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World Journal of Gastroenterology 2021年第24期27卷 3429-3439页

作者： Federico Piñero leonardo gomes da fonseca Hepatology and Liver Unit Hospital Universitario AustralSchool of MedicineAustral UniversityBuenos Aires B1629HJArgentina Clinical Oncology Insituto do Cancer do Estado de São PauloUniversity of São PauloSão Paulo 05403-000Brazil

Although hepatocellular carcinoma is considered a highly lethal malignancy,recent therapeutic advances have been achieved during the last 10 *** scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma,almost reaching 20-26 mo of overall survival after first-second line sequential *** advent of the combination of atezolizumab with bevacizumab showed,for the first time,superiority over sorafenib with improvement in overall ***,first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure,decompensated cirrhosis or other underlying medical *** a result,the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups,such as patients with unpreserved liver function,other comorbid conditions,a history of solid-organ transplantation,autoimmune disorders and those with a high risk of *** present text aims at discussing treatment strategies in these subgroups.

关键词： Eligibility Systemic therapies End-stage Hepatocellular carcinoma

Combination approaches in hepatocellular carcinoma:How systemic treatment can benefit candidates to locoregional modalities

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World Journal of Gastroenterology 2022年第28期28卷 3573-3585页

作者： leonardo gomes da fonseca Raphael L C Araujo Department of Medical Oncology Instituto do Cancer do Estado de Sao PauloUniversity of Sao PauloSão Paulo 01246-000São PauloBrazil Hospital e Maternidade Brasil-Rede D'Or São Luiz Santo André09030-590São PauloBrazil Department of Digestive Surgery Escola Paulista de Medicina-UNIFESPSão Paulo 04023-062São PauloBrazil

The management of hepatocellular carcinoma(HCC)is challenging because most patients have underlying cirrhosis,and the treatment provides,historically,a limited impact on the natural history of patients with advanced-stage ***,recurrence rates are high for those patients who receive local and locoregional modalities,such as surgical(resection and transplantation)or imageguided(ablation and intra-arterial)*** research has led to new concepts that are reshaping the current clinical *** advancements were achieved in the understanding of the hallmarks that drive *** has primed a successful incorporation of novel agents with different targets,such as anti-angiogenic drugs,targeted-therapies,and immune-checkpoint *** clinical trials have proven efficacy of systemic agents in advanced stage disease,there is no conclusive evidence to support their use in combination with loco-regional *** novel local modalities are being incorporated(e.g.,radioembolization,microwave ablation,and irreversible electroporation),emerging data indicate that locoregional treatments may induce tumor microenvironment changes,such as hyperexpression of growth factors,release of tumor antigens,infiltration of cytotoxic lymphocytes,and modulation of adaptative and innate immune *** trials that evaluated the use of antiangiogenic drugs in the adjuvant setting after ablation or chemoembolization fail to demonstrate a substantial *** efforts are directed to investigate the role of immunotherapy-based regimens in this *** present review aims to describe the current landscape of systemic and locoregional treatments for HCC,present evidence to support combination approaches,and address future perspectives.

关键词： Liver cancer Hepatocellular carcinoma Immunotherapy Systemic therapy Ablation Embolization

Updates in immunotherapy for hepatocellular carcinoma

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Hepatoma Research 2019年第10期5卷 19-31页

作者： leonardo G.da fonseca Flair JoséCarrilho Medical Oncology São Paulo Clínicas Liver Cancer GroupHospital das Clínicas ComplexInstituto do Cancer do Estado de São PauloUniversity of São Paulo School of MedicineSão PauloSP 05403-000Brazil Department of Gastroenterology São Paulo Clínicas Liver Cancer GroupHospital das Clínicas ComplexInstituto do Cancer do Estado de São PauloUniversity of São Paulo School of MedicineSão PauloSP 05403-000Brazil

Hepatocellular carcinoma(HCC)carries an unfavorable prognosis and novel therapeutic strategies are *** now,only few systemic agents have improved survival in patients with advanced stage *** changed the landscape in several tumor types by producing unprecedented clinical outcomes with a favorable safety *** presents a particular immune-suppressive microenvironment and HCC develops in a background of chronic inflammation in the vast majority of *** this regard,immunotherapy may be a suitable *** research focused on therapies involving immune cells and anti-tumor immune response for HCC has shown encouraging preliminary *** checkpoint inhibitors,such the anti-PD-1/PD-L1 monoclonal antibodies,have provided durable responses in patients with advanced stage disease,although the pioneers phaseⅢtrials did not confirm survival superiority over the available *** vaccines,adoptive cellular therapies and combinations of local modalities with immunotherapy are promising approaches under active research.

关键词： Hepatocellular carcinoma immunotherapy immunosuppression prognosis immunology antibody vaccine

TLBO with variable weights applied to shop scheduling problems

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CAAI Transactions on Intelligence Technology 2019年第3期4卷 148-158页

作者： leonardo Ramos Rodrigues Joao Paulo Pordeus gomes Electronics Division Institute of Aeronautics and SpacePraca Marechal Eduardo Gomes50Sao Josedos Campos 12228-904Brazil Computer Science Department Federal University of CearaRua Campus do PiciSnFortaleza 60440-554Brazil

The teaching–learning-based optimisation (TLBO) algorithm is a population-based metaheuristic inspired on the teaching–learning process observed in a classroom. It has been successfully used in a wide range of applications. In this study, the authors present a variant version of TLBO. In the proposed version, different weights are assigned to students during the student phase, with higher weights being assigned to students with better solutions. Three different approaches to assign weights are investigated. Numerical experiments with benchmark instances of the flow-shop and the job-shop scheduling problems are carried out to investigate the performance of the proposed approaches. They compare the proposed approaches with the original TLBO algorithm and with two variants of TLBOs proposed in the literature in terms of solution quality, convergence speed and simulation time. The results obtained by the application of a Friedman statistical test showed that the proposed approaches outperformed the original version of TLBO in terms of convergence, with no significant losses in the average makespan. The additional simulation time required by the proposed approaches is small. The best performance was achieved with the approach of assigning a fixed weight to half the students with the best solutions and assigning zero to other students.

关键词： TLBO variable weights shop scheduling problems

Animal models applied to acute-on-chronic liver failure:Are new models required to understand the human condition?

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World Journal of Clinical Cases 2022年第9期10卷 2687-2699页

作者： Jaciara Fernanda gomes Gama Liana Monteiro da fonseca Cardoso Jussara Machado Lagrota-Candido LuizAnastacio Alves Laboratory of Cellular Communication Oswaldo Cruz InstituteOswaldo Cruz FoundationRio de Janeiro 21045900Rio de JaneiroBrazil Laboratory of Immunopathology Department of ImmunobiologyFluminense Federal UniversityNiteroi 24210-200Rio de JaneiroBrazil

The liver is a multifaceted organ;its location and detoxifying function expose this organ to countless ***-on-chronic failure liver(ACLF)is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver *** infection environment,ascites,increased liver enzymes and prothrombin time,encephalopathy and fast-evolving multiorgan failure,leading to death,usually accompany *** pathophysiology remains poorly *** this context,animal models become a very useful tool in this regard,as understanding;the disease may be helpful in developing novel therapeutic methodologies for ***,although animal models display several similarities to the human condition,they do not represent all ACLF manifestations,resulting in significant *** initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-Ga IN,potentiating liver damage supports the methodologies applied to induce experimental *** entire methodology has been described mostly for ***,a quick Pub Med database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure *** findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.

关键词： Liver disease Acute-on-chronic liver failure Cirrhosis Acute decompensate event Translational study Animal models

Extraintestinal manifestations of inflammatory bowel disease, nitroxidative stress and dysbiosis: What is the link between them?

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BIOCELL 2021年第3期45卷 461-481页

作者： AMYLLY SANUELLY da PAZ MARTINS SAMARA BOMFIM gomes CAMPOS MARÍLIA OLIVEIRA fonseca GOULART FABIANA ANDRÉA MOURA Programa de Pós-Graduação da Rede Nordeste de Biotecnologia(RENORBIO) Universidade Federal de Alagoas(UFAL)MaceióAL 57072-970Brazil Programa de Pós-Graduação em Ciências da Saúde(PPGCS) Universidade Federal de Alagoas(UFAL)MaceióAL 57072-970Brazil Programa de Pós-Graduação em Química e Biotecnologia(PPGQB/UFAL) Campus A.C.SimõesAvenida Lourival Melo Motas/nTabuleiro dos MartinsMaceióAL 57072-970Brazil Programa de Pós-Graduação em Nutrição(PPGNU/UFAL) Programa de Pós-Graduação em Ciências Médicas(PPGCM/UFAL)Universidade Federal de Alagoas(UFAL)MaceióAL 57072-970Brazil

Inflammatory bowel disease(IBD),which includes Crohn’s disease and ulcerative colitis,has a not yet completely defined aetiology and is characterized by a progressive chronic inflammation that involves nitroxidative stress and *** manifestations can occur and affect several organs,including the liver and bile ducts,joints,skin,eyes,and less frequently,the heart,brain,and kidneys,increasing the risk of morbidity and *** repercussions may be associated with the activity or severity of *** present review proposes to report and analyse the participation of dysbiosis and nitroxidative stress in the genesis of extraintestinal manifestations,aiming to contribute to a better understanding of the disease and to focus on the development of individualized preventive and therapeutic strategies.

关键词： Oxidative stress Microbiota Bacterial translocation Ulcerative colitis Crohn disease

Droughts in Homogeneous Areas of South America and Associated Processes during the Months of Austral Spring and Summer

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Advances in Atmospheric Sciences 2024年第12期41卷 2337-2353页

作者： Mariah Sousa gomes Iracema fonseca de Albuquerque CAVALCANTI Gabriela V.MULLER General Coordination of Earth Science(CGCT) National Institute for Space Research(INPE)Avenida dos Astronautas1758CEP:12227-010Sao Josédos CamposSPBrasil National Scientific and Technical Research Council(CONICET) Argentina -Santa Fe Argentina

Droughts that occurred in selected areas located in homogeneous regions of South America during the austral springs(SON)and summers(DJF)from 1982 to 2019 are identified using the Standard Precipitation Index(SPI).Four areas were analyzed for droughts in SON,and three areas were analyzed for droughts in *** areas in the Amazon suffered from the majority of their droughts during El Niño years,while most of the droughts in the areas of southern Brazil,Uruguay,and North Argentina occurred during La Niña *** southeastern and central-western parts of Brazil,droughts occurred during both phases of El Nino-Southern Oscillation(ENSO)and also during neutral ***,other processes besides ENSO are likely related to the observed *** droughts were investigated for each area and month,and composites of atmospheric and oceanic variables during both seasons were analyzed for the selected *** and large-scale field composites were examined to identify the main processes associated with dry conditions in the different *** features were related to the influence of high pressure over southern and southeastern areas and the divergence of moisture flux in all *** circulations contributed to subsidence over the dry *** large-scale influential features include SST anomalies,wavetrains over the South Pacific Ocean with centers of action over South America that produced subsidence in the study areas,and convection anomalies in the Maritime continent and surrounding ***,the droughts were associated with a combination of regional and large-scale features that produced subsidence over the analyzed regions.

关键词： droughts South America regional features large-scale features

Energetic-protein supplementation in the last 60 days of gestation improves performance of beef cows grazing tropical pastures

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Journal of Animal Science and Biotechnology 2018年第1期9卷 208-216页

作者： Aline gomes da Silva Mário fonseca Paulino Edenio Detmann Henrique Jorge Fernandes Lincoln da Silva Amorim Román Enrique Maza Ortega Victor Valério de Carvalho Josilaine Aparecida da Costa Lima Felipe Henrique de Moura Mariana Benevides Monteiro Jéssika Almeida Bitencourt Universidade Federal de Vicosa VicosaMinas Gerais 36570-000Brazil Universidade Federal de Mato Grosso do Sul Campo GrandeMato Grosso do Sul 79074-460Brazil Universidade Estadual de Mato Grosso do Sul AquidauanaMato Grosso do Sul 79200-000Brazil Biotran Biotecnologia e Treinamento em Reproducao Animal AlfenasMinas Gerais 37130-000Brazil Universidade Federal do Acre Rio BrancoAcre 69920-900Brazil

Background： Nutrition is one of the most important factors that affect animal performance, and it therefore also impacts on financial results in beef systems. In this way, finding the best strategy for feeding supplements is of paramount importance. Aiming to evaluate the effect of supplement feeding strategies for beef cows in the last third of gestation, two experiments were conducted. In Experiment 1, 35 pregnant Nellore cows were assigned to a completely randomized design with four treatments： control, which received no supplement; supplementation for the last 30 d of gestation（30-d; 3.0 kg/d）; supplementation for the last 60 d of gestation（60-d; 1.5 kg/d）; or supplementation for the last 90 d of gestation（90-d; 1.0 kg/d）. All supplemented treatments received the same total amount of supplement throughout the experiment： 90 kg（20% of crude protein）. A second experiment（Experiment 2） was delineated to evaluate the effects of the amounts offered in Experiment 1 on intake and metabolism. Four multiparous pregnant Nellore cows were assigned to a 4 × 4 Latin square design, with periods of15 d ***： There was a linear effect of the number of days of supplementation on calving body weight（BW; P 〈 0.05）and a quadratic effect on BW change from parturition to d 31 post-calving（P 〈 0.05）, with cows on the 60-d strategy losing less BW post-calving. No difference was found in offspring birth BW（P 〉 0.10）. A significant linear effect on interval from parturition to conception（P 〈 0.05） was observed, with the highest calving to conception interval being observed in the 90-d strategy. The level of supplementation did not affect forage intake or neutral detergent fiber digestibility（P 〉 0.10）. Nitrogen excreted through urine tended to increase linearly with the level of supplementation（P 〈 0.10）.Conclusion： Providing 1.5 kg of supplement during the last 60 d of gestation improves cow performance after calving, reducing the magnitude of BW lost, and reduces the number of

关键词： Flushing Nutrition Parturition Reproduction

Radial Applanation Tonometry as an Adjuvant Tool in the Noninvasive Arterial Stiffness and Blood Pressure Assessment

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World Journal of Cardiovascular Diseases 2014年第5期4卷 225-235页

作者： Lucas Jose Sa da fonseca Marco Antonio Mota-gomes Luiza ARabelo Laboratorio de Reatividade Cardiovascular Setor de Fisiologia e FarmacologiaInstituto de Ciências Biologicas e da SaudeUniversidade Federal de AlagoasMaceioBrazil Centro de Pesquisas Clinicas do Hospital do Coracao de Alagoas—HCOR-AL MaceioBrazil Max-Delbruck-Center for Molecular Medicine BerlinGermany

Since antiquity, the human arterial pulse represents an important parameter in the clinical assessment. Besides being routinely assessed in the medical practice, such pulse is not observed in its completeness yet, once many of the data obtained through it cannot be evaluated using conventional methods. Taking into account such methods, the measurement of arterial blood pressure using sphygmomanometry, although broadly widespread in the assessment and follow-up of patients who require accompaniment of their cardiovascular status, is not able to properly guide about parameters related to the central hemodynamic status, the latter most strongly associated with cardiovascular risk. Such incapability is due to the centrifugal augmentation of the pressures taken at different points of the arterial bed, based on the properties of the closed arterial system through which the blood flow travels. In this context, methodologies capable of assessing central parameters estimated using the pulse wave analysis, such as applanation tonometry, represent a promising adjuvant for evaluating patients with cardiovascular diseases, by providing detailed information concerning hemodynamic parameters otherwise inaccessible. In this scenario, the present review focuses on the applanation tonometry and its assessment on the radial artery, highlighting the importance of this method in the cardiovascular assessment, as well as its relevance in the clinical practice, when determining parameters peripherally obtained capable of estimating the central hemodynamic status.

关键词： Arterial Pulse Arterial Stiffness Noninvasive Assessment Radial Tonometry Cardiovascular Risk

Columnar joints in the Patino Formation sandstones, Eastern Paraguay： a dynamic interaction between dyke intrusion, quartz dissolution and cooling-induced fractures

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Episodes 2008年第3期31卷 302-308页

作者： Victor Fernandez Velazquez Paulo Cesar fonseca Giannini Claudio Riccomini Alethea Ernandes Martins Sallun Jorge Hachiro Celso de Barros gomes Eseola de Artes Ciencias e Humanidades Universidade de Sao Paulo Rua Arlindo Betio 1000 03828-080 Sao Paulo Brasil Instituto de Geociencias Universidade de Sao Paulo Rua do Lago 562 05508-080 Sao Paulo Brasil Insfituto Geolegico Secretaria do Meio Ambiente Av. Miguel Estefano 3900 04301-903 Sao Paulo Brasil.

The Patiho Formation sandstones, which crop out in Aregud neighborhood in Eastern Paraguay and show columnar joints near the contact zone with a nephelinite dyke, have as their main characteristics the high pro- portion of syntaxial quartz overgrowth and a porosity originated from different processes, initially by dissolu- tion and later by partial filling and fracturing. Features like the presence of floating grains in the syntaxial cement, the transitional interpenetrative contact between the silica-rich cement and grains as well as the intense fracture porosity are strong indications that the cement has been formed by dissolution and reprecipita- tion of quartz from the framework under the effect of thermal expansion followed by rapid contraction. The increase of the silica-rich cement towards the dyke in association with the orthogonal disposition of the columns relative to dyke walls are indicative that the igneous body may represent the main heat source for the interstitial aqueous solutions previously existing in the sediments. At macroscopic scale, the increasing of inter- nal tensions in the sandstones is responsible for the nucleation of polygons, leading to the individualization of prisms, which are interconnected by a system of joints, formed firstly on isotherm surfaces of low tem- perature and later on successive adjacent planes towards the dyke heat source.

关键词：柱状连接砂岩巴拉圭南美洲动力学