Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real-world study

Background: Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off). Patients and methods: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan–Meier method was used to estimate survival and the log-rank test to make comparisons. Results: Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16). Conclusions: Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy

Modeling misconceptions in knowledge space theory

Building intelligent tutoring systems (ITSs) that are aware of the students\u2019 misconceptions has been one of the ambitions for many of the approaches to computerized assessment of knowledge and learning. In the present article we extend knowledge space theory (KST) to mistakes and misconceptions. The proposed approach completes and extends the work initiated by J. Lukas (1997, Modellierung von Fehlkonzepten in einer algebraischen Wissensstruktur [Modeling misconceptions in an algebraic knowledge structure], Kognitionswissenschaft, 6(4), 196\u2013204) on the application of information systems in KST for modeling misconceptions. The approach is divided into a deterministic and a probabilistic part. The notion of a \u201cpolytomous skill map\u201d (PSM) represents the cornerstone of the deterministic part. Properties of the PSM are established that assure a consistent link between item responses on the one hand and the (correct or buggy) cognitive rules applied by an individual on the other hand. A weaker notion of information system (named a \u201ccognitive rule system\u201d) is proposed for representing two types of dependencies among cognitive rules: precedence and compatibility. The probabilistic part consists of an extension of the basic local independence model to more than two response alternatives. This model can be used for knowledge diagnoses, as well as for empirically testing the deterministic assumptions from a PSM. An empirical application of this probabilistic model to the responses of 331 university students is illustrated and discussed using two different PSMs

Does green manure improve soil quality in a dry vineyard of Lake Garda?

Climate change and rainfall reduction have a negative effect on soil quality, that is the capability of maintaining biological productivity, environmental quality and promoting animal and plant health. Therefore, seeking solutions able to mitigate these effects is essential. This study, carried out in a dry vineyard in the Lake Garda area, is part of a project funded by GAL GARDAVALSABBIA2020 and analyses the effect of green manure on soil quality, assessed by chemical (nutrient availability) and biological (soil biological activity and biodiversity of microarthropod community) indicators. The vineyard was divided into three plots: CI (control with permanent grass), M1 (green manure mix enriched with legumes) and M2 (balanced green manure mix). After a year, green manure, even before mulching, contributed to sequester and gradually release nutrients during vine growing season, especially in M2. This was highlighted by the higher available concentrations of Mg, P and N in M2 than in the others. Additionally, legumes contributed to enrich of nitrogen the soil of plots with green manure, thanks to the nitrogen fixation by the symbiont bacteria. Biological activity measured as dynamic of soil respiration was greater in plots with green manure, although undergoing the combined effect of temperature and humidity. The microarthropod biodiversity indices showed higher values in autumn than in summer, being affected by seasonality; however, autumn increase was significant only in M1 and M2. These preliminary results show how green manure contributes to improving soil quality already after only one year of study, mitigating the negative effects of aridity

A class of k-modes algorithms for extracting knowledge structures from data

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