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Background: Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment. Objectives: To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM. Design: A multicentre, prospective, non-controlled, non-interventional, observational cohort study. Methods: Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected. Results: A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0–5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age ( p -value

This work aims to differentiate the rural land of Slovakia in view of the possibility of effective sunflower growing. The differentiation is based on pedo-climatic and production-economic parameters. Soil categorisation took into account the correlation between the site properties (soil and climatic conditions) and the biological and agrotechnical requirements of the crops. Sunflower requirements were included in yield databases using software filters such that a given site property excluded or limited sunflower growing, which was reflected in predicted production. The prediction was subsequently interpolated into four suitability categories: soils unsuitable for sunflower growing, less suitable soils, suitable soils and very suitable soils. A map of categories of soil suitability for sunflower growing was created using a Geographic Information System on the distribution of soil parameters in Slovakia. According to our calculation in Slovakia, 18.8% of farmland is very suitable for sunflower growing, 24.9% is suitable, 16.6% is less suitable, and 39.7% is unsuitable for sunflower growing. These categories are characterised and specified in detail in the paper in terms of geographical, soil, climatic, production and economic parameters. The analysis of the actual sowing of sunflowers between 2018 and 2021 showed that 51% of the areas were located in very suitable soils, 32% in suitable, 10% in less suitable soils and 7% in unsuitable soils for cultivation.

Lignin, a complex and heterogeneous biopolymer derived from wood, holds immense potential as a sustainable feedstock for various industrial applications. Kraft pulping, a widely employed process in the paper industry, generates black liquor containing lignin along with other organic and inorganic compounds. The precipitation of lignin from black liquor offers an opportunity for valorization, contributing to the circular economy and reducing the environmental impact. Although the precipitation process of softwood lignin is extensively documented and outlined in the existing literature, the identical process originating from hardwood-derived black liquor poses challenges attributed to the distinct composition of hardwood. This study systematically investigates the individual and combined influences of temperature and pH on the precipitation of hardwood lignin from kraft black liquor, utilizing a factorial design to evaluate lignin functional characteristics. The characterization of the precipitated lignin was performed using various analytical techniques, mainly NIR, elemental composition, UV-VIS, and calorimetry. The results reveal remarkable interactions between temperature and pH, indicating their synergistic effects on lignin precipitation. The optimal conditions for hardwood lignin precipitation were identified and successfully upscaled during piloting experiments conducted under industrial conditions. This research provides valuable insights into the fundamental factors governing hardwood lignin precipitation from kraft black liquor and offers a basis for the development of efficient and sustainable lignin recovery processes in the pulp and paper industry.

Abstract Long noncoding RNAs (lncRNAs) are linked to cancer via pathogenic changes in their expression levels. Yet, it remains unclear whether lncRNAs can also impact tumour cell fitness via function-altering somatic “driver” mutations. To search for such driver-lncRNAs, we here perform a genome-wide analysis of fitness-altering single nucleotide variants (SNVs) across a cohort of 2583 primary and 3527 metastatic tumours. The resulting 54 mutated and positively-selected lncRNAs are significantly enriched for previously-reported cancer genes and a range of clinical and genomic features. A number of these lncRNAs promote tumour cell proliferation when overexpressed in in vitro models. Our results also highlight a dense SNV hotspot in the widely-studied NEAT1 oncogene. To directly evaluate the functional significance of NEAT1 SNVs, we use in cellulo mutagenesis to introduce tumour-like mutations in the gene and observe a significant and reproducible increase in cell fitness, both in vitro and in a mouse model. Mechanistic studies reveal that SNVs remodel the NEAT1 ribonucleoprotein and boost subnuclear paraspeckles. In summary, this work demonstrates the utility of driver analysis for mapping cancer-promoting lncRNAs, and provides experimental evidence that somatic mutations can act through lncRNAs to enhance pathological cancer cell fitness.

Abstract While phosphodiesterase‐5 inhibition (PED5i) may prevent hypertrophy and failure in pressure‐overloaded heart in an experimental model, the impact of PDE5i on volume‐overload (VO)‐induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long‐term PDE5i and if this therapy affects renal function. The goal of this study was to elucidate the effect of PDE5i treatment in VO due to aorto‐caval fistula (ACF) and to compare PDE5i treatment with standard heart failure (HF) therapy with angiotensin‐converting enzyme inhibitor (ACEi). ACF/sham procedure was performed on male HanSD rats aged 8 weeks. ACF animals were randomized for PDE5i sildenafil, ACEi trandolapril, or placebo treatments. After 20 weeks, RV and LV function (echocardiography, pressure‐volume analysis), myocardial gene expression, and renal function were studied. Separate rat cohorts served for survival analysis. ACF led to biventricular eccentric hypertrophy (LV: +68%, RV: +145%), increased stroke work (LV: 3.6‐fold, RV: 6.7‐fold), and reduced load‐independent systolic function (PRSW, LV: −54%, RV: −51%). Both ACF ventricles exhibited upregulation of the genes of myocardial stress and glucose metabolism. ACEi but not PDE5i attenuated pulmonary congestion, LV remodeling, albuminuria, and improved survival (median survival in ACF/ACEi was 41 weeks vs. 35 weeks in ACF/placebo, p = .02). PDE5i increased cyclic guanosine monophosphate levels in the lungs, but not in the RV, LV, or kidney. PDE5i did not improve survival rate and cardiac and renal function in ACF rats, in contrast to ACEi. VO‐induced HF is not responsive to PDE5i therapy.

The subject of the presented article is the analysis of the spatial planning legislation that is currently valid and effective and its comparison with the spatial planning legislation that will come into effect on April 1, 2024, in the legal conditions of the Slovak Republic. The authors of the article focused primarily on the comparison of two basic spatial planning tools – spatial planning documents and spatial planning documentation. The issue of the spatial plan of the municipality is elaborated in more detail, while the article points to changes in its legal regulations in connection with the process of land consolidation and the battle against climate change.

The article tackles selected representations of animals in Ivan Laučík’s (1944 – 2004) poetry. From the wide range of animals which the poet invites into his verse, it focuses on the motifs of insects, birds, and whales. In the world of Laučík’s poetry, insects serve as a litmus test for the quality and viability of an ecosystem. The poet, however, also handles insects in relation to the question of the expressive possibilities of language. Laučík’s ethical and ecological worldview also encompasses numerous motifs of birds which serve functions similar to those of insects. The motif of the whale occupies an important position in the poet’s debut collection, Pohyblivý v pohyblivom ([Mobile within mobility] 1968) and is also an indicator of how people relate to fauna and nature in general: as either conquerors or explorers. The ideal of a peaceful cohabitation of humankind with other animals can be glimpsed in Laučík’s handling of the human as a “human animal.” Such ethos can be observed both in individual poems and in the poet’s system of values in general. It accentuates an eco-friendly attitude towards nature to which the human is radically related.

Poisson’s ratio is one of the fundamental characteristics in the material models that are used. In engineering practice, its values are assumed to be constant in the elastic and in the plastic region. In this paper, the conventionally used values of this number for steel materials and aluminum alloys are confronted with experimental results. By using non-contact strain measurements with the DIC (digital image correlation) method, the evolution of the Poisson ratio value in the regions of transition from the elastic to the plastic region as well as in the regions of large plastic deformations was documented. The obtained experimental results are graphically compared using the proposed strain scaling. The gradient of the Poisson ratio changes in the vicinity of the yield stress is significant, indicating the need for a refinement of the material models in this region. Deviations from the conventionally used value of this number were found in the large plastic deformation region. In conclusion, a possible approach for improving the accuracy of simulations in FEM softwares was formulated.

Problematika automatizovaných vozidiel už nie je len predmetom vedecko-fantastickej literatúry, ale čoraz viac členských štátov prijíma regulácie predmetného fenoménu. Predkladaný článok sa venuje problematike úzko súvisiacej – vzdialeného vodičovi. Rola vodiča, ktorý ovláda automatizované vozidla na diaľku môže byť iná z pohľadu povinností v tradičnom vnímaní vodiča motorového vozidla. Predkladaný článok sa zameriava na oblasť automatizovaných vozidiel z pohľadu role a povinností vzdialeného vodiča. Cieľom tohto článku je v prvom rade porovnať rolu vodiča klasického vozidla a vzdialeného vodiča automatizovaného vozidla. V druhom rade autori ponúkajú diskusiu a odporúčania pre právnu úpravu v kontexte povinností a otvorených otázok praktického fungovania vzdialeného vodiča.

Jaskiran K Khosa,1 Samuel Louie,2 Pamela Lobo Moreno,1 Dmitry Abramov,1 Daniel K Rogstad,1 Abdullah Alismail,3 Michael J Matus,1 Laren D Tan1 1Department of Internal Medicine, Loma Linda University Health, Loma Linda, CA, USA; 2Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA; 3Department of Cardiopulmonary Sciences, Loma Linda University Health, Loma Linda, CA, USACorrespondence: Laren D Tan, Department of Medicine, Division of Pulmonary, Critical Care, Hyperbaric, Allergy and Sleep Medicine, Loma Linda University Health, 11234 Anderson Street, Suite 6439, Loma Linda, CA, 92354, USA, Tel +1 909-558-8081, Fax +1 909-558-0581, Email LaTan@llu.eduAbstract: Uncontrolled asthma in the elderly is a public health issue recognized in developed countries such as the United States and among the European Union, both from patient safety and economic perspectives. Variations in the cutoff, which defines elderly age, contribute to epidemiological study difficulties. Nonetheless, the relevance of elderly asthma from a socioeconomic perspective is inarguable. The projected growth of the enlarging geriatric population in the United States portends an impending national health burden that may or may not be preventable with pharmacologic and non-pharmacologic treatments. Asthma in the elderly might be a consequence of uncontrolled disease that is carried throughout a lifetime. Or elderly asthmatics could suffer from uncontrolled asthma, which overlaps with other ailments common with advancing ages that merit consideration, eg, COPD, heart disease, OSA, diabetes mellitus, and other comorbidities. Because of the heterogeneity of asthma phenotypes and other conditions that could mimic the symptoms of elderly asthma, further cohort studies are needed to elucidate the elderly asthmatic pathophysiology and management. More studies to characterize elderly asthma can help address these patients’ unmet need for evidence-based guidelines. We introduce the 5 “Ps” (phenotypes, partnership, pharmacology, practice in acute exacerbations, and problems or barriers for the elderly asthmatics) that establish a framework approach for clinical practice.Keywords: asthma, elderly, uncontrolled asthma

Dangerous goods (DGs) not declared for transport as required by the regulations can give rise to risks, as they can endanger public safety or the environment. This study explains the risks posed by undeclared shipments by providing information about the most common undeclared DGs aboard aircraft and maritime ships, legal frameworks regulating the proper transportation of DGs, and key mechanisms for preventing the occurrence of undeclared DG shipments. This paper identifies the responsibilities of each stakeholder involved in the process of DG transportation. The main objective of this paper is to reveal human errors and dishonest techniques within the supply chain when DGs are transported by air and sea.

The article reads Miroslav Válek’s (1927 – 1991) poem “Večer [Evening]” published in the poet’s first collection of verse Dotyky ([Touches], 1959) as a deconstructive subversion of lyric tradition – of Ivan Krasko’s (1876 – 1958) symbolist model of the lyric and Edgar Allan Poe’s (1809 – 1849) “The Raven” (1845). The author argues that Válek subverts the tradition by the specific way he tackles the motifs of the night, rain, and raven known in the Slovak poetry mainly from the writing of Ivan Krasko and by the way the poet updates the lyric situation of Poe’s notoriously well-known poem and its central motif. Another aspect that gets subverted is the tragic-elegiac melancholic modality of the poem. The analysis notices the first line of the poem where the night setting is outlined, then moves on to the key image of rain “without melancholy” and the updated motif of the raven. Finally, it discusses the detachment of the speaker from what goes on in the poem – the speaker in the poem is different from the subject affected by emotions and moods modelled in the lines. The reading grasps Válek’s poem and sophisticated subversive deconstruction of the traditional model of symbolic poem concerned with romantic love.

The aim of the study was to clarify the role of the interplay between hypertension and the renin-angiotensin system (RAS) in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. We hypothesized that in the late phase of hypertension with already developed signs of end-organ damage, inappropriate RAS activation could impair cardiac tolerance to I/R injury. Experiments were performed in male Cyp1a1-Ren-2 transgenic rats with inducible hypertension. The early phase of ANG II-dependent hypertension was induced by 5 days and the late phase by the 13 days dietary indole-3-carbinol (I3C) administration. Noninduced rats served as controls. Echocardiography and pressure-volume analysis were performed, angiotensins’ levels were measured and cardiac tolerance to ischemia/reperfusion injury was studied. The infarct size was significantly reduced (by 50%) in 13 days I3C-induced hypertensive rats with marked cardiac hypertrophy, this reduction was abolished by losartan treatment. In the late phase of hypertension there are indications of a failing heart, mainly in reduced preload recruitable stroke work (PRSW), but only nonsignificant trends in worsening of some other parameters, showing that the myocardium is in a compensated phase. The influence of the RAS depends on the balance between the vasoconstrictive and the opposed vasodilatory axis. In the initial stage of hypertension, the vasodilatory axis of the RAS prevails, and with the development of hypertension the vasoconstrictive axis of the RAS becomes stronger. We observed a clear effect of AT1 receptor blockade on maximum pressure in left ventricle, cardiac hypertrophy and ANG II levels. In conclusion, we confirmed improved cardiac tolerance to I/R injury in hypertensive hypertrophied rats and showed that, in the late phase of hypertension, the myocardium is in a compensated phase.

The main objective of this paper is to underscore the significance of human error as a dominant cause of maritime accidents. The research is based on a comprehensive analysis of 247 maritime accidents, with the aim being to identify human failures occurring during onboard and port activities, as well as during the supervision process. The first step of the analysis was facilitating the Human Factor Analysis and Classification System (HFACS) as an advanced analytical tool for the identification and categorisation of human factors. Based on coding process, the most critical areas of human error are identified, based on the process of risk evaluation and assessment. Furthermore, a prediction model was developed for predicting the probability of fatality in a maritime accident. This model was constructed using logistic regression, considering the predominant causal factors and their interplay. Lastly, a set of preventive measures aimed at enhancing the efficiency and safety of maritime transport is provided.

Liquid marbles are widely known for their potential biomedical applications, especially due to their versatility and ease of preparation. In the present work, we prepared liquid marbles with various cores composed of water, agar-based hydrogels, magnetic fluids, or non-aqueous substances. As a coating material, we used biocompatible particles of plant origin, such as turmeric grains and Lycopodium pollen. Additionally, we provided marbles with magnetic properties by incorporating either magnetosomes or iron oxide nanoparticles as a powder or by injecting another magnetic fluid. Structures obtained in this way were stable and susceptible to manipulation by an external magnetic field. The properties of the magnetic components of our marbles were verified using electron paramagnetic resonance (EPR) spectroscopy and vibrating sample magnetometry (VSM). Our approach to encapsulation of active substances such as antibiotics within a protective hydrogel core opens up new perspectives for the delivery of hydrophobic payloads to the inherently hydrophilic biological environment. Additionally, hydrogel marbles enriched with magnetic materials showed promise as biocompatible heating agents under alternating magnetic fields. A significant innovation of our research was also the fabrication of composite structures in which the gel-like core was surrounded without mixing by a magnetic fluid covered on the outside by the particle shell. Our liquid marbles, especially those with a hydrogel core and magnetic content, due to the ease of preparation and favorable properties, have great potential for biomedical use. The fact that we were able to simultaneously produce, functionalize (by filling with predefined cargo), and manipulate (by means of an external magnetic field) several marbles also seems to be important from an application point of view.

High-frequency components such as microprocessors, transistors, antennas, voltage-controlled oscillators, and many others generate a large amount of heat. In the absence of satisfactory cooling, these components may suffer damage or even destruction. Therefore, it is important to find effective ways to cool these components. A possible solution is to use oil-based magnetic fluids. Magnetic fluids contain magnetic particles dispersed in oil, and their properties, including viscosity, affect their cooling capabilities. Viscosity can be changed by adding various additives or by adjusting the concentration of magnetic particles. The advantage of using oil-based magnetic fluids for cooling is that they allow for precise dosing and control of the amount of fluid applied to the component, reducing thermal losses and increasing cooling efficiency. In addition, oil-based magnetic fluids can also act as a dielectric, reducing electrical noise and increasing electromagnetic compatibility with the components. Analyzing the heating rate of magnetic fluids consisting of mineral oils in an alternating magnetic field with a frequency of 500 kHz, we have shown the capability of controlling thermal losses by adjusting the viscosity of the carrier liquid.

Introduction The majority of hepatitis E (HE) reports come from Western Europe. The aim of the study was to describe the typical epidemiological and clinical characteristics of HE in the Czech Republic. Material and methods The retrospective analysis of 173 patients with HE. Results At least 90% of cases were autochthonous (HEV-3 genotype). Seventeen patients were treated with ribavirin. Five underwent liver transplants because of fulminant HE. We noted neurological symptomatology in 9 cases. Six patients developed chronic HE. Conclusions There is a possibility of severe health complications caused by the hepatitis E virus in the Czech Republic.

This paper provides comprehensive research on the linearity between the efficiency and safety of inland waterway transport (IWT). For this purpose, methods of statistical analysis are used. The efficiency of IWT is expressed by the transportation outputs, which today are strongly affected by the COVID-19 pandemic. This paper aims to find whether the demand for IWT has an impact on the accident occurrence probability. The results show the linearity between shipping accidents and the outputs of freight and passenger IWT. The COVID-19 crisis has a higher impact on the efficiency of passenger navigation than on freight navigation. With reduced demand, the level of safety is higher but at the cost of declining efficiency in the transport sector.