BACKGROUND: Recent studies, including the TENSION trial, support the use of endovascular thrombectomy (EVT) in acute ischemic stroke with large infarct (Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5). OBJECTIVE: To evaluate the cost-effectiveness of EVT compared with best medical care (BMC) alone in this population from a German healthcare payer perspective. METHODS: A short-term decision tree and a long-term Markov model (lifetime horizon) were used to compare healthcare costs and quality-adjusted life years (QALYs) between EVT and BMC. The effectiveness of EVT was reflected by the 90-day modified Rankin Scale (mRS) outcome from the TENSION trial. QALYs were based on published mRS-specific health utilities (EQ-5D-3L indices). Long-term healthcare costs were calculated based on insurance data. Costs (reported in 2022 euros) and QALYs were discounted by 3% annually. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties. RESULTS: Compared with BMC, EVT yielded higher lifetime incremental costs (€24 257) and effects (1.41 QALYs), resulting in an ICER of €17 158/QALY. The results were robust to parameter variation in sensitivity analyses (eg, 95% probability of cost-effectiveness was achieved at a willingness to pay of >€22 000/QALY). Subgroup analyses indicated that EVT was cost-effective for all ASPECTS subgroups. CONCLUSIONS: EVT for acute ischemic stroke with established large infarct is likely to be cost-effective compared with BMC, assuming that an additional investment of €17 158/QALY is deemed acceptable by the healthcare payer.

• MeSH
• analýza nákladů a výnosů * metody   MeSH
• endovaskulární výkony * ekonomika   metody   MeSH
• ischemická cévní mozková příhoda * ekonomika   chirurgie   epidemiologie   MeSH
• kvalitativně upravené roky života MeSH
• lidé MeSH
• Markovovy řetězce * MeSH
• rozhodovací stromy * MeSH
• senioři MeSH
• trombektomie * ekonomika   metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Německo MeSH

In this study, we investigated the stability of the fully activated conformation of the orexin receptor 2 (OX2R) embedded in a pure POPC bilayer using MD simulations. Various thermodynamic ensembles (i.e., NPT, NVT, NVE, NPAT, μVT, and NPγT) were employed to explore the dynamical heterogeneity of the system in a comprehensive way. In addition, informational similarity metrics (e.g., Jensen-Shannon divergence) as well as Markov state modeling approaches were utilized to elucidate the receptor kinetics. Special attention was paid to assessing surface tension within the simulation box, particularly under NPγT conditions, where 21 nominal surface tension constants were evaluated. Our findings suggest that traditional thermodynamic ensembles such as NPT may not adequately control physical properties of the POPC membrane, impacting the plausibility of the OX2R model. In general, the performed study underscores the importance of employing the NPγT ensemble for computational investigations of membrane-embedded receptors, as it effectively maintains zero surface tension in the simulated system. These results offer valuable insights for future research aimed at understanding receptor dynamics and designing targeted therapeutics.

• MeSH
• fosfatidylcholiny * chemie   MeSH
• lipidové dvojvrstvy chemie   metabolismus   MeSH
• Markovovy řetězce * MeSH
• orexinové receptory * chemie   metabolismus   MeSH
• povrchové napětí * MeSH
• simulace molekulární dynamiky * MeSH
• termodynamika * MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Human papillomavirus (HPV) infections are highly prevalent sexually transmitted infections, notably associated with various cancers. This study analyses the health and economic impacts of HPV-associated diseases in the Czech Republic and evaluates the cost-effectiveness of a catch-up vaccination program. METHODS: Utilizing a Markov multistate model, the study assesses the lifetime impacts and costs related to HPV infections. Cohorts of ages 15-21 were simulated to assess the impact of catch-up vaccination outside the 11-year-old age group. RESULTS: The total quality-adjusted life years (QALYs) for the female and male cohorts (together 119,362 individuals) were higher in the vaccination scenario compared to the non-vaccination scenario. The increase in QALYs was 122,246 and 200,852 respectively, when considering the actual vaccination rates. Across both cohorts, 329 cancer-related deaths were prevented. In the probabilistic sensitivity analysis for the female population, vaccination was the dominant strategy in 99.3% of iterations. In the male population, vaccination was the dominant strategy in 80.3% of iterations. The implementation of catch-up vaccination for the 15-21 age group significantly increased QALY gains and reduced life-years-lost (LYLs). In the female cohort, all analysed rates of catch-up vaccination were the dominant strategy, while in the male cohort, the incremental cost-effectiveness ratios (ICERs) remained consistently below 42,000 CZK/QALY. CONCLUSIONS: The catch-up vaccination program for 15-21-year-olds is cost-effective and can prevent a significant number of HPV-related cancers in both men and women.

• MeSH
• analýza nákladové efektivity MeSH
• analýza nákladů a výnosů * MeSH
• dospělí MeSH
• infekce papilomavirem * prevence a kontrola   ekonomika   MeSH
• kvalitativně upravené roky života * MeSH
• lidé MeSH
• Markovovy řetězce * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• očkovací programy ekonomika   MeSH
• osobní újma zaviněná nemocí MeSH
• vakcíny proti papilomavirům * ekonomika   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• ekonometrické modely * MeSH
• elektroencefalografie metody   MeSH
• lidé MeSH
• neurovědy * metody   MeSH
• stochastické procesy MeSH
• teoretické modely MeSH
• Check Tag
• lidé MeSH

Calcium influx through plasma membrane calcium release-activated calcium (CRAC) channels, which are formed of hexamers of Orai1, is a potent trigger for many important biological processes, most notably in T cell-mediated immunity. Through a bioinformatics-led cell biological screen, we have identified Orai1 as a substrate for the rhomboid intramembrane protease RHBDL2. We show that RHBDL2 prevents stochastic calcium signaling in unstimulated cells through conformational surveillance and cleavage of inappropriately activated Orai1. A conserved disease-linked proline residue is responsible for RHBDL2's recognizing the active conformation of Orai1, which is required to sharpen switch-like signaling triggered by store-operated calcium entry. Loss of RHBDL2 control of CRAC channel activity causes severe dysregulation of downstream CRAC channel effectors, including transcription factor activation, inflammatory cytokine expression, and T cell activation. We propose that this surveillance function may represent an ancient activity of rhomboid proteases in degrading unwanted signaling proteins.

• MeSH
• aktivace lymfocytů MeSH
• buněčná membrána metabolismus   MeSH
• Drosophila melanogaster MeSH
• gating iontového kanálu MeSH
• HEK293 buňky MeSH
• konformace proteinů MeSH
• lidé MeSH
• membránové proteiny metabolismus   MeSH
• mutace MeSH
• proteasy chemie   MeSH
• protein ORAI1 chemie   MeSH
• serinové endopeptidasy metabolismus   MeSH
• signální transdukce MeSH
• stochastické procesy MeSH
• vápník metabolismus   MeSH
• vápníková signalizace fyziologie   MeSH
• vápníkové kanály chemie   MeSH
• vazba proteinů MeSH
• výpočetní biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dynamic modeling of biological systems is essential for understanding all properties of a given organism as it allows us to look not only at the static picture of an organism but also at its behavior under various conditions. With the increasing amount of experimental data, the number of tools that enable dynamic analysis also grows. However, various tools are based on different approaches, use different types of data and offer different functions for analyses; so it can be difficult to choose the most suitable tool for a selected type of model. Here, we bring a brief overview containing descriptions of 50 tools for the reconstruction of biological models, their time-course simulation and dynamic analysis. We examined each tool using test data and divided them based on the qualitative and quantitative nature of the mathematical apparatus they use.

• MeSH
• biologické modely * MeSH
• datové soubory jako téma MeSH
• genové regulační sítě MeSH
• lidé MeSH
• počítačová simulace MeSH
• software * MeSH
• stochastické procesy MeSH
• systémová biologie metody   MeSH
• ukládání a vyhledávání informací MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

In most temperate fruit trees, fruits are located on one-year old shoots. In Prunus species, flowers and fruits are born in axillary position along those shoots. The axillary bud fate and branching patterns are thus key components of the cultivar potential fruit production. The objective of this study was to analyze the branching and bearing behaviors of 1-year-old shoots of apricot cultivars and clones genetically closely related. Shoot structures were analyzed in terms of axillary bud fates using hidden semi-Markov chains and compared depending on the genotype, year and shoot length. The shoots were composed of three successive zones containing latent buds (basal zone), central flower buds (median zone) and vegetative buds (distal zone), respectively. The last two zones contained few associated flower buds. The zones length (in number of metamers) and occurrence strongly depended on shoot development in the two successive years. With decrease in the number of metamers per shoot, the last two zones become shorter or may not develop. While the number of metamers of the basal and distal zones and the number of associated flower buds correlated to the number of metamers of the shoot, the number of metamers of the median zone and the transition probability from the median to the distal zone were cultivar specific.

• MeSH
• biologické modely * MeSH
• genotyp MeSH
• květy fyziologie   MeSH
• Markovovy řetězce MeSH
• meruňka obecná genetika   fyziologie   MeSH
• neparametrická statistika MeSH
• ovoce fyziologie   MeSH
• výhonky rostlin fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• chromozomální aberace účinky záření   MeSH
• lidé MeSH
• mutageneze účinky záření   MeSH
• oprava DNA účinky záření   MeSH
• poškození DNA účinky záření   MeSH
• radiační poranění patologie   MeSH
• radiační účinky * MeSH
• rizikové faktory MeSH
• stochastické procesy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Ionizujícím zářením označujeme tok hmotných částic nebo fotonů elektromagnetického záření, jež mají schopnost ionizovat atomy prostředí, kterým procházejí. Na buněčné úrovni se poškození může projevit smrtí buňky či změnou její cytogenetické informace. Tyto děje mohou vést k nepříznivých tkáňovým reakcím (deterministickým účinkům), u kterých jsou projevy závislé na překročení dávkového prahu, nebo ke vzniku stochastických účinků, u nichž s dávkou stoupá pravděpodobnost poškození. Článek krátce shrnuje tyto účinky na lidský organismus.

Ionizing radiation refers to the flow of material particles or photons of electromagnetic radiation that can ionize atoms of the environment through which it passes. At the cellular level, damage can be manifested by cell death or changing their cytogenetic information. These events can lead to adverse tissue reactions (deterministic effects) in which manifestations depend on exceeding the dose threshold, or to the stochastic effects, when the probability of damage increases with the dose. This article briefly summarizes these effects on the human body.

• MeSH
• buňky * účinky záření   MeSH
• ionizující záření * MeSH
• lidé MeSH
• poškození DNA účinky záření   MeSH
• radiační účinky MeSH
• stochastické procesy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Neuronal firing rate is traditionally defined as the number of spikes per time window. The concept is essential for the rate coding hypothesis, which is still the most commonly investigated scenario in neuronal activity analysis. The estimation of dynamically changing firing rate from neural data can be challenging due to the variability of spike times, even under identical external conditions; hence a wide range of statistical measures have been employed to solve this particular problem. In this paper, we review established firing rate estimation methods, briefly summarize the technical aspects of each approach and discuss their practical applications.

• MeSH
• akční potenciály * MeSH
• algoritmy MeSH
• Bayesova věta MeSH
• interpretace statistických dat MeSH
• lidé MeSH
• modely neurologické MeSH
• neurony fyziologie   MeSH
• pravděpodobnost MeSH
• stochastické procesy MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH