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Abstract Background Gliomas are tumours arising mostly from astrocytic or oligodendrocytic precursor cells. These tumours are classified according to the updated WHO classification from 2021 in 4 grades depending on molecular and histopathological criteria. Despite novel multimodal therapeutic approaches, the vast majority of gliomas (WHO grade III and IV) are not curable. The circadian clock is an important regulator of numerous cellular processes and its dysregulation had been found during the progression of many cancers, including gliomas. Results In this study, we explore expression patterns of clock-controlled genes in low-grade glioma (LGG) and glioblastoma multiforme (GBM) and show that a set of 45 clock-controlled genes can be used to distinguish GBM from normal tissue. Subsequent analysis identified 17 clock-controlled genes with a significant association with survival. The results point to a loss of correlation strength within elements of the circadian clock network in GBM compared to LGG. We further explored the progression patterns of mutations in LGG and GBM, and showed that tumour suppressor APC is lost late both in LGG and GBM. Moreover, HIF1A, involved in cellular response to hypoxia, exhibits subclonal losses in LGG, and TERT, involved in the formation of telomerase, is lost late in the GBM progression. By examining multi-sample LGG data, we find that the clock-controlled driver genes APC, HIF1A, TERT and TP53 experience frequent subclonal gains and losses. Conclusions Our results show a higher level of disrgulation at the gene expression level in GBM compared to LGG, and indicate an association between the differentially expressed clock-regulated genes and patient survival in both LGG and GBM. By reconstructing the patterns of progression in LGG and GBM, our data reveals the relatively late gains and losses of clock-regulated glioma drivers. Our analysis emphasizes the role of clock-regulated genes in glioma development and progression. Yet, further research is needed to asses their value in the development of new treatments.

Abstract Background Antimicrobial stewardship (AMS) strategies worldwide focus on optimising the use of antibiotics. Selective susceptibility reporting is recommended as an effective AMS tool although there is a lack of representative studies investigating the impact of selective susceptibility reporting on antibiotic use. The aim of this study was to investigate the impact of selective susceptibility reporting of Staphylococcus aureus (S. aureus) on antibiotic consumption. Enhancing the use of narrow-spectrum beta-lactam antibiotics such as flucloxacillin/cefazolin/cefalexin is one of the main goals in optimising antibiotic therapy of S. aureus infections. Methods This interventional study with control group was conducted at a tertiary care hospital in Germany. During the one-year interventional period susceptibility reports for all methicillin-sensitive S. aureus (MSSA) were restricted to flucloxacillin/cefazolin/cefalexin, trimethoprim-sulfamethoxazole, clindamycin, gentamicin and rifampin/fosfomycin, instead of reporting all tested antibiotics. The impact of implementing selective reporting was analysed by monitoring total monthly antibiotic consumption in our hospital and in a reference hospital (recommended daily dose/100 occupied bed days: RDD/100 BD), as well as on an individual patient level by analysing days of therapy adjusted for bed days (DOT/ 100 BD) for patients with S. aureus bacteremia (SAB) and respectively skin and soft tissue infections (SSTI). Results MSSA-antibiograms were acquired for 2836 patients. The total use of narrow-spectrum beta-lactams more than doubled after implementing selective reporting (from 1.2 to 2.8 RDD/100 BD, P