Search

The endocannabinoid system (ECS) regulates body’s homeostasis and performs vital physiological functions. The thorough understanding of the role of endocannabinoids and the composition of cannabis containing phytocannabinoids and terpenoids play an important role in symptom management. Clinical effects of medical cannabis depend among others on the activity of the ECS in a given patient, the proportion of phytocannabinoids, and the doses used. Cannabinoids are used to treat symptoms in patients with cancer and chronic non-malignant diseases. Cannabinoids are usually not drugs of first choice and can be added to basic pharmacotherapy, which often improves the effectiveness of symptom treatment. Due to limited scientific evidence, experimental studies on the role of the ECS and clinical trials on the use of cannabinoids in the treatment of symptoms are recommended. In this article the role of the ECS and the use of cannabinoids in palliative care patients has been discussed.

The chimeric antigen receptor (CAR) technology has become one of the greatest breakthroughs in immunotherapy in recent years. CARs facilitate the attack of immune effector cells such as T cells or NK cells being directed at virtually any molecule presented on the surface of a cancer cell. The exceptional efficacy of CAR receptors has been demonstrated for the CD19 molecule found on B cell-derived tumors. However, the efficacy of CAR-T therapy targeting other antigens is less satisfactory while being quite frequently associated with a number of adverse effects. The adverse effects are mainly due to the effector cells being activated in a simplified manner; the most serious effect consists in the antigen being detected on healthy cells (“the on-target, off-tumor” effect). A number of ongoing studies aim at enhancing the safety profile of therapies making use of CAR--modified effector cells. In part, this can be achieved by optimizing the structure of the CAR receptor itself or by using transient transfection to modify the effector cells. A more complex solution consists in obtaining remote control over CAR-T lymphocytes within the patient’s body. This approach makes use of different types of systems that limit the functionality of CAR-T cells in the patient, such as suicide genes, regulation at the transcriptional and protein levels, different types of adapters being used to activate the CAR-T cells. The most advanced system consists in the use of logic gates which make it possible for CAR-T cells to recognize and „understand” incoming signals from the environment, allowing for a certain degree of autonomy in the activation of the cells’ cytotoxic potential. This study presents key strategies to improve the safety profiles of CAR-T therapies.

The main objective of this article is to assess the impact of the banking union on shaping the integration process on the European continent. This has been done by positioning the banking union as a stage leading to a full union of European countries. The basic research question of this study has been formulated as follows: is the banking union project an important element contributing to the full integration of EU banking systems, the implementation of which is necessary to protect the European Union from the effects of future banking crises? This issue was resolved on the basis of an analysis of the available literature and statistical data. The main conclusion of the research undertaken is that: the banking union is a necessary step towards further European integration and is a key element in the integration of European banking systems. However, even the full implementation of the banking union project will not completely eliminate the possibility of banking crises, but may reduce this risk to some extent and thus reduce the costs of potential crises. Głównym celem niniejszego artykułu jest ocena wpływu unii bankowej na kształtowanie procesu integracji na kontynencie europejskim. Zostało to dokonane poprzez umiejscowienie unii bankowej jako etapu prowadzącego do pełnej unii państw europejskich. Podstawowe pytanie badawcze niniejszego opracowania zostało sformułowane w następujący sposób: czy projekt unii bankowej jest istotnym elementem przyczyniającym się do pełnej integracji unijnych systemów bankowych, którego realizacja jest niezbędna w celu ochrony Unii Europejskiej przed skutkami przyszłych kryzysów bankowych? Kwestia ta została rozstrzygnięta na podstawie analizy dostępnej literatury oraz danych statystycznych. Podstawowy wniosek wynikający z podjętych badań brzmi następująco: unia bankowa stanowi niezbędny etap w kierunku dalszej integracji europejskiej i jest kluczowym elementem integracji europejskich systemów bankowych. Jednakże nawet pełne wdrożenie projektu unii bankowej całkowicie nie wyeliminuje możliwości wystąpienia kryzysów bankowych, lecz może w pewnym stopniu ograniczyć to ryzyko, a tym samym zredukować koszty potencjalnych kryzysów.

Pain is experienced by most cancer patients. According to the definition of the International Society for the Study of Pain (IASP), pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. This very “medical” definition indicates that pain is a mental, subjective, sensual, emotional, and unpleasant phenomenon. In palliative care, there is often a need for a better and deeper understanding of what “total” pain can be. The case of a young patient with lung cancer diagnosis presented an opportunity to describe characteristics of such pain, which encompasses physical, mental, social and spiritual suffering.

Proverbs are a part of traditional knowledge that has been increasingly acknowledged to be a valuable source of information for environmental policies. Proverbs on weather convey the cumulated experience of generations that provide guidelines for agricultural practices, everyday decisions, and other situations. Besides the value the proverbs have in their cultural setting, they also serve as an indicator of objective meteorological patterns. This study presents a comprehensive evaluation of the Polish temperature-related proverbs. From the collected corpus of more than 2000 Polish proverbs, 28 were related to temperature and provided concrete predictions and so were selected for further analysis. The proverbs were tested on the basis of temperature (minimum, maximum, and mean) data from 20 weather stations, located in Poland and the neighboring countries, for the period of 1951–2012. Harbingers and forecasts were identified and coded as 0 or 1. Proverb accuracies were then compared using Heidke skill scores and proportions of fulfilled proverbs. The proverbs’ spatial and temporal contingencies were tested via generalized linear mixed models. Some proverbs provided a high proportion (up to 79%) of fulfilled proverbs. Furthermore, the accuracy of the proverbs was reversely proportional to chronological date (decreased with time), with values increasing toward the east and north directions of station locations. The observed changes in proverb accuracies may be attributed to the shift of Polish borders following the Second World War and the respective migration of the population.

Diagnostics and mitigation of excessive moisture effects are some of the most frequent problems in historical buildings. In this article, an attempt was made to measure the moisture content of construction elements in the historical tenement house in Gubin. It is the largest town in the Krosno Poviat, in the area of the Lubuskie Voivodeship. The town suffered from military actions during World War II whereby approximately 90% of its urban development was destroyed. The tenement house at 14A, Śląska Street is one of the more well-preserved buildings, made in the classicist style with characteristic historical features. The whole history of the building is unknown but there are freemasonry symbols on the elevation, and probably the Military Police had its headquarters there after 1945.

Background One of the most important test in every quality assurances process of medical linear accelerators is the Winston-Lutz test, allowing an evaluation of the treatment isocentre in the light of uncertainty of the position of the collimator, the gantry and the couch. Aim The purpose of this work was analysis of the results of the Winston-Lutz test performed with three different phantoms for two different accelerators. Materials and methods Measurements were performed on two Varian machines: TrueBeam equipped with aS1200 EPID and TrueBeam equipped with aS1000 EPID. During the study three different phantoms dedicated for verification of the radiation isocentre were used: PTW Isoball, AQUILAB Isocentre Phantom and Varian Isocentre Cube. Analysis of the DICOM images was performed in Artiscan software. Results For TrueBeam with as1200 EPID, gantry MV isocentre was about 0.18 mm larger for Varian Isocentre Cube than for two other phantoms used in this study. The largest variability of this parameter was observed for the couch. The results differed to 1.16 mm. For TrueBeam with as1000 EPID, results for collimator isocentre with PTW Isoball phantom were about 0.10 mm larger than for two other phantoms. For the gantry, results obtained with Varian Isocentre Cube were 0.21 mm larger. Conclusion The obtained results for all three phantoms are within the accepted tolerance range. The largest differences were observed for treatment couch, which may be related to the phantom mobility during couch movement.

The problem of air pollution not only in Poland but also around the world has become an important topic of political, economic, scientific, and legal discourse. Its position is the result of international obligations and Poland's membership in the structures of the European Union. In Poland, air quality is very bad, which makes it one of the countries with the worst air quality indicators in the European Union. One of the methods to reduce this high level of air pollution is to intensify the development of renewable energy sources by introducing effective support mechanisms for investors of new user-friendly and environment-friendly energy. The aim of the article was to analyse the support system for the development of energy production from renewable sources using the so-called "green" certificates of origin mechanism, which in Poland already has a 14-year tradition. The article presents the model of the renewable energy production support system in force in Poland. It pointed to its strengths and weaknesses. The development trends of the RES support system were also presented.

Background Amyloid cardiomyopathy (CA) it is more frequently diagnosed due to rapidly developing imaging modalities. Misfolding of transthyretin (TTR) is the source of two distinct forms of amyloidosis (ATTR): acquired wild-type (ATTRwt) and hereditary (ATTRm). Types of TTR gene variants display genetic and ethnic variability. The aim of this prospective study was to assess the prevalence and types of pathogenic genetic variants associated with ATTRm amyloidosis in patients with unexplained left ventricle (LV) hypertrophy. Methods We evaluated prospectively 101 consecutive patients (37 (37%) females, age: 69.7±13.6 y.o.) in years 2016–2021. Analysis included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE), single-photon emission computed tomography (SPECT) with 3,3-disphono-1,2-propanodicarboxylic acid (DPD), and in selected cases cardiac or soft tissue biopsy. Patients with DPD cardiac uptake in SPECT or positive histopathology or family history of ATTR were subjected to genetic testing by an amplicon-based next-generation TTR sequencing approach. Results Enrolled patients presented with marked LV hypertrophy with maximum wall thickness of 18.9±4 mm. Based on performed tests 34 patients (33.7%) were diagnosed with amyloidosis, including 17 cases of light-chain amyloidosis (AL), 16 of ATTR, and 1 case of other type of amyloidosis. Overall, patients with CA presented with mean 2.6±0.9 NYHA class. In TTE there was LV maximum wall thickness of 19.5±4 mm and LV mass value index value of 182±48 g/m2, decreased global longitudinal strain value (GLS, −14.1±5%) and advanced diastolic dysfunction (EA 2.2±1.1, E/E' 22±9). Overall, there were 8 cases of ATTRwt and eight patients were diagnosed ATTRm. There were detected following types of TTR variants - c.302C>T p.(Ala101Val) in a single male patient, c.325G>A p.(Glu109Lys) in a single male patient and c.157T>C p.(Phe53Leu) in six patients. Overall, 10 patients with ATTR presented with polyneuropathy, additionally six had diagnosed carpal tunnel syndrome. All patients with ATTRm had positive family history for CA. Conclusions In patients with unexpected LV hypertrophy evaluated in a cardiology referral center a high number of patients may suffer from underlying CA. Types of detected TTR gene variants associated with CA included most often Phe53Leu, and rare variants Ala101Val, Glu109Lys. Funding Acknowledgement Type of funding sources: None.

(1) Background: Treatment of cardiac arrhythmias and conduction disorders with the implantation of a cardiac implantable electronic device (CIED) may lead to complications. Cardiac device-related infective endocarditis (CDRIE) stands out as being one of the most challenging in terms of its diagnosis and management. Developing molecular imaging modalities may provide additional insights into CDRIE diagnosis. (2) Methods: We performed a systematic literature review to critically appraise the evidence for the diagnostic performance of the following hybrid techniques: single photon emission tomography with technetium99m-hexamethylpropyleneamine oxime–labeled autologous leukocytes (99mTc-HMPAO-SPECT/CT) and positron emission tomography with fluorodeoxyglucose (18F-FDG PET/CT). An analysis was performed in accordance with PRISMA and GRADE criteria and included articles from PubMed, Embase and Cochrane databases. (3) Results: Initially, there were 2131 records identified which had been published between 1971–2021. Finally, 18 studies were included presenting original data on the diagnostic value of 99mTc-HMPAO-SPECT/CT or 18F-FDG PET/CT in CDRIE. Analysis showed that these molecular imaging modalities provide high diagnostic accuracy and their inclusion in diagnostic criteria improves CDRIE work-up. (4) Conclusions: 99mTc-HMPAO-SPECT/CT and 18F-FDG PET/CT provide high diagnostic value in the identification of patients at risk of CDRIE and should be considered for inclusion in the CDRIE diagnostic process.

The research problem is to determine the system composition for financing investments in renewable energy sources in Poland. The aim of the article is to identify, analyse and assess the elements that are absolutely essential for green energy transformation in Poland: the support of investments from public funds (the first part of the article), the mechanism for investing in commercial projects (the second part) and the financing of small projects provided by households (the third part). The research method in the first part is based on strategic documentation analysis, in the second part on individual interviews conducted with selected financial institutions, such as the European Investment Bank, and in the third part on Polish households surveys conducted by research companies and universities. The conclusions indicate the relatively low scale of public support for investments in renewable energy sources and the lack of clear preferences for technologies with unstable electricity generation characteristics and regulatory uncertainty. The terms and the financing model are not conducive to small projects and projects intended for household purposes. Opportunities for investment in the development of dispersed and smaller scale sources should be found in reducing technology costs and improving the competitiveness of energy prices on the market. Improving Polish and the EU financing system needs to maintain public support, better identify the financial needs and financial limitations, and increase the scope of financial advisory and guarantees for entities. Those undertakings will activate a significant number of small investors and local renewable energy generation.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Pfizer Research Grant (ID#57165999) Background Misfolding of transthyretin (TTR) is the source of two distinct forms of amyloidosis (ATTR): acquired or wild-type (ATTRwt) and hereditary (ATTRm), which is transmitted in an autosomal dominant inheritance with a variable penetrance. Types of transthyretin (TTR) gene mutations display genetic and ethnic variability. Purpose The aim of this prospective study was to assess the TTR gene variants, echocardiographic parameters and regional left ventricle 99mTc-DPD uptake among patients with ATTR and first-degree relatives. Methods We present data based on evaluation of first 25 patients (13 (52%) females), including 10 (40%) index patients with ATTR (age 66.4 ± 13 years) and 15 (60%) first-degree relatives who were studied between June 2020 and February 2021. Analysis included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE) with global longitudinal strain (GLS) analysis, single-photon emission computed tomography (SPECT) with 3,3-disphono-1,2-propanodicarboxylic acid (DPD), genetic testing by an amplicon-based next-generation TTR sequencing approach, and in selected cases cardiac or soft tissue biopsy. Results Overall, 6 index patients were diagnosed with ATTRm and 4 with ATTRwt presenting mixed, cardiac or neuropathic phenotype. There were detected following types of TTR variants - Phe53Leu, Ala101Val, Glu112Lys, Glu109Lys. Nine out of 10 index patients were diagnosed with amyloid cardiomyopathy (CA) with grade 2-3 tracer uptake in SPECT and symptomatic heart failure (NYHA 2.2 ± 1.1; NT-proBNP value 2224 ± 2799 pg/ml). In both ATTRm and ATTRwt there were patients presenting with either focal or diffuse tracer pattern evaluated by SPECT technique. In TTE there was marked left ventricle (LV) hypertrophy with maximum wall thickness of 22 ± 5 mm and LV mass value index value of 382 ± 111 g/m2. All patients with CA had abnormal global longitudinal strain (GLS, -14.5 ± 5%) and diastolic dysfunction (EA 1.56 ± 0.76, E/E’ 16 ± 11). None of relatives expressed tracer uptake in scintigraphy. Overall, 5 first-degree relatives were diagnosed with Phe53Leu variant, among them two patients presented with decreased GLS value. Conclusions Patients with ATTR presented in TTE with LV hypertrophy, decreased GLS value, diastolic dysfunction and grade 2-3 in scintigraphy with either focal or diffuse tracer uptake in SPECT technique. None of first-degree relatives expressed increased tracer uptake in scintigraphy. However, some of relatives who were diagnosed with pathogenic TTR variant presented with decreased GLS value.

Degloving injuries are traumatic avulsions usually resulting in large areas of soft tissue defects. The injury involves separation of skin and subcutaneous tissue from fascia and muscles. The complex nature of these injuries requires a patient-oriented multidisciplinary surgical approach and a wide variety of therapeutic options. Negative pressure wound therapy can be of benefit at every stage of the long-lasting treatment. In this paper, we present a case of a 29-year-old male after an occupational accident with a conveyor belt leading to a degloving injury of the right forearm treated in the Department of Plastic Surgery of the Medical University in Gdańsk. The use of NPWT, hyperbaric oxygen therapy, dermal regeneration templates, skin grafting, and early rehabilitation resulted in an excellent functional and aesthetic outcome.

Intratumoral dendritic cells play an important role in stimulating cytotoxic T cells and driving antitumor immunity. Using a metastatic ovarian tumor model in syngeneic mice, we explored whether therapy with a CXCR4 antagonist-armed oncolytic vaccinia virus activates endogenous CD103+ dendritic cell responses associated with the induction of adaptive immunity against viral and tumor antigens. The overall goal of this study was to determine whether expansion of CD103+ dendritic cells by the virally delivered CXCR4 antagonist augments overall survival and in situ boosting with a tumor antigen peptide-based vaccine. We found that locoregional delivery of the CXCR4-A-armed virus reduced the tumor load and the immunosuppressive network in the tumor microenvironment, leading to infiltration of CD103+ dendritic cells that were capable of phagocytic clearance of cellular material from virally infected cancer cells. Further expansion of tumor-resident CD103+ DCs by injecting the FMS-related tyrosine kinase 3 ligand, the formative cytokine for CD103+ DCs, provided a platform for a booster immunization with the Wilms tumor antigen 1 peptide-based vaccine delivered intraperitoneally with polyriboinosinic:polyribocytidylic acid as an adjuvant. The vaccine-induced antitumor responses inhibited tumor growth and increased overall survival, indicating that expansion of intratumoral CD103+ dendritic cells by CXCR4-A-armed oncovirotherapy treatment can potentiate in situ cancer vaccine boosting. Keywords: virotherapy, CXCR4 antagonist, cancer vaccine, dendritic cells, T cells

Clinical symptoms of food allergy may affect not only the digestive tract, but also the respiratory system, skin, or cardiovascular system. They may manifest themselves as gastrointestinal problems, asthma attacks, hives, or anaphylactic shock. Allergic reactions of the gastrointestinal tract may be IgE-independent (oral anaphylaxis syndrome, acute gastrointestinal reactions), mixed (eosinophilic gastrointestinal disorders), or IgE-independent (food-induced enterocolitis, proctitis, or enteropathy). The most serious conditions in which allergic background plays or can play an important role are: oral anaphylaxis syndrome, aphthous stomatitis, reflux disease, acute and chronic allergic reactions of gastric mucosa, irritable bowel syndrome, and eosinophilic gastrointestinal disorders.

Transversal competences constitute a set of the knowledge, skills, and attitudes required for various positions and in different professions. Such competences include: entrepreneurship, teamwork, creativity, and communicativeness; they are increasingly listed by employers in different countries as the key requirements in the labor market. The article presents the model of accelerating the process of acquiring transversal competences, developed based on the analysis of data collected in four countries of the European Union: Poland, Finland, Slovakia, and Slovenia. In the analysis, multivariate additive regression spline method was used, along with artificial neural networks, in order to create the best model describing the influence of different variables on the acceleration of acquiring transversal competences. Herewith, we demonstrated that by accelerating the acquisition of the transversal competence of entrepreneurship is influenced by the following factors: rank of the training method in the developed matrix, student numbers and the weighted average of the pace of acceleration regarding the acquisition of the remaining transversal competences, i.e., teamwork, communicativeness and creativity by the given student. The results validate our new method of the acceleration of acquiring transversal competences by students. Students may be from various higher education institutions in different countries. Developed results may be used in the course of education within the framework of the already planned vocational courses and for developing the skills required by employers for various positions and in different professions.

Objective Cost-utility analyses are becoming increasingly important in Central and Eastern Europe. We aimed to develop a Polish utility tariff for EQ-5D-5L health states. Methods Face-to-face, computer-assisted interviews were collected in a representative sample. Each respondent followed a standardised protocol to collect ten composite time trade-off and seven discrete choice experiment observations. In the Bayesian approach, several model specifications were compared based on model fit, the usability of the final value set and how they reflect the elicitation procedure (e.g. censoring). A hybrid approach (using composite time trade-off and discrete choice experiment data) was employed in the final set, which was compared with the existing ones: EQ-5D-3L and EQ-5D-5L cross-walk. Results Data from 1252 respondents (11,480 composite time trade-off valuations and 8764 discrete choice experiment pairs) were collected over the period June to October 2016. The final model accounted for random parameters, error scaling with fat tails, censoring at − 1, unwillingness to trade in time trade-off by the religious people and Cauchy distribution in discrete choice experiments. Pain/discomfort impacts the utility most: the disutility equals 0.575 when at level 5. In the value set, 4.4% of EQ-5D-5L states are worse than dead. The new value set has a comparable range (minimum of − 0.590 compared to − 0.523) and the same ordering of the first three dimensions (pain/discomfort, mobility, self-care) as the EQ-5D-3L value set and the EQ-5D-5L cross-walk value set. Moreover, it is more sensitive to a moderate decline in health. Conclusions The new value set supports consistency with past decisions in cost-utility studies, while offering a better assessment of even moderate improvements in health. It could represent an option for Central and Eastern Europe countries lacking their own value sets. Electronic supplementary material The online version of this article (10.1007/s40273-019-00811-7) contains supplementary material, which is available to authorized users.

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogeneous blood cancer characterized by abnormal expansion of immature B cells. Although intensive chemotherapy provides high cure rates in a majority of patients, subtypes harboring certain genetic lesions, such as MLL rearrangements or BCR-ABL1 fusion, remain clinically challenging, necessitating a search for other therapeutic approaches. Herein, we aimed to validate antioxidant enzymes of the thioredoxin system as potential therapeutic targets in BCP-ALL. We observed oxidative stress along with aberrant expression of the enzymes associated with the activity of thioredoxin antioxidant system in BCP-ALL cells. Moreover, we found that auranofin and adenanthin, inhibitors of the thioredoxin system antioxidant enzymes, effectively kill BCP-ALL cell lines and pediatric and adult BCP-ALL primary cells, including primary cells co-cultured with bone marrow-derived stem cells. Furthermore, auranofin delayed the progression of leukemia in MLL-rearranged patient-derived xenograft model and prolonged the survival of leukemic NSG mice. Our results unveil the thioredoxin system as a novel target for BCP-ALL therapy, and indicate that further studies assessing the anticancer efficacy of combinations of thioredoxin system inhibitors with conventional anti BCP-ALL drugs should be continued.

Objectives Occupational exposure to inhaled nanoparticles (NPs) represents a significant concern for worker health. Adolescent workers may face unique risks for exposure and resulting health effects when compared with adult workers. Methods This manuscript discusses key differences in risks for occupational exposures to inhaled NPs and resulting health effects between young workers and adult workers via an examination of both physiological and occupational setting factors. Results Previous studies document how adolescents often face distinct and unique exposure scenarios to occupational hazards when compared to adults. Moreover, they also face different and unpredictable health effects because biological functions such as detoxification pathways and neurological mechanisms are still developing well into late adolescence. Early exposure also increases the chances of developing long‐latency disease earlier in life. Taken together, adolescents’ rapid growth and development encompasses highly dynamic and complex processes. An aggravating factor is that these processes do not necessarily fall in line with legal classifications of adulthood, nor with occupational exposure limits created for adult workers. Conclusions The differences in exposures and health consequences from NPs on young workers are insufficiently understood. Research is needed to better understand what adolescent‐specific mitigation strategies may be most suitable to address these risk factors.

Functioning of modern agriculture and farms is dominated by increasing demand for energy. Meeting this demand is, however, a strategic problem which affects energy, food and environmental safety as well as operating costs of commercial farms and rural households. This paper discusses the problems of implementation of eco-innovation on the example of renewable energy sources in the Polish farm sector. The paper analyses energy intensity and structure of energy consumption in the Polish agricultural sector. It discusses the structure of energy consumption, taking into account rural areas, in Poland and Europe as well as analyzes energy costs in various types of agricultural production. Moreover, the paper assesses the potential of renewable energy sources in the Polish agriculture and presents barriers connected to their use.

International audience; Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of driver mutations of JAK2, CALR or MPL genes. Overexpression of WT1 is used as a marker of minimal residual disease in acute myeloid leukemia, especially after allogeneic stem cell transplantation (SCT). We investigated WT1 expression at diagnosis in 152 MPN patients and showed that the WT1 transcript was overexpressed in PMFs and PVs compared to controls. In particular, WT1 transcript levels were higher in PMF than in ET and PV. WT1 transcript levels were significantly increased during myelofibrotic transformation of ET or PV. Using multi-variate linear regression, high WT1 transcript levels in PMF were associated with age over 65, splenomegaly and thrombocytopenia. The ROC curve analysis showed that a level of WT1 transcript > 10 WT1 copies/10 4 ABL1 enabled the diagnosis of PMF with a specificity of 95.8% (PMF vs ET; ROC AUC = 0.91). In myelofibrosis, studying follow-ups of WT1 transcript showed that this marker is of interest after allogeneic SCT. These results demonstrate that WT1 overexpression is a simple marker of myelofibrosis in MPN and could be used during patient follow-up.

Introduction The level of fear of hymenoptera associated with stinging or envenomation may depend on situational factors and on trait anxiety characteristic of each patient. Aim To assess the relationship between fear of stinging insects on the one hand and state anxiety and trait anxiety on the other in a group of patients with hymenoptera venom allergy. Material and methods The study was conducted by the Department of Allergy, Clinical Immunology and Internal Diseases, Dr J. Biziel University Hospital No. 2 in Bydgoszcz, Poland. A total of 114 patients (71 women (63%) and 43 men (37%)) with hymenoptera venom allergy undergoing immunotherapy participated in the study. The State-Trait Anxiety Inventory (STAI) and a dedicated scale developed by the authors for this study were used. Results State anxiety was found to significantly (p < 0.05) correlate with anxiety in the present moment (R = 0.247), in a situation of real danger (appearance of an insect) (R = 0.223) and during the spring and summer seasons (R = 0.278). Trait anxiety was found to significantly (p < 0.05) correlate with anxiety before immunotherapy (R = 0.261), in the present moment (R = 0.257), in a situation of real danger (appearance of an insect) (R = 0.254), and after an insect sting (R = 0.236). These were also weak correlations. The correlation between trait anxiety and anxiety during the spring and summer seasons was moderate (R = 0.331). Conclusions The levels of trait and state anxiety are associated with the magnitude of the fear of the danger. Respondents showed a higher level of anxiety in a situation of danger and after an insect sting.

The need for quick and easy deflection calculations of various prefabricated slabs causes that simplified procedures and numerical tools are used more and more often. Modelling of full 3D finite element (FE) geometry of such plates is not only uneconomical but often requires the use of complex software and advanced numerical knowledge. Therefore, numerical homogenization is an excellent tool, which can be easily employed to simplify a model, especially when accurate modelling is not necessary. Homogenization allows for simplifying a computational model and replacing a complicated composite structure with a homogeneous plate. Here, a numerical homogenization method based on strain energy equivalence is derived. Using the method proposed, the structure of the prefabricated concrete slabs reinforced with steel spatial trusses is homogenized to a single plate element with an effective stiffness. There is a complete equivalence between the full 3D FE model built with solid elements combined with truss structural elements and the simplified homogenized plate FE model. The method allows for the correct homogenization of any complex composite structures made of both solid and structural elements, without the need to perform advanced numerical analyses. The only requirement is a correctly formulated stiffness matrix of a representative volume element (RVE) and appropriate formulation of the transformation between kinematic constrains on RVE boundary and generalized strains.

This article presents the effect of taking into account the subgrade coefficient on static work of a pontoon with an internal partition, made in one stage and treated computationally as a monolithic closed rectangular tank. An exemplary pontoon is a single, ready-made shipping element that can be used as a float for a building. By assembling several floats together, the structure can form a floating platform. Due to the increasingly violent weather phenomena and the necessity to ensure safe habitation for people in countries at risk of inundation or flooding, amphibious construction could provide new solutions. This article presents calculations for a real pontoon made in one stage for the purpose of conducting research. Since it is a closed structure without any joint or contact, it can be concluded that it is impossible for water to get inside. However, in order to exclude the possibility of the pontoon filling with water, its interior was filled with Styrofoam. For static calculations, the variational approach to the finite difference method was used, assuming the condition for the minimum energy of elastic deflection during bending, taking into account the cooperation of the tank walls with the Styrofoam filling treated as a Winkler elastic substrate and assuming that Poisson’s ratio ν = 0. Based on the results, charts were made illustrating the change in bending moments at the characteristic points of the analysed tank depending on acting loads. The calculations included hydrostatic loads on the upper plate and ice floe pressure as well as buoyancy, stability and metacentric height of the pontoon. The aim of the study is to show a finished product—a single-piece pontoon that can be a prefabricated element designed for use as a float for “houses on water”.

Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in patients with anxiety or mood disorders. In a small number of clinical trials, cannabinoids used to treat cancer, HIV, multiple sclerosis, hepatitis C, Crohn's disease, and chronic neuropathic pain report decreases in anxiety or depression symptoms and presented sedative and anxiolytic effects. Several studies have investigated the influence of potential genetic factors on psychosis and schizophrenia development after cannabis use. THC may increase the risk of psychosis, especially in young patients with an immature central nervous system. There is limited evidence from clinical trials that cannabinoids are effective therapy for sleep disorders associated with concomitant conditions. There is evidence for a possible role of cannabis as a substitute for alcohol and drugs, also in the context of the risks of opioid use (e.g., opioid-related mortality). In this narrative review of the recent evidence, we discuss the prospects of using the psychoactive effects of cannabinoids in treating mental and psychiatric disorders. However, this evidence is weak for some clinical conditions and well-designed randomized controlled trials are currently lacking. Furthermore, some disorders may be worsened by cannabis use.

Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment.This prospective study enrolled patients with oropharyngeal cancer treated between 2016 and 2018 in 3 centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the European Organisation for Research and Treatment of Cancer HN-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before radiation therapy, after receiving 20 Gy, and within 24 hours after treatment completion. Quantitative real-time polymerase chain reaction arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade3 xerostomia and 30 without.Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both the exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiation therapy had an area under the curve of 0.96 (95% confidence interval, 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (area under the curve 0.90; 95% confidence interval, 0.75-1.00). These results were confirmed in the validation group. In the validation group, preradiation therapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same 2 miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6% sensitivity and 55.2% specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0% sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0% sensitivity and 58.6% specificity.Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiation therapy or during therapy (after 20 Gy) had significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from that related to the dosimetric data.

We have demonstrated that oncolytic vaccinia virus synergizes with doxorubicin (DOX) in inducing immunogenic cell death in platinum-resistant ovarian cancer cells and increases survival in syngeneic and xenograft tumor models. However, the mechanisms underlying the virus- and doxorubicin-mediated cancer cell death remain unknown. In this study, we investigated the effect of the oncolytic virus and doxorubicin used alone or in combination on activation of the cytoplasmic transcription factor CREB3L1 (cyclic AMP [cAMP] response element-binding protein 3-like 1) in ovarian cancer cell lines and clinical specimens. We demonstrated that doxorubicin-mediated cell death in ovarian cancer cell lines was associated with nuclear translocation of CREB3L1 and that the effect was augmented by infection with oncolytic vaccinia virus or treatment with recombinant interferon (IFN)-β used as a viral surrogate. This combination treatment was also effective in mediating nuclear translocation of CREB3L1 in cancer cells isolated from ovarian tumor biopsies at different stages of disease progression. The measurement of CREB3L1 expression in clinical specimens of ovarian cancer revealed lack of correlation with the stage of disease progression, suggesting that understanding the mechanisms of nuclear accumulation of CREB3L1 after doxorubicin treatment alone or in combination with oncolytic virotherapy may lead to the development of more effective treatment strategies against ovarian cancer., Graphical abstract, Induction of immunogenic cell death by doxorubicin in combination with oncolytic vaccinia virus is associated with activation of the cytoplasmic transcription factor CREB3L1.

The increase in air temperature by 2100 projected by climate models will affect the value of thermal characteristics that are important from the point of view of the agriculture and energy sectors. Noticeable changes for each of the nine calculated indices are already visible in the so-called near future (2021–2050). At the end of the current century, they are projected to increase so dramatically that they will significantly affect the analysed sectors. The growing season in projections based on the RCP 8.5 scenario may be extended in some regions of Poland by up to 2 months and the frost-free period in almost the entire territory of Poland by at least 40 days. The annual number of growing degree days for both temperature thresholds (5 °C and 10 °C) will also increase significantly. From the energy consumption point of view, the positive effect of warming will be a significant reduction in the demand for energy used to heat buildings (heating degree days). This positive impact can, however, could be reduced by a large increase in energy demand due to refrigeration and air conditioning (cooling degree days). Even in warmer climates, there will still be some days with a high demand for energy for heating. An increase in the demand for energy for cooling during the warmest days may overload energy production and transmission systems.

Manufactured nanomaterials are currently used in numerous industrial sectors in order to produce innovative consumer products characterized by particular and specific properties. Their extensive production and distribution are responsible for increased human exposure and there is growing concern regarding their potential adverse health effects as scientific evidence shows that these substances may be responsible of several toxic effects. Consequently, the need to establish and apply appropriate regulatory standards and management policies in order to protect human health is evident. This chapter provides an overview of the main safety guidelines and regulatory policies for nanotechnology/nanomaterials in order to identify research areas and knowledge gaps that still need to be addressed. In this regard, key points to be taken into consideration in the near future include the harmonization and standardization of the risk assessment process and the definition of adequate occupational exposure limits based not only on mass concentration.

Background and aims: An inverse relationship between lipid levels and atrial fibrillation (AF) has been suggested, but whether the association is upheld for all age groups remains unclear. The aim of the study was to examine associations between lipid levels and AF by age groups in a nationwide study in Poland. Methods: Multivariate Poisson regression models were used to estimate prevalence ratios (PRs) for AF by lipid levels. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), non-HDL-C and LDL-C/HDL-C ratios were grouped into quartiles. Results: Of the 13,724 participants, 5.2% (n = 708) had AF. People with AF were older with more comorbidities, but lower lipid levels (all p < 0.05). The prevalence of AF was inversely associated with LDL-C (Adjusted PR (95% Confidence Interval) highest versus lowest quartile: 0.60 (0.48, 0.75)), TC (0.61 (0.49, 0.75)) and non-HDL-C (0.63 (0.51, 0.78)). The prevalence of AF was inversely associated with HDL-C (0.58 (0.46, 0.74)), but this was not statistically significant for people aged 75 years and older. For the LDL-C/HDL-C ratio, the prevalence of AF was only inversely associated with higher levels for people aged 75 years and older (0.75 (0.61, 0.94)). There was no statistically significant difference in prevalence of AF by TG levels. Conclusions: The results suggest an inverse relationship between lipid levels and AF. The inverse association between higher HDL-C and AF was only significant for people aged

Analysis of variability of the fetal heart rate (FHR) signals is very important for fetal well-being assessment. The beat-to-beat variability is described quantitatively by parameters originated from direct fetal electrocardiography, which provides the FHR signal in a form of time event series. Nowadays, monitoring instrumentation is based on the Doppler ultrasound technique. The fetal monitors provide the output signal in a form of evenly spaced measurements. The goal of this work is to present a new method for the FHR signal processing, which enables the extraction of time event series of consecutive heartbeat intervals from the evenly repeated measurements. The proposed correction algorithm enables the recognition and removal of the redundant measurements. Reliable evaluation of the proposed algorithm required the reference time event series, thus the testing FHR signals were obtained from abdominal fetal electrocardiograms.

Responsible business is the idea of running a business based on consistently maintaining relationships with all participants of the environment, respecting economics, ecology and ethics. One of the areas of economics and ethics is education, and its function is the training of competences of future employees of companies that influence the understanding and implementation of activities in the area of Corporate Social Responsibility (CSR). Due to the fact that CSR is a management function, taking into account the company’s responsibility for a specific reality in which it operates, it is important to define and define the role of the entity that allows proper management of information between institutions involved in educating social competences. The aim of the article is to present the assumptions and structure of the Educational and Economic Network of the Wielkopolska Region (EENWR), which is an example of Corporate Social Responsibility in the area of information management about the required social competences. The results of the research work cover a period of 48 months and include information obtained from more than 1,200 employers and 25,000 potential employees. System and tool solutions that are proposed in the framework of EENWR increase the effectiveness of the transformation of entities and their competitiveness.

In magnonics, a fast-growing branch of wave physics characterized by low energy consumption, it is highly desirable to create circuit elements useful for wave computing. However, it is crucial to reach the nanoscale so as to be competitive with the electronics, which vastly dominates in computing devices. Here, based on numerical simulations, we demonstrate the functionality of the spin-wave diode and the circulator to steer and manipulate spin waves over a wide range of frequency in the GHz regime. They take advantage of the unidirectional magnetostatic coupling induced by the interfacial Dzyaloshinskii-Moriya interaction, allowing the transfer of the spin wave between thin ferromagnetic layers in only one direction of propagation. Using the multilayered structure consisting of $\mathrm{Py}$ and $\mathrm{Co}$ in direct contact with heavy metal, we obtain submicrometer-size nonreciprocal devices of high efficiency. Thus, our work contributes to the emerging branch of energy-efficient magnonic logic devices, giving rise to the possibility of application as a signal-processing unit in the digital and analog nanoscaled spin-wave circuits.

Simple Summary Hypothyroidism is a common complication of therapeutic irradiation in the neck area. Several dose-response models have been proposed to predict its’ occurrence based on clinical and radiomic features. We aimed to externally validate the results of five such models in a prospectively recruited cohort of 108 patients with oropharyngeal cancer. Two of the evaluated models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance. Both models are based on mean thyroid dose and thyroid volume. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse. Short-term change in the level of thyroid-stimulating hormone (TSH) after radiation therapy was not indicative of hypothyroidism development in long term. We conclude that the models by Rønjom et al. and by Boomsma et al. are feasible for long-term prediction of hypothyroidism in oropharyngeal cancer survivors treated with intensity-modulated radiation therapy. Abstract We aimed to externally validate five normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RIHT) in a prospectively recruited cohort of 108 patients with oropharyngeal cancer (OPC). NTCP scores were calculated using original published formulas. Plasma thyrotropin (TSH) level was additionally assessed in the short-term after RT. After a median of 28 months of follow-up, thirty one (28.7%) patients developed RIHT. Thyroid mean dose and thyroid volume were significant predictors of RIHT: odds ratio equal to 1.11 (95% CI 1.03–1.19) for mean thyroid dose and 0.87 (95%CI 0.81–0.93) for thyroid volume in univariate analyses. Two of the evaluated NTCP models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance with accuracies of 0.87 (95%CI 0.79–0.93) and 0.84 (95%CI: 0.76–0.91), respectively. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse, overestimating the risk of RIHT in this patient cohort. A short-term TSH level change relative to baseline was not indicative of RIHT development in the follow-up (OR 0.96, 95%CI: 0.65–1.42, p = 0.825). In conclusion, the models by Rønjom et al. and by Boomsma et al. demonstrated external validity and feasibility for long-term prediction of RIHT in survivors of OPC treated with Intensity-Modulated Radiation Therapy (IMRT).

Bisphenol A (BPA) is classified as an endocrine disruptor (ED) and it can interact with variety of hormone receptors leading to hormonal disruption and increased risk of various adverse health effects. Reducing human exposure to BPA is one of the main challenges of public health, as it is constantly present in daily life. A low-cost and commonly applied method to enable determination of BPA in the patient's body has yet to be developed. Currently available techniques are expensive, time-consuming, and require access to highly equipped analytical chemistry laboratories. Here we describe a fast and cheap engineered lateral flow assay of our design, to detect of BPA in urine samples. The technology not only provides an opportunity to perform rapid medical diagnostics without the need for an access to the central laboratory but also a means for self-diagnosis by the patient. The addition of β-glucuronidase improves the sensitivity of detection as it releases the free BPA from glucuronide complexes in urine. This invention may become a demonstrated analytical means for lowering human exposure to BPA and probably also to other EDs and consequently, may be useful in decrease of the risk for several lifestyle diseases.

Convolutional neural networks (CNN) are utilized to encode the relation between initial configurations of obstacles and three fundamental quantities in porous media: porosity ($\varphi$), permeability $k$, and tortuosity ($T$). The two-dimensional systems with obstacles are considered. The fluid flow through a porous medium is simulated with the lattice Boltzmann method. It is demonstrated that the CNNs are able to predict the porosity, permeability, and tortuosity with good accuracy. With the usage of the CNN models, the relation between $T$ and $\varphi$ has been reproduced and compared with the empirical estimate. The analysis has been performed for the systems with $\varphi \in (0.37,0.99)$ which covers five orders of magnitude span for permeability $k \in (0.78, 2.1\times 10^5)$ and tortuosity $T \in (1.03,2.74)$., Comment: 12 pages, 9 figures

The main research problem discussed in this paper involves evaluation of the motives of agricultural producers for pursuing and developing organic production. The aim of this study is to identify and evaluate the role of social values in stimulating decisions of involvement in organic production. Analytical observations were conducted on the basis of responses to surveys on a nation-representative sample in Poland (350 conventional farms and 70 organic farms in 2011, 260 conventional farms and 65 organic farms in 2019). Analyses were conducted in relation to the potential and perspectives for development of organic farming. They were focused on identifying the original motives for such decisions (incentives and disincentives). This allowed for effective evaluation of both the trend and the pace of the studied processes. The development potential of organic farming in Poland was estimated at 5&ndash, 15% of the total number of farms. The most important factors encouraging farmers to take up production are associated with social values (care for the natural environment and family health). A significant chance for the development of organic production is the expected demand growth, which is also related to social values: the increasing environmental awareness and environmental change of consumption patterns.

International audience; Measurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10-5) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD

The fewer Karaims there are, the more complicated the study of Karaims becomes. The community is disappearing, and the adverse effects of endogamy are reaching their inevitable conclusion. Yet everything that concerns the lives, activities and long-term and short-term plans of the Karaim community seems to defy demographic figures. This is the starting point for an account of Karaims living in contemporary Poland. As in the past, contemporary “grand narratives” tend to marginalize such small groups as the Karaims, leading to their sense of alienation. This chapter attempts to describe some remarkably effective strategies for survival developed by the distant descendants of the Khazars, Polovtsy and Kipchaks. This tiny community has benefited from the various possibilities of maintaining their identity, which include media performances, shows, incidental and hybrid group ties, vociferous mobilizations, effective application of administrative regulations, the activities of their elites and leaders, and images of the group as seen by others. Karaimes have proved adept at presenting their identity with the aid of vehicles such as electronic media. It turns out that in constructing ethnic identity, the more people learn about Karaims, the more their numbers grow.

Graphitic carbon nitride (gCN(H)) is a semiconductor with high mechanical and thermal stability which provides good dispersion of metal particles. As it is resistant to corrosion, it constitutes an...

As a result of the environment changes, all Logistic Departments need to cover gaps between their needs and possibilities in regard to resources potential available in market and customer requirements. In addition to material re-sources, there are also intangible resources like knowledge, attitude and skills (part of HR). A pioneering mathematic-supported study was done with respect to technical skills of students from IT Departments at technical high schools. We achieve a mathematical model representing possible contributions of students into jobs through professional skills, subject to soft skills, common skills and other socio-economic variables in time. A general aim is to explore the effects between variables, the structure, stability and sensitivity of the model. Thus, the needs in Logistics are addressed through decision aid, educational improvements, programs and measurements. We take a genuine lead to networking and modelling side of HRM by modern Data Mining, Analytics and AI. Herewith, human and educational factors are addressed in Logistics, eventually for a best balance between job offers and demands. The resulting models are compared by the help of statistical performance criteria, they are discussed, interpreted, evaluated, and economic as well as educational implications are derived.