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Hepatotoxicity Induced by Biological Agents: Clinical Features and Current Controversies

Journal of Clinical and Translational Hepatology 2022年第3期10卷 486-495页

作者： Nelia Hernandez fernando bessone Hospital de Clinicas Universidad de la RepublicaMontevideoUruguay Hospital Provincial del Centenario University of Rosario School of MedicineRosarioArgentina

Novel biological agents including cytokines and recombinant fusion proteins are increasingly prescribed for cancer,rheumatologic,autoimmune,and inflammatory diseases,and are currently being evaluated in hepatocellular carcinoma(HCC).They are classified by their mechanism of action and include tumor necrosis factor-alpha(TNF-α)antagonists,T cell mediated antitumor inhibitors,interleukin receptor antagonists,and immune checkpoint inhibitors(ICIs).Some ICIs cause frequent hepatotoxicity with a variable clinical,biochemical,and serological presentation,especially in patients receiving another immunomodulatory *** of the cases of liver damage induced by biological agents spontaneously regress after drug withdrawal,but the others require steroid ***,there are no widely accepted recommendation for the use of corticosteroids in these patients,even though international cancer societies have their own *** drug-induced autoimmune hepatitis(DIAIH)from classic AIH is challenging for pathologists,but liver biopsy is valuable,particularly in cases with unclear clinical ***,novel histological patterns have been described in liver damage induced by these agents(i.e.,endothelitis,ring granuloma and secundary sclerosing cholangitis associated with lymphocytic infiltration of cytotoxic CD8+T cells).Here,we describe the clinical and biochemical characteristics of patients with hepatotoxicity induced by TNF-αantagonists and *** issues involved in the administration of corticosteroid therapy,and hepatitis B virus(HBV)reactivation induced by immunosuppressive therapy are also discussed.

关键词： Hepatotoxicity Checkpoint inhibitors Biologics Autoimmune hepatitis Drug-induced liver injury

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Checkpoint inhibitor-induced hepatotoxicity:Role of liver biopsy and management approach

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World Journal of Hepatology 2022年第7期14卷 1269-1276页

作者： fernando bessone Einar Stefan Bjornsson Department of Gastroenterology and Hepatology Facultad de Ciencias MédicasHospital Provincial del CentenarioUniversity of Rosario School of MedicineRosario 2000Santa FeArgentina Department of Gastroenterology Natl Univ Hosp IcelandSect Gastroenterol&HepatolDept Internal MedHringbraut 11DIS-101 ReykjavikIceland Landspitali University Hospital and Faculty of Medicine University of IcelandReykjavik Postal code 101State of ReykjavikIceland

Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different *** immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointestinal and endocrine organs as well as the *** injury has been reported in 3%-8%of patients with grade III-IV hepatitis in retrospective *** liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG *** role for liver biopsy(LB)in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical *** can be helpful when there is diagnostic uncertainty and pre-existing liver disease is *** there are no distinctive histological features,the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by *** natural history of hepatotoxicity of ICI therapy is not well *** studies have demonstrated that 33%-50%of patients improve spontaneously with discontinuation of *** patients with jaundice and/or coagulopathy corticosteroids are *** high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are *** it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose *** immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.

关键词： Hepatotoxicity Checkpoint inhibitors Biologics hepatitis Drug-induced liver injury Liver biopsy

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Non-steroidal anti-inflammatory drugs:What is the actual risk of liver damage?

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World Journal of Gastroenterology 2010年第45期16卷 5651-5661页

作者： fernando bessone Department of Gastroenterology and Hepatology University of Rosario School of Medicine2000RosarioArgentina

Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinfectious agents, list on the top for causes of DrugInduced Liver Injury (DILI). The incidence of liver disease induced by NSAIDs reported in clinical studies is fairly uniform ranging from 0.29/100 000 [95% confidence interval (CI): 0.17-051] to 9/100 000 (95% CI: 6-15). However, compared with these results, a higher risk of liver-related hospitalizations was reported (3-23 per 100 000 patients). NSAIDs exhibit a broad spectrum of liver damage ranging from asymptomatic, transient, hyper-transaminasemia to fulminant hepatic failure. However, under-reporting of asymptomatic, mild cases, as well as of those with transient liver-tests alteration, in conjunction with reports non-compliant with pharmacovigilance criteria to ascertain DILI and flawed epidemiological studies, jeopardize the chance to ascertain the actual risk of NSAIDs hepatotoxicity. Several NSAIDs, namely bromfenac, ibufenac and benoxaprofen, have been withdrawn from the market due to hepatotoxicity; others like nimesulide were never marketed in some countries and withdrawn in others. Indeed, the contro-versy concerning the actual risk of severe liver disease persists within NSAIDs research. The present work intends (1) to provide a critical analysis of the dissimilar results currently available in the literature concerning the epidemiology of NSAIDS hepatotoxicity; and (2) to review the risk of hepatotoxicity for each one of the most commonly employed compounds of the NSAIDs family, based on past and recently published data.

关键词： Non-steroidal anti-inflammatory drugs Side effects Fulminant hepatic failure Cholestasis Liver damage Liver injury Hepatitis Hepatotoxicity

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Overview on drug-induced liver injury in Brazil

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2021年第5期12卷 100-102页

作者： fernando bessone Department of Gastroenterology and Hepatology Hospital Provincial del CentenarioFacultad de Ciencias MédicasUniversity of Rosario School of MedicineRosario 2000Santa FeArgentina

Drug-induced liver injury(DILI)is an uncommon event in clinical practice,which makes knowing its true incidence ***,retrospective and registry-based studies are the most important methods to obtain epidemiological data on *** America(LA)has a historical lack of prospective studies on this *** definitions and the creation of hepatotoxicity registries have significantly improved the epidemiological understanding of hepatic drug reactions in several regions of the *** Latin American DILI network,referred to as LATINDILI,has been created in 2011,and recently published its own DILI recommendations describing the most relevant issues on the management of hepatotoxicity in general,and those based on findings from our own LA experience in *** most of the registries do not carry out population-based studies,they may provide important data related to the prevalence of *** joint work among researchers and the corresponding health and regulatory authorities should be stimulated due to the high impact that hepatotoxicity represents for public health.

关键词： Hepatotoxicity Drug-induced liver injury Drug-induced liver injury registries Herbs Hepatitis

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E-Commerce Fraud Detection Based on Machine Learning Techniques:Systematic Literature Review

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Big Data Mining and Analytics 2024年第2期7卷 419-444页

作者： Abed Mutemi fernando Bacao NOVA Information Management School(NOVA IMS) Universidade Nova de LisboaCampus de CampolideLisboa 1070-312Portugal

The e-commerce industry’s rapid growth,accelerated by the COVID-19 pandemic,has led to an alarming increase in digital fraud and associated *** establish a healthy e-commerce ecosystem,robust cyber security and anti-fraud measures are ***,research on fraud detection systems has struggled to keep pace due to limited real-world *** in artificial intelligence,Machine Learning(ML),and cloud computing have revitalized research and applications in this *** ML and data mining techniques are popular in fraud detection,specific reviews focusing on their application in e-commerce platforms like eBay and Facebook are lacking *** reviews provide broad overviews but fail to grasp the intricacies of ML algorithms in the e-commerce *** bridge this gap,our study conducts a systematic literature review using the Preferred Reporting Items for Systematic reviews and Meta-Analysis(PRISMA)*** aim to explore the effectiveness of these techniques in fraud detection within digital marketplaces and the broader e-commerce *** the current state of the literature and emerging trends is crucial given the rising fraud incidents and associated *** our investigation,we identify research opportunities and provide insights to industry stakeholders on key ML and data mining techniques for combating e-commerce *** paper examines the research on these techniques as published in the past *** the PRISMA approach,we conducted a content analysis of 101 publications,identifying research gaps,recent techniques,and highlighting the increasing utilization of artificial neural networks in fraud detection within the industry.

关键词： E-commerce Machine Learning(ML) systematic review fraud detection organized retail fraud

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Exploring multifaceted factors in chronic kidney disease risk: A comprehensive analysis of biochemistry, lifestyle, and inflammation in elderly Chinese individuals

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World Journal of Clinical Cases 2024年第5期12卷 1033-1035页

作者： fernando Cardona Unitat de Genètica Molecular Instituto de Biomedicina de Valencia–CSICValencia 46010Spain Centro de investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos IIIMadrid 28029Spain Departamento de Biotecnología Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural(ETSIAMN)Univeristat Politècnica de ValenciaValencia 46022Spain

This letter praises a recent article in the World Journal of Clinical Cases(Roles of biochemistry data,lifestyle,and inflammation in identifying abnormal renal function in old Chinese),examining factors affecting abnormal renal function in elderly Chinese using advanced machine *** highlights the importance of uric acid,age,hemoglobin,body mass index,sport hours,and systolic blood *** study's holistic approach,integrating lifestyle and inflammation,offers a nuanced understanding of chronic kidney disease risk *** letter suggests exploring mechanistic pathways of hyperuricemia,the link between anemia and renal function,and the connection between body mass index and estimated glomerular filtration *** advocates investigating physical activity's impact on renal health and the independent effects of blood *** study significantly contributes to chronic kidney disease understanding,proposing avenues for further exploration and *** are extended to the authors and the journal.

关键词： Biochemistry data Lifestyle Machine learning Renal function

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A new small baurioid therocephalian from the Lower Triassic Jiucaiyuan Formation, Xinjiang, China

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古脊椎动物学报（中英文） 2024年第3期62卷 201-224页

作者： LIU Jun fernando ABDALA Institute of Vertebrate Paleontology and Paleoanthropology Chinese Academy of Sciences Beijing 100044China College of Earth and Planetary Sciences University of Chinese Academy of Sciences Beijing 100049 Área de Paleontología Unidad Ejecutora LilloCONICETFundación Miguel Lillo Miguel Lillo 251TucumánArgentina Evolutionary Studies Institute University of the Witwatersrand Private Bag 3WITSJohannesburg2050South Africa

Several therocephalian species,mainly represented by cranial material from the late Permian,have been reported from China in recent *** we describe a tiny new baurioid therocephalian,Jiucaiyuangnathus confusus *** ***.,from the Jiucaiyuan Formation,Xinjiang,*** new taxon is represented by a partial snout with occluded partial lower jaw and two postcranial *** juvenile in stage,the new species is diagnosed by the following features:round pit in middle of lateral surface of maxilla;lacrimal contact nasal;fossa for dentary tooth on the posterior end of the premaxilla,lateral to the anterior choana;two small vertical triangular ridges extending dorsally and ventrally on the vomerine anterior portion,and bordering a thin vomerine foramen laterally;anterior projection of the lateral part of the frontal on the nasal;symphyseal region of the dentary projected anteriorly;5 upper premaxillary teeth,upper and lower canines absent,diastema between the last premaxillary upper incisor and first maxillary tooth present,no diastema separating anterior from posterior dentition in the mandible,10 maxillary teeth and 12 dentary teeth,posterior postcanine expands mesiodistally,having a main large cusps and tiny anterior and posterior accessory cusps in line;neural arches of the atlas fused by the neural spine,neural spine of the axis projected posteriorly,procoracoid foramen lies between procoracoid and *** of the dentition resembles those of the small baurioid Ericiolacerta parva from South Africa and Silphedosuchus orenburgensis from *** specimens provide the rare opportunity to know in detail the postcranial skeleton of baurioids.

关键词： Jimsar,Xinjiang Early Triassic Jiucaiyuan Formation Therocephalia,Baurioidea

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Time-Series Embeddings from Language Models:A Tool for Wind Direction Nowcasting

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Journal of Meteorological Research 2024年第3期38卷 558-569页

作者： Decio ALVES Fabio MENDONCA Sheikh Shanawaz MOSTAFA fernando MORGADO-DIAS University of Madeira Campus Universitário da Penteada9020-105FunchalPortugal Interactive Technologies Institute/Laboratory for Robotics and Engineering Systems and Agência Regional para o Desenvolvimento da Investigação Tecnologia e InovaçãoEdif.Madeira TecnopoloCaminho da Penteada piso-29020-105FunchalPortugal

Wind direction nowcasting is crucial in various sectors,particularly for ensuring aviation operations and *** this context,the TELMo(Time-series Embeddings from Language Models)model,a sophisticated deep learning architecture,has been introduced in this work for enhanced wind-direction *** by using three years of data from multiple stations in the complex terrain of an international airport,TELMo incorporates the horizontal u(east-west)and v(north-south)wind components to significantly reduce forecasting *** a day with high wind direction variability,TELMo achieved mean absolute error values of 5.66 for 2-min,10.59 for 10-min,and 14.79 for 20-min forecasts,processed within a swift 9-ms/step *** degree-based analysis,in comparison,yielded lower performance,emphasizing the effectiveness of the u and v *** contrast,a Vanilla neural network,representing a shallow-learning approach,underperformed in all analyses,highlighting the superiority of deep learning methodologies in wind direction *** is an efficient model,capable of accurately forecasting wind direction for air traffic operations,with an error less than 20°in 97.49%of the predictions,aligning with recommended international *** model design enables its applicability across various geographical locations,making it a versatile tool in global aviation meteorology.

关键词： wind nowcasting wind components wind direction time series prediction deep learning

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A Review of State-of-the-art Flexible Power Point Tracking Algorithms in Photovoltaic Systems for Grid Support:Classification and Application

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Journal of Modern Power Systems and Clean Energy 2024年第1期12卷 1-21页

作者： Mina Haghighat Mehdi Niroomand Hossein Dehghani Tafti Christopher D.Townsend Tyrone fernando the Department of Electrical Engineering University of IsfahanIsfahanIran the Department of Electrical Electronic and Computer EngineeringUniversity of Western AustraliaCrawley WA 6009Australia

To maximize conversion efficiency,photovoltaic(PV)systems generally operate in the maximum power point tracking(MPPT)***,due to the increasing penetra tion level of PV systems,there is a need for more developed control functions in terms of frequency support services and voltage control to maintain the reliability and stability of the power ***,flexible active power control is a manda tory task for grid-connected PV systems to meet part of the grid ***,a significant number of flexible pow er point tracking(FPPT)algorithms have been introduced in the existing *** purpose of such algorithms is to real ize a cost-effective method to provide grid support functional ities while minimizing the reliance on energy storage *** paper provides a comprehensive overview of grid support functionalities that can be obtained with the FPPT control of PV systems such as frequency support and volt-var *** of these grid support functionalities necessitates PV sys tems to operate under one of the three control strategies,which can be provided with FPPT *** three control strate gies are classified as:①constant power generation control(CP GC),②power reserve control(PRC),and③power ramp rate control(PRRC).A detailed discussion on available FPPT algo rithms for each control strategy is also *** paper can serve as a comprehensive review of the state-of-the-art FPPT algorithms that can equip PV systems with various grid support functionalities.

关键词： Maximum power point tracking(MPPT) flexi ble power point tracking(FPPT) power reserve control(PRC) power ramp rate control(PRRC) low voltage ride-through(LVRT) constant power generation(CPG)

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Predicting grain size-dependent superplastic properties in friction stir processed ZK30 magnesium alloy with machine learning methods

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Journal of Magnesium and Alloys 2024年第5期12卷 1931-1943页

作者： Farid Bahari-Sambran fernando Carreno C.M.Cepeda-Jiménez Alberto Orozco-Caballero Physical Metallurgy Department CENIM-CSICAv.Gregorio del Amo 828040 MadridSpain Department of Mechanical Engineering Chemistry and Industrial DesignPolytechnic University of MadridRonda de Valencia 328012MadridSpain

The aim of this work is to predict,for the first time,the high temperature flow stress dependency with the grain size and the underlaid deformation mechanism using two machine learning models,random forest(RF)and artificial neural network(ANN).With that purpose,a ZK30 magnesium alloy was friction stir processed(FSP)using three different severe conditions to obtain fine grain microstructures(with average grain sizes between 2 and 3μm)prone to extensive superplastic *** three friction stir processed samples clearly deformed by grain boundary sliding(GBS)deformation mechanism at high *** maximum elongations to failure,well over 400% at high strain rate of 10^(-2)s^(-1),were reached at 400℃ in the material with coarsest grain size of 2.8μm,and at 300℃ for the finest grain size of 2μ***,the superplastic response decreased at 350℃ and 400℃ due to thermal instabilities and grain coarsening,which makes it difficult to assess the operative deformation mechanism at such *** work highlights that the machine learning models considered,especially the ANN model with higher accuracy in predicting flow stress values,allow determining adequately the superplastic creep behavior including other possible grain size scenarios.

关键词： Machine learning Artificial intelligence Magnesium alloys Superplasticity Friction stir processing Grain coarsening

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