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1Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil显示文摘AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics. METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse- type gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher’s exact test to assess associations between methylation status and clinico- pathological characteristics. RESULTS: Hypermethylation frequencies of CDH1, FHIT, MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency wassignificantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender. CONCLUSION: Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.Mariana Ferreira Leal Eleonidas Moura Lima Patrícia Natália Oliveira Silva Paulo Pimentel Assumpo Danielle Queiroz Calcagno Spencer Luiz Marques Payo Rommel Rodríguez Burbano Marília de Arruda Cardoso Smith 2007World Journal of Gastroenterology2007,13,18:24
2Long-term outcomes of hepatocellular carcinoma that underwent chemoembolization for bridging or downstaging显示文摘BACKGROUND Prospective study of 200 patients with hepatocellular carcinoma(HCC)that underwent liver transplant(LT)after drug-eluting beads transarterial chemoembolization(DEB-TACE)for downstaging versus bridging.Overall survival and tumor recurrence rates were calculated,eligibility for LT,time on the waiting list and radiological response were compared.After TACE,only patients within Milan Criteria(MC)were transplanted.More patients underwent LT in bridging group.Five-year post-transplant overall survival,recurrence-free survival has no difference between the groups.Complete response was observed more frequently in bridging group.Patients in DS group can achieve posttransplant survival and HCC recurrence-free probability,at five years,just like patients within MC in patients undergoing DEB-TACE.AIM To determine long-term outcomes of patients with HCC that underwent LT after DEB-TACE for downstaging vs bridging.METHODS Prospective cohort study of 200 patients included from April 2011 through June 2014.Bridging group included patients within MC.Downstaging group(out of MC)was divided in 5 subgroups(G1 to G5).Total tumor diameter was≤8 cm for G1,2,3,4(n=42)and was>8 cm for G5(n=22).Downstaging(n=64)and bridging(n=136)populations were not significantly different.Overall survival and tumor recurrence rates were calculated by the Kaplan-Meier method.Additionally,eligibility for LT,time on the waiting list until LT and radiological response were compared.RESULTS After TACE,only patients within MC were transplanted.More patients underwent LT in bridging group 65.9%(P=0.001).Downstaging population presented:higher number of nodules 2.81(P=0.001);larger total tumor diameter 8.09(P=0.001);multifocal HCC 78%(P=0.001);more post-transplantation recurrence 25%(P=0.02).Patients with maximal tumor diameter up to 7.05 cm were more likely to receive LT(P=0.005).Median time on the waiting list was significantly longer in downstaging group 10.6 mo(P=0.028).Five-year posttransplant overall survival was 73.5%in downstaging and 72.3%bridging groups(P=0.31),and recurrence-free survival was 62.1%in downstaging and 74.8%bridging groups(P=0.93).Radiological response:complete response was observed more frequently in bridging group(P=0.004).CONCLUSION Tumors initially exceeding the MC down-staged after DEB-TACE,can achieve post-transplant survival and HCC recurrence-free probability,at five years,just like patients within MC in patients undergoing DEB-TACE.Breno Boueri Affonso Francisco Leonardo Galastri Joaquim Mauricio da Motta Leal Filho Felipe Nasser Priscila Mina Falsarella Rafael Noronha Cavalcante Marcio Dias de Almeida Guilherme Eduardo Goncalves Felga Leonardo Guedes Moreira Valle Nelson Wolosker 2019World Journal of Gastroenterology2019,25,37:21
3Role of mi RNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer显示文摘Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.Kelly Cristina da Silva Oliveira Taíssa Maíra Thomaz Araújo Camila Inagaki Albuquerque Gabriela Alcantara Barata Carolina Oliveira Gigek Mariana Ferreira Leal Fernanda Wisnieski Fernando Augusto Rodrigues Mello Junior André Salim Khayat Paulo Pimentel de Assumpcao Rommel Mário Rodriguez Burbano Marília Cardoso Smith Danielle Queiroz Calcagno 2016World Journal of Gastroenterology2016,22,35:11
4Interrelationship between chromosome 8 aneuploidy,C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma显示文摘AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immu- nostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneu- ploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level ofchromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal- type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic path- ways.Danielle Queiroz Calcagno Mariana Ferreira Leal Aline Damaceno Seabra Andre Salim Khayat Elizabeth Suchi Chen Samia Demachki Paulo Pimentel Assumpcao Mario Henrique Girao Faria Silvia Helena Barem Rabenhorst Márcia Valéria Pitombeira Ferreira Marília de Arruda Cardoso Smith Rommel Rodríguez Burbano 2006World Journal of Gastroenterology2006,12,38:9
5MYC and gastric adenocarcinoma carcinogenesis显示文摘MYC is an oncogene involved in cell cycle regulation,cell growth arrest,cell adhesion,metabolism,ribosome biogenesis,protein synthesis,and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review,we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis,including its association with Helicobacter pylori (H pylori) and clinical applications.Danielle Queiroz Calcagno Mariana Ferreira Leal Paulo Pimentel Assumpo Marília de Arruda Cardoso Smith Rommel Rodríguez Burbano 2008World Journal of Gastroenterology2008,14,39:8
6Clinical implication of 14-3-3 epsilon expression in gastric cancer显示文摘AIM:To evaluate for the first time the protein and mRNA expression of 14-3-3εin gastric carcinogenesis.METHODS:14-3-3εprotein expression was determined by western blotting,and mRNA expression was examined by real-time quantitative RT-PCR in gastric tumors and their matched non-neoplastic gastric tissue samples.RESULTS:Authors observed a significant reduction of 14-3-3εprotein expression in gastric cancer(GC)samples compared to their matched non-neoplastic tissue.Reduced levels of 14-3-3εwere also associated with diffuse-type GC and early-onset of this pathology.Our data suggest that reduced 14-3-3εmay have a role in gastric carcinogenesis process.CONCLUSION:Our results reveal that the reduced 14-3-3εexpression in GC and investigation of 14-3-3ε interaction partners may help to elucidate the carcino-genesis process.Mariana Ferreira Leal Danielle Queiroz Calcagno Smia Demachki Paulo Pimentel Assumpo Roger Chammas Rommel Rodríguez Burbano Marília de Arruda Cardoso Smith 2012World Journal of Gastroenterology2012,18,13:6
7The Use of Data Mining Techniques in Rockburst Risk Assessment显示文摘目前在世界范围内的很多地下矿山,岩爆已经成为一个与矿山采矿生产密切相关的重要现象。深入理解这类现象,不仅有助于岩爆管理,而且还有可能节约采矿成本,减少人身伤亡事故。其中,实验室实验是深入研究岩爆机理的一个重要途径。在本文作者前期的研究中,已经建立了实验室岩爆实验数据库。与此同时,借助于数字采矿技术,也建立了岩爆最大应力和岩爆风险指数的预测模型。为实现基于矿山地质条件和矿山井巷建筑结构特性对岩爆类型即岩爆强度等级的准确预测,本文的重点是,基于对岩爆实例的分析来建立岩爆影响矩阵,明确岩爆现象的诱发因子,并厘清这些影响因子之间的相互关系。运用人工神经网络(ANN)和初始贝叶斯分类器等数字矿山技术,对矿山岩爆数据库进行了更深入的研究。最后给出了研究得出的各项结论。Luis Ribeiro e Sousa Tiago Miranda Rita Leal e Sousa Joaquim Tinoco 2017Engineering2017,3,4:6
8Evaluation of functional, autonomic and inflammatory outcomes in children with asthma显示文摘Asthma is common in childhood. This respiratory disease is characterized by persistent inflammation of the airways even when the child is not in thethroes of an attack. Chronic inflammation is caused by an imbalance between pro-inflammatory and antiinflammatory mechanisms as well as autonomic dysfunction, which plays an important role in the pathogenesis and control of this condition. The impact of these physiopathological aspects leads to inactivity and a sedentary lifestyle, which exerts an influence on functional capacity and control of the disease. The main objective of non-pharmacological therapy is the clinical control of asthma and the minimization of airway obstruction and hyperinflation during an attack. These factors can be controlled with noninvasive ventilation. The aim or the present review was to describe important neural, inflammatory and functional mechanisms that affect children with asthma.Evelim Leal de Freitas Dantas Gomes Dirceu Costa 2015World Journal of Clinical Cases2015,3,3:5
9Improved Non-Covalent Biofunctionalization of Multi-Walled Carbon Nanotubes Using Carbohydrate Amphiphiles with a Butterfly-Like Polyaromatic Tail显示文摘We have developed an efficient strategy for the non-covalent functionalization of multi-walled carbon nanotubes(MWCNTs)which allows a biomimetic presentation of carbohydrates on their surface byπ-πstacking interactions.The strategy is based on the use of sugar-based amphiphiles functionalized with tetrabenzo[a,c,g,i]fluorene(Tbf),a polyaromatic compound with a topology that resembles a butterfly with open wings.The new carbohydrate-tethered Tbf amphiphiles have been synthesized in a straightforward manner using click chemistry.The reported method has been developed in order to improve the rather low ability of pyrene-based systems to exfoliate MWCNTs in water.By means of thermogravimetric analysis(TGA),ultraviolet(UV),infrared(IR),and fluorescence spectroscopies the interaction between MWCNTs and the Tbf group has been found to be stronger than those involving pyrene-based amphiphilic carbohydrates.The resulting aggregates with a multivalent sugar exposition on their surface are able to engage in specific ligand-lectin interactions similar to glycoconjugates on a cell membrane.Mohyeddin Assali Manuel Pernía Leal Inmaculada Fernández Pablo Romero-Gomez Rachid Baati Noureddine Khiar 2010Nano Research2010,3,11:3
10Rice Drying,Storage and Processing:Effects of Post-Harvest Operations on Grain Quality显示文摘Various post-harvest processes of rice are commonly employed,especially during the off-season,to ensure its consumption feasibility,which often affect the grain quality.Different forms of drying,storage and processing of rice are evaluated to identify their effects on grain quality.Microwave drying has emerged as an alternative to the widely-used intermittent-drying and fixed-bed-dryer methods of drying paddy rice.Control of drying-air temperatures(between 40℃ and 60℃)according to the rice variety can improve quality,especially for exotic varieties.Keeping stored grain in hygroscopic balance,with water content between 11%to 15%,at temperatures between 16℃ and 20℃ and with intergranular relative humidity near 60%,allows 12 months of storage in a controlled environment without significant deterioration.Other innovations,notably the application of artificial refrigeration to grain stored in bulk in vertical cylindrical silos and the use of impermeable packaging for storage,ensure the conservation of grain mass.The different stages and equipments used to obtain polished,brown and parboiled rice result in significant changes in the nutritional value of rice because of the removal of the outermost layers of the grains.Polishing reduces the nutritional value and physical homogeneity of rice.Brown rice retains more bioactive compounds and nutrients because it does not lose the outer layer of the grains in the polishing processes.Parboiled rice,although less nutritious than brown rice,has better grain integrity and milling yield and less loss of nutrients than white rice.Amanda MÜLLER Marcela Trojahn NUNES Vanessa MALDANER Paulo Carteri CORADI Rosana Santos de MORAES Samuel MARTENS Andressa Fernandes LEAL Vladison Fogliato PEREIRA Cristielle König MARIN 2022Rice science2022,29,1:3
11Dealing with robot-assisted surgery for rectal cancer:current status and perspectives显示文摘The laparoscopic approach for treatment of rectal cancer has been proven feasible and oncologically safe, and is able to offer better short-term outcomes than traditional open procedures, mainly in terms of reduced length of hospital stay and time to return to working activity. In spite of this, the laparoscopic technique is usually practised only in high-volume experienced centres, mainly because it requires a prolonged and demanding learning curve. It has been estimated that over 50 operations are required for an experienced colorectal surgeon to achieve proficiency with this technique. Robotic surgery enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, thus promising to overcome some of the technical difficulties associated with standard laparoscopy. It has high-definition threedimensional vision, it translates the surgeon's hand movements into precise movements of the instruments inside the patient, the camera is held and moved by the first surgeon, and a fourth robotic arm is available as a fixed retractor. The aim of this review is to summarise the current data on clinical and oncologic outcomes of robot-assisted surgery in rectal cancer, focusing on short- and long-term results, and providing original data from the authors' centre.Roberto Biffi Fabrizio Luca Paolo Pietro Bianchi Sabina Cenciarelli Wanda Petz Igor Monsellato Manuela Valvo Maria Laura Cossu Tiago Leal Ghezzi Kassem Shmaissany 2016World Journal of Gastroenterology2016,22,2:3
12rate of adverse events of gastroduodenal snare polypectomy for non-flat polyp is low: A prospective and multicenter study显示文摘AIM To evaluate the rate of adverse events(AEs) during consecutive gastric and duodenal polypectomies in several Spanish centers. METHODS Polypectomies of protruded gastric or duodenal polyps ≥ 5 mm using hot snare were prospectively included. Prophylactic measures of hemorrhage were allowed in predefined cases. AEs were defined and graded according to the lexicon recommended by the American Society for Gastrointestinal Endoscopy. Patients were followed for 48 h, one week and 1 mo after theprocedure. RESULTS308 patients were included and a single polypectomy was performed in 205. Only 36(11.7%) were on prior anticoagulant therapy. Mean polyp size was 15 ± 8.9 mm(5-60) and in 294 cases(95.4%) were located in the stomach. Hemorrhage prophylaxis was performed in 219(71.1%) patients. Nine patients presented AEs(2.9%), and 6 of them were bleeding(n = 6, 1.9%)(in 5 out of 6 AE, different types of endoscopic treatment were performed). Other 24 hemorrhagic episodes could be managed without any change in the outcome of the endoscopy and, consequently, were considered incidents. We did not find any independent risk factor of bleeding.CONCLUSION Gastroduodenal polypectomy using prophylactic measures has a rate of AEs small enough to consider this procedure a safe and effective method for polyp resection independently of the polyp size and location.Henry Córdova Lidia Argüello Carme Loras Antonio Naranjo Rodríguez Faust Riu Pons Joan B Gornals David Nicolás-Pérez Xavier Andújar Murcia Luis Hernández Santos Santolaria Carles Leal Carles Pons Enrique Pérez-Cuadrado-Robles Orlando García-Bosch Michel Papo Berger José Luis Ulla Rocha Cristina Sánchez-Montes Gloria Fernández-Esparrach 2017World Journal of Gastroenterology2017,23,47:3
13Pair-copulas modeling in finance显示文摘Beatriz Mendes Mariangela Semeraro Ricardo Leal 2010Financial Markets and Portfolio Management2010,,2:3
14Reversible and athermal photo-vitrification of As50 ·Se50 thin films deposited onto silicon wafer and glass substrates 显示文摘PRIETO - ALCON R MARQUEZ E GONZALEZ- LEAL J M 1999Appl Phys A1999,68,:2
15The role of cytokines and pathogen recognition molecules in fungal keratitis – Insights from human disease and animal models显示文摘Sixto M. Leal Eric Pearlman 2012Cytokine2012,,1:2
16Development and Optimization of an Alternative Methodology for Detection of Milk Adulteration by Water显示文摘Wesley William Gongalves Nascimento Marcone Augusto Leal de Oliveira1 Marcone Augusto Leal de Oliveira Marco Antonio Moreira Furtado Virgilio de Carvalho dos Anjos Maria Jose Valenzuela Bell 2013Journal of Food Science and Engineering2013,3,7:2
17Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats显示文摘Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury(SCI). However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein(GFAP) and S100 calcium-binding protein B(S100B)(astrocytic reactivity classical markers) and global histone H4 acetylation levels. Sixty-one male Wistar rats(aged ~3 months) were divided into the following groups: sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases(first phase: no changes in the 6, 24 and 48 hours post-SCI groups; second phase: increased levels in the 72 hours post-SCI group; and a third phase: return to levels similar to control in the 7 days post-SCI group). Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.Mayara Ferraz de Menezes Fabricio Nicola Ivy Reichert Vital da Silva Adriana Vizuete Viviane Rostirola Eisner Leder Leal Xavier Carlos Alberto Saraiva Goncalves Carlos Alexandre Netto Regis Gemerasca Mestriner 2018Neural Regeneration Research2018,13,11:2
18Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease显示文摘AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease.METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease(MELD) and Pediatric End Stage Liver Disease(PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition(Z-score <-1.00) and malnutrition(Z-score <-2.00). Interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median(25th-75 th centile) age of the study population was 60(17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease(72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values were increased in patients at nutritional risk(34.9%) compared with those who were well-nourished [7.12(0.58-34.23) pg/m L vs 1.63(0.53-3.43) pg/m L; P = 0.02], correlating inversely with triceps skinfold-for-age z-score(rs =-0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score(P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. CONCLUSION: High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients.Daniele Santetti Maria Inês de Albuquerque Wilasco Cristina Toscani Leal Dornelles Isabel Cristina Ribas Werlang Fernanda Urruth Fontella Carlos Oscar Kieling Jorge Luiz dos Santos Sandra Maria Goncalves Vieira Helena Ayako Sueno Goldani 2015World Journal of Gastroenterology2015,21,29:2
19Role of diet and nutrition in inflammatory bowel disease显示文摘Inflammatory bowel diseases(IBDs)are closely linked to nutrition.The latest research indicates that diet and nutrition are significantly involved in the etiopathogenesis of the disease,although their specific role throughout its clinical course still remains unclear.This study reviewed how diet and nutrition are associated with IBD development and management.Even though specific diets have been shown to bring about positive outcomes,there is currently no scientific consensus regarding an appropriate diet that would benefit all IBD patients.We suggest that individualized dietary recommendations are of the greatest importance and that diets should be planned to provide individual IBD patients with specific nutrient requirements while keeping all the clinical aspects of the patients in mind.Further research is clearly necessary to investigate nutritional factors involved in IBD development and,especially,to evaluate the applications of the diets during the course of the disease.Marina Moreira de Castro Lívia Bitencourt Pascoal Karine Mariane Steigleder Beatriz Piatezzi Siqueira Ligiana Pires Corona Maria de Lourdes Setsuko Ayrizono Marciane Milanski Raquel Franco Leal 2021World Journal of Experimental Medicine2021,11,1:2
20The quality of teacher–student interactions: Associations with first graders’ academic and behavioral outcomes显示文摘Joana Cadima Teresa Leal Margaret Burchinal 2010Journal of School Psychology2010,,6:2
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