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Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis

World Journal of Gastroenterology 2008年第10期14卷 1521-1527页

作者： Emilio Cuadrado marta alonso Maria Dolores de Juan Pilar Echaniz Juan Ignacio Arenas Immunology and Digestive units Hospital Donostia Donostia 20014 Spain

AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report four cases of corticosteroid- dependent ulcerative colitis (UC) and two Crohn’s disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25high (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β (mRNA) did not parallel that of FoxP3 mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.

关键词： Adsorptive leukocytapheresis Regulatory T cells Inflammatory bowel diseases Adacolumn Granulocyte-monocyte adsortive apheresis

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Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases

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World Journal of Gastroenterology 2022年第44期28卷 6230-6248页

作者： J Alfredo Martínez marta alonso-Bernáldez Diego Martínez-Urbistondo Juan A Vargas-Nuñez Ana Ramírezde Molina Alberto Dávalos Omar Ramos-Lopez Precision Nutrition and Cardiometabolic Health Madrid Institute of Advanced Studies-Food InstituteMadrid 28049Spain Department of Internal Medicine Hospital Universitario HM SanchinarroMadrid 28050Spain Servicio de Medicina Interna Hospital Universitario Puerta de Hierro MajadahondaMadrid 28222MajadahondaSpain Molecular Oncology and Nutritional Genomics of Cancer Madrid Institute of Advanced Studies-Food InstituteMadrid 28049Spain Laboratory of Epigenetics of Lipid Metabolism Madrid Institute of Advanced Studies-Food InstituteMadrid 28049Spain Medicine and Psychology School Autonomous University of Baja CaliforniaTijuana 22390Baja CaliforniaMexico

The liver is a key organ involved in a wide range of functions,whose damage can lead to chronic liver disease(CLD).CLD accounts for more than two million deaths worldwide,becoming a social and economic burden for most *** the different factors that can cause CLD,alcohol abuse,viruses,drug treatments,and unhealthy dietary patterns top the *** conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic *** stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma(HCC).Despite the advances achieved in this field,new approaches are needed for the prevention,diagnosis,treatment,and prognosis of *** this context,the scientific community is using machine learning(ML)algorithms to integrate and process vast amounts of data with unprecedented *** techniques allow the integration of anthropometric,genetic,clinical,biochemical,dietary,lifestyle and omics data,giving new insights to tackle CLD and bringing personalized medicine a step *** review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatoryrelated,hepatitis viruses-induced,and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.

关键词： Machine learning Liver inflammation Liver disease Viral diseases Comorbidity

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Pharmacogenetics of hepatocellular carcinoma and cholangiocarcinoma

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Cancer Drug Resistance 2019年第3期2卷 680-709页

作者： marta alonso-Peña Anabel Sanchez-Martin Paula Sanchon-Sanchez Meraris Soto-Muñiz Ricardo Espinosa-Escudero Jose J.G.Marin Experimental Hepatology and Drug Targeting(HEVEFARM) IBSALUniversity of SalamancaSalamanca 37007Spain Center for the Study of Liver and Gastrointestinal Diseases(CIBERehd).Carlos III National Institute of Health Madrid 28029Spain.

Primary liver cancers constitute the fourth most deadly group of *** poor prognosis is due in part to the pre-existence and/or development,often during treatment,of powerful mechanisms accounting for the poor response of cancer cells to antitumor *** include both impaired gene expression and the appearance of spliced variants,polymorphisms and mutations,affecting the function of genes leading to the reduction in intracellular concentrations of active agents,changes in molecular targets and survival pathways,altered tumor microenvironment and phenotypic *** present review summarizes available information regarding the role of germline and somatic mutations affecting drug transporters,enzymes involved in drug metabolism,organelles and signaling molecules related to liver cancer chemoresistance.A more complete picture of the actual complexity of this problem is urgently needed for carrying out further pharmacogenomic studies aimed to improve the management of patients suffering from hepatocellular carcinoma or cholangiocarcinoma.

关键词： Anticancer drug chemoresistance chemotherapy cholangiocarcinoma germline mutation hepatoma liver cancer somatic mutation

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Increased Susceptibility to Pneumococcal Disease in Sjogren Syndrome Patients

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World Journal of Vaccines 2014年第2期4卷 45-49页

作者： Maria Ercibengoa marta alonso Jose M.Marimon Jose Ramon Saenz-Domínguez Emilio Perez-Trallero Biomedical Research Centre Network for Respiratory Diseases(CIBERES) San SebastianSpain Servicio de Microbiología-Instituto Biodonostia Hospital Universitario DonostiaSan SebastiánSpain Department of Preventive Medicine and Public Health Faculty of MedicineBasque Country UniversityUPV/EHUSan SebastiánSpain

Susceptibility to pneumococcal infections in Sj?gren syndrome (SS)―an autoimmune inflammatory disease―patients is not well known, although these patients frequently develop respiratory diseases. The relative risk of developing pneumococcal disease in SS patients versus diabetes mellitus type 2 (DM-2) patients, matched by age, gender, and length of enrolment was studied. From January 1998 to September 2013 the records of Donostia University Hospital were analyzed, which among other patient’s data includes: number and type of hospital admissions and number and type of laboratory determinations. Streptococcus pneumoniae isolates of the same serotype causing recurrent infections were characterized by PFGE. The study comprised 127 patients in the SS group (69 primary and 58 secondary) and 127 in the DM-2 group as control. In 12 SS patients, (9.4%) 22 pneumococcal disease episodes were detected. Two patients (1.6%) with a single episode each one were observed among DM-2 patients, p = 0.01, RR for SS patients 6 (95% CI 1.4 to 26.3). No differences could be demonstrated between the two groups of patients in infections caused by Staphylococcus aureus or Streptococcus agalactiae. Most pneumococcal serotypes in SS patients belonged to the 13-valent (50%) and 23-valent (75%) anti-pneumococcal vaccine. SS patients are associated with and increased risk of suffering from pneumococcal disease. Vaccination should be considered in this group of patients.

关键词： Sjogren Syndrome Diabetes Mellitus Type 2 Pneumococcal Vaccine Streptococcus pneumoniae

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Constructive thinking,rational intelligence and irritable bowel syndrome

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World Journal of Gastroenterology 2009年第25期15卷 3106-3113页

作者： Enrique Rey marta Moreno Ortega Monica Olga Garcia alonso Manuel Diaz-Rubio Department of Digestive Diseases Hospital Clinico San Carlos (IMSALUD)and Faculty of MedicineComplutense University

AIM： To evaluate rational and experiential intelligence in irritable bowel syndrome （IBS） sufferers. METHODS： We recruited 100 subjects with IBS as per Rome 11 criteria （50 consulters and 50 non-consulters） and 100 healthy controls, matched by age, sex and educational level. Cases and controls completed a clinical questionnaire （including symptom characteristics and medical consultation） and the following tests： rational- intelligence （Wechsler Adult Intelligence Scale, 3rd edition）; experiential-intelligence （Constructive Thinking Inventory）; personality （NEO personality inventory）; psychopathology （MMPI-2）, anxiety （state-trait anxiety inventory） and life events （social readjustment rating scale）. Analysis of variance was used to compare the test results of IBS-sufferers and controls, and a logistic regression model was then constructed and adjusted for age, sex and educational level to evaluate any possible association with IBS. RESULTS： No differences were found between IBS cases and controls in terms of IQ （102.0 ± 10.8 vs 102.8 ± 12.6）, but IBS sufferers scored significantly lower in global constructive thinking （43.7± 9.4 vs 49.6 ± 9.7）. In the logistic regression model, global constructive thinking score was independently linked to suffering from IBS [OR 0.92 （0.87-0.97）], without significant OR for total IQ. CONCLUSION： IBS subjects do not show lower rational intelligence than controls, but lower experiential intelligence is nevertheless associated with IBS.

关键词： Constructive thinking Intelligence tests Intelligence Irritable bowel syndrome

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Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance

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World Journal of Gastroenterology 2017年第18期23卷 3367-3373页

作者： Angel Cosme Milagrosa Montes Begona Ibarra Esther Tamayo Horacio alonso Usua Mendarte Jacobo Lizasoan marta Herreros-Villanueva Luis Bujanda Gastroenterology Department Hospital Universitario Donostia/Instituto BiodonostiaUniversidad del País VascoCentro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas Biomedical Research Center Network for Respiratory Diseases Microbiology Department Hospital Universitario Donostia-Instituto Biodonostia Faculty of Life Sciences Universidad Isabel I

To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic *** total of 1034 patients infected by Helicobacter pylori (H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori-resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg ***., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori-resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg ***., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a ***-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them *** susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

关键词： Helicobacter pylori Resistance Eradication rate Antimicrobial susceptibility Therapies

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Non-guided self-learning program for high-proficiency optical diagnosis of diminutive and small colorectal lesions: A single-endoscopist pilot study

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World Journal of Gastroenterology 2019年第10期25卷 1278-1287页

作者： Marco Bustamante-Balén Carla Satorres Lorena Puchades Belén Navarro Natalia García-Morales Noelia alonso marta Ponce Lidia Argüello Vicente Pons-Beltrán Gastrointestinal Endoscopy Research Group Gastrointestinal Endoscopy UnitDigestive Diseases DepartmentLa Fe Polytechnic University Hospital Digestive Diseases Department La Fe Polytechnic University Hospital Gastrointestinal Endoscopy Unit Digestive Diseases DepartmentLa Fe Polytechnic University Hospital

BACKGROUND The implementation of optical diagnosis(OD) of diminutive colorectal lesions in clinical practice has been hampered by differences in performance between community and academic settings. One possible cause is the lack of a standardized learning tool. Since the factors related to better learning are not well described, strong evidence upon which a consistent learning tool could be designed is lacking. We hypothesized that a self-designed learning program may be enough to achieve competency in OD of diminutive lesions of the *** To assess the accuracy of OD of diminutive lesions in real colonoscopies after application of a self-administered learning *** This was a single-endoscopist prospective pilot study, in which an experienced endoscopist followed a self-designed, self-administered learning program in OD of colorectal lesions. An assessment phase divided in two halves with a 6-mo period in between without performance of OD was developed in a populationbased colorectal cancer screening program. The accomplishment of the Preservation and Incorporation of Valuable Endoscopic Innovations criteria and performance measures were calculated overall and in the two halves of the assessment phase, assessing their response to the 6-mo stopping period. The evolution of performance through blocks of 50 lesions was also *** Overall, 152 patients and 522 lesions(≤ 5 mm: 399, and 6-9 mm: 123) were included. The negative predictive value for the OD of adenoma in rectosigmoid lesions diagnosed with high confidence was 91.7% [95% confidence interval(CI):87.3-96.6]. The proportion of agreement on surveillance interval between OD and pathological diagnosis was higher than 95%. Overall accuracy for diminutive lesions diagnosed with high confidence was 89.5%(95%CI: 86.3-92.7). The overall accuracy of OD was similar in the two halves of the assessment phase [90.1(95%CI: 85.6-94.7) vs 88.2(95%CI: 87.9-95.9)]. All the other performance parameters we

关键词： Optical diagnosis Accuracy Learning Polyp Colonoscopy Education

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LDAP Injection Techniques

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Wireless Sensor Network 2009年第4期1卷 233-244页

作者： Jose Maria alonso Antonio GUZMAN marta BELTRAN Rodolfo BORDON 不详

The increase in the number of databases accessed only by some applications has made code injection attacks an important threat to almost any current system. If one of these applications accepts inputs from a client and executes these inputs without first validating them, the attackers are free to execute their own queries and therefore, to extract, modify or delete the content of the database associated to the application. In this paper a deep analysis of the LDAP injection techniques is presented. Furthermore, a clear distinction between classic and blind injection techniques is made.

关键词： Web Applications Security Code Injection Techniques LDAP

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Boron nitride nanoresonators for phonon-enhanced molecular vibrational spectroscopy at the strong coupling limit

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Light(Science & Applications) 2017年第1期6卷 55-62页

作者： marta Autore Peining Li Irene Dolado Francisco J Alfaro-Mozaz Ruben Esteban Ainhoa Atxabal Fèlix Casanova Luis E Hueso Pablo alonso-González Javier Aizpurua Alexey Y Nikitin Saül Vélez Rainer Hillenbrand CIC nanoGUNE Donostia-San Sebastián 20018Spain Donostia International Physics Center(DIPC) Donostia-San Sebastián 20018Spain IKERBASQUE Basque Foundation for ScienceBilbao 48013Spain Departamento de Física Universidad de OviedoOviedo 33007Spain Centro de Física de Materiales(MPC CSIC-UPV/EHU)Donostia-San Sebastián 20018Spain Current address:Department of Materials ETH ZürichZürich 8093Switzerland CIC nanoGUNE and UPV/EHU Donostia-San Sebastián 20018Spain

Enhanced light-matter interactions are the basis of surface-enhanced infrared absorption(SEIRA)spectroscopy,and conventionally rely on plasmonic materials and their capability to focus light to nanoscale spot *** polariton nanoresonators made of polar crystals could represent an interesting alternative,since they exhibit large quality factors,which go far beyond those of their plasmonic *** recent emergence of van der Waals crystals enables the fabrication of highquality nanophotonic resonators based on phonon polaritons,as reported for the prototypical infrared-phononic material hexagonal boron nitride(h-BN).In this work we use,for the first time,phonon-polariton-resonant h-BN ribbons for SEIRA spectroscopy of small amounts of organic molecules in Fourier transform infrared ***,the interaction between phonon polaritons and molecular vibrations reaches experimentally the onset of the strong coupling regime,while numerical simulations predict that vibrational strong coupling can be fully *** polariton nanoresonators thus could become a viable platform for sensing,local control of chemical reactivity and infrared quantum cavity optics experiments.

关键词： boron nitride phonon polaritons strong coupling surface-enhanced infrared absorption spectroscopy SEIRA

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Impact of the Transboundary Transport of Air Pollutants on Air Quality in Spain

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Journal of Environmental Protection 2012年第9期3卷 1167-1175页

作者： marta G. Vivanco Inmaculada Palomino Juan Luis Garrido Ma ángeles González Gonzalo alonso Fernando Martín Centro de Investigaciones Energéticas Medioambientales y Teconológicas (CIEMAT) Air Pollution Unit Madrid Spain

Although compliance with the European limit values for air pollutants has been achieved over large parts in Spain, some challenges remain for O3 on the maximum daily 8-hour mean and information limit values, for particulate matter on the PM10 annual and daily limit values and for NO2 on annual and hourly limit values. Transboundary transport of air pollutants has started to be recognized as a mechanism affecting air quality. Nevertheless, as a consequence of the complexity of atmospheric chemistry it is not easy to determine the importance of this effect. Photochemical models constitute an adequate tool to address this challenge, allowing the identification of pollutant pathways and the quantifi- cation of the influence of long-range transport of air pollutants. In this paper we evaluate the influence of out-of-Spain emissions on this non-compliance picture by using the CHIMERE photochemical model. For this purpose the model was run at a 0.2?-horizontal resolution for a European domain. Although at this resolution not all the local effects can be captured, transboundary transport of air pollutants can be examined. Several simulations were performed considering different emission scenarios. To see all out-of-Spain emissions influence, all the emissions were set to zero, excepting those in Spain. This includes examining European and ships effects on air quality in Spain. A second simulation was performed setting to zero just European-countries emissions, to see the effect of Europe. The third and fourth simulations were carried out by setting to zero France and Portugal emissions respectively. Ozone has been found to be the pollutant more affected by this transboundary transport, in particular in the summer period. The model indicates that the incoming air masses contributed in 2009 to the non-compliance with the European normative regulating the maximum daily 8-hour mean.

关键词： Transboundary Transport Air Pollution

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