BACKGROUND: Plants, like all living organisms, metamorphose their bodies during their lifetime. All the developmental and growth events in a plant's life are connected to specific points in time, be it seed germination, seedling emergence, the appearance of the first leaf, heading, flowering, fruit ripening, wilting, or death. The onset of automated phenotyping methods has brought an explosion of such time-to-event data. Unfortunately, it has not been matched by an explosion of adequate data analysis methods. RESULTS AND DISCUSSION: In this paper, we introduce the Bayesian approach towards time-to-event data in plant biology. As a model example, we use seedling emergence data of maize under control and stress conditions but the Bayesian approach is suitable for any time-to-event data (see the examples above). In the proposed framework, we are able to answer key questions regarding plant emergence such as these: (1) Do seedlings treated with compound A emerge earlier than the control seedlings? (2) What is the probability of compound A increasing seedling emergence by at least 5 percent? CONCLUSION: Proper data analysis is a fundamental task of general interest in life sciences. Here, we present a novel method for the analysis of time-to-event data which is applicable to many plant developmental parameters measured in field or in laboratory conditions. In contrast to recent and classical approaches, our Bayesian computational method properly handles uncertainty in time-to-event data and it is capable to reliably answer questions that are difficult to address by classical methods.

• Klíčová slova
• Bayesian inference, Data analysis, Plant development, Plant phenotyping, Statistics, Survival analysis, Time-to-event data, Uncertainty,
• Publikační typ
• časopisecké články MeSH

Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models. The method is applied to two datasets from immunogenicity sub-studies of vaccine phase 3 clinical trials for zoster and dengue vaccines. Results show that using immunogenicity-based estimation of efficacy in subgroups using time-to-event models is more precise than the standard estimation. Incorporating immune correlate data in time-to-event models improves precision in estimating efficacy (i.e., yields narrower confidence intervals), which can assist vaccine developers and public health authorities in making informed decisions.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Developmental coordination disorder (DCD) is described as a motor skill disorder characterized by a marked impairment in the development of motor coordination abilities that significantly interferes with performance of daily activities and/or academic achievement. Since some electrophysiological studies suggest differences between children with/without motor development problems, we prepared an experimental protocol and performed electrophysiological experiments with the aim of making a step toward a possible diagnosis of this disorder using the event-related potentials (ERP) technique. The second aim is to properly annotate the obtained raw data with relevant metadata and promote their long-term sustainability. RESULTS: The data from 32 school children (16 with possible DCD and 16 in the control group) were collected. Each dataset contains raw electroencephalography (EEG) data in the BrainVision format and provides sufficient metadata (such as age, gender, results of the motor test, and hearing thresholds) to allow other researchers to perform analysis. For each experiment, the percentage of ERP trials damaged by blinking artifacts was estimated. Furthermore, ERP trials were averaged across different participants and conditions, and the resulting plots are included in the manuscript. This should help researchers to estimate the usability of individual datasets for analysis. CONCLUSIONS: The aim of the whole project is to find out if it is possible to make any conclusions about DCD from EEG data obtained. For the purpose of further analysis, the data were collected and annotated respecting the current outcomes of the International Neuroinformatics Coordinating Facility Program on Standards for Data Sharing, the Task Force on Electrophysiology, and the group developing the Ontology for Experimental Neurophysiology. The data with metadata are stored in the EEG/ERP Portal.

• Klíčová slova
• developmental coordination disorder, electroencephalography, event-related potentials, reaction time, visual and audio stimulation,
• MeSH
• akustická stimulace MeSH
• datové kurátorství MeSH
• dítě MeSH
• elektroencefalografie MeSH
• evokované potenciály MeSH
• komorbidita MeSH
• kvantitativní znak dědičný MeSH
• lidé MeSH
• počítačová simulace MeSH
• poruchy motorických dovedností diagnóza   MeSH
• reakční čas MeSH
• reprodukovatelnost výsledků MeSH
• software MeSH
• světelná stimulace MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The research on using process mining in learning analytics of cybersecurity exercises relies on datasets that reflect the real behavior of trainees. Although modern cyber ranges, in which training sessions are organized, can collect behavioral data in the form of event logs, the organization of such exercises is laborious. Moreover, the collected raw data has to be processed and transformed into a specific format required by process mining techniques. We present two datasets with slightly different characteristics. While the first exercise with 52 participants was not limited in time, the second supervised exercise with 42 trainees lasted two hours. Also, the cybersecurity tasks were slightly different. A total of 11757 events were collected. Of these, 3597 were training progress events, 5669 were Bash commands, and 2491 were Metasploit commands. Joint CSV files distilled from the raw event data can be used as input for existing process mining tools.

• Klíčová slova
• Education, Host-based data collection, Learning analytics, Puzzle-based gamification,
• Publikační typ
• časopisecké články MeSH

Ecological Momentary Assessment (EMA) enables the real-time capture of health-related behaviours, their situational contexts, and associated subjective experiences. This study aimed to evaluate the feasibility of an EMA targeting physical and eating behaviours, optimise its protocol, and provide recommendations for future large-scale EMA data collections. The study involved 52 participants (age 31±9 years, 56% females) from Czechia, France, Germany, and Ireland completing a 9-day free-living EMA protocol using the HealthReact platform connected to a Fitbit tracker. The EMA protocol included time-based (7/day), event-based (up to 10/day), and self-initiated surveys, each containing 8 to 17 items assessing physical and eating behaviours and related contextual factors such as affective states, location, and company. Qualitative insights were gathered from post-EMA feedback interviews. Compliance was low (median 49%), particularly for event-based surveys (median 34%), and declined over time. Many participants were unable or unwilling to complete surveys in certain contexts (e.g., when with family), faced interference with their daily schedules, and encountered occasional technical issues, suggesting the need for thorough initial training, an individualised protocol, and systematic compliance monitoring. The number of event-based surveys was less than desired for the study, with a median of 2.4/day for sedentary events, when 4 were targeted, and 0.9/day for walking events, when 3 were targeted. Conducting simulations using participants' Fitbit data allowed for optimising the triggering rules, achieving the desired median number of sedentary and walking surveys (3.9/day for both) in similar populations. Self-initiated reports of meals and drinks yielded more reports than those prompted in time-based and event-based EMA surveys, suggesting that self-initiated surveys might better reflect actual eating behaviours. This study highlights the importance of assessing feasibility and optimising EMA protocols to enhance subsequent compliance and data quality. Conducting pre-tests to refine protocols and procedures, including simulations using participants' activity data for optimal event-based triggering rules, is crucial for successful large-scale data collection in EMA studies of physical and eating behaviours.

• MeSH
• cvičení * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• okamžité posouzení v přirozeném prostředí * MeSH
• průzkumy a dotazníky MeSH
• sběr dat * metody   MeSH
• stravovací zvyklosti * MeSH
• studie proveditelnosti MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Visual cognitive responses (P300) to moving stimuli were tested in 36 subjects with the aim to find the normal range of P300 parameters. Concomitantly, the circadian intra-individual variability of the P300 was studied in a subgroup of 6 subjects. Visual stimuli consisted of either coherent (frequent stimulus) or non-coherent motion (random stimulus). The oddball paradigm was applied for recording cognitive responses. P300 to rare stimuli had an average latency of 447.3 +/- 46.6 ms and amplitude of 12.9 +/- 6.0 microV. The average reaction time was in the range from 322 to 611 ms and there was no correlation between the reaction time and P300 latency. We did not find any significant circadian changes of the P300 parameters in the 6 subjects tested four times during the same day. Cognitive (event-related) responses (P300) displayed distinctly greater inter-individual variability (S.D. of 50 ms) when compared with pattern-reversal and motion-onset VEPs (S.D. of 6.0 ms and 14 ms, respectively). For this reason, the clinical use of P300 elicited by this kind of visual stimuli seems to be rather restricted and the evaluation of its intra-individual changes is preferable.

• MeSH
• cirkadiánní rytmus fyziologie   MeSH
• dospělí MeSH
• kognitivní evokované potenciály P300 fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• reakční čas fyziologie   MeSH
• světelná stimulace MeSH
• vnímání pohybu fyziologie   MeSH
• zrakové evokované potenciály fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Motivated by a longitudinal oral health study, we propose a flexible modeling approach for clustered time-to-event data, when the response of interest can only be determined to lie in an interval obtained from a sequence of examination times (interval-censored data) and on top of that, the determination of the occurrence of the event is subject to misclassification. The clustered time-to-event data are modeled using an accelerated failure time model with random effects and by assuming a penalized Gaussian mixture model for the random effects terms to avoid restrictive distributional assumptions concerning the event times. A general misclassification model is discussed in detail, considering the possibility that different examiners were involved in the assessment of the occurrence of the events for a given subject across time. A Bayesian implementation of the proposed model is described in a detailed manner. We additionally provide empirical evidence showing that the model can be used to estimate the underlying time-to-event distribution and the misclassification parameters without any external information about the latter parameters. We also provide results of a simulation study to evaluate the effect of neglecting the presence of misclassification in the analysis of clustered time-to-event data.

• Klíčová slova
• Bayesian approach, Mismeasured continuous response, Multivariate survival data,
• MeSH
• Bayesova věta MeSH
• časové faktory MeSH
• dítě MeSH
• lidé MeSH
• longitudinální studie * MeSH
• orální zdraví statistika a číselné údaje   MeSH
• počítačová simulace MeSH
• shluková analýza * MeSH
• statistické modely * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Untargeted metabolomic approaches offer new opportunities for a deeper understanding of the molecular events related to toxic exposure. This study proposes a metabolomic investigation of biochemical alterations occurring in urine as a result of dioxin toxicity. Urine samples were collected from Czech chemical workers submitted to severe dioxin occupational exposure in a herbicide production plant in the late 1960s. Experiments were carried out with ultra-high pressure liquid chromatography (UHPLC) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry. A chemistry-driven feature selection was applied to focus on steroid-related metabolites. Supervised multivariate data analysis allowed biomarkers, mainly related to bile acids, to be highlighted. These results supported the hypothesis of liver damage and oxidative stress for long-term dioxin toxicity. As a second step of data analysis, the information gained from the urine analysis of Victor Yushchenko after his poisoning was examined. A subset of relevant urinary markers of acute dioxin toxicity from this extreme phenotype, including glucuro- and sulfo-conjugated endogenous steroid metabolites and bile acids, was assessed for its ability to detect long-term effects of exposure. The metabolomic strategy presented in this work allowed the determination of metabolic patterns related to dioxin effects in human and the discovery of highly predictive subsets of biologically meaningful and clinically relevant compounds. These results are expected to provide valuable information for a deeper understanding of the molecular events related to dioxin toxicity. Furthermore, it presents an original methodology of data dimensionality reduction by using extreme phenotype as a guide to select relevant features prior to data modeling (biologically driven data reduction).

• Klíčová slova
• Biomarkers, Dimensionality reduction, Dioxin, Extreme phenotype, Steroidomics, Toxicity,
• MeSH
• biologické markery moč   MeSH
• data mining MeSH
• játra účinky léků   metabolismus   MeSH
• lidé MeSH
• metabolomika metody   MeSH
• monitorování životního prostředí metody   MeSH
• oxidační stres účinky léků   MeSH
• polychlorované dibenzodioxiny toxicita   MeSH
• pracovní expozice analýza   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• polychlorované dibenzodioxiny MeSH

The scarcity of long-term observational data has limited the use of statistical or machine-learning techniques for predicting intraannual ecological variation. However, time-stamped citizen-science observation records, supported by media data such as photographs, are increasingly available. In the present article, we present a novel framework based on the concept of relative phenological niche, using machine-learning algorithms to model observation records as a temporal sample of environmental conditions in which the represented ecological phenomenon occurs. Our approach accurately predicts the temporal dynamics of ecological events across large geographical scales and is robust to temporal bias in recording effort. These results highlight the vast potential of citizen-science observation data to predict ecological phenomena across space, including in near real time. The framework is also easily applicable for ecologists and practitioners already using machine-learning and statistics-based predictive approaches.

• Klíčová slova
• citizen science, digital data, ecological monitoring, phenological niche, seasonality prediction,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. OBJECTIVE: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. METHODS: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. RESULTS: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006). CONCLUSION: Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.

• Klíčová slova
• disease modifying treatment (DMT), disease registry, multiple sclerosis, real world evidence (RWE), treatment switching,
• Publikační typ
• časopisecké články MeSH