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This study focuses on the application of hyperspectral imaging techniques for the genetic preservation of historic trees, specifically investigating the 600-year-old "Dedek" Oak in Maksimir Park, Croatia. The research aims to contribute to the conservation of Croatia's natural heritage and underscore the potential of hyperspectral imaging in tree preservation. The Croatian Forest Research Institute has been actively involved in preserving the pedunculate oak trees, recognizing their cultural and ecological significance. Efforts have been made to cultivate seedlings from the original genetic material, thereby preventing the loss of valuable genes and ensuring their long-term preservation. Spectral signatures of "Dedek" Oak and its clones were captured using high-performance hyperspectral push broom cameras, including the HySpex VNIR-1800 and SWIR-384. Spectral camera scanning was conducted in the field and laboratory. The comparative analysis of the spectral samples revealed unique characteristics and demonstrated the effectiveness of hyperspectral imaging in studying historic trees for preservation purposes. The spectral signatures of vegetation display dynamic characteristics in terms of spectral resolution. Collecting and documenting these signatures is considerably more challenging, and their integration into spectral libraries should be approached with careful consideration. There are several spectral libraries that are organized by chapters and consist of samples that have a sufficient number of analysis and documentation to determine the quality of the spectrum. In this study, spectral signatures of pedunculate oak (Quercus robur L.) called Dedek and its clones were singled out. The objective of this research was to establish a foundation for a spectral library that would facilitate future research on the application of hyperspectral scanners for detecting protected tree species and their clones, all for the purpose of preservation of the genetic diversity of protected trees in Croatia. The findings of this research contribute to the conservation of Croatia's natural heritage by providing valuable insights into the genetic preservation of the 600-year-old "Dedek" Oak. Also, determining the spectral signatures of clones can help us with the identification of specific tree species (especially during aerial imaging, which is planned to be conducted in the future). In conclusion, this research showcases the importance of preserving historic trees and the potential of hyperspectral imaging as a valuable tool for genetic preservation efforts. The study's outcomes contribute to the long-term conservation of Croatia's natural heritage and provide a foundation for future research in the field of tree preservation and spectral library inception.

Abstract We perform a detailed study of the covariance properties of the symplectic potential of general relativity on a null hypersurface, and of the different polarizations that can be used to study conservative as well as leaky boundary conditions. This allows us to identify a one-parameter family of covariant symplectic potentials. We compute the charges and fluxes for the most general phase space with arbitrary variations. We study five symmetry groups that arise when different restrictions on the variations are included. Requiring stationarity as in the original Wald-Zoupas prescription selects a unique member of the family of symplectic potentials, the one of Chandrasekaran, Flanagan and Prabhu. The associated charges are all conserved on non-expanding horizons, but not on flat spacetime. We show that it is possible to require a weaker notion of stationarity which selects another symplectic potential, again in a unique way, and whose charges are conserved on both non-expanding horizons and flat light-cones. Furthermore, the flux of future-pointing diffeomorphisms at leading-order around an outgoing flat light-cone is positive and reproduces a tidal heating plus a memory term. We also study the conformal conservative boundary conditions suggested by the alternative polarization and identify under which conditions they define a non-ambiguous variational principle. Our results have applications for dynamical notions of entropy, and are useful to clarify the interplay between different boundary conditions, charge prescriptions, and symmetry groups that can be associated with a null boundary.

Participants in studies investigating COVID-19 vaccines commonly report reactogenicity events, and concerns about side effects may lead to a reluctance to receive updated COVID-19 vaccinations. A real-world, post hoc analysis, observational 2019nCoV-406 study was conducted to examine reactogenicity within the first 2 days after vaccination with either a protein-based vaccine (NVX-CoV2373) or an mRNA vaccine (BNT162b2 or mRNA-1273) in individuals who previously completed a primary series. Propensity score adjustments were conducted to address potential confounding. The analysis included 1130 participants who received a booster dose of NVX-CoV2373 (n = 303) or an mRNA vaccine (n = 827) during the study period. Within the first 2 days after vaccination, solicited systemic reactogenicity events (adjusted) were reported in 60.5% of participants who received NVX-CoV2373 compared with 84.3% of participants who received an mRNA vaccine; moreover, 33.9% and 61.4%, respectively, reported ≥3 systemic reactogenicity symptoms. The adjusted mean (95% CI) number of systemic symptoms was 1.8 (1.6–2.0) and 3.2 (3.0–3.4), respectively. Local reactogenicity events (adjusted) were reported in 73.4% and 91.7% of participants who received NVX-CoV2373 and mRNA vaccines, respectively; the adjusted mean (95% CI) number of local symptoms was 1.5 (1.33–1.61) and 2.4 (2.31–2.52), respectively. These results support the use of adjuvanted, protein-based NVX-CoV2373 as an immunization option with lower reactogenicity than mRNAs.

The targeted compounds in this research, resveratrol analogs 1–14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes’ structure and identify the non-covalent interactions responsible for the complex’s stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.

Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f+, and non-CSCs (CD49f−) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (p < 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound 1 resulted in statistically meaningful increased apoptosis, including both early and late apoptosis (p < 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group (p < 0.001).

Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19+ B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity. Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy.

Summary: Background: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. Methods: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. Findings: We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. Interpretation: Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses. Funding: German Center for Infection Research, German Center for Lung Research, German Research Foundation, Excellence Strategy EXC 2155 “RESIST” and European Regional Development Fund.

Lavender (Lavandula angustifolia Mill.) is a perennial, aromatic, medicinal, and decorative plant widespread in the Mediterranean. Due to the high content of essential oil and numerous beneficial properties, it is an extremely valued plant species. In Bosnia and Herzegovina, lavender is cultivated mainly for the needs of the cosmetic and pharmaceutical industries. In this research, the antioxidant activity and acetylcholinesterase inhibition of essential oil (EO) and extracts isolated from lavender were evaluated. L. angustifolia EO was isolated using whole plant material in the flowering period by steam distillation and analyzed by gas chromatography (GC) with flame-ionization (FID) and mass spectrometric (MS) detection. Extracts were prepared by ultrasonic extraction in solvents of different polarities. Total phenolic content in extracts was determined using Folin–Ciocalteu reagent. The antioxidant activity of EO and extracts was examined by two methods, 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging activities and ferric reducing/antioxidant power (FRAP), while the acetylcholinesterase (AChE) inhibitory potential was determined using modified Ellman’s method. The EO was high in content of linalool (27.72%) and linalyl acetate (22.82%), followed by α-pinene (9.82%), lavandulol acetate (7.32%), trans-caryophyllene (5.70%), and others. In total, 24 components were identified. Total phenol content was highest in water and ethanol extracts (45.3 and 14.40 mg gallic acid equivalent (GAE)/g dry extract). Polar extracts indicate good antioxidant power according to both methods, while EO can be considered as good inhibitor of AChE.

Triazoles and triazolium salts are very common subunits in the structures of various drugs. Medicaments with a characteristic 1,2,3-triazole core are also being developed to treat neurodegenerative disorders associated with cholinesterase enzyme activity. Several naphtho- and thienobenzo-triazoles from our previous research emerged as being particularly promising in that sense. For this reason, in this research, new naphtho- and thienobenzo-triazoles 23–34, as well as 1,2,3-triazolium salts 44–51, were synthesized and tested. Triazolium salts 44–46 showed excellent activity while salts 47 and 49 showed very good inhibition toward both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes. In contrast, neutral photoproducts were shown to be selective towards BChE but with very good inhibition potential as molecules 24–27. The representative of newly prepared compounds, 45 and 50, were stable in aqueous solution and revealed intriguing fluorimetric properties, characterized by a strong Stokes shift of >160 nm. Despite their condensed polycyclic structure shaped similarly to well-known DNA-intercalator ethidium bromide, the studied compounds did not show any interaction with ds-DNA, likely due to the unfavorable steric hindrance of substituents. However, the studied dyes bind proteins, particularly showing very diverse inhibition properties toward AChE and BChE. In contrast, neutral photoproducts were shown to be selective towards a certain enzyme but with moderate inhibition potential. The molecular docking of the best-performing candidates to cholinesterases’ active sites identified cation–π interactions as the most responsible for the stability of the enzyme–ligand complexes. As genotoxicity studies are crucial when developing new active substances and finished drug forms, in silico studies for all the compounds synthesized have been performed.

Summary: Background: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. Methods: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established “biological-ageing-clock”) in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. Findings: Biological age in adults with DS is (on average) 18.4–19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. Interpretation: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. Funding: Main funding came from the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the “Acknowledgements”.

Rad istražuje različite znanstvene pristupe proučavanju i definiranju lažnih vijesti, s naglaskom na divergentnost tumačenja i analizu dobivenih rezultata. Cilj je ovoga istraživanja u okviru informacijskih i komunikacijskih znanosti definirati „lažne vijesti“. Glavna teza rada naglašava da lažne vijesti nisu zasebna vrsta informacija narušena integriteta, nego se pojavljuju kao oblik dezinformacije. Autori uspoređuju različite perspektive pristupu lažnim vijestima, ističući kako razumijevanje njihove prirode zahtijeva analizu širega konteksta informacijskoga i komunikacijskoga okružja. Zaključci istraživanja ukazuju na nužnost prilagodbe definicija lažnih vijesti, uključujući i slučajeve gdje lažne vijesti nisu nužno namjerne dezinformacije, nego rezultat nesporazuma ili nekritičkoga širenja netočnih podataka. Divergentnost pristupa uočena tijekom istraživanja sugerira da postoji potreba za integriranim i interdisciplinarnim pristupom kako bi se dinamika lažnih vijesti bolje razumjela. Konačno, istraživanje potiče na daljnje napore u razvoju strategija prepoznavanja i suzbijanja lažnih vijesti kao oblika dezinformacija koje uzimaju u obzir raznolikost formata njihove pojave.

The present paper focuses on teacher’s role in social justice and explores how teachers perceive and react upon diversity and inequality in their classrooms. Through a literature review, we aimed to answer three research questions: 1) what are diversity awareness and critical consciousness in education; 2) why are diversity awareness and critical consciousness important; and 3) how can diversity awareness and critical consciousness be supported in teachers. The literature review has revealed that most papers on teachers’ diversity awareness and critical consciousness have been published within the last few years and that the importance of the two concepts has been recognized for a wide range of educators. There seems to be a growing interest in this topic due to the increase of the diversity in classrooms and the recognition of the teachers’ role in addressing diversity and inequality. However, large-scale studies would be a needed contribution to the field, as most of the existing studies are small-scale. Based on this review, we argue that both diversity awareness and critical consciousness need to be supported through preservice and in-service teacher professional development programs, if we are to make education systems more inclusive for all.

Abstract Background Parents of children who have a congenital anomaly can experience significant worry about their child’s health. Access to clear, helpful, and trustworthy information can provide a valuable source of support. In this study the aim was to explore the information needs of parents/carers of children with congenital anomalies across Europe. Method A cross-sectional online survey was developed in nine languages to measure parents’ information needs, including: (1) the ‘helpfulness’/’trustworthiness’ of information received from eight relevant sources, and (2) overall satisfaction with information received. Parents/carers of children (0–10 years) with cleft lip, spina bifida, congenital heart defect [CHD] requiring surgery, and/or Down syndrome were recruited online via relevant organisations in 10 European countries from March-July 2021. Quantitative analyses using multivariable logistic regressions were performed. Results One thousand seventy parents/carers of children with a cleft lip (n = 247), spina bifida (n = 118), CHD (n = 366), Down syndrome (n = 281), and Down syndrome with CHD (n = 58) were recruited in Poland (n = 476), the UK (n = 120), Germany (n = 97), the Netherlands/Belgium (n = 74), Croatia (n = 68), Italy (n = 59), other European countries (n = 92), and not specified/non-European countries (n = 84). Most participants were mothers (92%) and aged 31–40 years (71%). Participants were most likely to rate support groups (63%), patient organisations (60%), specialist doctors/nurses (58%), and social media (57%) as ‘very helpful’ information sources. ‘Very trustworthy’ ratings remained high for specialist doctors/nurses (61%), however, they declined for support groups (47%), patient organisations (48%), and social media (35%). Germany had the highest proportion of participants who were ‘very satisfied’ (44%, 95% CI = 34%-54%) with information, whereas this percentage was lowest in Croatia (11%, 95% CI = 3%-19%) and Poland (15%, 95% CI = 11%-18%). Parents of children with Down syndrome had significantly lower satisfaction ratings than parents of children with CHD; 13% (95% CI = 8%-18%) reported being ‘very satisfied’ compared to 28% (95% CI = 23%-33%) in the CHD group. Conclusions Findings suggest that informal sources of information (e.g. support groups) are of value to parents, however, they are not deemed as trustworthy as specialist medical sources. Satisfaction ratings differed across countries and by anomaly, and were particularly low in Croatia and Poland, as well as for parents of children with Down syndrome, which warrants further investigation.

In our previous research, some screened 1,3-thiazole fragments were found to be potent by inhibiting LPS-induced TNF$\alpha $ and IL-8 release with IC50 values in the $\mu $M range without cytotoxic activity. In the current study, 1,3-thiazole fragments were further investigated as potent cholinesterase inhibitors prompted by the previously documented anti-inflammatory effect of AChE inhibitors. Molecular docking enabled insight into stabilizing interactions between the selected thiazoles and the active site of AChE and BChE. According to these experimental results, the cholinesterase inhibitory and anti-inflammatory activity of 1,3-thiazoles were correlated and confirmed that the same compounds inhibited LPS-stimulated TNF$\alpha $ cytokine production in PBMCs and enzymes cholinesterases.

Vaccines against SARS-CoV-2 have changed the course of the COVID-19 pandemics, but waning immunity necessitates repeated immunization. Authors here show that immunity declines faster following two doses of vector-based vaccine compared to a first dose of vector-based vaccine followed by boosting with an mRNA vaccine, but application of an mRNA vaccine as a third dose minimises the difference between the two groups.