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Effective use of FibroTest to generate decision trees in hepatitis C

World Journal of Gastroenterology 2009年第21期15卷 2617-2622页

作者： Dana Lau-Corona Luís Alberto Pineda Héctor Hugo Avilés gabriela gutiérrez-reyes Blanca Eugenia Farfan-Labonne Rafael Núez-Nateras Alan Bonder Rosalinda Martínez-García Clara Corona-Lau Marco Antonio Olivera-Martínez Maria Concepción gutiérrez-Ruiz Guillermo Robles-Díaz David Kershenobich Department of Experimental Medicine School of MedicineUniversidad Nacional Autonoma de MexicoGeneral Hospital of Mexico Department of Computer Sciences Institute for Applied Mathematics and SystemsUniversidad Nacional Autonoma de Mexico Department of Gastroenterology Lomas Altas Clinic

AIM： To assess the usefulness of FibroTest to forecast scores by constructing decision trees in patients with chronic hepatitis C.METHODS： We used the C4.5 classification algorithm to construct decision trees with data from 261 patients with chronic hepatitis C without a liver biopsy. The FibroTest attributes of age, gender, bilirubin, apolipoprotein, haptoglobin, α2 macroglobulin, and γ-glutamyl transpeptidase were used as predictors, and the FibroTest score as the target. For testing, a 10-fold cross validation was used.RESULTS： The overall classification error was 14.9% （accuracy 85.1%）. FibroTest＇s cases with true scores of FO and F4 were classified with very high accuracy （18/20 for FO, 9/9 for FO-1 and 92/96 for F4） and the largest confusion centered on F3. The algorithm produced a set of compound rules out of the ten classification trees and was used to classify the 261 patients. The rules for the classification of patients in FO and F4 were effective in more than 75% of the cases in which they were tested.CONCLUSION： The recognition of clinical subgroups should help to enhance our ability to assess differences in fibrosis scores in clinical studies and improve our understanding of fibrosis progression,

关键词： Hepatitis C FibroTest Decision trees C4.5algorithm Non-invasive biomarkers

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Collagen matrix scaffolds:Future perspectives for the management of chronic liver diseases

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World Journal of Clinical Cases 2023年第6期11卷 1224-1235页

作者： Moises Martinez-Castillo Itzel Altamirano-Mendoza Rafal Zielinski Waldemar Priebe Cristina Piña-Barba gabriela gutierrez-reyes Liver Pancreas and Motility LaboratoryUnit of Experimental MedicineSchool of MedicineUniversidad Nacional Autonoma de MexicoMexico City 06726Mexico CityMexico Department of Experimental Therapeutics The University of Texas MD Anderson Cancer CenterHoustonTX 77054United States Materials Research Institute Universidad Nacional Autónoma de MéxicoMexico City 06726Mexico CityMexico

Approximately 1.5 billion chronic liver disease(CLD)cases have been estimated worldwide,encompassing a wide range of liver damage ***,liver disease causes approximately 1.75 million deaths per *** is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process,cell death,over deposition of extracellular matrix proteins,and dysregulated ***,these processes impair the correct function of this vital *** and liver cancer are the main complications of CLD,which accounts for 3.5%of all deaths *** transplantation is the optimal therapeutic option for advanced liver *** liver is one of the most common organs transplanted;however,only 10%of liver transplants are *** this context,regenerative medicine has made significant progress in the design of biomaterials,such as collagen matrix scaffolds,to address the limitations of organ transplantation(e.g.,low donation rates and biocompatibility).Thus,it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.

关键词： Liver Chronic liver disease Collagen matrix scaffold Transplant Management

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Human CD4 ＋ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells

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Cellular & Molecular Immunology 2013年第3期10卷 261-274页

作者： gabriela Gonzalez-Perez Norma C Segovia Amaranta Rivas-Carvalho Diana P reyes Honorio Torres-Aguilar Sergio R Aguilar-Ruiz Claudine Irles Gloria Soldevila Carmen Sainchez-Torres 1Department of Molecular Biomedicine Centre de Investigacion y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN) Mexico City Mexico Department of Physiology Facultad de Medicina Mexico City Mexico Department of Immunology Institute de Investigaciones Biomedicas Universidad Nacional Autonoma de Mexico (UNAM) Mexico City Mexico

The peripheral repertoire of CD4＋ T lymphocytes contains autoreactive cells that remain tolerant through several mechanisms. However, nonspecific CD4＋ T cells can be activated in physiological conditions as in the course of an ongoing immune response, and their outcome is not yet fully understood. Here, we investigate the fate of human naive CD4＋ lymphocytes activated by dendritic cells （DCs） presenting endogenous self-peptides in comparison with lymphocytes involved in alloresponses. We generated memory cells （Tmem） from primary effectors activated with mature autologous DCs plus interleukin （IL）-2 （Tmauto）, simulating the circumstances of an active immune response, or allogeneic DCs （Tmallo）. Tmem were generated from effector cells that were rested in the absence of antigenic stimuli, with or without IL-7. Tmem were less activated than effectors （demonstrated by CD25 downregulation） particularly with IL-7, suggesting that this cytokine may favour the transition to quiescence. Tmauto and TmaHo showed an effector memory phenotype, and responded similarly to polyclonal and antigen-specific stimuli. Biochemically, IL-7-treated Tma^o were closely related to conventional memory lymphocytes based on Erk-l/2 activation, whereas Tmauto were more similar to effectors. Autologous effectors exhibited lower responses to IL-7 than allogeneic cells, which were reflected in their reduced proliferation and higher cell death. This was not related to IL-7 receptor expression but rather to signalling deficiencies, according to STAT5 activation These results suggest that ineffective responses to IL-7 could impair the transition to memory cells of naive CD4＋ T lymphocytes recognizing self-peptides in the setting of strong costimulation.

关键词： human CD4+ T cells IL-7 memory self-peptides

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Malnutrition negatively impacts the quality of life of patients with cirrhosis: An observational study

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World Journal of Hepatology 2017年第5期9卷 263-269页

作者： gabriela Rojas-Loureiro Alfredo Servín-Caamano Elizabeth Pérez-reyes Luis Servín-Abad Fátima Higuerade la Tijera Liver Clinic Gastroenterology DepartmentHospital General de México“Dr.Eduardo Liceaga” Internal Medicine Department Hospital General de México“Dr.Eduardo Liceaga” Gastroenterologist at Lakeland Regional Medical Center

AIMTo verify how malnutrition is related to health-related quality of life (HRQL) impairment in patients with cirrhosis. METHODSData was retrospectively abstracted from medical records and obtained by direct interview. We included patients with cirrhosis from any etiology, evaluated at the Liver Clinic from Gastroenterology Department in a tertiary healthcare center, from June 2014 to June 2016. Child-Pugh score, data about complications, and demographic, clinical and anthropometric characteristics of patients were obtained. Nutritional status was evaluated by the Subjective Global Assessment (SGA). HRQL was evaluated through the Chronic Liver Disease Questionnaire. Patients were requested to assess their global HRQL with the following code: 0 = impairment of HRQL, when it was compared with other healthy subjects; 1 = good HRQL, if it was similar to the quality of life of other healthy subjects. To compare the primary outcome between malnourished and well-nourished groups, the χ2 test, Fisher’s exact test or Student’s t-test were used, based on the variable type. Associations between predictor variables and deterioration of HRQL were determined by calculating the hazard ratio and 95% confidence interval using Cox proportional hazards regression. RESULTSA total of 127 patients with cirrhosis were included, and the mean age was 54.1 ± 12.3 years-old. According to Child-Pugh scoring, 25 (19.7%) were classified as A (compensated), 76 (59.8%) as B, and 26 (20.5%) as C (B/C = decompensated). According to SGA, 58 (45.7%) patients were classified as well-nourished. Sixty-nine patients identified HRQL as good, and 76 patients (59.8%) perceived impairment of their HRQL. Multivariate analysis to determine associations between predictor variables and self-perception of an impairment of HRQL found strong association with malnutrition (P P CONCLUSIONMalnutrition is a key factor related to impairment of HRQL in patients with cirrhosis.

关键词： Malnutrition Subjective global assessment Health-related quality of life Cirrhosis Chronic liver disease questionnaire

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Early transmission dynamics of COVID-19 in a southern hemisphere setting:Lima-Peru:February 29^(th)-March 30^(th),2020

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Infectious Disease Modelling 2020年第1期5卷 338-345页

作者： César V.Munayco Amna Tariq Richard Rothenberg gabriela G.Soto-Cabezas Mary F.reyes Andree Valle Leonardo Rojas-Mezarina César Cabezas Manuel Loayza Gerardo Chowell 无 Centro Nacional de Epidemiología Prevencion y Control de EnfermedadesPeruvian Ministry of HealthLimaPeru Department of Population Health Sciences School of Public HealthGeorgia State UniversityAtlantaGAUSA Instituto Nacional de Salud Peruvian Ministry of HealthLimaPeru Peru COVID-19 working group

The COVID-19 pandemic that emerged in Wuhan China has generated substantial morbidity and mortality impact around the world during the last four *** daily trend in reported cases has been rapidly rising in Latin America since March 2020 with the great majority of the cases reported in Brazil followed by Peru as of April 15th,*** Peru implemented a range of social distancing measures soon after the confirmation of its first case on March 6th,2020,the daily number of new COVID-19 cases continues to accumulate in this *** assessed the early COVID-19 transmission dynamics and the effect of social distancing interventions in Lima,*** estimated the reproduction number,R,during the early transmission phase in Lima from the daily series of imported and autochthonous cases by the date of symptoms onset as of March 30th,*** also assessed the effect of social distancing interventions in Lima by generating short-term forecasts grounded on the early transmission dynamics before interventions were put in *** to the implementation of the social distancing measures in Lima,the local incidence curve by the date of symptoms onset displays near exponential growth dynamics with the mean scaling of growth parameter,p,estimated at 0.96(95%CI:0.87,1.0)and the reproduction number at 2.3(95%CI:2.0,2.5).Our analysis indicates that school closures and other social distancing interventions have helped slow down the spread of the novel coronavirus,with the nearly exponential growth trend shifting to an approximately linear growth trend soon after the broad scale social distancing interventions were put in place by the *** the interventions appear to have slowed the transmission rate in Lima,the number of new COVID-19 cases continue to accumulate,highlighting the need to strengthen social distancing and active case finding efforts to mitigate disease transmission in the region.

关键词： COVID-19 SARS-CoV-2 Transmission potential Short-term forecast Reproduction number Generalized growth model

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肝纤维化和慢性病毒性肝炎（上）

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传染病网络动态 2007年第10期 14-16页

作者： gabriela gutierrez-reyes 李冰（编译）杨月（审校）

丙型肝炎病毒（HCV）和乙型肝炎病毒（HBV）感染后可导致慢性肝炎，进而有发展至肝纤维化的危险，甚至会进一步发展为肝硬化或原发性肝癌。随着对肝纤维化这一概念的理解，目前对于HCV和HBV感染的理解也越发深入。通常认为纤维化是线性... 详细信息

丙型肝炎病毒（HCV）和乙型肝炎病毒（HBV）感染后可导致慢性肝炎，进而有发展至肝纤维化的危险，甚至会进一步发展为肝硬化或原发性肝癌。随着对肝纤维化这一概念的理解，目前对于HCV和HBV感染的理解也越发深入。通常认为纤维化是线性发展的过程，但是临床证据表明纤维化的过程并不是以一成不变的速度或者是按照线性的模式发展，肝纤维化发展的实际过程有时是慢速发展有时又是快速发展。无论是慢性HCV或HBV感染，

关键词：慢性病毒性肝炎肝纤维化乙型肝炎病毒(HBV) HBV感染丙型肝炎病毒原发性肝癌慢性肝炎临床证据

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肝纤维化和慢性病毒性肝炎（下）

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传染病网络动态 2007年第12期 16-17页

作者： gabriela gutierrez-reyes 李冰（编译）杨月（审校）

慢性病毒性肝炎经常表现为隐匿性发展，相当数量的病人在没有意识到感染的情况下持续感染达数十年。细胞和体液的自然免疫反应不能根除感染，而导致一种持续的肝脏低水平炎症反应。肝脏是许多细胞因子的来源，这些细胞因子能够影响肝脏... 详细信息

慢性病毒性肝炎经常表现为隐匿性发展，相当数量的病人在没有意识到感染的情况下持续感染达数十年。细胞和体液的自然免疫反应不能根除感染，而导致一种持续的肝脏低水平炎症反应。肝脏是许多细胞因子的来源，这些细胞因子能够影响肝脏的功能。慢性病毒性肝炎存在时已观察到这些细胞因子中的TNF-α、IL—1α和β、IL-2、IL-6和IL-8在肝脏中的表达增加。外周血单核细胞（PBMCs）也能够产生不同的细胞因子，可能涉及病毒导致的肝脏损伤。

关键词：慢性病毒性肝炎肝纤维化多细胞因子外周血单核细胞肝脏损伤持续感染自然免疫反应 IL-2

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肝纤维化和慢性病毒性肝炎（中）

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传染病网络动态 2007年第11期 13-15页

作者： gabriela gutierrez-reyes 李冰（编译）杨露绮（审校）

载脂蛋白E（APOE）的多态性、细胞毒性T淋巴细胞相关蛋白4（CTLA4）、血色病基因（HFE）、低密度脂蛋白受体（LDRL）、髓过氧化物酶（MPO）、微粒体甘油三脂转移蛋白（MTP）、锰过氧化物歧化酶（SOD2）以及趋化因子受体56（CCR56）和肝... 详细信息

载脂蛋白E（APOE）的多态性、细胞毒性T淋巴细胞相关蛋白4（CTLA4）、血色病基因（HFE）、低密度脂蛋白受体（LDRL）、髓过氧化物酶（MPO）、微粒体甘油三脂转移蛋白（MTP）、锰过氧化物歧化酶（SOD2）以及趋化因子受体56（CCR56）和肝脏纤维化的进展均相关，已被共同使用以阐明作为肝脏纤维化快速进展可能预测指标的一个特殊的范畴。本文研究了参与HCV感染后的免疫反应及淋巴细胞选择性地补充到肝脏的趋化因子受体CCR5、CCR2、CCR3和它们的配体；

关键词：慢性病毒性肝炎趋化因子受体CCR5 肝纤维化细胞毒性T淋巴细胞低密度脂蛋白受体肝脏纤维化过氧化物歧化酶髓过氧化物酶

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Branched Polyamines Functionalized with Proposed Reaction Pathways Based on <sup>1</sup>H-NMR, Atomic Absorption and IR Spectroscopies

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American Journal of Analytical Chemistry 2014年第16期5卷 1090-1101页

作者： Vicente Cervantes-Mejía Elizabeth Baca-Solis Judith Caballero-Jiménez Rosario Merino-García Jesús Cruz-Gatica gabriela Moreno-Martínez Yasmi reyes-Ortega Chemical Center Sciences Institute Autonomous University of Puebla Puebla México

Three novel branched polyamines N,N,N’,N’-tetrakis-[3((pyridine-2-methyl)-amine) propyl]-1,4- butanediamine (1), N,N,N’,N’-tetrakis-[N-((2-methylpyridine)ethyl)propanamide]ethylenediamine (2) and N,N,N’,N’-tetrakis-[3((2-hidroxibenziliden)-amine)propyl]-1,4-butanediamine (3), were synthesized starting from 2-pyridinecarboxaldeyde with DAB-Am-4 for 1, PAMAM G0 for 2 and from salicylaldehyde with DAB-Am-4 for 3. The pathway reactions have been proposed by 1H-NMR, IR and Atomic Absorption Spectroscopy. The optimal reaction time was set by IR spectroscopy following aldehyde? peak modification. 1 and 2 were obtained as both hydrochlorides and as free amines and 3 only as free imine. These polyamines were characterized by UV-Vis, IR, 1H-NMR and 13C-NMR and Mass Spectrometry.

关键词： Branched Polyamines Functionalization Reactions IR NMR Atomic Absorption Spectroscopy

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Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients

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World Journal of Hepatology 2021年第2期13卷 218-232页

作者： Moises Martinez-Castillo Abigail Hernandez-Barragan Ivonne Flores-Vasconcelos Marina Galicia-Moreno Dorothy Rosique-Oramas Jose Luis Perez-Hernandez Fatima Higuera-De la Tijera Eduardo E Montalvo-Jave Aldo Torre-Delgadillo Paula Cordero-Perez Linda Muñoz-Espinosa David Kershenobich gabriela gutierrez-reyes Liver Pancreas and Motility LaboratoryUnit of Experimental MedicineSchool of MedicineGeneral Hospital of MexicoUniversidad Nacional Autonoma de MexicoMexico City 06726Mexico Department of Molecular Biology and Genomics Institute of Molecular Biology in Medicine and Gene TherapyHealth Science University CenterUniversity of GuadalajaraGuadalajara 06726Mexico Department of Gastroenterology General Hospital of Mexico“Dr.Eduardo Liceaga”Mexico City 06726Mexico Department of General Surgery General Hospital of Mexico“Dr.Eduardo Liceaga”School of MedicineUniversidad Nacional Autonoma de MexicoMexico City 06726Mexico Hepatology and Liver Transplant National Institute of Medical Sciences and Nutrition“Salvador Zubirán”Mexico City 06726Mexico University Hospital“Dr.JoséEleuterio González ”Autonomous University of Nuevo LeonMonterrey 06726Mexico

BACKGROUND Matrix metalloproteinases(MMPs)participate in the degradation of extracellular matrix compounds,maintaining the homeostasis between fibrogenesis and fibrolytic processes in the ***,there are few studies on the regulation of liver MMPs in fibrosis progression in *** To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C(CHC).METHODS A prospective,cross-sectional,multicenter study was *** patients were categorized in fibrosis grades through FibroTest®and/or FibroScan®.Serum MMP-2,-7,and-9 were determined by western blot and multiplex suspension array *** were validated by the Kruskal-Wallis and Mann-Whitney U *** Spearman correlation coefficient and area under the receiver operating characteristic curve were *** and gelatinase activity was determined through the Azocoll substrate and zymogram test,whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot *** Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy ***-7 distinguished early and advanced stages,with a correlation of 0.32(P<0.001),and the area under the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in F4(area under the receiver operating characteristic,0.705;95%confidence interval:0.605-0.805;P<0.001).Collagenolytic activity was detected at F0 and F1,whereas gelatinase activity was not detected at any fibrosis *** inhibitor of metalloproteinase-1 determination showed upregulation in F0 and F1 but downregulation in F2(P<0.001).CONCLUSION High concentrations of inactive MMPs were present in the serum of CHC patients,reflecting the impossibility to restrain liver fibrosis *** could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.

关键词： Extracellular matrix Matrix metalloproteinases Liver fibrosis Chronic hepatitis C Fibrogenesis Fibrolysis

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