Background Glioblastoma is the most common primary malignancy of the central nervous system with dismal prognosis. Genomic signatures classify isocitrate dehydrogenase 1 (IDH)-wildtype glioblastoma into three subtypes: proneural, mesenchymal and classical. Dasatinib, an inhibitor of proto-oncogene kinase Src (SRC), is one of many therapeutics which, despite promising preclinical results, has failed to improve overall survival in glioblastoma patients in clinical trials. We examined whether glioblastoma subtypes differ in their response to dasatinib and could hence be evaluated for patient enrichment strategies in clinical trials. Methods We carried out in silico analyses on glioblastoma gene expression (TCGA) and single-cell RNA-Seq data. In addition, in vitro experiments using glioblastoma stem-like cells (GSCs) derived from primary patient tumors were performed, with complementary gene expression profiling and immunohistochemistry analysis of tumor samples. Results Patients with the mesenchymal subtype of glioblastoma showed higher SRC pathway activation based on gene expression profiling. Accordingly, mesenchymal GSCs were more sensitive to SRC inhibition by dasatinib compared to proneural and classical GSCs. Notably, SRC phosphorylation status did not predict response to dasatinib treatment. Furthermore, serpin peptidase inhibitor clade H member 1 (SERPINH1), a collagen related heat-shock protein associated with cancer progression, was shown to correlate with dasatinib response and with the mesenchymal subtype. Conclusion This work highlights further molecular-based patient selection strategies in clinical trials and suggests the mesenchymal subtype as well as SERPINH1 to be associated with response to dasatinib. Our findings indicate that stratification based on gene expression subtyping should be considered in future dasatinib trials.

Infections caused by pathogens of the Mycobacterium tuberculosis complex, i. e., tuberculosis (TB), and the non-infectious, autoimmune disease sarcoidosis are among the most common granulomatous diseases worldwide. Typically, the lung is the primary site of infection and manifestation, respectively which makes the two diseases important differential diagnoses. Both diseases can affect virtually all organ systems, albeit with significantly lower incidence. Case presentation We report the case of a 50-year-old Indian man presenting with a tuberculous perihepatic abscess and a systemic inflammatory response after being diagnosed with neurosarcoidosis presenting as a single granuloma in the frontal lobe with lymphadenopathy in 2014. On day of admission the patient presented with right upper abdominal pain and fever for two weeks. With increased inflammatory parameters in serum and after finding of external CT images, a perihepatic abscess was suspected. This encapsulated cave was drained percutaneously under CT control. A high concentration of acid-fast rods was detected using ZN, PCR was positive for M. tuberculosis. Several samples of sputum and urine were microscopically negative but yielded growth of Mycobacteria after four weeks. Discussion This is a case presenting with two different granulomatous diseases, each of which manifested itself in an atypical form. The tuberculous liver abscess might either be explained as a flare-up of latent tuberculosis under azathioprine therapy or as a reinfection acquired during one of several visits in the high-prevalence country India. In addition, it must be discussed whether the cerebral granuloma in 2014 could have been an early stage of tuberculous granuloma. Sensitivity of ZN staining is significantly reduced in cerebral samples, and negative PCR-results might be due to low germ load or methodical issues, e. g., decreased sensitivity in formalin fixated samples.

In this article, engagement in the Fridays for Future (FFF) movement is examined from an educational point of view. Framing active engagement in the FFF movement theoretically as a learning opportunity, selected findings from an online survey (n=194) are presented. In a theoretical perspective, specific characteristics of the FFF movement are outlined with regard to learning and educational processes. Starting point of the empirical analyses are different possibilities of participation. On the one hand, an insight into the various participation formats is given. On the other hand, it is asked what motivates those involved to work for sustainable development and whether differences in motives and self-efficacy can be found depending on the form of participation. The results will be linked back to the theoretical frame of reference and discussed further.