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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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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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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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Helicobacter pylori infection:How does age influence the inflammatory pattern?

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World Journal of Gastroenterology 2022年第4期28卷 402-411页

作者： Glauber Rocha lima Araújo Hanna santos Marques Maria Luísa Cordeiro santos Filipe Antônio França daSilva Breno Bittencourt da Brito gabriel lima correa santos Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094Brazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45083-900Brazil

The inflammatory pattern during Helicobacter pylori(H.pylori)infection is changeable and complex.During childhood,it is possible to observe a predominantly regulatory response,evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-β1 and IL-10,in addition to high expression of the transcription factor FOXP3.On the other hand,there is a predominance of cytokines associated with the Th1 and Th17 responses among H.pylori-positive adults.In the last few years,the participation of the Th17 response in the gastric inflammation against H.pylori infection has been highlighted due to the high levels of TGF-β1 and IL-17 found in this infectious scenario,and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection.Moreover,this cytokine profile might play a pivotal role in the effectiveness of anti-H.pylori vaccines.It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H.pylori,and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.

关键词： Helicobacter pylori Inflammation Treg response Th1 response Th17 response Gastric diseases

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Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

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World Journal of Gastroenterology 2023年第14期29卷 2202-2221页

作者： Fabian Fellipe Bueno Lemos Caroline Tianeze de Castro Mariana santos Calmon Marcel Silva Luz Samuel Luca Rocha Pinheiro Clara Faria Souza Mendes dos santos gabriel lima correa santos Hanna santos Marques Henrique Affonso Delgado Kádima Nayara Teixeira Cláudio lima Souza Márcio Vasconcelos Oliveira Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45029094BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919899ParanáBrazil

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(H.pylori)-induced chronic gastritis.Clinical practice guidelines currently recommend H.pylori eradication as the preferred initial treatment for early-stage GML.To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is imperative.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September 2022.Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H.pylori-positive patients.The risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal Tools.The pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects model.Heterogeneity and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P50%,respectively.Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.RESULTS The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text reading.Finally,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational studies.The overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 H.pylori-positive early-stage GML patients,in whom H.pylori was successfully eradicated,were included in the analysis.The pooled CR of H.pylori-p

关键词： Lymphoma B-cell Marginal zone Gastric mucosa-associated lymphoid tissue lymphoma Stomach lymphoma Helicobacter pylori Therapeutics Eradication therapy

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Transmission of severe acute respiratory syndrome coronavirus 2 via fecal-oral:Current knowledge

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World Journal of Clinical Cases 2021年第28期9卷 8280-8294页

作者： Filipe Antônio França da Silva Breno Bittencourt de Brito Maria Luísa Cordeiro santos Hanna santos Marques Ronaldo Teixeira da Silva Júnior Lorena Sousa de Carvalho Samuel de Sousa Cruz gabriel Reis Rocha gabriel lima correa santos Kathlen Coutinho de Souza Rebeca gabrielle Almeida Maciel Daiana Silva Lopes Natália Oliveira e Silva Márcio Vasconcelos Oliveira Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45002175BahiaBrazil Departamento de Ciências Naturais Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45002175BahiaBrazil Departamento de Bioquímica e Biofísica Universidade Federal da BahiaSalvador 40.110-100BahiaBrazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 93 million cases and 2 million deaths in the world.SARS-CoV-2 respiratory tract infection and its main clinical manifestations such as cough and shortness of breath are well known to the scientific community.However,a growing number of studies have reported SARS-CoV-2-related gastrointestinal involvement based on clinical manifestations,such as diarrhea,nausea,vomiting,and abdominal pain as well as on the pathophysiological mechanisms associated with coronavirus disease 2019.Furthermore,current evidence suggests SARS-CoV-2 transmission via the fecal-oral route and aerosol dissemination.Moreover,studies have shown a high risk of contamination through hospital surfaces and personal fomites.Indeed,viable SARS-CoV-2 specimens can be obtained from aerosols,which raises the possibility of transmission through aerosolized viral particles from feces.Therefore,the infection by SARS-CoV-2 via fecal-oral route or aerosolized particles should beconsidered.In addition,a possible viral spread to sources of drinking water,sewage,and rivers as well as the possible risk of viral transmission in shared toilets become a major public health concern,especially in the least developed countries.Since authors have emphasized the presence of viral RNA and even viable SARS-CoV-2 in human feces,studies on the possible fecal-oral coronavirus disease 2019 transmission become essential to understand better the dynamics of its transmission and,then,to reinforce preventive measures against this infection,leading to a more satisfactory control of the incidence of the infection.

关键词： COVID-19 SARS-CoV-2,Transmission Via fecal-oral

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Bone marrow-derived products: A classification proposal – bone marrow aspirate, bone marrow aspirate concentrate or hybrid?

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World Journal of Stem Cells 2020年第4期12卷 241-250页

作者： Joseph Purita JoséFábio santos Duarte Lana Morey Kolber Bruno lima Rodrigues Tomas Mosaner gabriel Silva santos Carolina Caliari-Oliveira Stephany Cares Huber Institute of Regenerative Medicine Boca RatonFL 33432United States Institute of Bone and Cartilage IndaiatubaSP 13334-170Brazil Department of Physical Therapy Nova Southeastern UniversityFort LauderdaleFL 33314United States University of Campinas CampinasSP 13083-970Brazil In Situ Cell Therapy Ribeirao PretoSP 14056-680Brazil

Degenerative musculoskeletal disorders are one of the top causes of pain and disability in the adult population.Current available alternatives to mitigate symptoms include conservative treatments such as the administration of pharmacological agents and an educative approach towards lifestyle modification.The use of certain analgesics,such as opiates and corticosteroids,delivers short term results but do not address the etiological source of pain and disability.Also,prolonged use of such medications may cause additional complications.Therefore,the demand for musculoskeletal tissue regeneration has led to an alternative approach referred to as“orthobiologics”.This alternative is based on cellular and molecular components capable of inducing and promoting tissue repair.Bone marrow(BM)aspirate(BMA)and concentrate are well-known orthobiologics used to treat musculoskeletal conditions.Orthobiologics derived from the BM have been discussed in the literature;however,the lack of standardization regarding collection and processing protocols presents a challenge for generalization of study outcomes and determination of efficacy.Since BM-derived orthobiologics have not yet been classified,to our knowledge,this manuscript proposes the ACH classification system,which speaks to BMA(A),BMA and concentrate(C)and hybrid(H),which combines A and C.This classification proposes and describes 8 parameters that are relevant for the quality of biological products.The more parameters used would imply greater characterization and complexity of the evaluation of the biological product used.The ACH classification envisages a necessary contribution to the comprehension of both clinical procedures and research outcomes,ultimately ushering in a standardization of best practice.

关键词： Bone-marrow classification Bone-marrow aspirate concentrate Regenerativemedicine Stem cells Musculoskeletal disorders Orthobiologics

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Strategies for the analysis of single-tree plot experiments in Eucalyptus plantations

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Journal of Forestry Research 2021年第6期32卷 2437-2445页

作者： Heloisa Guimaraes santos Flavia Maria Avelar Goncalves Jose Luis lima Aurelio Mendes Aguiar gabriel Dehon Sampaio Pecanha Rezende Bruno Marco de lima Magno Antonio Patto Ramalho Departamento de Biologia Setor de Genetica E Melhoramento de PlantasUniversidade Federal de Lavras-UFLALavrasMGBrasil Suzano Papel E Celulose Sao PauloSPBrasil Bracell SP Celulose Ltda Lencóis PaulistaSPBrasil

To verify if the response by Eucalyptus clones in a single-tree plot is influenced by neighboring plants and to determine the effect of missing and/or dominated plants,seven eucalyptus trials in four Brazilian states were analyzed in a randomized complete block design with one plant/plot and 30 replications.Mean annual increment(MAI,m^(3)ha^(-1)per year)was determined for three-year-old clones.The influence of neighboring clones was estimated by a linear regression coefficient between the MAI of each clone/plot and the average of a clonal MAI and its eight neighbors.To determine the effect of missing and/or dominated trees,a correction between the MAI and the area available/plant was applied.Subsequent analysis considered unadjusted and adjusted data for missing and dominated trees.Estimate of accuracy and index of coincidence were used to compare the adjustments.In single-tree plots,clone performances were not influenced by neighboring plants.Experimental accuracy was not increased by any of the adjustments employed and the clone ranking was not altered,and therefore did not justify their use.

关键词： Single-tree plot Missing plant adjustment Eucalyptus breeding

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Photobiomodulation therapy for osteoarthritis: Mechanisms of action

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World Journal of Translational Medicine 2022年第3期10卷 29-42页

作者： Fábio Pericinoto Giolo gabriel Silva santos Victor Fontes Pacheco Stephany Cares Huber Kaue Franco Malange Bruno lima Rodrigues Fernanda Bassora Tomas Mosaner gabriel Azzini Lucas Leite Ribeiro Carlos Amilcar Parada JoséFábio santos Duarte Lana Department of Physical Therapy Brazilian Institute of Regenerative MedicineIndaiatuba 13334-170Brazil Biomedical Science Brazilian Institute of Regenerative MedicineIndaiatuba 13334-170Brazil Department of Orthopedics Brazilian Institute of Regenerative MedicineIndaiatuba 13334-170Brazil Neurobiology of Pain and Regenerative Medicine The University of CampinasCampinas 13083-862Brazil Department of Hematology The University of CampinasCampinas 13083-878Brazil

Photobiomodulation(PBM)is a non-invasive therapeutic modality with demonstrated effects in many fields related to regenerative medicine.In the field of orthopedics,in particular,PBM at various wavelengths has demonstrated the capacity to trigger multiple biological effects associated with protective mechanisms in musculoskeletal tissues.The articles cited in this review show that devices operating close to or within the near infrared range at low intensities can provoke responses which favor the shift in the predominant catabolic microenvironment typically seen in degenerative joint diseases,especially osteoarthritis(OA).These responses include proliferation,differentiation and expression of proteins associated with stable cell cycles.Additionally,PBM can also modulate oxidative stress,inflammation and pain by exerting regulatory effects on immune cells and blocking the transmission of pain through sensory neuron fibers,without adverse events.Collectively,these effects are essential in order to control the progression of OA,which is in part attributed to exacerbated inflammation and degradative enzymatic reactions which gradually contribute to the destruction of joint tissues.PBM may offer medical experts ease of application,financial viability,efficacy and lack of serious adverse events.Therefore,it may prove to be a suitable ally in the management of mild to moderate degrees of OA.This review explores and discusses the principal biological mechanisms of PBM and how the produced effects may contribute to the amelioration of osteoarthritic progression.Literature was reviewed using PubMed and Google Scholar in order to find studies describing the mechanisms of PBM.The investigation included a combination of nomenclature such as:“photobiomodulation”,“phototherapy”,“laser therapy”,“PBM”,“osteoarthritis”,low level light therapy”,“inflammation”and“cartilage”.We considered only articles written in English,with access to the full text.

关键词： Photobiomodulation Low-level laser therapy Osteoarthritis Inflammation Regenerative medicine

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Sepsis after Administering an Intramuscular Iron Injection in the Arm of an Elder Patient with Multiple Comorbidities: A Case Report

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Journal of Biosciences and Medicines 2023年第5期11卷 158-165页

作者： Michele Paula dos santos Taís Michele Werle Mariana Martins Dantas santos Carolina Boeira Soares Carlos Augusto Treviso Italo Trois Maestri Stella Duarte Pinto Carolina Hack Alves Laura Gomes Boabaid de Barros Maria Eduarda Perobelli Buzetto Guilherme Boeira Soares gabriel Lorentz Trein Aline Porto Bárbara Adelmann de lima Fernanda Bercht Merten Luane Pereira Gomes Rafaela Siviero Caron-Lienert Miriam Viviane Baron School of Medicine Pontifical Catholic University of Rio Grande do Sul (PUCRS) Porto Alegre Brazil Course of Medicine Lutheran University of Brazil (ULBRA) Canoas Brazil School of Medicine and Health Sciences Pontifical Catholic University of Rio Grande do Sul (PUCRS) Porto Alegre Brazil Interdisciplinary Institute of Science and Health Education Porto Alegre Brazil

Background: Skin reactions and musculoskeletal injuries caused by intramuscular injection are an increased risk for skin and soft tissue infections and may culminate in sepsis. Objective: To describe the history of an elderly patient who developed a lesion in her right arm after home administration of intramuscular iron injection in this arm and its outcome. Methods: This is a case report of a patient who participated in a study in an intensive care unit. Results: This study describes a 65-year-old patient with multiple comorbidities who was admitted to the hospital complaining of pain for two months and difficulty in moving her right shoulder associated with skin and soft tissue infections in her right arm after intramuscular iron administration by a relative for the treatment of multifactorial anemia and refractory melena. The patient worsened her general condition and was transferred to the intensive care unit. Despite the therapy instituted, the patient developed sepsis of cutaneous origin, multiple organ dysfunction, and death. Conclusions: The administration of intramuscular medication requires the participation of qualified professionals, such as nurses, mainly within the scope of the Brazilian public health system which commonly comprises patients in a context of vulnerability.

关键词： Critical Care Education Continuing Injectables Septicemia Soft Tissue Infections Suppuration

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