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Abstract Development of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, highly exposed individuals may develop immunity against re-infection with the same strain. Retrospective epidemiological studies have shown that vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provide a degree of cross-protection against Ng infection. We conducted a clinical trial (NCT04297436) of 4CMenB (Bexsero, GSK), a licensed Nm vaccine containing OMVs and recombinant antigens, comprising a single arm, open label study of two doses with 50 adults in coastal Kenya who have high exposure to Ng. Data from a Ng antigen microarray established that serum IgG and IgA reactivities against the gonococcal homologs of the recombinant antigens in the vaccine peaked at 10 but had declined by 24 weeks. For most reactive OMV-derived antigens, the reverse was the case. A cohort of similar individuals with laboratory-confirmed gonococcal infection were compared before, during, and after infection: their reactivities were weaker and differed from the vaccinated cohort. We conclude that the cross-protection of the 4CMenB vaccine against gonorrhoea could be explained by cross-reaction against a diverse selection of antigens derived from the OMV component.

Learning disabilities, specifically dyslexia, affect learning processes and school performance of pupils and students at all levels of education. The aim of this narrative synthesis is to outline the topics that are investigated in relation to the university studies of people with dyslexia, while the mapping of this empirical knowledge has the potential to reflect these studies at their different stages. From 923 studies registered between 2001 and 2020 in the Web of Science database, we included 65 studies, which represent an overview of knowledge about decisions about university studies, adjustment in the university environment, study strategies of individuals with dyslexia and support that is provided by university. The results show that dyslexia and its symptoms can be a barrier to successful university studies, yet these students can overcome these barriers with adequate support.

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure. Methods 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed. Results SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects. Conclusions Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.

This paper addresses the growing global concern regarding energy consumption and its adverse environmental impacts, particularly the increase of greenhouse gas emissions linked to economic development and population growth. To comprehensively assess the environmental implications of energy consumption, a decomposition analysis employing the Index decomposition analysis (IDA) method with the logarithmic mean Divisia index (LMDI) approach was conducted, focusing on the drivers behind energy consumption and greenhouse gas emissions in the EU 27 from 1998 to 2018. This analysis discerns disparities between wealthier and less affluent countries. The findings highlight substantial reductions in greenhouse gas emissions and energy consumption within the EU, primarily attributed to the growing emphasis on reducing the emission intensity targeted by EU policies. Nonetheless, disparities persist among member states, primarily driven by economic activity levels. In relation to the unique economic structures of EU countries results however advocate for diversified approaches tailored to the unique conditions of each Member State to meet the set targets, with an emphasis on fostering collaboration, technology transfer, innovation, and renewable energy adoption to advance sustainability of the region.

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. Methods This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. Discussion PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. Trial Registration NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020–000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020–01, version 3.2, date 18.09.2020.

Climate change is expected to affect the frequency and magnitude of floods, which are among the costliest hazards in Europe. As natural hazards have a significant impact on infrastructure and people's lives and their habitats, novel measures to cope with climate change need to be considered. Different types of measures, such as green, grey and hybrid solutions, can be used to mitigate the impacts of natural hazards. Green measures (also referred to as nature-based solutions) are currently being promoted in the European Union, but several barriers to implementing these measures exist. The question arises as to what hinders the wider implementation of green measures and therefore results in a preference for conventional grey measures in some countries. This study examines the differences in the perceived effectiveness, feasibility and acceptance of different types of flood risk management measures in three European countries (Slovenia, Czechia, and the Netherlands). The results show statistically significant differences in the perceived effectiveness, feasibility and acceptance of the studied measures. With respect to individual measures, respondents in all three countries tend to view conventional grey measures (dams and cisterns) as more effective and acceptable than green and hybrid measures. However, grey measures are perceived as difficult to implement. The results reveal that the perceived effectiveness and acceptability of the measures are related. The major drivers affecting the differences in the perceptions of different measures are the countries of the respondents and the sociodemographic variables of income and age. In contrast to other studies, experiences with past floods and private insurance are not statistically significant. Our results thus indicate that, along with individual behaviour, aggregate social drivers should be considered when implementing flood risk management measures across the EU.

Central and Eastern European (CEE) countries have recently implemented reforms to health care provider payment systems, which include changing payment methods and related systems such as contracting, management information systems, and accountability mechanisms. This study examines factors influencing provider payment reforms implemented since 2010 in Bulgaria, Croatia, Czechia, Estonia, Latvia, Lithuania, Hungary, Poland, and Romania. A four-stage mixed methods approach was used: developing a theoretical framework and data collection form using existing literature, mapping payment reforms, consulting with national health policy experts, and conducting a comparative analysis. Qualitative analysis included inductive thematic analysis and deductive approaches based on an existing health policy model, distinguishing context, content, process, and actors. We analyzed 27 payment reforms that focus mainly on hospitals and primary health care. We identified 14 major factor themes influencing those reforms. These factors primarily related to the policy process (pilot study, coordination of implementation systems, availability of funds, IT systems, training for providers, reform management) and content (availability of performance indicators, use of clinical guidelines, favorability of the payment system for providers, tariff valuation). Two factors concerned the reform context (political willingness or support, regulatory framework, and bureaucracy) and two were in the actors’ dimension (engagement of stakeholders, capacity of stakeholders). This study highlights that the content and manner of implementation (process) of a reform are crucial. Stakeholder involvement and their capacities could influence every dimension of the reform cycle. The nine countries analyzed share similarities in barriers and facilitators, suggesting the potential for cross-country learning.

Abstract Background/Aim The study aims to describe the role of diabetes in patients with heart failure. Methods In all, 1052 chronic heart failure patients were included in the FARmacology and NeuroHumoral Activation (FAR NHL) multicenter prospective registry. They had ejection fraction below 50% and were on stable medication for at least 1 month. Results More than one‐third (38.9%) of the patients had diabetes mellitus (DM). Diabetic patients (N = 409) were older (median 67 vs. 64, p

Aim: To describe current scientific knowledge on cognitive impairment and emotional disturbances (anxiety and depression) in younger adult patients after ischemic stroke. Design: A scoping review. Methods: For the search, the following scientific databases were utilized: Web of Science, MEDLINE (Ovid), ScienceDirect (Elsevier), PsycInfo (EBSCO), Scopus (Elsevier), and ProQuest. Relevant studies were identified by searching publications from 2000 to July 2023. Results: A total of eight studies were ultimately included in the review. Cognitive impairment occurred in a range between 39.4% and 40%. This encompassed various aspects of cognitive function, such as working memory, processing speed, global cognitive function, immediate and delayed memory, attention, and executive functioning. Depression had an incidence rate ranging from 10.8% to 16.8%. Several risk factors were associated with a higher likelihood of developing generalized anxiety. These included younger age, more depressive symptoms, lower education, unemployment, a history of depression, and alcohol use. In the context of depressive symptoms, a higher risk was linked to lower education and unemployment. Conclusion: The included studies highlighted the need to assess these issues not only at the time of patient discharge but, more importantly, during the stage of further recovery. This can contribute to the creation of tailored interventions for these individuals.

Background Limited evidence of young adult patient-reported outcomes and experiences after ischaemic stroke has been conducted. Aim To investigate the meaning of the lived experiences of stroke patients in working age 12–24 months after their first IS. Material and Methods The exploratory qualitative study used an interpretative phenomenological analysis (IPA) design. Nine ischaemic stroke patients (with age ranges from 41 to 50 years) took part in semi-structured qualitative interviews. Results Even with mild residual neurological deficit, IS negatively impacted the quality of life daily and social life. Six subthemes and three interconnected group experiential themes were generated: (i) From confusion to understanding (ii) Triggers for rebuilding; and (iii) Challenges and benefits. Conclusion The study highlights the current gaps and limitations in supporting the needs of stroke patients in working age in long-term post-stroke care. The findings are crucial for healthcare professionals to develop improved age- and mild- impairment-appropriate strategies or tailor self-management interventions for stroke patients of working age. ClinicalTrials.gov: NCT04839887.

AbstractBackground Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent COVID-19 has spread world-wide and become pandemic with about 7 million deaths reported so far. Interethnic variability of the disease has been described, but a significant part of the differences remain unexplained and may be attributable to genetic factors.Aim To analyse genetic factors potentially influencing COVID-19 susceptibility and severity in European Roma minority.Subjects and methods Two genetic determinants, within OAS-1 (2-prime,5-prime-oligoadenylate synthetase 1, a key protein in the defence against viral infection; it activates RNases that degrade viral RNAs; rs4767027 has been analysed) and LZTFL1 (leucine zipper transcription factor-like 1, expressed in the lung respiratory epithelium; rs35044562 has been analysed) genes were screened in a population-sample of Czech Roma (N = 302) and majority population (N = 2,559).Results For both polymorphisms, Roma subjects were more likely carriers of at least one risky allele for both rs4767027-C (p

Incorporating C4 photosynthetic traits into C3 crops is a rational approach for sustaining future demands for crop productivity. Using classical plant breeding, engineering this complex trait is unlikely to achieve its target. Therefore, it is critical and timely to implement novel biotechnological crop improvement strategies to accomplish this goal. However, a fundamental understanding of C3, C4, and C3–C4 intermediate metabolism is crucial for the targeted use of biotechnological tools. This review assesses recent progress towards engineering C4 photosynthetic traits in C3 crops. We also discuss lessons learned from successes and failures of recent genetic engineering attempts in C3 crops, highlighting the pros and cons of using rice as a model plant for short‐, medium‐ and long‐term goals of genetic engineering. This review provides an integrated approach towards engineering improved photosynthetic efficiency in C3 crops for sustaining food, fibre and fuel production around the globe. [ABSTRACT FROM AUTHOR]

Abstract Background Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes (BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, BRIP1/FANCJ, and RAD51C/FANCO) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, but the role of GPVs in 17 other FA genes remains unclear. Methods Here, we investigated the association of germline variants in FANCG/XRCC9 with BC and OC risk. Results The frequency of truncating GPVs in FANCG did not differ between BC (20/10,204; 0.20%) and OC (8/2966; 0.27%) patients compared to controls (6/3250; 0.18%). In addition, only one out of five tumor samples showed loss‐of‐heterozygosity of the wild‐type FANCG allele. Finally, none of the nine functionally tested rare recurrent missense FANCG variants impaired DNA repair activities (FANCD2 monoubiquitination and FANCD2 foci formation) upon DNA damage, in contrast to all tested FANCG truncations. Conclusion Our study suggests that heterozygous germline FANCG variants are unlikely to contribute to the development of BC or OC.

Aldo-keto reductases (AKRs), a superfamily of NADP(H)-dependent oxidoreductases, catalyze the oxidoreduction of a wide variety of eobiotic and xenobiotic aldehydes and ketones. In mammals, AKRs play essential roles in hormone and xenobiotic metabolism, oxidative stress, and drug resistance, but little is known about these enzymes in the parasitic nematode Haemonchus contortus. In the present study, 22 AKR genes existing in the H. contortus genome were investigated and a phylogenetic analysis with comparison to AKRs in Caenorhabditis elegans, sheep and humans was conducted. The constitutive transcription levels of all AKRs were measured in eggs, larvae, and adults of H. contortus, and their expression was compared in a drug-sensitive strain (ISE) and a benzimidazole-resistant strain (IRE) previously derived from the sensitive strain by imposing benzimidazole selection pressure. In addition, the inducibility of AKRs by exposure of H. contortus adults to benzimidazole anthelmintic flubendazole in vitro was tested. Phylogenetic analysis demonstrated that the majority of AKR genes in H. contortus lack orthologues in the sheep genome, which is a favorable finding for considering AKRs as potential drug targets. Large differences in the expression levels of individual AKRs were observed, with AKR1, AKR3, AKR8, and AKR10 being the most highly expressed at most developmental stages. Significant changes in the expression of AKRs during the life cycle and pronounced sex differences were found. Comparing the IRE and ISE strains, three AKRs were upregulated, and seven AKRs were downregulated in adults. In addition, the expression of three AKRs was induced by flubendazole exposure in adults of the ISE strain. Based on these results, AKR1, AKR2, AKR3, AKR5, AKR10 and AKR19 in particular merit further investigation and functional characterization with respect to their potential involvement in drug biotransformation and anthelmintic resistance in H. contortus.

The abundance and species composition of adult ladybird communities (Coleoptera: Coccinellidae) were investigated on two congeneric trees, native Norway spruce (Picea abies) and the introduced blue spruce (Picea pungens), at four locations in Slovakia (central Europe). For two years (2021–2022), coccinellid adults were sampled using a standard method involving beating branches at monthly intervals from April to November. Although the species composition of the communities on both spruce species was similar, the abundance of the entire coccinellid community as well as the abundance of individual species was significantly greater on Norway spruce than on blue spruce. With the current decline of Norway spruce as a result of several negative factors, blue spruce has emerged as a suitable substitute host plant for coccinellid communities in urban areas.

IntroductionResearch on adolescents’ academic performance has mostly focused on the contribution of objective factors, such as socioeconomic situation of the family or individual cognitive skills and school results. Evidence with a focus on adolescents’ subjective experiences is scarce. The aim of this qualitative study was to explore factors related to adolescents’ academic performance from their perspectives.MethodsWe used data from 11 group semi-structured interviews conducted in 2020/2021 with 45 adolescents in the first year of high school in Slovakia (mean age = 14.98; 22.2% boys). Participants were selected from three types of high school with regards to the graduation system. We analysed the data using consensual qualitative research and thematic analysis.ResultsBased on the statements of the adolescents, we identified five main themes of factors that affect their academic performance. Adolescents reported that the following contribute to their academic performance: the contents and methods of teaching; how teachers behave and do their jobs; the way in which adolescents study and what motivates them; support within and outside the school, and the environment and appearance of the school. Adolescents reported that improving the curricula and using teaching methods that balance theoretical information with practical skills training would help their academic performance immensely.ConclusionWe identified several factors related to adolescents’ academic performance using their own perspectives and experiences. Strengthening the capacities of teachers may largely benefit adolescents’ educational process and further academic performance.

ObjectivesThis repeated cross-sectional study aimed to (a) report trends in adolescents’ perceived family, friend, classmate, and teacher support, (b) estimate the extent to which each source of support related to life satisfaction across space and time, and (c) ascertain whether sociodemographic factors moderated the relationship in question.MethodsWe relied on data pertaining to the 2013/14, 2017/18, and 2021/22 waves of the Health Behaviour in School-aged Children study. The examined sample covered 44 countries and regions (n = 716,083; MAGE = 13.6; SDAGE = 1.64; 50.7% female).ResultsThe level of all sources of perceived social support slightly decreased over the examined period (all ω2 < .01). Family support involved the largest association with life satisfaction (β = 0.16); friend support, the lowest one (β = 0.03). These associations varied only tenuously across space and time. Sociodemographic factors moderated the link between perceived social support and life satisfaction to a negligible-to-weak extent.ConclusionLevels of perceived social support and their associations with life satisfaction subtly changed. Future research may attempt to pinpoint the macrosocial levers of these temporal dynamics.

Learning assessment is an essential part of the educational process, and it is even more important when dealing with Teacher Education courses. Assessment procedures will be present throughout the future teaching career of students and, moreover, can be understood as another opportunity for knowledge construction, either in the preparation for exams or as practical experience. The educational practices of Teacher Education courses need to be in constant innovation to ensure that the educational quality extends to the schools. The present article brings the first findings of an Action Research in Education that aims to promote improvements in the final evaluation of a Pedagogy course. The text is structured in a reflexive-propositional dialogue of students and examiners' speeches with the scientific literature about the theme. In this first phase of the qualitative research, semi structured interviews were carried out with eight Pedagogy students and five examiners in the same course. The results identified two main issues: psychological suffering of students and lack of information about the final assessment. From that, changes in the assessment process of the course were put into practice to follow up the action research that, currently, is in the second moment of evaluation with students who are going through the final assessment with new practices.