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.

• Keywords
• COVID-19, Czech Republic, refugees, social determinants of health, vaccination hesitancy,
• MeSH
• COVID-19 * prevention & control   psychology   MeSH
• Adult MeSH
• Trust * psychology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Vaccination Hesitancy * psychology   statistics & numerical data   MeSH
• Politics MeSH
• Cross-Sectional Studies MeSH
• Surveys and Questionnaires MeSH
• SARS-CoV-2 MeSH
• Aged MeSH
• Social Media MeSH
• Socioeconomic Factors MeSH
• Vaccination * psychology   MeSH
• COVID-19 Vaccines * administration & dosage   MeSH
• Health Literacy * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• COVID-19 Vaccines * MeSH

Continuous manufacturing (CM) of solid dosage forms in the pharmaceutical industry offers several advantages over batch processing. The most straightforward CM pathway within the pharmaceutical industry is continuous direct compression (CDC), which consists of three main consecutive steps: loss-in-weight feeding, continuous blending and tableting (die-filling and compaction). However, as the majority of the newly developed APIs are cohesive materials with a mean particle size of < 100 μm, a wide particle size distribution (PSD) and a high tendency to agglomerate, they are difficult to handle on CM lines. In this research paper, the impact of a diverse selection of glidants on the continuous blending unit was assessed. Two cohesive APIs (acetaminophen micronized and metoprolol tartrate) and three different glidants (Aerosil\protect \relax \special {t4ht=®} 200, Aerosil\protect \relax \special {t4ht=®} R972 and Syloid\protect \relax \special {t4ht=®} 244 FP) were included. Via multivariate data analysis, quantitative relationships were established between glidant concentration, blending responses (hold-up mass (HM), bulk residence time (BRT), blender fill fraction (BFF %) and relative standard deviation of the blend uniformity (RSDBU)), blend properties and process settings. The dry-coating of APIs with small quantities of glidants efficiently improved the flowability of cohesive powders, thereby optimizing the gravimetric feeding performance. Dry powder coating of the API altered its bulk properties which affected the bulk properties of the final blend as well as the blending responses (HM, BRT, BFF %). This was mainly attributed to the changes in basic flow energy (BFE), conditioned bulk density (CBD), flowability rate index (FRI) and flow function coefficient (ffc), which are all correlated to HM, BRT and BFF %. It was also observed that glidants did not improve RSDBU during continuous blending within the investigated experimental space. Moreover, adding higher concentrations of glidants can even increase RSDBU due to fluidization segregation and less paddle interactions. However, the overal RSDBU values obtained with the continuous blender were relatively low.

• Keywords
• Continuous blending, Continuous direct compression, Flow enhancers, Formulation development, Glidants, Particle engineering,
• MeSH
• Chemistry, Pharmaceutical methods   MeSH
• Technology, Pharmaceutical methods   MeSH
• Metoprolol * chemistry   MeSH
• Bulk Drugs MeSH
• Acetaminophen chemistry   MeSH
• Excipients * chemistry   MeSH
• Powders MeSH
• Drug Compounding * methods   MeSH
• Tablets chemistry   MeSH
• Particle Size MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Metoprolol * MeSH
• Bulk Drugs MeSH
• Acetaminophen MeSH
• Excipients * MeSH
• Powders MeSH
• Tablets MeSH

A prediction model based on the processing of FTIR spectra and partial least squares regression (PLS) was developed for the determination of thehydroperoxide number of diesel fuels. The sets of calibration and validation standards were composed of fresh and aged diesel fuels. The hydroperoxide number determined via the standard titration method ranged from 0 to 65 mg·kg-1. While the calibration standards were utilized for the model construction, the validation standards were used for its optimization and validation. Several preprocessing methods, together with various numbers of latent variables, were utilized to improve model prediction ability. The model with the lowest Root Mean Square Error of Prediction was developed using mean centering, variance scaling, second derivative, and smoothing methods. Both examined smoothing techniques, i.e., Savitzky-Golay and Gap-Segment derivative, provided similar results. The use of the commonly available and affordable FTIR method, allowing rapid analysis, proved to be cost effective alternative to highly erroneous and laborious titration methods utilizing toxic reagents. In general, the developed model showed good predictive ability and is a perfect solution for fast screening of oxidative aging level of conventional hydrocarbon-based fuels.

• Keywords
• FTIR spectroscopy, Hydroperoxide, Hydroperoxide number, Multivariate calibration, Partial least squares regression,
• Publication type
• Journal Article MeSH

Compositional data are characterized by the fact that their elemental information is contained in simple pairwise logratios of the parts that constitute the composition. While pairwise logratios are typically easy to interpret, the number of possible pairs to consider quickly becomes too large even for medium-sized compositions, which may hinder interpretability in further multivariate analysis. Sparse methods can therefore be useful for identifying a few important pairwise logratios (and parts contained in them) from the total candidate set. To this end, we propose a procedure based on the construction of all possible pairwise logratios and employ sparse principal component analysis to identify important pairwise logratios. The performance of the procedure is demonstrated with both simulated and real-world data. In our empirical analysis, we propose three visual tools showing (i) the balance between sparsity and explained variability, (ii) the stability of the pairwise logratios, and (iii) the importance of the original compositional parts to aid practitioners in their model interpretation.

• Keywords
• Compositional data, Geochemical data, Pairwise logratios, Sparse PCA,
• Publication type
• Journal Article MeSH

OBJECTIVES: To evaluate the temporal trends in types of urinary diversion (UD) used after radical cystectomy (RC) in a large, multicentre, international cohort over the past two decades. MATERIALS AND METHODS: We analysed 6469 patients who underwent RC between 2004 and 2024 at 23 international tertiary referral centres. Trends in UD type (cutaneous ureterostomy [UCS], ileal conduit [IC], and neobladder) were assessed using estimated annual percentage change (EAPC). Multivariable analysis (MVA) models identified preoperative predictors of UD type. EAPC was applied to evaluate temporal changes in the patient characteristics associated with UD type. RESULTS: Overall, 882 (14%), 3611 (56%) and 1976 patients (31%) underwent UCS, IC, and neobladder procedures, respectively. IC remained the most common UD, without significant temporal change (P = 0.1). UCS use increased from 2% to 22% (EAPC 9.9%; P < 0.001), while neobladder use declined from 41% to 19% (EAPC -2%; P = 0.009). MVA showed that older age, comorbidities, and advanced disease were associated with higher rates of UCS and lower rates of neobladder use (all P < 0.005). Neoadjuvant chemotherapy (NAC) was inversely linked to UCS, while robot-assisted RC and male sex favoured neobladder use (all P < 0.005). EAPC showed rising proportions of male patients (EAPC 6.7%), patients aged >70 years (1.2%), patients with a Charlson Comorbidity Index ≥3 (8.3%), patients who received NAC (10.4%) and patients with cT2-cN0 disease (0.5%; all P < 0.05). CONCLUSION: Over two decades, a marked increase in UCS use has been observed, alongside a decline in neobladder reconstruction. These trends coincided with a shift toward older, more comorbid patients undergoing RC. Evolving patient profiles and surgical practices underscore the need for tailored UD strategies and optimised peri-operative management.

• Keywords
• bladder cancer, radical cystectomy, robotic surgery, urinary diversion, urothelial cancer,
• Publication type
• Journal Article MeSH

BACKGROUND: Sacituzumab govitecan (SG) is approved for metastatic triple-negative breast cancer in ≥ 2 line setting at 10 mg/kg IV on Days 1 and 8 (21-day cycle). Trials confirmed its superiority over 8 mg/kg with manageable safety. In practice, precautionary dose reductions are used despite no formal guidance. In Poland, fixed 200 mg vials and unreimbursed drug waste lead to early dose adjustments. METHODS: This retrospective study evaluated the impact of initial SG dose reduction on treatment outcomes and tolerability in Polish patients. Medical records provided data on baseline features, treatment, survival, and safety. Kaplan-Meier and chi-square tests were used for survival and group comparisons. A multivariate Cox model assessed the independent effect of dose reduction on overall survival (OS) and progression-free survival (PFS). Significance was set at p < 0.05. RESULTS: Among 83 patients (median age 55, range 30-86), initial dose reductions ≥ 10% were observed in 16 patients (19.3%), including 9 (10.8%) with dose reduced ≥ 20%. Administrative adjustments (reductions > 10% to flat doses of 200 mg multiplications) accounted for 18.1% of the entire cohort. Grade ≥ 2 and ≥ 3 adverse events occurred in 83.1% and 56.6%, respectively. In a multivariate analysis, a ≥ 20% initial dose reduction remained an independent predictor of shorter PFS (HR: 2.6; 95% CI: 1.1-6.6; p = 0.04) and OS (HR: 6; 95% CI: 2-17.5; p = 0.001). Initial dose reduction did not affect toxicity. CONCLUSIONS: In this preliminary report initial dose reduction of SG negatively impacted PFS and OS without reducing toxicity, highlighting the need for further studies and dosing policy adjustments.

• Keywords
• Dose reduction, Metastases, Real world data, Sacituzumab govitecan, Triple negative breast cancer,
• MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * administration & dosage   adverse effects   MeSH
• Immunoconjugates MeSH
• Camptothecin * analogs & derivatives   administration & dosage   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Triple Negative Breast Neoplasms * drug therapy   pathology   mortality   MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Poland MeSH
• Names of Substances
• Antibodies, Monoclonal, Humanized * MeSH
• Immunoconjugates MeSH
• Camptothecin * MeSH
• sacituzumab govitecan MeSH Browser

Despite regulatory actions, lead (Pb) exposure remains a major environmental health concern worldwide due to its widespread occurrence and potential adverse effects. The aims of this study were to explore internal Pb exposure in EU citizens, identify its main sociodemographic determinants, and investigate temporal variations over the last decades. Blood Pb data from a total of 17,790 individuals from 9 biomonitoring studies conducted between 2003 and 2019 in four European countries [Belgium (FLEHS I-IV), teenagers and adults; Czech Republic (SZU), children and adults; Spain (BIOAMBIENT.ES), adults; Germany (ESB, GerES IV and V), with all three age groups] were used. The European Human Biomonitoring Initiative (HBM4EU) harmonized and integrated the different datasets. Linear mixed-model analyses were performed to explore exposure determinants related to Pb concentrations. All participants showed detectable blood Pb concentrations, with an overall mean concentration (± standard deviation) of 20.6 (± 16.7) µg/L. In multivariable analyses, older age at recruitment, smoking habit and residence in more urbanized areas were associated with higher Pb levels, whereas more recent sampling year and higher educational level with lower concentrations. After pooled analysis of individual data, no significant differences were found in the Pb levels of the European citizens studied, probably due to the heterogeneity of the studies included. Collaborative efforts between public health agencies, environmental regulators and communities must continue to monitor trends, explore emerging sources of exposure and refine strategies to ensure sustained progress in reducing Pb levels and protecting the health of European population.

• Keywords
• Blood, Europe, HBM4EU, Human biomonitoring, Lead, Regulation policies,
• MeSH
• Biological Monitoring MeSH
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Lead * blood   MeSH
• Aged MeSH
• Sociodemographic Factors MeSH
• Environmental Exposure * MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe epidemiology   MeSH
• Names of Substances
• Lead * MeSH

OBJECTIVES: To explore the prevalence and distribution of ultrasound-detected lesions indicating structural damage at the enthesis (e.g., bone erosions, enthesophytes, and calcifications) in patients with spondyloarthritis (SpA), comparing those with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), and to investigate the demographic, clinical, and metabolic factors linked to these lesions. METHODS: A cross-sectional analysis was conducted using data from the DEUS study, a multicentre investigation involving 20 rheumatology centres and including 413 patients with SpA (224 with axSpA and 189 with PsA). All participants underwent standardized clinical and ultrasound assessment of the large lower limb entheses (quadriceps tendon, proximal and distal patellar tendons, Achilles tendon, and plantar fascia). Entheseal structural lesions were explored by ultrasound and classified according to OMERACT definitions. Bivariate analyses and multivariate logistic regression were used to assess associations between ultrasound lesions and SpA patients' characteristics. RESULTS: In SpA patients, enthesophytes were the most common lesion (78.7 %), followed by calcifications (43.6 %) and bone erosions (24.9 %). Enthesophytes were more prevalent in PsA (86.8 %) compared to axSpA (71.9 %) (p < 0.001), with no significant differences in erosions and calcifications. However, lesion distribution varied across different entheses. Multivariate analysis revealed that entheseal erosions were significantly associated with inflammatory markers, HLA-B27 positivity, clinical enthesitis, and longer disease duration. Enthesophytes were significantly linked to PsA, psoriasis, clinical enthesitis, and longer disease duration. Calcifications were positively associated with hypertension, metabolic syndrome, and obesity. All lesions were associated with biologic DMARD use. CONCLUSIONS: This study reveals a high prevalence of ultrasound-detected structural damage at the enthesis and identifies distinct SpA phenotypes based on these findings.

• Keywords
• Calcifications, Enthesitis, Enthesophytes, Erosions, OMERACT, Structural damage, Ultrasound,
• MeSH
• Achilles Tendon diagnostic imaging   MeSH
• Adult MeSH
• Enthesopathy * diagnostic imaging   MeSH
• Phenotype MeSH
• Middle Aged MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Arthritis, Psoriatic * diagnostic imaging   MeSH
• Spondylarthritis * diagnostic imaging   MeSH
• Ultrasonography MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

OBJECTIVES: Pharmacovigilance efforts for COVID-19 vaccines have largely focused on severe adverse events (AEs), while nonserious, yet distressing, AEs, such as oral AEs, remain underexamined. This study aimed to analyse oral AE reporting patterns in the German national pharmacovigilance database. METHODS: A retrospective analysis of individual case safety reports (ICSRs) from the Paul-Ehrlich-Institut (PEI) database was conducted for December 2020 to December 2023. The absolute reporting ratio was calculated as cases per 1000 ICSRs for each oral AE. Secondary analyses included: (1) cross-database comparisons with the U.S. Vaccine Adverse Event Reporting System (VAERS); (2) disproportionality analysis using a hybrid approach combining frequentist and Bayesian conditions to establish signals of disproportionate reporting (SDRs); (3) subgroup analyses based on demographic and vaccine-related factors; and (4) multivariable regression to adjust for potential confounders. RESULTS: Gustatory AEs, such as ageusia and dysgeusia; other oral sensory AEs, including oral paraesthesia and oral hypoaesthesia; and specific mucosal AEs, such as oral herpes and aphthous stomatitis, were the most frequently reported oral AEs in the PEI dataset. Cross-database analysis not only confirmed the prominence of gustatory and other sensory AEs but also highlighted differences, with VAERS reporting higher rates of swollen tongue and lip swelling. Disproportionality analysis identified 21 oral AEs as true SDRs. Female susceptibility was evident in several oral AEs, and age-stratified analysis revealed higher reporting among minors and seniors compared to middle-aged adults. Differences in oral AE reporting between mRNA and viral vector vaccines lacked a consistent pattern, and booster doses were associated with increased reporting of select oral AEs. CONCLUSIONS: Within the limitations of passive surveillance data, this study highlights the need for further research on oral AEs using self-controlled case-series designs for clinically significant events. Integrating oral AEs into vaccine safety monitoring could improve postmarketing surveillance, while validated AEs may warrant inclusion in product information for transparency.

• Keywords
• Adverse Drug Reaction Reporting Systems, COVID-19 vaccines, Germany, Oral manifestations, Pharmacovigilance,
• MeSH
• COVID-19 * prevention & control   MeSH
• Databases, Factual MeSH
• Child MeSH
• Adult MeSH
• Pharmacovigilance * MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mouth Diseases * epidemiology   chemically induced   etiology   MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Adverse Drug Reaction Reporting Systems MeSH
• Vaccination * adverse effects   MeSH
• COVID-19 Vaccines * adverse effects   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Germany epidemiology   MeSH
• Names of Substances
• COVID-19 Vaccines * MeSH

BACKGROUND: Approximately 50% of patients with advanced melanoma treated with first-line anti-PD-1 immunotherapy achieve clinical benefit. However, to date, there are no validated biomarkers for objective response (ORR), progression-free survival (PFS), or overall survival (OS) with this treatment. METHODS: We performed a unicentric retrospective analysis of ORR, PFS, and OS in 138 patients with advanced melanoma treated with first-line anti-PD-1 monoclonal antibodies. Baseline blood parameters were analyzed as potential predictive or prognostic biomarkers. ORR was assessed using both RECIST (Response Evaluation Criteria In Solid Tumors) v.1.1 and iRECIST (Immune Response Evaluation Criteria In Solid Tumors). Survival analysis was performed using Kaplan-Meier curves, and comparisons were made using the log-rank test. Multivariate Cox regression analysis was used to determine independent prognostic factors for survival, and a logistic regression model was used for response. RESULTS: The median follow-up was 44.1 (95% confidence interval [CI]: 40.4-49.4) months. Elevated pretreatment lactate dehydrogenase (LDH) level and systemic immune-inflammation index (SII) were negative prognostic factors for PFS. However, only LDH remained statistically significant on multivariate analysis [hazard ratio (HR) 1.72, 95% CI: 1.09-2.70, p = 0.019, HR 1.69, 95% CI: 0.95-3.00, p = 0.072]. Increased pretreatment LDH level and SII were both negative prognostic factors for OS on multivariate analysis (HR 2.25, 95% CI: 1.35-3.75, p = 0.002, HR 2.37, 95% CI: 1.29-4.37, p = 0.006). CONCLUSIONS: Elevated pretreatment levels of SII and LDH were shown to be independent negative prognostic factors for OS. According to the nomogram for OS, which considers a combination of pretreatment parameters including LDH and SII, it is possible to predict 24-month OS in the first line of anti-PD-1 therapy.

• Keywords
• LDH, SII, advanced melanoma, anti‐PD‐1, immunotherapy, prognostic biomarkers, sunshield melanoma,
• MeSH
• Programmed Cell Death 1 Receptor * antagonists & inhibitors   immunology   MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Immune Checkpoint Inhibitors * therapeutic use   MeSH
• Kaplan-Meier Estimate MeSH
• Response Evaluation Criteria in Solid Tumors MeSH
• L-Lactate Dehydrogenase blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melanoma * drug therapy   mortality   blood   immunology   pathology   MeSH
• Biomarkers, Tumor blood   MeSH
• Skin Neoplasms * drug therapy   mortality   blood   pathology   immunology   MeSH
• Nivolumab therapeutic use   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Programmed Cell Death 1 Receptor * MeSH
• Immune Checkpoint Inhibitors * MeSH
• L-Lactate Dehydrogenase MeSH
• Biomarkers, Tumor MeSH
• Nivolumab MeSH
• PDCD1 protein, human MeSH Browser