BACKGROUND: Current experimental data on RNA interactions remain limited, particularly for non-coding RNAs, many of which have only recently been discovered and operate within complex regulatory networks. Researchers often rely on in-silico interaction detection algorithms, such as TargetScan, which are based on biochemical sequence alignment. However, these algorithms have limited performance. RNA-seq expression data can provide valuable insights into regulatory networks, especially for understudied interactions such as circRNA-miRNA-mRNA. By integrating RNA-seq data with prior interaction networks obtained experimentally or through in-silico predictions, researchers can discover novel interactions, validate existing ones, and improve interaction prediction accuracy. RESULTS: This paper introduces Pi-GMIFS, an extension of the generalized monotone incremental forward stagewise (GMIFS) regression algorithm that incorporates prior knowledge. The algorithm first estimates prior response values through a prior-only regression, interpolates between these prior values and the original data, and then applies the GMIFS method. Our experimental results on circRNA-miRNA-mRNA regulatory interaction networks demonstrate that Pi-GMIFS consistently enhances precision and recall in RNA interaction prediction by leveraging implicit information from bulk RNA-seq expression data, outperforming the initial prior knowledge. CONCLUSION: Pi-GMIFS is a robust algorithm for inferring acyclic interaction networks when the variable ordering is known. Its effectiveness was confirmed through extensive experimental validation. We proved that RNA-seq data of a representative size help infer previously unknown interactions available in TarBase v9 and improve the quality of circRNA disease annotation.

• Klíčová slova
• Bayesian network, Circular RNA, Functional annotation, Penalized regression, Structure inference,
• MeSH
• algoritmy MeSH
• genové regulační sítě MeSH
• kruhová RNA * genetika   metabolismus   MeSH
• lidé MeSH
• lineární modely MeSH
• messenger RNA * genetika   metabolismus   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• sekvenční analýza RNA metody   MeSH
• sekvenování transkriptomu * metody   MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kruhová RNA * MeSH
• messenger RNA * MeSH
• mikro RNA * MeSH

BACKGROUND: The composition of the microbiome plays an important role in human health and disease. Whether there is a direct association between the cervicovaginal microbiome and the host's epigenome is largely unexplored. RESULTS: Here we analyzed a total of 448 cervicovaginal smear samples and studied both the DNA methylome of the host and the microbiome using the Illumina EPIC array and next-generation sequencing, respectively. We found that those CpGs that are hypo-methylated in samples with non-lactobacilli (O-type) dominating communities are strongly associated with gastrointestinal differentiation and that a signature consisting of 819 CpGs was able to discriminate lactobacilli-dominating (L-type) from O-type samples with an area under the receiver operator characteristic curve (AUC) of 0.84 (95% CI = 0.77-0.90) in an independent validation set. The performance found in samples with more than 50% epithelial cells was further improved (AUC 0.87) and in women younger than 50 years of age was even higher (AUC 0.91). In a subset of 96 women, the buccal but not the blood cell DNA showed the same trend as the cervicovaginal samples in discriminating women with L- from O-type cervicovaginal communities. CONCLUSIONS: These findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.

• Klíčová slova
• Cervicovaginal microbiome, DNA methylation, Epigenome–microbiome interaction, Penalized regression,
• MeSH
• cervix uteri mikrobiologie   MeSH
• CpG ostrůvky MeSH
• dospělí MeSH
• epigenom genetika   MeSH
• epitelové buňky metabolismus   MeSH
• Lactobacillus genetika   růst a vývoj   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• mikrobiota genetika   MeSH
• prediktivní hodnota testů MeSH
• vagina mikrobiologie   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

The exposure of the Arctic ecosystem to persistent organic pollutants (POPs) was assessed through a review of literature data. Concentrations of 19 chemicals or congeneric groups were estimated for the highest levels of the Arctic food chain (Arctic cod, ringed seals, and polar bears). The ecotoxicological risk for seals, bears, and bear cubs was estimated by applying the concentration addition (CA) concept. The risk of POP mixtures was very low in seals. By contrast, the risk was 2 orders of magnitude higher than the risk threshold for adult polar bears and even more (3 orders of magnitude above the threshold) for bear cubs fed with contaminated milk. Based on the temporal trends available for many of the chemicals, the temporal trend of the mixture risk for bear cubs was calculated. Relative to the 1980s, a decrease in risk from the POP mixture is evident, mainly because of international control measures. However, the composition of the mixture substantially changes, and the contribution of new POPs (particularly perfluorooctane sulfonate) increases. These results support the effectiveness of control measures, such as those promulgated in the Stockholm Convention, as well as the urgent need for their implementation for new and emerging POPs. Environ Toxicol Chem 2017;36:1181-1192. © 2017 SETAC.

• Klíčová slova
• Arctic, Mixture, Penalized regression smoothers, Persistent organic pollutants (POPs), Risk assessment,
• MeSH
• ekosystém MeSH
• halogenované difenylethery chemie   metabolismus   MeSH
• látky znečišťující životní prostředí chemie   metabolismus   MeSH
• medvědovití metabolismus   MeSH
• polychlorované bifenyly chemie   metabolismus   MeSH
• potravní řetězec * MeSH
• riziko MeSH
• tuleňovití metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Arktida MeSH
• Názvy látek
• halogenované difenylethery MeSH
• látky znečišťující životní prostředí MeSH
• polychlorované bifenyly MeSH

OBJECTIVES: This 4th report aimed to provide insights into patient characteristics, outcomes and standardized outcome ratios of patients implanted with durable Mechanical Circulatory Support across participating centres in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) registry. METHODS: All registered patients receiving durable mechanical circulatory support up to August 2024 were included. The expected number of events was predicted using penalized logistic regression. Standardized outcome ratios (Observed/Expected events) were presented in plots to assess 30-day and 1-year mortality, ischaemic stroke and major bleeding outcomes. Expected events were estimated using penalized logistic regression using demographics and comorbidities as predictors. Centres with <90% follow-up completeness were excluded from standardized outcome ratio assessment. RESULTS: Analysis included 6962 implants in 6408 patients (457 patients underwent repeated implants) registered in EUROMACS from 17 countries (32 centres) (median age: 58 years, 83% males, 17% Interagency Registry for Mechanically Assisted Circulatory Support class 1). Thirty-day mortality, major bleeding and ischaemic stroke probabilities were 9.6, 12.6% and 2.1%, respectively. Standardized mortality ratios showed variability between centres, ranging from 0 (95% CI 0-0) to 1.4 (95% CI 1.2-1.7). Higher standardized bleeding outcome ratios correlated with higher standardized ischaemic stroke ratio's (Spearman r: 0.56, P = 0.008). CONCLUSIONS: Most included centres perform as expected given the demographics and comorbidities of patients. A positive correlation was found between standardized bleeding and ischaemic stroke ratios, reflecting the need of continuously monitoring of adverse events by quality improvement programs.

• Klíčová slova
• EUROMACS, Left ventricular assist device, Mechanical circulatory support,
• MeSH
• lidé středního věku MeSH
• lidé MeSH
• podpůrné srdeční systémy * škodlivé účinky   statistika a číselné údaje   MeSH
• registrace * MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

UNLABELLED: We examined observation-based fog occurrence at three Czech monitoring sites: Praha 4 - Libuš, Košetice and Churáňov, representing different environments - urban, rural and mountain - over a time span of 27 years (1989-2015). We searched for a simple model describing fog occurrence fitting the observed air pollution and meteorological data. For our analysis we used a generalized additive model, GAM, with (penalized) spline components to capture possible nonlinear and a priori unknown functional relationships. In order to cope with the binary nature of the data (indicators of fog presence on individual days), we employed a logistic regression GAM model fitted by a maximizing penalized likelihood (where the penalty coefficients were estimated via cross-validation). After testing several physically motivated models, being guided by AIC and physical interpretation of the components, we arrived at a model which uses the following explanatory variables: relative humidity, ambient SO2 concentrations, ambient NOx concentrations, air temperature and seasonality. All associations between the response and the analysed explanatory variables were highly significant. According to our results, the most important explanatory variables modelling the fog probability were relative humidity and air pollutants. Interestingly, we observed an increasing trend in fog occurrence at all three sites under review starting around the mid 2000s. CAPSULE: The most important explanatory variables modelling the fog probability at three Central European sites were humidity, SO2 and NOx. An increasing trend in fog occurrence has been observed since the mid 2000s.

• Klíčová slova
• Air pollution, Fog, Generalized additive model, Meteorology,
• Publikační typ
• časopisecké články MeSH

The authors aim to understand how lymphocyte populations could predict the course of multiple sclerosis (MS) in people treated with interferon-β (IFN-β). Twenty-five male patients and 72 female patients were analyzed in the study. Peripheral blood samples were taken before and 5 years after the treatment with IFN-β. Lymphocyte subsets were analyzed by flow cytometry. The authors compared lymphocyte parameters between confirmed sustained progression (CSP) and non-CSP groups by using Welch's one-way analysis of means or a chi-square test of independence. A penalized (lasso) logistic regression model was fitted to identify the combination of lymphocyte parameters for potential biomarkers. The combination of lymphocyte counts, relative CD3+/CD25+ cells, absolute CD8 T cells, absolute CD8+/CD38+ cells, absolute CD38+ cells, and relative CD5+/CD19+ cells was identified as potential biomarker for the IFN-β treatment to monitor MS development in relation to CSP. The results suggest that other biomarkers aid in patient observation, predict a favorable outcome, and assist in the decision-making process for the early therapy escalation.

• Klíčová slova
• biomarkers, interferon-β, lymphocytes, multiple sclerosis,
• MeSH
• dospělí MeSH
• interferon beta terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocyty patologie   MeSH
• mladý dospělý MeSH
• počet lymfocytů MeSH
• roztroušená skleróza krev   farmakoterapie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferon beta MeSH

OBJECTIVES: We present results from a secondary prevention trial of coronary heart disease (CHD) in the Czech male population from northern Bohemia with the history of myocardial infarction (MI) and high prevalence of metabolic syndrome. We compare several approaches to analyzing survival data from our study in terms of respective model assumptions. METHODS: While both the Cox and Weibull survival regression models assume proportionality of the hazard functions over time, in many instances this assumption appears incompatible with the data at hand. Gray's implementation of flexible models using penalized splines allows for a more realistic assessment of the covariate effects which may vary over time. RESULTS: Gray's model results revealed a steady decline in the age-adjusted intervention effect over time, which remained significant until about 2.7 years of follow-up. This was in contrast with the results obtained from the Cox and Weibull models which suggested an overall risk reduction due to intervention during the total follow-up of 6.7 years. Survival estimates based on the Cox and Gray models are shown for the two treatment groups and selected sample quantiles of the age distribution for illustration. CONCLUSIONS: Gray's time-varying coefficients model facilitated a more realistic assessment of the intervention effect. Using suitable historical controls with MI history the effect of intervention was found to gradully diminish over time.

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• infarkt myokardu komplikace   MeSH
• koronární nemoc komplikace   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom komplikace   epidemiologie   MeSH
• prevalence MeSH
• proporcionální rizikové modely MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Background: Glatiramer acetate (GA) is an effective treatment for the earliest stages of multiple sclerosis (MS)-clinically isolated syndrome (CIS) or clinically definite MS (CDMS). Objective: This study aims to determine the differences in the lymphocyte population (at baseline and the course of five years) between confirmed sustained progression (CSP) and non-CSP groups and to identify potential biomarkers among these parameters that can predict a positive response to the treatment. Methods: Twelve male and 60 female patients were included in the study. Peripheral blood samples were collected before and five years after treatment with GA. The authors compared lymphocyte parameters between the CSP and non-CSP groups by statistical analyses. Univariate and penalized logistic regression models were fitted to identify the best lymphocyte parameters at baseline and their combination for potential biomarkers. Subsequently, the ROC analysis was used to identify cut-offs for selected parameters. Results: The parameter CD4+/CD45RO+ was identified as the best single potential biomarker, demonstrating the ability to identify patients with CSP. Moreover, a combination of four lymphocyte parameters at baseline, relative lymphocyte counts, CD3+/CD69+, CD4+/CD45RO+, and CD4+/CD45RA+ab, was identified as a potential composite biomarker. This combination explains 23% of the variability in CSP, which is better than the best univariate parameter when compared to CD4+/CD45RO+ at baseline. Conclusions: The results suggest that other biomarkers can help monitor the conditions of patients and predict a favourable outcome.

• Klíčová slova
• CD4+/CD45RO+, biomarker, disease progression, glatiramer acetate, multiple sclerosis, patients,
• MeSH
• antigeny CD45 krev   MeSH
• biologické markery MeSH
• biomarkery farmakologické MeSH
• diferenciační antigeny krev   MeSH
• dospělí MeSH
• glatiramer acetát terapeutické užití   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocyty imunologie   MeSH
• mladý dospělý MeSH
• počet lymfocytů metody   MeSH
• progrese nemoci MeSH
• roztroušená skleróza farmakoterapie   imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD45 MeSH
• biologické markery MeSH
• biomarkery farmakologické MeSH
• diferenciační antigeny MeSH
• glatiramer acetát MeSH

Background: It is not well-understood why symptom severity varies between patients with peanut allergy (PA). Objective: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity. Methods: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity. Results: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54-0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC. Conclusions: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient.

• Klíčová slova
• EuroPrevall, IgE, clinical background, component-resolved diagnostics, iFAAM, peanut allergy, prediction, severity,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/μL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

• Klíčová slova
• Takotsubo syndrome, embolism, outcome, risk score, thrombus,
• MeSH
• časové faktory MeSH
• elektrokardiografie MeSH
• embolie diagnóza   epidemiologie   etiologie   MeSH
• hodnocení rizik metody   MeSH
• incidence MeSH
• koronární angiografie MeSH
• lidé MeSH
• magnetická rezonance kinematografická MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• nemoci srdce diagnóza   epidemiologie   etiologie   MeSH
• radioisotopová ventrikulografie MeSH
• registrace * MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční komory MeSH
• takotsubo kardiomyopatie komplikace   diagnóza   MeSH
• trombóza diagnóza   epidemiologie   etiologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Austrálie epidemiologie   MeSH
• Evropa epidemiologie   MeSH
• Spojené státy americké epidemiologie   MeSH