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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia Castillo-gonzález elena gonzález-rey Institute of Parasitology and Biomedicine Lopez-Neyra(IPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

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Clinicopathological differences,risk factors and prognostic scores for western patients with intestinal and diffuse-type gastric cancer

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World Journal of Gastrointestinal Oncology 2022年第6期14卷 1162-1174页

作者： Cristina Díaz del Arco Lourdes Estrada Muñoz Luis Ortega Medina elena Molina Roldán MÁngeles Cerón Nieto Soledad García Gómez de las Heras M Jesús Fernández Aceñero Department of Surgical Pathology Hospital Clínico San CarlosMadrid 28040Spain Department of Legal Medicine Psychiatry and PathologyComplutense University of MadridMadrid 28040Spain Department of Surgical Pathology Hospital Rey Juan CarlosMadrid 28933Spain Department of Basic Medical Sciences Rey Juan Carlos UniversityMadrid 28933Spain

BACKGROUND In the molecular era,the Laurén system is still a cost-effective and widely implemented classification for gastric cancer(GC)and it has been recently associated with clinical,histological and molecular features of these *** recent advances in the understanding of the molecular biology of GC,there is a need to develop new prognostic tools for patient stratification in clinical ***,the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in *** To identify clinicopathological differences,risk factors,and to develop costeffective prognostic scores for patients with intestinal and diffuse-type *** Retrospective study of all patients undergoing surgery for GC at a tertiary referral center from 2001 to 2019.286 cases met inclusion criteria(intestinal:190,diffuse:96).Clinical data and gross findings were *** specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was *** tissue microarrays(TMAs)were constructed and sections of the TMA block were immunostained for HERCEPTEST,MSH2,MSH6,MLH1 and *** analyses were performed and prognostic scores were developed based on hazard *** Intestinal and diffuse-type GC showed different epidemiological,clinicopathological and prognostic *** tumors were significantly associated with younger age,less symptomatology,flat morphology,deeper invasion,perineural infiltration,advanced stage at diagnosis,administration of adjuvant therapy and poorer *** lesions were fungoid or polypoid,showed necrosis,desmoplasia,microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier *** depth,desmoplasia,macroscopic type and lymph node involvement were independently related to the Laurén ***,intestinal and diffuse GC were asso

关键词： Gastric cancer Clinicopathological Score Prognosis Laurén Molecular

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High interpretable machine learning classifier for early glaucoma diagnosis

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International Journal of Ophthalmology(English edition) 2021年第3期14卷 393-398页

作者： Carlos Salvador Fernandez Escamez elena Martin Giral Susana Perncho Martinez Nicolas Toledano Fernandez Ophthalmology Department Hospital de FuenlabradaMadrid 28942Spain Doctorate Program in Heath Sciences Universidad Rey Juan CarlosAlcorcon 28922MadnidSpain

AIM:To develop a classifier for differentiating between healthy and early stage glaucoma eyes based on peripapillary retinal nerve fiber layer(RNFL)thicknesses measured with optical coherence tomography(OCT),using machine learning algorithms with a high ***:Ninety patients with early glaucoma and 85 healthy eyes were *** glaucoma eyes showed a visual field(VF)defect with mean deviation>-6.00 d B and characteristic glaucomatous *** thickness in every quadrant,clock-hour and average thickness were used to feed machine learning *** analysis was conducted to detect and exclude *** gradient boosting algorithms were used to calculate the importance of parameters on the classifier and to check the relation between their values and its impact on the *** with the lowest importance were excluded and a weighted decision tree analysis was applied to obtain an interpretable *** under the ROC curve(AUC),accuracy and generalization ability of the model were estimated using cross validation ***:Average and 7 clock-hour RNFL thicknesses were the parameters with the highest impor *** between parameter values and impact on classification displayed a stepped pattern for average *** tree model revealed that average thickness lower than 82μm was a high predictor for early *** scores had AUC of 0.953(95%CI:0.903-0998),with an accuracy of 89%.CONCLUSION:Gradient boosting methods provide accurate and highly interpretable classifiers to discriminate between early glaucoma and healthy *** and 7-hour RNFL thicknesses have the best discriminant power.

关键词： machine learning glaucoma diagnosis optical coherence tomography

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The GSTP1 gene variant rs1695 is not associated with an increased risk of multiple sclerosis

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Cellular & Molecular Immunology 2015年第6期12卷 777-779页

作者： Jose AG Agundez elena Garcia-Martin Carmen Martinez Julian Benito-Leon Julian Benito-Leon Jorge Millan-PascualMaria Diaz-Sanchez Patricia Calleja Diana Pisa Laura Turpin-Fenoll Hortensia Alonso-Navarro Lucia Ayuso-Peralta Dolores Torrecillas Esteban Garcla-Albea Jose Francisco Plaza-Nieto Felix Javier Jimenez-Jimenez Department of Pharmacology University of Extremadura CAceres Spain Department of Biochemistry and Molecular Biology University of Extremadura Caceres Spain CiBERNED Centro de InvestigaciOn BiomEdica en Red de Enfermedades Neurodegenerativas Instituto de Salud Carlos III Spain Service of Neurology Hospital Universitario Doce de Octubre Madrid Spain Department of Medicine University Complutense Madrid Spain Section of Neurology Hospital La Mancha-Centro Alcazar de San Juan (Ciudad Real) Spain Centro de Biologfa Molecular Severo Ochoa (CSIC-UAM) Facultad de Ciencias Universidad Autonoma Cantoblanco 28049 Madrid Spain Department of Medicine-Neurology Hospital 'Principe de Asturias' Universidad de Alcala Alcala de Henares (Madrid) Spain Section of Neurology Hospital Universitario del Sureste Arganda del Rey (Madrid) Spain Correspondence: Dr FJ Jimenez-Jimenez C/Marroquina 14 3° B E-28030 Madrid Spain.

We analyzed the allelic and genotypic frequencies of the glutathione-S-transferase P1 （GSTPI） rs1695 single nucleotide polymorphism （SNP） in 290 patients with multiple sclerosis （MS） and in 310 healthy controls. We found no significant association between the rs1695 variant and MS. Among MS patients, there was no relationship between the rs1695 variant and either gender, clinical type of MS or the age of onset of MS.

关键词： associated increased sclerosis

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