Why flipping the classroom is not enough: Digital curriculum making after the pandemic.

To slow down the proliferation of Covid-19, governments virtually shut down public life, temporarily closed schools, and forced teaching to be done exclusively on a remote basis. These measures offer an opportunity to reexamine conventional teaching and learning arrangements, test new digital and analogue concepts, and provide essential inspiration for curriculum making in the twenty-first century. This article addresses the historical development of schooling in the classroom as differentiated from "homeschooling". On one hand, the question of how school closures and digitally supported teaching settings may affect an increase in educational inequalities is investigated using an international comparison. On the other hand, the pedagogical and didactical implications of distance learning and a digital teaching culture, which constitute the foundation for digital curriculum making, are examined.

miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction.

MicroRNAs (miRs) are important posttranscriptional regulators of gene expression. Besides their well-characterized inhibitory effects on mRNA stability and translation, miRs can also activate gene expression. In this study, we identified a novel noncanonical function of miR-574-5p. We found that miR-574-5p acts as an RNA decoy to CUG RNA-binding protein 1 (CUGBP1) and antagonizes its function. MiR-574-5p induces microsomal prostaglandin E synthase-1 (mPGES-1) expression by preventing CUGBP1 binding to its 3'UTR, leading to an enhanced alternative splicing and generation of an mPGES-1 3'UTR isoform, increased mPGES-1 protein expression, PGE2 formation, and tumor growth in vivo. miR-574-5p-induced tumor growth in mice could be completely inhibited with the mPGES-1 inhibitor CIII. Moreover, miR-574-5p is induced by IL-1ß and is strongly overexpressed in human nonsmall cell lung cancer where high mPGES-1 expression correlates with a low survival rate. The discovered function of miR-574-5p as a CUGBP1 decoy opens up new therapeutic opportunities. It might serve as a stratification marker to select lung tumor patients who respond to the pharmacological inhibition of PGE2 formation.-Saul, M. J., Baumann, I., Bruno, A., Emmerich, A. C., Wellstein, J., Ottinger, S. M., Contursi, A., Dovizio, M., Donnini, S., Tacconelli, S., Raouf, J., Idborg, H., Stein, S., Korotkova, M., Savai, R., Terzuoli, E., Sala, G., Seeger, W., Jakobsson, P.-J., Patrignani, P., Suess, B., Steinhilber, D. miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction.

The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation.

Regulatory T cells (Tregs) use different mechanisms to exert their suppressive function, among them the conversion of ATP to adenosine initiated by the ectonucleotidase CD39. In humans, the expression of CD39 on Tregs shows a high interindividual variation, and is especially high at sites of inflammation, like the synovia of patients with arthritis. How CD39 expression is regulated, and the functional consequences of different levels of CD39 expression is not known. We show here that stimulation of CD39(-) Tregs results in a modest upregulation of CD39, which cannot explain the high levels observed in many donors. Moreover, CD39(+) Tregs are present in naïve compartments such as cord blood and thymus, and the individual frequency of CD39(+) Tregs remains stable over time, suggesting inherent regulation of CD39 expression. Indeed, we show that a single nucleotide polymorphism in the CD39 gene determines expression levels in Tregs. CD39(+) Tregs suppress T cell proliferation and inflammatory cytokine production more efficiently than CD39(-) Tregs. Accordingly, Tregs from donors with the GG (high CD39) genotype have a higher capacity to suppress IFN-γ and IL-17 production by effector cells than Tregs from AA (low CD39) donors. Our study demonstrates that the expression of CD39 in Tregs is primarily genetically driven, and this may determine interindividual differences in the control of inflammatory responses.

First experiences with a surgery supporting computer system in regard to education, efficiency and complications.

Purpose: Since October 2019 a computer software named SPM (surgical process manager) is used in a Level I Trauma center. Workflows were developed for distinct surgical procedures (distal radius fractures, proximal femur fractures, ankle fractures, proximal humerus fractures and vertebral fractures). In addition, these workflows were separated in a shortened "Expert"-versions for consultants and a more detailed "Learner"- versions for residents.This investigation was intended to show, if and what kind of benefits in regard to efficiency (incision to suture and suture to incision time), education and complications a surgery supporting software can bring. Methods: SPM was used in 90 cases during October 2019 to June 2022. A control trial with 108 patients was developed, including patients of the same age, having same kind of injuries, receiving the same surgery technique without using the SPM.The software was installed on the computer in the operation room, projected on head monitors and operated by a foot pedal. Complications could also be documented using the pedal.Groups were divided in surgical procedures and fracture type, qualification of the surgeon, complications and surgery time. Surgery times were taken from the hospital computer system (SAP IS-H). A statistical analysis was performed by using the chi square and Fischer exact test with significance set at a P value <0.05. Results: In 51 cases the software was used for the distal radius (control group 54 patients), in 20 cases for Weber fractures (control group 21 patients), in 9 cases for the proximal femur (control group 19 patients), in 5 cases for vertebral fractures (control group 7 patients) and in 5 cases for the proximal humerus (control group 6 patients).Time from incision to closure was significant higher in the intervention group (49 vs 42 min, p- value 0,018) and wasn't significant lower in the "expert" group, fixing radius and ancle fractures (39 to 46 min, p value 0,186).Comparing the SPM and control group concerning closing to incision time, no difference could be observed (56 to 58,5 min, p value 0,828).The greatest time deviation between "Learners"und "Experts"was observed in reduction and fixation (p value 0,006) in ankle fractures. The "Expert"group also needed less time for the approach (p value 0,008) in case of distal radius fractures.Unexpected events were more often observed in the intervention group (5,5 vs 3,7 %). Conclusions: A surgery supporting computer system might be a good tool for detecting and optimizing workflows in the operation room and for improving and analyzing the training of residents and surgical assistants.In addition, it offers the opportunity to document intraoperative complications. However, a saving of time wasn't observed in this study. Further investigations with bigger number of cases and a longer follow-up are necessary to proof these findings statistically.

Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells.

MicroRNAs (miRs) are one of the most important post-transcriptional repressors of gene expression. However, miR-574-5p has recently been shown to positively regulate the expression of microsomal prostaglandin E-synthase-1 (mPGES-1), a key enzyme in the prostaglandin E2 (PGE2) biosynthesis, by acting as decoy to the RNA-binding protein CUG-RNA binding protein 1 (CUGBP1) in human lung cancer. miR-574-5p exhibits oncogenic properties and promotes lung tumor growth in vivo via induction of mPGES-1-derived PGE2 synthesis. In a mass spectrometry-based proteomics study, we now attempted to characterize this decoy mechanism in A549 lung cancer cells at a cellular level. Besides the identification of novel CUGBP1 targets, we identified that the interaction between miR-574-5p and CUGBP1 specifically regulates mPGES-1 expression. This is supported by the fact that CUGBP1 and miR-574-5p are located in the nucleus, where CUGBP1 regulates alternative splicing. Further, in a bioinformatical approach we showed that the decoy-dependent mPGES-1 splicing pattern is unique. The specificity of miR-574-5p/CUGBP1 regulation on mPGES-1 expression supports the therapeutic strategy of pharmacological inhibition of PGE2 formation, which may provide significant therapeutic value for NSCLC patients with high miR-574-5p levels.

Mass Spectrometry-Based Proteomics Approach Characterizes the Dual Functionality of miR-328 in Monocytes.

MicroRNAs (miRs) are small noncoding RNAs which control the expression of target genes by either translational repression or RNA degradation, known as canonical miR functions. The recent discovery that miR-328 has a noncanonical function and can activate gene expression by antagonizing the activity of heterogeneous ribonuclear protein E2 (hnRNP E2) opens an unexplored and exciting field of gene expression regulation. The global importance of such noncanonical miR function is not yet known. In order to achieve a better understanding of the new miR activity, we performed a compartment specific tandem mass tag (TMT)-based proteomic analysis in differentiated MonoMac6 (MM6) cells, to monitor gene expression variations in response to miR-328 knockdown. We identified a broad spectrum of novel potential miR-328/hnRNP E2 and miR-328 targets involved in regulation of compartment specific cellular processes, such as inflammation or RNA splicing. This study provides first insights of the global significance of noncanonical miR function.