Methodological Challenges for Measuring Behavioral Changes in a Longitudinal Travel Survey Under Pandemic Conditions

The outbreak of the COVID-19 pandemic has had an enormous impact on everyday life. In an attempt to stop the virus spread, unprecedented containment measures are being taken worldwide. These preventive measures are consequently affecting everyone\u27s life and how we move. Equally remarkable is the speed at which these observed and massive changes occur and the lack of statistical evidence. In the annual cycle, the German Mobility Panel (MOP) launched an additional questionnaire for the general population, containing approximately 4,000 respondents. This paper provides insights into the MOP data quality issues and changes in daily travel under pandemic conditions

Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy

Purpose!#!The role of streptozocin-based chemotherapy (STZ CTx) in advanced, well-differentiated pancreatic neuroendocrine tumours (PanNET) and the best sequence of treatments in advanced PanNET are unclear. We examined the outcomes after STZ CTx in patients who had been selected according to the current therapeutic guidelines.!##!Methods!#!Data from 50 PanNET patients consecutively treated with STZ CTx between 2010 and 2018 were analysed. The endpoints of the study were the objective-response rate (ORR), progression-free survival (PFS), and overall survival (OS).!##!Results!#!STZ CTx was the first-line treatment in 54% of patients. The PanNET grades were as follows: 6% G1, 88% G2, and 6% well-differentiated G3. The ORR was 38%. Stable disease was the best response in 38% of patients and 24% showed progressive disease. Treatment was discontinued because of toxicity in one patient. Median PFS and OS were 12 (95% confidence interval (CI), 8.5-15.5) and 38 months (95% CI, 20.4-55.6), respectively. In the Kaplan-Meier analysis, the median OS was 89 months (95% CI, 34.9-143.1) for STZ CTx as first-line therapy compared with 22 months (95% CI, 19.3-24.7; p = 0.001, log-rank test) for subsequent lines. Bone metastases negatively impacted survival (HR, 2.71, p = 0.009, univariate analysis, HR, 2.64, p = 0.015, multivariate analysis, and Cox regression).!##!Conclusions!#!In patients selected according to current guidelines, PFS, and OS after STZ CTx were lower than previously reported, whereas ORR was unchanged. First-line treatment was positively associated with OS and the presence of bone metastases was negatively associated with OS. Pre-treatment with targeted or peptide-receptor radionuclide therapy did not alter ORR, PFS, or OS

Molecular and Enzymatic Characterization of Flavonoid 3′-Hydroxylase of Malus × domestica

Malus × domestica (apple) accumulates particularly high amounts of dihydrochalcones in various tissues, with phloridzin (phloretin 2′-O-glucoside) being prevalent, although small amounts of 3-hydroxyphloretin and 3-hydroxyphloridzin are also constitutively present. The latter was shown to correlate with increased disease resistance of transgenic M. × domestica plants. Two types of enzymes could be involved in 3-hydroxylation of dihydrochalcones: polyphenol oxidases or the flavonoid 3′-hydroxylase (F3′H), which catalyzes B-ring hydroxylation of flavonoids. We isolated two F3′H cDNA clones from apple leaves and tested recombinant Malus F3′Hs for their substrate specificity. From the two isolated cDNA clones, only F3′HII encoded a functionally active enzyme. In the F3′HI sequence, we identified two putatively relevant amino acids that were exchanged in comparison to that of a previously published F3′HI. Site directed mutagenesis, which exchanged an isoleucine into methionine in position 211 restored the functional activity, which is probably because it is located in an area involved in interaction with the substrate. In contrast to high activity with various flavonoid substrates, the recombinant enzymes did not accept phloretin under assay conditions, making an involvement in the dihydrochalcone biosynthesis unlikely