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T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

Cellular & Molecular Immunology 2017年第6期14卷 497-510页

作者： jose-Ignacio Rodriguez-Barbosa carlos Fernandez-Renedo Ana Maria Bravo Moral Leo Biihler Maria-Luisa del Rio Transplantation Immunobiology Section Institute of Biomedicine University of Leon and Castilla and Leon Regional Transplantation Coordination Leon University Hospital Leon Spain Department of Veterinary Clinical Sciences University of Santiago de Compostela Veterinary Faculty Lugo Spain Visceral and Transplantation Surgery Department of Surgery University Hospitals of Geneva and Faculty of Medicine Geneva Switzerland

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

关键词： BTLA (CD272) humoral immunity HVEM (TNFRSF14, CD270) T follicular helper cells transplantation

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Inner ear hair cell regeneration A look from the past to the future

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Neural Regeneration Research 2013年第24期8卷 2284-2289页

作者： Francisco Santaolalla carlos Salvador Agustín Martínez jose María Sánchez Ana Sánchez del Rey Department of Otorhinolaryngology Basurto University Hospital Department of Dermatology Ophthalmology and Otorhinolaryngology School of Medicine University of the Basque Country (UPV/EHU)

Most recent studies on regeneration of inner ear hair cells focus on use of stem cells, gene therapy and neurotrophic factors. Cochlear gene therapy has been successfully used in the treatment of neu- rosensory hearing loss. This suggests that cochlear hair cell regeneration is possible. The objective of this paper is to review research and clinical application of inner near hair cell regeneration.

关键词： neural regeneration reviews hearing loss hair cells cochlea genes stem cells viral vectors regeneration neuroregeneration

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An international guideline with six personalised titration schedules for preventing myocarditis and pneumonia associated with clozapine

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General Psychiatry 2022年第3期35卷 157-162页

作者： jose de Leon Can-Jun Ruan Georgios Schoretsanitis Christopher Rohde Elif Anıl Yağcıoğlu Trino Baptista Oleg O Kirilochev carlos De las Cuevas Christoph U Correll Mental Health Research Center Eastern State HospitalLexingtonKentuckyUSA 2 Biomedical Research Centre in Mental Health Net(CIBERSAM)Hospital Santiago ApóstolVitoria-GasteizSpain 3 Laboratory of Clinical PsychopharmacologyBeijing An Ding HospitalBeijingChina 4 The National Clinical Research Centre for Mental Disorders&Beijing Key Lab of Mental DisordersBeijing An Ding HospitalBeijingChina 5 PsychiatryUniversity of ZürichZurichSwitzerland 6 Psychiatry ResearchZucker Hillside HospitalGlen OaksNew YorkUSA 7 Affective DisordersAarhus University HospitalAarhusDenmark 8 Clinical MedicineAarhus UniversitetAarhusDenmark 9 PsychiatryHacettepe UniversitesiAnkaraTurkey 10PhysiologyLos Andes University Medical SchoolMeridaBolivarian Republic of Venezuela 11Clinical PharmacologyAstrakhan State Medical UniversityAstrakhanAstrahanskaâRussian Federation 12Department of Internal MedicineDermatology and Psychiatry and Instituto Universitario de Neurociencia(IUNE)Universidad de La LagunaLa LagunaSpain 13Child and Adolescent PsychiatryCharitéUniversitätsmedizin BerlinBerlinGermany

White blood cell(WBC)monitoring has reduced clozapinetreated patient deaths associated with agranulocytosis to a ***,clozapine protocols and package inserts worldwide provide no instructions for preventing myocarditis or pneumonia during clozapine *** worldwide are largely unaware of ***,as they worry about agranulocytosis,their clozapine-treated patients are at risk of dying from pneumonia or ***,an international guideline with 104 authors from 50 countries/regions was recently published to provide personalised clozapine titration schedules for adult *** forum article reviews pneumonia and myocarditis occurring during clozapine titration,as well as the three most innovative aspects of this new guideline:(1)personalised titration,(2)C reactive protein(CRP)measures,and(3)dose predictions based on blood *** metabolism is influenced by 3 levels of complexity:(1)ancestry groups,(2)sex-smoking subgroups,and(3)presence/absence of poor metabolizer *** 3 groups of variables should determine the maintenance dose and speed of clozapine titration;they are summarised in a table in the *** international clozapine titration guideline recommends measuring CRP levels simultaneously with WBC,at baseline and weekly at least for the first 4 weeks of titration,the highest risk period for clozapine-induced myocarditis.

关键词： titration subgroups absence

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Recalcitrant cell wall of Ulva lactuca seaweed is degraded by a single ulvan lyase from family 25 of polysaccharide lyases

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Animal Nutrition 2022年第2期9卷 184-192页

作者： Monica M.Costa Luís B.Pio Pedro Bule Vania A.Cardoso Marlene Duarte Cristina M.Alfaia Diogo F.Coelho Joana A.Bras carlos M.G.A.Fontes jose A.M.Prates CIISA-Centro de Investigaçao Interdisciplinar em Sanidade Animal Faculdade de Medicina Veterinari1Universidade de Lisbo1Alto da Ajud11300-477 Lisbo1Portugal NZYTech-Genes and Enzymes Estrada do Paço do LumiarCampus do LumiarEdifício E1649-038 Lisbo1Portugal

Green macroalgae,e.g.,Ulva lactuca,are valuable bioactive sources of nutrients;but algae recalcitrant cell walls,composed of a complex cross-linked matrix of polysaccharides,can compromise their utilization as feedstuffs for monogastric *** study aimed to evaluate the ability of pre-selected Carbohydrate-Active enZymes(CAZymes)and sulfatases to degrade *** cell walls and release nutritive compounds.A databank of 199 recombinant CAZymes and sulfatases was tested in vitro for their action towards *** cell wall *** enzymes were incubated with the macroalga,either alone or in combination,to release reducing sugars and decrease fluorescence intensity of Calcofluor White stained cell *** individual action of a polysaccharide lyase family 25(PL25),an ulvan lyase,was shown to be the most efficient in cell wall *** ulvan lyase treatment,in triplicate measures,promoted the release of 4.54 g/L(P0.05),proteins(P?0.861)or pigments(P>0.05)was *** results highlight the capacity of a single recombinant ulvan lyase(PL25 family)to incompletely disrupt *** cell *** enzyme could enhance the bioaccessibility of *** bioactive products with promising utilization in the feed industry.

关键词： Macroalga Ulva lactuca Carbohydrate-active enzyme Ulvan lyase Cell wall degradation

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Facial nerve palsy following parotid gland surgery:A machine learning prediction outcome approach

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第4期9卷 271-279页

作者： carlos M.Chiesa‐Estomba jose A.González‐García Ekhiñe Larruscain Jon A.Sistiaga Suarez Miquel Quer Xavier León Paula Martínez‐Ruiz de Apodaca Celia López‐Mollá Miguel Mayo‐Yanez Alfonso Medela Department of Otorhinolaryngology—Headand Neck Surgery Donostia University HospitalDonosti‐San SebastiánSpain Head&Neck Study Group of Young‐Otolaryngologists of the International Federations of Oto‐rhino‐laryngological Societies(YO‐IFOS) ParisFrance Biodonostia Health Research Institute San SebastiánSpain Department of Otorhinolaryngology Hospital Santa Creu I Sant PauUniversitatAutònoma de BarcelonaBarcelonaSpain Department of Otorhinolaryngology Doctor Peset University HospitalValenciaSpain Otorhinolaryngology—Head and Neck Surgery Department Complexo Hospitalario Universitario A Coruña(CHUAC)A CoruñaGaliciaSpain Clinical Research in Medicine International Center for Doctorate and Advanced Studies(CIEDUS)Universidade de Santiago deCompostela(USC)Santiago de CompostelaGaliciaSpain LEGIT Health BilbaoSpain

Introduction:Machine learning (ML)‐based facial nerve injury (FNI) forecasting grounded on multicentric data has not been released up to *** distinct ML models,random forest (RF),K‐nearest neighbor,and artificial neural network (ANN),for the prediction of FNI were evaluated in this ***:A retrospective,longitudinal,multicentric study was performed,including patients who went through parotid gland surgery for benign tumors at three different university ***:Seven hundred and thirty‐six patients were *** most compelling aspects related to risk escalation of FNI were as follows:(1) location,in the mid‐portion of the gland,near to or above the main trunk of the facial nerve and at the top part,over the frontal or the orbital branch of the facial nerve;(2) tumor volume in the anteroposterior axis;(3) the necessity to simultaneously dissect more than one level;and (4) the requirement of an extended resection compared to a lesser extended *** contrast,in accordance with the ML analysis,the size of the tumor (>3 cm),as well as gender and age did not result in a determining favor in relation to the risk of ***:The findings of this research conclude that ML models such as RF and ANN may serve evidence‐based predictions from multicentric data regarding the risk of ***:Along with the advent of ML technology,an improvement of the information regarding the potential risks of FNI associated with patients before each procedure may be achieved with the implementation of clinical,radiological,histological,and/or cytological data.

关键词： gland machine learning parotid personalized medicine surgery

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Novel nanocomposites based on a strawberry-like gold-coated magnetite （Fe@Au） for protein separation in multiple myeloma serum samples

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Nano Research 2015年第4期8卷 1189-1198页

作者： jose E. Araujo carlos Lodeiro jose L. Capelo Benito Rodrfguez-Gonzalez Alcindo A. dos Santos~ Hugo M. Santos Javier Ferna.ndez-Lodeiro BIOSCOPE Research Group UCIBIO-REQUIMTE Department of Chemistry Faculty of Science and Technology University NOVA of Lisbon 2829-516 Caparica Portugal PROTEOMASS Scientific Society Madan Parque Rua dos Inventores 2825-182 Caparica Portuga Scientific and Technological Research Assistance Centre (CACTI) University of Vigo Vigo Spain Instituto de Quimica Universidade de Sao Paulo Av. Prof. Lineu Prestes 748 CxP 26077 Sao Paulo 05508-000 Brazil

在水的媒介生产与像草莓的金 nanoparticles 部分涂的磁铁矿的一个新过程被报导。对磁场和金基于 nanoparticle 的胶体的系统的光性质的快反应是这新 Fe@Au nanomaterial 的二个主要优点。这些优点允许为在 proteomics 和 biomedicine ... 详细信息

在水的媒介生产与像草莓的金 nanoparticles 部分涂的磁铁矿的一个新过程被报导。对磁场和金基于 nanoparticle 的胶体的系统的光性质的快反应是这新 Fe@Au nanomaterial 的二个主要优点。这些优点允许为在 proteomics 和 biomedicine 的各种各样的目的这新胶体的 nanomaterial 的使用当蛋白质能也绑在表面，和表面罐头，是 functionalized。作为 proof-of-concept，新 Fe@Au nanoparticles 为蛋白质的集中前和分离作为一个工具在 biomarker 发现被估计了从复杂 proteomes。到这个目的，从健康的人的 sera 与从与多重骨髓瘤诊断的病人的 sera 相比。与集体 spectrometry 相结合的这新 Fe@Au nanomaterial 的应用程序允许 53 的鉴定蛋白质，和它也证明了热吃惊蛋白质 HSP75 和血浆朊酶 C1 禁止者是为多重骨髓瘤前进的诊断和控制的潜在的 biomarkers。

关键词：蛋白质分离多发性骨髓瘤血清样品磁铁矿纳米复合材料镀金草莓金纳米粒子

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Neoadjuvant treatment in non-small cell lung cancer:New perspectives with the incorporation of immunotherapy

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World Journal of Clinical Oncology 2022年第5期13卷 314-322页

作者： carlos Aguado Luis Chara Mónica Antonanzas jose Maria Matilla Gonzalez Unai Jiménez Raul Hernanz Xabier Mielgo-Rubio Juan carlos Trujillo-Reyes Felipe Counago Department of Medical Oncology Hospital Clínico Universitario San CarlosMadrid 28040Spain Department of Medical Oncology Hospital Universitario de GuadalajaraGuadalajara 19002Spain Department of Thoracic Surgery Hospital Clínico Universitario de ValladolidValladolid 47005Spain Department of Thoracic Surgery Hospital Universitario CrucesBarakaldoBizkaia 48903Basque CountrySpain Department of Radiation Oncology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Medical Oncology Hospital Universitario Fundación AlcorcónAlcorcón 28922MadridSpain Department of Thoracic Surgery Hospital de la Santa Creu I Sant PauBarcelona 08029CataloniaSpain Department of Surgery Universitat Autonoma de BarcelonaBarcelona 08029CataloniaSpain Department of Radiation Oncology Hospital Universitario Quirónsalud MadridPozuelo de Alarcón 28223MadridSpain Department of Radiation Oncology Hospital La LuzMadrid 28003Spain Medicine Department School of Biomedical SciencesUniversidad Europea de MadridVillaviciosa de Odón 28670MadridSpain

The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical *** chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable *** with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional *** immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term ***,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative ***,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival *** we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

关键词： Non-small cell lung cancer Neoadjuvant Immune checkpoint inhibitors Immunotherapy Anti-PD1 Anti-PD-L1 Complete pathological response

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An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair

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Regenerative Biomaterials 2019年第6期6卷 335-347页

作者： Filippo Cipriani Blanca Arino Palao Israel Gonzalez de Torre Aurelio Vega Castrillo Hector jose Aguado Hernandez Matilde Alonso Rodrigo Angel jose Alvarez Barcia Ana Sanchez Veronica Garcıa Diaz Monica Lopez Pena jose carlos Rodriguez-Cabello Technical Proteins Nanobiotechnology S.L. Paseo Belen 9AValladolid 47011Spain Departamento de traumatologıa Hospital Clınico de ValladolidAv.Ramon y Cajal 3Valladolid 47003Spain Bioforge University of Valladolid CIBER-BBNPaseo de Belen 19Valladolid 47011Spain SIBA-UVA:servicio investigacion y bienestar animal University of ValladolidC/Plaza de Santa Cruz 8Valladolid 47002Spain Instituto de Biologıa y Genetica Molecular(IBGM) Universidad de Valladolid y CSICCalle Sanz y Fores 3Valladolid 47003Spain Facultad de veterinaria Campus UniversitarioAvda.Carballo Calero s/nLugo 27002Spain

The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral *** the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells(rMSCs)were tested for the regeneration of critical subchondral defects in 10 New Zealand ***,cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4months for histological and gross evaluation of features of biomaterial performance,including integration,cellular infiltration,surrounding matrix quality and the new matrix in the *** both approaches helped cartilage regeneration,the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration,whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline *** conclusion,the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.

关键词： biopolymer animal test cartilage bone

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Assessment of hybrid geoids in Chile and Spain,combining GGM and GNSS/Leveling observations

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Geodesy and Geodynamics 2021年第2期12卷 65-92页

作者： jose Antonio Tarrio Mosquera Marcelo Caverlotti Silva Fernando Isla carlos Prado University of Santiago of Chile(USACH) Faculty of EngineeringGeographical Engineering DepartmentChile Geographic Military Institute Chile

This research presents the results for analyses done to five geopotential global models(GGM),comparing them with ground data from GNSS and leveling in heterogenic zones from the geodetic perspective,in Chile and *** the official and complete implementation of the International Height Reference Frame(IHRF)has not yet been established,the vertical geodetic system of many countries is not calculated on a global scale;instead,it is calculated by the variation of relative heights between one or more local tide gauges,such as in the case of Spain and *** aspect creates regional and specific altimetry data,which disables the use of GGM to directly obtain the orthometric height of the vertical reference system(VRS)from the GNSS *** models currently reach centimetric precision due to their high resolution but are directly incompatible for a local *** solve this,we expose in this article the contrast between geometric geoidal undulation(ellipsoidal heights and orthometric data from the leveling networks in Spain and Chile)with the geoidal undulation in more recent models and higher resolution:Earth Gravitational Model 2008(EGM08),European Improved Gravity model of the Earth by New techniques(EIGEN6 C4),Gravity Observation Combination(GOCO05 C),Experimental Gravity Field Model(XGM2016),and Ultra-High Resolution Global Geopotential Model(SGG-UGM),adjusting the residual between both referential heights by different parametric models and polynomials of determined *** evaluated,their geoidal undulations are combined with GNSS/leveling data from the corresponding VRS to generate a correcting surface,which is also known as a hybrid geoid,resulting in a model of optimal adjustment for the combination of five parameters of the EIGEN-6 C4 with orthometric heights and ellipsoids of both Chile and *** results show 2-3 cm precisions,which were statistically analyzed to determine the suitability for *** final products are three grids of indep

关键词： GNSS levelling Correcting surface IHRS SIRGAS EIGEN-6C4

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Autoregressive spatial analysis and individual tree modeling as strategies for the management of Eremanthus erythropappus

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Journal of Forestry Research 2016年第3期27卷 595-603页

作者： Henrique Ferraco Scolforo jose Roberto Soares Scolforo jose Marcio de Mello Anto nio carlos Ferraz Filho Diogo Francisco Rossoni Thiza Falqueto Altoe Antonio Donizette Oliveira Renato Ribeiro de Lima Department of Forest Science Federal University of Lavras PO Box: 3037 Lavras MG 37200-000 Brazil Department of Statistics State University of Maringa Av. Colombo 5.790 Jd. Universitario Bloco E90 Maringa PR 87020-900 Brazil Department of Statistics Federal University of Lavras PO Box: 3037 Lavras MG 37200-000 Brazil

The objectives of this study were to apply statistical techniques to discriminate fertilization treatments of Eremanthus erythropappus（DC.） Mac *** autoregressive modeling, and to develop individual tree models for diameter and crown area（CA） projection to define management strategies for candeia plantations subjected to different fertilization treatments. This is an important tree species originating from the Brazilian Atlantic Rain forest and Savannah biomes, intensively used in the cosmetic industry. Nonetheless, to date, research has not addressed the management of natural stands or plantations of the species. Our experiment was located in Baependi, Minas Gerais, Brazil, and comprised of four randomized blocks and 13 treatments. The treatments consisted of 12 different regimes of fertilization plus a control. Each sample plot was composed of 50 plants plus two border plants in a planting spacing of 2.5 9 2.0 m and undergoing pruning at 5 and 6 years of age. Starting in the second year, total tree height（H） and circumference（at 1.30 m from the ground or breast height, CBH） were measured every 6 months. Starting in the fifth year CA was measured. Tree growth varied by fertilization *** were detected by using an autoregressive approach, considering that standard statistical methods were not powerful enough to detect significant *** growth groups were formed, and maximum growth was obtained for treatment 10（NPK, 8-28-16）. Management guidelines are provided based on individual tree models for different fertilization levels.

关键词： Management strategies Candeia Fertilization level Brazil Crown area

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