Are e-books effective tools for learning? Reading speed and comprehension: iPad®i vs. paper

Recently, electronic books (e-books) have become prevalent amongst the general population, as well as students, owing to their advantages over traditional books. In South Africa, a number of schools have integrated tablets into the classroom with the promise of replacing traditional books. In order to realise the potential of e-books and their associated devices within an academic context, where reading speed and comprehension are critical for academic performance and personal growth, the effectiveness of reading from a tablet screen should be evaluated. To achieve this objective, a quasi-experimental within-subjects design was employed in order to compare the reading speed and comprehension performance of 68 students. The results of this study indicate the majority of participants read faster on an iPad, which is in contrast to previous studies that have found reading from tablets to be slower. It was also found that comprehension scores did not differ significantly between the two media. For students, these results provide evidence that tablets and e-books are suitable tools for reading and learning, and therefore, can be used for academic work. For educators, e-books can be introduced without concern that reading performance and comprehension will be hindered.Keywords: comprehension; electronic books; reading; spee

The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering

Despite decades of intensive attention directed to creation of genetically altered cells (e.g., as in development of chimeric antigen receptor (CAR) T-cells) and/or to achieve requisite in vitro accumulation of desired immunologic effectors (e.g., elaboration of virus-specific T cells, expansion of NK cells, differentiation of dendritic cells, isolation, and propagation of Tregs, etc.), there has been essentially no interest in the most fundamental of all hurdles: assuring tissue-specific delivery of administered therapeutic cells to sites where they are needed. With regards to use of CAR T-cells, the absence of information on the efficacy of cell delivery is striking, especially in light of the clear association between administered cell dose and adverse events, and the obvious fact that pertinent cell acquisition/expansion costs would be dramatically curtailed with more efficient delivery of the administered cell bolus. Herein, based on information garnered from studies of human leukocytes and adult stem cells, the logic underlying the use of cell surface glycoengineering to enforce E-selectin ligand expression will be conveyed in the context of how this approach offers strategies to enhance delivery of CAR T-cells to marrow and to tumor beds. This application of glycoscience principles and techniques with intention to optimize cell therapeutics is a prime example of the emerging field of “translational glycobiology.

Teachers' professional dispositions and orientation towards tablet technology: towards a more nuanced understanding of teachers' adoption of technology in South African private secondary schools

A research report submitted to the School of Education, Faculty of Humanities, University of the Witwatersrand in partial fulfilment of the requirements for the degree of Masters of Education Johannesburg March 2014Rapid improvements in technology have resulted in increasing calls to integrate educational technology into classrooms. Much of the contemporary educational technology literature premised on constructivist pedagogic practices, have offered promissories of radical change to traditional pedagogic practices and formal education due to the use of educational technology. Past research has shown that teachers do not automatically choose to adopt technology in the classroom nor radically change their pedagogic practice, simply due to the presence of technology. Recent technological innovations such as mobile technologies, and more specifically tablets, are once more being advocated as a powerful means for radically transforming teachers’ teaching practices and enhancing learning in schools. Calls to incorporate tablet technology into the classroom are being driven by the groundswell of popular opinion demanding its inclusion, as well as contemporary research advocating constructivist pedagogic practices. Educational research thus far has explored classroom practices where technology has been adopted and has tended to focus on the resulting changes in teaching and learning. Research aimed at explicitly understanding teachers’ orientations to the new technology at stake, coupled with an understanding of the reasons behind teachers’ choices to adopt or not adopt technology have not yet been fully explored. With the intention of developing a more nuanced understanding of teachers’ technology adoption choices, a conceptual framework using the constructs of teachers’ Professional Dispositions and their Orientation towards Tablet Technology has been derived from the work of Bernstein on the pedagogic discourse, Hoadley and Ensor on Professional Dispositions and Hooper and Rieber on educational technology adoption. Using a mixed methods research methodology, data was collected at three advantaged private secondary schools in which it was found that a relationship does indeed exist between teachers’ Professional Dispositions and their Orientations towards Tablet Technology. From the study it is clear that teachers have principled reasons in relation to their technology adoption, with teachers’ pedagogic mode being critical in shaping decision to adopt or not adopt technology and their construal of their subject knowledge structure influencing the type of technology adoption activities used by teachers, with internet access and productivity being the most widespread and collaboration of learning being the least. Furthermore, it was found that teachers across all Professional Dispositions expect the use of tablets in educational contexts in the future to increase. Keywords: Educational Technology, Tablet Technology, Professional Disposition, Orientation towards Tablet Technology, Pedagogical Discourse, Technology Adoptio

The engagement of selectins and their ligands in colorectal cancer liver metastases

The colonization of the liver by colorectal cancer (CRC) cells is a complicated process which includes many stages, until macrometastases occur. The entrapment of malignant cells within the hepatic sinusoids and their interactions with resident non-parenchymal cells are considered very important for the whole metastatic sequence. In the sinusoids, cell connection and signalling is mediated by multiple cell adhesion molecules, such as the selectins. The three members of the selectin family, E-, P- and L-selectin, in conjunction with sialylated Lewis ligands and CD44 variants, regulate colorectal cell communication and adhesion with platelets, leucocytes, sinusoidal endothelial cells and stellate cells. Their role in CRC liver metastases has been investigated in animal models and human tissue, in vivo and in vitro, in static and shear flow conditions, and their key-function in several molecular pathways has been displayed. Therefore, trials have already commenced aiming to exploit selectins and their ligands in the treatment of benign and malignant diseases. Multiple pharmacological agents have been developed that are being tested for potential therapeutic applications

Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation

Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A), and a-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLeX/A, to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLeX/A antibodies in both IDC tissue and cell lines, and expression of a-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the ‘CF1_T cell line’. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLeX/A expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.The authors acknowledge the financial support from the LPCC/Pfizer 2011 and Portuguese Foundation for Science and Technology (FCT)—SFRH/BD/100970/ 2014 (MAC), SFRH/BD/81860/2011 (MS), and the United States National Institutes of Health National Heart Blood Institute (NHLBI Grant HL107146, RS). We also thank Dr Nicole Okeley from Seattle Genetics for the valuable help and opinions

Understanding the influence of teachers’ beliefs and professional dispositions on technology use in South African secondary schools before and during COVID

Those advocating for technology integration within education claim that teachers need to reform their pedagogic practices to make learning more engaging and relevant. While educational technology researchers claim teachers are primarily responsible for these failures, it seems teachers do not embrace technology unquestionably. This paper aims to develop an understanding of how teachers’ beliefs and professional dispositions (PDs) influence technology use within different social and educational contexts. A set of three interviews were conducted at four South African secondary schools with vastly different social contexts, over different periods of time (before and during COVID) with cross-case analyses. Findings show that the provision of technology does not guarantee integration as use varies amongst teachers within technology-rich schools, with teachers who hold more positive Internal Beliefs (IBs) of technology not only focusing less on External Structure (ES) barriers, but also utilising technology in more varied ways, even to enhance and transform their pedagogic practices. Furthermore, teachers’ PDs seem to exist on a continuum and do not appear to be the sole influencer of technology use, with the context alongside the school’s technology policy and related technology structures influencing teachers’ IBs and resulting technology use. In addition, while mandatory use of technology during COVID led to more positive IBs as teachers understood the value of the technology, this only appears to be true if external structures (ESs) supported the learners as well. Moreover, all teachers expressed their belief that technology is no replacement for face-to-face teaching. Finally, the rich data from the interviews underlined the intricacies of factors influencing the use of technology in classrooms, indicating a need for a meta-theory to gain a holistic understanding of technology use by teachers.http://www.easychair.org/publications/EPiC/Computingam2023Informatic

Defibrotide inhibits donor leucocyte-endothelial interactions and protects against acute graft-versus-host disease

Altres ajuts: This study has been funded by Josep Carreras Leukaemia Foundation (Grant 11R/2016 and 03R/2019).Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective therapy for the treatment of high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. Acute graft-versus-host disease (aGvHD) remains the most frequent cause of non-relapse mortality following allo-HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi-target drug successfully employed for prophylaxis and treatment of veno-occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo-HCT. Using a fully MHC-mismatched murine model of allo-HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD-associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo-HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte-endothelial interactions by down-regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo-HCT, paving the way for new therapeutic approaches

mRNA-mediated glycoengineering ameliorates deficient homing of human stem cell-derived hematopoietic progenitors

Generation of functional hematopoietic stem and progenitor cells (HSPCs) from human pluripotent stem cells (PSCs) has been a long-sought-after goal for use in hematopoietic cell production, disease modeling, and eventually transplantation medicine. Homing of HSPCs from bloodstream to bone marrow (BM) is an important aspect of HSPC biology that has remained unaddressed in efforts to derive functional HSPCs from human PSCs. We have therefore examined the BM homing properties of human induced pluripotent stem cell-derived HSPCs (hiPS-HSPCs). We found that they express molecular effectors of BM extravasation, such as the chemokine receptor CXCR4 and the integrin dimer VLA-4, but lack expression of E-selectin ligands that program HSPC trafficking to BM. To overcome this deficiency, we expressed human fucosyltransferase 6 using modified mRNA. Expression of fucosyltransferase 6 resulted in marked increases in levels of cell surface E-selectin ligands. The glycoengineered cells exhibited enhanced tethering and rolling interactions on E-selectin-bearing endothelium under flow conditions in vitro as well as increased BM trafficking and extravasation when transplanted into mice. However, glycoengineered hiPS-HSPCs did not engraft long-term, indicating that additional functional deficiencies exist in these cells. Our results suggest that strategies toward increasing E-selectin ligand expression could be applicable as part of a multifaceted approach to optimize the production of HSPCs from human PSCs