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Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

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World journal of Gastrointestinal oncology 2024年第1期16卷 234-243页

作者： joão Gramaça Isabel gomes Fernandes Carolina Trabulo joana Gonçalves Rita Gameiro dos Santos Adriano Baptista Idília Pina Centro Hospitalar Barreiro Montijo Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal Medical oncology Unit Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal

BACKGRoUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.on the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CoNCLUSIoN our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

关键词： Metastatic colorectal cancer Rat sarcoma virus mutational status Liquid biopsy Rat sarcoma virus wild-type Neo-rat sarcoma virus wild-type Anti-epidermal growth factor receptor therapy Case report

Is magnesium deficiency the major cause of needle chlorosis of Pinus taeda in Brazil?

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journal of Forestry Research 2024年第2期35卷 209-221页

作者： Antônio Carlos Vargas Motta Shizuo Maeda Valdécio dos Santos dos Santos Rodrigues Tamires Maiara Ercole Stephen Arthur Prior Ana Elisa Lyra Brumat Amanda Pacheco Cardoso Moura Julierme Zimmer Barbosa joão Bosco Vasconcellos gomes Department of Soil Sciences and Agriculture Engineering Federal University of ParanáR.dos Funcionários1540.CuritibaParanáCEP 80035‑050Brazil Brazilian Agricultural Research Company Embrapa FlorestasEstr.da Ribeira–Br‑476Km 111–Parque Monte Castelo.ColomboParanáCEP 83411‑000Brazil United States Department of Agriculture‑Agricultural Research Service USDA-ARS National Soil Dynamics Laboratory411 South Donahue DriveAuburnAL 36832USA Reforestation Remasa Rodovia PR 170–Km 522.BiturunaParanáCEP 84640‑000Brazil Federal Institute of Southeast of Minas Gerais R.Luz Interior360.Juiz de ForaMinas Gerais CEP 36030‑713Brazil

Needle chlorosis(NC)in Pinus taeda L.systems in Brazil becomes more frequent after second and third harvest rotation cycles.In a study to identify factors contributing to yellowing needle chorosis(YNC),trees were grown in soils originating from contrasting parent materials,and soils and needles(whole,green and chlorotic portions)from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on P.taeda were analyzed for various elements and properties.All soils had very low base levels(Ca^(2+),Mg^(2+)and K^(+))and P,suggesting a possible lack of multiple elements.YNC symptoms started at needle tips,then extended toward the needle base with time.First flush needles had longer portions with YNC than second flush needles did.Needles from the lower crown also had more symptoms along their length than those higher in the canopy.Symptoms were similar to those reported for Mg.In chlorotic portions,Mg and Ca concentrations were well below critical values;in particular,Mg levels were only one third of the critical value of 0.3 g kg^(-1).Collectively,results suggest that Mg deficiency is the primary reason for NC of P.taeda in various parent soils in Brazil.

关键词： Nutritional deficiency Forest management Soil depletion Pine foliar analysis Needle chlorosis

Is magnesium deficiency the major cause of needle chlorosis of Pinus taeda in Brazil?

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

journal of Forestry Research 2024年第2期 213-225页

作者： Ant?nio Carlos Vargas Motta Shizuo Maeda Valdécio dos Santos dos Santos Rodrigues Tamires Maiara Ercole Stephen Arthur Prior Ana Elisa Lyra Brumat Amanda Pacheco Cardoso Moura Julierme Zimmer Barbosa jo?o Bosco Vasconcellos gomes Department of Soil Sciences and Agriculture Engineering Federal University of Paraná Brazilian Agricultural Research Company Embrapa Florestas 3. United States Department of Agriculture-Agricultural Research Service USDA-ARS National Soil Dynamics Laboratory 4. Reforestation Remasa 5. Federal Institute of Southeast of Minas Gerais

Needle chlorosis(NC) in Pinus taeda L. systems in Brazil becomes more frequent after second and third harvest rotation cycles. In a study to identify factors contributing to yellowing needle chorosis(YNC), trees were grown in soils originating from contrasting parent materials, and soils and needles(whole, green and chlorotic portions) from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on P. taeda were analyzed for various elements and properties. All soils had very low base levels(Ca2+, Mg2+and K+) and P, suggesting a possible lack of multiple elements. YNC symptoms started at needle tips, then extended toward the needle base with time. First flush needles had longer portions with YNC than second flush needles did. Needles from the lower crown also had more symptoms along their length than those higher in the canopy. Symptoms were similar to those reported for Mg. In chlorotic portions, Mg and Ca concentrations were well below critical values; in particular, Mg levels were only one third of the critical value of 0.3 g kg-1. Collectively, results suggest that Mg deficiency is the primary reason for NC of P. taeda in various parent soils in Brazil.

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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

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico

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journal of Clinical and Translational Hepatology 2023年第5期11卷 1023-1034页

作者： Alexis jose-Abrego Sonia Roman joão Renato Rebello Pinho Michele Soares gomes-Gouvêa Arturo Panduro Department of Genomic Medicine in Hepatology Civil Hospital of Guadalajara“Fray Antonio Alcalde”GuadalajaraJaliscoMexico Health Sciences Center University of GuadalajaraGuadalajaraJaliscoMexico LIM07 Department of GastroenterologyUniversity of São PauloSão PauloBrazil Hospital Israelita Albert Einstein São PauloBrazil

Background and Aims:Lamivudine(3TC),telbivudine(LdT),entecavir(ETV),adefovir(ADF),and tenofovir(TFV)are drugs used to treat hepatitis B virus(HBV)infection,but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities.These mutations have not been thoroughly investigated in Mexico.This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.Methods:This cross-sectional study analyzed 158 samples.HBV DNA was extracted,amplified,and sequenced in serum samples using the spin column method,PCR assay,and Sanger’s sequencing,respectively.HBV genotypes were determined,and HBV mutations were tested using the Geno2pheno tool.Results:overall,68.4%(108/158)of HBV patients were infected with genotype H,followed by G(11.4%,18/158),A2(10.8%,17/158),F1b(6.9.0%,11/158),D(1.9%,3/158),and E(0.6%,1/158),and 5.1%(8/158)had evidence of recombination.The prevalence of resistance mutations was 8.2%(13/158)and the most common combined mutation was rt180M+rt204V.Notably,we found the combinations rt180M+rt204V+rt173L(n=2)and rt180M+rt204V+rt202G(n=1)that confer multidrug resistance to 3TC,LdT,and ETV.Resistance mutations were found in genotypes A2(11.8%,2/17),and H(10.2%,11/108),and escape mutations were detected in HBV genotypes A2(11.8%,2/17),H(10.2%,11/108),F1b(9.1%,1/11)and G(5.6%,1/18).Conclusions:The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H.The earliest cases of HBV multidrug resistance were detected in Mexico.

关键词： Hepatitis B virus Drug resistance mutations Multidrug resistance strain Immune escape

Intimate partner violence against women. Does violence decrease after the entry of the alleged offender into the criminal justice system?

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Forensic Sciences Research 2022年第1期7卷 53-60页

作者： Paulo Vieira-Pinto joséIgnacio Muñoz-Barús Tiago Taveira-gomes Maria joão Vidal-Alves Teresa Magalhães Department of Forensic Sciences PathologyGynaecology and ObstetricsPaediatricsInstitute of Forensic SciencesUniversity of Santiago de CompostelaSantiago de CompostelaSpain IINFAC TS-Institute of Research and Advanced Training in Health Sciences Department of SciencesCESPUUniversity Institute of Health Sciences(IUCS)GandraPortugal cFaculty of Medicine University of PortoPortoPortugal CINTESIS-Centre of Health Technology and Service Research University of PortoPortoPortugal Fernando Pessoa University PortoPortugal

Intimate partner violence(IPV)is simultaneously assumed as a serious crime and a major public health issue,having recurrences as one of its main characteristics and,consequently,re-entries of some alleged offenders in the criminal justice system(CJS).The main goal of this study is to assess if in cases of female victims of IPV,violence decreases after the first entry of the alleged offender in the CJS.A retrospective study was performed based on the analysis of police reports of alleged cases of IPV during a 4-year period.The final sample(n=1488)was divided into two groups according to the number of entries in the CJS(single or multiple)followed by a comparative approach.Results suggest that violence decreases after the first entry of alleged offenders in the CJS.Re-entries were found in only 15.5%of the cases but they were accountable for 3.3 times more crimes on average.Besides,victims of recidivism presented more injuries and required more medical care.Thus,a small group of alleged offenders seems to be more violent and accountable for most of the IPV crimes registered in the CJS suggesting that regardless of legal sanctions aiming to deter violence,these measures may not be enough for a certain group of offenders.This study sustains the need for a predictive model to quantify the risk of repeated IPV cases within the Portuguese population.

关键词： Forensic sciences intimate partner violence women re-entry recidivism criminal justice system

Scalable fabrication,compartmentalization and applications of living microtissues

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Bioactive Materials 2023年第1期19卷 392-405页

作者： Maik Schot Nuno Araújo-gomes Bas van Loo Tom Kamperman Jeroen Leijten Department of Developmental Bioengineering Faculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteDrienerlolaan 57522NBEnschedethe Netherlands

Living microtissues are used in a multitude of applications as they more closely resemble native tissue physiology,as compared to 2D cultures.Microtissues are typically composed of a combination of cells and materials in varying combinations,which are dictated by the applications’design requirements.Their applications range wide,from fundamental biological research such as differentiation studies to industrial applications such as cruelty-free meat production.However,their translation to industrial and clinical settings has been hindered due to the lack of scalability of microtissue production techniques.Continuous microfluidic processes provide an opportunity to overcome this limitation as they offer higher throughput production rates as compared to traditional batch techniques,while maintaining reproducible control over microtissue composition and size.In this review,we provide a comprehensive overview of the current approaches to engineer microtissues with a focus on the advantages of,and need for,the use of continuous processes to produce microtissues in large quantities.Finally,an outlook is provided that outlines the required developments to enable large-scale microtissue fabrication using continuous processes.

关键词： Tissue engineering Micromaterials Microfluidics Upscaling Clinical translation Industrial translation

Genotype-environment interaction in Cordia trichotoma(Vell.)Arráb.Ex Steud.progenies in two different soil conditions

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journal of Forestry Research 2022年第1期33卷 309-319页

作者： Wanderley dos Santos Bruno Marchetti de Souza Daniele Fernanda Zulian Gilberto Terra Ribeiro Alves joão Bosco Vasconcellos gomes Mário Luiz Teixeira de Moraes Valderês Aparecida de Sousa Ananda Virginia de Aguiar Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista“Júlio Mesquita Filho”Ilha Solteira 15385-000Brazil Sucupira Agroflorestas Fazenda SucupiraValença 45400-000Brazil EMBRAPA Florestas Empresa Brasileira de Pesquisa AgropecuáriaColombo 83411-000Brazil

Investment in silvicultural techniques is noticeably lacking,especially in breeding programs for non-conventional wood species.Studying genotype×environment interaction(G×E)is essential to the development of breeding programs.Thus,this study aimed to estimate genetic diversity of and the effects of G×E interaction on two progeny tests of Cordia trichotoma,including the estimation of genetic gain and genetic diversity after selection.For the experiment,30 progenies of C.trichotoma were tested at two sites with differing soil textures.Diameter at breast height(1.30 m above soil surface,dbh-cm),total height,diameter at 30 cm from the soil,first branch height,and survival were all monitored for four years.Statistical deviance,best linear unbiased estimator,and harmonic mean of relative performance of genetic values(MHPRVG)were all calculated to predict breeding values,estimate genetic parameters,and analyze deviance.All quantified traits varied significantly among progenies by soil type,with greatest variation recorded for genetic variability.Heritability of the progenies led to predictions of genetic gain,ranging from 7.73 to 15.45%,for dbh at four years of age.The calculated decrease in genetic diversity after selection showed that this parameter should be monitored in subsequent breeding cycles.G×E was low for all tests.The best-performing progenies proved most stable and best adapted to the different environmental conditions tested.

关键词： Effective population number Native species Productivity Stability and adaptability Tree improvement

Ecophysiology and multivariate analysis for production of Tachigali vulgaris in Brazil:Influence of rainfall seasonality and fertilization

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林业研究:英文版 2023年第5期34卷 1289-1305页

作者： Pedro Henrique oliveira Simoes Candido Ferreira de oliveira Neto Manoel Tavares de Paula Dênmora gomes de Araújo Rodrigo Silva do Vale joao olegário Pereira de Carvalho Universidade Federal de Mato Grosso Campus Universitario de SinopSinop 78550728Mato GrossoBrazil Universidade Federal Rural da Amazonia Campus BelemBelem 66077830ParaBrazil Universidade do Estado do Para Centro de Ciencias Naturais e TecnologiaBelem 66095015ParaBrazil Universidade Federal Rural da Amazonia Campus Capitao-PocoCapitao Poco 68650000ParaBrazil

Studies on fertilization management of species native to the Amazon for energy plantations contribute to the diversity of species use and reduce biological risk due to the excessive use of clones or hybrids of Eucalyptus.This study evaluates the effect of precipitation seasonality and phosphorus and potassium fertilization on gas exchange in a Tachigali vulgaris plantation.Three levels of P(zero,65.2,130.4 kg ha^(-1))and three of K(zero,100.0,200.0 kg ha^(-1))were applied in a 3×3 factorial randomized block design.Gas exchange measurements were conducted in April and November 2018.In low rainfall,high irradiance period,photo synthetic rates were up to four times higher than in the high rainfall period,reaching 20.3μmol m^(-2)s^(-1)in the treatment with 130.4 g kg^(-1)of P and 100.0 g kg^(-1)of K.Factor analysis and principal component analysis reduced the initial eight gas exchange variables to two and three principal components in periods of high and low rainfall,respectively.The multivariate method used in this study readily identified variations in the variables as a function of rainfall,with high reliability in explaining the data set.

关键词： Photosynthesis rate Stomatal conductance Principal component analysis Factor analysis Tachigali vulgaris