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showing 10 items of 1724 documents

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

2020

Contains fulltext : 218274.pdf (Publisher’s version ) (Closed access) Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called "episignatures"). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging pa…

0301 basic medicine[SDV]Life Sciences [q-bio]Computational biology030105 genetics & heredityBiologyPediatricsArticleCohort Studiesmolecular diagnostics03 medical and health sciencessymbols.namesakeGenetic HeterogeneityGene duplicationGeneticsHumansHunter-McAlpine syndromeGenetics (clinical)Mass screening030304 developmental biologyEpiSignGenetics0303 health sciencesNeurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]DNA methylationGenetic heterogeneity030305 genetics & heredityCorrectionSyndromeDNA MethylationMolecular diagnosticsPhenotypePenetranceHuman genetics3. Good healthepisignaturegenomic DNA030104 developmental biologyPhenotypeNeurodevelopmental DisordersDNA methylationuncertain clinical casesMendelian inheritancesymbolsIdentification (biology)VUS classification
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An overview of the molecular mechanisms underlying development and progression of bicuspid aortic valve disease

2019

Bicuspid aortic valve (BAV) is a common congenital heart malformation frequently associated with the development of aortic valve diseases and severe aortopathy, such as aortic dilatation, aneurysm and dissection. To date, different genetic loci have been identified in syndromic and non- syndromic forms of BAV. Among these, genes involved in the regulation of extracellular matrix remodelling, epithelial to mesenchymal transition and nitric oxide metabolism appear to be the main contributors to BAV pathogenesis. However, no- single gene model explains BAV inheritance, suggesting that more factors are simultaneously involved. In this regard, characteristic epigenetic and immunological profiles…

0301 basic medicineaneurysm; aortic dilatation; aortic stenosis; aortopathy; bicuspid aortic valve; NOTCH1Aortic stenosibicuspid aortic valveHeart malformationAortic DiseasesHeart Valve Diseasesaortopathy610 Medicine & healthDisease030204 cardiovascular system & hematologyBioinformatics2705 Cardiology and Cardiovascular Medicine11459 Center for Molecular CardiologyPathogenesis03 medical and health sciences0302 clinical medicineAneurysmBicuspid aortic valveNOTCH1Bicuspid Aortic Valve Disease1312 Molecular BiologymedicineSettore MED/05 - Patologia ClinicaAnimalsHumansEpithelial–mesenchymal transitionEpigeneticsMolecular BiologyAortic dilatationbusiness.industryaortic stenosisaortic dilatationmedicine.disease030104 developmental biologyAortic ValveaneurysmDisease Progressioncardiovascular systemCardiology and Cardiovascular MedicinebusinessJournal of Molecular and Cellular Cardiology
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SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

2017

AbstractBiogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we…

0301 basic medicineconformation:Diseases::Wounds and Injuries::Fractures Bone::Hip Fractures [Medical Subject Headings]:Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings]Polimorfismo de nucleótido simpleGene ExpressionboneOsteoblastosDensidad ósea:Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]Cohort StudiesGene Frequencysingle nucleotide polymorphismBone DensityBone cellOssosgeneticsFracturas osteoporóticasCells CulturedGeneticsBone mineralMicroARNsMultidisciplinarymicroRNAbiologyQalleleR:Diseases::Wounds and Injuries::Fractures Bone::Osteoporotic Fractures [Medical Subject Headings]clinical trialMiddle Agedcohort analysisPhenotypeHumanosFenotipmedicine.anatomical_structureCancellous BoneosteoblastMedicine:Diseases::Musculoskeletal Diseases::Bone Diseases [Medical Subject Headings]:Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings]:Anatomy::Cells::Connective Tissue Cells::Osteoblasts [Medical Subject Headings]AlelosFenotipomusculoskeletal diseasesmedicine.medical_specialtyGenotypeScienceSingle-nucleotide polymorphismBiologychemistryPolymorphism Single NucleotideArticleBone and Bones:Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Cancellous Bone [Medical Subject Headings]03 medical and health sciencesCalcification PhysiologicInternal medicinemicroRNAmedicineHumanshumanproceduresAllele:Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings]AllelesFemoral neckGenetic associationAgedcell culture:Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Bone Density [Medical Subject Headings]:Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism Genetic::Polymorphism Single Nucleotide [Medical Subject Headings]OsteoblastsEnfermedades óseasFracturas de caderaComputational BiologyCuello femoral:Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Antisense Elements (Genetics)::RNA Antisense::MicroRNAs [Medical Subject Headings]MicroRNAs030104 developmental biologyEndocrinologymulticenter studybone mineralizationNucleic Acid ConformationOsteoporosispathology:Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Bones of Lower Extremity::Leg Bones::Femur::Femur Neck [Medical Subject Headings]TranscriptomemetabolismGenotipoFractures
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Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive err…

2020

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects …

0301 basic medicinegenetic structuresMedicine (miscellaneous)EmmetropiaGenome-wide association studyVARIANTSGenome-wide association studiesSensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Cornea0302 clinical medicineRisk FactorsCorneaDatabases GeneticMULTIPLEMyopiaGene Regulatory NetworksEXPRESSION PATTERNS10. No inequalitylcsh:QH301-705.5POPULATIONGeneticseducation.field_of_studymedicine.diagnostic_testHERITABILITYCorneal DiseasesAsian Continental Ancestry Group ; Axial Length Eye ; Cornea ; Corneal Topography ; Databases Genetic ; European Continental Ancestry Group ; Gene Regulatory Networks ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Myopia ; Phenotype ; Polymorphism Single Nucleotide ; Refractometry ; Risk Assessment ; Risk FactorsCorneal topographyEYE SIZE3. Good healthAxial Length EyePhenotypemedicine.anatomical_structureGeneral Agricultural and Biological SciencesExtracellular matrix organizationKeratoconusCorneal diseasesPopulationBiologyPolymorphism Single NucleotideRisk AssessmentArticleWhite PeopleGeneral Biochemistry Genetics and Molecular BiologyOCULAR COMPONENT DIMENSIONS03 medical and health sciencesSPHERICAL EQUIVALENTAsian PeoplemedicineHumansGenetic Predisposition to DiseaseKERATOCONUS3125 Otorhinolaryngology ophthalmologyeducationCorneal Topographymedicine.diseaseCOLLAGENeye diseasesRefractometry030104 developmental biologylcsh:Biology (General)Genetic LociRE3111 Biomedicinesense organs030217 neurology & neurosurgeryGenome-Wide Association StudyCommunications Biology
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Antigen specificity and clinical significance of IgG and IgA autoantibodies produced in situby tumor-infiltrating b cells in breast cancer

2018

An important role for tumor infiltrating B lymphocytes (TIL-B) in the immune response to cancer is emerging; however, very little is known about the antigen specificity of antibodies produced in situ. The presence of IgA antibodies in the tumor microenvironment has been noted although their biological functions and clinical significance are unknown. This study used a 91-antigen microarray to examine the IgG and IgA autoantibody repertoires in breast cancer (BC). Tumor and adjacent breast tissue supernatants and plasma from BC patients together with normal breast tissue supernatants and plasma from healthy controls (patients undergoing mammary reduction and healthy blood donors) were analyze…

0301 basic medicinelcsh:Immunologic diseases. AllergyAdultMaleautoantibodiesIgGT cellImmunologytumor-infiltrating B cellsBreast Neoplasms03 medical and health sciences0302 clinical medicineImmune systemLymphocytes Tumor-Infiltratingbreast cancerAntigenAntibody SpecificityAntigens NeoplasmImmunology and AllergyMedicineHumansAgedOriginal ResearchTumor microenvironmentB-Lymphocytesbiologybusiness.industryAutoantibodyGerminal centerGénéralitésMiddle AgedImmunoglobulin A030104 developmental biologymedicine.anatomical_structure030220 oncology & carcinogenesisImmunoglobulin GImmunologybiology.proteinFemaleAntibodybusinesslcsh:RC581-607Ex vivoIgAtertiary lymphoid structures
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IL-25 dampens the growth of human germinal center-derived B-cell non Hodgkin Lymphoma by curtailing neoangiogenesis

2018

Interleukin (IL)-25, a member of the IL-17 cytokine superfamily, is produced by immune and non-immune cells and exerts type 2 pro-inflammatory effects in vitro and in vivo. The IL-25 receptor(R) is composed of the IL-17RA/IL-17RB subunits. Previous work showed that germinal centre (GC)-derived B-cell non Hodgkin lymphomas (B-NHL) expressed IL-17AR, formed by IL-17RA and IL-17RC subunits, and IL-17A/IL-17AR axis promoted B-NHL growth by stimulating neoangiogenesis. Here, we have investigated expression and function of IL-25/IL-25R axis in lymph nodes from human GC-derived B-NHL, i.e. Follicular Lymphoma (FL,10 cases), Diffuse Large B Cell Lymphoma (6 cases) and Burkitt Lymphoma (3 cases). Tu…

0301 basic medicinelcsh:Immunologic diseases. AllergyPathologymedicine.medical_specialtyAngiogenesismedicine.medical_treatmentImmunologyFollicular lymphomalcsh:RC254-282Angiogenesis; B lymphocytes; B-NHL; Cytokines; IL-25; Tumor immunology; Immunology and Allergy; Immunology; Oncology03 medical and health sciencesangiogenesisIL-25immune system diseaseshemic and lymphatic diseasesmedicineImmunology and AllergyCytokineOriginal ResearchB lymphocyteChemistryGerminal centerInterleukinmedicine.diseaselcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogenscytokinesLymphomaAngiogenesi030104 developmental biologyCytokineOncologyCancer researchB-Cell Non-Hodgkin LymphomaTumor immunologyB-NHLb lymphocyteslcsh:RC581-607Diffuse large B-cell lymphoma
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Clinical validation of 13-gene DNA methylation analysis in oral brushing samples for detection of oral carcinoma: an Italian multicenter study

2021

Background The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. Methods Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. Results DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patien…

0301 basic medicinemedicine.medical_specialtyBisulfite sequencingalgorithm; bisulfite sequencing; diagnostic test; oral brushing; oral squamous cell carcinoma; quantitative DNA methylation analysisGastroenterologyoral brushing03 medical and health sciences0302 clinical medicineInternal medicineHealthy volunteersCarcinomamedicineHumansquantitative DNA methylation analysisMouth neoplasmalgorithmbusiness.industryDNA Methylationmedicine.diseaseDna amplificationoral squamous cell carcinomastomatognathic diseases030104 developmental biologyItalyOtorhinolaryngologyMulticenter studyHead and Neck Neoplasmsdiagnostic test030220 oncology & carcinogenesisDNA methylationCarcinoma Squamous Cellbisulfite sequencingMouth NeoplasmsbusinessOral medicine
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Deconvolution of the cellular origin in hepatocellular carcinoma: Hepatocytes take the center stage.

2016

The expression of biliary/progenitor markers by hepatocellular carcinoma (HCC) is often associated with poor prognosis and stem cell-like behaviors of tumor cells. Hepatocellular adenomas (HCA) also often express biliary/progenitor markers and frequently act as precursor lesions for HCC. However, the cell of origin of HCA and HCC that expresses these markers still remains unclear. Therefore, to evaluate if mature hepatocytes give rise to HCA and HCC tumors, and to understand the molecular pathways involved in tumorigenesis, we lineage-labeled hepatocytes by injecting adeno-associated virus (AAV) containing thyroxine-binding globulin (TBG) promoter driven-Cre into RosaYFP mice. Yellow fluore…

0301 basic medicinemedicine.medical_specialtyCarcinoma HepatocellularHepatologyLiver NeoplasmsBiologymedicine.diseaseGastroenterologydigestive system diseasesArticle03 medical and health sciences030104 developmental biologyCellular originInternal medicineHepatocellular carcinomamedicineCancer researchCarcinomaHepatocytesHumansCenter (algebra and category theory)DeconvolutionStage (cooking)Hepatology (Baltimore, Md.)
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In response to the article published by Fukaya et al., entitled: “Relationships between the center of pressure and the movements of the ankle and kne…

2017

International audience

0301 basic medicinemedicine.medical_specialtyKnee JointMovementOsteoarthritisKnee Jointbiomechanicsknee osteoarthritisBiomechanical Phenomena[ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system03 medical and health sciences0302 clinical medicinePhysical medicine and rehabilitationCenter of pressure (terrestrial locomotion)center of pressuremedicineHumansOrthopedics and Sports MedicineIn patientGaitComputingMilieux_MISCELLANEOUS030203 arthritis & rheumatologybusiness.industryBiomechanicsknee braceOsteoarthritis Kneemedicine.diseaseBiomechanical Phenomenalocomotion030104 developmental biologymedicine.anatomical_structureAnkleAnklebusinessAnkle JointMedial knee
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Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional ad…

2021

BACKGROUND: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. METHODS: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-prove…

0301 basic medicinemedicine.medical_specialtyPopulationlaw.inventionTumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14]03 medical and health sciencesFolinic acidAll institutes and research themes of the Radboud University Medical Center0302 clinical medicineRandomized controlled triallawTumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]medicineClinical endpointeducationeducation.field_of_studyPerformance statusbusiness.industryTotal mesorectal excisionOxaliplatinSurgery030104 developmental biologyOncology030220 oncology & carcinogenesisbusinessChemoradiotherapymedicine.drugThe Lancet Oncology
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