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This paper explores children's encounters with migration in global contexts through storytelling. Children from two primary schools in Manchester, UK and Cape Town, South Africa, developed stories of self through object elicitation, poetry and self-made artefacts. The children had either directly or indirectly experienced migration across borders. We combined objects that were brought from home, drawings and annotations in exploring the significance of children's ordinary everyday encounters. While the children's story work captures their individual perceptions of self, the collections of objects, drawings and artefacts reflect ideas about what it means to be a child in a world of mobility where human and more-than-human are entangled together. We explore children's stories in relation to mobility, belonging and more-than-human connections. However, we acknowledge that the interpretation of the 'final' stories is incomplete as they continue to change in a process of becoming.

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pneumonia with extremely heterogeneous clinical presentation, ranging from asymptomatic to severely ill patients. Previous studies have reported links between the presence of host genetic variants and the outcome of the COVID-19 infection. In our study, we used whole exome sequencing in a cohort of 444 SARS-CoV-2 patients, admitted to hospital in the period October-2020–April-2022, to search for associations between rare pathogenic/potentially pathogenic variants and COVID-19 progression. We used gene prioritization-based analysis in genes that have been reported by host genetic studies. Although we did not identify correlation between the presence of rare pathogenic variants and COVID-19 outcome, in critically ill patients we detected known mutations in a number of genes associated with severe disease related to cardiovascular disease, primary ciliary dyskinesia, cystic fibrosis, DNA damage repair response, coagulation, primary immune disorder, hemoglobin subunit β, and others. Additionally, we report 93 novel pathogenic variants found in severely infected patients who required intubation or died. A network analysis showed main component, consisting of 13 highly interconnected genes related to epithelial cilium. In conclusion, we have detected rare pathogenic host variants that may have influenced the COVID-19 outcome in Bulgarian patients.

Abstract Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP–SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP–SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP–SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP–SNP interaction detection accuracy.

Abstract Introduction A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort. Methods This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15–180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone. Results The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02). Conclusions xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy.

The fenestration in Fontan operation consists in creation of a communication between venous circulation and the pulmonary venous atrium, allowing direct passage of blood from the venous to the systemic circulation (right-to-left shunt). There is no general agreement concerning the mean pulmonary artery pressure (mPAP) level above which fenestration is indicated. There are no strict guidelines for the indications for fenestration closure as well. Here we present our data about invasive hemodynamic assessment before and after temporary closure of the fenestration in patients after Fontan operation. Our recommendations regarding comprehensive evaluation of patients with fenestrations after Fontan surgery are also presented.

Abstract Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal nonsyndromic craniosynostosis (sNCS) presenting as the most common CS phenotype. Previous genome-wide association and targeted sequencing analyses of sNCS have identified multiple associated loci, with the strongest association on chromosome 20. Herein, we report the first whole-genome sequencing study of sNCS using 63 proband-parent trios. Sequencing data for these trios were analyzed using the transmission disequilibrium test (TDT) and rare variant TDT (rvTDT) to identify high-risk rare gene variants. Sequencing data were also examined for copy number variants (CNVs) and de novo variants. TDT analysis identified a highly significant locus at 20p12.3, localized to the intergenic region between BMP2 and the noncoding RNA gene LINC01428. Three variants (rs6054763, rs6054764, rs932517) were identified as potential causal variants due to their probability of being transcription factor binding sites, deleterious combined annotation dependent depletion scores, and high minor allele enrichment in probands. Morphometric analysis of cranial vault shape in an unaffected cohort validated the effect of these three single nucleotide variants (SNVs) on dolichocephaly. No genome-wide significant rare variants, de novo loci, or CNVs were identified. Future efforts to identify risk variants for sNCS should include sequencing of larger and more diverse population samples and increased omics analyses, such as RNA-seq and ATAC-seq.

Abstract Background Autosomal recessive spastic ataxia ofCharlevoix–Saguenay (ARSACS) is a rare neurodegenerative disorder characterizedby early‐onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lowerlimb spasticity. We present clinical andgenetic data of the first Bulgarian patients diagnosed with ARSACS by wholeexome sequencing (WES). Methods Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing. All patients underwent clinical examination and testingincluding the standard rating scales for spastic paraplegia and ataxia. Results Five different SACS gene variants, three of which novel, have been identified inpatients from three different ethnic groups. In addition to the classicalclinical triad, brain MRI revealed cerebellar atrophy, linear pontineT2‐hypointensities, and hyperintense rim lateral tothalamus combined with retinal nerve fiber layer thickening on opticcoherence tomography (OCT). Conclusion We expand the mutation, geographic, and phenotypic spectrum of ARSACS, adding Bulgaria to the world map of the disease, and drawing attention to the fact that it is still misdiagnosed. We demonstrated that brain MRI and OCT are necessary clinical tests for ARSACS diagnosis, even if one of the cardinal clinical features is lacking

The cytochrome P450 superfamily consists of hemeproteins involved in the detoxication of different xenobiotics, including drugs. The CYP2 gene family is responsible for the metabolism of 80% of the drugs in clinical use. There are considerable interindividual and interethnic variabilities in the rate of drug metabolism as a result of genetic polymorphisms. The goal of our study was to determine the frequency of 10 genetic polymorphisms in CYP2 family genes to give light on the pharmacogenetic defects of the main CYPs, involved in drug metabolism, in Bulgarian individuals. We detected high allele frequency for CYP2D6*10 (0.27), CYP2D6*4 (0.22), and CYP2B6*9 (0.24), followed by CYP2C19*2 (0.14), CYP2C9*3 (0.11) and CYP2C9*2 (0.09). The genotype frequencies were also determined for all investigated variants. In total 47.2% of the analyzed individuals carried CYP2D6 genetic polymorphisms – 5.6% carried a single variant and 41.6% were found to have two or more such variants. Homozygotes for CYP2D6 variants were established among 14% of Bulgarian individuals. Determination of the prevailing pharmacogenetic polymorphisms of the CYPs, most responsible for drug metabolism, will lead to a lower risk of drug toxicity, increased drug efficacy, and drug dose optimization.

Purpose. The routine diagnosis of enterobiasis consists of a microscopic examination of perianal imprints on a transparent scotch tape for the presence of parasitic eggs. However, this method has low sensitivity when the number of eggs is small. The development of highly sensitive and specific methods, such as PCR, will increase the possibilities of detecting the parasite and will enable its genetic characterization. Material/Methods. The study was conducted from May 2022 to September 2022 and comprised 24 patients infected with Enterobius vermicularis. DNA was extracted from parasite eggs/adult worms using PureLink Genomic DNA Mini Kit (INVITROGEN), according to the manufacturer's instructions. Nested polymerase chain reaction (PCR) for detection of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene was applied with two sets of primers. Results. The developed and described method for genetic determination of Enterobius vermicularis in samples from infected individuals is suitable and applicable to improve the diagnosis of the disease, as well as for further phylogenetic research of the parasite, which is of great importance for its successful treatment and control. Conclusions. Regardless of existing morphological diagnostic methods, genotyping studies concerning Enterobius vermicularis need to be deepened. Molecular-biological analyses increase diagnostic sensitivity, provide valuable knowledge about the geographic distribution and diversity of helminths, and allow the monitoring of therapy.

BackgroundProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.MethodsIn total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.ResultsThe final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.ConclusionsWe demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

The Salamanca Statement and subsequent international calls to action around inclusive education aim to meet Education for All goals and foster inclusive communities for learners within mainstream education. However, there are diverse interpretations of what inclusion means in practice that vary across local, national and international contexts. In developing inclusive pedagogies with teachers at the forefront of providing support, the use of labels to categorise particular groups of learners according to perceived learning needs can further marginalise them, affecting their sense of belonging in school and their academic and social identities. We present case studies drawn from two doctoral studies conducted in contextually and culturally different settings to understand learners' experiences of marginalisation in education. The experiences of learners of English as an additional language transferring from primary to secondary school in England illustrate marginalised positioning assigned by teachers' perceptions. The ability to 'settle in' to school of street-connected children transitioning (back) into education in Kenya is influenced by their interactions with peers, teachers and the wider community on and after the street. Findings emphasise the need for understanding experiences through shared narratives and dialogue, starting with learners' experiences to develop pedagogies and foster inclusive communities within and beyond schools.

Metabolic syndrome (MetS) is defined by the World Health Organisation (WHO) as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidaemia. The components of MetS and the associated cardiovascular risks may disrupt the vascular endothelial function and the structure of the vascular wall, increasing the risk of atherosclerosis and vascular diseases. In this study we evaluated the relationship between the carotid intima–media thickness (CIMT), the redox balance parameters of plasma asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), and heme oxygenase 1 (HO-1), and the expression of oxidative stress-related nuclear factor kappa B (NF-kB), nuclear factor erythroid 2-related factor 2 (Nrf2), and HO-1 in peripheral blood mononuclear cells (PBMCs) in MetS. Significantly higher CIMT was established in MetS patients aged ≥ 55 years as compared with the control group (0.96 ± 0.29 vs. 0.74 ± 0.21, p < 0.05). Expression was higher in MetS patients aged < 55 years (83% for NF-kB, p < 0.05; 251% for Nrf2, p < 0.05, and 337% for HO-1, p < 0.05) in comparison to the control group. Similarly, expression was higher in CIMT < 0.90 mm than the control group by 80% for NF-kB, p < 0.01; 260% for Nrf2, p < 0.05, and 303% for HO-1, p < 0.05. In contrast, gene expression was under-regulated in the subgroups of MetS patients aged ≥ 55 years and MetS patients with CIMT ≥ 0.90 mm. Significantly higher plasma levels for MDA, ADMA, and HO-1 were established in the age < 55 and age ≥ 55 MetS subgroups and the CIMT < 0.90 mm and CIMT ≥ 0.90 mm subgroups. In conclusion, MetS individuals aged ≥ 55 are at higher risk of increased CIMT and impaired redox balance.

Tribocatalysis is a promising environmental remediation technique that utilizes the triboelectric effect, produced when dissimilar materials interact through friction, to generate charges promoting catalytic reactions. In this work, the tribocatalytic degradation of an organic dye—Rhodamine B (RhB)—has been experimentally realized using pure and 2 mol.% La-modified/ZnO powders, synthesized via a simple hydrothermal method. The effects of annealing on the tribocatalytic activity of the La/ZnO catalysts are also studied at 100 and 500 °C. The La/ZnO-modified catalysts showed an enhanced RhB degradation efficiency with 92% removal within 24 h, compared to only 58% for the pure ZnO. The effects of annealing were found to be detrimental, with RhB removal efficiencies dropping from 92 to 69% in the 100–500 °C range. The catalysts’ cycling stability was found to be excellent within three cycles. Ultimately, it is demonstrated that by utilizing La/ZnO powders, contaminated wastewater can be efficiently treated through employing tribocatalysis.

Tribocatalysis is an emerging advanced oxidation process that utilizes the triboelectric effect, based on friction between dissimilar materials to produce charges that can initiate various catalytic reactions. In this study, pure and rare-earth-modified ZnO powders (La2O3, Eu2O3, 2 mol %) were demonstrated as efficient tribocatalysts for the removal of the tetracycline antibiotic doxycycline (DC). While the pure ZnO samples achieved 49% DC removal within 24 h at a stirring rate of 100 rpm, the addition of Eu2O3 increased the removal efficiency to 67%, and La2O3-modified ZnO powder exhibited the highest removal efficiency, reaching 80% at the same stirring rate. Additionally, increasing the stirring rate to 300 and 500 rpm led to 100% DC removal in the ZnO/La case within 18 h, with the pronounced effect of the stirring rate confirming the tribocatalytic effect. All tribocatalysts exhibited excellent recycling properties, with less than a 3% loss of activity over three cycles. Furthermore, a scavenger assay confirmed the importance of superoxide radical generation for the overall reaction rate. The results of this investigation indicate that the rare-earth-modified ZnO tribocatalysts can effectively utilize mechanical energy to decompose pollutants in contaminated water.

The current study aims to synthesize and analyze both pure and La-doped TiO2, and evaluate the photocatalytic and antibacterial activity of as-prepared samples. Doped and undoped samples were prepared by the non-hydrolytic sol–gel method from titanium(IV) chloride, benzyl alcohol, and lanthanum(III) nitrate followed by thermal treatment. Lanthanum content in synthesized samples was 0.4, 1, and 5 mol%. The resulting nanopowders’ structure and morphology were described using XRD, IR, and UV–Vis analysis. The average particle sizes of pure and doped TiO2 were about 6–15 nm and anatase was found to be a dominant crystalline phase in the samples. It was observed that particle sizes decreased on increasing La content. The photocatalytic activity of the pure and La-doped sol–gel powders was estimated in the decomposition of paracetamol in distilled water using ultraviolet light illumination. Doping with lanthanum ions has been shown to increase the photocatalytic properties on the degradation of paracetamol. Furthermore, the annealed catalysts (pure and La3+ doped) showed increased photocatalytic activity and degradation of the analgesic in comparison with non-annealed materials. In both cases, the highest photocatalytic efficiency is observed at the optimal La3+ (1 mol%) concentration. The antimicrobial activity of 1 mol% La/TiO2 was tested against a reference strain E. coli in the presence of ultraviolet light and in dark conditions. The number of viable bacterial cells was determined by a spread plate method, and kill curves were performed. The results showed that photoactivated 1 mol% La/TiO2 exhibited a strong bactericidal effect, and in concentration, 1 mg/mL efficiently killed bacteria at an initial cell density of about 105 colony forming units in 1 mL within 15 min.

Summary: Background: Tumour-promoting inflammation is a “hallmark” of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P 70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. Findings: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10–1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20–1.69, q-value = 0.055, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53–0.81, q-value = 0.067, PPH4 = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88–0.97, q-value = 0.15, PPH4 = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48–4.10, q-value = 0.072, PPH4 = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk. Interpretation: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated. Funding: Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654).

INTRODUCTION: Infections caused by parasites still represent an important global health problem. Although parasitic infections are responsible for significant morbidity and mortality in developing countries, they are also prevalent in developed countries. This study aims to establish the dynamics of the parasitic infections registered in the country (local and imported) and to analyze the situation, based on data from the previous years. METHODS: We used the annual reports of regional health inspectorates, diagnostic laboratories, medical universities, and data from the National center of infectious and parasitic diseases about all individuals infected with parasitic diseases in the country. RESULTS: A total of 635,522 persons were examined in 2022, of whom 1.82% were diagnosed with various parasitic infections. In the local helminthic zoonoses such as echinococcosis and trichinellosis, a significant decrease in morbidity was observed,1.3%₀₀₀ (n = 89) for cystic echinococcosis and 0.16%₀₀₀ (n = 9) for trichinellosis. For soil-transmitted helminthiases (ascariasis and trichuriasis), the incidence was 6.7%₀₀₀ and 0.5%₀₀₀, respectively. Data on enterobiasis does not show any particular dynamics in 2022 either. The registered prevalence for the country was 1.48%, and for children from various childcare facilities - 2.45%. During the year, seven cases of vector-borne parasitic diseases were registered in the country: imported malaria was diagnosed in 5 patients (4 Bulgarian citizens and one foreigner), and autochthonous visceral leishmaniasis - in two persons. CONCLUSIONS: The analysis shows that, in spite of a trend of declining morbidityfor some socially significant protozoan and helminth infections, human parasitic diseases still represent a significant problem with social and medical consequences for the population of our country. Therefore, it is necessary to preserve and strengthen the surveillance and control network by including new personnel in the medical parasitology structures.

Plaque-induced gingivitis is one of the most widely distributed periodontal disorder during childhood. The control of the pathogenic potential of the plaque is associated with oral hygiene status at individual, group, and population levels. We hypothesize that regular application of complex oral hygiene-prophylaxis could beneficially modulate salivary amino acids profile in children with different stage of plaque-induced gingivitis. Therefore, we aimed to study the salivary amino acids’ profile in relation to certain clinical indicators and environmental variables for plaque-induced gingivitis in children.

Inflammatory Bowel Disease (IBD) is a group of chronic intestinal diseases, among which Crohn’s disease (CD) and ulcerative colitis (UC) represent the two main types. The differential diagnosis of these two disorders is often a significant challenge, as there is a lack of specific and non-invasive biomarkers. In this study, we assessed the serum profile of proinflammatory mediators (E- and P-selectin, CCL2, IL-1α, IL-12p70, TNF-α) in patients with IBD to identify biomarkers helpful in the differential diagnosis of CD and UC. The conducted statistical analyses revealed a significant increase in E-selectin, P-selectin, IL-1α, and IL-12p70 levels in the serum of CD patients compared to UC. The performed ROC curve analysis identified moderate values of E-selectin (AUC 0.752), P-selectin (AUC 0.733), and IL-1α (AUC 0.731) in differentiating CD from UC, while IL-12p70 presented a satisfactory value (AUC 0.695). Simultaneous measurements of each biomarker with serum calprotectin improved the ability of E-selectin (AUC 0.752 vs. 0.829), P-selectin (AUC 0.733 vs. 0.75), IL-1α (AUC 0.731 vs. 0.778), and IL-12p70 (AUC 0.695 vs. 0.714) to differentiate CD from UC. Moreover, we identified a significant relationship between the concentration of CCL2 (r = 0.566, p < 0.005) and TNF-α (r = 0.431, p < 0.05) and the disease activity expressed as the Mayo score in the UC group. We also identified a significant relationship between the concentration of E-selectin (r = 0.372, p < 0.05), CCL-2 (r = 0.55, p < 0.05), IL-1α (r = 0.637, p < 0.005), and TNF-α in the group of patients with UC. Another significant correlation in the UC group was noted in the case of E-selectin and IL-12p70 (r = 0.542, p < 0.05), as well as between IL1-α and P-selectin (r = 0.514, p < 0.05). The results obtained in this study indicate the potential use of E-selectin, P-selectin, IL-1α, and IL-12p70 serum profiles in differentiating CD from UC. Regarding the significant relationship of CCL2 and TNF-α with the Mayo score, these two biomarkers might be useful in assessing and monitoring the disease activity during UC.

A complex evaluation of colorectal cancer (CRC) in relation to screening, diagnosis, stage determination, prognosis, and treatment requires valuable biomarkers. The aim of this study was to measure selected biomarkers—uric acid (UA), lactate, Na+, Cl−, and osmolality—in CRC patients and to assess their diagnostic value to distinguish between CRC and healthy controls. Plasma lactate (2.21 ± 0.11 vs. 2.88 ± 0.19, p < 0.01), Na+ (130.79 ± 0.42 vs. 133.23 ± 0.25, p < 0.001), Cl− (102.59 ± 0.45 vs. 103.94 ± 0.23, p < 0.01), and osmolality (266.44 ± 0.86 vs. 271.72 ± 0.62, p < 0.001) were found to be significantly lower in CRC patients as compared to the healthy controls group. Among them, with satisfactory diagnostic potential, were plasma Na+ concentrations and osmolality (AUCNa+ = 0.752, p < 0.0001; AUCosmolality = 0.757, p < 0.05), respectively. UA concentrations were detected at higher concentrations in CRC patients (333.67 ± 13.05 vs. 295.88 ± 13.78, p < 0.05). The results of this study contribute to the elucidation of molecular mechanisms of CRC pathogenesis and the role of studied metabolic parameters in this process. Plasma uric acid, lactate, and osmolality parameters can be used for screening and monitoring colorectal cancer. Further studies are required to elucidate the molecular mechanisms of their action in cancer development. The action of circulating plasma lactate may be different from those locally produced in the tumor microenvironment.

Background: Pulmonary involvement in systemic juvenile idiopathic arthritis (SJIA) is a rare but dangerous complication. The main risk factors are already known, such as macrophage activation syndrome, a refractory course of systemic juvenile arthritis, infusion reaction to interleukin 1 and/or interleukin 6 blockers, trisomy 21, and eosinophilia. However, information about respiratory system involvement (RSI) at the onset of SJIA is scarce. Our study aimed to evaluate the specific features of children with SJIA with RSI and their outcomes. Methods: In a single-center retrospective cohort study, we compared the information from the medical records of 200 children with SJIA according to ILAR criteria or SJIA-like disease (probable/possible SJIA) with and without signs of RSI (dyspnea, shortness of breath, pleurisy, acute respiratory distress syndrome, and interstitial lung disease (ILD)) at the disease onset and evaluated their outcomes (remission, development of chronic ILD, clubbing, and pulmonary arterial hypertension). Results: A quarter (25%) of the SJIA patients had signs of the RSI at onset and they more often had rash; hepato- and splenomegaly; heart (pericarditis, myocarditis), central nervous system, and kidney involvement; hemorrhagic syndrome; macrophage activation syndrome (MAS, 44.4% vs. 9.0%, p = 0.0000001); and, rarely, arthritis with fewer active joints, compared to patients without RSI. Five patients (10% from the group having RSI at the onset of SJIA and 2.5% from the whole SJIA cohort) developed fibrosing ILD. All of them had a severe relapsed/chronic course of MAS; 80% of them had a tocilizumab infusion reaction and further switched to canakinumab. Unfortunately, one patient with Down’s syndrome had gone. Conclusion: Patients with any signs of RSI at the onset of the SJIA are required to be closely monitored due to the high risk of the following fibrosing ILD development. They required prompt control of MAS, monitoring eosinophilia, and routine checks of night oxygen saturation for the prevention/early detection of chronic ILD.

The single crystals of CsI-Yb2+ were grown, and their spectroscopic studies were conducted. The observed luminescence in CsI-Yb2+ is due to 5d–4f transitions in Yb2+ ions. Using time-resolved spectroscopy, spin-allowed and spin-forbidden radiative transitions of ytterbium ions at room temperature were found. The excitation spectra of Yb2+ luminescence bands were obtained in the range of 3–45 eV. The mechanism of charge compensation of Yb2+ ions in a CsI crystal was also studied, the spectrum of the thermally stimulated depolarization current was measured, and the activation energies of the two observed peaks were calculated. These peaks belong to impurity–vacancy complexes in two different positions. The charge compensation of Yb2+ occurs via cation vacancies in the nearest-neighbor and next-nearest-neighbor positions.The Yb2+ ions are promising dopants for CsI scintillators and X-ray phosphors in combination with SiPM photodetectors.

This study describes the impact of surfactant molecular weights (PEG 2000 and PEG 4000) on the photocatalytic activity of TiO2 films, deposited via dip-coating from a PEG-stabilized suspension and silver-functionalized photo-fixation of Ag+ under UV illumination. The photocatalytic activity of pure and Ag/TiO2 films is assessed in the aqueous-phase degradation of Malachite green and Methylene blue in distilled and tap water under UV and visible illumination. The results indicate a positive effect of both the higher-molecular-weight non-ionic surfactant and Ag-functionalization yield higher photocatalytic efficiency. Notably, films photo-fixed with 10−2 M Ag+ show the highest degradation percentages in all experimental conditions. A direct correlation between the concentration of Ag+ ions and the enhancement of the photocatalytic activity is revealed: pure TiO2 < Ag, 10−4/TiO2 < Ag, 10−3/TiO2 < Ag, 10−2/TiO2. Flame atomic absorption spectrometry is used to study the Ag+ leeching from the Ag/TiO2 films. The structural properties of the nanostructures are investigated through scanning electron microscopy, Brunauer–Emmett–Teller analysis, energy-dispersive X-ray spectroscopy, and X-ray diffraction. Additionally, after three cycles of operation, Ag, 10−2/TiO2 (PEG 4000) films can maintain their photocatalytic activity, suggesting a potential application in the treatment of dye wastewater.

Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity was estimated in strip preparations from pinealectomized (pin, melatonin deficiency) and sham-operated (sham, normal melatonin) adult rats using the forced oscillations method. In the untreated aortic wall pin, the viscoelasticity was not significantly altered. However, combined with 10−9 M fentanyl, the pin increased the natural frequency (f0) and modulus of elasticity (E’) compared to the sham-operated. Independently, fentanyl treatment decreased f0 and E’ compared separately to untreated sham and pin preparations. The effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced E’. Additional studies are needed that may improve the clinical decisions for pain management and anesthesia for certain patients with co-occurring chronic low levels of blood plasma melatonin and some diseases.

The wound-healing effect of St. John’s Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study investigates how “free” HP-rich SJW extract (incorporated into a bigel; B/SJW) and extract “protected” by nanostructured lipid carriers (also included in a biphasic semisolid; B/NLC-SJW) affect tissue regeneration in a rat skin excision wound model. Wound diameter, histological changes, and tissue gene expression levels of fibronectin (Fn), matrix metalloproteinase 8 (MMP8), and tumor necrosis factor-alpha (TNF-α) were employed to quantify the healing progress. A significant wound size reduction was achieved after applying both extract-containing semisolids, but after a 21-day application period, the smallest wound size was observed in the B/NLC-SJW-treated animals. However, the inflammatory response was affected more favorably by the bigel containing the “free” SJW extract, as evidenced by histological studies. Moreover, after the application of B/SJW, the expression of Fn, MMP8, and TNF-α was significantly higher than in the positive control. In conclusion, both bigel formulations exhibited beneficial effects on wound healing in rat skin, but B/SJW affected skin restoration processes in a comprehensive and more efficient way.

In this study, pure TiO2 gels were synthesized by applying the sol–gel method, using Ti(IV) butoxide with the addition of two different solvents, namely ethylene glycol (EG) and isopropanol (isop), with only air moisture present. It was established using XRD that the gel prepared with the addition of EG was amorphous even at 400 °C, while the other gel was amorphous up to 300 °C. It was found that TiO2 (anatase) had a dominant crystalline phase during heating to 600 °C, while at 700 °C, TiO2 (rutile) appeared. The as-obtained powdered materials were annealed at 500 °C and subsequently underwent photocatalytic tests with paracetamol. Additionally, the TiO2 samples were modified with Ag+ co-catalysts (10−2 M), using photofixation by UV illumination. The photocatalytic activity of the Ag-modified powders was also tested in the photodegradation of a commonly used paracetamol in aqueous solution under UV light illumination. The obtained data exhibited that the annealed samples had better photocatalytic efficiency and decomposed paracetamol faster in comparison to the non-annealed sol–gel powders. The highest degradation efficiency was observed for the TBT/isop/Ag material, with degradation efficiencies average values of 65.59% and 75.61% paracetamol achieved after the third cycle of photocatalytic treatment. The co-catalytically modified powders had higher photocatalytic efficiency in comparison to the pure nanosized powders. Moreover, the sol–gel powders of TBT/EG, TBT/EG/Ag (10−2 M), TBT/isop, and TBT/isop/Ag (10−2 M) demonstrated the ability to retain their photocatalytic activity even after three cycles of use, suggesting that they could find practical use in the treatment of pharmaceutical wastewater. The observed photocatalytic efficiency and positive impact of silver make the prepared powders a desirable choice for pharmaceutical drug degradation, helping to promote environmentally friendly and effective wastewater treatment technology.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the “classical” borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer—the process of tumor neoangiogenesis.

The article is aimed at systematizing the experience of formation and implementation of tax policy in the European Union Member States, defining the main dominants of this policy. The article analyzes the level of tax burden (the tax-to-GDP ratio) for the EU-27 countries for the period of 1995–2021 and determines that the average value of the indicator in the mentioned sample is 40.48%. The relationship between the tax burden and economic growth rates is examined. Although it is believed that the level of taxation is one of the main reasons for the existence of the shadow economy, the study proves that in countries where the level of tax burden is one of the lowest (Bulgaria, Romania, Lithuania, and Latvia), the shadow economy is twice as high as in Sweden, where the level of taxation is higher by more than 15% of GDP. In 27 of the EU countries, labor taxes occupy the highest share in the tax structure. The lowest level of labor taxation is present in Bulgaria and Romania – 10.0%, while in nine another EU countries the marginal rate of personal income tax exceeds 50%. Consumption taxes are the second most fiscally important component of tax revenues in the EU countries. There is a tendency to increase the standard VAT rate in the EU countries. In the European Union, a regime of reduced VAT rates is applied, aimed at reducing the tax burden, stimulating consumption and business activity, which is of great social significance. It is determined that in the EU when administering VAT, the issues of using digital products and technologies are of great importance. This allows to increase the fiscal efficiency of the tax by improving the quality of tax control, which is based on the risk-oriented approach. The EU has unified the rules for calculating and paying excise duty in the terms of excisable goods, as well as the procedure and conditions for their storage, movement, control over the production and circulation of excisable products. It is noted that the tax climate, together with the fundamental institutional foundations for economic development, are guidelines for entrepreneurs regarding the possibilities of opening or scaling a business. That is why recently there has been a further reduction in corporate tax rates – by an average of 9 percentage points. Ensuring fairness of taxation and criteria for equality of the tax system are among the important benchmarks of the EU fiscal policy. Property taxes are important in the tax systems of the EU member States. These taxes are the basis for filling local budgets with their own revenues, the relevant revenues are quite stable and predictable. It is concluded that, in general, the tax policy of the EU Member States is constantly adapting to socioeconomic conditions, which is manifested in changes in the parameters of rates, base, provision of targeted benefits, etc. This together is aimed at creating incentives for economic growth and ensuring social justice.

During the period 2009–2016, brown hares (Lepus europeus L.) from different regions of Bulgaria were investigated for infections with liver parasites as well as for seroprevalence of protozoan Toxoplasma gondii. Three helminth species were found in the liver: one trematode – Dicrocoelium dendriticum, one cestode – larval form of Taenia pisiformis – Cysticercus pisiformis and one nema¬tode – Micipsella numidica. Dicrocoeliasis was found in all parts of the country with infected hares originating mainly from the western regions. The total prevalence of infection with D. dendriticum was 10.59%. The intensity of infection ranged from 1 to 184, 26.67 on the average. The total prevalence of infection with C. pisiformis was 16.8%. The prevalence of infection was highest among hares from the southern parts of the country, and no cysticercosis was registered in the western parts. The extent of infestation with cysticerci was different – from single cysticerci on the omentum or serosa of some organs in the abdominal cavity to innumerable ones that affected also the organs in the thoracic cavity. However, cases in which the animals were slightly affected, predominated. The total prevalence of infection with M. numidica was 5.31%, and the intensity of infection varied between 1 and 6 parasites in one animal. The nematodiasis was established mainly in hares from southern Bulgaria. The total seroprevalence of T. gondii was 6.15% and the protozoan-positive animals originated from three districts: Stara Zagora, Plovdiv, and Burgas. The current studies also showed that the prevalence of D. dendriticum infection among animals increased with age. No correlation was observed between prevalence of infection with C. pisiformis and M. numidica and host age. No correlation was found between the prevalence of the helminth infections and sex of the animals.

Abstract Background Endocrine-resistant HR+/HER2- breast cancer (BC) and triple-negative BC (TNBC) are of interest for molecularly informed treatment due to their aggressive natures and limited treatment profiles. Patients of African Ancestry (AA) experience higher rates of TNBC and mortality than European Ancestry (EA) patients, despite lower overall BC incidence. Here, we compare the molecular landscapes of AA and EA patients with HR+/HER2- BC and TNBC in a real-world cohort to promote equity in precision oncology by illuminating the heterogeneity of potentially druggable genomic and transcriptomic pathways. Methods De-identified records from patients with TNBC or HR+/HER2- BC in the Tempus Database were randomly selected (N = 5000), with most having stage IV disease. Mutations, gene expression, and transcriptional signatures were evaluated from next-generation sequencing data. Genetic ancestry was estimated from DNA-seq. Differences in mutational prevalence, gene expression, and transcriptional signatures between AA and EA were compared. EA patients were used as the reference population for log fold-changes (logFC) in expression. Results After applying inclusion criteria, 3433 samples were evaluated (n = 623 AA and n = 2810 EA). Observed patterns of dysregulated pathways demonstrated significant heterogeneity among the two groups. Notably, PIK3CA mutations were significantly lower in AA HR+/HER2- tumors (AA = 34% vs. EA = 42%, P

The aim of this study was to investigate the potential association of rs11206510 in PCSK9 gene with coronary artery disease (CAD) and myocardial infarction (MI) in Bulgarians.