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Engineering osteoarthritic cartilage model through differentiating senescent human mesenchymal stem cells for testing disease-modifying drugs

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Science China(Life Sciences) 2022年第2期65卷 309-327页

作者： Ning Wang Yuchen He Silvia Liu Meagan J.Makarcyzk Guanghua Lei Alexander Chang Peter G Alexander Tingjun Hao Anne-Marie Padget Nuria de Pedro tsapekos menelaos Hang Lin Department of Orthopaedic Surgery University of Pittsburgh School of MedicinePittsburgh PA 15219USA Department of Orthopedic Surgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of Pathology University of Pittsburgh School of MedicinePittsburgh PA 15219USA Department of Bioengineering University of Pittsburgh Swanson School of EngineeringPittsburgh PA 15219USA Department of Bioinformatics University of Pittsburgh School of MedicinePittsburgh PA 15219USA McGowan Institute for Regenerative Medicine University of Pittsburgh School of MedicinePittsburgh PA 15219USA Department of Biology University of Pittsburgh Dietrich School of Arts and SciencePittsburgh PA 15219USA Department of Research B2B Life Length SLMadrid 28010Spain Xiangya Third Hospital Central South UniversityChangsha 410013China

Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis(OA).In this study,we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs(DMOADs).Spe-cifically,human bone marrow-derived mesenchymal stromal cells(MSCs)were expanded in vitro up to passage 10(P10-MSCs).Following their senescent phenotype formation,P10-MSCs were subjected to pellet culture in chondrogenic *** from qRT-PCR,histology,and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents,when compared to that from normal passage 4(P4)-***,the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples,as demonstrated by RNA sequencing data and other analysis ***,the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and *** results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in *** P4-and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans.

关键词： osteoarthritis MSC senescence cartilage tissue engineering disease-modifying OA drug senolytic

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The cost of privacy on blockchain:A study on sealed-bid auctions

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Blockchain(Research and Applications) 2023年第3期4卷 1-10页

作者： menelaos Kokaras Magda Foti Department of Electrical and Computer Engineering University of ThessalyVolos38221Greece UBITECH Research Department UBITECH Ltd15231AthensGreece

In order to preserve privacy in a blockchain ecosystem,the main objective is to keep a transaction's data private,such as the sender,the receiver,and the amount *** current work studies the cryptographic tools commonly used to achieve this type of privacy,primarily focusing on the Ethereum *** tools usually require many computational and storage resources,leading to additional *** anonymous auction protocol was developed as a case study to explore these costs,where hiding the identity and the amount of the bids utilizes a variety of cryptographic *** proposed implementation was compared against three sealed-bid auction protocols,which utilize similar cryptographic tools for preserving privacy throughout the auction *** results show that providing an additional level of anonymity,such as hiding someone's identity,can increase the gas cost significantly,up to 2.5 times,depending on the choice of the cryptographic tools,which determine the usage of the blockchain's storage and computational *** adjusting the level of decentralization on the application level by moving some operations off-chain and maintaining the role of the auctioneer,we show that we can maintain anonymity while reducing the gas cost by 40%.

关键词： Privacy Anonymity Blockchain Distributed ledger technology Auction

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Sorafenib in breast cancer treatment:A systematic review and overview of clinical trials

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World Journal of Clinical Oncology 2016年第4期7卷 331-336页

作者： menelaos Zafrakas Panayiota Papasozomenou Christos Emmanouilides Research Laboratory for Mastology Gynecology and ObstetricsSchool of Health and Medical CareAlexander Technological Institute of Thessaloniki Interbalkan European Medical Center of Thessaloniki

AIM:To evaluate the current role of sorafenib,an oral multikinase inhibitor in the treatment of breast ***:An extensive search of the literature until March 2016 was carried out in Medline and ***,by using the search terms "sorafenib" and "breast cancer".Papers found were checked for further relevant ***,21 relevant studies were found,18 in advanced breast cancer(16 in stage Ⅳ and two in stages Ⅲ-Ⅳ) and three in early breast ***:Among studies in advanced breast cancer,there were two trials with sorafenib as monotherapy,four trials of sorafenib in combination with taxanes,two in combination with capecitabine,one with gemcitabine and/or capecitabine,one with vinorelbine,one with bevacizumab,one with pemetrexed and one with ixabepilone,three trials of sorafenib in combination with endocrine therapy and two trials in women with brain metastases undergoing whole brain *** addition,there was one trial of sorafenib added to standard chemotherapy in the adjuvant setting,and two trials in the neoadjuvant *** general,sorafenib was well tolerated in breast cancer patients,though its dosage had to be adjusted in some trials,and discontinuation rates were high,particularly for the combination of sorafenib with *** monotherapy and combinations with taxanes,bevacizumab and ixabepilone showed inadequate efficacy,while efficacy results from combinations with gemcitabine and/or capecitabine and possibly tamoxifen were more ***:At present,sorafenib should not be used for the treatment of breast cancer outside of clinical trials and more clinical data are needed in order to support its standard use in breast cancer therapy.

关键词： Breast cancer Sorafenib Kinase inhibitors BRAF Mitogen-activated protein kinase

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Experimental study of neuromorphic node based on a multiwaveband emitting two-section quantum dot laser

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Photonics Research 2021年第4期9卷 I0007-I0015页

作者： George Sarantoglou menelaos Skontranis Adonis Bogris Charis Mesaritakis Department of Information and Communication Systems Engineering University of the AegeanPalama 2Karlovassi 83200 SamosGreece Department of Informatics and Computer Engineering University of West AtticaAghiou Spiridonos12243 EgaleoAthensGreece

In this work,we present experimental results concerning excitability in a multiband emitting quantum-dot-based photonic *** experimental investigation revealed that the same two-section quantum dot laser can be tuned through a simple bias adjustment to operate either as a leaky integrate and fire or as a resonate and fire ***,by exploiting the inherent multiband emission of quantum-dot devices revealed by the existence of multiple lasing thresholds,a significant enhancement in the neurocomputational capabilities,such as spiking duration and firing rate,is *** firing rate increased by an order of magnitude that leads to an enhancement in processing speed and,more importantly,neural spike duration was suppressed to the picosecond scale,which corresponds to a significant temporal resolution *** new regimes of operation,when combined with thermal insensitivity,silicon cointegration capability,and the fact that these multiband mechanisms are also present in miniaturized quantum-dot devices,render these neuromorphic nodes a proliferating platform for large-scale photonic spiking neural networks.

关键词： laser quantum section

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Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer:A systematic review

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World Journal of Gastrointestinal Surgery 2023年第8期15卷 1808-1818页

作者： Stylianos Fiflis menelaos Papakonstantinou Alexandros Giakoustidis Gregory Christodoulidis Eleni Louri Vasileios N Papadopoulos Dimitrios Giakoustidis A’Department of Surgery General Hospital PapageorgiouThessaloniki 56429Greece Department of General Surgery University Hospital of LarissaLarissa 41110Greece

BACKGROUND Gastric cancer(GC)is a major health concern *** resection and chemotherapy is the mainstay treatment for gastric carcinoma,however,the optimal approach remains unclear and should be different in each *** can be administered both pre-and postoperatively,but a multidisciplinary approach is preferred when *** is particularly relevant for locally advanced GC(LAGC),as neoadjuvant chemotherapy(NAT)could potentially lead to tumor downsizing thus allowing for a complete resection with curative *** though the recent progress has been impressive,European and International guidelines are still controversial,thus attenuating the need for a more standardized approach in the management of locally advanced *** To investigate the effects of NAT on the overall survival(OS),the disease-free survival(DFS),the morbidity and the mortality of patients with LAGC in comparison to upfront surgery(US).METHODS For this systematic review,a literature search was conducted between November and February 2023 in PubMed,Cochrane Library and *** for studies including patients with *** independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion *** Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic *** Eighteen studies with 4839 patients with LAGC in total were included in our systematic *** were separated into two groups;one receiving NAT before the gastrectomy(NAT group)and the other undergoing upfront surgery(US group).The OS ranged from 41.6%to 74.2%in the NAT group and from 30.9%to 74%in the US *** DFS was also longer in the NAT group and reached up to 80%in certain *** complications related to the chemotherapy or the surgery ranged from 6.4%to 38.1%in

关键词： Gastric cancer Locally advanced gastric cancer Neoadjuvant chemotherapy Surgery Survival

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Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 514-526页

作者： Stylianos Fiflis Grigorios Christodoulidis menelaos Papakonstantinou Alexandros Giakoustidis Stergos Koukias Paraskevi Roussos Marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas Dimitrios Giakoustidis First Department of Surgery General Hospital PapageorgiouThessaloniki 56429Greece Department of General Surgery University Hospital of LarissaLarissa 41110Greece

BACKGROUND Gastric cancer is the third most common cause of cancer related death *** with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain *** indexes have been proposed in the past few years in order to estimate the survival of patients undergoing *** preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been *** aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative *** To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction *** A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI *** PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic *** review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic *** patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual *** 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included st

关键词： Prognostic nutritional index Gastric adenocarcinoma Gastroesophageal junction cancer Prognosis Overall survival

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Anyang:A Case Study of Foreign University Involvement in Chinese Sustainable New Town Planning

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China City Planning Review 2012年第4期21卷 56-65页

作者： menelaos Triantafillou David J.Edelman School of Planning University of Cincinnati

Over the last ten to fifteen years,planning and design professionals in the United States and Europe have increasingly been engaged in consulting work in *** Architectural & Engineering firms from the United Kingdom and the United States,for example,have been opening offices in Beijing and ***,the concern with sustainable urban development and China's policies to alleviate pressures of urbanization has been an engine for commissions for new town plans and city expansion plans across China's *** the 2007-2009 academic years,the School of Planning at the University of Cincinnati prepared a conceptual plan for the expansion of the City of Anyang through a collaborative agreement between the city and *** experience of the faculty leading this project with field work,the planning process,plan preparation,and the engagement of students has revealed some important issues that need to be addressed by planning schools and planning professionals engaged in planning in provincial ***,this paper is a case study of foreign university involvement in Chinese sustainable new town planning,and the following sections discuss the Anyang Eastern New Town Conceptual Plan,identify the key issues regarding preparing the plan,contracting and payment,data availability,data sharing and field investigation,and finally discuss the lessons learned regarding the planning process,project program and expectations.

关键词： sustainable new town planning planning in provincial China Anyang Eastern New Town Conceptual Plan issues in Chinese planning

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Laparoscopic cholecystectomy: A report from a single center

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World Journal of Gastroenterology 2006年第24期12卷 3887-3890页

作者： Konstantinos Vagenas Stavros N Karamanakos Charalambos Spyropoulos Spyros Panagiotopoulos menelaos Karanikolas Michalis Stavropoulos Department of Surgery School of Medicine University of PatrasRion University Hospital26500 PatrasGreece Department of Anaesthesiology and Critical Care Medicine School of Medicine University of PatrasRion University Hospital26500 PatrasGreece

AIM： To review and evaluate our experience in laparoscopic cholecystectomy. METHODS： A retrospective analysis was performed on data collected during a 13-year period （1992-2005） from 1220 patients who underwent laparoscopic cholecystectomy. RESULTS： Mortality rate was 0%. The overall morbidity rate was 5.08% （n = 62）, with the most serious complications arising from injuries to the biliary tree and the cystic artery. In 23 （1.88%） cases, cholecystectomy could not be completed laparoscopically and the operation was converted to an open procedure. Though the patients were scheduled as day-surgery cases, the average duration of hospital stay was 2.29 d, as the complicated cases with prolonged hospital stay were included in the calculation. CONCLUSION： Laparoscopic cholecystectomy is a safe, minimally invasive technique with favorable results for the patient.

关键词： Laparoscopy Cholecystectomy Minimallyinvasive

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Pituitary hormone circadian rhythm alterations in cirrhosis patients with subclinical hepatic encephalopathy

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World Journal of Gastroenterology 2008年第26期14卷 4190-4195页

作者： Dimitrios Velissaris menelaos Karanikolas Andreas Kalogeropoulos Ekaterini Solomou Panagiotis Polychronopoulos Konstantinos Thomopoulos Chrissoula Labropoulou-Karatza Department of Anaesthesiology and Intensive Care Medicine University Hospital of PatrasRion 26500Greece Department of Anaesthesiology and Intensive Care Medicine University Hospital of Patras Rion 26500Greece Department of Internal Medicine University Hospital of PatrasRion 26500Greece Department of Radiology University Hospital of Patras Rion 26500Greece Department of Neurology University Hospital of Patras Rion 26500Greece

AIM:To analyze pituitary hormone and melatonin circadian rhythms, and to correlate hormonal alterations with clinical performance, hepatic disease severity and diagnostic tests used for the detection of hepatic encephalopathy in cirrhosis. METHODS:Twenty-six patients with cirrhosis were enrolled in the study. Thirteen patients hospitalized for systemic diseases not affecting the liver were included as controls. Liver disease severity was assessed by the Child-Pugh score. All patients underwent detailed neurological assessment, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), assays of pituitary hormone, cortisol and melatonin, and complete blood chemistry evaluation. RESULTS: Pituitary hormone and melatonin circadian patterns were altered in cirrhosis patients without clinical encephalopathy. Circadian hormone alterations were different in cirrhosis patients compared with controls. Although cortisol secretion was not altered in any patient with cirrhosis, the basal cortisol levels were lowand correlated with EEG and brain MRI abnormalities. Melatonin was the only hormone associated with the severity of liver insufficiency. CONCLUSION: Abnormal pituitary hormone and melatonin circadian patterns are present in cirrhosis before the development of hepatic encephalopathy. These abnormalities may be early indicators of impending hepatic encephalopathy. Factors affecting the human biologic clock at the early stages of liver insufficiency require further study.

关键词： Liver cirrhosis Minimal hepatic encepha-Iopathy Circadian rhythms Melatonin Pituitary hormones

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The Challenge of Improving IVF Results in Normogonadotrophic (Unexpected) Young Poor Ovarian Responders: The Predictive Value of a Flexible Treatment Protocol Based on the “Biophysical Profile of the Uterus”

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Open Journal of Obstetrics and Gynecology 2015年第11期5卷 654-664页

作者： menelaos J. Tzafetas Theoharis Tantanasis Vassiliki Zournatzi Konstantinos Lathouras Aristotle Loufopoulos B’ Department of Obstetrics and Gynecology Aristotle University Thessaloniki Greece IVF and Infertility Centre Interbalcan European Hospital Thessaloniki Greece

Objective: To study whether the unexpected poor ovarian responders optimization of uterine receptivity with a flexible controlled ovarian hyper stimulation protocol based on the Biophysical Profile of the Uterus, has an impact on their reproductive performance. Design: Observational Prospective study. Setting(s): i) General hospital-IVF and Infertility Centre;ii) University hospital. Patient(s): 44 normogonadotrophic young women (26 - 38 yrs) with previous “unexpected” poor ovarian response underwent IVF/ICSI treatment on a protocol based on the Biophysical Profile of their uterus (Group A). The same patients were used as controls in a preceded IVF cycle on the conventional stimulation protocol. Intervention(s): None. Main outcome measure(s): Pregnancy, miscarriage and home take baby rates, amount and duration of gonadotropins required, number and quality of embryos resulted, Biophysical Profile of the Uterus score. Result(s). Treatment in Group A in comparison to Group B resulted in significantly larger number of eggs retrieved per patient, and improved fertilization rates and higher number of embryos/ET (p = 0.011, 0.010 and 0.034 respectively). Group A also demonstrated a trend for higher rates of clinical pregnancy (29.5% v.s. 15.9%), viable stage pregnancies ≥ 24 weeks (33.3% v.s. 20%) and home take babies (26.6% v.s. 16%). The amount of gonadotropins used per patient (IU) was similar in the two groups (p = 0.264). Cancellation, implantation and miscarriage rates as well as embryos quality, although superior in the treatment Group A, showed no significant difference. The number of pregnancies achieved in Group A, were directly related with the score in the Biophysical Profile of the Uterus 12 point scale. Conclusion(s): Unexpected Poor Ovarian Responders on the flexible IVF/ICSI protocol (Group A), adjusting the management according to the Biophysical Profile of their uterus (duration of stimulation, day of HCG and day of embryo transfer), had a significantly b

关键词： Normo-Gonadotrophic Unexpected Young Poor Ovarian Responders Biophysical Profile of the Uterus Ovarian Stimulation in Vitro Fertilization

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