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ACCEpTED: December 18, 2020 Introduction: Exercise stress test (ergometry) in pediatric cardiology practice is used to examine the condition and functional ability of the heart in children. It is performed using a bicycle ergometer or treadmill, estimating and measuring the amount of physical activity, heart rate, blood pressure values and electrocardiogram.1,2 The aim of article was to present the role and importance of exercise stress test in everyday clinical pediatric cardiac practice.

S. Hober, C. Hellström, Jennie Olofsson, E. Andersson, Sofia Bergström, August Jernbom Falk, Shaghayegh Bayati, Sára Mravinacová et al.

The COVID‐19 pandemic poses an immense need for accurate, sensitive and high‐throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high‐throughput multiplex bead‐based serological assay.

N. Fernandez-Anez, A. Krasovskiy, Mortimer M. Müller, H. Vacik, J. Baetens, E. Hukić, Marijana Kapović Solomun, I. Atanassova et al.

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009–2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action “Fire and the Earth System: Science & Society” funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.

Moving beyond notions of cosmopolitanism as a form of elitism, a condition of globalization, or a predominantly transnational orientation (to the exclusion of local affiliations), the volume draws on international survey data to posit an alternative view of cosmopolitanism, characterized by interlinkages and tensions between cosmopolitan and local identities and forms of belonging. Elaborating on what is termed ‘‘the cosmopolitan spirit,’’ Part II identifies four equally significant types of cosmopolitan expression, reflecting divergent processes of cosmopolitan socialization. A key argument here is that individuals can both be and become cosmopolitan in specific ways. The four forms of cosmopolitan orientation correspond to the aesthetic, cultural, ethical, and political dimensions of the cosmopolitan spirit and encompass different sets of cosmopolitan capabilities and virtues. The volume cogently explains and then illustrates the various cosmopolitan expressions with effective, sufficiently detailed international case studies and empirical work. Part II thus vitally provides sociologists and other academics with conceptual tools and typologies to examine and understand cosmopolitanism as it takes shape through people’s specific, situated relationships to the world. For this reader, however, the volume made less of how to apply these tools in conducting research ‘‘on the ground’’ and with regard to potential, tangible research sites. As such, the book’s main contribution is largely conceptual, in that it represents a valuable attempt to rework well-established sociological ideas (rather than relegate them to the theoretical dustbin) within a cosmopolitan sociology and to reassert their relevance in a cosmopolitan world. More than this, however, it commendably extends such ideas by advancing a typology of the cosmopolitan spirit’s different manifestations, providing new directions for research in the vein of a cosmopolitan sociology. Well-written and insightful, the book achieves its stated primary objective, which is ‘‘to locate cosmopolitan theories amidst social actors’ experiences of a shared and plural world, moving away from cosmopolitanism as a theoretical and normative perspective in order to examine the tangible, ordinary mechanisms of global society that are shaping the cultural imaginaries and the lives of individuals today’’ (p. xviii). In particular, it provides a nuanced understanding of contemporary cosmopolitanism, considering its different dimensions, contradictions, and ambivalent character, particularly as it unfolds and is grounded in quotidian processes of socialization. The volume is an important read for scholars and advanced students interested in cosmopolitanism in terms of its relationship to globalization, its key characteristics, and contemporary expressions. It may be less accessible to those without an introductory understanding of cosmopolitanism and the pivotal debates in cosmopolitan thought. Nonetheless, the book would be a valuable, welcome addition to the required readings for graduate seminars on the sociology of globalization and the sociology of cosmopolitanism, as well as seminars on socialization and identity formation, which now occur in a plural and shared global society.

Tanja Maksimović, N. Janjić, Biljana Lubarda

Background: Drought is one of the major abiotic factors leading to diminishing growth, development and productivity of plants worldwide. Considering that germination is the first phase of growth which in large measure determines plant quality and yield, knowing the effects of different factors on this process is of major importance. This paper studies the effect of drought-induced stress on seed germination and seedling growth of Zea mays L. (the Sweet corn and the hybrid Pioneer B23). Methods: The effect of water stress was caused by different concentrations of mannitol: 5%, 10% and 20%. In the control, we used distilled water. The germination test was performed in three trials of 45 seeds each. The germination percentage, germination potential, drought resistance index were calculated at 3, 5 and 7 days. Growth of seedlings and biomass content were calculate at 14 days.Result: The results show significant differences between the variety and hybrid examined. The pioneer B23 seed germinated in larger number and more quickly. The Sweet corn variety seedling growth was completely absent after treatment with mannitol. The observed difference is certainly not just a consequence of higher mannitol concentrations, but also a difference in the water-retention capability of the variety and hybrid studied. 

Asmira Delic, E. Mariussen, Erik D. Roede, A. Krivokapić, A. Erbe, M. Lindgren, M. Benelmekki, M. Einarsrud

Intrinsically fluorescent carbon dots may form the basis for a safer and more accurate sensor technology for digital counting in bioanalytical assays. This work presents a simple and inexpensive synthesis method for producing fluorescent carbon dots embedded in hollow silica particles. Hydrothermal treatment at low temperature (160 °C) of microporous silica particles in presence of urea and citric acid results in fluorescent, microporous and hollow nanocomposites with a surface area of 12 m2 /g. High absolute zeta potential (-44 mV) at neutral pH demonstrates the high electrosteric stability of the nanocomposites in aqueous solution. Their fluorescence emission at 445 nm is remarkably stable in aqueous dispersion under a wide pH range (3-12) and in the dried state. The biocompatibility of the composite particles is excellent, as the particles were found to show low genotoxicity at exposures up to 10 μg/cm2 .

C. Phanthunane, R. Wijers, M. D. De Herdt, T. Langeveld, S. Koljenović, S. Dasgupta, S. Sleijfer, R. J. D. de Jong et al.

ABSTRACT In oral-cancer, the number of tumor-infiltrating lymphocytes (TILs) associates with improved survival, yet the prognostic value of the cellular composition and localization of TILs is not defined. We quantified densities, localizations, and cellular networks of lymphocyte populations in 138 patients with T1-T2 primary oral-tongue squamous cell carcinoma treated with surgical resections without any perioperative (chemo)radiotherapy, and correlated outcomes to overall survival (OS). Multiplexed in-situ immunofluorescence was performed for DAPI, CD4, CD8, CD20, and pan-cytokeratin using formalin-fixed paraffin-embedded sections, and spatial distributions of lymphocyte populations were assessed in the tumor and stroma compartments at the invasive margin (IM) as well as the center of tumors. We observed a high density of CD4, CD8, and CD20 cells in the stroma compartment at the IM, but neither lymphocyte densities nor networks as single parameters associated with OS. In contrast, assessment of two contextual parameters within the stroma IM region of tumors, i.e., the number of CD20 cells within 20 µm radii of CD20 and CD4 cells, termed the CD20 Cluster Score, yielded a highly significant association with OS (HR 0.38; p = .003). Notably, the CD20 Cluster Score significantly correlated with better OS and disease-free survival in multivariate analysis (HR 0.34 and 0.47; p = .001 and 0.019) as well as with lower local recurrence rate (OR: 0.13; p = .028). Taken together, our study showed that the presence of stromal B-cell clusters at IM, in the co-presence of CD4 T-cells, associates with good prognosis in early oral-tongue cancer patients.

S. Zanini, E. Šečić, T. Busche, M. Galli, Ying Zheng, J. Kalinowski, K. Kogel

The hemibiotrophic fungus Magnaporthe oryzae (Mo) is the causative agent of rice blast and can infect aerial and root tissues of a variety of Poaceae, including the model Brachypodium distachyon (Bd). To gain insight in gene regulation processes occurring at early disease stages, we comparatively analyzed fungal and plant mRNA and sRNA expression in leaves and roots. A total of 310 Mo genes were detected consistently and differentially expressed in both leaves and roots. Contrary to Mo, only minor overlaps were observed in plant differentially expressed genes (DEGs), with 233 Bd-DEGs in infected leaves at 2 days post inoculation (DPI), compared to 4978 at 4 DPI, and 138 in infected roots. sRNA sequencing revealed a broad spectrum of Mo-sRNAs that accumulated in infected tissues, including candidates predicted to target Bd mRNAs. Conversely, we identified a subset of potential Bd-sRNAs directed against fungal cell wall components, virulence genes and transcription factors. We also show a requirement of operable RNAi genes from the DICER-like (DCL) and ARGONAUTE (AGO) families for fungal virulence. Overall, our work elucidates the extensive reprogramming of transcriptomes and sRNAs in both plant host (Bd) and fungal pathogen (Mo), further corroborating the critical role played by sRNA species in the establishment of the interaction and its outcome.

Background: The human angiotensin I converting enzyme 1 (ACE1) gene insertion/deletion (I/D) polymorphism is classified based on the presence or absence of a 287 bp Alu sequence. The ACE1 D allele is associated with higher ACE1 concentrations in tissues. Previous research has shown that susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is primarily determined by the affinity between the viral receptor-binding domain and the host human receptor angiotensin-converting enzyme 2 (hACE2) receptor. In the human genome, ACE2 is identified as a homolog to ACE1. Objective: The purpose of this study was to characterize the ACE1 D allele distribution in Bosnia and Herzegovina (B&H), so as to compare it to population data from other European countries and to investigate the potential correlation between D allele frequencies and coronavirus disease 2019 (COVID-19) epidemiological findings in selected European populations. Methods: The ACE1 D allele frequencies in 18 selected European populations were analyzed and compared with COVID-19 prevalence, mortality, and severity using multivariate linear regression analysis. Results and Discussion: The ACE1 D allele distribution within the B&H population was similar to its distribution in other European populations. Regression analysis showed no significant correlation between the D allele frequency and the incidence of infections between the examined populations, nor with the rates of fatality and severe cases. Conclusion: There is no clear statistical evidence that the ACE1 D allele is associated with increased or decreased COVID-19 incidence, mortality, and case severity within the investigated populations.

Dunja Šamec, E. Karalija, Ivana Šola, Valerija Vujčić Bok, B. Salopek-Sondi

Abiotic stressors such as extreme temperatures, drought, flood, light, salt, and heavy metals alter biological diversity and crop production worldwide. Therefore, it is important to know the mechanisms by which plants cope with stress conditions. Polyphenols, which are the largest group of plant-specialized metabolites, are generally recognized as molecules involved in stress protection in plants. This diverse group of metabolites contains various structures, from simple forms consisting of one aromatic ring to more complex ones consisting of large number of polymerized molecules. Consequently, all these molecules, depending on their structure, may show different roles in plant growth, development, and stress protection. In the present review, we aimed to summarize data on how different polyphenol structures influence their biological activity and their roles in abiotic stress responses. We focused our review on phenolic acids, flavonoids, stilbenoids, and lignans.

Abstract Studies published earlier this year demonstrated the association of the solute carrier SLC6A20 gene with the risk and severity of COVID-19. The SLC6A20 protein product (Sodium-dependent Imino Transporter 1 (SIT1)) is involved in the transport of amino acids, including glycine. Here we summarized the results of recent studies demonstrating the interaction of SIT1 with the ACE2 receptor for SARS-CoV-2 as well as an observed association of SLC6A20 with the risk and traits of Type 2 diabetes (T2D). Recently, it was also proposed that SLC6A20 represents the novel regulator of glycine levels and that glycine has beneficial effects against the proinflammatory cytokine secretion induced by SARS-CoV-2 infection. Ivermectin, as a partial agonist of glycine-gated chloride channels, was also recently suggested to interfere with the COVID-19 cytokine storm by inducing the activation of glycine receptors. Furthermore, plasma glycine levels are found to be decreased in diabetic patients. Thus, further clinical trials are warranted to confirm the potential favorable effects of targeting the SIT1 transporter and glycine levels in the treatment of COVID-19, particularly for the severe case of disease associated with hyperglycemia, inflammation, and T2D. These findings suggest that SIT1 may potentially represent one of the missing pieces in the complex puzzle observed between these two pandemic diseases and the potential novel target for their efficient treatment.

M. del Río, M. Vergarechea, T. Hilmers, Josu G. Alday, Admir Avdagić, Franz Binderh, M. Bošeľa, L. Dobor et al.

Abstract Spruce-fir-beech mixed forests cover a large area in European mountain regions, with high ecological and socio-economic importance. As elevation-zone systems they are highly affected by climate change, which is modifying species growth patterns and productivity shifts among species. The extent to which associated tree species can access resources and grow asynchronously may affect their resistance and persistence under climate change. Intra-specific synchrony in annual tree growth is a good indicator of species specific dependence on environmental conditions variability. However, little attention has been paid to explore the role of the inter-specific growth asynchrony in the adaptation of mixed forests to climate change. Here we used a database of 1790 tree-ring series collected from 28 experimental plots in spruce-fir-beech mixed forests across Europe to explore how spatio-temporal patterns of the intra- and inter-specific growth synchrony relate to climate variation during the past century. We further examined whether synchrony in growth response to inter-annual environmental fluctuations depended on site conditions. We found that the inter-specific growth synchrony was always lower than the intra-specific synchrony, for both high (inter-annual fluctuations) and low frequency (mid- to long-term) growth variation, suggesting between species niche complementarity at both temporal levels. Intra- and inter-specific synchronies in inter-annual growth fluctuations significantly changed along elevation, being greater at higher elevations. Moreover, the climate warming likely induced temporal changes in synchrony, but the effect varied along the elevation gradient. The synchrony strongly intensified at lower elevations likely due to climate warming and drying conditions. Our results suggest that intra- and inter-specific growth synchrony can be used as an indicator of temporal niche complementarity among species. We conclude that spruce-fir-beech mixtures should be preferred against mono-specific forests to buffer climate change impacts in mountain regions.

R. Gacesa, A. Vich Vila, V. Collij, Z. Mujagic, A. Kurilshikov, M.D. Voskuil, E. Festen, C. Wijmenga et al.

ABSTRACT Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies. We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing. Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing–based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7). HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.

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