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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： Luis Guilherme de Oliveira Silva Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos Santos Calmon Gabriel Lima Correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

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Complexed amino acid minerals vs. bis-glycinate chelated minerals:Impact on the performance of old laying hens

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Animal Nutrition 2024年第1期16卷 395-408页

作者： Marcos J.B.Santos Maria C.M.M.Ludke Leandro M.Silva Carlos B.V.Rabello Mércia R.Barros Fabiano S.Costa Clariana S.Santos Jamille S.S.Wanderley Department of Animal Science Rural Federal University of Pernambuco Department of Veterinary Science Rural Federal University of Pernambuco

The present study was to evaluate the effect of trace minerals(Zn, Mn, and Cu) from complexed amino acid minerals(ZMCAA) and bis-glycinate chelated minerals(ZMCGly) in laying hen diets on performance,internal and external egg quality, yolk mineral deposition, intestinal morphometry, and bone characteristics. From 78 to 98 weeks of age, 400 White LSL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per treatment. Treatments were distributed in a 2 ×2 factorial arrangement using either Zn, Mn, and Cu of ZMCAA or ZMCGly source at 2 levels: low(20, 20,and 3.5 mg/kg of Zn, Mn, and Cu, respectively) or high(40, 40, and 7 mg/kg of Zn, Mn, and Cu,respectively). The analysis of variance was performed, and in cases where differences were observed, the means were compared using Tukey?s test(P < 0.05). The source and level of trace mineral supplementation had a significant impact on the performance of laying hens. Hens fed ZMCAA had higher egg production(P = 0.01), egg weight(P = 0.02), egg mass(P = 0.01), and lower feed conversion ratio(P =0.05) compared to those fed ZMCGly. The ZMCAA supplementation showed higher albumen height(P =0.01), albumen weight(P = 0.01), and eggshell thickness(P < 0.01). The deposition of Zn(P < 0.01), Mn(P< 0.01), and Cu(P < 0.01) in the egg yolk was greater for hens received ZMCAA. Tibia weight(P = 0.04)and bone densitometry(P < 0.01) in the tibia were higher with ZMCAA supplementation. In the small intestine, ZMCAA resulted in longer villi(P = 0.02) and shorter crypt depth(P = 0.01) in the duodenum.Jejunum and ileum measurements were influenced by the level and source of trace minerals(P < 0.05).Laying hens fed ZMCAA exhibited superior performance, egg quality, deposition of trace minerals in the egg yolk, and bone density compared to hens fed ZMCGly. In this study, older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.

关键词： Bis-glycinates Metal-amino acids Radiodensity Trace minerals

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Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy

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World Journal of Gastroenterology 2024年第6期30卷 579-598页

作者： Fabian Fellipe Bueno Lemos Caroline Tianeze de Castro Marcel Silva Luz Gabriel Reis Rocha Gabriel Lima Correa Santos Luís Guilherme de Oliveira Silva Mariana Santos Calmon Cláudio Lima Souza Ana Carla Zarpelon-Schutz Kádima Nayara Teixeira Dulciene Maria de Magalhães Queiroz Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919-899ParanáBrazil Laboratory of Research in Bacteriology UFMGBelo Horizonte 30130-100Minas GeraisBrazil

BACKGROUND Helicobacter pylori(H.pylori)infection has been well-established as a significant risk factor for several gastrointestinal disorders.The urea breath test(UBT)has emerged as a leading non-invasive method for detecting H.pylori.Despite numerous studies confirming its substantial accuracy,the reliability of UBT results is often compromised by inherent limitations.These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H.pylori infection.AIM To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H.pylori infection in adult patients with dyspepsia.METHODS We conducted an independent search of the PubMed/MEDLINE,EMBASE,and Cochrane Central databases until April 2022.Our search included diagnostic accuracy studies that evaluated at least one of the index tests(^(13)C-UBT or ^(14)C-UBT)against a reference standard.We used the QUAdaS-2 tool to assess the methodo-logical quality of the studies.We utilized the bivariate random-effects model to calculate sensitivity,specificity,positive and negative test likelihood ratios(LR+and LR-),as well as the diagnostic odds ratio(DOR),and their 95%confidence intervals.We conducted subgroup analyses based on urea dosing,time after urea administration,and assessment technique.To investigate a possible threshold effect,we conducted Spearman correlation analysis,and we generated summary receiver operating characteristic(SROC)curves to assess heterogeneity.Finally,we visually inspected a funnel plot and used Egger’s test to evaluate publication bias.endorsing both as reliable diagnostic tools in clinical practice.CONCLUSION In summary,our study has demonstrated that ^(13)C-UBT has been found to outperform the ^(14)C-UBT,making it the preferred diagnostic approach.Additionally,our results emphasize the significance of carefully considering urea dosage,assessment timing,and measurement techniques for both tests to enhance diagnostic precision.Nevertheless,it is cru

关键词： Helicobacter pylori Urea breath test Diagnosis Diagnostic test accuracy Meta-analysis

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Plant growth and metabolism of exotic and native Crotalaria species for mine land rehabilitation in the Amazon

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Journal of Forestry Research 2024年第1期35卷 143-154页

作者： Hemelyn Soares das Chagas Rafael Silva Guedes Markus Gastauer Paula Godinho Ribeiro Allan Klynger da Silva Lobato Cecílio Frois Caldeira Fabrício William deÁvila AndréRodrigues dos Reis Silvio Junio Ramos Instituto Tecnológico Vale Rua Boaventura da Silva955BelémPA 66055-090Brazil universidade federal do Sul e Sudeste do Pará XinguaraPABrazil Núcleo de Pesquisa Vegetal Básica e Aplicada Universidade Federal Rural da AmazôniaParagominasPABrazil Departamento de Engenharia Florestal Universidade Estadual do Centro-Oeste/UNICENTROIratiPRBrazil School of Sciences and Engineering São Paulo State University(UNESP)TupãSP.CEP 17602-496Brazil

Despite its enormous benefits,mining is respon-sible for intense changes to vegetation and soil properties.Thus,after extraction,it is necessary to rehabilitate the mined areas,creating better conditions for the establishment of plant species which is challenging.This study evaluated mineral and organic fertilization on the growth,and carbon and nitrogen(N)metabolism of two Crotalaria species[Cro-talaria spectabilis(exotic species)and Crotalaria maypu-rensis(native species from Carajás Mineral Province(CMP)]established on a waste pile from an iron mine in CMP.A control(without fertilizer application)and six fertilization mixtures were tested(i=NPK;ii=NPK+micronutrients;iii=NPK+micronutrients+organic compost;iv=PK;v=PK+micronutrients;vi=PK+micronutrients+organic compost).Fertilization contributed to increased growth of both species,and treatments with NPK and micronutrients had the best results(up to 257%cf.controls),while organic fertilization did not show differences.Exotic Crotalaria had a greater number of nodules,higher nodule dry mass,chlorophyll a and b contents and showed free ammonium as the predominant N form,reflecting greater increments in biomass compared to native species.Although having lower growth,the use of this native species in the rehabilitation of mining areas should be considered,mainly because it has good development and meets current government legislation as an opportunity to restore local biodiversity.

关键词： Biological nitrogen fixation Mining Nitrogen metabolism Plant nutrition

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Immune pathway through endometriosis to ovarian cancer

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World Journal of Clinical Oncology 2024年第4期15卷 496-522页

作者： Mariana Santos Calmon Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Luis Guilherme de Oliveira Silva Gabriel Lima Correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

关键词： Ovarian neoplasms Endometriosis Endometriosis-associated ovarian cancers Immune response Immunotherapy

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Increasing dietary fiber intake for type 2 diabetes mellitus management: A systematic review

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World Journal of Diabetes 2024年第5期15卷 1001-1010页

作者： Douglas Nitzke Juliana Czermainski Carolina Rosa Chaline Coghetto Sabrina Alves Fernandes Randhall B Carteri Department of Nutrition Centro Universitário CESUCACachoeirinha 94935-630Brazil Department of Hepatology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90430-080Brazil Postgraduate Program in Hepatology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90050-170Brazil Postgraduate Program in Hepatology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil

BACKGROUND Type 2 diabetes is a chronic,non-communicable disease with a substantial global impact,affecting a significant number of individuals.Its etiology is closely tied to imbalanced dietary practices and sedentary lifestyles.Conversely,increasing die-tary fiber(DF)intake has consistently demonstrated health benefits in numerous studies,including improvements in glycemic control and weight management.AIM To investigate the efficacy of DF interventions in the management of type 2 diabetes mellitus(T2DM).METHODS A systematic literature review was conducted to explore the association between DF intake and the management of T2DM.Following the inclusion and exclusion criteria,a total of 26 studies were included in this review.RESULTS The main strategies implied to increased DF intake were:High DF diet plus acarbose(2 studies);DF supplements(14 studies);and high DF diets(10 studies).Overall,most studies indicated that increased DF intake resulted in im-provements in glycemic control and weight management in T2DM patients.CONCLUSION DF represents a valuable strategy in the treatment of type 2 diabetes,improving health outcomes.DF intake offers the potential to improve quality of life and reduce complications and mortality associated with diabetes.Likewise,through supplements or enriched foods,DF contributes significantly to the control of several markers such as HbA1c,blood glucose,triglycerides,low-density lipoprotein,and body weight.

关键词： Type 2 diabetes mellitus Soluble fibers Insoluble fibers Probiotics Blood glucose Nutrition

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Geostatistical seismic inversion and 3D modelling of metric flow units,porosity and permeability in Brazilian presalt reservoir

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Petroleum Science 2024年第3期21卷 1699-1718页

作者： Rodrigo Penna Wagner Moreira Lupinacci Exploratory Interpretation and Reservoir Characterization Group (GIECAR) Department of Geology and Geophysics Universidade Federal Fluminense Petrobras

Flow units(FU) rock typing is a common technique for characterizing reservoir flow behavior, producing reliable porosity and permeability estimation even in complex geological settings. However, the lateral extrapolation of FU away from the well into the whole reservoir grid is commonly a difficult task and using the seismic data as constraints is rarely a subject of study. This paper proposes a workflow to generate numerous possible 3D volumes of flow units, porosity and permeability below the seismic resolution limit, respecting the available seismic data at larger scales. The methodology is used in the Mero Field, a Brazilian presalt carbonate reservoir located in the Santos Basin, who presents a complex and heterogenic geological setting with different sedimentological processes and diagenetic history. We generated metric flow units using the conventional core analysis and transposed to the well log data.Then, given a Markov chain Monte Carlo algorithm, the seismic data and the well log statistics, we simulated acoustic impedance, decametric flow units(DFU), metric flow units(MFU), porosity and permeability volumes in the metric scale. The aim is to estimate a minimum amount of MFU able to calculate realistic scenarios porosity and permeability scenarios, without losing the seismic lateral control. In other words, every porosity and permeability volume simulated produces a synthetic seismic that match the real seismic of the area, even in the metric scale. The achieved 3D results represent a high-resolution fluid flow reservoir modelling considering the lateral control of the seismic during the process and can be directly incorporated in the dynamic characterization workflow.

关键词： Flow units Geostatistical inversion Presalt reservoir 3D reservoir modelling Petrophysical modelling

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Simulated rainfall in Brazil:An alternative for assesment of soil surface processes and an opportunity for technological development

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International Soil and Water Conservation Research 2024年第1期12卷 29-42页

作者： Camila Calazans da Silva Luz Wilk Sampaio de Almeida Adilson Pacheco de Souza Nivaldo Schultz Jamil Alexandre Ayach Anache daniel Fonseca de Carvalho Postgraduate Program in Agronomy-Soil Sciences Federal Rural University of Rio de JaneiroSeropédicaRJBrazil Agronomy Department Federal Institute of EducationScience and Technology of RondôniaAriquemesROBrazil federal University of Mato Grosso SinopMTBrazil federal rural University of Rio de Janeiro SeropédicaRJBrazil federal University of Mato Grosso do Sul Campo GrandeMSBrazil

Rainfall simulators(RS)have been used,above all,to evaluate hydrological processes related to soil water infiltration,surface runoff and soil erosion.They allow repeatability of rain application with different precipitation intensities in field and/or laboratory conditions and should produce events with physical characteristics similar to natural rain.In this manuscript,we carried out a bibliometric and scientometric analysis of studies with simulated rainfall in Brazil to assess the temporal evolution of publications,the main topics addressed and the degree of technological development of the equipment.We searched for the terms“rainfall simulator”OR“simulated rainfall”AND“Brazil”in the Scopus,Web of Science,SciELO and Google Scholar databases.We found 143 articles published in the last 37 years(1985-2022).Our findings indicate that the main research areas covered in papers are soil erosion(57.34%),soil water infiltration(24.47%),nutrient losses(9.8%)and RS development and calibration/assessment(8.39%).In recent years,the number of published papers in international high-impact factor journals has increased.Most of the papers(49.65%)refer to studies carried out by institutions located in the south and southeast regions of Brazil.Moreover,there is a large gap of studies on simulated rainfall in other regions of Brazil,where important biomes such as the Cerrado,Amazon,Caatinga,and their transitions are located.This study informs research priorities on soil erosion under simulated rainfall and provides a bibliographic database that can assist in more detailed future analyses.

关键词： Rainfall simulator Soil and water losses Soil water infiltration Bibliometrics Scientific review

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In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori

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World Journal of Clinical Oncology 2024年第5期15卷 653-663页

作者： Rafaela Viana Vieira Gabrielle Caroline Peiter Fabrício Freire de Melo Ana Carla Zarpelon-Schutz Kádima Nayara Teixeira universidade federal do Paraná Campus ToledoToledo 85919-899Brazil universidade Tecnológica federal do Paraná Campus ToledoParaná85902-490Brazil universidade federal da Bahia Instituto Multidisciplinar em Saúde-Campus Anísio TeixeiraVitória da Conquista 45029-094Brazil universidade federal do Paraná-Setor Palotina Programa de Pós-graduação em BiotecnologiaPalotina 85950-000Brazil

BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants with the aim of eliminating the pathogen;however,the possibility of blocking H.pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed.This type of study is expensive and time-consuming,requiring in vitro and/or in vivo tests,which can be solved using bioinformatics.Therefore,prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H.pylori.METHODS In this in silico study,the structures of the phenolic compounds(ligands)kaempferol,myricetin,quercetin,ponciretin(flavonoids),and chlorogenic acid(phenolic acid)were selected from the PubChem database.These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H.pylori infection.The three-dimensional structure model of the CagA oncoprotein of H.pylori(receptor)was obtained through molecular modeling using computational tools from the I-Tasser platform,employing the threading methodology.The primary sequence of CagA was sourced from GenBank(BAK52797.1).A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands,utilizing the GRaSP online platform.Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4(ADT)software,and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software.Two sets of simulations were performed:One involving the central region of CagA with phenolic compounds,and another involving the carboxy-terminus region of CagA with phen

关键词： CagA oncoprotein Phenolic compounds Helicobacter pylori In silico analyses Medicinal plants Prospective analysis

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Litter production and leaf nutrient concentration and remobilization in response to climate seasonality in the central Amazon

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Journal of Forestry Research 2024年第3期35卷 131-141页

作者： Ricardo Antonio Marenco Saul Alfredo Antezana-Vera daniela Pereira Dias Luiz Antonio Candido Instituto Nacional de Pesquisas da Amazonia Coordenagao de Uso da Terra e Mudanca ClimaticaAv.Andre Araujo 2936ManausAM69067-375Brazil Programa de pos-Graduagao em Agricultura no Tropico Umido Instituto Nacional de Pesquisas da Amazonia-INPAManausAMBrazil Unidade Academica de Ciencias Agrarias Universidade Federal de JataiBR 364km 195JataiGO 75801-615Brazil

Litterfall is the largest source of nutrients to for-est soils of tropical rainforests.However,variability in lit-terfall production,nutrient remobilization,and changes in leaf nutrient concentration with climate seasonality remain largely unknown for the central Amazon.This study meas-ured litterfall production,leaf nutrient remobilization,and leaf area index on a forest plateau in the central Amazon.Litterfall was measured at monthly intervals during 2014,while nitrogen,phosphorus,potassium,calcium and mag-nesium concentrations of leaf litter and canopy leaves were measured in the dry and rainy seasons,and remobilization rates determined.Leaf area index was also recorded in the dry and rainy seasons.Monthly litterfall varied from 33.2(in the rainy season)to 87.6 g m^(-2) in the dry season,while leaf area index increased slightly in the rainy season.Climatic seasonality had no effect on concentrations of nitrogen,calcium,and magnesium,whereas phosphorous and potassium responded to rainfall seasonality oppositely.While phosphorous increased,potassium decreased during the dry season.Over seasons,nitrogen,potassium,and phosphorous decreased in leaf litter;calcium increased in leaf litter,while magnesium remained unaffected with leaf aging.Regardless,the five nutrients had similar remobilization rates over the year.The absence of climate seasonality on nutrient remobilization suggests that the current length of the dry season does not alter nutrient remobilization rates but this may change as dry periods become more prolonged in the future due to climate change.

关键词： Throughfall Nutrient cycling Climatic seasonality Leaf mass per area

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