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Abstract This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration. To interrogate the mechanistic role of DEK in B-cell lymphoma, we generated a DEK knockout cell line model, which demonstrated DEK depletion caused reduced proliferation and altered expression of key cell cycle and apoptosis-related proteins, including Bcl-2, Bcl-xL, and p53. Notably, DEK depleted cells showed increased sensitivity to apoptosis-inducing agents, including venetoclax and staurosporine, which underscores the therapeutic potential of targeting DEK in B-cell lymphomas. Overall, our study contributes to a better understanding of DEK’s role as an oncoprotein in B-cell lymphomas, highlighting its potential as both a promising therapeutic target and a novel biomarker for aggressive LGBCL. Further research elucidating the molecular mechanisms underlying DEK-mediated tumorigenesis could pave the way for improved treatment strategies and better clinical outcomes for patients with B-cell lymphoma.

Project-based learning (PBL) is gaining momentum as a rich and multifaceted instructional approach that is motivating and engaging. Miranda S. Fitzgerald and Annemarie Sullivan Palincsar argue that PBL provides a particularly rich context for fostering students' literacy motivation and engagement. One reason for this is that characteristic features of PBL closely align with research-supported instructional practices for fostering literacy motivation and engagement, such as peer collaboration, communicating with real audiences, and solving meaningful problems. They describe supporting research and share how educators can use the SMILE concept - sharing, me, importance, liking, engagement - to design and implement PBL to foster literacy motivation and engagement in K-12 classrooms.

Angelman syndrome (AS) is a neurogenetic disorder caused by the loss of ubiquitin ligase E3A (UBE3A) gene expression in the brain. The UBE3A gene is paternally imprinted in brain neurons. Clinical features of AS are primarily due to the loss of maternally expressed UBE3A in the brain. A healthy copy of paternal UBE3A is present in the brain but is silenced by a long non-coding antisense transcript (UBE3A-ATS). Here, we demonstrate that an artificial transcription factor (ATF-S1K) can silence Ube3a-ATS in an adult mouse model of Angelman syndrome (AS) and restore endogenous physiological expression of paternal Ube3a. A single injection of adeno-associated virus (AAV) expressing ATF-S1K (AAV-S1K) into the tail vein enabled whole-brain transduction and restored UBE3A protein in neurons to ∼25% of wild-type protein. The ATF-S1K treatment was highly specific to the target site with no detectable inflammatory response 5 weeks after AAV-S1K administration. AAV-S1K treatment of AS mice showed behavioral rescue in exploratory locomotion, a task involving gross and fine motor abilities, similar to low ambulation and velocity in AS patients. The specificity and tolerability of a single injection of AAV-S1K therapy for AS demonstrate the use of ATFs as a promising translational approach for AS.

Interrupted time series (ITS) studies are frequently used to examine the impact of population-level interventions or exposures. Systematic reviews with meta-analyses including ITS designs may inform public health and policy decision-making. Re-analysis of ITS may be required for inclusion in meta-analysis. While publications of ITS rarely provide raw data for re-analysis, graphs are often included, from which time series data can be digitally extracted. However, the accuracy of effect estimates calculated from data digitally extracted from ITS graphs is currently unknown. Forty-three ITS with available datasets and time series graphs were included. Time series data from each graph was extracted by four researchers using digital data extraction software. Data extraction errors were analysed. Segmented linear regression models were fitted to the extracted and provided datasets, from which estimates of immediate level and slope change (and associated statistics) were calculated and compared across the datasets. Although there were some data extraction errors of time points, primarily due to complications in the original graphs, they did not translate into important differences in estimates of interruption effects (and associated statistics). Using digital data extraction to obtain data from ITS graphs should be considered in reviews including ITS. Including these studies in meta-analyses, even with slight inaccuracy, is likely to outweigh the loss of information from non-inclusion.

Background: Successful rescue after elective surgery is associated with increased healthcare costs, but costs vary widely. Treating all rescue events the same may overlook targeted opportunities for improvement. The purpose of this study was to predict high-cost rescue after elective colorectal surgery. Methods: We identified adult patients in the National Inpatient Sample (2016–2021) who underwent elective colectomy or proctectomy. Rescued patients were defined as those who underwent additional major procedures. Three groups were stratified: 1) uneventful recovery; 2) Low-cost rescue; 3) High-cost rescue. Multivariable Poisson regression was used to identify preoperative clinical predictors of high-cost versus low-cost rescue. Results: We identified 448,590 elective surgeries, and rescued patients composed 4.8 %(21,635) of the total sample. The median increase in costs in rescued patients was $25,544(p

We report on a meta-analysis designed to test the theory that instruction that involves direct teaching of academic vocabulary and teaching strategies to determine the meaning of unknown words develops students' abilities to infer new words' meanings and builds students' overall vocabulary knowledge. We meta-analyzed 39 experimental and quasi-experimental intervention studies conducted in grades K-5 to examine the effects of these instructional approaches. Results indicate that interventions that targeted word meaning instruction do not show overall positive effects on measures of breadth of vocabulary knowledge. Although strategy interventions are effective in improving word solving skills on near transfer measures, strategy interventions do not significantly impact students' overall breadth of vocabulary knowledge. These findings suggest that direct teaching of vocabulary words may not be effective for building overall vocabulary knowledge among elementary-grade students. More research is needed to examine the potential of teaching strategies to determine the meaning of unknown words.

Although research related to the Science of Reading has documented the positive effects of explicit, systematic reading instruction for all students, students from historically marginalized groups often experience differential opportunities to learn and are likely to perform lower than their peers on large scale measures of reading achievement. These differences may be further exacerbated by summer learning loss (SLL), in which student academic progress stagnates or declines during the summer months. Providing summertime academic interventions, specifically in reading, has been one proposed solution for mitigating SLL. The present exploratory study examined the impact of a comprehensive approach to summer literacy intervention that included evidence-based reading instruction in foundational reading skills (phonemic awareness, phonics, fluency) and more advanced disciplinary literacy skills on student reading-related outcomes for rising 1st-3rd grade students. on student reading-related outcomes for rising first, second, and third graders from an under-resourced, urban school. The majority of students who participated in the programming were from historically marginalized populations and low-income families and included students with diverse literacy needs. with 70% of students qualifying for free or reduced-price lunch, and included students with diverse literacy skills, students with developmental disabilities, and emergent bilingual learners. Students were assessed pre-post using norm-referenced assessments of phonemic segmentation, nonsense word reading, and oral reading fluency as well as curriculum embedded Mastery Tests. Results indicated that students made significant growth or maintained measured reading skills. Results indicated that rising first grade students made significant growth pre-post on measures of phonemic segmentation fluency, nonsense word reading, and Mastery Tests. Rising 2nd grade students demonstrated significant growth on Mastery Tests measures and maintained on other measures. Rising 3rd grade students demonstrated significant growth on aspects of nonsense word reading and maintained on other measures. Findings from this study indicate that a summer literacy intervention designed to address both foundational and disciplinary literacy skills may improve reading-related outcomes for students from economically and culturally diverse backgrounds.

In this conceptual paper, we present a discussion of how we have embraced two challenges, posed by Aukerman and Schuldt, in their call for a more socially just science of reading, to which this special issue is responsive. Specifically, we share lessons learned from years of designing texts that (a) advance knowledge-building in the context of project-based science teaching and (b) advance readers’ textual dexterity. Our research is conducted in the context of project-based learning in science, and we approach our inquiry from multiple theoretical perspectives. We argue for the importance of text in science instruction. We present theories, empirical support, and national standards consistent with the integration of text in science. We discuss the role that texts can play in project-based science instruction. We also illustrate the design and optimization of texts and tasks, as well as the role of the teacher in this instruction.

Ms. Lane's (all names are pseudonyms) class of third-graders excitedly gathered their notebook sheets, pencils, and clipboards and lined up at the classroom door, eager to explore the environment around [...]

In this paper, a computational approach based on numerical dissipation is proposed to simulate rocking blocks. A rocking block is idealized as a solid body interacting with its foundation through a contact-based formulation. An implicit time integration scheme with numerical dissipation, set to optimally treat dissipation in contact problems, is employed. The numerical dissipation is ruled by the time step and the rocking dissipative phenomenon at impacts is accurately predicted without any damping model. A broad numerical campaign is conducted to define a regression law in analytic form for the setting of the time step, depending on the block size and aspect ratio, the contact stiffness, as well as the coefficient of restitution selected. The so-obtained regression law appears accurate and an a posteriori validation with cases not in the training dataset confirms the effectiveness of the approach. Finally, the comparison with available experimental tests highlights the approach efficacy for free rocking and harmonic loading cases (in a deterministic sense), and for earthquake-like loading cases (in a statistical sense). It is found that rocking blocks with sizes of interest for structural engineering (e.g., cultural heritage structures) can be simulated with time steps within 10–3 ÷ 10–1 s, so allowing very fast computations. [ABSTRACT FROM AUTHOR]

In this conceptual paper, we present a discussion of how we have embraced two challenges, posed by Aukerman and Schuldt, in their call for a more socially just science of reading, to which this special issue is responsive. Specifically, we share lessons learned from years of designing texts that (a) advance knowledge-building in the context of project-based science teaching and (b) advance readers' textual dexterity. Our research is conducted in the context of project-based learning in science, and we approach our inquiry from multiple theoretical perspectives. We argue for the importance of text in science instruction. We present theories, empirical support, and national standards consistent with the integration of text in science. We discuss the role that texts can play in project-based science instruction. We also illustrate the design and optimization of texts and tasks, as well as the role of the teacher in this instruction. [ABSTRACT FROM AUTHOR]