SerIoT is a Research and Innovation Project funded by the European Commission to demonstrate secure networks for the Internet of Things (IoT). This paper presents an overview of the design for smart and secure network infrastructures for the IoT, based on Software Defined Networks (SDN), named the SerCPN system, whose main component is a smart SDN-Controller with online cognitive security surveillance and reporting, which establishes and dynamically modifies paths that enhance security for IoT devices and end users, and offers a high quality of service (QoS) with required security constraints. This online cognitive surveillance and path management is based on the Cognitive Packet Network (CPN) principle and uses Random Neural Networks (RNN) for decision making.

Nitrogen (N) is an essential nutrient and plays an important role in plant growth and physiology. In addition, N is also the limiting nutrient in most terrestrial ecosystems. The increasing use of N fertilizers increases agricultural production, but also has negative impacts on biodiversity, water quality and increases emissions of greenhouse gases such as nitrogen oxides (NOx) and nitrous oxide (N2O) into the atmosphere. N2O is a strong greenhouse gas and the product of microbial transformation processes of N introduced into soil and groundwater (nitrification and denitrification). The production of N2O in soils is highly dependent on oxygen and water content, soil temperature and texture and the available amount of reactive nitrogen (NO3- or NH4+). In agricultural soils, N2O emissions are also influenced by the type of fertilizer used, crops grown, soil pH and NO3- concentration. Refined forms of land management, such as the cultivation of legumes, can reduce the use of fertilizers and thus also the emission of N2O. Legumes can use symbiotic nodule bacteria (rhizobia) to bind atmospheric N2 and make it available to the plant. Non-symbiotic soil microorganisms such as cyanobacteria or other heterotrophic and autotrophic prokaryotes are also able to fix N2. Furthermore, the N2-fixing enzyme nitrogenase, which is specific for most organisms, is not specific for other N2 compounds, especially N2O. To study the N2 and N2O fixation potential of soils and legumes, experiments with isotope-enriched N-gases (100 mol% 15N2 and 15N2O) were performed. Three different soil types (forest, meadow and wetland) as well as legume plants inoculated with rhizobia bacteria (Rhizobium leucaneae) (Leucaena leucocephala) were incubated in microcosms with different mixing ratios of N2 and N2O over a period of one week. The measured 15N enrichment was then used to determine the biological uptake rates. Both in plants and in soils admixtures of up to 40% N2O had no influence on the N2 fixation rate. N2 uptake rates were 1.2 ± 0.4 ug N gdw-1 d- 1in forest and grassland soils and 3.9 ± 1.2 ug N gdw-1 d- 1 in wetland soils. In contrast, the N2 fixation rates of leguminous plants were significantly higher (130 ± 40 ug N gdw-1 d- 1), with the highest accumulation not in root nodules but in the roots. In both plants and soil, the N2O fixation of 0.2 ± 0.1 ug N gdw-1 d- 1 could only be measured from a concentration of 4 vol%. The results indicate that both soils and legumes have a high potential to bind atmospheric nitrogen in the form of both N2 but not N2O. The fate of nitrogen in soil needs to be further investigated. N2 fixation seems to play an important role in wetland soils. Legumes in particular have the potential for NH4+ input and N2O reduction, as most of the solid nitrogen has been transferred to the roots, which can contribute significantly to soil nutrient input.

The early generative phase of cauliflower (Brassica oleracea var. botrytis) curd ripening is sensitive to the water deficit. Mitochondrial responses under drought within Brassica genus are poorly understood. The main goal of this study was to investigate the mitochondrial biogenesis of three cauliflower cultivars varying with drought tolerance. Diverse quantitative changes (down-regulations mostly) in the mitochondrial proteome were assayed by 2D PAGE coupled with LC-MS/MS. Respiratory (e.g. CII, CIV and ATP synthase subunits), transporter (including diverse porin isoforms) and matrix multifunctional proteins (e.g. components of RNA editing machinery) appeared diversely affected in their abundance under two drought levels. Western immunoassays showed also cultivar-specific responses of selected mitochondrial proteins. Dehydrin-related tryptic peptides found in few 2D spots that appeared immunopositive with dehydrin-specific antisera highlighted the relevance of mitochondrial dehydrin-like proteins for the drought response. The level of selected messengers participating in drought response was also determined. We conclude that the mitochondrial biogenesis was strongly, but diversely affected in various cauliflower cultivars and associated with drought tolerance on the proteomic and functional levels. However, transcriptomic and proteomic regulations were largely uncoordinated due to the suggested altered availability of messengers for translation, mRNA/ribosome interactions and/or miRNA impact on transcript abundance and translation.

We examined the effects of different malolactic bacteria fermentation techniques, including a spontaneous process – a variant with a high risk of undesirable metabolites – on the bioconversion of aromatic compounds in cool-climate grape wines. During three wine seasons, red and white grape wines were produced by three different methods of malolactic fermentation induction: coinoculation, sequential inoculation, and spontaneous malolactic fermentation. Volatiles (diacetyl and the products of its metabolism, as well as selected ethyl fatty acids esters) were extracted by solid phase microextraction. Compounds were identified with multidimensional gas chromatograph GCxGC-ToFMS with ZOEX cryogenic (N₂) modulator. Sensory evaluation of the wines was also performed. We found, that the fermentation-derived metabolites examined in this study were affected by the malolactic bacteria inoculation regime. Quantitatively, ethyl lactate, diethyl succinate and ethyl acetate dominated as esters with the largest increase in the concentration. The total concentration of ethyl esters was highest for the coinoculation scenario. Whereas the highest concentration of diacetyl was noted for the spontaneous processes. A controlled malolactic fermentation, especially using the coinoculation technique, can be proposed as a safe and efficient enological practice for producing quality, cool-climate grape wines enriched with fruity, fresh and floral aromas.

This paper discusses Green Infrastructure, which can be considered a useful tool in the process of ensuring the sustainable development of urban structures in the Carpathian region. It allows for achieving a better quality of the environment of human life and healthy wildlife linkages. The element that supports defining information about the existing state of Green Infrastructure and its resources is the Green Infrastructure fragmentation coefficient based on edge effect calculations, which is the relation between the edge of the patch (circumference) to its surface area [1, 2]. With the use of model analysis of Green Infrastructure, it is possible to implement the provisions of the Carpathian Convention and coordinate planning documents that facilitate the sustainable development of spatial structures. Our study on the state of Green Infrastructure in rural areas of the Polish Carpathian Mountains is a source of knowledge about the quality of this area, its natural environment and fragmentation. Determining the territory’s Green Infrastructure fragmentation coefficient provides an opportunity for higher-precision studies and the detection of threats and integration of GI fragments and addressing proper solutions in conflict areas.

The Covid-19 pandemic has forced the transfer of local government public ser-vices to the virtual world. Remote handling of matters in government offices has be-come the norm rather than the exception. The 2016 EU directive on public sector web-sites and mobile applications and the 2019 European Digital Accessibility Act made it mandatory that these services be provided electronically and accessible to people with disabilities. The purpose of the study conducted by the authors was to determine whether the Covid-19 pandemic resulted in the implementation of European solutions in the Polish legal order and whether this implementation resulted in the actual adap-tation of digital activities of local government units (LGUs) to the needs of people with disabilities. The research was conducted in Q4 2022 in two trial formats: 1. In the form of a survey (about 250 LGUs), which covered compliance with for-mal requirements, the level of readiness of the officials to create digitally accessible documents and content, and organizational readiness of the offices. 2. In the form of an analysis of the source code of the websites of 66 Polish cities with county rights - due to the availability of results of the same sample from 2015. The completed research showed that the LGUs in Poland: 1. met the formal and organizational requirements for digital accessibility, 2. did not make the necessary efforts to prepare employees to create digitally ac-cessible documents and content, 3. the surveyed websites had inferior source code in terms of meeting the WCAG standard in 2022 than in 2015. It seems reasonable to conclude that the Covid-19 pandemic had a formal, rather than real, impact on the digital accessibility of services provided by Polish LGUs.

Purpose: The evaluation of the efficacy of topical hypotensive treatment and/or systemic corticosteroids therapy in patients with elevated intraocular pressure and Graves’ orbitopathy (GO). Methods: 172 eyes in 86 individuals with duration of GO ≥ 3 months, intraocular pressure in either eye ≥ 25.0 mmHg and GO ranked ≥ 3 at least in one eye in modified CAS form, were included. The study subjects were divided into three treatment subgroups: subgroup I was administered latanoprost QD; subgroup II was administered a combined preparation of brimonidine and timolol BID; subgroup III was the control group, not receiving any topical hypotensive treatment. All the study participants received systemic treatment – intravenous corticosteroid therapy at the same dose, according to the EUGOGO guideline Results: On the final visit, the mean IOP value was significantly lower in all treatment subgroups comparing to the initial values. In both subgroups receiving topical treatment the IOP reduction was higher than in the control group receiving systemic corticosteroids only. However, the latanoprost eye drops decreased intraocular pressure more effectively than drops containing brimonidine and timolol. Conclusion: Topical ocular hypotensive treatment is effective in reducing intraocular pressure in GO and decreases intraocular pressure more effectively than systemic corticosteroid therapy alone.

Background: To investigate the distribution of refractive errors and their characteristics in older adults. Methods: The study design was cross-sectional study. A total of 1107 men and women were interviewed and underwent detailed ophthalmic examinations, 998 subjects underwent refraction. Myopia was defined as spherical equivalent (SER) refraction ≤ −0.5 dioptres (D) and hyperopia was defined as SER ≥ +0.5 dioptres (D). Results: Among those who were refracted the distribution of myopia and hyperopia was 24.1% (95% CI 21.4–26.7) and 37.5% (95% CI 34.5–40.5), respectively. Myopia decreased from 28.7% in subjects aged 35-59 years to 19.3% in those aged 60 years or older and hyperopia increased from 21.8% at 35–59 years of age to 53.3% in subjects aged ≥60 years. Multiple regression analysis showed decreasing age (OR 0.98, 95% CI 0.96–1.00), female gender (OR 1.87, 95% CI 1.18–2.95) and presence of cataract (OR 2.40 , 95% CI 1.24–4.63) were independent risk factors associated with myopia. Conclusions: The distribution of refractive errors found in our study is similar to those reported in other Caucasian populations and differs from Asian populations. Myopia was positively associated with younger age, female gender and presence of cataract.

Retinoblastoma is the most common intraocular paediatric eye cancer. It accounts for approximately 11% of primary cancers occurring in the first age of life, with 95% of diagnoses before 5 years of age [1-3]. Since retinoblastoma is very aggressive, early diagnosis and prompt treatment are vital for children to preserve their sight and life. In western countries in Europe and North America, retinoblastoma is diagnosed early so the chances of saving the patient’s life and preserving vision are good. However, in large regions of Africa and Asia, where the diagnosis of retinoblastoma is delayed, the deadly effect is observed [2-5]. In these regions, socioeconomic factors and poor recognition of the seriousness of the disease result in a high mortality rate of up to 70%. At the same time, the mortality rate in Europe and North America is 3-5 % [2]. Besides, the incidence of retinoblastoma also varies by race and region, from 40 to 60 per million live births, which corresponds to 1 per 16,000 - 24,000 live births, with the greatest disease burden recorded in the countries of Asia and Africa where the highest birth rates are recorded [2,3 However, the nationwide studies of the retinoblastoma epidemiology have been conducted in many countries, such as Sweden, Finland, Netherlands, Singapore, Great Britain, United States of America, Korea and Taiwan, there is a lack of data from Eastern European countries like Poland [1,3-11]. The management of retinoblastoma may also differ between developed and developing countries. The current strategy of retinoblastoma treatment aims to save the life, eye, vision and cosmetics of the child, in order of priority. Medical management of retinoblastoma includes surgical treatment (enucleation), external beam radiotherapy, systemic chemotherapy with or without focal therapies such as cryotherapy, laser photocoagulation and plaque radiotherapy. Recently, intra-arterial and intravitreal chemotherapies have been used to treat retinoblastoma with the ability to save globes that otherwise would have been enucleated [2,3]. The present study aimed to investigate the incidence and characteristics of retinoblastoma in the overall population of Poland in the years 2010-2017 and to report the changes that occurred during that period.

The aim of the paper is to assess the accessibility for people with disabilities of flagship cultural attractions, that is museums located in Krakow, a city with a rich historical heritage entered onto the UNESCO World Cultural and Natural Heritage List and distinguished by the Access City Award. The research shows to what degree the museums have been adapted to receive visitors with disabilities. Assessment was also conducted of access to the museums’ websites, and the possibility for virtual tours of their collections. The research results indicate that Krakow museums are well-prepared for receiving people with physical disabilities and seniors, but are less well adapted to receiving visually impaired and blind people, and hearing impaired and deaf people. Analysis of the museums’ websites shows that they are well-prepared in terms of compatibility and comprehensibility, but that they received a worse assessment for their perceivability and functionality. Visitors to the museums are principally adults, adolescents and seniors. People with disabilities make up 10% of all visitors.

The thermal decomposition of siderite and its decomposition products in a vacuum atmosphere was investigated for the first time using in situ high-temperature transmission Mössbauer spectroscopy. These measurements were supported by X-ray diffraction, Raman spectroscopy, X-ray fluorescence, and magnetic measurements. In situ Mössbauer spectra were collected from room temperature (RT) to 750 oC with a temperature step of 50 oC. After that, the sample was cooled down to RT with step 100 oC. Raw siderite samples contain siderite as the only iron-bearing mineral, and after heating the samples at high temperatures, hematite and magnetite are only Fe-bearing phases. In the temperature range of 300 oC - 500 oC, siderite decomposition occurs. The analysis shows that siderite transforms directly into magnetite, and then hematite generation occurs as long as siderite is present in the sample. Changing hyperfine parameters like isomer shift, quadrupole splitting, or hyperfine magnetic field versus temperature were obtained for siderite and iron oxides (hematite, magnetite). The measurements also show that magnetite formed during the decomposition of siderite is a composition of particles of various sizes and a low degree of crystallization.

Berberis vulgaris L. is currently widely studied for its antioxidant and chemopreventive proper-ties, especially given the beneficial properties of its fruits in this regard. Although the bark and roots have been well known and used in traditional medicine since ancient times, little is known about the other parts of this plant. The aim of the research was to determine the antioxidant and LOX inhibitory activity effects of extracts obtained from leaves, fruits, and stems. Another aim of the work was to carry out the quantitative and qualitative analysis of phenolic acids, flavonoid aglycones, and flavonoid glycosides. Extracts were obtained with the use of ASE (accelerated solvent extraction). The total content of polyphenols was determined and was found to vary de-pending on the organ, with the highest amount of polyphenols found in the leaves extract. The free radical scavenging activity of the extracts was determined spectrophotometrically in relation to the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, with results ranging from 63.88 mgTE/g for leaves to 65.25 mgTE/g for the stem. Antioxidant activity was also assessed using the ABTS test. The lowest value was recorded for the barberry fruit (117.93 mg TE/g) and the highest level was found for the barberry leaves (140.49 mgTE/g). The oxygen radical absorption capacity test (ORAC) showed the lowest value for the stem (167.70 mgTE/g) and the highest level for the leaves (267.81 mgTE/g). The range of percentage inhibition of LOX was determined as well. The percentage inhibition of the enzyme was positively correlated with the sum of flavonoids, TPC, TFC, and the content of selected flavonoids. For the first time, phenolic acids, flavonoid agly-cones, and flavonoid glycosides were determined qualitatively and quantitatively in individual parts of Berberis vulgaris L. The content of phenolic acids, flavonoid aglycones, and flavonoid glycosides was determined with the LC-MS/MS method. For the first time, the following phenol-ic acids were quantitatively and qualitatively identified in individual parts of Berberis vulgaris: 3-caffeoylquinic acid, protocatechuic acid, 5-caffeoylquinic acid, flavonoid glycosides: eleuthero-side E, rutin, isoquercitin, luteoloside, nar-cissoside, naringenin-7-glucoside, isorhamnetin-3-glucoside, afzeline, and quercitrin. Flavonoid aglycones: catechin, luteolin, and eriodictyol were determined qualitatively and quantitatively for the first time as well.

The main focus of this work is to extend the knowledge about the complexity of issues of oxidative stress. Natural compounds play a serious role in multiple aspects of both human, leading to clear health-promoting effects. This work is focused on the potential application cosmetic formulations containing including but not limited to of clove water and isolated clove oils on their aid in the control of the diseases. The aim of our work was to prepare to evaluate cosmetic formulations containing clove oil, eugenol or new eugenol ester derivative (eugenyl dichloroacetate - EDChA) but also cosmetic formulations containing the aqueous phase obtained after separation of essential oil following the clove buds steam distillation. To evaluate the antioxidants transdermal delivery system, in vitro permeation experiments in a Franz diffusion cell were performed using pig skin. The antioxidative capacity of the cosmetic formulations obtained was determined by the DPPH free radical reduction method. In the next stage, the antioxidant activity (DPPH, ABTS, and Folin–Ciocalteu methods) of the fluid that penetrated through pig skin and of the fluid obtained after skin extraction, were also evaluated. For comparison, studies of cosmetic formulation containing alone dichloroacetic acid (DChAA) were as well carried out. The obtained cosmetic formulations were characterized by of antioxidant activity estimated after 24 hours of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The results of this work contribute to the development of cosmetic formulations with antioxidant potential, emphasizing that the water phases are waste from the process of cloves steam distillation and are not used to prepare cosmetic formulations. The use of waste water from the clove buds steam distillation process is environmentally friendly and not allows us to waste, containing however valuable biologically active compounds (furfural, methyl salicylate, 4-allilofenol, eugenol, α- and β-caryophyllene, eugenyl acetate, β-caryophyllene oxide). Together, these results suggest that cosmetic formulations may be potential drug candidates for chemopreventive, antineoplastic and antimutagenic therapy.

This work investigates the utility of the National Oceanic and Atmospheric Administration’s National Water Model (NWM) for water management operations by assessing the total inflow into a select number of reservoirs across the Central and Western U.S. Total inflow is generally an unmeasured quantity, though critically important for anticipating both floods and shortages in supply over a short-term (hourly) to sub-seasonal (monthly) time horizon. The NWM offers such information at over 5,000 reservoirs across the U.S., however, its skill at representing inflow processes is largely unknown. The goal of this work is to understand the drivers for both well performing and poor performing NWM inflows such that managers can get a sense of the capability of NWM to capture natural hydrologic processes and in some cases, the effects of upstream management. We analyzed the inflows for a subset of Bureau of Reclamation (BoR) reservoirs within the NWM over the long-term simulations (retrospectively, seven years) and for short, medium and long-range operational forecast cycles over a one-year period. We utilize ancillary reservoir characteristics (e.g. physical and operational) to explain variation in inflow performance across the selected reservoirs. In general, we find that NWM inflows in snow-driven basins outperform those in rain-driven, and that assimilated basin area, upstream management, and calibrated basin area all influence the NWM’s ability to reproduce daily reservoir inflows. The final outcome of this work proposes a framework for how the NWM reservoir inflows can be useful for reservoir management, linking reservoir purposes with the forecast cycles and retrospective simulations.

Background: The assessment of the incidence and characteristic of acute and chronic post-operative endophthalmitis (POE) after cataract surgery in Poland during 2010 - 2015. Patients and methods: All hospitalizations of patients, in the National Database of Hospitalizations, who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015, with a billing code of endophthalmitis, were selected. Acute endophthalmitis was identified if symptoms occurred within 1 - 42 days from the cataract surgery and chronic endophthalmitis if symptoms occurred ≥ 43 days after cataract surgery, respectively. Results: In total, 1331 cases of POE after 1,218,777 cataract extractions were identified. The overall incidence of POE decreased from 0.125% in 2010 to 0.066% in 2015. In multiple logistic regression analyses, increasing age was significantly associated with acute POE, while type II diabetes mellitus, extracapsular cataract extraction and one-day surgery were significantly associated with chronic POE. The combined cataract surgery and male sex were significant risk factors for both acute and chronic POE. A total of 62.51% of all eyes affected by POE received antibiotic treatment and 37.49% had vitrectomy treatment. Conclusions: During the study period, the total incidence of post-operative endophthalmitis after cataract surgery decreased significantly.

The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) became recommended for every patient suspected of PCa before performing a biopsy. It enabled targeted sampling of the suspicious prostate regions, improving the accuracy of the traditional systematic biopsy. However, mpMRI is associated with high costs, relatively low availability, long and separate procedure or exposure to the contrast agent. The novel ultrasound modalities such as shear wave elastography (SWE), contrast-enhanced ultrasound (CEUS) or high frequency micro-ultrasound (MicroUS) may be capable of maintaining the performance of mpMRI without its limitations. Moreover, the real-time lesion visualization during biopsy would significantly simplify the diagnostic process. Another value of these new techniques is the ability to enhance the performance of mpMRI by creating the image fusion of multiple modalities. Such models might be further analyzed by artificial intelligence to mark the regions of interest for investigators and help to decide about the biopsy indications. The dynamic development and promising results of new ultrasound-based techniques should encourage researchers to thoroughly study their utilization in prostate imaging.

To design properly and optimizate liquid-assisted processes such as reactive infiltration for fabricating light weight and corrosion resistant SiC/TiSi2 composites, the interfacial phenomena taking place when liquid Si-rich Si-Ti alloys are in contact with glassy carbon (GC) were investigated for the first time by wetting tests performed by both the sessile and pendant drop methods at T = 1450°C. Specifically, two different Si-rich Si-Ti alloys were selected, and the obtained results in terms of contact angle values, spreading kinetics, reactivity, and developed interface microstructures were compared with experimental observations previously obtained for the liquid Si-rich Si-Ti eutectics processed under the same operating conditions. The increase of the Si content did not affected the final contact angle values. Contrarily, the final developed microstructure at the interface as well as the spreading kinetics were observed as weakly dependent on the composition. From the practical point of view, Si-Ti alloy compositions with a Si-content falling in the simple eutectic region of the phase diagram might be potentially used as infiltrant materials of C- and SiC-based composites.

The endogenous pool of phytoregulators in plant tissues supplied with microbial secondary metabolites may be crucial for the development of winter wheat seedlings during cool springs. Phytohormones may be synthesized by psychrotrophic microorganisms in lower temperatures occurring in temperate climate. Two fungal isolates from the Spitzbergen soils after the microscopic observations and ITS region molecular characterization were identified as Mortierella antarctica (MA DEM 7) and Mortierella verticillata (MV DEM32). To study the synthesis of indoleacetic acid (IAA) and gibberellic acid (GA) Mortierella strains were grown on media supplemented with precursors of phytohormones (tryptophan or methionine) at 9, 15 and 20 °C for 9 days. The highest amount of IAA synthesis was observed in MV DEM 32 9-day culture at 15 °C with 1.5 mM of tryptophan. At the same temperature the significant promoting effect (about 40% root and shoot fresh weight) of this strain on seedlings was observed. However, only MA DEM 7 had the ACC-deaminase activity with the highest efficiency in 9 °C and at this temperature synthesized IAA without tryptophan also at the same conditions the strain confirmed the strong promoting effect (about 40% root and 24% shoot fresh weight) on seedlings. Both strains synthesized GA in all tested terms and temperatures. Tested Mortierella strains had some important traits to consider them as microbial biofertilizers component improving plant growth in difficult temperate climate.

Background: To assess the incidence and characteristic of cataract surgery in Poland from 2010 to 2015 and to interpret these findings. Patients and methods: Data from all patients who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015 were evaluated. Patient data were from the national database of hospitalizations maintained by National Health Fund, data on the population of Poland were obtained from Central Statistical Office of Poland. Results: In total 1,218,777 cataract extractions (alone or combined with other procedures) were performed in 1,081,345 patients during 2010 -2015. Overall, the incidence of cataract surgery increased from 5.22/1000 person-years in year 2010 to 6.17/1000 person-years in year 2015. Phacoemulsification was performed in 97.46% of cataract extractions, and 3.02% of cataract extractions were combined procedures. The rate of one-day procedures increased from 28.3% in year 2010 to 43.1% in year 2015. The probability of second-eye surgery 12 months after the first-eye surgery increased from 44% in 2010 to 73% in 2015 (log-rank test p<0.0001). Conclusion: In Poland, from 2010 to 2015 the total incidence of cataract surgery, the number of people who underwent surgery, and the numbers of one-day and combined cataract surgeries, increased significantly.

Advanced paternal age increases the risk of transmitting de novo germline mutations, particularly missense mutations activating the receptor tyrosine kinase (RTK) signaling pathway, exemplified by the FGFR3 mutation linked to achondroplasia (ACH). This risk is attributed to the expansion of spermatogonial stem cells carrying the mutation, forming sub-clonal clusters in the ageing testis, thereby increasing the frequency of mutant sperm and the number of affected offspring from older fathers. While prior studies proposed a correlation between sub-clonal cluster expansion in the testis and elevated mutant sperm production in older donors, limited data exist on the universality of this phenomenon. Our study addresses this gap by examining the testis expansion patterns, as well as increases of mutations in sperm for two FGFR3 variants: c.1138G>A (p.G380R) and c.1948A>G (p.K650E)- associated with ACH or thanatophoric dysplasia (TDII), respectively. Unlike the ACH mutation, which showed sub-clonal expansion events in an aged testis and a significant increase of mutant sperm with the donor’s age, the TDII mutation formed sub-clonal clusters, but exhibited reduced transmission into sperm and no significant age-related increase. The mechanism behind this divergence remains unclear, suggesting potential pleiotropic effects of aberrant RTK signaling in the male germline, possibly hindering differentiation requiring meiosis. This study provides further insights into transmission risks of micro-mosaics associated with advanced paternal age in the male germline.

The purpose of this review is to summarize current knowledge on lymph node dissection (LND) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Despite a growing body of evidence, utility, therapeutic and prognostic value of such approach as well as optimal extent of LND, remain unsolved issues. Although LND is the most accurate staging procedure, the direct therapeutic effect is still not evident from the current literature which limits the possibility of establishing clear recommendations. This indicates the need for further robust and adequately designed high quality clinical trials.

Nowadays molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and immune system action. An example could be renal cell carcinoma (RCC) which has deep interactions with immune mediators such as Interleukin 17 (IL-17) - an inflammatory cytokine reacting to tissue damage and external pathogens. RCC is one of the most fatal urological cancer because of its often late diagnosis and poor susceptibility to therapies. IL-17 and its relation with tumors is extremely complex and constitute a recent topic for numerous research. What is worth highlighting is IL-17 dual character in cancer development - it could be pro- as well as antitumorigenic. The aim of this review is to summarize the newest data considering multiple connections between IL-17 and RCC.

This paper concerns a new methodology for accuracy assessment of global positioning system verified experimentally with LiDAR (Light Detection and Ranging) data alignment at continent scale for autonomous driving safety analysis. Accuracy of GPS (Global Positioning System) positioning of an autonomous driving vehicle within a lane on the road is one of the key safety considerations. Safety is addressed as a geometry of the problem, where the aim is to maintain knowledge that the vehicle (its bounding box) is within its lane. Accuracy of GPS positioning is checked by comparing it with mobile mapping tracks in the recorded high definition source. The aim of the comparison is to see if the GPS positioning remains accurate up to the dimensions of the lane where the vehicle is driving. For this reason, a new methodology is proposed. Methodology is composed of six elements: 1) Mobile mapping system minimal setup, 2) Global positioning data processing, 3) LiDAR data processing, 4) Alignment algorithm, 5) Accuracy assessment confirmation and 6) Autonomous driving safety analysis. The research challenge is to assess positioning accuracy of moving cars taking into account the constraints of the coverage of limited access highways in the United States of America. The available coverage limits the possibility of repeatable measurements and introduces an important challenge being the lack the ground truth data. State-of-the-art methods are not applicable for this particular application, therefore a novel approach is proposed. The method is to align all the available LiDAR car trajectories to confirm the GNSS+INS (Global Navigation Satellite System + Inertial Navigation System) accuracy. For this reason, the use of LiDAR metric measurements for data alignment implemented using SLAM (Simultaneous Localization and Mapping) was investigated, assuring no systematic drift by applying GNSS+INS constraints. SLAM implementation used state-of-the-art observation equations and the Weighted Non-Linear Least Square optimization technique that enables integration of the required constraints. The methodology was verified experimentally using arbitrarily chosen measurement instruments (NovAtel GNSS+INS, LiDAR Velodyne HDL32) mounted onto mobile mapping systems. The accuracy was assessed and confirmed by the alignment of 32785 trajectories with total length of 1,159,956.9~km and of total $186.4*10^{9}$~optimized parameters (six degrees of freedom of poses) that cover the United States region in the 2016--2019 period. It is demonstrated that the alignment improves the trajectories, thus final map is consistent. The proposed methodology extends the existing methods of global positioning system accuracy assessment focusing on realistic environmental and driving conditions. The impact of global positioning system accuracy on autonomous car safety is discussed. It is shown that 99\% of the assessed data satisfies the safety requirements (driving within lanes of 3.6~m) for Mid-Size (width 1.85~m, length 4.87~m) vehicle and 95\% for 6-Wheel Pickup (width 2.03--2.43~m, length 5.32--6.76~m). The conclusion is that this methodology has great potential for global positioning accuracy assessment at global scale for autonomous driving applications. LiDAR data alignment is introduced as a novel approach to GNSS+INS accuracy confirmation. Further research is needed to solve the identified challenges.

Magnetic Fe3O4 nanoparticles (MNPs) functionalized with (3-aminopropylo)trietoksysilan (APTES) or N-carboxymethylchitosan (CMC) were proposed as nanocarriers of methotrexate (MTX) against ovarian cancer cell lines. The successful functionalization of the obtained nanostructures was confirmed by FT-IR spectroscopy. Nanoparticles were characterized by transmission electron spectroscopy (TEM) and dynamic light scattering (DLS) techniques. Their potential zeta, magnetization, and hyperthermic properties were also explored. MTX was conjugated with nanocarriers by ionic bonds or by amide bonds. For all three types of nanostructures, the drug release kinetics were examined at different pH and temperatures. The MTT assay showed no toxicity of MNPs[APTES] and MNPs[CMC]. Finally, the cytotoxicity of the nanostructures with MTX attached was measured towards the ovarian cancer cells model sensitivity and resistance to methotrexate in simplistic 2D and spheroid 3D conditions. The results of cytotoxicity tests of the tested nanostructures showed similar values for inhibiting the proliferation of ovarian cancer cells as methotrexate in its free form. Conjugating MTX with nanoparticles allows the drug to be directed to the target site using an external magnetic field, reducing overall toxicity. Combining this approach with hyperthermia could enhance the therapeutic effect in vivo compared to free MTX, though further research on advanced 3D models is needed.

Objectives: To assess the concordance of the preoperative application of the #Enzian classification (#ENZIANi) with the postoperative result (#ENZIANs) using surgical findings as the reference standard. Methods: This retrospective study included 282 consecutive patients with deep endometriosis undergoing surgical treatment. Preoperative assessment with transvaginal sonography and magnetic resonance imaging was compared with postoperative assessment. Concordance and diagnostic test evaluation were calculated. Results: The highest concordance was observed in the F (abdominal wall endometriosis) with k Cohen of 0.837, following the values for pelvic locations, with 0.795 for T left, 0.791 for T right, 0.776 for F (adenomyosis), 0.766 for C (rectum), and 0.75 and 0.72 for O right k and O left, respectively. The highest sensitivity was demonstrated for the P compartment *(98%), T compartment (both sides 97%), and A, B, C (94%- 96%), corresponding with deep endometriosis. Conclusions: Preoperative assessment using TVS/TAS+MRI with the ENZIANi score correlates well with the ENZIANs postoperative score and demonstrates good concordance in the detection and localization of deep endometriosis, thereby minimizing false negative results and ensuring accurate preoperative staging. The ENZIAN classification is well-suited to surgeons&#39; needs and benefits from continuous development. Future improvements, such as adding the expanded C module, may be considered in the next edition.

Background: to analyze the impact of COVID-19 pandemic on characteristics and management of uveal melanoma (UM) in National Referral Center in Poland. Materials and Methods: the retrospective analysis of 1336 patients who were newly diagnosed with UM at Department of Ophthalmology and Ophthalmic Oncology, Jagiellonian University Collegium Medicum Krakow, Poland between January 1, 2018 and December 31, 2021. The demographic and clinical data were compiled including localization, size and treatment methods of tumors. Results: In total, 728 patients with UM were included before COVID-19 pandemic in years 2018-2019 and 608 were included during COVID-19 pandemic in years 2020-2021. Fixed-base dynamics indicators for the incidence of uveal melanoma (base year 2018) in the national referral center in Poland were 80.22% and 86.81% in year 2020 and 2021, respectively. UMs were statistically significantly larger and more frequently localized anterior to the equator of the eye globe in year 2021 than in year 2018 (Chi^2 Pearson test p= 0.0001 and p= 0.0077, respectively). The rate of patients treated with enucleation increased from 15.94% in year 2018 to 26.90% in year 2021 (Chi^2 Pearson test p=0.0005). Conclusions: statistically significant differences were found in the management of uveal melanoma in National Referral Center in Poland during COVID-19 pandemic with tumors being larger, more frequently localized anterior to the equator of the eye globe and more often enucleated.

Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was identification of serum biomarkers of early response to NAC. Methods: We conducted this prospective study in the MSCNRIO, in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers signed informed consent. Complete blood count, blood chemical tests, carcinoembryonic antigen (CEA) carcinoma antigen 125 (CA125), carcinoma an-tigen 19.9 (CA19.9), d-dimer, fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Results: Of all the measured parameters, only IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in complete pathological re-sponse (pCR) vs non-pCR group (3.71 pg/mL vs 7.63 pg/mL, p=0,004). In all patients with IL-6 levels below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs ypN0 (7.69 pg/mL vs 2.89 pg/mL, p=0.022). Conclusions: The trial showed that elevated level of IL-6 prior to treatment and C2 might be a predictor of pathologic response to NAC.

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impact on the functions of the cardiovascular system and the liver. The aim of this study is to stipulate and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, CCAAT/enhancer binding protein α, sterol regulatory ele-ment-binding protein 1c, fatty acid synthase, endothelial lipase, carnitine palmitoyltransferase 1A, and adiponectin receptor 2 in liver tissue; lipoprotein lipase, visceral adipose tissue-derived serine protease inhibitor, and retinol-binding protein 4 in visceral adipose tissue; resistive index of com-mon carotid arteries and aortas, and histopathological changes in CCAs. Obtained outcomes are referred to the results of our previous works. Moreover, our study, to our knowledge, test the in-fluence of Cornus derivative on CPT1A, AdipoR2, RBP4, LIPG, and vaspin for the first time, with a relevant outcome for the first three. Oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and de-creased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigation in atheromatous changes in rabbits’ CCAs was also observed. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

Background: The incidence of intravesical recurrence (IVR) following radical nephroureterectomy (RNU) is reported in up to 50% of patients with upper tract urothelial carcinoma (UTUC). It was suggested that preoperative diagnostic ureteroscopy (URS) could increase the IVR rate after RNU, however, the available data are often conflicting. Thus, in this systematic review and meta-analysis we sought to synthesize that available data for the impact of pre-RNU URS for UTUC on IVR and other oncological outcomes; Materials and methods: A systematic literature search of the PubMed, Embase and Cochrane Library databases was performed in June 2020. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CI) were conducted. The primary endpoint was intravesical recurrence-free survival (IVRFS), with the secondary endpoints being cancer-specific survival (CSS), overall survival (OS), and metastasis-free survival (MFS); Results: Among a total of 5489 patients included in the sixteen selected papers, 2387 (43.4%) underwent diagnostic URS before RNU and 3102 (56.6%) did not. Pre-RNU diagnostic URS was significantly associated with worse IVRFS after RNU (HR=1.44, 95% CI: 1.29-1.61, p&lt;0.001) than RNU alone. However, subgroup analysis including patients without biopsy during URS revealed no significant impact of diagnostic URS on IVRFS (HR=1.28, 95% CI: 0.90-1.80, p=0.16). The results of other analyses showed no significant differences in CSS (HR=0.94, p=0.63), OS (HR: 0.94, p=0.56), and MFS (HR: 0.91, p=0.37) between patients who underwent URS before RNU and those who did not. Conclusions: The results of this meta-analysis confirm that diagnostic URS prior to RNU is significantly associated with worse IVRFS, albeit with no concurrent impact on the other long-term survival outcomes. Our results indicate that URS has a negative impact on IVRFS only when combined with endoscopic biopsy. Future studies are warranted to assess the role of immediate postoperative intravesical chemotherapy in patients undergoing biopsy during URS for suspected UTUC.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with a distinct set of facial features, growth limitations, and limb anomalies. Its clinical spectrum is broad and presents significant challenges in pediatric diagnosis and management. The variable presentation of the disorder, due to cohesin complex mutations, requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients, alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, with an emphasis on innovations in genetic testing, including the detection of mosaicism and novel genetic variations. The aim is to synthesise case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment, and aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of antiproliferative action of the plant’s methanolic root extract (BVR) against colon cancer cells. Cytotoxicity and pro-apoptotic activity were determined in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3; 46.1 and 50.2 µg/mL for LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. RT-qPCR with relative quantification method showed significant changes in the expression of genes related to apoptosis in both colon cancer cell lines. The genes BCL2L1 (126.84-366.66%), BCL2L2 (277.08-330.12%), CASP3 (180.36-261.36%) and CASP9 (158.08-213.46%) had significantly elevated expression, while BCL2 (23.08-52.06%) had reduced expression. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93±0.01, 122.92±0.01, and 220.29±0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+ and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62,60±0.87% of enzyme inhibition. The chemical composition of BVR was determined using UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). This is the first such extensive assessment of the biological activity of BVR. The results are very promising and encourage for the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer.

Introduction. Grilling more and more sophisticated dishes is often a popular activity. Marshmallows are confectionery products popular among children and teenagers worldwide. They are available in many supermarkets ready to be grilled. As such, grilled marshmallows can be a source of exposure to harmful compounds, including carcinogenic polycyclic aromatic hydrocarbons (PAHs). Method. PAHs analysis in marshmallows grilled under different conditions included the dilution stage with deionized water and liquid-liquid extraction with cyclohexane and solid- phase extraction (SPE on silica gel columns). PAH fractions were initially analyzed via planar chromatography (HPTLC-high performance thin layer chromatography) and PAH concentrations were determined via GC-MS/MS (gas chromatography with a tandem mass detector) using the selective reaction monitoring (SRM) mode. This study on the consumption of grilled marshmallows was conducted among approximately 300 children and adolescents. Results. The preliminary results of HPTLC and GC-MS/MS analysis indicated that “raw” marshmallows did not contain PAHs. However, the obtained data suggested a high exposure of young people to carcinogenic PAHs from grilled marshmallows. Carcinogenic BaP was determined in all samples and constituted, on average, 36% of total PAH4. Conclusions. The profile of PAH concentrations in the extracts isolated from various grilled types of marshmallows was very similar (r 2 &gt; 0.8), regardless of the grilling method. Compared to the white sugar confection, the higher concentrations of PAHs were determined in multicolored marshmallows. The lack of social awareness about the exposure to carcinogenic substances is alarming.