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Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

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World Journal of Clinical Oncology 2024年第5期15卷 587-590页

作者： leonardo S Lino-silva Sabrina B Martínez-Villavicencio Luisa Fernanda Rivera-Moncada Department of Pathology Oncology National Cancer Institute(Mexico)TlalpanMexico City 14080Mexico

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

关键词： Primary central nervous system lymphoma Zanubrutinib Bruton’s tyrosine kinase Prognosis Myeloid differentiation primary response 88 gene Cluster of differentiation 79B gene

Gravity-Driven Listric Growth Fault and Sedimentation in the Lagoa do Peixe, Rio Grande do Sul Coastal Plain, Brazil

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Open Journal of Geology 2024年第4期14卷 594-616页

作者： Bruno silva da Fontoura Adelir José Strieder Iran Carlos Stalliviere Corrêa Paulo Rogério mendes Instituto de Geociê ncias UFRGS Porto Alegre Brazil Engenharia Geoló gica Centro de Engenharias UFPel Pelotas Brasil HIDROSERV— Servi&#231os Geol&#243gicos e Geof&#237sicos Ltda. Porto Alegre Brazil

High frequency, high resolution GPR surveys are successfully applied to investigate near-surface stratification architecture of sedimentary units in coastal plains and to define their depositional conditions. However, low frequency GPR surveys to investigate fault-related depositional systems at greater depths are scarce. This survey was designed investigate a > 100 km long linear escarpment that controls the northwest margin of the Lagoa do Peixe, an important lagoon in Rio Grande do Sul Coastal Plain (RGSCP, Brazil). The traditional approach points that RGSCP was developed by juxtaposition of four lagoons/barrier systems as consequence of sea level changes;no deformational structure is admitted to exist before. The low frequency GPR (50 MHz, RTA antenna) and geological surveys carried out in the RGSCP showed the existence of a large, gravity-driven listric growth fault controlling the Lagoa do Peixe escarpment and hangingwall sedimentation. The radargrams in four subareas along the Lagoa do Peixe Growth Fault could be interpreted following the seismic expression of rift-related depositional systems. The radargrams enabled to distinguish three main lagoonal deposition radarfacies. The lower lagoonal radarfacies is a convex upward unit, thicker close to growth fault;the radarfacies geometry indicates that fault displacement rate surpasses the sedimentation rate, and its upper stratum is aged ~3500 l4C years BP. The second lagoonal radarfacies is a triangular wedge restricted to the lagoon depocenter, whose geometry indicates that fault displacement and the sedimentation rates kept pace. The upper lagoonal radarfacies is being deposited since 1060 ± 70 l4C years BP, under sedimentation rate higher than fault displacement rate. The results indicate that low frequency GPR surveys can help in investigating fault-related depositional systems in coastal zones. They also point to a new approach in dealing with RGSCP stratigraphy.

关键词： GPR (Ground-Penetrating Radar) Growth Fault Sedimentation Radarfacies Coastal Plain

Gravity Fault Subsidence and Beach Ridges Progradation in Quinta-Cassino (RS) Coastal Plain, Brazil

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Open Journal of Geology 2024年第2期14卷 177-195页

作者： Bruno silva da Fontoura Adelir José Strieder Iran Carlos Stalliviere Corrêa Paulo Rogério mendes Alexandre Felipe Bruch Angélica Cirolini Programa de Pós-Graduaç &#227o em Geoci&#234ncias (PPGeo) Instituto de Geoci&#234ncias UFRGS Porto Alegre Brazil Engenharia Geológica Centro de Engenharias UFPel Pra&#231a Domingos Rodrigues 2 Pelotas Brasil HIDROSERV-Serviç os Geológicos e Geofísicos Ltda. Rua Senegal 152 Porto Alegre Brazil Colégio Politécnico UFSM Santa Maria Brasil

Ground penetrating radar (GPR) surveys have being applied to investigate very near-surface stratification of sedimentary units in coastal plains and to define their depositional conditions. This paper presents, however, low-frequency GPR survey to investigate fault-related depositional systems at greater depths. The Quinta-Cassino area in the Rio Grande do Sul Coastal Plain (RGSCP, Brazil) shows a wide strandplain that is made off by very long, continuous, and linear geomorphic features (beach ridges). This strandplain extends for ~70 km southward. The beach ridges show low-angle truncations against the Quinta escarpment, and also truncations in the strandplain. The traditional approach points that RGSCP was developed by juxtaposition of four lagoons/barrier systems as consequence of sea level changes;previous model assumes that no deformational episode occurred in RGSCP. The geophysical and geological surveys carried out in this area showed the existence of listric fault controlling the beach ridges in the escarpments and hanging-wall blocks. The radargrams could distinguish Pleistocene basement unit anticlockwise rotation, thickening of beach ridges radarfacies close to listric normal faults, and horst structures. These deformational features indicate that the extensional zone of a large-scale gravity-driven structure controlled the mechanical subsidence, the Holocene sedimentation and its stratigraphic and geomorphic features in the Quinta-Cassino area to build up an asymmetric delta. The results point to a new approach in dealing with RGSCP Holocene evolution.

关键词： Gravity Tectonics Normal Faults Ground Penetrating Radar Survey Beach-Ridges Progradation

CITED2 and the modulation of the hypoxic response in cancer

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World Journal of Clinical Oncology 2020年第5期11卷 260-274页

作者： Mónica T Fernandes Sofia M Calado leonardo mendes-silva JoséBraganca School of Health Universidade do AlgarveCampus of GambelasFaro 8005-139Portugal Centre for Biomedical Research Universidade do AlgarveCampus of GambelasFaro 8005-139Portuga Algarve Biomedical Centre Faro 8005-139Portugal Department of Biomedical Sciences and Medicine Universidade do AlgarveCampus of GambelasFaro 8005-139Portugal

CITED2(CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain,2)is a ubiquitously expressed protein exhibiting a high affinity for the CH1 domain of the transcriptional co-activators CBP/p300,for which it competes with hypoxia-inducible factors(HIFs).CITED2 is particularly efficient in the inhibition of HIF-1α-dependent transcription in different contexts,ranging from organ development and metabolic homeostasis to tissue regeneration and immunity,being also potentially involved in various other physiological processes.In addition,CITED2 plays an important role in inhibiting HIF in some diseases,including kidney and heart diseases and type 2-diabetes.In the particular case of cancer,CITED2 either functions by promoting or suppressing cancer development depending on the context and type of tumors.For instance,CITED2 overexpression promotes breast and prostate cancers,as well as acute myeloid leukemia,while its expression is downregulated to sustain colorectal cancer and hepatocellular carcinoma.In addition,the role of CITED2 in the maintenance of cancer stem cells reveals its potential as a target in non-small cell lung carcinoma and acute myeloid leukemia,for example.But besides the wide body of evidence linking both CITED2 and HIF signaling to carcinogenesis,little data is available regarding CITED2 role as a negative regulator of HIF-1αspecifically in cancer.Therefore,comprehensive studies exploring further the interactions of these two important mediators in cancer-specific models are sorely needed and this can potentially lead to the development of novel targeted therapies.

关键词： Cancer Cancer stem cell CBP/p300 CITED2 Hypoxia-inducible factors 1α

Parallel evolution of fish bi-modal breathing and expansion of olfactory receptor(OR)genes:toward a universal ORs nomenclature

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遗传学报:英文版 2023年第8期50卷 600-610页

作者： Liliana silva Tito mendes Luana Ramos Guojie Zhang Agostinho Antunes CIIMAR/CIMAR Interdisciplinary Centre of Marine and Environmental ResearchUniversity of PortoTerminal de Cruzeiros do Porto de LeixõesAv.General Norton de Matoss/n4450-208PortoPortugal Department of Biology Faculty of SciencesUniversity of PortoRua do Campo Alegre4169-007PortoPortugal Villum Centre for Biodiversity Genomics Section for Ecology and EvolutionDepartment of BiologyUniversity of CopenhagenDK-2100 CopenhagenDenmark BGI-Shenzhen Beishan Industrial ZoneShenzhenGuangdong 518083China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China

Olfactory receptors(ORs)play a key role in the prime sensorial perception,being highly relevant for intra/interspecific interactions.ORs are a subgroup of G-protein coupled receptors that exhibit highly complex subgenomes in vertebrates.However,OR repertoires remain poorly studied in fish lineages,precluding finely retracing their origin,evolution,and diversification,especially in the most basal groups.Here,we conduct an exhaustive gene screening upon 43 high-quality fish genomes exhibiting varied gene repertoires(2e583 genes).While the early vertebrates performed gas exchange through gills,we hypothesize that the emergence of new breathing structures(swim bladder and paired lungs)in early osteichthyans may be associated with expansions in the ORs gene families sensitive to airborne molecules.Additionally,we verify that the OR repertoire of moderns actinopterygians has not increased as expected following a whole genome duplication,likely due to regulatory mechanisms compensating the gene load excess.Finally,we identify 25 distinct OR families,allowing us to propose an updated universal nomenclature for the fish ORs.

关键词： Fish OR repertoires Updated ORs nomenclature ORs expansion Bi-modal breathing WGD and ORs diversification

Toxicological effects of mining hazard elements

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Energy Geoscience

Energy Geoscience 2022年第3期3卷 255-262页

作者： leonardo Lucas da silva-Rego leonardo Augusto de Almeida Juciano Gasparotto Instituto de Ciencias Biomedicas-Universidade Federal de Alfenas AlfenasMinas GeraisRua Gabriel Monteiro da Silva700CEP:37130-001Centro-Alfenas/MGBrazil

Mining plays a prominent role in the economy worldwide since human efforts have been more concentrated in extraction than recycling of natural resources.Ores composed of various minerals vary according to the geological evolution.These are raw materials for the conventional industries or fossil fuels for power generation.They can also be used in new technologies.The mining industry triggers intense environmental impacts.Human exposure to multiple small particles from mining effluent,such as dust,uranium,iron,lead,zinc,silicon,titanium,sulfur,nitrogen,platinum,chromium,vanadium,manganese,and mercury,is a health risk.Such elements can have several pathological effects,such as respiratory and cardiovascular,multiple chronic inflammation,and neurodegenerative diseases.Additionally,mining results in severe soil,water(surface and aquifer),and air contamination,reaching large areas far away from the source.Negligence of mining companies,with the recovery of ancient mined areas during the early development of environmental laws and regulations,compromises environmental integrity for more extended periods,increasing coverage of the affected areas.This review evaluates the toxicological effects on humans exposed to the mining wastes and the impact of these compounds on the ecosystem.The results of our evaluation can be used by the government,manufacturers,scientists,private environmental organizations,decision-makers,and readers from different areas of knowledge to explore the potential risk of mining to the ecosystem and human health.

关键词： Mining operation Toxicology Environmental impact Ecosystem Human health

Validation of the Portuguese version of the social isolation scale with a sample of community-dwelling older adults

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International Journal of Nursing Sciences 2023年第2期10卷 151-157页

作者： João Tavares Ana Faria Delphine Gonçalves Diana mendes Sofia silva Liliana Sousa Health School University of AveiroAveiroPortugal Center for Health Technology and Services Research(CINTESIS@RISE) Portugal Health Sciences Research Unit:Nursing(UICISA:E) Portugal Department of Education and Psychology University of AveiroAveiroPortugal The Polytechnic Institute of Coimbra Coimbra Education SchoolCoimbraPortugal

Objectives The aim of this study was to analyze the psychometric properties(reliability and validity)of the Social Isolation Scale(SIS)in a sample of Portuguese community-dwelling older adults.Methods A transversal descriptive study was carried out with a convenience sample of 250 community-dwelling older adults(≥65 years).The survey comprised a sociodemographic questionnaire,SIS,Geriatric Depression Scale-4(GDS-4),6-item Lubben Social Network Scale(LSNS-6),a loneliness self-assessment question,and Satisfaction with Life Scale(SWLS).Construct validity(confirmatory factor analysis)and convergent validity were analyzed,and ISI internal reliability(composite reliability),external reliability(test-retest,intraclass correlation coefficient)and inter-rater reliability(Cohen’s kappa coefficient)were evaluated.Results Confirmatory factor analysis showed a two-factor model with an excellent index of fit.The SIS showed significant correlations with LSNS-6(rs=0.47),SWLS(rs=0.26),the loneliness self-assessment question(rs=0.35),and GDS-4(rs=−0.16).SIS composite reliability was good(0.708).The inter-class correlation coefficient varied from 0.84 to 0.98.The Cohen’s kappa coefficient ranged from 0.936 to 1.Conclusions SIS has been shown to be a valid and reliable instrument for assessing social isolation among Portuguese community-dwelling older adults.Healthcare professionals,particularly nurses working in community settings,can use SIS to assess social isolation in older adults to design,implement,and evaluate interventions.

关键词： Aged Loneliness Portugal Psychometrics Social isolation

Distinct T helper cell-mediated antitumor immunity:T helper 2 cells in focus

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Cancer Pathogenesis and Therapy 2023年第1期1卷 76-86页

作者： Rafael Cardoso Maciel Costa silva Marcela Freitas Lopes leonardo Holanda Travassos Laboratory of Immunoreceptors and Signaling Carlos Chagas Filho Biophysics InstituteFederal University of Rio de JaneiroRio de Janeiro 21941-902Brazil Laboratory of Immunity Biology George DosReis Carlos Chagas Filho Biophysics InstituteFederal University of Rio de JaneiroRio de Janeiro 21941-902Brazil

The adaptive arm of the immune system is crucial for appropriate antitumor immune responses.It is generally accepted that clusters of differentiation 4^(+)(CD4^(+))T cells,which mediate T helper(Th)1 immunity(type 1 immunity),are the primary Th cell subtype associated with tumor elimination.In this review,we discuss evidence showing that antitumor immunity and better prognosis can be associated with distinct Th cell subtypes in experimental mouse models and humans,with a focus on Th2 cells.The aim of this review is to provide an overview and understanding of the mechanisms associated with different tumor outcomes in the face of immune responses by focusing on the(1)site of tumor development,(2)tumor properties(i.e.,tumor metabolism and cytokine receptor expression),and(3)type of immune response that the tumor initially escaped.Therefore,we discuss how low-tolerance organs,such as lungs and brains,might benefit from a less tissue-destructive immune response mediated by Th2 cells.In addition,Th2 cells antitumor effects can be independent of CD8^(+)T cells,which would circumvent some of the immune escape mechanisms that tumor cells possess,like low expression of major histocompatibility-I(MHC-I).Finally,this review aims to stimulate further studies on the role of Th2 cells in antitumor immunity and briefly discusses emerging treatment options.

关键词： Cancer Immunology Adaptive immunity Immunotherapy Immunogenetics Antitumor immune response

Development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

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Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João Ezequiel Oliveira Carlos Roberto Jorge Soares Ana Cláudia Camargo Miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia Luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael Gomes da silva Luiza Mascarenhas Balieiro Joel mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging