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Abstract The major driver oncogenes MYC, mutant KRAS, and mutant TP53 often coexist and cooperate to promote human neoplasia, which results in anticancer therapeutic opportunities within their downstream molecular programs. However, little research has been conducted on whether redundancy and competition among oncogenes affect their programs and ability to drive neoplasia. By CRISPR‒Cas9-mediated downregulation we evaluated the downstream proteomics and transcriptomics programs of MYC, mutant KRAS, and mutant TP53 in a panel of cell lines with either one or three of these oncogenes activated, in cancers of the lung, colon and pancreas. Using RNAi screening of the commonly activated molecular programs, we found a signature of three proteins - RUVBL1, HSPA9, and XPO1, which could be efficiently targeted by novel drug combinations in the studied cancer types. Interestingly, the signature was controlled by the oncoproteins in a redundant or competitive manner rather than by cooperation. Each oncoprotein individually upregulated the target genes, while upon oncogene co-expression each target was controlled preferably by a dominant oncoprotein which reduced the influence of the others. This interplay was mediated by redundant routes of target gene activation - as in the case of mutant KRAS signaling to c-Jun/GLI2 transcription factors bypassing c-Myc activation, and by competition - as in the case of mutant p53 and c-Myc competing for binding to target promoters. The global transcriptomics data from the cell lines and patient samples indicate that the redundancy and competition of oncogenic programs are broad phenomena, that may constitute even a majority of the genes dependent on oncoproteins, as shown for mutant p53 in colon and lung cancer cell lines. Nevertheless, we demonstrated that redundant oncogene programs harbor targets for efficient anticancer drug combinations, bypassing the limitations for direct oncoprotein inhibition.

IntroductionPain assessment in horses presents a significant challenge due to their nonverbal nature and their tendency to conceal signs of discomfort in the presence of potential threats, including humans. Therefore, this study aimed to identify pain-associated behaviors amenable to automated AI-based detection in video recordings. Additionally, it sought to determine correlations between pain intensity and behavioral and postural parameters by analyzing factors such as time budgets, weight shifting, and unstable resting. The ultimate goal is to facilitate the development of AI-based quantitative tools for pain assessment in horses.Materials and methodsA cohort of 20 horses (mean age 15 ± 8) admitted to a university equine hospital underwent 24-h video recording. Behaviors were manually scored and retrospectively analyzed using Loopy® software. Three pain groups were established based on the Pain Score Vetmeduni Vienna : pain-free (P0), mild to moderate pain (P1), and severe pain (P2).ResultsWeight shifting emerged as a reliable indicator for discriminating between painful and pain-free horses, with significant differences observed between pain groups (p

Abstract Background The European bison (Bison bonasus) is a near threatened species and requires health monitoring. The aim of the present study was to determine the prevalence of antibodies to pathogens known to cause respiratory and digestive illness in ruminants. Results In the studied 328 European bison, the highest seroprevalence was observed for Bovine herpesvirus-1 (BoHV-1) (50.27%), Bovine Coronavirus (BCoV) (26.36%), and Bluetongue Virus (BTV) (12.83%). For Mycoplasma bovis strains and Bovine Viral Diarrhea Virus (BVDV), positive results were rare. Interestingly, a higher prevalence of BTV antibodies was noted in the northeastern populations and older animals. Conclusions Our findings indicate that the Polish European bison population appears to have considerable contact with BoHV-1; however, this does not appear to be of great significance, as clinical symptoms and post-mortem lesions are rarely noted in Polish European bison population. The high seroprevalence of BTV in the north-east of Poland is an ongoing trend, also noted in previous studies. It is possible that European bison may perpetuate the virus in this region. This is the first report of antibodies for BCoV in European bison.

Abstract The public health problem of tick-borne diseases has attracted much attention in recent years due to an increasing incidence in humans and animals. The aim of this study was to compare the risk of exposure to ticks and tick-borne infections in dogs and cats in recreational and urbanized areas in the Lesser Poland and Silesian Provinces. For molecular testing for the presence of the selected pathogens, 207 I. ricinus females collected from 119 dogs and 50 cats, and 2 I. hexagonus females collected from 2 domestic dogs, were examined. Overall, A. phagocytophilum was found in 3.7% of the I. ricinus specimens, B. microti in 27.1%, and B. burgdorferi s.l. in 0.9%. In urban areas of both provinces, A. phagocytophilum was found in 4.8% of the I. ricinus specimens, B. microti in 41.6% and B. burgdorferi s.l. in 3.9%. Pathogens were detected B. microti in both studied I. hexagonus specimens. These findings may indicate the important role that these animals play in the circulation of these pathogens in nature.

MiRNAs could play an important role in tumorigenesis and progression. The oncoprotein MDM2 (murine double minute 2) was identified as a negative regulator of the tumour suppressor p53. This study aims to analyse the expression of the MDM2 target miRNA candidates (miR-3613-3p, miR-371b-5p and miR-3658) and the MDM2 gene in oral squamous cell carcinoma tumour and margin samples and their association with the selected socio-demographic and clinicopathological characteristics. The study group consisted of 50 patients. The miRNAs and MDM2 gene expression levels were assessed by qPCR. The expression analysis of the miRNAs showed the expression of only one of them, i.e., miR-3613-3p. We found no statistically significant differences in the miR-3613-3p expression in tumour samples compared to the margin samples. When analysing the effect of smoking on miR-3613-3p expression, we demonstrated a statistically significant difference between smokers and non-smokers. In addition, we showed an association between the miR-3613-3p expression level and some clinical parameters in tumour samples (T, N and G). Our study demonstrates that miR-3613-3p overexpression is involved in the tumour progression of OSCC. This indicates that miR-3613-3p possesses potential prognostic values.

Abstract The European roe deer (Capreolus capreolus) is the most common deer species in Europe. The species can be a reservoir of some tick-borne diseases but it is primarily recognized for its contribution as an amplifier host. In Central Europe, two roe deer ecotypes are living in adjacent areas: field and forest. We investigated differences in tick load and species composition on these two ecotypes. We collected ticks from 160 (80 the forest ecotype and 80 the field ecotype) roe deer culled in Wielkopolska Region (West-Central Poland). The most common was Ixodes ricinus (n = 1610; 99%) followed by Ixodes hexagonus (n = 22; 1%). The dominant life stage of the ticks was female. Prevalence was higher for forest roe deer. Mean number of ticks found on the forest ecotype was almost fivefold higher than on the field ecotype (3.75 ± 0.83 vs. 0.77 ± 0.20 ticks). The mean probability of tick occurrence was threefold higher in the forest (0.915 ± 0.050) than the field ecotype (0.279 ± 0.125). The most infested body parts of roe deer from both ecotypes were the neck and the head.

Mycobacterial infections are significant issues in zoo animals, influencing animal welfare, conservation efforts, and the zoonotic potential of pathogens. Although tuberculosis is recognised to be highly dangerous, paratuberculosis can also lead to animal losses and is potentially dangerous for humans. The aim of the current study was to confirm whether Mycobacterium avium spp. paratuberculosis (MAP) infections are currently present in zoos in Poland. Faeces samples (n = 131) were collected from different animal species from eight zoos in Poland. The faeces were decontaminated and inoculated into Herrold’s Egg Yolk Media. The species was determined using commercial DNA testing. The IS900 was checked using RT-PCR. The culture was positive in seven samples: five with M. avium, one with Mycobacterium fortiatum, and one without any identified Mycobacterium species. RT-PCR confirmed MAP genetic material in nine animals. Our findings represent the first confirmation of MAP in bongo (Tragelaphus eurycerus), indicating that it is present in Polish zoological gardens. Fortunately, the disease can be monitored more easily due to recent legislation (the Animal Health Law).

Drug-eluting stents (DES) demonstrated superior efficacy when compared to bare metal stents and plain-old balloon angioplasty and are nowadays used in almost all percutaneous revascularization procedures. The design of the stent platforms is constantly improving to maximize its efficacy and safety. Constant development of DES includes adoption of new materials used for scaffold production, new design types, improved overexpansion abilities, new polymers coating and, finally, improved antiproliferative agents. Especially nowadays, with the immense number of available DES platforms, it is crucial to understand how different aspects of stents impact the effect of their implantation, as subtle differences between various stent platforms could impact the most important issue—clinical outcomes. This review discusses the current status of coronary stents and the impact of stent material, strut design and coating techniques on cardiovascular outcomes.

ON THE BIOGRAPHY OF THE METROPOLITAN ANDREI SHEPTYTS’KYI – RESEARCH, SOURCES AND METHODS The text discusses the state of research, sources and methods of studying which concern the metropolitan Andrei Sheptyts’kyi, his life and activities. It indicates institutions and archives, where scholars can search for documents on his biography. The author of the text has summed up the state of research on Sheptyts’kyi’s biography, referring readers to numerous publications, including bibliographic sources. Moreover, she has underlined the high rank of studies on Andrei Sheptyts’kyi in the world historiography. The author stated that these considerations need further international research. The text also recognises the areas that require further scholarly studies and complementary analysis.

COQ8A-ataxia is a mitochondrial disease in which a defect in coenzyme Q10 synthesis leads to dysfunction of the respiratory chain. The disease is usually present as childhood-onset progressive ataxia with developmental regression and cerebellar atrophy. However, due to variable phenotype, it may be hard to distinguish from other mitochondrial diseases and a wide spectrum of childhood-onset cerebellar ataxia. COQ8A-ataxia is a potentially treatable condition with the supplementation of coenzyme Q10 as a main therapy; however, even 50% may not respond to the treatment. In this study we review the clinical manifestation and management of COQ8A-ataxia, focusing on current knowledge of coenzyme Q10 supplementation and approach to further therapies. Moreover, the case of a 22-month-old girl with cerebellar ataxia and developmental regression will be presented.

Germline variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) gene have recently been described in about 50 patients with developmental delay and cardiac, facial, and digital anomalies (CAFDADD). We aimed to depict further the clinical and genetic spectrum associated with TRAF7 germline variants in two additional patients, broaden the mutational spectrum, and support the characteristic clinical variety to facilitate the diagnostics of the syndrome among physician involved in the evaluation of patients with developmental delay/congenital malformations.

Objective: Ultrasound estimation of foetal weight is a very important aspect of antenatal care. The role of amniotic fluid volume as a potential factor which may impede the relevance of ultrasonographic foetal weight estimation is still questionable. The aim of our study was to evaluate the impact of isolated oligohydramnios on the accuracy of ultrasound foetal weight estimation in at term pregnancies when examination was performed within 48 h before delivery. Materials and methods: The retrospective cohort study included 1831 women with low-risk, singleton, at term pregnancy. Estimated foetal weight (EFW) was calculated using Hadlock-4 formula. Exclusion criteria consisted of multiple pregnancies, active phase of labour, preeclampsia, foetal growth restriction, foetal anomalies, gestational diabetes mellitus and the evidence of intrauterine infection. Isolated oligohydramnios was defined as Amniotic Fluid Index (AFI) ≤50 mm without any other foetal anomalies. EFW and actual birth weight (ABW) were compared by calculation of: absolute error (AE), absolute percentage error (APE) and substantial error (SE) = APE >10%. Results: Participants were divided into 2 groups: Group 1: patients with normal AFI (50 ≤ AFI ≤250 mm; n = 1602) and Group 2: (isolated oligohydramnios, n = 229). There were not observed statistically significant differences between mean ABW and mean EFW in both groups (Group 1: p = 0.525; Group 2: p = 0.317). Mean AE in Group 1 was 221.8 g and 223.1 g in Group 2 (p = 0.919). Mean APE was 6.54% and 6.64% in Group 1 and 2 respectively (p = 0.816). SE ratio was 21.9% in Group 1 and 19.2% in Group 2. Underestimation to overestimation ratio in Group 1 was 1.01 and 0.84 in Group 2. Conclusions: Amniotic fluid volume has limited impact on ultrasound foetal weight estimation. In oligohydramnios group there might be a tendency of overestimation of neonatal ABW. Keywords: Estimated foetal weight, Amniotic fluid index, Ultrasound examination, AFI, EFW

Bacteria have evolved multiple systems to transport effector proteins to their surface or into the surrounding milieu. These proteins have a wide range of functions, including attachment, motility, nutrient acquisition, and toxicity in the host. Porphyromonas gingivalis

Zwierzęta towarzyszące ludziom, w tym zwierzęta domowe odgrywają ważną rolę w otaczającym nas środowisku. Jednak większość z nich może być narażona na kontakt z gatunkami pasożytniczych roztoczy i owadów, o dużym znaczeniu medycznym i weterynaryjnym, stanowiących zagrożenie dla zdrowia zarówno zwierząt, jak i ludzi. Do najbardziej rozpowszechnionych ektopasożytów skórnych zwierząt należą: Demodex canis, D. cati, D. criceti, D. aurati, D. caviae, Otodectes cynotis, Sarcoptes scabiei, Cheyletiella yasguri, C. blakei, Chirodiscoides caviae, Ctenocephalides canis, C. felis, Trichodectes canis, Linognathus setosus, Felicola subrostratus, Notoedres cati, Dubininia melopsittaci, Sideroferus lunula, Neopsittaconirmus gracilis, Gliricola porcelli, Trixacarus caviae, Ixodes ricinus, I. hexagonus, I. crenulatus, I. rugicollis i Dermacentor reticulatus. Różne gatunki pasożytów zewnętrznych, które mogą być również przenoszone na ludzi są odpowiedzialne za najczęstsze choroby pasożytnicze skóry zwierząt: sarkoptozę, otodektozę, ktenocefalidozę, wszawicę, wszołowicę, demodekozę i chejletielozę. Ponadto kleszcze z rodziny Ixodidae odgrywają znaczącą rolę w przenoszeniu chorób, do najważniejszych z nich należą: borelioza z Lyme, babeszjoza, riketsjoza, erlichioza, tularemia. W niniejszej pracy przedstawiono najczęściej występujące ektopasożyty skórne u zwierząt domowych takich jak: pies domowy (Canis familiaris), kot domowy (Felis catus), papużka falista (Melopsittacus undulatus), kawia domowa (Cavia porcellus ), chomik syryjski (Mesocricetus auratus), mysz domowa (Mus musculus).

Ixodes ricinus (castor bean tick) is a ruthless parasite with the greatest medical and veterinary significance out of all the ticks found in the Polish fauna. The research on the incidence and spread of this species was conducted in six selected research areas in the urban area of Bielsko-Biała and in the rural areas of Ujsoły and Złatna. Another variable covered by the research was the seasonal activity of I. ricinus in three selected research areas in Ujsoły. The researched locations include recreational areas near rivers, forests, and hiking trails. They are frequented by tourists and cyclists. In studies faunal a total of 60 tick specimens belonged to the I. ricinus and were collected with the flagging method. The ticks were stored in test tubes filled with 96% ethanol. The analysis focused on the parasite’s taxonomic position and developmental stages. During the observation of the seasonal tick activity, the parasites were placed in dry tubes. Once their taxonomic position and developmental stages were diagnosed, they were released into the wild (a total of 875 ticks were collected belonged to the I. ricinus). The observations and studies indicate the widespread and increasingly high incidence of this dangerous parasite, which means there is a high risk of tick-borne diseases in both urban and mountain areas of the Żywiec and Silesian Beskids.

In Poland, 82% of forests are State-owned, and only 17% of forests constitute private property. Each year, forests are converted to other land-use types, mainly for road construction. The afforestation rate on privately-owned low-productivity land is decreasing steadily. The owners and perpetual usufructuaries of this kind of land are eligible to government subsidies to cover establishment expenditures in whole or in part, provided that the afforestation scheme complies with the local zoning plan or an outline planning permission. The above creates a dilemma for farmers—is this a profitable option of managing low-productivity land? Owners of small farms particularly often face such dilemmas. Owners of small farms, which consist of low-yield agricultural land, can be regarded as investors operating on the real estate market, but those investors have features characteristic of agricultural producers. This study relied on the net present value (NPV) criterion, which is popularly used to assess the effectiveness of investments on the real estate market. A financial feasibility assessment performed with the use of such method in view of afforestation statistics and the 5% discount rate on the Polish forest market revealed the highest increase in net cumulative cash flows in the first five years, followed by a gradual decrease in successive years. The first negative cash flow was reported in year 20. NPV would remain negative because farmers would be charged with periodic maintenance expenditures until the stand reaches harvestable age at approximately 40 years. The longer the investment period, the lower the profits, even if discount rate is excluded. Investments of the type are difficult to terminate because forests younger than 20 years are difficult to sell at a price that covers growing outflows. Afforestation projects are also influenced by other economic and non-economic factors. The paper validates the research hypothesis that afforestation is a long-term investment that delivers benefits for future generations.

Beaver ponds remain a challenge for forest management in those countries where expansion of beaver (Castor fiber) is observed. Despite undoubted economic losses generated in forests by beaver, their influence on hydrology of forest streams especially in terms of increasing channel retention (amount of water stored in the river channel), is considered a positive aspect of their activity. In our study, we compared water storage capacities of a lowland forest stream settled by beaver in order to unravel the possible temporal variability of beaver’s influence on channel retention. We compared distribution, total damming height, volumes and areas of beaver ponds in the valley of Krzemianka (Northeast Poland) in the years 2006 (when a high construction activity of beaver was observed) and in 2013 (when the activity of beaver decreased significantly). The study revealed a significant decrease of channel retention of beaver ponds from over 15,000 m3 in 2006 to 7000 m3 in 2013. The total damming height of the cascade of beaver ponds decreased from 6.6 to 5.6 m. Abandoned beaver ponds that transferred into wetlands, where lost channel retention was replaced by soil and groundwater retention, were more constant over time and less vulnerable to the external disturbance means of water storage than channel retention. We concluded that abandoned beaver ponds played an active role in increasing channel retention of the river analyzed for approximately 5 years. We also concluded that if the construction activity of beaver was used as a tool (ecosystem service) in increasing channel retention of the river valley, the permanent presence of beaver in the riparian zone of forest streams should have been assured.

The article analyses the history of the Einfühlung concept. Theories of ‘feeling into’ Nature, works of art or feelings and behaviours of other persons by German philosophers of the second half of the nineteenth century Robert and Friedrich Vischer and Theodor Lipps are evoked, as well as similar theory of understanding (Verstehen) by Wilhelm Dilthey and Friedrich Schleiermacher, to which Dilthey refers. The meaning of the term Einfühlung within Edith Stein’s thought is also analysed. Both Einfühlung and Verstehen were criticized as non-objective and naive methods consisting only in the identification of the subject with the object or the projection of feelings onto the object. The article refers to criticism by Georg Gadamer and Bertolt Brecht and proposes ways to restitute the concept of Einfühlung after this criticism, recalling the theory of empathy by Dominick Lacapra, in terms of its advantages for the historical enquiry, or the myth of Narcissus analyzed in the spirit of psychoanalysis by Julia Kristeva. The article proposes a reformulation of the concept of mimesis, connected to the Einfühlung, understood as the identification, analogy, imitation of feelings (as it was described by Lipss and Vischer). Mimesis does not necessarily mean a passive repetition and reconstruction of the feelings of the object, but serves only as a starting point for the interest of the subject for the outside world or for experiences of historical protagonists. Then there is no identification or projection of feelings, but the creative, active and critical reformulation of knowledge. It is stated that empathy is not a passive, uncritical process, but that it deals with the critical choice of the object of empathy and with an active approach to the perceived feelings and appearances. In addition to this cognitive aspect, empathy may also contribute to the analytical and valuable introspection. Furthermore empathy allows us to connect the analysis of the facts with a personal narrative and understanding of individual identity in historical knowledge.

Purpose. To investigate the expression of innate immunity components and cytokines in the gastric mucosa among H. pylori infected and uninfected children. Materials and Methods. Biopsies of the antral gastric mucosa from children with dyspeptic symptoms were evaluated. Gene expressions of innate immunity receptors and cytokines were measured by quantitative real-time PCR. The protein expression of selected molecules was tested by immunohistochemistry. Results. H. pylori infection did not lead to a significant upregulation of MyD88, TLR2, TLR4, CD14, TREM1, and TREM2 mRNA expression but instead resulted in high mRNA expression of IL-6, IL-10, IFN-γ, TNF-α, and CD163. H. pylori cagA(+) infection was associated with higher IL-6 and IL-10 mRNA expression, as compared to cagA(−) strains. H. pylori infected children showed increased IFN-γ and TNF-α protein levels. IFN-γ mRNA expression correlated with both H. pylori density of colonization and lymphocytic infiltration in the gastric mucosa, whereas TNF-α protein expression correlated with bacterial density. Conclusion. H. pylori infection in children was characterized by (a) Th1 expression profile, (b) lack of mRNA overexpression of natural immunity receptors, and (c) strong anti-inflammatory activities in the gastric mucosa, possibly resulting from increased activity of anti-inflammatory M2 macrophages. This may explain the mildly inflammatory gastric inflammation often observed among H. pylori infected children.

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Abstract Background. The New Medicine Service (NMS) was developed in England more than ten years ago, as a three-stage consultation led by community pharmacists to support patients taking new medication for a chronic disease. In Poland, the scheme was officially introduced in January 2023. However, its implementation into common practice has been presented with various obstacles, including the need to develop relationships with general practitioners, resolve the payment structure, and provide training with adequate supporting materials. Hence, written materials have been designed for use as an optional tool for counselling patients receiving an NMS in community pharmacies. Methods. The present study evaluates the ability of these materials to inform patients about the need to adhere to anti-hypertensive medication. A group of 401 randomly-selected adult visitors to pharmacies and/or healthcare centres were surveyed; one third had hypertension in their history. Results. The structure, grammar and readability of the text achieved the required threshold of 40% according to the Plain Language Index. The designed materials effectively informed the patients about anti-hypertensive medication, reflected in an increased score in a knowledge test, and were rated positively regarding information level, comprehensibility and presentation. Conclusion. The proposed material may serve as an additional, “patient-friendly” educational tool for use as part of an NMS.

Blues to muzyka silniejsza niż niewola. Być może właśnie to sprawiło, że blues na swojej drodze do globalnej i transkulturalnej kariery nie tylko pokonał społeczne oraz rasowe bariery i zerwał łańcuchy narzucone jego oryginalnym twórcom, ale też z łatwością przeniknął nawet tak dobrze ufortyfikowane granice, jak żelazna kurtyna, zyskując gorących zwolenników w miejscach tak odległych geograficznie, jak Gruzja. Mimo iż blues cieszy się w Gruzji znaczną popularnością, to jego historia i rozwój jako lokalnego gatunku muzycznego pozostają jak dotąd zjawiskiem nieopisanym w literaturze fachowej, a materiały źródłowe są rozproszone i fragmentaryczne. W konsekwencji, podejmując próbę zgłębienia owych procesów, trzeba oprzeć się przede wszystkim na bezpośrednich relacjach osób oraz źródłach w postaci nagrań, okładek płyt, wywiadów i innych materiałów archiwalnych. W artykule wykorzystano informacje zebrane w toku wywiadów bezpośrednich przeprowadzonych w marcu 2023 roku z krytykami muzycznymi: Koką Tskitiszwilim i Laszą Gabunią oraz z muzykami: Dawidem Manidżaszwilim, Paulem Rimplem i Tamazem Tkinwalelim.