Peer creation and sharing of mnemonics in collaborative documents for pathology education: a pilot study.

BACKGROUND: Mnemonic techniques are memory aids that could help improve memory encoding, storage, and retrieval. Using the brain's natural propensity for pattern recognition and association, new information is associated with something familiar, such as an image, a structure, or a pattern. This should be particularly useful for learning complex medical information. Collaborative documents have the potential to revolutionize online learning because they could increase the creativity, productivity, and efficiency of learning. The purpose of this study was to investigate the feasibility of combining peer creation and sharing of mnemonics with collaborative online documents to improve pathology education. METHODS: We carried out a prospective, quasi-experimental, pretest-posttest pilot study. The intervention group was trained to create and share mnemonics in collaborative documents for pathological cases, based on histopathological slides. The control group compared analog and digital microscopy. RESULTS: Both groups consisted of 41 students and did not reveal demographic differences. Performance evaluations did not reveal significant differences between the groups' pretest and posttest scores. Our pilot study revealed several pitfalls, especially in instructional design, time on task, and digital literacy, that could have masked possible learning benefits. CONCLUSIONS: There is a gap in evidence-based research, both on mnemonics and on CD in pathology didactics. Even though, the combination of peer creation and sharing of mnemonics is very promising from a cognitive neurobiological standpoint, and collaborative documents have great potential to promote the digital transformation of medical education and increase cooperation, creativity, productivity, and efficiency of learning. However, the incorporation of such innovative techniques requires meticulous instructional design by teachers and additional time for students to become familiar with new learning methods and the application of new digital tools to promote also digital literacy. Future studies should also take into account validated high-stakes testing for more reliable pre-posttest results, a larger cohort of students, and anticipate technical difficulties regarding new digital tools.

Buzz groups facilitate collaborative learning and improve histopathological competencies of students.

INTRODUCTION: Traditional teacher-centered histopathology training is based on theoretical lectures and practical tutorials. We hypothesize that learning outcomes improve if students are activated by demonstrating cardinal features of slides to each other and discussing their pathogenesis. Buzz groups (BGs) could facilitate this. The aim of this study was to investigate the effectiveness of student-centered BGs, i.e., peer-teaching, versus traditional teacher-centered histopathology teaching. Furthermore, we compared digital with analog microscopy. MATERIALS AND METHODS: In addition to traditional guided instruction and explanation of slides, neighboring students demonstrated to each other histopathological features and discussed associated pathogenesis. RESULTS: After only 4 course lessons, the BG students did much better than the control group (ANCOVA p = 0.002; F = 9.7). Then the control group also applied the BG technique. After another 4 lessons, the control group was able to catch up almost completely (ANCOVA p = 0.36; F = 0.9). Overall, there was no difference in time on task. DISCUSSION: Collaborative BGs improve the learning of histopathological competencies. They motivate and activate students to learn. The course also increased the appreciation of students for histopathology. For BGs, digital microscopy was better suited than traditional analog microscopy. The application of BGs in the context of analyzing microscopic images should be disseminated and studied on larger cohorts.

A family with limb girdle muscular dystrophy type 1B and multiple exostoses.

INTRODUCTION: Next-generation sequencing in cases of hereditary neuromuscular disorders often yields multiple candidate gene variants. Here, we describe a case with mutations in two genes, lamin A/C (LMNA) and exostosin glycosyltransferase 2 (EXT2), which led to hereditary myopathy combined with multiple exostoses. CASE HISTORY: A 51-year-old German woman with a history of removal of multiple exostoses during childhood presented with proximal limb-girdle muscular dystrophy and a newly diagnosed cardiomyopathy with atrioventricular conduction block. Because her younger son had exostoses and her younger brother had died at age 44 after heart transplantation due to dilated cardiomyopathy, an autosomal dominant inheritance was suspected. RESULTS: Muscle biopsy revealed features of chronic myopathy associated with focal myofibrillar disintegration. Electron microscopy showed myonuclear, myofibrillar, and Z-disc alterations, accumulations of granulofilamentous material, and a large sporadic osmiophilic inclusion body reminiscent of a nemaline body. Mendeliome and Sanger sequencing detected both a c.1129>T LMNA mutation of known pathogenicity and a c.1101_1102delAG (E368Kfs*18) truncating EXT2 mutation in the patient and her affected son. DISCUSSION: The clinical, genetic, and muscle biopsy findings suggest that both mutations are pathogenic. The EXT2 mutation was most likely responsible for the multiple exostoses phenotype in mother and son, whereas the myopathy was probably caused by a combined effect of the LMNA and EXT2 mutations.

Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis: a translational cross-sectional study.

BACKGROUND: Stress hyperglycaemia (SHG) is a common complication in sepsis associated with poor outcome. Chemerin is an adipocytokine associated with inflammation and impaired glucose homeostasis in metabolic diseases such as type 2 diabetes (T2D). We aimed to investigate how alterations of circulating chemerin levels and corresponding visceral adipose tissue (VAT) expression are linked to glucose metabolism and prognosis in sepsis. METHODS: Clinical data and tissue samples were taken from a cross-sectional study including control, T2D and sepsis patients, all undergoing laparotomy. A second independent patient cohort of patients with sepsis was included to evaluate associations with prognosis. This was complemented by a murine model of peritoneal infection and a high-fat diet. We analysed circulating chemerin by enzyme-linked immunosorbent assay and VAT messenger RNA (mRNA) expression by real-time polymerase chain reaction. RESULTS: Circulating chemerin was increased in sepsis 1.69-fold compared with controls (p = 0.012) and 1.47-fold compared with T2D (p = 0.03). Otherwise, chemerin VAT mRNA expression was decreased in patients with sepsis (p = 0.006) and in septic diabetic animals (p = 0.009). Circulating chemerin correlated significantly with intra-operative glucose (r = 0.662; p = 0.01) and in trend with fasting glucose (r = 0.528; p = 0.052). After adjusting for body mass index or haemoglobin A1c, chemerin correlated in trend with insulin resistance evaluated using the logarithmised homeostasis model assessment of insulin resistance (r = 0.539, p = 0.071; r = 0.553, p = 0.062). Chemerin was positively associated with Acute Physiology and Chronic Health Evaluation II score in patients with sepsis (p = 0.036) and with clinical severity in septic mice (p = 0.031). In an independent study population, we confirmed association of chemerin with glucose levels in multivariate linear regression analysis (ß = 0.556, p = 0.013). In patients with sepsis with SHG, non-survivors had significantly lower chemerin levels than survivors (0.38-fold, p = 0.006), while in patients without SHG, non-survivors had higher chemerin levels, not reaching significance (1.64-fold, p = 0.089). No difference was apparent in patients with pre-existing T2D (p = 0.44). CONCLUSIONS: We show, for the first time to our knowledge, that chemerin is increased in sepsis and that it associates with impaired glucose metabolism and survival in these patients. It could be further evaluated as a biomarker to stratify mortality risk of patients with SHG.

Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies.

Potocki-Shaffer syndrome (PSS) is a contiguous gene disorder due to the interstitial deletion of band p11.2 of chromosome 11 and is characterized by multiple exostoses, parietal foramina, intellectual disability (ID), and craniofacial anomalies (CFAs). Despite the identification of individual genes responsible for multiple exostoses and parietal foramina in PSS, the identity of the gene(s) associated with the ID and CFA phenotypes has remained elusive. Through characterization of independent subjects with balanced translocations and supportive comparative deletion mapping of PSS subjects, we have uncovered evidence that the ID and CFA phenotypes are both caused by haploinsufficiency of a single gene, PHF21A, at 11p11.2. PHF21A encodes a plant homeodomain finger protein whose murine and zebrafish orthologs are both expressed in a manner consistent with a function in neurofacial and craniofacial development, and suppression of the latter led to both craniofacial abnormalities and neuronal apoptosis. Along with lysine-specific demethylase 1 (LSD1), PHF21A, also known as BHC80, is a component of the BRAF-histone deacetylase complex that represses target-gene transcription. In lymphoblastoid cell lines from two translocation subjects in whom PHF21A was directly disrupted by the respective breakpoints, we observed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional regulation. Our finding that disruption of PHF21A by translocations in the PSS region is associated with ID adds to the growing list of ID-associated genes that emphasize the critical role of transcriptional regulation and chromatin remodeling in normal brain development and cognitive function.

Treatment of elastase-induced intracranial aneurysms in New Zealand white rabbits by use of a novel neurovascular embolization stent device.

INTRODUCTION: This study aims to test a novel balloon expandable stent covered with a polytetrafluoroethylene membrane (neurovascular embolization cover (NEC), NFocus Neuromedical, Palo Alto, California) regarding angiographic and histologic aneurysm occlusion. Radiopacity, stent placement, navigation, flexibility, and intimal proliferation were also evaluated. METHODS: Eight aneurysms were induced in New Zealand white rabbits. Digital subtraction angiography (DSA) was performed directly after stent placement and after 5 and 10 min. Four and 8 weeks after stent placement, an intra-arterial DSA control was performed. The animals were then sacrificed and the aneurysms histologically evaluated. RESULTS: The radiopaque markers were clearly visible. Although all the stents were easily navigated into the subclavian artery, the limited flexibility of the stent resulted in straightening of the vessel in four cases. As a result, exact stent placement was achieved and acutely confirmed in only two cases. However, at sacrifice, angiographic and histologic occlusion was noted at follow-up in five aneurysms. CONCLUSION: In tortuous anatomy, the relative stiffness of the stent makes exact stent placement challenging. This may have been exacerbated by the movement of the vessels due to proximity to the heart in this model. Future studies should evaluate whether existing residual flow into an aneurysm lumen might lead to embolization without any additional treatment. Anticoagulation remains a very important part of aneurysm treatment with stents. The trend toward aneurysm occlusion by excluding it from the blood circulation seems a promising method in future endovascular therapy. The NEC device shows good potential.

Knowledge Transfer and Networking Upon Implementation of a Transdisciplinary Digital Health Curriculum in a Unique Digital Health Training Culture: Prospective Analysis.

Background: Digital health has been taught at medical faculties for a few years. However, in general, the teaching of digital competencies in medical education and training is still underrepresented. Objective: This study aims to analyze the objective acquisition of digital competencies through the implementation of a transdisciplinary digital health curriculum as a compulsory elective subject at a German university. The main subject areas of digital leadership and management, digital learning and didactics, digital communication, robotics, and generative artificial intelligence were developed and taught in a transdisciplinary manner over a period of 1 semester. Methods: The participants evaluated the relevant content of the curriculum regarding the competencies already taught in advance during the study, using a Likert scale. The participants' increase in digital competencies were examined with a pre-post test consisting of 12 questions. Statistical analysis was performed using an unpaired 2-tailed Student t test. A P value of <.05 was considered statistically significant. Furthermore, an analysis of the acceptance of the transdisciplinary approach as well as the application of an alternative examination method (term paper instead of a test with closed and open questions) was carried out. Results: In the first year after the introduction of the compulsory elective subject, students of human medicine (n=15), dentistry (n=3), and medical biotechnology (n=2) participated in the curriculum. In total, 13 participants were women (7 men), and 61.1% (n=11) of the participants in human medicine and dentistry were in the preclinical study stage (clinical: n=7, 38.9%). All the aforementioned learning objectives were largely absent in all study sections (preclinical: mean 4.2; clinical: mean 4.4; P=.02). The pre-post test comparison revealed a significant increase of 106% in knowledge (P<.001) among the participants. Conclusions: The transdisciplinary teaching of a digital health curriculum, including digital teaching methods, considers perspectives and skills from different disciplines. Our new curriculum facilitates an objective increase in knowledge regarding the complex challenges of the digital transformation of our health care system. Of the 16 student term papers arising from the course, robotics and artificial intelligence attracted the most interest, accounting for 9 of the submissions.

Expanding multimodal microscopy by high spectral resolution coherent anti-Stokes Raman scattering imaging for clinical disease diagnostics.

Over the past years fast label-free nonlinear imaging modalities providing molecular contrast of endogenous disease markers with subcellular spatial resolution have been emerged. However, applications of these imaging modalities in clinical settings are still at the very beginning. This is because single nonlinear imaging modalities such as second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) have only limited value for diagnosing diseases due to the small number of endogenous markers. Coherent anti-Stokes Raman scattering (CARS) microscopy on the other hand can potentially be added to SHG and TPEF to visualize a much broader range of marker molecules. However, CARS requires a second synchronized laser source and the detection of a certain wavenumber range of the vibrational spectrum to differentiate multiple molecules, which results in increased experimental complexity and often inefficient excitation of SHG and TPEF signals. Here we report the application of a novel near-infrared (NIR) fiber laser of 1 MHz repetition rate, 65 ps pulse duration, and 1 cm(-1) spectral resolution to realize an efficient but experimentally simple SGH/TPEF/multiplex CARS multimodal imaging approach for a label-free characterization of composition of complex tissue samples. This is demonstrated for arterial tissue specimens demonstrating differentiation of elastic fibers, triglycerides, collagen, myelin, cellular cytoplasm, and lipid droplets by analyzing the CARS spectra within the C-H stretching region only. A novel image analysis approach for multispectral CARS data based on colocalization allows correlating spectrally distinct pixels to morphologic structures. Transfer of this highly precise but compact and simple to use imaging approach into clinical settings is expected in the near future.

Tumor margin identification and prediction of the primary tumor from brain metastases using FTIR imaging and support vector machines.

Infrared spectroscopy enables the identification of tissue types based on their inherent vibrational fingerprint without staining in a nondestructive way. Here, Fourier transform infrared microscopic images were collected from 22 brain metastasis tissue sections of bladder carcinoma, lung carcinoma, mamma carcinoma, colon carcinoma, prostate carcinoma and renal cell carcinoma. The scope of this study was to distinguish the infrared spectra of carcinoma from normal tissue and necrosis and to use the infrared spectra of carcinoma to determine the primary tumor of brain metastasis. Data processing follows procedures that have previously been developed for the analysis of Raman images of these samples and includes the unmixing algorithm N-FINDR, segmentation by k-means clustering, and classification by support vector machines (SVMs). Upon comparison with the subsequent hematoxylin and eosin stained tissue sections of training specimens, correct classification rates of the first level SVM were 98.8% for brain tissue, 98.4% for necrosis and 94.4% for carcinoma. The primary tumors were correctly predicted with an overall rate of 98.7% for FTIR images of the training dataset by a second level SVM. Finally, the two level discrimination models were applied to four independent specimens for validation. Although the classification rates are slightly reduced compared to the training specimens, the majority of the infrared spectra of the independent specimens were assigned to the correct primary tumor. The results demonstrate the capability of FTIR imaging to complement histopathological tools for brain tissue diagnosis.

A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics.

The past years have seen increasing interest in nonlinear optical microscopic imaging approaches for the investigation of diseases due to the method's unique capabilities of deep tissue penetration, 3D sectioning and molecular contrast. Its application in clinical routine diagnostics, however, is hampered by large and costly equipment requiring trained staff and regular maintenance, hence it has not yet matured to a reliable tool for application in clinics. In this contribution implementing a novel compact fiber laser system into a tailored designed laser scanning microscope results in a small footprint easy to use multimodal imaging platform enabling simultaneously highly efficient generation and acquisition of second harmonic generation (SHG), two-photon excited fluorescence (TPEF) as well as coherent anti-Stokes Raman scattering (CARS) signals with optimized CARS contrast for lipid imaging for label-free investigation of tissue samples. The instrument combining a laser source and a microscope features a unique combination of the highest NIR transmission and a fourfold enlarged field of view suited for investigating large tissue specimens. Despite its small size and turnkey operation rendering daily alignment dispensable the system provides the highest flexibility, an imaging speed of 1 megapixel per second and diffraction limited spatial resolution. This is illustrated by imaging samples of squamous cell carcinoma of the head and neck (HNSCC) and an animal model of atherosclerosis allowing for a complete characterization of the tissue composition and morphology, i.e. the tissue's morphochemistry. Highly valuable information for clinical diagnostics, e.g. monitoring the disease progression at the cellular level with molecular specificity, can be retrieved. Future combination with microscopic probes for in vivo imaging or even implementation in endoscopes will allow for in vivo grading of HNSCC and characterization of plaque deposits towards the detection of high risk plaques.

In vivo characterization of atherosclerotic plaque depositions by Raman-probe spectroscopy and in vitro coherent anti-stokes Raman scattering microscopic imaging on a rabbit model.

Visualization as well as characterization of inner arterial plaque depositions is of vital diagnostic interest, especially for the early recognition of vulnerable plaques. Established clinical techniques provide valuable visual information but cannot deliver information about the chemical composition of individual plaques. Here, we employ Raman-probe spectroscopy to characterize the plaque compositions of arterial walls on a rabbit model in vivo, using a miniaturized filtered probe with one excitation and 12 collection fibers integrated in a 1 mm sleeve. Rabbits were treated with a cholesterol-enriched diet. The methodology can improve the efficiency of animal experiments and shows great potential for applications in cardiovascular research. In order to further characterize the plaque depositions visually, coherent anti-Stokes Raman scattering (CARS) microscopy images have been acquired and are compared with the Raman-probe results.

Advances in optical biopsy--correlation of malignancy and cell density of primary brain tumors using Raman microspectroscopic imaging.

Raman spectroscopy is a promising tool towards biopsy under vision as it provides label-free image contrast based on intrinsic vibrational spectroscopic fingerprints of the specimen. The current study applied the spectral unmixing algorithm vertex component analysis (VCA) to probe cell density and cell nuclei in Raman images of primary brain tumor tissue sections. Six Raman images were collected at 785 nm excitation that consisted of 61 by 61 spectra at a step size of 2 micrometers. After data acquisition the samples were stained with hematoxylin and eosin for comparison. VCA abundance plots coincided well with histopathological findings. Raman spectra of high grade tumor cells were found to contain more intense spectral contributions of nucleic acids than those of low grade tumor cells. Similarly, VCA endmember signatures of Raman images from high grade gliomas showed increased nucleic acid bands. Further abundance plots and endmember spectra were assigned to tissue containing proteins and lipids, and cholesterol microcrystals. Since no sample preparation is required, an important advantage of the Raman imaging methodology is that all tissue components can be observed - even those that may be lost in sample staining steps. The results demonstrate how morphology and chemical composition obtained by Raman imaging correlate with histopathology and provide complementary, diagnostically relevant information at the cellular level.

Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis.

We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle of human patients with peritoneal sepsis and a sepsis model of C57BL/6J mice. Patients undergoing open surgery were included in a cross-sectional study and blood and skeletal muscle samples were taken. Key markers of the UPR and cluster of differentiation 68 (CD68) as surrogate of inflammatory injury were evaluated by real-time PCR and histochemical staining. CD68 mRNA increased with sepsis in skeletal muscle of patients and animals (p < 0.05). Mainly the inositol-requiring enzyme 1α branch of the UPR was upregulated as shown by elevated X-box binding-protein 1 (XBP1u) and its spliced isoform (XBP1s) mRNA (p < 0.05, respectively). Increased expression of Gadd34 indicated activation of PRKR-Like Endoplasmic Reticulum Kinase (PERK) branch of the UPR, and was only observed in mice (p < 0.001) but not human study subjects. Selected cell death signals were upregulated in human and murine muscle, demonstrated by increased bcl-2 associated X protein mRNA and TUNEL staining (p < 0.05). In conclusion we provide a first characterization of the UPR in skeletal muscle in human sepsis.

Publication activities relating to digital teaching and learning in the GMS Journal for Medical Education - a descriptive analysis (1984-2020).

Aims and objectives: Digital teaching, learning and assessment have been part of medical education and continuing education for decades. The objective of this review paper is to highlight developments and perspectives in these areas in the GMS Journal for Medical Education (GMS JME). Methodology: In the spring of 2020, we conducted a systematic literature search of the Journal for Medical Education (JME) and analysed the articles with regard to different categories such as article type, digital tools used or mode of data collection. Results: Of the 132 articles analysed, 78 were digital interventions (53 of which were exploratory-descriptive), 28 were project descriptions, 16 were surveys of needs or equipment and 10 were concept papers. About one-third of the studies and project reports each dealt with virtual patients or case-based learning, whereas no articles were published on trends such as serious games or virtual reality. Overall, our analysis shows that in many respects, the studies on digital teaching were more broadly based, especially between 2006 and 2010, after which this trend tended to decline again. Conclusions: Our analysis shows that publications in the JME consider some key aspects of digital teaching in medical education and continuing education, such as educational videos or virtual patients. The variability of information and methods of presentation advocate the use of guidelines to optimise the quality of scientific papers. Furthermore, clues for future research topics and experimental study designs are identified.

Prospective study of p-[123I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma.

PURPOSE: The differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[123I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions. METHODS: This prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA intravenously after overnight fasting. SPECT images at 30 min and 3 h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging. RESULTS: Twenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%). CONCLUSION: In patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed.

A case with coincidental diagnosis of primary central nervous system lymphoma and lymph node sarcoidosis.

Primary central nervous system lymphoma (PCNSL) is rare. Clinical and histological differential diagnosis of systemic lymphoma and sarcoidosis continues to be a challenge. The first case report in the German and English literature of PCNSL and synchronous sarcoidosis is presented. Synchronous mediastinal lymphadenopathy suggestive of non-Hodgkin's lymphoma (NHL) or sarcoidosis was noted. Both conditions require alternative therapeutic and prognostic considerations to PCNSL. A regime of intrathecal and adjuvant systemic chemotherapy led to transient clinical improvement prior to the patient's demise through overwhelming sepsis and multiorgan failure. Post mortem findings confirmed synchronous PCNSL with mediastinal lymph node sarcoidosis.

The online inverted classroom model (oICM). A blueprint to adapt the inverted classroom to an online learning setting in medical and health education.

This article was migrated. The article was marked as recommended. The idea of this paper is to offer a blueprint, with that facilitators have a guide to set up a complete digital teaching scenario according to the latest insights of didactical research. The corona pandemic forced higher education institutions all around the world to radically shift their curricula from a mix of face-to-face and remote teaching methods to a fully remote curriculum. Though challenging, this time provides opportunities to implement new educational methods and improve the quality of digital teaching. The classical concept of the inverted classroom was modified to meet the special needs of online settings. The proposed online Inverted Classroom Model (oICM) includes the following phases: (1) pre-phase, (2) self-learning-phase, (3) Synchronous online face-to-face phase, (4) transfer-phase, (5) evaluation. Recommendations and potential tools are provided for each phase. The oICM is an innovative and easy to use approach to shape digital teaching and learning processes during and after the CoVid19 pandemic. This blueprint is developed by the committee "Digitalization" of the German Association for Medical Education (GMA) for facilitators without any prior experience with the ICM, but also for those who already teach in a traditional ICM.

Genome wide expression profiling identifies specific deregulated pathways in meningioma.

Genome-wide expression signatures improve the understanding of tumor biology. We performed expression profiling of 24 meningioma including 8 of each WHO grade and 2 dura controls analyzing 55.000 transcripts including 18.300 known genes. We compared expression in meningioma vs. dura, expression of low grade (WHO I) vs. higher-grade (WHO II and WHO III) tumors and expression of meningothelial and syncytial meningioma vs. fibroblastic meningioma. Overall expression was significantly decreased in meningioma compared to dura and in meningothelial and syncytial compared to fibroblastic meningioma. Gene expression was exemplarily confirmed by immunohistochemistry using independent samples. Applying our statistical gene set analysis toolkit "GeneTrail", we identified significantly deregulated biochemical pathways using Kyoto encyclopedia of genes and genomes and Transpath databases. Kyoto encyclopedia of genes and genomes pathways with decreased expression in meningioma included cell adhesion molecules (p<0.0001) and cytokine-cytokine receptor interactions (p<0.0001). Pathways with increased expression included several metabolic pathways. Extended expression profiling by a novel statistical gene set enrichment identified pathways that have previously not been associated with meningioma.

Metastatic glioblastoma cells use common pathways via blood and lymphatic vessels.

Generally, gliomas do not metastasize. Therefore, larger series are not available to investigate the pathways of tumour spread. Here, we present the case of a young man with a glioblastoma multiforme WHO grade IV and distant metastases in several tissues. The glioblastoma multiforme WHO grade IV of a young male patient recurred within a very short time along the surgical resection pathway within the temporalis muscle. After removal of the tumour bulk, the patient developed a distant intracranial tumour lesion around the contralateral ventricular system and a pulmonary tumour. Later on, the patient underwent an operation on a facial lesion representing a local extracranial glioblastoma recurrence and containing metastases within lymph nodes and lymphatic vessels. Our case report indicated a lymphatic pathway of metastasis, which could be demonstrated by our histopathological analysis. We suggest that altered gene expression stimulated by glioblastoma-environment interaction altered the properties of glioblastoma cells, whether caused by a spontaneous genetic shift or induced by factors provided by the extracranial tissue.