Colorectal cancer remains a major health burden, and its early detection is crucial for effective treatment. This study investigates the use of a handheld Raman spectrometer in combination with machine learning to classify colorectal tissue samples collected during colonoscopy. A dataset of 330 spectra from 155 participants was preprocessed using a standardized pipeline, and multiple classification models were trained to distinguish between healthy and pathological tissue. Due to the strong class imbalance and limited data size, a custom grid search approach was implemented to optimize both model hyperparameters and preprocessing parameters. Unlike standard GridSearchCV, our method prioritized balanced accuracy on the test set to reduce bias toward the dominant class. Among the tested classifiers, the Decision Tree (DT) and Support Vector Classifier (SVC) achieved the highest balanced accuracy (71.77% for DT and 70.77% for SVC), outperforming models trained using traditional methods. These results demonstrate the potential of Raman spectroscopy as a rapid, non-destructive screening tool and highlight the importance of tailored model selection strategies in biomedical applications. While this study is based on a limited dataset, it serves as a promising step toward more robust classification models and supports the feasibility of this approach for future clinical validation.

• Klíčová slova
• Balanced accuracy, Colorectal cancer, Machine learning, Preprocessing pipeline, Raman spectroscopy, Spectral classification,
• MeSH
• kolorektální nádory * diagnóza   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Ramanova spektroskopie * metody   MeSH
• rozhodovací stromy MeSH
• strojové učení * MeSH
• support vector machine MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The possible clinical utility of endocan, a novel inflammatory biomarker involved in the initiation and progression of atherosclerosis, is largely unknown. We aimed to evaluate its diagnostic and prognostic performance in chest pain patients presenting to the emergency department (ED). METHODS: We prospectively enrolled patients presenting with suspected myocardial infarction (MI) to the ED in an international multicenter study. Endocan, high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin T (hs-cTnT) were measured in blood samples obtained at presentation. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI and current guidelines. Non-ST-elevation MI (NSTEMI) was the diagnostic endpoint and 5-year cardiovascular death was the primary prognostic endpoint. RESULTS: Among 4728 patients, 843 (17.8 %) had NSTEMI. The diagnostic discrimination of endocan for NSTEMI was low (area under the curve (AUC) 0.585 [95 % CI: 0.563-0.607]. Its combination with hs-cTnT (0.939 [95 % CI: 0.931-0.947]) did not improve the discriminative performance of hs-cTnT alone (0.937 [95 % CI: 0.930-0.950]). Long-term prognostic accuracy of endocan was higher versus hs-CRP, but lower versus hs-cTnT (AUC 0.730 [0.710-0.760] vs 0.650 [0.620-0.680] vs 0.810 [0.790-0.830], respectively). Endocan was associated with an increased 5-year risk for cardiovascular mortality. However, it did not provide relevant incremental prognostic value when added on top of a base model that included SCORE2 risk factors and hs-cTnT. CONCLUSION: Endocan has a low diagnostic accuracy for NSTEMI, and moderate long-term prognostic accuracy for cardiovascular death. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587https://clinicaltrials.gov/ct2/show/NCT00470587.

• Klíčová slova
• Endocan, Inflammatory biomarkers, Myocardial infarction, Troponin,
• MeSH
• biologické markery krev   MeSH
• infarkt myokardu * diagnóza   krev   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové proteiny * krev   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• proteoglykany * krev   MeSH
• senioři MeSH
• troponin T krev   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
• pozorovací studie MeSH
• Názvy látek
• biologické markery MeSH
• ESM1 protein, human MeSH Prohlížeč
• nádorové proteiny * MeSH
• proteoglykany * MeSH
• troponin T MeSH

In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity. As the first-generation of geldanamycin-derivative drugs were withdrawn from clinical trials due to hepatotoxicity, we designed second-generation compounds with C19-substituted structures in order to inhibit glutathione conjugation-mediated hepatotoxicity. In this study, using a variety of in vitro and in vivo cancer models, we found that C19-substituted 17DMAG compounds maintain their enhanced toxicity profile and synthetic lethal interaction with NRF2-NQO1-activated cancer cells. Importantly, using a xenograft mouse tumor model, we found that C19-substituted 17DMAG displayed significant anticancer efficacy against NRF2-NQO1-activated cancer cells without causing hepatotoxicity. These results clearly demonstrate the improved clinical potential for this new class of HSP90 inhibitor anticancer drugs, and suggest that patients with NRF2-NQO1-activated esophageal carcinoma may benefit from this novel therapeutic approach.

• Klíčová slova
• C19-position substituted geldanamycin derivatives, ESCC, HSP90, NQO1, NRF2-NQO1-activated cancer,
• MeSH
• benzochinony * farmakologie   chemie   MeSH
• faktor 2 související s NF-E2 * metabolismus   genetika   MeSH
• lidé MeSH
• makrocyklické laktamy * farmakologie   chemie   MeSH
• myši nahé MeSH
• myši MeSH
• NAD(P)H dehydrogenasa (chinon) * metabolismus   genetika   MeSH
• nádorové buněčné linie MeSH
• nádory jícnu * farmakoterapie   metabolismus   patologie   MeSH
• proteiny tepelného šoku HSP90 antagonisté a inhibitory   metabolismus   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• skvamózní karcinom jícnu * farmakoterapie   metabolismus   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzochinony * MeSH
• faktor 2 související s NF-E2 * MeSH
• geldanamycin MeSH Prohlížeč
• makrocyklické laktamy * MeSH
• NAD(P)H dehydrogenasa (chinon) * MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• NQO1 protein, human MeSH Prohlížeč
• proteiny tepelného šoku HSP90 MeSH
• protinádorové látky * MeSH

Pluronics, also known as poloxamers, are amphiphilic triblock copolymers widely employed in drug delivery systems due to their tunable self-assembly and biocompatibility. Among them, Pluronic F68 (Poloxamer 188) exhibits thermoresponsive behavior in aqueous solution, forming ordered supramolecular structures at high concentrations and temperatures. In this work, we investigate the morphological and rheological properties of a 45 wt% Pluronic F68 aqueous system at different temperatures through a combination of experimental and computational approaches. Rheological measurements and Small-Angle X-ray Scattering (SAXS) confirm the formation of a body-centered cubic (BCC) structure at higher temperatures and highlight the emergence of viscoelastic solid-like behavior. To support and extend these findings, Dissipative Particle Dynamics (DPD) simulations are employed to model the nanostructure evolution and the impact of temperature on self-assembly and material properties. This integrated approach provides a consistent framework to characterize the temperature-induced transition from fluid-like to solid-like states and sets the groundwork for future simulation studies incorporating drug cargo. The results offer valuable insights into the design of thermoresponsive drug delivery systems and demonstrate the potential of DPD in capturing complex structure-property relationships in amphiphilic polymer systems.

• Klíčová slova
• Dissipative particle dynamics, Drug delivery systems, Pluronics, Rheology, Self-assembly,
• MeSH
• maloúhlový rozptyl MeSH
• nosiče léků * chemie   MeSH
• poloxamer * chemie   MeSH
• povrchové vlastnosti MeSH
• reologie MeSH
• teplota MeSH
• velikost částic MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nosiče léků * MeSH
• poloxamer * MeSH
• voda * MeSH

Inbred mouse strains provide phenotypic homogeneity between individual mice. However, stochastic morphogenetic events combined with epigenetic changes due to exposure to environmental factors and ontogenic experience result in variability among mice with virtually identical genotypes, reducing the reproducibility of experimental mouse models. Here we used microscopic and cytometric techniques to identify individual patterns in gut-associated lymphoid tissue (GALT) that are induced by exposure to microbiota. By comparing germ-free (GF), conventional (CV) and gnotobiotic mice colonized with a defined minimal mouse microbiota (oMM12) MHC II-EGFP knock-in mice we quantified antigen-presenting cells (APCs) in the lamina propria, cryptopatches (CP), isolated lymphoid follicles (ILFs), Peyer's patches (PPs) and specific sections of the mesenteric lymphoid complex. We found that GF mice had a significantly larger outer intestinal surface area compared to CV and oMM12-colonized mice, which partially compensated for their lower density of the villi in the distal ileum. GF mice also contained fewer APCs than oMM12 mice in the Iamina propria of the villi and had a significantly smaller volume of the solitary intestinal lymphoid tissue (SILT). In both GF and oMM12 mice, PP follicles were significantly smaller compared to CV mice, although number was similar. Concomitantly, the number of pDCs in PPs was significantly lower in GF mice than in CV mice. Moreover, the cecal patch was dispersed into small units in GF mice whereas it was compact in CV mice. Taken together, we here provide further evidence that microbiota regulates SILT differentiation, the size and morphology of PPs, the cellular composition of mesenteric lymph nodes (MLNs) and the morphology of cecal patch. As such, microbiota directly affect not only the functional configuration of the immune system but also the differentiation of lymphoid structures. These findings highlight how standardized microbiota, such as oMM12, can promote reproducibility in animal studies by enabling microbiologically controlled experiments across laboratories.

• Klíčová slova
• Germ-free and gnotobiotic models, Gut-associated lymphoid tissue (GALT), Lymphoid tissue morphogenesis, MHCII-EGFP knock-in mice, Microbiota-induced immunity, Phenotypic plasticity,
• MeSH
• antigen prezentující buňky imunologie   MeSH
• gnotobiologické modely MeSH
• lymfoidní tkáň * imunologie   cytologie   mikrobiologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• Peyerovy pláty imunologie   cytologie   MeSH
• střevní mikroflóra * imunologie   MeSH
• střevní sliznice imunologie   mikrobiologie   cytologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus that invades the central nervous system, leading to severe neurological manifestations. In this study, we developed a reporter virus comprising TurboGFP-expressing TBEV (tGFP-TBEV) as a versatile tool for advancing TBEV research. The tGFP-TBEV facilitates quantitative measurement of viral replication, enables precise tracking of individual infected cells, and supports high-throughput screening of potential antiviral compounds and virus-neutralization assays. Furthermore, tGFP-TBEV proved effective as a model for studying TBEV infection in rat organotypic cerebellar slices cultured ex vivo and for visualizing TBEV infection in the mouse brain. Using tissue-clearing protocols and light-sheet fluorescence microscopy, we achieved high-resolution, three-dimensional mapping of the TBEV distribution in the mouse brain. This analysis uncovered distinct patterns of TBEV tropism, with infections concentrated in regions associated with neurogenesis, olfactory processing, and specific neuroanatomical pathways. The ability to visualize infection at both the cellular and whole-organ level provides a new tool for detailed investigations into viral tropism, replication, and interactions with host tissues, paving the way for deeper insights into TBEV biology and the pathogenesis of tick-borne encephalitis.

• Klíčová slova
• TBEV, light-sheet microscopy, neurotropism, organotypic cerebellar slices, reporter viruses, tissue clearing,
• MeSH
• klíšťová encefalitida * virologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• luminescentní proteiny genetika   metabolismus   MeSH
• mozek * virologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• replikace viru MeSH
• reportérové geny MeSH
• tropismus virů MeSH
• viry klíšťové encefalitidy * genetika   fyziologie   MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• luminescentní proteiny MeSH

OBJECTIVES: The aim of this study was to evaluate the pharmacokinetics and lung penetration of zanamivir in healthy rats and rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI). MATERIALS AND METHODS: Three pharmacokinetic (PK) studies have been conducted to evaluate systemic PK and local exposure of zanamivir in male Wistar rats (n = 62, 16 weeks old). Zanamivir was administered to healthy rats and rats with LPS-induced ALI intravenously (IV) and by inhalation (INH) via nebulisation. Serum and bronchoalveolar lavage (BAL) fluid concentrations were analysed to assess drug permeation across barriers. All zanamivir concentrations were determined using the HPLC-MS/MS method. RESULTS: The concentrations of zanamivir in BAL after IV dosing were approximately 3.1-, 4.0- and 5.0-fold higher in healthy animals compared with ALI at 30, 60 and 240 min after dosing, respectively (p = 0.005, 0.001 and 0.016). Zanamivir permeation between BAL fluid and serum was compared for IV and INH administrations, revealing that the BAL AUC30-240 following IV administration was 6.5-fold lower than after INH. Furthermore, the AUC30-240 in BAL fluid after IV administration was approximately 3.3 times higher in healthy animals than those with ALI (35,815 vs. 10,886 ng/mL × h). ALI also reduced the rate and extent of systemic absorption compared to healthy conditions. The absolute bioavailability of nebulised zanamivir was 1.91%. CONCLUSIONS: Our findings confirm PK superiority of INH administration to achieve local intrapulmonary exposition and indicate that ALI significantly impairs zanamivir penetration into the lungs from systemic circulation.

• Klíčová slova
• Bronchoalveolar lavage, bioavailability, inhalation drug delivery, lung inflammation, respiratory diseases,
• MeSH
• akutní poškození plic * farmakoterapie   chemicky indukované   metabolismus   MeSH
• antivirové látky * farmakokinetika   aplikace a dávkování   MeSH
• aplikace inhalační MeSH
• bronchoalveolární lavážní tekutina chemie   MeSH
• intravenózní podání MeSH
• krysa rodu Rattus MeSH
• lipopolysacharidy MeSH
• modely nemocí na zvířatech MeSH
• plíce metabolismus   MeSH
• potkani Wistar MeSH
• tandemová hmotnostní spektrometrie MeSH
• zanamivir * farmakokinetika   aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky * MeSH
• lipopolysacharidy MeSH
• zanamivir * MeSH

Vaccine hesitancy remains a significant public health challenge, particularly during pandemics when high immunization rates are crucial. While individual psychological antecedents of vaccine hesitancy have been extensively studied, limited empirical evidence exists on how contextual determinants, such as socioeconomic status, political trust, and digital literacy, collectively shape vaccine-related behaviors, particularly in Central European populations. This study explores the key determinants of COVID-19 vaccine hesitancy among Czech adults. A cross-sectional study was conducted using data from the 48th wave of the Czech national panel survey Život během pandemie [Life During Pandemic], carried out in March 2023. The data were obtained via an online questionnaire administered to a nationally representative sample of Czech adults (n = 1,708). Sociodemographic, socioeconomic, and anamnestic variables were examined alongside political attitudes. Psychological antecedents of vaccination were assessed using the 5C model (confidence, complacency, constraints, risk calculation, and collective responsibility), and digital vaccine literacy was measured using seven items covering trust in official sources, trust in social media, and the ability to evaluate and apply vaccine information. Statistical analyses included bivariate tests and multivariable regression models to identify vaccine uptake and intent determinants. Higher trust in constitutional institutions, including the president (OR = 1.55; 95/ CI: 1.38-1.74), government (1.60; 1.38-1.85), Chamber of Deputies (1.73; 1.48-2.02), and Senate (1.47; 1.29-1.69), was significantly associated with higher vaccine uptake. Similarly, positive attitudes toward the integration of Ukrainian refugees into Czech society - across domains such as work (1.63; 1.39-1.90), housing (1.59; 1.36-1.86), school (1.64; 1.41-1.92), language (1.57; 1.34-1.84), and culture (1.74; 1.50-2.03) - were positively associated with uptake. Greater confidence in vaccine safety and effectiveness was also a significant predictor (1.51; 1.44-1.58). In contrast, lower education (0.64; 0.56-0.73), lower income (0.91; 0.86-0.95), female sex (0.60; 0.47-0.76), and higher complacency (0.76; 0.73-0.80) were associated with reduced uptake. Respondents with better digital vaccine literacy, particularly those more adept at identifying misinformation, showed significantly greater vaccine confidence (mean score: 3.62 vs. 3.30, p < .001). Beyond psychological antecedents, institutional trust, political orientation, and digital vaccine literacy significantly shape COVID-19 vaccination behaviors. These findings underscore the importance of targeted interventions that address political and digital influences on vaccine hesitancy, and they highlight the need for future research to examine the causal pathways and longitudinal dynamics underlying these associations, particularly within Central and Eastern European contexts.

• Klíčová slova
• COVID-19, Czech Republic, refugees, social determinants of health, vaccination hesitancy,
• MeSH
• COVID-19 * prevence a kontrola   psychologie   MeSH
• dospělí MeSH
• důvěra * psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• odkládání očkování * psychologie   statistika a číselné údaje   MeSH
• politika MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• sociální média MeSH
• socioekonomické faktory MeSH
• vakcinace * psychologie   MeSH
• vakcíny proti COVID-19 * aplikace a dávkování   MeSH
• zdravotní gramotnost * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• vakcíny proti COVID-19 * MeSH

BACKGROUND: Intraluminal irreversible electroporation (IRE) can be used for recanalizing occluded metal stents. However, optimal IRE parameters for consistent effects across different stent designs remain unclear. The aim of this study was to simulate the process of stent recanalization in silico by employing finite element analysis. METHODS: A virtual model of an occluded biliary stent with an experimental 3-electrode IRE catheter was developed. Electric field distribution, temperature changes, and potential ablation volumes were simulated across various parameters: IRE voltage (300 - 1300 V), stent wire width (0.1 - 0.5 mm) and stent mesh size (0.7 - 5.58 mm). Simulations incorporated five representative stent types commonly used in clinical practice. 685 unique simulations were conducted, analyzing 1162 unique values. RESULTS: Higher voltages generally led to larger ablation zones and increased temperatures. Thinner stent wires and larger mesh sizes also increased the extent of ablation zone. While in-stent ablation was largely independent of stent design, out-of-stent ablation was significantly impacted by mesh size and tissue thickness between the stent and irreversible electroporation electrodes. Voltages above 1000 V produced significant thermal effects, with substantial volumes of tissue heated above 50 °C. Specific stent designs exhibited variations in maximum temperature (72.1 - 83.1 °C) and ablation volume (8.7 - 14.7 mm3). CONCLUSION: Tailored IRE protocols for different stent designs are required due to differences in in- and out-stent ablation volumes. High voltages (>1000 V) induce both thermal and nonthermal ablation mechanisms.

• Klíčová slova
• Irreversible electroporation, ablation, computer simulation, metal stents, temperature distribution,
• MeSH
• elektroporace * metody   MeSH
• lidé MeSH
• stenty * MeSH
• teoretické modely * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Beta-alanine (βA) is a non-essential amino acid purportedly used to enhance aerobic exercise performance. While previous research indicates the benefits of βA on time to exhaustion (TTE) and aerobic capacity (VO2peak) in adults, evidence is lacking in adolescent athletes. Thus, the purpose of this study was to determine the effects of 4 weeks of βA supplementation on aerobic performance in adolescent runners. METHODS: Twenty-seven middle- and long-distance runners (aged 17.36 ± 2.17 years) were randomly divided into a βA or placebo (PL) group (maltodextrin). Subjects performed maximal graded exercise tests (GXT) and submaximal trials (SMT; 80% of VO2peak for 1500 m) on a treadmill before and after 14 and 28 days of supplementation or PL. Respiratory (VE) metabolic (VO2, RER, lactate [La]), and cardiovascular (HR) variables were measured during the GXT and SMT, along with the first (VT1) and second ventilatory threshold (VT2) and TTE monitored during the GXT only. Within- and between-group differences were assessed using a repeated-measures mixed-model analysis of variance. RESULTS: Findings indicated that despite a trivial increase in VO2peak over 4 weeks, the βA group increased TTE by 6.5% compared to 1.4% in the PL group (d = 0.46). Additionally, small effects in HRmax, VE, [La], and TTE were observed between groups favoring βA. Regarding the SMT, both average HR and RER decreased by 4% in the βA group, with no changes for the PL. CONCLUSIONS: Despite no evidence to suggest increases in VO2peak, practitioners should note that improvements in TTE may be observed after 28 days of βA supplementation in adolescent runners.

• Klíčová slova
• Dietary supplements, VO2max, VO2peak, aerobic performance, running performance,
• MeSH
• běh * fyziologie   MeSH
• beta-alanin * aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• fyzická vytrvalost * účinky léků   MeSH
• kyselina mléčná krev   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• potravní doplňky * MeSH
• sportovní výkon * fyziologie   MeSH
• spotřeba kyslíku účinky léků   MeSH
• tolerance zátěže účinky léků   MeSH
• zátěžový test MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• beta-alanin * MeSH
• kyselina mléčná MeSH