Emerging Therapies in CLL in the Era of Precision Medicine

Over the past decade, the treatment landscape of CLL has vastly changed from the conventional FC (fludarabine and cyclophosphamide) and FCR (FC with rituximab) chemotherapies to targeted therapies, including inhibitors of Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) as well as inhibitors of BCL2. These treatment options dramatically improved clinical outcomes; however, not all patients respond well to these therapies, especially high-risk patients. Clinical trials of immune checkpoint inhibitors (PD-1, CTLA4) and chimeric antigen receptor T (CAR T) or NK (CAR NK) cell treatment have shown some efficacy; still, long-term outcomes and safety issues have yet to be determined. CLL remains an incurable disease. Thus, there are unmet needs to discover new molecular pathways with targeted or combination therapies to cure the disease. Large-scale genome-wide whole-exome and whole-genome sequencing studies have discovered genetic alterations associated with disease progression, refined the prognostic markers in CLL, identified mutations underlying drug resistance, and pointed out critical targets to treat the disease. More recently, transcriptome and proteome landscape characterization further stratified the disease and revealed novel therapeutic targets in CLL. In this review, we briefly summarize the past and present available single or combination therapies, focusing on potential emerging therapies to address the unmet clinical needs in CLL

VeriSIM: A model-based learning pedagogy for fostering software design evaluation skills in computer science undergraduates

AbstractEvaluating a software design is an important practice of expert software designers. They spend significant time evaluating their solution, by developing an integrated mental model of the software design and the requirements. However, sufficient emphasis has not been given on teaching and learning of evaluation practices in software design courses, and hence, graduating students find it difficult to critically analyse an existing design and improve upon it. In this paper, we describe a model-based learning pedagogy for teaching–learning of software design evaluation. Model-based learning has been extensively used in science education and entails helping students construct, refine, revise, evaluate, and validate scientific models. We argue that modelling practices in software design evaluation are analogous to these practices. We adapted the model-based learning paradigm and operationalised it into a technology-enhanced learning environment (TELE) for fostering software design evaluation skills in computer science undergraduates. We conducted a research study with 22 undergraduate students to explore how the TELE and its features help students effectively evaluate a given software design. Students attempted a pre-test and post-test which asked them to identify defects in the design. We used the content analysis method to identify categories of defects from student responses in the pre-test and post-test. We also analysed student interaction logs and conducted focus group interviews to identify how features in the TELE contributed towards student learning. Findings from the study showed that students’ understanding of evaluation improved, from merely adding new functionalities and requirements, to a process which involved identifying alternate scenarios in the design which violate the given requirements. Students perceived that pedagogical features of the TELE were useful in helping them effectively evaluate software designs. Findings from the study provide evidence for the model-based learning paradigm as an appropriate pedagogy for software design and also opens the space for researchers to investigate model-based learning in other aspects of software design, such as designs of different types and varying complexities.</jats:p

Emerging Therapies in CLL in the Era of Precision Medicine

Over the past decade, the treatment landscape of CLL has vastly changed from the conventional FC (fludarabine and cyclophosphamide) and FCR (FC with rituximab) chemotherapies to targeted therapies, including inhibitors of Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) as well as inhibitors of BCL2. These treatment options dramatically improved clinical outcomes; however, not all patients respond well to these therapies, especially high-risk patients. Clinical trials of immune checkpoint inhibitors (PD-1, CTLA4) and chimeric antigen receptor T (CAR T) or NK (CAR NK) cell treatment have shown some efficacy; still, long-term outcomes and safety issues have yet to be determined. CLL remains an incurable disease. Thus, there are unmet needs to discover new molecular pathways with targeted or combination therapies to cure the disease. Large-scale genome-wide whole-exome and whole-genome sequencing studies have discovered genetic alterations associated with disease progression, refined the prognostic markers in CLL, identified mutations underlying drug resistance, and pointed out critical targets to treat the disease. More recently, transcriptome and proteome landscape characterization further stratified the disease and revealed novel therapeutic targets in CLL. In this review, we briefly summarize the past and present available single or combination therapies, focusing on potential emerging therapies to address the unmet clinical needs in CLL.</jats:p

Additional file 1 of VeriSIM: A model-based learning pedagogy for fostering software design evaluation skills in computer science undergraduates

Additional file 1. Scenario branching worksheet

Additional file 2 of VeriSIM: A model-based learning pedagogy for fostering software design evaluation skills in computer science undergraduates

Additional file 2. Pre-test

Additional file 3 of VeriSIM: A model-based learning pedagogy for fostering software design evaluation skills in computer science undergraduates

Additional file 3. Post-test