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Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

World Journal of Gastroenterology 2014年第42期20卷 15820-15829页

作者： xabier garcía-albéniz Rosa Gallego Ralf Dieter Hofheinz Gloria Fernández-Esparrach Juan Ramón Ayuso-Colella Josep Antoni Bombí Carles Conill Miriam Cuatrecasas Salvadora Delgado Angels Ginés Rosa Miquel Mario Pagés Estela Pineda Verónica Pereira Aarón Sosa Oscar Reig Iván Victoria Luis Feliz Antonio María de Lacy Antoni Castells Iris Burkholder Andreas Hochhaus Joan Maurel Department of Epidemiology Harvard School of Public Health Department of Medical Oncology Hospital Clínic ICMHO IDIBAPS CIBEREHD University of Barcelona Interdisciplinary Tumor Center Mannheim and Ⅲ Medical Clinic University Hospital Mannheim University of Heidelberg Department of Gastroenterology Endoscopy Unit Hospital Clínic ICMDiM IDIBAPS CIBEREHD University of Barcelona Department of Radiology Hospital Clínic CDI IDIBAPS University of Barcelona Department of Pathology Hospital Clínic IDIBAPS University of Barcelona Department of Radiation Oncology Hospital Clínic ICMHO University of Barcelona Department of Gastrointestinal Surgery Hospital Clínic ICMDiM IDIBAPS CIBEREHD University of Barcelona Department of Gastroenterology Hospital Clínic ICMDiM IDIBAPS CIBEREHD University of Barcelona Department of Nursing and Health University of Applied Sciences of the Saarland Department for Hematology and Oncology Clinic for Internal Medicine Ⅱ Jena University Hospital

AIM:To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.METHODS:Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy.Laparoscopic surgery was planned after 5-8 wk.Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol.Patients with ypT1-2N0 or ypT3-4 or N+were offered 5-fluorouracil-based adjuvant treatment on an individual basis.An external cohort was used as a reference for the findings.RESULTS:One hundred and seventy six patients were treated with induction chemoradiotherapy and 170underwent total mesorectal excision.Cancer staging of ypT0N0 was achieved in 26/170(15.3%)patients.After a median follow-up of 58.3 mo,patients withypT0N0 had five-year disease-free and overall survival rates of 96%(95%CI:77-99)and 100%,respectively.We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation.The inherent good prognosis of these patients will have implications for clinical trial design and care of patients.CONCLUSION:Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.

关键词： Exercise Follow-up Gastrointestinal dis-eases Irri

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Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

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Genes & Diseases 2024年第3期11卷 22-25页

作者： alberto Gomez-Carballa Maria Jose Curras-Tuala Sara Pischedda Miriam Cebey-Lopez Jose Gomez-Rial Irene Rivero-Cale Jacobo Pardo-seco xabier Bello Sandra Viz-Lasheras Antonio Justicia-Grande Julian Montoto-Louzao alba Camino-Mera Isabel Ferreiros-Vidal Maximo Fraga Jose RAntunez Rodolfo Gomez Federico Martinon-Torres Antonio Salas Genetics Vaccines and Infections Research Group(GENVIP)Instituto de Investigacion Sanitaria de SantiagoSantiagode CompostelaGalicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Laboratorio de Inmunologia Servicio de Andlisis ClinicosHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Unidade de Xenetica Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigacion SanitariaHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Musculoskeletal Pathology Group Instituto de Investigacion Sanitaria de SantiagoServicio Galego de Saude(SERGAS)Santiago de CompostelaGalicia 15706Spain Department of Pathology Hospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Unidad Integrada de BiobancosBiomodelos 3D y Modelos Animales IDIS(lnstituto de Investigacion Sanitaria de Santiagode Compostela)Galicia15706Spain Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias(CIBER-ES) MadridSpain

Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)gene.However,the molecular mechanisms underlying HO remain poorly understood.As a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.

关键词： stimulating driving asi

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Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

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World Journal of Nephrology 2024年第2期13卷 5-15页

作者： xabier Pérez-Aizpurua Ramiro Cabello Benavente Gonzalo Bueno Serrano JoséMaría Alcázar Peral Blanca Gómez-Jordana Mañas Jaime Tufet i Jaumot Joaquín Ruiz de Castroviejo Blanco Felipe Osorio Ospina Carmen Gonzalez-Enguita Department of Urology Hospital Universitario Fundación Jiménez DíazMadrid 28015MadridSpain

Obstructive uropathy is defined as the structural or functional interruption of urinary outflow at any level in the urinary tract.It is regarded as one of the most prevalent causes of acute kidney injury(AKI),accounting for 5%–10%of cases.Acute severe obstruction of the urinary tract is a potentially threatening situation for the kidneys and therefore requires prompt identification and management to relieve obstruction.The aim of the present article is to review and synthesize available evidence on obstructive uropathy,providing a clinical guideline for clinicians.A literature review on obstructive uropathy in the context of AKI was performed,focusing on the least clarified aspects regarding diagnosis and management.Recent literature searching was conducted in English and top-level evidence articles including systematic reviews,metanalyses and large series were prioritized.Acute obstruction of the urinary tract is a diagnostic and therapeutical challenge that may lead to important clinical complications together with direct structural and hemodynamic damage to the kidney.Early recognition of the leading cause and its exact location is essential to ensure prompt urinary drainage together with the most suitable drainage technique selection.A multidisciplinary approach,including urologists,nephrologists,and other medical specialties,is best suited to correctly manage concomitant hemodynamic changes,fluid and electrolyte imbalances,and other related issues.Obstructive uropathy is one of the leading causes of AKI.Recognition of patients suitable for early diversion and feasibility or adequate selection of the indicated technique is sometimes challeng-ing.A thorough understanding of the physiopathology behind the development of urinary obstruction is vital for correct diagnosis and management.

关键词： Obstructive uropathy Urinary tract obstruction Obstruction of the urinary tract Acute kidney injury Urinary diversion Renal recovery

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Simultaneous analysis of the intestinal parasites and diet through eDNA metabarcoding

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Integrative Zoology 2023年第3期18卷 399-413页

作者： xabier CABODEVILLA Benjamín Juan GÓMEZ-MOLINER Naiara ABAD María JoséMADEIRA Department of Zoology and Animal Cell Biology Faculty of PharmacyUniversity of the Basque Country(UPV/EHU)AlavaSpain Instituto de Investigación en Recursos Cinegéticos(IREC)(CSIC-UCLM-JCCM) Ciudad RealSpain

Agricultural expansion and intensiﬁcation are having a huge impact on plant and arthropod diversity and abun-dance,affecting food availability for farmland birds.Difﬁcult food access,in turn,can lead to immunosuppression and a higher incidence of parasites.In the studies designed to examine changes in the diet of birds and their par-asites,metabarcoding is proving particularly useful.This technique requires mini-barcodes capable of amplifying the DNA of target organisms from fecal environmental DNA.To help to understand the impact of agricultural expansion on biodiversity,this study sought to design and identify mini-barcodes that might simultaneously as-sess diet and intestinal parasites from the feces of farmland birds.The capacity to identify diet and parasites of 2 existing and 3 newly developed mini-barcodes was tested“in silico”in relation to the behavior of a reference eukaryotic barcode.Among the newly designed mini-barcodes,MiniB18S_81 showed the higher taxonomic cover-age of eukaryotic taxa and a greater ampliﬁcation and identiﬁcation capacity for diet and parasite taxa.Moreover,when it was tested on fecal samples from 5 different steppe bird species,MiniB18S_81 showed high taxonomic resolution of the most relevant diet and parasite phyla,Arthropoda,Nematoda,Platyhelminthes,and Apicomplexa at the order level.Thus,the mini-barcode developed emerges as an excellent tool to simultaneously provide detailed information regarding the diet and parasites of birds,essential for conservation and management.

关键词： biomonitoring broad-spectrum primers eukaryotic mini-barcodes fecal eDNA farmland birds parasitology

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Neoadjuvant immunotherapy in non-small-cell lung cancer:Times are changing—and fast

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World Journal of Clinical Oncology 2022年第9期13卷 758-761页

作者： Carlos Aguado Unai Jiménez Maestre xabier Mielgo-Rubio Department of Medical Oncology Hospital Universitario Clínico San CarlosMadrid 28040Spain Department of Thoracic Surgery Hospital Universitario CrucesBarakaldo 48903BizkaiaSpain Department of Medical Oncology Hospital Universitario Fundación AlcorcónAlcorcón 28922MadridSpain

Recent data from a phase 3 trial have shown that the addition of immunotherapy to neoadjuvant chemotherapy improves event-free survival in patients with nonsmall-cell lung cancer(NSCLC).This is the first positive phase 3 trial in this setting,although several phase 3 trials are currently investigating the efficacy of neoadjuvant and adjuvant immunotherapy in resectable NSCLC.

关键词： Neoadjuvant Immunotherapy NSCLC Perioperative Checkmate-816 nivolumab Chemo-immunotherapy

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Biliary spillage a new prognostic factor in gallbladder cancer?

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Hepatobiliary Surgery and Nutrition 2019年第5期8卷 537-538页

作者： xabier de Aretxabala Department of Surgery Clínica Alemana de SantiagoSantiagoChile

Gallbladder cancer is considered a rare disease associatedwith a dismal prognosis(1-3).However,since the irruptionof laparoscopic cholecystectomy,incidental cases haveincreased and prognosis improved.The main reason f... 详细信息

关键词： prognosis cancer gallbladder

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LIBRA:an adaptative integrative tool for paired single-cell multi-omics data

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Quantitative Biology 2023年第3期11卷 246-259页

作者： xabier Martinez-de-Morentin Sumeer AKhan Robert Lehmann Sisi Qu alberto Maillo Narsis AKiani Felipe Prosper Jesper Tegner David Gomez-Cabrero Navarrabiomed Complejo Hospitalario de Navarra(CHN)Universidad Pública de Navarra(UPNA)IdiSNAPamplona 31001Spain Biological and Environmental Sciences and Engineering Division King Abdullah University of Science and TechnologyThuwal 23955Saudi Arabia Algorithmic Dynamic Lab Department of Oncology and PathologyCenter for Molecular MedicineKarolinska InstituteStockholm 17177Sweden Division of Hemato-Oncology Center for Applied Medical Research CIMACancer Center University of Navarra(CCUN)Navarra Institute for Health Research(IDISNA)CIBERONCPamplona 31008Spain Department of Hematology Clinica Universidad de NavarraCIBERONC Pamplona 31008Spain Computer Electrical and Mathematical Sciences and Engineering DivisionKing Abdullah University of Science and TechnologyThuwal 23955Saudi Arabia

Background:Single-cell multi-omics technologies allow a profound system-level biology understanding of cells and tissues.However,an integrative and possibly systems-based analysis capturing the different modalities is challenging.In response,bioinformatics and machine learning methodologies are being developed for multi-omics single-cell analysis.It is unclear whether current tools can address the dual aspect of modality integration and prediction across modalities without requiring extensive parameter fine-tuning.Methods:We designed LIBRA,a neural network based framework,to learn translation between paired multi-omics profiles so that a shared latent space is constructed.Additionally,we implemented a variation,aLIBRA,that allows automatic fine-tuning by identifying parameter combinations that optimize both the integrative and predictive tasks.All model parameters and evaluation metrics are made available to users with minimal user iteration.Furthermore,aLIBRA allows experienced users to implement custom configurations.The LIBRA toolbox is freely available as R and Python libraries at GitHub(TranslationalbioinformaticsUnit/LIBRA).Results:LIBRA was evaluated in eight multi-omic single-cell data-sets,including three combinations of omics.We observed that LIBRA is a state-of-the-art tool when evaluating the ability to increase cell-type(clustering)resolution in the integrated latent space.Furthermore,when assessing the predictive power across data modalities,such as predictive chromatin accessibility from gene expression,LIBRA outperforms existing tools.As expected,adaptive parameter optimization(aLIBRA)significantly boosted the performance of learning predictive models from paired data-sets.Conclusion:LIBRA is a versatile tool that performs competitively in both“integration”and“prediction”tasks based on single-cell multi-omics data.LIBRA is a data-driven robust platform that includes an adaptive learning scheme.

关键词： single-cell multi-omic Autoencoder auto-finetuning

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Master of one trade:Arbutus unedo relies on plasticity to persist under habitats differing in water availability

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Journal of Plant Ecology 2017年第5期10卷 869-881页

作者： xabier Santiso Rubén Retuerto Área de Ecología Facultad de BiologíaCampus VidaUniversidade de Santiago de Compostela15782 Santiago de CompostelaSpain

Aims the limited water supply in the Mediterranean Basin will be exacerbated in the immediate future as result of severe drought events.thus,the study of the intraspecific variability in functional traits of plant species is important,because such variability modulates species’responses.Here,we aimed to analyse the variability in plasticity of physiological and structural traits of Arbutus unedo L.in response to water availability and to determine whether the levels of phenotypic plasticity varied in plants of different provenances.Methods We kept two sets of plants under contrasted water regimes(high water and low water)and calculated a phenotypic plasticity index to determine the plastic response to water stress.We compared the response among kind of traits and provenance.We also per-formed analysis of variance to assess the trait and provenance effect.Important Findings We found that biomass and key physiological traits decrease under drought conditions,while the water use efficiency increased.Plasticity differed between groups of traits,being higher in structural and gas exchange parameters,but the provenance did not account for signifi-cant variation in plasticity.A.unedo has evolved a‘good saver’strat-egy,involving decreasing growth and water use-when this resource is unavailable-together with the dissipation of excess of radiation that it cannot process.the homogeneous response between provenances may be the result of a canalization event.this strategy,based on a high degree of plasticity,is a probable determining factor in the success of the species over its wide range of environmental conditions and will be critical to withstand the ongoing environmental changes.

关键词： adaptation canalization contrasted provenances drought global change phenotypic plasticity

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Pitfalls of barcodes in the study of worldwide SARSCoV-2 variation and phylodynamics

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Zoological Research 2021年第1期42卷 87-93页

作者： Jacobo Pardo-Seco alberto Gómez-Carballa xabier Bello Federico Martinón-Torres Antonio Salas Unidade de Xenética Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigación Sanitaria(IDIS)Hospital Clínico Universitario de Santiago(SERGAS)Galicia 15706Spain Genetics Vaccines and Pediatric Infectious Diseases Research Group(GENVIP)Instituto de Investigación Sanitaria de Santiago(IDIS)and Universidad de Santiago de Compostela(USC)Galicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clínico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain

DEAR EDITOR,Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks.We show that purely mathematical procedures for site selection should be supervised by known phylogeny(i)to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties,and(ii)to avoid phylogenetic redundancy.We propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites(as a proxy for phylogenetic-based criteria).This procedure demonstrates that,for short barcodes(e.g.,11 sites),there are thousands of informative site combinations that improve previous proposals.We also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny,such that most representative genomes in these ancestral nodes are no longer in circulation.Consequently,coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.

关键词： dynamics properly purely

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High-resolution patterns of palaeoenvironmental changes during the Little Ice Age and the Medieval Climate Anomaly in the northwestern Iberian Peninsula

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Geoscience Frontiers 2020年第5期11卷 1461-1475页

作者： Daniel Castro Martin Souto Maria Isabel Fraga Eduardo garcia-Rodeja Sebastian Perez-Diaz Jose Antonio Lopez Saez xabier Pontevedra-Pombal Dpto.Botanica Fac.BioloxiaUniversidade de Santiago de CompostelaGaliciaSpain Dpto.Edafoloxia e Quimica Agricola Fac.BioloxiaUniversidade de Santiago de CompostelaGaliciaSpain Dpto.Geografia Urbanismo y Ordenacion Del TerritorioETS CaminosCanales y PuertosUniversidad de CantabriaSpain GI Arqueobiologia Instituto de HistoriaCCHS–CSICMadridSpain

to identify plant macrofossils,estimate peat humification and calculate hydroclimatic indices based on current bog species,with the overall aim of determining the climate conditions associated with evolution of the bog during the Medieval Climate Anomaly and the Little Ice Age.These proxies,together with historical and climate data,proved to be good indicators of the changes in bog surface wetness.Analysis:of the core led to identification of 9 different periods:two corresponding to the so-called Medieval Climate Anomaly(930 to 1345 AD,1075–665 calibrated years before present[cal.yr BP]);four corresponding to the Little Ice Age(1345 to 1905 AD;665–105 cal yr BP);and three corresponding to the last century(1905 to 2000 AD).The findings revealed a generally dry climate that lasted until the 14th century,followed by a transition to a long period with a more humid,but characteristically very variable climate,which ended at the beginning of the 20th century and was followed by a rapid transition to more humid conditions and finally,a change to drier conditions.The Medieval Climate Anomaly was indicated by the abundance of dry-adapted mosses(Leucobryum glaucum,Hypnum cupressiforme)and characterized by warm dry conditions and high levels of peat humification,with alternating wet phases.The LIA period was dated by a large abundance of Sphagnum species(an indicator of wetness)and a gradual increase in the humification index.However,four different climate phases were differentiated in this period.High-resolution reconstruction of the evolution of the CVM bog and the multiproxy approach have together enabled a more detailed identification of climatic variations in this area,which are generally consistent with the global models,as well as better definition of the elusive climatic oscillations in the last millennium and confirmation of the importance of local modulation of global models.The study provides new information and a detailed chronology of climatic events that will help to refine local modulation of the climate evol

关键词： Last millennium Raised bog Plant macrofossil Humification analysis Southwest Europe Climate change

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