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Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans

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Neural Regeneration Research 2020年第3期15卷 425-437页

作者： Magdalini Tsintou kyriakos dalamag.as Nikos Makris Departments of Psychiatry and Neurology Services Center for Neural Systems InvestigationsCenter for Morphometric AnalysisAthinoula A.Martinos Center for Biomedical ImagingMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Department of Psychiatry Psychiatry Neuroimaging LaboratoryBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA University College of London Division of Surgery&Interventional Science Center for Nanotechnology&Regenerative MedicineUniversity College LondonLondonUK Department of Physical Medicine and Rehabilitation The University of Texas Health Science Center at HoustonHoustonTXUSA The Institute for Rehabilitation and Research Memorial Hermann Research Center The Institute for Rehabilitation and Research Memorial Hermann HospitalHoustonTXUSA Department of Anatomy&Neurobiology Boston University School of MedicineBostonMAUSA

The central nervous system is known to have limited regenerative *** only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such *** the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more *** and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system *** an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to *** review considers some regenerative therapies for central nervous system repair that hold promise for future clinical *** addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.

关键词： animal models central nervous system regeneration clinical translation exosomes hydrogels neural tissue engineering nonhuman primates spinal cord injury stem cells stroke

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Event-Triggered Optimal Adaptive Control Algorithm for Continuous-Time Nonlinear Systems

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IEEE/CAA Journal of Automatica Sinica 2014年第3期1卷 282-293页

作者： kyriakos G.Vamvoudakis the Center for Control Dynamicalsystems and Computation(CCDC)University of California

This paper proposes a novel optimal adaptive eventtriggered control algorithm for nonlinear continuous-time *** goal is to reduce the controller updates,by sampling the state only when an event is triggered to maintain stability and *** online algorithm is implemented based on an actor/critic neural network structure.A critic neural network is used to approximate the cost and an actor neural network is used to approximate the optunal event-triggered *** in the algorithm proposed there are dynamics that exhibit continuous evolutions described by ordinary differential equations and instantaneous jumps or impulses,we will use an impulsive system approach.A Lyapunov stability proof ensures that the closed-loop system is asymptotically ***,we illustrate the effectiveness of the proposed solution compared to a timetriggered controller.

关键词： Learning (artificial intelligence) Heuristic algorithms Neural networks Nonlinear systems Bandwidth Linear systems Adaptive control

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Stem cells for spinal cord injuries bearing translational potential

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Neural Regeneration Research 2018年第1期13卷 35-42页

作者： kyriakos dalamag.as Magdalini Tsintou Alexander M.Seifalian Department of Tissue Engineering Harvard Medical School Nanotechnology & Regenerative Medicine Centre Division of Surgery and Interventional Science University College London Nanotechnology & Regenerative Medicine Commercialisation Centre (Ltd). The London Bio Science Innovation Centre

Spinal cord injury （SCI） is a highly debilitating neurological disease, which still lacks effective treatment strategies, causing significant financial burden and distress to the affected families. Nevertheless, nanotechnology and regenerative medicine strategies holding promise for the development of novel therapies that would reach from bench to bedside to serve the SCI patients. There has already been significant progress in the field of cell-based therapies, with the clinical application for SCI, currently in phase II of the clinical trial. Stem cells （e.g., induced pluripotent stem cells, fetal stem cells, human embryonic stem cells, and olfactory ensheathing cells） are certainly not to be considered the panacea for neural repair but, especially when combined with rehabilitation or other combinatorial approaches using the help of nanotechnology, they seem to be the source of some of the most promising and clinical translatable cell-based therapies that could help solving impactful problems on neural repair.

关键词： spinal cord injury stem cells neuroregeneration plasticity repair

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Novel time slicing approach for customer defection models in e-commerce:a case study

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Data Science and Management 2022年第3期5卷 149-162页

作者： kyriakos Georgiou Alexandros Chasapis Data Science Department Finloup S.A.2 Evristheos11854AthensGreece Department of Statistics and Stochastic Modeling and Applications Laboratory Athens University of Economics and Business6 Patission Str10434AthensGreece

In this study,we examine the problem of predicting customer defection in a noncontractual *** by recent work on machine learning using multiple time slices,we develop a novel training and testing framework,the sliding multi-time slicing(SMTS)*** apply this method to data from the largest marketplace in Greece,namely,Skroutz,considering the standard features that account for the important characteristics of customer activity and custom performance metrics aimed at capturing business-related goals established by the *** dataset comprises customers over a relatively short period,since April 2018,the number of which has also exhibited a significant increase in recent *** these difficulties and the inherent seasonality of customer defection,our results demonstrate that,with SMTS,developing models that outperform previous approaches and optimize decision-making is *** validate the approach to a benchmark dataset from the commerce sector and discuss the practical considerations and requirements of the proposed method.

关键词： E-commerce Defection Seasonality Machine learning

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Highly flexible,foldable,and rollable microsupercapacitors on an ultrathin polyimide substrate with high power density

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Microsystems & Nanoengineering 2018年第1期4卷 223-233页

作者： Juan Pu Xiaohong Wang Renxiao Xu Sixing Xu kyriakos Komvopoulos Department of Microelectronics and Nanoelectronics Tsinghua UniversityBeijing 100084China Institute of Microelectronics Tsinghua UniversityBeijing 100084China Tsinghua National Laboratory for Information Science and Technology Beijing 100084China Department of Mechanical Engineering University of CaliforniaBerkeleyCA 94720USA

The design and functionality of extremely flexible,foldable,and rollable microsupercapacitors(MSCs)with in-plane interdigital electrodes that consist of single-walled carbon nanotube(SWCNT)networks on an ultrathin polyimide substrate are demonstrated through experiments and finite element *** all-solid-state MSCs can be reversibly bent,folded,and rolled purely elastically without degradation of their electrical *** simulation results confirm that the deformation in bent,folded,and rolled MSCs is purely *** high power density(1125W cm^(–3))and small time constant(1 ms)of the present MSCs are comparable to those of aluminum electrolytic *** MSCs operate at scan rates of up to 1000 V s^(–1),are characterized by a volumetric capacitance of 18 F cm^(–3) and an energy density of 1.6 mWh cm^(–3),and exhibit superior electrochemical stability with 96% capacity retention even after 100,000 charge/discharge *** developed MSCs demonstrate high potential for integration in flexible and wearable electronic systems.

关键词： purely Highly power

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Radiofrequency ablation-assisted liver resection a step toward bloodless liver resection

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Hepatobiliary & Pancreatic Diseases International 2015年第1期14卷 69-74页

作者： Athanasios Petrou kyriakos Neofytou Constantinos Mihas Jessamy Bagenal Michael Kontos John Griniatsos Evangelos Felekouras Nicosia Surgical Department Division of Hepatobiliary Pancreatic Surgery Nicosia General Hospital First Department of Surgery University of Athens Medical School LAIKO Teaching Hospital Bristol Heart Institute Severn School of Surgery

BACKGROUND： Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The application of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency ablation-assisted liver ***： A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resection was performed. Intraoperative blood loss, need for transfusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all ***： Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 m L, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients（8.3%）. The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients（32.4%） with postoperative complications. There is no mortality within 30 days after surgery. CONCLUSIONS： Radiofrequency ablation-assisted liver resection permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality.

关键词： bleeding complications hepatectomy radiofrequency ablation Pringle maneuver

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Pleiotropic effects of apolipoprotein A-Ⅱ on high-density lipoprotein functionality, adipose tissue metabolic activity and plasma glucose homeostasis

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The Journal of Biomedical Research 2020年第1期34卷 14-26页

作者： Evangelia Zvintzou Eva Xepapadaki Christina Kalogeropoulou Serafoula Filou kyriakos EKypreos Department of Pharmacology University of Patras Medical SchoolRio AchaiasTK 26500Greece

Apolipoprotein A-Ⅱ(APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein(HDL)synthesized mainly by the liver and to a much lesser extent by the intestine. Transgenic mice overexpressing human APOA-Ⅱ present abnormal lipoprotein composition and are prone to atherosclerosis, though in humans the role for APOA-Ⅱ in coronary heart disease remains controversial. Here, we investigated the effects of overexpressed APOA-Ⅱ on HDL structure and function, adipose tissue metabolic activity, glucose tolerance and insulin sensitivity. C57BL/6 mice were infected with an adenovirus expressing human APOA-Ⅱ or a control adenovirus Ad GFP, and five days post-infection blood and tissue samples were isolated. APOA-Ⅱ expression resulted in distinct changes in HDL apoproteome that correlated with increased antioxidant and anti-inflammatory activities. No effects on cholesterol efflux from RAW 264.7 macrophages were observed. Molecular analyses in white adipose tissue(WAT) indicated a stimulation of oxidative phosphorylation coupled with respiration for ATP production in mice overexpressing APOA-Ⅱ. Finally, overexpressed APOA-Ⅱ improved glucose tolerance of mice but had no effect on the response to exogenously administered insulin. In summary, expression of APOA-Ⅱ in C57BL/6 mice results in pleiotropic effects with respect to HDL functionality, adipose tissue metabolism and glucose utilization, many of which are beneficial to health.

关键词： apolipoprotein A-Ⅱ high-density lipoprotein adipose tissue glucose tolerance insulin sensitivity

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The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke:a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches

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Neural Regeneration Research 2021年第4期16卷 605-613页

作者： Magdalini Tsintou kyriakos dalamag.as Tara LMoore Yogesh Rathi Marek Kubicki Douglas LRosene Nikos Makris Departments of Psychiatry and Neurology Services Center for Neural Systems InvestigationsCenter for Morphometric AnalysisAthinoula A.Martinos Center for Biomedical ImagingMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Department of Psychiatry Psychiatry Neuroimaging LaboratoryBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA University College of London Division of Surgery&Interventional Science Center for Nanotechnology&Regenerative MedicineUniversity College LondonLondonUK Department of Physical Medicine and Rehabilitation The University of Texas Health Science Center at HoustonHoustonTXUSA The Institute for Rehabilitation and Research Memorial Hermann Research Center The Institute for Rehabilitation and Research Memorial Hermann HospitalHoustonTXUSA Department of Anatomy&Neurobiology Boston University School of MedicineBostonMAUSA

Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)*** is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNS therapeutics *** the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury *** vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell *** the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative *** review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable *** rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the *** sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration ***,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of m

关键词： cortical injury exosomes extracellular vesicles hydrogels neural tissue engineering neural tissue repair neuroregeneration non-human primates stroke

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Uterine-ileal perforation post pregnancy related dilatation and curettage managed by laparoscopic small bowel resection and primary anastomosis: A case report

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Laparoscopic, Endoscopic and Robotic Surgery 2020年第3期3卷 94-96页

作者： Melissa kyriakos Saad Saleem Abdel Baki Elias Saikaly General Surgery Department Saint George Hospital University Medical CenterBeirutLebanon

Although rare,small bowel perforation post pregnancy related dilation and curettage presents a serious ***,we reported a case of 34-year-old female patient presenting for uterine-ileal perforation post pregnancy relat... 详细信息

关键词： Dilatation and curettage Small bowel perforation Laparoscopic small bowel resection Primary anastomosis

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Economic evaluation of the hepatitis C elimination strategy in Greece in the era of affordable direct-acting antivirals

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World Journal of Gastroenterology 2019年第11期25卷 1327-1340页

作者： Ilias Gountas Vana Sypsa George Papatheodoridis kyriakos Souliotis Kostas Athanasakis Homie Razavi Angelos Hatzakis Department of Hygiene Epidemiology and Medical StatisticsMedical SchoolNational and Kapodistrian University of Athens Hellenic Scientific Society for the Study of AIDS and Sexually Transmitted Diseases Department of Gastroenterology Medical SchoolNational and Kapodistrian University of AthensLaiko General Hospital Faculty of Social and Political Sciences University of Peloponnese Department of Health Economics National School of Public Health Center for Disease Analysis

BACKGROUND Hepatitis C virus(HCV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HCV-elimination by 2030. This study aims to estimate the required interventions to achieve elimination using updated information for direct-acting antiviral(DAA) treatment coverage, to compute the total costs(including indirect/societal costs) of the strategy and to identify whether the elimination strategy is cost-effective/cost-saving in *** To estimate the required interventions and subsequent costs to achieve HCV elimination in *** A previously validated mathematical model was adapted to the Greek HCVinfected population to compare the outcomes of DAA treatment without the additional implementation of awareness or screening campaigns versus an HCV elimination strategy, which includes a sufficient number of treated patients. We estimated the total costs(direct and indirect costs), the disability-adjusted life years and the incremental cost-effectiveness ratio using two different price *** Without the implementation of awareness or screening campaigns,approximately 20000 patients would be diagnosed and treated with DAAs by2030. This strategy would result in a 19.6% increase in HCV-related mortality in2030 compared to 2015. To achieve the elimination goal, 90000 patients need to be treated by 2030. Under the elimination scenario, viremic cases would decrease by78.8% in 2030 compared to 2015. The cumulative direct costs to eliminate the disease would range from 2.1-2.3 billion euros(€) by 2030, while the indirect costs would be €1.1 billion. The total elimination cost in Greece would range from €3.2-3.4 billion by 2030. The cost per averted disability-adjusted life year is estimated between €10100 and €13380, indicating that the elimination strategy is very costeffective. Furthermore, HCV elimination strategy would save €560-895 million *** Without

关键词： Hepatitis C elimination Cost effectiveness Cost of elimination Indirect costs Projections Mathematical modelling Awareness and screening programs World Health Organization targets

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