Differential expression of ABCF2 in newly diagnosed and dasatinib-treated chronic myeloid leukemia patients

sem informação1001PB173168568520th Congress of European-Hematology-Associatio

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial

BackgroundPatients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population.MethodsThis was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy.ResultsThe composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts.ConclusionsThe combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need

Aequorin-based measurements of intracellular Ca(2+)-signatures in plant cells

Due to the involvement of calcium as a main second messenger in the plant signaling pathway, increasing interest has been focused on the calcium signatures supposed to be involved in the patterning of the specific response associated to a given stimulus. In order to follow these signatures we described here the practical approach to use the non-invasive method based on the aequorin technology. Besides reviewing the advantages and disadvantages of this method we report on results showing the usefulness of aequorin to study the calcium response to biotic (elicitors) and abiotic stimuli (osmotic shocks) in various compartments of plant cells such as cytosol and nucleus

Guidelines for the diagnosis, classification, prophylaxis and treatment of chronic graft-versus-host disease

The lack of widely-used standardized diagnostic criteria may impair both the true evaluation of chronic graft-versus-host disease and the correlation of its severity with transplant-related mortality. At the I Consensus of the Brazilian Society of Bone Marrow Transplantation - SBTMO that took place in June 2009, the Group of GVHD Studies Brazil-Seattle (GEDECH), presented the guidelines for diagnosis, classification, prophylaxis and treatment of chronic GVHD as proposed by the National Institutes of Health and based on the reality in Brazilian Centers. These proposals, including standardization of features used in diagnosis and tools to score involved organs and to assess the overall severity, should be used in clinical studies of chronic graft-versus-host disease. These criteria are useful to better analyze the incidence of this disease, in addition to evaluate the extension of the involvement of organs or the site affected and its influence on late transplantation mortality. Prophylaxis and treatment proposed for this important complication of hematopoietic stem cell transplantations were discussed and graded according to the levels of evidence established by the National Institutes of Health.A falta de critérios diagnósticos padronizados, amplamente utilizados, pode comprometer tanto a avaliação real da incidência da doença contra hospedeiro crônica bem como a correlação de sua gravidade com a taxa de mortalidade pós-transplante. Na I Reunião de Diretrizes da Sociedade Brasileira de Transplante de Medula Óssea, realizada em junho de 2009, o Grupo de Estudos de DECH Brasil - Seattle (GEDECH), baseado na realidade dos Centros brasileiros, apresentou as recomendações para diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica propostas pelo National Institutes of Health. Estas propostas incluíram padronização das características utilizadas no diagnóstico e ferramentas para a pontuação dos órgãos envolvidos e avaliação global da gravidade a serem utilizados em estudos clínicos da doença enxerto contra hospedeiro crônica. Estes critérios são úteis para uma melhor análise da incidência desta doença, além de poder avaliar a gravidade do comprometimento de um órgão ou sítio envolvido e a influência na mortalidade tardia do transplante. A profilaxia e os tratamentos propostos para esta importante complicação dos transplantes de células-tronco hematopoéticas foram discutidos e graduados de acordo com níveis de evidência estabelecidos pelo National Institutes of Health.223

Applying design patterns in the search-based optimization of software product line architectures

The design of the product line architecture (PLA) is a difficult activity that can benefit from the application of design patterns and from the use of a search-based optimization approach, which is generally guided by different objectives related, for instance, to cohesion, coupling and PLA extensibility. The use of design patterns for PLAs is a recent research field, not completely explored yet. Some works apply the patterns manually and for a specific domain. Approaches to search-based PLA design do not consider the usage of these patterns. To allow such use, this paper introduces a mutation operator named “Pattern-Driven Mutation Operator” that includes methods to automatically identify suitable scopes and apply the patterns Strategy, Bridge and Mediator with the search-based approach multi-objective optimization approach for PLA. A metamodel is proposed to represent and identify suitable scopes to receive each one of the patterns, avoiding the introduction of architectural anomalies. Empirical results are also presented, showing evidences that the use of the proposed operator produces a greater diversity of solutions and improves the quality of the PLAs obtained in the search-based optimization process, regarding the values of software metrics

Pedagogical interventions to support student belonging and employability: four case studies

Employability is not just about focusing on building the students’ workplace experience but about developing their social and cultural capital through learning. In higher education, the selected pedagogies are central to that development (Pegg, 2012). Thoughtful curricular design which maximises student engagement and adopts pedagogies for career and employability learning can help to prepare students for the reality of the workplace. These pedagogies with social connection at their heart can enhance student wellbeing and their perceived sense of belonging to their course and wider world. This can thus build more confident, reflective and collaborative graduates who should ultimately be more employable (Rowe et al, 2023). This paper uses a qualitative approach to outline four course-based case study examples of pedagogies that strengthen the behaviours and skills that enhance students’ employability. The curricular and pedagogic practices of each are examined, and significant themes from each are then synthesised. Together they demonstrate how thoughtful course design and inclusive, integrated, contextualised pedagogic approaches support the development of students’ employability learning and graduate skills (Healy, 2023). The common themes from the case studies focused on self-directed, student-centred, authentic learning which encouraged students to i) work with industry and communities to build early professional networks, ii) engage in connected learning where the curriculum and its supporting activities and pedagogy facilitate collaborative learning, iii) develop confidence, a sense of belonging and professional identities through using these inclusive, collaborative learning approaches. In addition, six practical pedagogic principles are identified for course teams to utilise. These include i) focus on inclusive practice, ii) building students’ professional identity, iii) developing students’ belonging, iv) deep critical thinking v) the demystification of the workplace through the activities selected vi) students leading their own learning. This paper integrates a series of reflective questions (mapped to each principle) for educational developers to consider as they design future learning activities which foster graduate skills during career and employability learning