Correction to: How to support dental students in reading radiographs: effects of a gaze‑based compare‑and‑contrast intervention

Advances in Health Sciences Education -     

RASSF1A independence and early galectin‐1 upregulation in PIK3CA‐induced hepatocarcinogenesis: new therapeutic venues

Aberrant activation of the phosphoinositide 3‐kinase (PI3K)/AKT/mTOR and Ras/mitogen‐activated protein kinase (MAPK) pathways is a hallmark of hepatocarcinogenesis. In a subset of hepatocellular carcinomas (HCCs), PI3K/AKT/mTOR signaling dysregulation depends on phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, catalytic subunit alpha (PIK3CA) mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressor Ras association domain‐containing protein 1 (RASSF1A). To evaluate a possible cocarcinogenic effect of PIK3CA activation and RASSF1A knockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wild‐type mice by hydrodynamic tail vein injection combined with sleeping beauty‐mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce HCCs in mice irrespective of RASSF1A mutational background. The related tumors displayed a lipogenic phenotype with upregulation of fatty acid synthase and stearoyl‐CoA desaturase‐1 (SCD1). Galectin‐1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co‐inhibitory treatment with PIK3CA inhibitors and the galectin‐1 inhibitor OTX008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.     

Cervical anterior transpedicular screw fixation. Part I: Study on morphological feasibility,indications, and technical prerequisites

Multilevel cervical spine procedures can challenge the stability of current anterior cervical screw-and-plate systems, particularly in cases of severe three-column subaxial cervical spine injuries and multilevel plated reconstructions in osteoporotic bone. Supplemental posterior instrumentation is therefore recommended to increase primary construct rigidity and diminish early failure rates. The increasing number of successfully performed posterior cervical pedicle screw fixations have enabled more stable fixations, however most cervical pathologies are located anteriorly and preferably addressed by an anterior approach. To combine the advantages of the anterior approach with the superior biomechanical characteristics of cervical pedicle screw fixation, the authors developed a new concept of a cervical anterior transpedicular screw-and-plate system. An in vivo anatomical study was performed to explore the feasibility of anterior transpedicular screw fixation (ATPS) in the cervical spine. The morphological study was conducted based on 29 cervical spine CT scans from healthy patients and measurements were performed on the pedicle sizes, angulations, vertebral body depth, height and width at C2 to T1. Significant morphologic parameters for the new technique are discussed. These parameters include the sagittal and transverse intersection points of the pedicle axis with the anterior vertebral body wall, as well as the distances between sagittal intersection points from C2 to T1. On the basis of these results, standard spine models were reconstructed and used for the conceptual development of a preclinical release prototype of an anterior transpedicular screw-and-plate system. The morphological feasibility of the new technique is demonstrated, and its indications, biomechanical considerations, as well as surgical prerequisites are thoroughly discussed. In the future, the technique of cervical anterior transpedicular screw fixation might diminish the number of failures in the reconstruction of multilevel and three-column cervical spine instabilities, and avoid the need for supplemental posterior instrumentation.     

Identification and In-Depth Analysis of the Novel FGFR2-NDC80 Fusion in a Cholangiocarcinoma Patient: Implication for Therapy

Fibroblast growth factor receptor 2 (FGFR2) fusions have emerged as a new therapeutic target for cholangiocarcinoma in clinical practice following the United States Food and Drug Administration (FDA) approval of Pemigatinib in May 2020. FGFR2 fusions can result in a ligand-independent constitutive activation of FGFR2 signaling with a downstream activation of multiple pathways, including the mitogen-activated protein (MAPK) cascade. Until today, only a limited number of fusion partners have been reported, of which the most prevalent is BicC Family RNA Binding Protein (BICC1), representing one-third of all detected FGFR2 fusions. Nonetheless, in the majority of cases rare or yet unreported fusion partners are discovered in next-generation sequencing panels, which confronts clinicians with a challenging decision: Should a therapy be based on these variants or should the course of treatment follow the (limited) standard regime? Here, we present the case of a metastasized intrahepatic cholangiocarcinoma harboring a novel FGFR2-NDC80 fusion, which was discussed in our molecular tumor board. The protein NDC80 kinetochore complex component (NDC80) is an integral part of the outer kinetochore, which is involved in microtubule binding and spindle assembly. For additional therapeutic guidance, an immunohistochemical analysis of the predicted fusion and downstream effector proteins was performed and compared to cholangiocarcinoma samples of a tissue microarray. The FGFR2-NDC80 fusion resulted in strong activation of the FGFR2 signaling pathway. These supporting results led to a treatment recommendation of Pemigatinib. Unfortunately, the patient passed away before the commencement of therapy.     

Why Sketching May Aid Learning From Science Texts: Contrasting Sketching With Written Explanations

The goal of this study was to explore two accounts for why sketching during learning from text is helpful: (1) sketching acts like other constructive strategies such as self-explanation because it helps learners to identify relevant information and generate inferences; or (2) that in addition to these general effects, sketching has more specific benefits due to the pictorial representation that is constructed. Seventy-three seventh-graders (32 girls, M = 12.82 years) were first taught how to either create sketches or self-explain while studying science texts. During a subsequent learning phase, all students were asked to read an expository text about the greenhouse effect. Finally, they were asked to write down everything they remembered and then answer transfer questions. Strategy quality during learning was assessed as the number of key concepts that had either been sketched or mentioned in the self-explanations. The results showed that at an overall performance level there were only marginal group differences. However, a more in-depth analysis revealed that whereas no group differences emerged for students implementing either strategy poorly, the sketching group clearly outperformed the self-explanation group for students who applied the strategies with higher quality. Furthermore, higher sketching quality was strongly related to better learning outcomes. Thus, the study's results are more in line with the second account: Sketching can have a beneficial effect on learning above and beyond generating written explanations; at least, if well deployed.