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SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applying next-generation sequencing (NGS) with a 117 myeloid gene custom panel, we analyzed the co-occurrence of SF3B1 with other mutations to reveal their clinical, biological, and prognostic implications in very low/low- and intermediate-risk MDS patients. Mutations in addition to those of SF3B1 were present in 80.4% of patients (median of 2 additional mutations/patient, range 0–5). The most frequently mutated genes were as follows: TET2 (39.2%), DNMT3A (25.5%), SRSF2 (10.8%), CDH23 (5.9%), and ASXL1, CUX1, and KMT2D (4.9% each). The presence of at least two mutations concomitant with that of SF3B1 had an adverse impact on survival compared with those with the SF3B1 mutation and fewer than two additional mutations (median of 54 vs. 87 months, respectively: p = 0.007). The co-occurrence of SF3B1 mutations with specific genes is also linked to a dismal prognosis: SRSF2 mutations were associated with shorter overall survival (OS) than SRSF2wt (median, 27 vs. 75 months, respectively; p = 0.001), concomitant IDH2 mutations (median OS, 11 [mut] vs. 75 [wt] months; p = 0.001), BCOR mutations (median OS, 11 [mut] vs. 71 [wt] months; p = 0.036), and NUP98 and STAG2 mutations (median OS, 27 and 11 vs. 71 months, respectively; p = 0.008 and p = 0.002). Mutations in CHIP genes (TET2, DNMT3A) did not significantly affect the clinical features or outcome. Our results suggest that a more comprehensive NGS study in low-risk MDS SF3B1mut patients is essential for a better prognostic evaluation.

The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified.

Somatic mutations in patients with myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (HSTC) are associated with adverse outcome, but the role of chronic graft-versus-host disease (cGVHD) in this subset of patients remains unknown. We analyzed bone marrow samples from 115 patients with MDS collected prior to HSCT using next-generation sequencing. Seventy-one patients (61%) had at least one mutated gene. We found that patients with a higher number of mutated genes (more than 2) had a worse outcome (2 years overall survival [OS] 54.8% vs. 31.1%, p = 0.035). The only two significant variables in the multivariate analysis for OS were TET2 mutations (p = 0.046) and the development of cGVHD, considered as a time-dependent variable (p < 0.001), correlated with a worse and a better outcome, respectively. TP53 mutations also demonstrated impact on the cumulative incidence of relapse (CIR) (1 year CIR 47.1% vs. 9.8%, p = 0.006) and were related with complex karyotype (p = 0.003). cGVHD improved the outcome even among patients with more than 2 mutated genes (1-year OS 88.9% at 1 year vs. 31.3%, p = 0.02) and patients with TP53 mutations (1-year CIR 20% vs. 42.9%, p = 0.553). These results confirm that cGVHD could ameliorate the adverse impact of somatic mutations in patients with MDS with HSCT.

Air pollution has become a global issue due to rapid urbanization and industrialization. Bad air quality is Europe’s most significant environmental health risk, causing serious health problems. External air pollution is not the only issue; internal air pollution is just as severe and can also lead to adverse health outcomes. IoT is a practical approach for monitoring and publishing real-time air quality information. Numerous IoT-based air quality monitoring systems have been proposed using micro-sensors for data collection. These systems are designed for outdoor air quality monitoring. They use sensors to measure air quality parameters such as CO2, CO, PM10, NO2, temperature, and humidity. The data are acquired with a set of sensors placed on an electric car. They are then sent to the server. Users can subscribe to the list and receive information about local pollution. This system allows real-time localized air quality monitoring and sending data to customers. The work additionally presents a secure data transmission protocol ensuring system security. This protocol provides system-wide attack resiliency and interception, which is what existing solutions do not offer.

How agricultural ecosystems adapt to climate change is one of the most important issues facing agronomists at the turn of the century. Understanding agricultural ecosystem responses requires assessing the relative shift in climatic constraints on crop production at regional scales such as the temperate zone. In this work we propose an approach to modeling the growth, development and yield of Triticum durum Desf. under the climatic conditions of north-eastern Poland. The model implements 13 non-measurable parameters, including climate conditions, agronomic factors, physiological processes, biophysical parameters, yield components and biological yield (latent variables), which are described by 33 measurable predictors as well as grain and straw yield (manifest variables). The agronomic factors latent variable was correlated with nitrogen fertilization and sowing density, and biological yield was correlated with grain yield and straw yield. An analysis of the model parameters revealed that a one unit increase in agronomic factors increased biological yield by 0.575. In turn, biological yield was most effectively determined by climate conditions (score of 60–62) and biophysical parameters (score of 60–67) in the 2nd node detectable stage and at the end of heading. The modeled configuration of latent and manifest variables was responsible for less than 70% of potential biological yield, which indicates that the growth and development of durum wheat in north-eastern Europe can be further optimized to achieve high and stable yields. The proposed model accounts for local climate conditions and physiological processes in plants, and it can be implemented to optimize agronomic practices in the cultivation of durum wheat and, consequently, to expand the area under T. durum to regions with a temperate climate.

Europium-based compounds exhibit a wide range of intriguing properties due to the element’s ability to exist in two valence states: Eu , which carries a strong magnetic moment, and non-magnetic Eu , as well as due to interactions between localized f -electrons and conduction electrons. In this work, we present a comprehensive study of EuSnP single crystals using X-ray diffraction, heat capacity, dc and ac magnetic susceptibility, magnetization, and Mössbauer spectroscopy measurements. EuSnP undergoes an antiferromagnetic transition at K. However, our results indicate that magnetic correlations emerge well above the transition temperature. Mössbauer spectroscopy revealed that Eu valence in EuSnP is 2+ contradicting earlier suggestions of its mixed-valent state. It also shows exceptionally high values of the effective magnetic field (39 T) and large electric field gradient at Eu nuclei likely due to the short distances between Eu atoms and their nearest neighbors. Based on our studies, we propose two possible magnetic ordering schemes of Eu magnetic moments. In the first one, moments are aligned ferromagnetically within each Eu-P plane and there is an antiferromagnetic coupling between Eu-P planes forming a bilayer. In the second one, there is a ferromagnetic order within the entire bilayer and neighboring bilayers are coupled antiferromagnetically. In both scenarios magnetic moments are oriented along or close to the crystallographic c -axis.

The tumor microenvironment is a complex network of various interactions between immune cells and non-cellular components such as the extracellular matrix, exosomes and interleukins. Moreover, tumor heterogeneity and its constant modification may alter the immunophenotype and become responsible for its resistance regarding the therapies applied However, it should be remembered that in a strongly immunosuppressive neoplastic microenvironment, the immune system cells undergo reprogramming and most often cease to fulfill their original function. Therefore, understanding what happens within the tumor microenvironment, and which mechanisms are responsible for tumor development and progression should let us know how cancer could protect itself against the immune system. The presented review summarizes the latest information on the interactions between the tumor microenvironment and the cellular and non-cellular components, as well as their impact on cancer development, progression and immune system exhaustion.

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS , NRAS , and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS , and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF , FBXW7 , and TP53 , that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.

European rivers are disconnected by more than one million man-made barriers that physically limit aquatic species migration and contribute to modification of freshwater habitats. Here, a Conceptual Habitat Alteration Model for Ponding is developed to aid in evaluating the effects of impoundments on fish habitats. Fish communities present in rivers with low human impact and their broad environmental settings enable classification of European rivers into 15 macrohabitat types. These classifications, together with the estimated fish sensitivity to alteration of their habitat are used for assessing the impacts of six main barrier types (dams, weirs, sluices, culverts, fords, and ramps). Our results indicate that over 200,000 km or 10% of previously free-flowing river habitat has been altered due to impoundments. Although they appear less frequently, dams, weirs and sluices cause much more habitat alteration than the other types. Their impact is regionally diverse, which is a function of barrier height, type and density, as well as biogeographical location. This work allows us to foresee what potential environmental gain or loss can be expected with planned barrier management actions in rivers, and to prioritize management actions. European rivers have over a million barriers hindering aquatic species migration and altering freshwater habitats. This study quantifies the spatial extent of upstream fish habitat alteration caused by physical blockage and shows that impoundments have altered 10% or 200,000 km of free-flowing river habitat in Europe.

A new efficient method for the chemical decomposition of polyamide 6.6 by the glycolysis and amino-glycolysis processes was proposed. The glycolysis was conducted using the mass excess of ethylene glycol (EG) as a decomposing agent in the presence of a catalyst. Also, a mixture of EG and triethylenetetramine was used as another decomposing agent in the amino-glycolysis process. The described process of decomposition did not require the use of elevated pressure. The hydroxyl and amine numbers, rheology behavior and the presence of characteristic chemical groups in the obtained glycolysates and aminoglycolysates were determined in order to characterize the reaction products. The decomposition products were defined as non-Newtonian fluids that could be described by suitable mathematical models. The conducted studies showed that the properties of the obtained intermediates depend on the mass excess of the decomposing agent used. The resulting semi-products are suitable for reusing in the synthesis of polyurethanes, which has been confirmed by the exemplary synthesis. In the reaction, 10 and 15 wt% of commercial polyol were replaced with the recovered intermediates.