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Abstract Somatic copy number alterations play a critical role in oncogenesis. Loss of chromosomal regions containing tumor suppressors can lead to collateral deletion of passenger genes. This can be exploited therapeutically if synthetic lethal partners of such passenger genes are known and represent druggable targets. Here, we report that VPS4B gene, encoding an ATPase involved in ESCRT‐dependent membrane remodeling, is such a passenger gene frequently deleted in many cancer types, notably in colorectal cancer (CRC). We observed downregulation of VPS4B mRNA and protein levels from CRC patient samples. We identified VPS4A paralog as a synthetic lethal interactor for VPS4B in vitro and in mouse xenografts. Depleting both proteins profoundly altered the cellular transcriptome and induced cell death accompanied by the release of immunomodulatory molecules that mediate inflammatory and anti‐tumor responses. Our results identify a pair of novel druggable targets for personalized oncology and provide a rationale to develop VPS4 inhibitors for precision therapy of VPS4B‐deficient cancers.

In 2020 it is estimated that 281 million people were international migrants. Migrants constitute a potentially vulnerable population in terms of facing discrimination, poor living and housing conditions, and insufficient access to healthcare services. Due to the armed conflict in Ukraine in 2022, almost 10 million people crossed the Polish border within a year of the outbreak of the conflict. The objective of this paper is to present the use of primary healthcare services by people migrating from Ukraine to Poland and identify the barriers in access to healthcare by this group of persons. This study used a qualitative research technique in the form of an expert interview using individual in-depth interviews (IDI). The study group consisted of professionally active primary healthcare providers (doctors, nurses, and facility managers) in Poland. Research was carried out in the areas regarding the availability of healthcare, the potential threats and challenges, and possible system solutions. The results showed that the most common cause for doctor's appointments among migrants are respiratory infections, including COVID-19. Many cases were related to back pain, mainly resulting from the physical work of the patients. Additionally, some barriers to access and the provision of healthcare services for patients from Ukraine were identified. The majority (75%) of respondents indicated language as a significant barrier when providing services. Based on the study results, we recommend creating a dedicated website and telephone hotline for this group of persons as well as the use of traditional media to distribute information about access to healthcare services. It is also essential to focus on assistance for older people, since they may experience more difficulties with language and navigating the healthcare system. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is one of the leading causes of cancer deaths around the world. The main risk factor associated with development of this disease is smoking, with about 80% of lung cancer deaths being related to smoking. However, non-smokers can also develop lung cancer due to an exposure to other harmful substances such as asbestos, radon and other carcinogens. The aim of our study is to present the trends and most recent studies aimed at lung cancer screening. Further research aimed at screening and smoking cessation interventions is recommended. Lung cancer is the leading cause of death among all the oncological diseases worldwide. This applies to both women and men; however, the incidence and mortality among women is on the rise. In 2020, lung cancer was responsible for 1.8 million deaths (18%). More than 90% of lung cancer cases and 77.1% of lung cancer deaths occur in countries with high and very high HDI (human development index) values. The aim of our study is to the present trends and most recent studies aimed at lung cancer screening. In the face of the persistently high mortality rate, conducting research aimed at extending already-implemented diagnostic algorithms and behavioural interventions focused on smoking cessation is recommended. [ABSTRACT FROM AUTHOR]

Infection with Trichinella nematodes elicits non-specific and specific immune responses; these depend on the dose of infection, the nematode, and the host species. Few studies have examined the presence of specific antibodies against Trichinella spp. in the meat juice of wild animals. The aims of the study were to determine the prevalence of antibodies against Trichinella spp. in meat juice and to identify the specific proteins reacting with the meat juice from free-living carnivores naturally infected with the parasite. Meat juice samples were taken from foxes, badgers, raccoon dogs, and martens and tested with indirect ELISA. Antibodies against Trichinella spp. were detected in 10% of foxes and 46% of raccoon dogs. The ELISA results were confirmed by immunoblot, which revealed different protein patterns in meat juice from red foxes, raccoon dogs, and badgers. The most frequently observed bands were sent for further analysis by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for the detection of Trichinella britovi immunogenic proteins. The results confirm the presence of proteins such as serine protease and heat shock proteins associated with Trichinella infection. These findings provide that meat juice is a useful matrix for proteomic analysis.

This study used laboratory experiments to compare the effects of coal tar creosote on the activity of oxidoreductive enzymes in sandy loam, loamy sand and sandy clay loam soils. Different amounts of coal tar creosote were added to soil samples as follows: 0 (control), 2, 10 or 50 g [kg.sup.-1] dry matter. The activity of soil dehydrogenases (DHAs), o-diphenol oxidase (o-DPO), catalase (CAT), nitrate reductase (NR) and peroxidases (POX) was determined. Contamination of soil with coal tar creosote affected oxidoreductase activity. Oxidoreductive enzyme activity following soil contamination with coal tar creosote was in the following order: DHAs > CAT > NR > POX > o-DPO in loamy sand and in sandy loam; and DHAs > POX > CAT > NR > o-DPO in sandy clay loam. The index of soil oxidoreductive activity ([I.sub.Ox]) introduced in this study confirms the negative effect of coal tar creosote on oxidoreductase activity in soil. DHAs were the most sensitive to the contamination of soil with coal tar creosote. Moreover, the greatest changes in oxidoreductase activities were observed in loamy sand. Knowledge of the mechanism underlying the effects of coal tar creosote on oxidoreductive processes may enable development of a method for the bioremediation of polycyclic aromatic hydrocarbon-contaminated soils. Additional keywords: catalase, dehydrogenases, nitrate reductase, peroxidases, polycyclic aromatic hydrocarbons, resistance index. Received 13 March 2019, accepted 31 July 2019, published online 23 September 2019, Introduction Coal tar creosote is a mixture of coal tar distillation products that are boiled at temperatures ranging from 200 to 400[degrees]C. It primarily consists of aromatic compounds (Ye et [...]

The plants of the genus Rubus (R.) are applied as antiseptic agents in the treatment of skin diseases. Despite the great interest in plants of this genus, there are few reports on the antioxidant and biological activities of preparations obtained from the leaves of these plants. Therefore, we decided to evaluate the antioxidant activity of preparations from leaves of wild plant species of the genus Rubus using the frequently applied DPPH, ABTS, and FRAP methods, as well as to determine the total polyphenol content using the Folin–Ciocalteau method and perform qualitative evaluation by gas chromatography–mass spectrometry (GC-MS). The bactericidal and fungicidal activities of the obtained preparations were evaluated by applying laboratory tests: using the disc and the well methods based on the standards EN 13697:2019, EN 13697:2015, and EN 1500:2013. Microbiological tests of the plant preparations against bacteria, fungi, and yeasts isolated from the environment and against reference strains were performed. Moreover, antimicrobial testing of antibiotics against the tested strains was performed for comparison. The n-octanol/water partition coefficient of the obtained preparations was determined by the shake-flask method to determine their lipophilicity. According to the results, a high content of polyphenols and other antioxidant and biologically active compounds can be thought of as the parameter responsible for the effective activity of plant preparations obtained from wild plant species of the genus Rubus. The methods for determining bactericidal and fungicidal activity clearly demonstrates that preparations with reduced ethanol content exhibit bactericidal and fungicidal activity on surfaces. Testing of hand disinfection by means of rubbing with the preparations confirmed their antimicrobial activity against Escherichia coli K12 NCTC 10538. The obtained results show that the tested preparations exhibit on average two times lower activity against the reference bacterial strains than comparable antibiotics. The preparations obtained from the leaves of R. idaeus L. and R. fruticosus L. could complement classical antibiotics. While environmental bacteria showed a similar response to the preparations and antibiotics, their sensitivity was about one-third less than that of the reference strains. Our studies have shown that the obtained preparations are highly hydrophilic (logP < 0). Thus, these preparations can only be used in lipid bilayers in the aqueous core of liposomes, not in the lipid envelope.

The sheep population of native breeds, despite their unique features and the ability to adapt to harsh environmental conditions, has significantly decreased in recent years. Due to the low profitability of breeding, many local breeds of sheep in Poland were exposed to the risk of extinction. Many years of crisis in sheep farming have exacerbated this situation. The aim of this paper was to present the current situation of native sheep breeding in Poland, in terms of significance and effects of genetic resources protection programmes. The conservation of genetic resources of sheep aims to maintain and increase the population size while striving to maintain the greatest possible genetic variability. There are 17 native breeds included in the Polish sheep genetic resources conservation programme. A positive element of the implementation of the conservation of genetic resources programme for sheep is the accompanying measures which are based on the use of the non-productive role of the species. Extensive sheep grazing, as a form of nature conservation, serves to preserve valuable natural landscapes and the culture of local communities associated with sheep farming. Production and promotion of quality products, especially using niche markets and short production chains, are essential to ensure the economic viability of farms. These activities must be accompanied by raising public awareness of indigenous breeds and their alternative use in environmental activities, as well as their role in preserving the cultural heritage of local communities, for example through mountain grazing and the production of traditional products.

Background Obesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma is controversial. We aim to investigate the prognostic role of body mass index (BMI) in patients with metastatic melanoma receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint inhibitors (ICIs) alone or their sequence.Methods Data on patients with metastatic melanoma receiving ≥1 line of systemic treatment were retrieved from prospectively collected databases. Progression-free survival (PFS) and overall survival (OS) were analyzed by means of multivariable stratified Cox regression models; disease control rate (DCR) was analyzed by multivariable stratified logistic regression models. Subgroup analyzes according to the type of treatments received, and in BRAF-mutated patients were pre-planned. All multivariable models included BMI, age, gender, American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment sequencing strategy as covariates.Results Between November 2010 and November 2018, 688 patients from three Italian and two Polish centers were enrolled. 379 (57%) patients had M1c/d disease, 273 (41%) were female and the mean BMI was 27.1 (SD=4.9). Considering first-line treatment, 446 patients (66.8%) received ICIs and 222 MAPKi. No impact of BMI on OS was detected either considering the first line of ICIs, or ICIs sequencing (HR=1.02, 95% CI: 0.99 to 1.05, p=0.202, and HR=1.02, 95% CI: 0.99 to 1.04, p=0.237, respectively). A late effect of BMI on OS was found in patients treated with MAPKi: for five units increment, a 51% of risk reduction at 18 months and a 76% of risk reduction at 30 months were observed. No significant effect of BMI on PFS and DCR was found in any of the subgroup analyzes.Conclusion In patients with metastatic melanoma receiving ICIs, there is no impact of BMI on DCR, PFS and OS. The late prognostic effect of BMI in patients treated with MAPKi should be considered hypothesis generating and needs to be further investigated.

A green and effective approach for the synthesis of structurally diversed α-hydroxyphosphonates via hydrophosphonylation of aldehydes under solventless conditions and promoted by biosourced catalysts, called ecocatalysts “Eco-MgZnOx” is presented. Ecocatalysts were prepared from Zn-hyperaccumulating plant species Arabidopsis halleri, with simple and benign thermal treatment of leaves rich in Zn, and without any further chemical treatment. The elemental composition and structure of Eco-MgZnOx were characterized by MP–AES, XRPD, HRTEM, and STEM–EDX techniques. These analyses revealed a natural richness in two unusual and valuable mixed zinc–magnesium and iron–magnesium oxides. The ecocatalysts were employed in this study to demonstrate their potential use in hydrophosphonylation of aldehydes, leading to various α-hydroxyphosphonate derivatives, which are critical building blocks in the modern chemical industry. Computational chemistry was performed to help discriminate the role of some of the constituents of the mixed oxide ecocatalysts. High conversions, broad substrate scope, mild reaction conditions, and easy purification of the final products together with simplicity of the preparation of the ecocatalysts are the major advantages of the presented protocol. Additionally, Eco-MgZnOx-P could be recovered and reused for up to five times.