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

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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Tolerance in liver transplantation: Biomarkers and clinical relevance

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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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Alpha7 nicotinic receptors as potential theranostic targets for experimental stroke

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neural Regeneration Research 2024年第5期19卷 939-940页

作者： Maider Garbizu laura Aguado Abraham martín Achucarro Basque Center for neuroscience LeioaSpain CIC biomaGUnE Basque Research and Technology AllianceSan SebastianSpain Ikerbasque Basque Foundation for Science BilbaoSpain

Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen invasion.Likewise,this inflammatory response is limited by rapid,localized,and adaptive anti-inflammatory responses which are crucial for maintaining homeostasis.Hence,the loss of these responses converts a limited and protective inflammatory response into an excessive and harmful response.Anti-inflammatory responses are integrated into the central nervous system,since the central nervous system accumulates information about harmful events,activates defenses,and builds memory for survival.At the same time,it has been demonstrated that hypothalamic neuronal signaling can be altered by inflammation in peripheral tissues.Additionally,immune cells release neuropeptides and neurotransmitters such as acetylcholine(ACh),the main neurotransmitter of the parasympathetic autonomic nervous system,evidencing the communication between the immune and nervous systems(Tracey,2002).

关键词： protective invasion Alpha

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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 ng in the possibility of needing a transplant oneself in the future(P nation(P ng kidney donation(P nce of a donated liver segment from a family member if one were needed(P ng discussed the subject with one's family(P nd friends(P ner's opinion about the subject(P ng out activities of an altruistic nature; and(12) fear of the possible mutilation of the body after donation(P nCLUSIOn: 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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nickel-based cerium zirconate inorganic complex structures for CO_(2)valorisation via dry reforming of methane

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Journal of Environmental Sciences 2024年第6期140卷 12-23页

作者： Juan Luis martín-Espejo Loukia-Pantzechroula Merkouri Jesús Gándara-Loe José Antonio Odriozola Tomas Ramirez Reina laura Pastor-Pérez Department of Inorganic Chemistry and Material Sciences Institute of Seville University of Seville-CSICSeville 41092Spain Department of Chemical and Process Engineering University of SurreyGuildford GU27XHUnited Kingdom

The increasing anthropogenic emissions of greenhouse gases(GHG)is encouraging extensive research in CO_(2)utilisation.Dry reforming of methane(DRM)depicts a viable strategy to convert both CO_(2)and CH4into syngas,a worthwhile chemical intermediate.Among the different active phases for DRM,the use of nickel as catalyst is economically favourable,but typically deactivates due to sintering and carbon deposition.The stabilisation of ni at different loadings in cerium zirconate inorganic complex structures is investigated in this work as strategy to develop robust ni-based DRM catalysts.XRD and TPR-H2analyses confirmed the existence of different phases according to the ni loading in these materials.Besides,superficial ni is observed as well as the existence of a CeniO_(3)perovskite structure.The catalytic activity was tested,proving that 10 wt.%ni loading is the optimum which maximises conversion.This catalyst was also tested in long-term stability experiments at 600and 800℃in order to study the potential deactivation issues at two different temperatures.At 600℃,carbon formation is the main cause of catalytic deactivation,whereas a robust stability is shown at 800℃,observing no sintering of the active phase evidencing the success of this strategy rendering a new family of economically appealing CO_(2)and biogas mixtures upgrading catalysts.

关键词： CO_(2)conversion Dry reforming of methane nickel catalysts Pyrochlore Cerium zirconate

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Targeting MYC-driven lymphoma:lessons learned and future directions

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Cancer Drug Resistance 2023年第2期6卷 205-222页

作者： Sandra martínez-martín Marie-Eve Beaulieu laura Soucek 无 Peptomyc S.L. Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Preclinical&Translational Research Program Vall d’Hebron Institute of Oncology(VHIO)Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Department of Biochemistry and Molecular Biology Universitat Autònoma de BarcelonaBellaterra 08193Spain InstitucióCatalana de Recerca i Estudis Avançats(ICREA) Barcelona 08010Spain

MYC plays a central role in tumorigenesis by orchestrating cell proliferation,growth and survival,among other transformation mechanisms.In particular,MYC has often been associated with lymphomagenesis.In fact,MYC overexpressing lymphomas such as high-grade B-cell lymphoma(HGBL)and double expressor diffuse large B-cell lymphomas(DLBCL),are considered addicted to MYC.In such a context,MYC targeting therapies are of special interest,as MYC withdrawal is expected to result in tumor regression.However,whether high MYC levels are always predictive of increased sensitivity to these approaches is not clear yet.Even though no MYC inhibitor has received regulatory approval to date,substantial efforts have been made to investigate avenues to render MYC a druggable target.Here,we summarize the different classes of molecules currently under development,which mostly target MYC indirectly in aggressive B-cell lymphomas,paying special attention to subtypes with MYC/BCL2 or BCL6 translocations or overexpression.

关键词： High-grade B-cell lymphoma double expressor lymphoma MYC MYC therapies

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A novel semantic segmentation approach based on U-net,WU-net,and U-net++deep learning for predicting areas sensitive to pluvial flood at tropical area

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International Journal of Digital Earth 2023年第1期16卷 3661-3679页

作者： laura Melgar-García Francisco martínez-álvarez Dieu Tien Bui Alicia Troncoso Data Science&Big Data Lab Pablo de Olavide UniversitySevilleSpain GIS Group Department of Business and ITUniversity of South-Eastern NorwayGullbringvegen 36B?i Telemark3800Norway

Floods remain one of the most devastating weather-induced disastersworldwide, resulting in numerous fatalities each year and severelyimpacting socio-economic development and the environment.Therefore, the ability to predict flood-prone areas in advance is crucialfor effective risk management. The objective of this research is to assessand compare three convolutional neural networks, U-net, WU-net, andU-net++, for spatial prediction of pluvial flood with a case study at atropical area in the north of Vietnam. They are relative new convolutionalgorithms developed based on U-shaped architectures. For this task, ageospatial database with 796 historical flood locations and 12 floodindicators was prepared. For training the models, the binary crossentropywas employed as the loss function, while the Adaptive momentestimation (ADAM) algorithm was used for the optimization of themodel parameters, whereas, F1-score and classification accuracy (Acc)were used to assess the performance of the models. The results unequivocally highlight the high performance of the three models,achieving an impressive accuracy rate of 96.01%. The flood susceptibility maps derived from this research possess considerable utility for local authorities, providing valuable insights and informationto enhance decision-making processes and facilitate the implementation of effective risk management strategies.

关键词： Flash-flood assessment convolutional networks climate change GIS

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Forage offering and seasonal intake comparisons to evaluate European rabbit threat in nothofagus forests of southern Patagonia

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Ecological Processes 2022年第1期11卷 604-617页

作者： Alejandro Huertas Herrera Mónica Toro‑Manríquez laura Borrelli María Vanessa Lencinas Guillermo martínez Pastur Centro de Investigación en Ecosistemas de la Patagonia(CIEP) Camino Baguales s/n Km 4CoyhaiqueChile Ulterarius Consultores Ambientales y Científicos Ltda. Ignacio Serrano 420CoyhaiqueChile Instituto nacional de Tecnología Agropecuaria(InTA) EEA BarilocheModesta Victoria 44508400 San Carlos de BarilocheRío NegroArgentina Laboratorio de Recursos Agroforestales Centro Austral de Investigaciones Científicas(CADIC)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Houssay 2009410 UshuaiaTierra del FuegoArgentina.

Background:The European rabbit(Oryctolagus cuniculus L.1758)was introduced into different regions of the world,generating significant trade‑offs that critically impacted native vegetation.Here,we evaluate the rabbit’s forage intakes in three vegetation types(forests,shrublands,and grasslands)along the four seasons in a temperate forest landscape in Southern Patagonia and discuss the potential threats over native vegetation.We formulated the following questions:(i)what is the forage offer at each vegetation type?(ii)what is the rabbit’s forage intake and how it varied across the seasons along the year?and(iii)which vegetation types and plant life forms were more used according to the rabbit’s forage intakes?Methods:We censused understory vegetation to characterize the forage offer at each vegetation type and determined seasonal dietary intakes using microhistological analysis of pellets.The plant species identified in the field were grouped according to life form classes(tree regeneration,shrubs,forbs,graminoids,orchids,ferns,bryophytes,and hemiparasites).Data were analysed through uni‑and multi‑variate analyses,determining relationships between forage offer and the rabbit’s forage intakes.Results:Forage intakes revealed changes in plant life form consumption across vegetation types,where intake pressure was considerably different for tree regeneration(p=0.001),graminoids(p=0.001),and hemiparasites(p=0.001).Besides,significant changes in consumption among seasons were detected for shrubs(p=0.001),ferns(p=0.030),and hemiparasites(p=0.002).Although many species play an important role in the rabbit’s forage intake networks(e.g.,Chiliotrichum diffusum,Holcus lanatus),the strongest intake linkages were found in exotic grasses(e.g.,Poa pratensis and Festuca sp.),native hemiparasites(e.g.,Misodendrum sp.),native shrubs(e.g.,Empetrum rubrum),and native trees(e.g.,nothofagus sp.).The summer and autumn seasons presented higher intake compared to the winter and spring seasons.Furthermore,hemiparasites intake(e.g.,Misodendrum

关键词： Forest ecology Oryctolagus cuniculus Plant-animal interaction Vegetation type Herbivory Habitat use

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MYC inhibitors in multiple myeloma

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Cancer Drug Resistance 2021年第4期4卷 842-865页

作者： Sandra martínez-martín laura Soucek Preclinical&Translational Research Program Vall d’Hebron Institute of Oncology(VHIO)Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Peptomyc S.L. Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Department of Biochemistry and Molecular Biology Universitat Autònoma de BarcelonaBellaterra 08193Spain InstitucióCatalana de Recerca i Estudis Avançats(ICREA) Barcelona 08010Spain

The importance of MYC function in cancer was discovered in the late 1970s when the sequence of the avian retrovirus that causes myelocytic leukemia was identified.Since then,over 40 years of unceasing research have highlighted the significance of this protein in malignant transformation,especially in hematologic diseases.Indeed,some of the earliest connections among the higher expression of proto-oncogenes(such as MYC),genetic rearrangements and their relation to cancer development were made in Burkitt lymphoma,chronic myeloid leukemia and mouse plasmacytomas.Multiple myeloma(MM),in particular,is a plasma cell malignancy strictly associated with MYC deregulation,suggesting that therapeutic strategies against it would be beneficial in treating this disease.However,targeting MYC was-and,somehow,still is-challenging due to its unique properties:lack of defined three-dimensional structure,nuclear localization and absence of a targetable enzymatic pocket.Despite these difficulties,however,many studies have shown the potential therapeutic impact of direct or indirect MYC inhibition.Different molecules have been tested,in fact,in the context of MM.In this review,we summarize the current status of the different compounds,including the results of their clinical testing,and propose to continue with the efforts to identify,repurpose,redesign or improve drug candidates to combine them with standard of care therapies to overcome resistance and enable better management of myeloma treatment.

关键词： MYC inhibition multiple myeloma undruggable target targeted therapies transcription factor epigenetics MYC downregulation

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Parental perception of child's weight,their attitudes towards child's dietary habits and the risk of obesity

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World Journal of Pediatrics 2022年第7期18卷 482-489页

作者： Lorena Garcia-Blancol Arantxa Berasaluce Andrea Romanos-nanclares Miguel Angel martinez-Gonzalez laura Moreno-Galaraga nerea martin-Calvo San Juan Primary Care Health Center.Servicio navarro de Salud-Osasunbidea PamplonaSpain IdisnA.Instituto de Investigacion Sanitaria de navrra.Pamplona Spain Department of Preventive Medicine and Public Health School of Medicine.University of NavarraC/Irunlarrea l.31080 Pamplona.Spain Biomedical Research Centre network On Obesity and Nutrition(CIBERobn).Physiopathology of Obesity and NutritionInstituteof Health Carlos Ⅲ.Av.Monforte de Lemos.3-528029 MadridSpain Department of nutrition.Harvard T.H.Chan School of Public Health Boston.MA 02115.USA Department of Pediatrices.Complejo Hospialario de navarra B.Pamplona.Spain

Background The association between parental perception of child's weight and their attitudes towards his/her dietary habits has not been reported yet.This study aimed to assess the association between parental underestimation of child's weight and parental attitudes towards child's dietary habits.Methods We conducted a cross-sectional analysis of SEnDO cohort participants recruited between January 2015 and June 2020.All information was collected through online questionnaires completed by parents.We calculated crude and multivariable-adjusted odds ratio(OR)and 95%confidence intervals(CI)for unhealthy attitudes towards child's dietary habits associated with parental underestimation of child's weight.Results Sixteen percent of children in the SEnDO project had parents who underestimated their weight.Parents who under-estimated their child's weight status were more likely to have unhealthy attitudes toward his/her dietary habits[OR 3.35;95%CI(1.71-6.53)].Conclusions Parental underestimation of child's weight was associated with unhealthy attitudes towards child's dietary hab-its.Pediatricians and public health practitioners should pay attention to the parental perception of child's weight to identify parents who underestimate it as an at-risk group in which to inquire about lifestyle and dietary habits.

关键词： Childhood obesity Dietary atitudes Eating habits Overweight Weight perception

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