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Tolerance in liver transplantation: Biomarkers and clinical relevance

World Journal of Gastroenterology 2016年第34期22卷 7676-7691页

作者： Alberto Baroja-Mazo Beatriz Revilla-Nuin pascual Parrilla laura Martínez-Alarcón Pablo Ramírez José Antonio Pons Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU) 30120 Murcia Spain Division of Gastroenterology and Hepatology and Liver Transplant Unit University Hospital Virgen de la Arrixaca 30120 Murcia Spain

Transplantation is the optimal treatment for end-stage organ failure,and modern immunosuppression has allowed important progress in short-term outcomes. However,immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus,a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor Fox P3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise,other immune cells,such as dendritic cells,monocyte/macrophages or natural killer cells,have been described as part of the process known as "operational tolerance". However,translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way,a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multicenter clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.

关键词： Liver transplantation Operational tolerance Regulatory T cells Dendritic cells Biomarkers

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Innovative Education and Training in high power laser plasmas(PowerLaPs) for plasma physics, high power laser-matter interactions and high energy density physics-theory and experiments

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High Power Laser Science and Engineering 2019年第2期7卷 22-26页

作者： John Pasley Georgia Andrianaki Andreas Baroutsos Dimitri Batani Emmanouil P.Benis Marco Borghesi Eugene Clark Donna Cook Emmanuel D'Humieres Vasilios Dimitriou Brendan Dromey Michael Ehret Ioannis Fitilis Anastasios Grigoriadis Satya Kar Evaggelos Kaselouris Ondrej Klimo Michel Koenig Kyriaki Kosma George Koundourakis Milan Kucharik Aveen Lavery Jiri Limpouch Yannis Orphanos Nektarios A.Papadogiannis Stelios Petrakis Dave Riley Maria Serena Rivetta Laura Tejada Pascual Joao Jorge Santos Alexandros Skoulakis Ioannis Tazes Vladimir Tikhonchuk Jocelain Trela Calliope Tsitou Luca Volpe Steven White Mark Yeung Michael Tatarakis York Plasma Institute University of York Technological Educational Institute of Crete School of Applied SciencesCentre for Plasma Physics and Lasers-CPPL Universitéde Bordeaux CNRSCEACELIA(Centre Lasers Intenses et Applications) Department of Physics University of Ioannina Centre for Plasma Physics School of Mathematics and PhysicsQueen’s University Belfast Faculty of Nuclear Sciences and Physical Engineering Czech Technical University in Prague LULI-CNRS Ecole Polytechnique CEA:UniversitéParis-Saclay UPMC Univ Paris 06:Sorbonne Universités CLPU Laser-Plasma Chair University of Salamanca Centro de Láseres Pulsados(CLPU) Edificio M5.Parque Cientfico.C/Adaja

The Erasmus Plus programme’Innovative Education and Training in high power laser plasmas’,otherwise known as PowerLaPs,is described.The PowerLaPs programme employs an innovative paradigm in that it is a multi-centre programme where teaching takes place in five separate institutes with a range of different aims and styles of delivery.The ’in class’ time is limited to four weeks a year,and the programme spans two years.PowerLaPs aims to train students from across Europe in theoretical,applied and laboratory skills relevant to the pursuit of research in laserplasma interaction physics and inertial confinement fusion(ICF).Lectures are intermingled with laboratory sessions and continuous assessment activities.The programme,which is led by workers from the Technological Educational Institute(TEI)of Crete,and supported by co-workers from the Queen’s University Belfast,the University of Bordeaux,the Czech Technical-University in Prague,Ecole Polytechnique,the University of Ioannina,the University of Salamanca and the University of York,has just completed its first year.Thus far three Learning Teaching Training(LTT)activities have been held,at the Queen’s University Belfast,the University of Bordeaux and the Centre for Plasma Physics and Lasers(CPPL)of TEI Crete.The last of these was a two-week long Intensive Programme(IP),while the activities at the other two universities were each five days in length.Thus far work has concentrated upon training in both theoretical and experimental work in plasma physics,high power laser-matter interactions and high energy density physics.The nature of the programme will be described in detail and some metrics relating to the activities carried out to date will be presented.

关键词： higher education inertial confinement fusion laser-plasma interactions post-graduate education

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Innovative education and training in high power laser plasmas(PowerLaPs) for plasma physics, high power laser matter interactions and high energy density physics: experimental diagnostics and simulations

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High Power Laser Science and Engineering 2020年第1期8卷 30-36页

作者： John Pasley Georgia Andrianaki Andreas Baroutsos Dimitri Batani Emmanouil PBenis Andrea Ciardi Donna Cook Vasilios Dimitriou Brendan Dromey Ioannis Fitilis Giancarlo Gatti Anastasios Grigoriadis Marine Huault Jose Antonio Pérez Hernández Evaggelos Kaselouris Ondrej Klimo Michel Koenig George Koundourakis Milan Kucharik Jiri Limpouch Richard Liska Carlos Salgado Lopez Sophia Malko Susana Olmos-Miguelanez Yannis Orphanos Valeria Ospina Nektarios APapadogiannis Stelios Petrakis Jan Psikal Maria Serena Rivetta Maria-ose Rodriguez-Conde Joao Jorge Santos Milan Sinor Alexandros Skoulakis Ioannis Tazes Laura Tejada Pascual Calliope Tsitou Pavel Vachal Luca Volpe Jiri Vyskocil Steven White Mark Yeung Ghassan Zerouli Michael Tatarakis York Plasma Institute University of YorkHeslingtonYork YO105DQUK Hellenic Mediterranean University Institute of Plasma Physics and Lasers-IPPL74100 Rethymnon73133 ChaniaCreteGreece University of Bordeaux CNRSCEACELIA(Centre Lasers Intenses et Applications)UMR 5107F-33405 TalenceFrance Department of Physics University of IoanninaGR 45110 IoanninaGreece LULI-CNRS CEASorbonne UniversiesEcole PolytechniqueInstitut Polytechnique de Paris-F-91128 Palaiseau CedexFrance Observatoire de Paris 5 Place J JanssenMeudon 92195France Centre for Plasma Physics School of Mathematics and PhysicsQueen’s University BelfastBelfast BT71NNUK Centro de Láseres Pulsados(CLPU) Edificio M5Parque CientficoC/Adaja 837185 VillamayorSalamancaSpain University of Salamanca 37008 SalamancaSpain Faculty of Nuclear Sciences and Physical Engineering Czech Technical University in PragueBrehova 711519Prague 1Czech Republic University Institute for Educational Sciences University of Salamanca37008 SalamancaSpain Group of Research“Interaction and e Learning”(GRIAL) University of Salamanca37008 SalamancaSpain CLPU Laser-Plasma Chair at University of Salamanca 37008 SalamancaSpain

The second and final year of the Erasmus Plus programme’Innovative Education and Training in high power laser plasmas’,otherwise known as PowerLaPs,is described.The PowerLaPs programme employs an innovative paradigm in that it is a multi-centre programme,where teaching takes place in five separate institutes with a range of different aims and styles of delivery.The’in-class’time is limited to 4 weeks a year,and the programme spans 2 years.PowerLaPs aims to train students from across Europe in theoretical,applied and laboratory skills relevant to the pursuit of research in laser plasma interaction physics and inertial confinement fusion.Lectures are intermingled with laboratory sessions and continuous assessment activities.The programme,which is led by workers from the Hellenic Mediterranean University and supported by co-workers from the Queen’s University Belfast,the University of Bordeaux,the Czech Technical University in Prague,Ecole Polytechnique,the University of Ioannina,the University of Salamanca and the University of York,has just finished its second and final year.Six Learning Teaching Training activities have been held at the Queen’s University Belfast,the University of Bordeaux,the Czech Technical University,the University of Salamanca and the Institute of Plasma Physics and Lasers of the Hellenic Mediterranean University.The last of these institutes hosted two 2-week-long Intensive Programmes,while the activities at the other four universities were each 5 days in length.In addition,a’Multiplier Event’was held at the University of Ioannina,which will be briefly described.In this second year,the work has concentrated on training in both experimental diagnostics and simulation techniques appropriate to the study of plasma physics,high power laser matter interactions and high energy density physics.The nature of the programme will be described in detail,and some metrics relating to the activities carried out will be presented.In particular,this paper will focus on the overall assessment of the programme.

关键词： laser plasma interactions postgraduate education

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Severe COVID-19 after liver transplantation, surviving the pitfalls of learning on-the-go: Three case reports

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World Journal of Hepatology 2020年第10期12卷 870-879页

作者： Felipe Alconchel Pedro A Cascales-Campos Jose A Pons María Martínez Josefa Valiente-Campos Urszula Gajownik María L Ortiz laura Martínez-Alarcón pascual Parrilla Ricardo Robles Francisco Sánchez-Bueno Santiago Moreno Pablo Ramírez Department of Surgery and Organ Transplantation Virgen de la Arrixaca University HospitalMurcia 30120Spain Department of Digestive Endocrine and Abdominal Surgery and TransplantationBiomedical Research Institute of Murcia(IMIBVirgen de la Arrixaca)Murcia 30120Spain Department of Hepatology Virgen de la Arrixaca University HospitalMurcia 30120Spain Department of Intensive Care Unit Virgen de la Arrixaca University HospitalMurcia 30120Spain Department of Infectious Diseases Ramon y Cajal HospitalMadrid 28034Spain

BACKGROUND The novel coronavirus 2019(COVID-19)pandemic has dramatically transformed the care of the liver transplant patient.In patients who are immunosuppressed and with multiple comorbidities,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been associated with increased severity and mortality.The main objective of this report is to communicate our experience in the therapeutic management of SARS-CoV-2 infection in 3 liver transplant patients.Secondly,we stress the management and investigation of the contagious spreading into a liver transplant ward.CASE SUMMARY The patients were two women(aged 61 years and 62 years)and one man(aged 68 years),all of them having recently received a liver transplant.All three patients required intensive care unit admission and invasive mechanical ventilation.Two of them progressed severely until death.The other one,who received tocilizumab,had a good recovery.In the outbreak,the wife of one of the patients and four healthcare professionals involved in their care were also infected.CONCLUSION We illustrate in detail the evolution of a nosocomial COVID-19 outbreak in a liver transplant ward.We believe that these findings will contribute to a better understanding of the natural history of the disease and will improve the treatment of the liver transplant patient with COVID-19.

关键词： Liver transplantation COVID-19 SARS-CoV-2 Cross infection Nosocomial infection Case report

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Intertwined leukocyte balances in tumours and peripheral blood as robust predictors of right and left colorectal cancer survival

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World Journal of Gastrointestinal Oncology 2022年第1期14卷 295-318页

作者： Ramón Cantero-Cid Karla Marina Montalbán-Hernández Jenny Guevara Alejandro pascual-Iglesias Elisa Pulido JoséCarlos Casalvilla Cristóbal Marcano Cristina Barragán Serrano Jaime Valentín Gloria Cristina Bonel-Pérez JoséAvendaño-Ortiz Verónica Terrón Roberto Lozano-Rodríguez Alejandro Martín-Quirós Elvira Marín Eva Pena laura Guerra-Pastrián Eduardo López-Collazo Luis Augusto Aguirre Tumor Immunology Laboratory The Innate Immune Response GroupHospital La Paz Institute for Health Research(IdiPAZ)Madrid 28046Spain Digestive Surgery Service La Paz University HospitalMadrid 28046Spain Emergency Department and Emergent Pathology Research Group Hospital La Paz Institute for Health Research(IdiPAZ)Madrid 28046Spain Pathologic Anatomy Service Hospital La PazMadrid 28046Spain

BACKGROUND Colorectal cancer(CRC)accounts for 9.4%of overall cancer deaths,ranking second after lung cancer.Despite the large number of factors tested to predict their outcome,most patients with similar variables show big differences in survival.Moreover,right-sided CRC(RCRC)and left-sided CRC(LCRC)patients exhibit large differences in outcome after surgical intervention as assessed by preoperative blood leukocyte status.We hypothesised that stronger indexes than circulating(blood)leukocyte ratios to predict RCRC and LCRC patient outcomes will result from combining both circulating and infiltrated(tumour/peritumour fixed tissues)concentrations of leukocytes.AIM To seek variables involving leukocyte balances in peripheral blood and tumour tissues and to predict the outcome of CRC patients.METHODS Sixty-five patients diagnosed with colon adenocarcinoma by the Digestive Surgery Service of the La Paz University Hospital(Madrid,Spain)were enrolled in this study:43 with RCRC and 22 with LCRC.Patients were followed-up from January 2017 to March 2021 to record overall survival(OS)and recurrence-free survival(RFS)after surgical interventions.Leukocyte concentrations in peripheral blood were determined by routine laboratory protocols.Paraffin-fixed samples of tumour and peritumoural tissues were assessed for leukocyte concentrations by immunohistochemical detection of CD4,CD8,and CD14 marker expression.Ratios of leukocyte concentration in blood and tissues were calculated and evaluated for their predictor values for OS and RFS with Spearman correlations and Cox univariate and multivariate proportional hazards regression,followed by the calculation of the receiver-operating characteristic and area under the curve(AUC)and the determination of Youden’s optimal cutoff values for those variables that significantly correlated with either RCRC or LCRC patient outcomes.RCRC patients from the cohort were randomly assigned to modelling and validation sets,and clinician-friendly nomograms were developed to predict OS and RFS from the

关键词： Left colorectal cancer Leukocyte ratios Prognostic variables Recurrence-free survival Right colorectal cancer Overall survival

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Paclobutrazol and Its Use in Fruit Production:A Review

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Phyton-International Journal of Experimental Botany 2022年第1期91卷 1-12页

作者： laura Raquel Orozco-Meléndez Ofelia Adriana Hernández-Rodríguez Oscar Cruz-Álvarez Loreto Robles-Hernández Graciela Dolores Avila-Quezada Esteban Sánchez Chavez DamiánAarón Porras-Flores Dámaris Leopoldina Ojeda-Barrios Facultad de Ciencias Agrotecnológicas Universidad Autónoma de ChihuahuaAvenida Pascual OrozcoChihuahua31350México Centro de Investigación y Desarrollo A.C. DeliciasChihuahua33089México

There are documentary records referring to paclobutrazol(PBZ)as a growth bioregulator that inhibits the gibberellin synthesis and its application increases yields in fruit and vegetable crop productions.Its agronomic management includes it as an emerging technology to reduce vigour,promote flower induction and flower development in fruit trees with increased economic returns.Its use is banned in some countries because of concerns about residues that can cause harmful effects on the environment.Therefore,the aim of this article was to collect,analyse and summarise relevant information on the use of PBZ in fruit tree production and its possible risks to the environment.The results obtained indicated that the application of PBZ can be effective in solving some problems related to flowering if it is applied in the right amount and at the right time.However,it is necessary to elucidate the physiological processes with which it is associated and its response to be taken into account to increase yield.PBZ is currently used in fruit trees such as mango,lime,apple and guava,increasing their productivity.However,some studies have shown its residual effect on the environment.Therefore,PBZ is a viable strategy,because it presents a series of advantages in the production of fruit trees.However,it is vital to generate protocols that seek its regulation with a rational and sustainable approach.

关键词： Environment flower induction gibberellin biosynthesis growth bioregulator vegetative growth

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Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

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World Journal of Gastroenterology 2016年第25期22卷 5800-5813页

作者： Antonio Ríos Ana Isabel López-Navas Ana Isabel López-López Francisco Javier Gómez Jorge Iriarte Rafael Herruzo Gerardo Blanco Francisco Javier Llorca Angel Asunsolo Pilar Sánchez-Gallegos Pedro Ramón Gutiérrez Ana Fernández María Teresa de Jesús laura Martínez-Alarcón Alberto Lana Lorena Fuentes Juan Ramón Hernández Julio Virseda José Yelamos José Antonio Bondía Antonio Miguel Hernández Marco Antonio Ayala Pablo Ramírez pascual Parrilla International Collaborative Donor Project ('Proyecto Colaborativo Internacional Donante' 30007 Casillas Murcia Spain Department of Surgery Paediatrics Obstetrics and Gynaecology University of Murcia Avenida de las Fuerzas Armadas 30800 Espinardo Murcia Spain Transplant Unit Surgery Service IMIB - Virgen de la Arrixaca University Hospital Carretera Madrid-Cartagena s/n 30120 El Palmar Murcia Spain Regional Transplant Centre Consejeria de Sanidad y Consumo de la Region de Murcia 30008 Ronda de Levante Murcia Spain Hospital Clinico Universitario Virgen de la Arrixaca Departamento de Cirugia General y del Aparato Digestivo Unidad de Trasplantes 30007 Casillas Murcia Spain Department of Psychology Universidad Catolica San Antonio (UCAM) Avenida de los Jeronimos 30107 Guadalupe Murcia Spain Department of Urology San Juan University Hospital of Alicante 03010 Calle Pintor Baeza Alicante Spain Universidad de Granada Avenida del Hospicio s/n 18010 Granada Spain Universidad de Navarra Campus Universitario 31080 Pamplona Navarra Spain Universidad Autonoma de Madrid Ciudad Universitaria de cantoblanco 28049 Madrid Spain Servicio de Cirugia HBP y Trasplante Hepatico Complejo Hospitalario Universitario de Badajoz Hospital Infanta Cristina Avenida Elvas s/n 06006 Badajoz Spain Universidad de Cantabria Avenida los Castros s/n 39005 Santander Cantabria Spain Departamento de Cirugia Ciencias Medicas y Sociales Facultad de Medicina y Ciencias de la Salud Universidad de Alcala Campus Cientifico-Tecnologico Plaza de San Diego s/n 28801 Alcala de Henares Madrid Spain Facultad de Medicina Universidad de Malaga 29071 Avenida de Cervantes Malaga Spain Servicio de Urologia (Complejo Hospitalario Universitario de Canarias CHUC) y Departamento de Cirugia (Universidad de La Laguna ULL) Calle Molinos de Agua s/n 38207 San Cristobal de La Laguna Santa Cruz de Tenerife Spain Departamento de Ciencias Biomedicas Basicas Facultad de Ciencias Biomedicas Universidad Europea de

AIM: To analyze the attitude of Spanish medical students toward living liver donation(LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain(n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire(PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student′s t test, χ2 test and logistic regression analysis.RESULTS: The completion rate was 95.7%(n = 9275). 89%(n = 8258) were in favor of related LLD, and 32%(n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude:(1) age(P = 0.008);(2) sex(P < 0.001);(3) academic year(P < 0.001);(4) geographical area(P = 0.013);(5) believing in the possibility of needing a transplant oneself in the future(P < 0.001);(6) attitude toward deceased donation(P < 0.001);(7) attitude toward living kidney donation(P < 0.001);(8) acceptance of a donated liver segment from a family member if one were needed(P < 0.001);(9) having discussed the subject with one's family(P < 0.001) and friends(P < 0.001);(10) a partner's opinion about the subject(P < 0.001);(11) carrying out activities of an altruistic nature; and(12) fear of the possible mutilation of the body after donation(P < 0.001).CONCLUSION: Spanish medical students have a favorable attitude toward LLD.

关键词： Attitude Living liver donation Medical students Transplantation Organ donation Psychosocial variable

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