IVDCheckR - simplifying documentation for laboratory developed tests according to IVDR requirements by introducing a new digital tool.

OBJECTIVES: A recent challenge for clinical laboratories is the lack of clear guidelines for handling significant modifications of CE-marked assays. The modifications may involve, for example, extending measurement intervals, changing dilution procedures or using non-validated sample materials. The challenge arises due to the amended Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), which is now poised for implementation, despite the extended transition periods. The IVDR application imposes challenges not only for diagnostic companies but also for clinical laboratories when using laboratory developed tests (LDTs), often referred to as in-house assays. In this context, a coherent and meticulously structured LDT documentation is highly beneficial. While laboratories are obliged to meet the IVDR requirements, the absence of a streamlined framework or guideline hampers the ability to gain a comprehensive overview on the requirements and possible options for their fulfilment. METHODS: To address this issue, we introduce a web based digital tool powered by an R Shiny web application. This tool facilitates a seamless implementation of IVDR requirements for LDTs across diverse laboratory environments in terms of their transparency and validity. Our approach focuses on adequate handling of significant modifications of CE-marked in vitro diagnostic medical devices (IVD). RESULTS: IVDRCheckR is an open-source tool that is easily accessible and free from system dependencies. The tool promotes a seamless process and a guide to enhance transparency, reliability, and validity of laboratory examination results based on LDTs. Additionally, the tool further provides modules for evaluating quality control data and quantitative method comparison data. CONCLUSIONS: Our Shiny web application-based platform is a digitised, user-friendly tool that simplifies the documentation for LDTs according to IVDR requirements with special emphasis on solutions for handling modifications to CE-marked assays.

Resting-state brain signal complexity discriminates young healthy APOE e4 carriers from non-e4 carriers.

It is well established that the e4 allele of the APOE gene is associated with impaired brain functionality and cognitive decline in humans at elder age. However, it is controversial whether and how the APOE e4 allele is associated with superior brain function among young healthy individuals, thus indicates a case of antagonistic pleiotropy of APOE e4 allele. Signal complexity is a critical aspect of brain activity that has been associated with brain function. In this study, the multiscale entropy (MSE) of resting-state EEG signals among a sample of young healthy adults (N = 260) as an indicator of brain signal complexity was investigated. It was of interest whether MSE differs across APOE genotype groups while age and education level were controlled for and whether the APOE genotype effect on MSE interacts with MSE time scale, as well as EEG recording condition. Results of linear mixed models indicate overall larger MSE in APOE e4 carriers. This genotype-dependent difference is larger at high as compared with low time scales. The interaction effect between APOE genotype and recording condition indicates increased between-state MSE change in young healthy APOE e4 carriers as compared with non-carriers. Because higher complexity is commonly taken to be associated with better cognitive functioning, the present results complement previous findings and therefore point to a pleiotropic spectrum of the APOE gene polymorphism.

Exploring Neural Signal Complexity as a Potential Link between Creative Thinking, Intelligence, and Cognitive Control.

Functional connectivity studies have demonstrated that creative thinking builds upon an interplay of multiple neural networks involving the cognitive control system. Theoretically, cognitive control has generally been discussed as the common basis underlying the positive relationship between creative thinking and intelligence. However, the literature still lacks a detailed investigation of the association patterns between cognitive control, the factors of creative thinking as measured by divergent thinking (DT) tasks, i.e., fluency and originality, and intelligence, both fluid and crystallized. In the present study, we explored these relationships at the behavioral and the neural level, based on N = 77 young adults. We focused on brain-signal complexity (BSC), parameterized by multi-scale entropy (MSE), as measured during a verbal DT and a cognitive control task. We demonstrated that MSE is a sensitive neural indicator of originality as well as inhibition. Then, we explore the relationships between MSE and factor scores indicating DT and intelligence. In a series of across-scalp analyses, we show that the overall MSE measured during a DT task, as well as MSE measured in cognitive control states, are associated with fluency and originality at specific scalp locations, but not with fluid and crystallized intelligence. The present explorative study broadens our understanding of the relationship between creative thinking, intelligence, and cognitive control from the perspective of BSC and has the potential to inspire future BSC-related theories of creative thinking.

What Does Temporal Brain Signal Complexity Reveal About Verbal Creativity?

Recent empirical evidence reveals that creative idea generation builds upon an interplay of multiple neural networks. Measures of temporal complexity yield important information about the underlying mechanisms of these co-activated neural networks. A few neurophysiological studies investigated brain signal complexity (BSC) during the production of creative verbal associations and resting states, aiming to relate it with creative task performance. However, it is unknown whether the complexity of brain signals can distinguish between productions of typical and original verbal associations. In the present study, we investigated verbal creativity with multiscale entropy (MSE) of electroencephalography (EEG) signals, which quantifies complexity over multiple timescales, capturing unique dynamic features of neural networks. MSE was measured in verbal divergent thinking (DT) states while emphasizing on producing either typical verbal associations or original verbal associations. We hypothesized that MSE differentiates between brain states characterizing the production of typical and original associations and is a sensitive neural marker of individual differences in producing original associations. Results from a sample of N = 92 young adults revealed slightly higher average MSE for original as compared with typical association production in small and medium timescales at frontal electrodes and slightly higher average MSE for typical association production in higher timescales at parietal electrodes. However, measurement models failed to uncover specificity of individual differences as MSE in typical vs. original associations was perfectly correlated. Hence, individuals with higher MSE in original association condition also exhibit higher MSE during the production of typical associations. The difference between typical and original association MSE was not significantly associated with human-rated originality of the verbal associations. In sum, we conclude that MSE is a potential marker of creative verbal association states, but replications and extensions are needed, especially with respect to the brain-behavior relationships.

The reliability and psychometric structure of Multi-Scale Entropy measured from EEG signals at rest and during face and object recognition tasks.

BACKGROUND: Multi-Scale Entropy (MSE) is a widely used marker of Brain Signal Complexity (BSC) at multiple temporal scales. METHODOLOGICAL IMPROVEMENT: There is no systematic research addressing the psychometric quality and reliability of MSE. It is unknown how recording conditions of EEG signals affect individual differences in MSE. These gaps can be addressed by means of Structural Equation Modeling (SEM). RESULTS: Based on a large sample of 210 young adults, we estimated measurement models for MSE derived from multiple epochs of EEG signal measured during resting state conditions with closed and open eyes, and during a visual task with multiple experimental manipulations. Factor reliability estimates, quantified by the McDonald's ω coefficient, are high at lower and acceptable at higher time scales. Above individual differences in signal entropy observed across all recording conditions, persons specifically differ with respect to their BSC in open eyes resting state condition as compared with closed eyes state, and in task processing state MSE as compared with resting state. COMPARISON WITH EXISTING METHODS: By means of SEM, we decomposed individual differences in BSC into different factors depending on the recording condition of EEG signals. This goes beyond existing methods that aim at estimating average MSE differences across recording conditions, but do not address whether individual differences are additionally affected by the type of EEG recording condition. CONCLUSION: Eyes closed and open and task conditions strongly influence individual differences in MSE. We provide recommendations for future studies aiming to address BSC using MSE as a neural marker of cognitive abilities.