science University of NottinghamSutton Bonington CampusLeicestershireUK

Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body *** many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic *** contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system *** vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain ***,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well *** attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative *** on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and *** to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the *** review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.

关键词： biomarkers cell-mediated therapy central nervous system diseases diagnosis exosomes extracellular RNAs extracellular vesicles microRNAs microvesicles neurodegenerative diseases

Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury

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Neural Regeneration Research 2021年第2期16卷 357-361页

作者： Rustem R.Islamov Farid V.Bashirov Mikhail E.Sokolov Andrei A.Izmailov Filip O.Fadeev Vage A.Markosyan Maria A.Davleeva Olga V.Zubkova Maxim M.Smarov Denis Yu.Logunov Boris S.Naroditskyi Ilnur I.Salafutdinov albert a.rizvanov Ramil G.Turaev Kazan State Medical University KazanRussia Gamaleya Research Institute of Epidemiology and Microbiology MoscowRussia Kazan Federal University KazanRussia The Republican Blood Center of the Ministry of Health of the Republic of Tatarstan KazanRussia

We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases,neurotrauma,and *** this study,using a mini pig model of spinal cord injury,we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene *** obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector(Ad5/35 F)that carried an enhanced green fluorescent protein(EGFP)reporter gene in the plastic blood *** day after blood donation,the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate.A week after gene-modified leucoconcentrate therapy,fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion *** the spleen the groups of EGFP-positive cells located in the lymphoid follicles were *** vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by ***,the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological *** paper presents a proof-of-concept of simple,safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate *** animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No.5)on May 27,2014.

关键词： chimeric Ad5/35F virus enhanced green fluorescent protein gene-modified leucoconcentrate mini pig peripheral blood personalized ex vivo gene therapy plastic blood bag spinal cord injury

Recent development and challenges in enhancing fire performance on wood and wood-based composites:A 10-year review from 2012 to 2021

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Journal of Bioresources and Bioproducts 2024年第1期9卷 27-42页

作者： Charles Michael albert Kang Chiang Liew Faculty of Tropical Forestry Universiti Malaysia SabahKota Kinabalu 88400Kota KinabaluSabah 88400Malaysia

Due to their durability,versatility,and aesthetic value,wood and wood-based composites are widely used as building *** fact that these materials are flammable,however,raises a major worry since they might cause fire hazards and significant loss of life and *** article investigates the variables that affect fire performance as well as the various fire-retardant treatments and their *** current developments and challenges in improving the fire performance of wood and wood-based composites treated with fire-retardant materials are summarized in this ***,organic chemicals,and densification are some recent developments in fire-retardant treatments that are also *** points from the review are summarized,along with potential areas for further research and development.

关键词： Fire performance Fire-retardant materials Wood Wood-based composite Nanoparticles coating Surface charring Bio-based fire retardant Densification

NFA:A neural factorization autoencoder based online telephony fraud detection

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Digital Communications and Networks 2024年第1期10卷 158-167页

作者： Abdul Wahid Mounira Msahli albert Bifet Gerard Memmi Department of Computer Sciences and Networks(INFRES) LTCITelecom ParisInstitut Polytechnique de ParisPalaiseau91120France Artificial Intelligence Institute The University of WaikatoPrivate Bag 31053240HamiltonNew Zealand

The proliferation of internet communication channels has increased telecom fraud,causing billions of euros in losses for customers and the industry each *** constantly find new ways to engage in illegal activity on the *** reduce these losses,a new fraud detection approach is *** fraud detection involves identifying a small number of fraudulent calls from a vast amount of call *** an effective strategy to combat fraud has become *** much effort has been made to detect fraud,most existing methods are designed for batch processing,not real-time *** solve this problem,we propose an online fraud detection model using a Neural Factorization Autoencoder(NFA),which analyzes customer calling patterns to detect fraudulent *** model employs Neural Factorization Machines(NFM)and an Autoencoder(AE)to model calling patterns and a memory module to adapt to changing customer *** evaluate our approach on a large dataset of real-world call detail records and compare it with several state-of-the-art *** results show that our approach outperforms the baselines,with an AUC of 91.06%,a TPR of 91.89%,an FPR of 14.76%,and an F1-score of 95.45%.These results demonstrate the effectiveness of our approach in detecting fraud in real-time and suggest that it can be a valuable tool for preventing fraud in telecommunications networks.

关键词： Telecom industry Streaming anomaly detection Fraud analysis Factorization machine Real-time system Security

Potential applications and implications of large language models in primary care

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Family Medicine and Community Health 2024年第S1期12卷 6-11页

作者： albert Andrew Medical Student The University of Auckland School of MedicineAucklandNew Zealand

The recent release of highly advanced generative artificial intelligence(AI)chatbots,including ChatGPT and Bard,which are powered by large language models(LLMs),has attracted growing mainstream interest over its diverse applications in clinical practice,including in health and *** potential applications of LLM-based programmes in the medical field range from assisting medical practitioners in improving their clinical decision-making and streamlining administrative paperwork to empowering patients to take charge of their own ***,despite the broad range of benefits,the use of such AI tools also comes with several limitations and ethical concerns that warrant further consideration,encompassing issues related to privacy,data bias,and the accuracy and reliability of information generated by *** focus of prior research has primarily centred on the broad applications of LLMs in *** the author’s knowledge,this is,the first article that consolidates current and pertinent literature on LLMs to examine its potential in primary *** objectives of this paper are not only to summarise the potential benefits,risks and challenges of using LLMs in primary care,but also to offer insights into considerations that primary care clinicians should take into account when deciding to adopt and integrate such technologies into their clinical practice.

关键词： primarily benefits administrative

Low-power SiPM readout BETA ASIC for space applications

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Nuclear Science and Techniques 2024年第3期35卷 153-169页

作者： Anand Sanmukh Sergio Gómez albert Comerma Joan Mauricio Rafel Manera Andreu Sanuy Daniel Guberman Roger Catala albert Espinya Marina Orta Oscar de la Torre David Gascon Departament de Física Quàntica i Astrofísica(FQA) Institut de Ciències del Cosmos(ICCUB)Universitat de Barcelona(UB)08028 BarcelonaSpain Institut d’Estudis Espacials de Catalunya(IEEC) 08034 BarcelonaSpain Electronics Department Serra Hunter fellow at Polytechnic University of Catalonia(UPC)08019 BarcelonaSpain

The BETA application-specific integrated circuit(ASIC)is a fully programmable chip designed to amplify,shape and digitize the signal of up to 64 Silicon photomultiplier(SiPM)channels,with a power consumption of approximately~1 mW/*** to its dual-path gain,the BETA chip is capable of resolving single photoelectrons(phes)with a signal-to-noise ratio(SNR)>5 while simultaneously achieving a dynamic range of~4000 ***,BETA can provide a cost-effective solution for the readout of SiPMs in space missions and other applications with a maximum rate below 10 *** this study,we describe the key characteristics of the BETA ASIC and present an evaluation of the performance of its 16-channel version,which is implemented using 130 nm *** ASIC also contains two discriminators that can provide trigger signals with a time jitter down to 400 ps FWHM for 10 *** linearity error of the charge gain measurement was less than 2%for a dynamic range as large as 15 bits.

关键词： Radiation detectors Silicon photomultipliers Photon sensors Front-end electronics Mixed-mode ASICs Space technology

Media coverage and price reactions to earnings news

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China Journal of Accounting Research 2024年第3期17卷 1-24页

作者： Miao Yu Hangsoo Kyung albert Tsang School of Accountancy Shandong University of Finance and EconomicsChina School of Accounting and Finance Hong Kong Polytechnic UniversityChina SUSTech Business School Southern University of Science and TechnologyChina

In this study,we find that relative to firms with less media coverage,stock price sensitivity to positive(negative)earnings surprises in earnings announcements of firms with greater media coverage is stronger(weaker).This asymmetry in the effect of media coverage on stock price sensitivity to positive versus negative earnings surprises suggests that greater media coverage of earnings announcements intensifies stock price reactions to positive earnings surprises but attenuates reactions to negative earnings ***,we find that negative earnings news is less persistent for firms with greater media ***,our findings support the conjecture that greater media coverage increases managers’incentive to avoid future negative news,thereby reducing the persistence of poor financial performance and weakening price reactions to negative earnings news.

关键词： Earnings announcement Asymmetric stock market reactions Media coverage Earnings persistence