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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 *** RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT *** the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR *** SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May *** 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 *** 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

Monoclonal gammopathy of renal significance:Diagnostic workup

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World Journal of Nephrology 2017年第2期6卷 72-78页

作者： sofia O Correia sofia santos Jorge Malheiro António Cabrita La Salete Martins Josefina santos Nephrology and Transplant Department Centro Hospitalar do Porto4099-001 PortoPortugal

The clinical spectrum of diseases associated withmonoclonal gammopathies is wide and they are most commonly the consequence of renal deposition of monoclonal immunoglobulin or its components. The differential diagnosis is difficult and renal biopsy is essential. To distinguish many of these pathologies is necessary to use techniques that are not always avai-lable, even in tertiary central hospitals. This review will discuss the clinical presentation, pathologic features, treatment, prognosis and common diagnostic diffculties of these entities.

关键词： Algorithm Immunoglobulin Monoclonal gammopathy of renal significance M protein Mono-clonal gammopathy of undetermined signifcance

Species richness and density evaluation for plants with aggregated distributions:fixed *** area methods

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Journal of Plant Ecology 2017年第5期10卷 765-770页

作者： rita de Cássia Quitete Portela Alexandra dos santos Pires Maria Isabel Guedes Braz Eduardo Arcoverde de Mattos Departamento de Ecologia Instituto de BiologiaUniversidade Federal do Rio de JaneiroCaixa Postal 68020Ilha do FundãoRio de JaneiroRJ 21941-590Brasil Departamento de Ciências Ambientais Instituto de FlorestasUniversidade Federal Rural do Rio de JaneiroRod.BR 465Km 07Cidade UniversitáriaSeropédicaRio de JaneiroRJ 23890-000Brasil

Aims Knowledge of species richness is of prime importance to both basic and applied aspects of ecological ***,quantifying plant species richness in the tropics is potentially time-consuming because of high species *** species richness estimates are also frequently biased,because many rare species are not *** address these problems,the use of a variable area method has been proposed as an alternative to fixed area methods,but its appli-cability to plants with aggregated distributions has been questioned based on simulation *** use empirical data to compare the efficiency and accuracy of a variable area method and a fixed area method for estimating species richness,density and basal area for plants with aggregated distributions,using palms as a model *** Adult palms were sampled in twenty 10×30 m transects in an Atlantic Forest in Rio de Janeiro state,*** individuals were considered in the fixed area method,while in the variable area method only the first six adults in each transect were sampled;in this case,transect length was defined according to the distance of the sixth adult from the beginning of the *** fewer than six individuals were observed in a given transect,transect length was extended up to 50 m to search for additional *** efficiency of both methods was compared based on species rarefaction curves,using the chao 1 statistic(for abundance data).For each species we calculated mean density per transect and basal area,according to each sampling *** effort in terms of the number of individual plants and the area necessary to characterize maximum species richness in each sampling method,as well as mean time taken to sample a single transect,were compared as measures of *** findings An accurate estimate of species richness was achieved using both methods,but in the variable area method,a quarter of the number of individuals and half the area was sufficient

关键词： basal area biodiversity inventory palms taxon sampling

Towards curative therapy in gastric cancer:Faraway, so close!

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World Journal of Gastroenterology 2015年第41期21卷 11609-11620页

作者： Marília Cravo Catarina Fidalgo rita Garrido Tania Rodrigues Gon?alo Luz Carolina Palmela Marta santos Fábio Lopes Rui Maio Gastroenterology Department Surgery and Oncology ClinicsHospital Beatriz Angelo

Although recent diagnostic and therapeutic advances have substantially improved the survival of patients with gastric cancer(GC), the overall prognosis is still poor. Surgery is the only curative treatment and should be performed in experienced centers. Due to high relapse following surgery, complementary and systemic treatment aimed at eradicating micrometastasis should be performed in most cases. Cytotoxic treatments are effective in downstaging locally advanced cancer, but different sensitivities and toxicities probably exist in different GC subtypes. Current treatment protocols are based primarily on clinical data and histological features, but molecular biomarkers that would allow for the prediction of treatment responses are urgently needed. Understanding how host factors are responsible for inter-individual variability of drug response or toxicity will also contribute to the development of more effective and less toxic treatments.

关键词： Gastric cancer Multidisciplinary treatment Therapeutic strategies Curative surgery

Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

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World Journal of Stem Cells 2015年第6期7卷 956-975页

作者： Jorge Ribeiro Tiago Pereira Ana rita Caseiro Paulo Armada-da-Silva Isabel Pires Justina Prada Irina Amorim Sandra Amado Miguel Franca Carolina Goncalves Maria Ascensao Lopes Jose Domingos santos Dina Morais Silva Stefano Geuna Ana Lúcia Luís Ana Colette Maurício Departmento de Clínicas Veterinárias and+UPVet Instituto de Ciencias Biomedicas de Abel Salazar(ICBAS)and Centro de Estudos de Ciencia Animal(CECA)Instituto de CienciasTecnologias e Agroambiente da Universidade do Porto(ICETA)Rua de Jorge Viterbo Ferreira4050-313 PortoPortugal Centro Interdisciplinar de Estudo de Performance Humana(CIPER) Faculdade de Motricidade Humana(FMH)Universidade de Lisboa(UL)Estrada da Costa1499-002 Cruz QuebradaDafundoPortugal CECAV and Departamento de Ciencias Veterinárias Universidade de Trás-os-Montes e Alto Douro(UTAD)5001-801 Vila RealPortugal Departmento de Patologia e de Imunologia Molecular Instituto de Ciencias Biomedicas de Abel SalazarRua de Jorge Viterbo Ferreira4050-313 PortoPortugal Instituto Português de Patologia e Imunologia Molecular da Universidade do Porto(IPATIMUP) Rua Dr.Roberto Frias s/n4200-465 PortoPortugal UIS-IPL:Unidade de Investigacao em Saúde da Escola Superior de Saúde de Leiria Instituto Politécnico de Leiria2411-901 LeiriaPortugal CEMUC Departamento de Engenharia Metalúrgica e MateriaisFaculdade de Engenharia da Universidade do Porto(FEUP)Rua Dr.Roberto Frias4200-465 PortoPortugal Biosckin Molecular and Cell Therapies S.A.Tec MaiaRua Engenheiro Frederico Ulrich 26504470-605 MaiaPortugal Neuroscience Institute of the Cavalieri Ottolenghi Foundation and Department of Clinical and Biological Sciences University of Turin

AIM: To study the therapeutic effect of three tubeguides with electrical conductivity associated to mesenchymal stem cells(MSCs) on neuro-muscular regeneration after ***: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol(PVA), PVA-carbon nanotubes(CNTs) and MSCs, and PVA-polypyrrole(PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functionalindex(SSI), and by withdrawal reflex latency(WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs(P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group(P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the "minimal Feret's diameter" respectively. Stereological analysis disclosed a significantly(P < 0.05) increased myelin thickness(M), ratio myelin thickness/axon diameter(M/d) and ratio axon diameter/fiber diameter(d/D; g-ratio) in PVA-CNT-MSCs group(P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible th

关键词： Nerve regeneration Neurotmesis Tubeguides Mesenchymal stem cells Carbon nanotubes Functional assessment Gait biomechanical analysis Histomorfometry Polyvinyl alcohol

XBAT35, a Novel Arabidopsis RING E3 Ligase Exhibiting Dual Targeting of Its Splice Isoforms, Is Involved in Ethylene-Mediated Regulation of Apical Hook Curvature

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Molecular Plant 2012年第6期5卷 1295-1309页

作者： sofia D. Carvalho rita Saraiva Teresa M. Maia Isabel A. Abreu Paula Duquea Instituto Gulbenkian de Ciencia Rua da Quinta Grande 6 2780-156 Oeiras Portugal Instituto de Tecnologia Quimica e Biologica Universidade Nova de Lisboa Av. da Republica 2780-157 Oeiras Portugal

The Arabidopsis XBAT35 is one of five structurally related ankyrin repeat-containing Really Interesting New Gene （RING） E3 ligases involved in ubiquitin-mediated protein degradation, which plays key roles in a wide range of cel- lular processes. Here, we show that the XBAT35 gene undergoes alternative splicing, generating two transcripts that are constitutively expressed in all plant tissues. The two splice variants derive from an exon skipping event that excludes an in-frame segment from the XBAT35 precursor mRNA, giving rise to two protein isoforms that differ solely in the presence of a nuclear localization signal （NLS）. Transient expression assays indicate that the isoform lacking the NLS localizes in the cytoplasm of plant cells, whereas the other is targeted to the nucleus, accumulating in nuclear speckles. Both isoforms are functional E3 ligases, as assessed by in vitro ubiquitination assays. Two insertion mutant alleles and RNA-interference （RNAi） silencing lines for XBAT35 display no evident phenotypes under normal growth conditions, but exhibit hyper- sensitivity to the ethylene precursor 1-aminocyclopropane-l-carboxylate （ACC） during apical hook exaggeration in the dark, which is rescued by an inhibitor of ethylene perception. Independent expression of each XBAT35 splice variant in the mutant background indicates that the two isoforms may differentially contribute to apical hook formation but are both functional in this ethylene-mediated response. Thus, XBAT35 defines a novel player in ethylene signaling involved in negatively regulating apical hook curvature, with alternative splicing controlling dual targeting of this E3 ubiquitin ligase to the nuclear and cytoplasmic compartments.

关键词： alternative splicing apical hook Arabidopsis thaliana ethylene signaling RiNG E3 ligase ubiquitination.

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center:Access, resource utilization and outcomes

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World Journal of Gastroenterology 2020年第7期26卷 759-769页

作者： sofia Nene Lorant Gonczi Zsuzsanna Kurti Isabelle Morin Kelly Chavez Christine Verdon Jason Reinglas rita Kohen Talat Bessissow Waqqas Afif Gary Wild Ernest Seidman Alain Bitton Peter Laszlo Lakatos Division of Gastroenterology McGill University Health CentreQuebecMontreal H3G1A4Canada First Department of Medicine Semmelweis UniversityBudapest H-1083Hungary

BACKGROUND Emergency situations in inflammatory bowel diseases(IBD)put significant burden on both the patient and the healthcare *** To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service(RAC)at a tertiary IBD *** Patient access,resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational *** comparing resource utilization and healthcare costs,emergency department(ED)visits of IBD patients with no access to RAC services were evaluated between January 2018 and January *** to appointment,diagnostic methods,change in medical therapy,unplanned ED visits,hospitalizations and surgical admissions were calculated and *** 488 patients(Crohn’s disease:68.4%/ulcerative colitis:31.6%)contacted the RAC with a valid medical *** time to visit with an IBD specialist following the index contact was 2 *** had objective clinical and laboratory assessment(C-reactive protein and fecal calprotectin in 91%and 73%).Fast-track colonoscopy/sigmoidoscopy was performed in 24.6%of the patients,while computed tomography/magnetic resonance imaging in only 8.1%.Medical therapy was changed in 54.4%.ED visits within 30 d following the RAC visit occurred in 8.8%(unplanned ED visit rate:5.9%).Diagnostic procedures and resource utilization at the ED(n=135 patients)were substantially different compared to RAC users:Abdominal computed tomography was more frequent(65.7%,P<0.001),coupled with multiple specialist consults,more frequent hospital admission(P<0.001),higher steroid initiation(P<0.001).Average medical cost estimates of diagnostic procedures and services per patient was$403 CAD vs$1885 CAD comparing all RAC and ED *** Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care,optimized resource uti

关键词： Crohn’s disease Ulcerative colitis Rapid access Quality-of-care Emergency department

Regeneration of critical-sized defects, in a goat model, using a dextrin-based hydrogel associated with granular synthetic bone substitute

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Regenerative Biomaterials 2021年第1期8卷 73-82页

作者： Isabel Pereira Jose Eduardo Pereira Luis Maltez Alexandra Rodrigues Catarina Rodrigues Manuela Oliveira Dina MSilva Ana rita Caseiro Justina Prada Ana Colette Mauricio Jose Domingos santos Miguel Gama CEB Centre of Biological EngineeingUniversity of MinhoCampus de GualtarBraga 4710-057Portugal CECAV Animal and Veterinary Research CentreUniversity of Trias-os-Montes e Alto DouroVila Real 5001-801Portugal Department of Veterinary Sciences University of Tras-os-Montes e Alto DouroVila Real 5001-801Portugal Bios ckin Molecular and Cell Therapies S.A.Laboratorio CriovidaTecMaiaRua Engenheiro Frederico Ulrich 2650Moreira da Maia 4470-605Portugal Departamento de Clinicas Veterinarias Instituto de Ciencias Biomedicas de Abel Salazar(ICBAS)Universidade do Porto(UP)Rua de Jorge Viterbo Ferreiran°228Porto 4050-313Portugal Centro de Estudos de Ciencia Animal(CECA) Instituto de CienciasTecnologias e Agroambiente da Universidade do Porto(ICETA)Rua D.Manuel IApartado 55142Porto 4051-401 Portugal Centro de Investigaqao Vasco da Gama(CIVG)/Escola Universitaria Vasco da Gama(EUVG) Avenida Jose R.Sousa Femandesn°197 LordemaoCoimbra 3020-210Portugal REQUIMTE/LAQV Departamento de Engenharia Metalurgica e MateriaisFaculdade de EngenhariaUniversidade do PortoRua Dr Roberto FriasPorto 4200-495Portugal

The development of injectable bone substitutes(IBS)have obtained great importance in the bone re-generation field,as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular *** this scenario,the association of injectable hydrogels and bone graft granules is emerging as a well-established ***,in situ forming hydrogels have arisen as a new IBS *** in situ forming and injectable dextrin-based hydrogel(HG)was developed,aiming to act as a carrier of granular bone substitutes and bioactive *** this work,the HG was associated to a granular bone substitute(Bonelike)and implanted in goat critical-sized calvarial defects(14mm)for 3,6 and *** results showed that HG improved the han-dling properties of the Bonelike granules and did not affect its osteoconductive features,neither impairing the bone regener ation *** multipotent mesenchymal stromal cells from the umbilical cord,extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the *** bioactive agents did not enhance the new bone formation significantly under the conditions tested,according to micro-computed tomography and histological analysis.

关键词： polysaccharide injec table hydrogel granular ceramics Bonelike' bone regen eration calvarial defect

Design multifunctional Mg–Zr coatings regulating Mg alloy bioabsorption

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Journal of Magnesium and Alloys 2024年第4期12卷 1461-1478页

作者： Zohra Benzarti Sandesh Itani JoséDavid Castro Sandra Carvalho Ana sofia Ramos University of Coimbra CEMMPREARISEDepartment of Mechanical EngineeringRua Luís Reis Santos3030-788CoimbraPortugal Laboratory of Multifunctional Materials and Applications(LaMMA) Department of PhysicsFaculty of Sciences of SfaxUniversity of SfaxSoukra Road km 3.5B.P.1171Sfax3000Tunisia

Magnesium(Mg)alloys are widely used for temporary bone implants due to their favorable biodegradability,cytocompatibility,hemocompatibility,and close mechanical properties to ***,rapid degradation and inadequate strength limit their *** overcome this,the direct current magnetron sputtering technique is employed for surface coating in Mg-based alloys using various zirconium(Zr)*** approach presents a promising strategy for simultaneously improving corrosion resistance,maintaining biocompatibility,and enhancing strength without compromising *** leveraging Mg’s inherent biodegradability,it has the potential to minimize the need for secondary surgeries,thereby reducing costs and *** paper is a systematic study aimed at understanding the corrosion mechanisms of Mg–Zr coatings,denoted Mg-xZr(x=0–5 at.%).Zr-doped coatings exhibited columnar growth leading to denser and refined structures with increasing Zr *** analysis confirmed the presence of the Mg(00.2)basal plane,shifting towards higher angles(1.15°)with 5 at.%Zr doping due to lattice parameter changes(i.e.,decrease and increase of“c”and“a”lattice parameters,respectively).Mg–Zr coatings exhibited“liquidphilic”behavior,while Young’s modulus retained a steady value around 80 GPa across all ***,the hardness has significantly improved across all samples’coating,reaching the highest value of(2.2±0.3)GPa for 5 at.%*** testing in simulated body fluid(SBF)at 37℃ revealed a significant enhancement in corrosion resistance for Mg–Zr coatings containing 1.0–3.4 at.%*** with the 5 at.%Zr coating which exhibited a corrosion rate of 32 mm/year,these coatings displayed lower corrosion rates,ranging from 1 to 12 mm/*** synergistic enhancement in mechanical properties and corrosion resistance,achieved with 2.0–3.4 at.%Zr,suggests potential ability for reducing stress shielding and controlled degradation performance,and consequentl

关键词： Mg-Zr coatings Magnetron sputtering Nanoindentation Corrosion resistance Bone implants