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Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

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World Journal of Gastroenterology 2024年第14期30卷 1982-1989页

作者： Julieta Trinks María F Mascardi Adrián Gadano sebastián marciano Instituto de Medicina Traslacional e Ingeniería Biomédica-Consejo nacional de Investigaciones Científicas y Técnicas-Instituto Universitario del Hospital Italiano-Hospital Italiano de Buenos Aires Ciudad Autónoma de Buenos Aires C1199ACLArgentina Consejo nacional de Investigaciones Científicas y Técnicas Ciudad Autónoma de Buenos Aires C1425FQBArgentina Liver Unit Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina Department of Research Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk *** ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still *** novel biomarkers could represent a meaningful improvement to current risk *** this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past *** the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and *** we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily *** article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

关键词： Metabolic dysfunction-associated steatotic liver disease non-alcoholic steatohepatitis Biomarker Risk stratification Omics

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Imatinib-induced fatal acute liver failure

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World Journal of Gastroenterology 2007年第48期13卷 6608-6611页

作者： Ezequiel Ridruejo Roberto Cacchione Alejandra G Villamil sebastián marciano Adrián C Gadano Oscar G Mandó Hepatology Section Hematology Section Department of Medicine Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" CEMIC Buenos Aires Argentina Liver Unit Hospital Italiano de Buenos Aires Buenos Aires Argentina

Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia (CML) in blast crisis, accelerated or chronic phase, and also for advanced gastrointestinal stromal tumors. Severe hepatic toxicity and three deaths from hepatic failure have been reported. We report the case of a 51-year-old woman who was admitted to our institution with severe acute hepatitis. She was diagnosed with CML and began treatment with imatinib mesylate at a dose of 400 mg/d. Five months after beginning treatment, she developed severe hepatitis associated with coagulopathy, and was admitted to our institution. She had been consuming acetaminophen 500-1000 mg/d after the onset of symptoms. She had a progressive increase in bilirubin level and a marked decrease of clotting factor Ⅴ. Five days after admission, grade Ⅱ encephalopathy developed and she was referred for liver transplantation. Her clinical condition progressively deteriorated, and 48 h after being referred for transplantation she suffered a cardiac arrest and died. This report adds concern about the possibility of imatinib-mesylate-induced hepatotoxicity and liver failure, particularly in the case of concomitant use with acetaminophen. Liver function tests should be carefully monitored during treatment and, with the appearance of any elevation of liver function tests, treatment should be discontinued.

关键词： Imatinib mesylate Hepatotoxicity Acute liver failure Liver transplantation

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Unresolved issues in the prophylaxis of bacterial infections in patients with cirrhosis

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World Journal of Hepatology 2018年第12期10卷 892-897页

作者： Melisa Dirchwolf sebastián marciano José Martínez Andrés Eduardo Ruf nidad de Hígado Hospital Privado de Rosario Rosario 2000 Argentina Unidad de Hígado and Departamento de Investigación del Hospital Italiano de Buenos Aires Buenos Aires 1424 Argentina

Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial infections in high-risk subgroups of patients with cirrhosis has been the standard of care for decades. Patients with prophylaxis indications include those at risk for a first episode of spontaneous bacterial peritonitis(SBP) due to a low ascitic fluid protein count and impaired liver and kidney function, patients with a prior episode of SBP and those with an episode of gastrointestinal bleeding. Only prophylaxis due to gastrointestinal bleeding has a known and short-time duration. All other indications imply longlasting exposure to antibiotics-once the threshold requirement for initiating prophylaxis is met-without standardized criteria for re-assessing antibiotic interruption. Despite the fact that the benefit of antibiotic prophylaxis in reducing bacterial infections episodes and mortality has been thoroughly reported, the extended use of antibiotics in patients with cirrhosis has also had negative consequences, including the emergence of multi-drug resistant ***, it is not clear whether restricting the use of broad and fixed antibiotic regimens, tailoring the choice of antibiotics to local bacterial epidemiology or selecting non-antibiotic strategies will be the preferred antibiotic prophylaxis strategy for patients with cirrhosis in the future.

关键词： Cirrhosis Antibiotic Prophylaxis Multi-drug resistant bacteria Spontaneous bacterial peritonitis Bacterial infections

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Intermediate-advanced hepatocellular carcinoma in Argentina:Treatment and survival analysis

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World Journal of Gastroenterology 2019年第27期25卷 3607-3618页

作者： Federico Pinero sebastián marciano nora Fernández Jorge Silva Margarita Anders Alina Zerega Ezequiel Ridruejo Gustavo Romero Beatriz Ameigeiras Claudia D’Amico Luis Gaite Carla Bermúdez Virginia Reggiardo Luis Colombato Adrián Gadano Marcelo Silva Hospital Universitario Austral Facultad de Ciencias BiomédicasUniversidad AustralBuenos Aires B1629HJArgentina Latin American Liver Research Educational and Awareness network(LALREAn) Buenos Aires B1629HJArgentina Hospital Italiano de Buenos Cuidad Autónoma de Buenos AiresBuenos Aires C1424BYEArgentina Hospital Británico Cuidad Autonoma de Buenos AiresBuenos Aires C1280AEBArgentina Hospital G Rawson San Juan 5400Argentina Hospital Aleman Cuidad Autonoma de Buenos AiresBuenos Aires C1280AEBArgentina Sanatorio Allende from Córdoba Córdoba 5016Argentina Centro de Educación Médica e Investigaciones Clínicas“norberto Quirno”(CEMIC) Ciudad de Buenos Aires 1431Argentina Hospital Udaondo Cuidad Autonoma de Buenos Aires C1264AAAArgentina Hospital Ramos Mejía Ciudad de Buenos Aires C1221ADCArgentina Centro Especialidades Medicas Ambulatorias(CEMA) Mar del PlataBuenos Aires 7600Argentina Clínica de nefrología Santa Fe 3000Argentina Hospital del Centenario RosarioSanta Fe S2002KDTArgentina

BACKGROUnD Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of *** To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic *** This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or *** Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage *** median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P ng BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival (HR = 0.15(CI: 0.04-0.56, P = 0.005))Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71);P= 0.013].COnCLUSIOn In this real setting, our results we

关键词： Hepatocellular carcinoma Therapeutics Survival Real-life

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Fatty liver disease,an emerging etiology of hepatocellular carcinoma in Argentina

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World Journal of Hepatology 2018年第1期10卷 41-50页

作者： Federico Pinero Josefina Pages sebastián marciano nora Fernández Jorge Silva Margarita Anders Alina Zerega Ezequiel Ridruejo Beatriz Ameigeiras Claudia D’Amico Luis Gaite Carla Bermúdez Manuel Cobos Carlos Rosales Gustavo Romero Lucas McCormack Virginia Reggiardo Luis Colombato Adrián Gadano Marcelo Silva Hepatology and Liver Transplantation Unit Hospital Universitario AustralBuenos Aires 1629Argentina Hepatology Section Liver Transplant ProgramDepartment of Academic ResearchHospital Italiano from Buenos AiresBuenos Aires 1424Argentina Sanatorio Trinidad San Isidro Buenos Aires 1642Argentina Clínica Privada San Fernando Buenos Aires 2013Argentina Hepatology and Gastroenterology Hospital BritánicoBuenos Aires 1280Argentina Hepatobiliary Surgery Hospital G RawsonSan Juan 5400Argentina Department of Hepatology and Liver Transplant Program Hospital AlemanBuenos Aires 1118Argentina Department of Hepatology and Liver Transplantation Sanatorio AllendeCórdoba 5016Argentina Hepatology Section Department of MedicineCentro de Educación Médica e Investigaciones Clínicas Norberto Department of Hepatology Hospital Ramos MejíaBuenos Aires 1221Argentina Department of Hepatology Centro Especialidades Medicas Ambulatorias(CEMA)Mar del Plata 7600Argentina Department of Hepatology and Liver Transplantation Clínica de Nefrología de Santa FeSanta Fe 3000Argentina Department of Hepatology and Gastroenterology Hospital C Bonorino UdaondoBuenos Aires 1264Argentina Department of Hepatology and Gastroenterology Hospital CentenarioSanta Fe 2002Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(nAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical *** A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, nAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to nAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P ngly, a higher prevalence of diabetes mellitus was present in nAFLD-HCC group 61.7% when compared to other than nAFLD-HCC 23.3%(P n AFP values at HCC diagnosis were observed between nAFLD-HCC and non-nAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). neither nAFLD nor other HCC etiologies were associated with higher *** The growing incidence of nAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

关键词： Hepatocellular carcinoma Etiology Fatty liver South America

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Aging and Dynamics of Information: The Deeper Side of Biology (An Interdisciplinary Commentary)

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Advances in Aging Research 2025年第1期14卷 22-36页

作者： Jorge Barragán sebastián Sánchez Department of Histology Universidad del Gran Rosario Rosario Argentina

The relationship between the evolution of the basal metabolic rate (BMR) and the evolution of mass estimated as body weight in complex organisms such as human beings show the association between dissipated energy and information recovered as material structure. In such a context, it is necessary to highlight that the metabolic rate estimated as the energy dissipated per unit of mass presents the same rate of change as the mechanical speed estimated as distance traveled per unit of time. We describe this as a logical equivalence that has consequences on the geometry of the system. Our study proposes to describe the relationships between BMR, body weight, and the geometry of these systems in the same way that relativistic mechanics describes the relationships between matter, speed, and the geometry of the space in which the variables of a physical system are defined. It is exactly the same mechanical description, but considering five dimensions instead of four. The concept of information density limit is decisive in this theoretical framework since it contributes to explaining the changes in the geometry of these systems, their order-chaos transitions, and their general holographic description.

关键词： Margalef’s Principle Hologram Metabolic Rate Bekenstein Boundary Temporal Perimeter Size and Dimension

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La3+ substitution-adjusted magnetic and optical properties with enhanced photocatalytic activity and stability of copper zinc nickel ferrites for wastewater treatment applications

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Journal of Rare Earths 2025年第2期43卷 319-328页

作者： n.S.Al-Bassami General Studies Department Jubail Industrial College

Copper-zinc-nickel（Cu-Zn-ni） ferrite nanoparticles are used for wastewater treatment ***,low degradation efficiency and stability are two main issues that make them unsuitable for actual production *** this paper,the citrate-nitrate auto-combustion method was applied for the formation of Cu0.5Zn0.25ni0.25LaxFe2-xO4;（0≤x≤0.1;step 0.02）(CZnL) *** the substitution process entails the replacement of a small ion with a larger one,the lattice constant and crystallite size does not exhibit a consistent incremental *** behavior is justified and *** size of all the CZnL ferrite nanoparticles is in the range of 8-12 nm,and the lattice constant is in the range of 8.6230 to 8.4865 *** morphological analysis conducted using field emission-scanning electron microscopy（FE-SEM） reveals that the CZnL exhibits agglomerated spherical *** energy dispersive X-ray spectrameter（EDAX） analysis was employed to confirm the elemental composition of CZnL *** the process entails the substitution of Fe3+magnetic ions with nonmagnetic ions La3+,the magnetic parameters of CZnL nanoferrites show a general decreasing trend as *** 20 K,saturation magnetization Ms shows an overall drop in its values from 59.302 emu/g at x=0.0-41.295 emu/g at x=0.1,the smallest value of 37.87 emu/g is recorded at x=*** highest coercivity（Hc=125.9 Oe） and remanence（Mr=13.32 emu/g） are recorded for x=0.08 and x=0.04 nanoferrite,*** band gap of all the CZnL nanoferrites was determined using the Kubelka-Munk function and Tauc plot for direct permitted *** doping modifies the band gap（within 1.86-1.75 eV）,increases light absorption,induces efficient e/h separation and charge migration to *** nanoferrite Cu0.5Zn0.25ni0.25La0.06Fe1.94O4achieves a degradation efficiency of 97.3% for methylene blue（MB） dye removal after just 60 *** five recycling processes,the nanoc

关键词： Copper-zinc-nickel Ferrite Photocatalytic properties Rare earths Wastewater treatment

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nucleoside modified mRnA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák Antal nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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Green synthesis of glycolic acid through the electrocatalytic reduction of oxalic acid over black TiO_(2): An experimental and theoretical study

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Journal of Energy Chemistry 2025年第1期100卷 544-556页

作者： Hugo Olvera-Vargas Oscar Andrés Jaramillo-Quintero Luis Darío Alarcón León Orlando Castro-Ocampo Christian A.Celaya Marina E.Rincón Jesús Muñiz Instituto de Energías Renovables Universidad Nacional Autónoma de México(IER-UNAM)Priv.Xochicalco s/nCol.CentroTemixcoMorelos.CP 62580Mexico Centro de nanociencias y nanotecnología Universidad Nacional Autónoma de México(UNAM)Km 107Carretera Tijuana-EnsenadaEnsenadaB.C.C.P.22800Mexico

Herein,we present the electrocatalytic four-electron hydrogenation of oxalic acid into glycolic acid using black TiO_(2)as an *** acid is an abundant compound found in several sources of organic *** results showed a high selectivity of black TiO_(2)toward glycolic acid,with the formation of glyoxylic acid being the rate-limiting step (glyoxylic acid is the two-electron intermediate).The highest Faradaic efficiency (FE) of 69.6%±8.3% was achieved at 10.2 mA cm^(-2)in 4 h of electrolysis using an H-type cell operated at room temperature,with 50.2%±3.8% of oxalic acid conversion (degradation kinetic constant k=0.0042±0.0001 min-1),58.8%±7.0%of reaction yield and 1.2±0.18 g L-1of glycolic acid production.A theoretical model of black TiO_(2)coming from anatase TiO_(2)was implemented by introducing Ti3+defects,which gave black TiO_(2)the theoretical capability to easily transform oxalic acid into glycolic acid as experimentally *** reaction mechanism was supported and described in detail by density functional theory calculations,which revealed that surface Ti^(3+)states were the main catalytic *** is the first time that a detailed step-by-step mechanism at the atomic level has been proposed for this electrocatalytic reaction,which represents a valuable contribution to the understanding of this process of high energy/environmental *** is also the first time that black TiO_(2)has been used as an electrocatalyst for this sustainable process.

关键词： Chemical energy storage Electrochemical hydrogenation Density functional theory Renewable energy Oxalic acid

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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