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Abstract Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 rate was 25.6% (50/195). We additionally identified several pre-therapy factors predictive of inferior CR1 including male gender (P = 0.026), ≥2 autosomal monosomies (P 25% (P = 0.002), TP53 splice junction mutations (P = 0.007) and antecedent treated myeloid neoplasm (P = 0.001). In addition, mutations/deletions in CUX1, U2AF1, EZH2, TET2, CBL, or KRAS (‘EPI6’ signature) predicted inferior OS24 (HR = 2.0 [1.5–2.8]; P

В данной статье на основе анализа теоретических положений, законодательных положений,опроса судей, адвокатов-защитников, в том числе различных публикаций СМИ определяется, какиесубъекты фактически чаще всего выступают в качестве непрофессиональных защитников. Таковыми в половине случаев выступают родственники обвиняемого. Сделан вывод, что сложившаяся практика стремится к допуску в качестве защитников профессионалов, обладающих соответствующимизнаниями, опытом и навыками. Обозначено отсутствие законодательных положений, регулирующих статус непрофессионального защитника, также требований, предъявляемых к его действиямпо защите подозреваемого, обвиняемого в уголовном процессе, ввиду чего в правоприменительнойпрактике сложилось различное отношение к статусу непрофессиональных защитников по уголовному делу и необходимости их участия. Сформулированы выводы по конкретизации процессуального статуса непрофессиональных защитников, а также об использовании возможных способов правовой оценки их деятельности.

Major (EPMA) and trace (SIMS) element geochemistry in olivine, low-Са pyroxene and mesostasis from porphyritic and barred chondrules, as well as the pyroxene-olivine aggregate and matrix of equilibrated ordinary Borodino chondrite (Н5) is discussed. No differences in major element concentrations in the silicate minerals of the chondrules and matrix of the meteorite were found. The minerals of porphyritic olivine-pyroxene and barred chondrules display elevated trace element concentrations, indicating the rapid cooling of chondrule melt in a nebula, and are consistent with experimental data. The trace element composition of low-Са pyroxene is dependent on the position of a pyroxene grain inside a chondrule (centre, rim, matrix) and the composition of mesostasis is controlled by the type of the object (porphyritic and barred chondrules, pyroxene-olivine aggregate). The depletion in trace elements of low-Са pyroxene from the rims of chondrules in comparison with those from the centre and matrix of the meteorite was revealed. The chondrule rim is affected by interaction with surrounding gas in a nebula, possibly resulting in the exchange of moderately volatile trace elements in low-Са pyroxene and depletion in these elements relative to pyroxene from the centre of the chondrule or matrix of the meteorite. The mesostasis of barred and porphyritic olivine-pyroxene chondrules contains more trace elements than that of porphyritic olivine chondrule and pyroxene-olivine aggregate, suggesting the rapid cooling of these objects or their high liability to thermal metamorphism, which results in the recrystallization of chondrule glass into plagioclase. However, no traces of the elevated effect of thermal metamorphism on the above objects have been revealed. The results obtained indicate no traces of the equilibration of the trace element composition of silicate minerals in equilibrated chondrites.

This study investigates a unique and complex eye phenotype characterized by minimal iris defects, foveal hypoplasia, optic nerve coloboma, and severe posterior segment damage. Through genetic analysis and bioinformatic tools, a specific nonsynonymous substitution, p.(Asn114Ser), within the PAX6 gene’s paired domain is identified. Although this substitution is not in direct contact with DNA, its predicted stabilizing effect on the protein structure challenges the traditional understanding of PAX6 mutations, suggesting a gain-of-function mechanism. Contrary to classical loss-of-function effects, this gain-of-function hypothesis aligns with research demonstrating PAX6’s dosage sensitivity. Gain-of-function mutations, though less common, can lead to diverse phenotypes distinct from aniridia. Our findings emphasize PAX6’s multifaceted influence on ocular phenotypes and the importance of genetic variations. We contribute a new perspective on PAX6 mutations by suggesting a potential gain-of-function mechanism and showcasing the complexities of ocular development. This study sheds light on the intricate interplay of the genetic alterations and regulatory mechanisms underlying complex eye phenotypes. Further research, validation, and collaboration are crucial to unravel the nuanced interactions shaping ocular health and development.

The prevalence of allergic diseases has increased tremendously in recent decades, which can be attributed to growing exposure to environmental triggers, changes in dietary habits, comorbidity, and the increased use of medications. In this context, the multiplexed diagnosis of sensitization to various allergens and the monitoring of the effectiveness of treatments for allergic diseases become particularly urgent issues. The detection of allergen-specific antibodies, in particular, sIgE and sIgG, is a modern alternative to skin tests due to the safety and efficiency of this method. The use of allergen microarrays to detect tens to hundreds of allergen-specific antibodies in less than 0.1 mL of blood serum enables the transition to a deeply personalized approach in the diagnosis of these diseases while reducing the invasiveness and increasing the informativeness of analysis. This review discusses the technological approaches underlying the development of allergen microarrays and other protein microarrays, including the methods of selection of the microarray substrates and matrices for protein molecule immobilization, the obtainment of allergens, and the use of different types of optical labels for increasing the sensitivity and specificity of the detection of allergen-specific antibodies.

This investigation looks at the transformative potential of upcycling agricultural waste to make ecologically friendly food packaging. Agricultural wastes, which are frequently ignored, might be valuable resources in reversing the sustainable destiny of the packaging sector. We review recent research on plant-based byproducts, including proteins, polysaccharides, lipids, pigments, and minerals, that are isolated from agricultural waste. Creating edible and (bio)degradable packaging solutions that can include biobased active components, including flavorings, antioxidants, and antimicrobials, can begin with these compounds. Utilizing plant fibers from agricultural waste reduces environmental contamination while increasing packing efficiency. The review concentrates on packaging solutions that are good for the environment, like edible coatings and films with antioxidant and antibacterial qualities and active packaging made of phenolic chemicals. These innovations, derived from various foods and agricultural waste, satisfy customer demand for premium foods with longer shelf lives. A practical way to lessen the excessive use of non-biodegradable plastics is to create edible materials, especially in light of the global push for sustainability. These formulations can enhance food packaging performance since they are made from biowastes and biopolymers. Our comprehensive research synthesizes existing knowledge to shed light on the extraction, processing, and application of agricultural byproducts in packaging materials. The broad spectrum includes regulatory systems, processing techniques, biodegradability parameters, and the properties of various byproducts. By providing an all-encompassing viewpoint, this evaluation draws attention to current achievements and indicates avenues for more research and development. It provides a roadmap for the ecologically friendly upcycling of agricultural waste into sustainable food packaging, which helps to shift the packaging industry's paradigm continuously.

Food packaging is undergoing a revolutionary change because of nanotechnology. This paper examines the influence of nanofillers on improving food packaging materials. Due to their distinctive qualities, nanofillers like nanoparticles and nanocomposites change food product protection, preservation, and appearance. The advantages of nanofillers, which may be controlled in terms of mechanical, barrier, thermal, optical, and surface characteristics, are described in the article along with their definition. Systematic examination exposes the many functions of nanofillers, from maintaining food safety with antibacterial Nano silver to increasing shelf life with better barriers. They also support sustainability and clever packaging. Innovative applications for real-time food monitoring are investigated, along with case examples demonstrating their efficacy, including nanocomposite materials, nanosensors, and nanotags. The use of nanofillers is evaluated concerning safety, compliance, cost-effectiveness, and environmental impact. Future research trends that will influence food packaging are outlined. A critical step toward developing safer, more robust, and environmentally friendly packaging solutions is represented by nanofillers. This review is a valuable tool for anyone involved in food packaging since it provides information on disruptive technology transforming food packaging into an intelligent, environmentally friendly guardian of food quality and safety.

We employed a structural bioinformatics approach to develop novel peptides with predicted affinity to the binding site for negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGluR5). Primary screening in zebrafish (Danio rerio) revealed a stimulatory effect of two peptides, LCGM-10 and LCGM-15. Target validation studies using calcium ion flux imaging and a luciferase reporter assay confirmed mGluR5 as the target. LCGM-10 showed greater potency than LCGM-15; it was comparable to that of the mGluR5 NAM 2-methyl-6-(phenylethynyl) pyridine (MPEP). Rodent behavioral screening in the open field and elevated plus maze revealed increased locomotor activity in both tests after acute LCGM-10 treatment, supported by further analysis of home cage spontaneous locomotor activity (SLA). The stimulating effect of a single LCGM-10 administration on SLA was evident up to 60 min after administration and was not accompanied by hypokinetic rebound observed for caffeine. According to our results, LCGM-10 has therapeutic potential to treat hypo- and dyskinesias of various etiologies. Further investigation of LCGM-10 effects in the delay discounting model of impulsive choice in rats revealed reduced trait impulsivity after single and chronic administrations, suggesting potential implication for attention deficit hyperactivity disorder, obsessive compulsive disorder, and addictions.

Chronic myeloid leukemia (CML) is associated with several breakpoint regions that result in different BCR::ABL1 fusion transcripts. These include the major breakpoint region (M-BCR), minor breakpoint region (m-BCR), and mu breakpoint region (u-BCR) corresponding to p210, p190, and p230 fusion transcripts, respectively. This patient is a 38-year-old female with a new diagnosis of CML in chronic phase. A novel p210 fusion transcript splice variant was detected with qualitative reverse transcription PCR and capillary electrophoresis. Subsequent FISH study was performed, which revealed 86.5% positive for the BCR::ABL1 fusion. Quantitative real-time polymerase chain reaction (PCR) showed a negative result for the p210 fusion transcript. The variant was further characterized by Sanger sequencing. This variant is in-frame and predicted to be functional. This case illustrates the need for a combination of different testing techniques to fully characterize the rare BCR::ABL1 fusion transcripts.

Oligomers of poly-3-hydroxybutyrate (PHB) were prepared by aminolysis of high molecular weight PHB with ethylenediamine and 1,4-diaminobutane. Polymer-oligomer blends (10, 30, and 50% content of the oligomers) were prepared as films by solution casting. As the content of oligomers increased, a gradual increase in the hydrophilicity of the polymer surface was observed, resulting reflected in the water contact angle decrease from 84° to 72–76°. In addition, a moderate decrease in elongation at break, Young's modulus, and tensile strength for the blends were observed as more oligomer was added to the film. Finally, the viability of NIH-3T3 mouse fibroblasts was higher compared to intact PHB when growing in non-prepared polymer/oligomer mixtures. These findings confirm the benefits of the introduction of a hydrophilic functionalized oligomer into the PHB matrix in terms of improving the biocompatibility of the resulting polymer/oligomer blends.

Detection of a combination of aplasia of the inferior vena cava and retroaortic left renal vein is extremely rare. A description of a clinical case with similar anomalies in the development of the inferior vena cava and the left renal vein is given. In our case, the combination of an anomaly of the inferior vena cava and the left renal vein in a 59-year-old male patient was an incidental finding during examination and treatment for acute cerebrovascular accident. Asymptomatic aplasia of the prerenal and hepatic sections of the inferior vena cava with drainage into the azygous vein was revealed. The hepatic veins empty into the right atrium. The identified variant of aplasia of the prerenal and hepatic sections of the inferior vena cava with drainage into the unpaired vein is the result of atrophy of the right subcardinal vein. A rare unclassified type of retroaortic left renal vein was found, the lower branch of which flows into the inferior vena cava, and the upper branch into the unpaired vein. The retroaortic left renal vein is formed while maintaining the anastomosis between the right and left supracardinal veins. The possibility of accidental radiographic findings of anomalies in the development of the inferior vena cava and its tributaries in humans before clinical manifestations has been established. Given the possible manifestation of an anomaly of the inferior vena cava in people over 40 years of age with a clinic of peripheral venous thrombosis, and the manifestation of the retroaortic left renal vein - the development of congestive venous hypertension in the kidney, the patient was given the necessary recommendations.

There have been studied the influence of feeding plant raw material obtained from Hungarian sainfoin having an immunostimulating effect on the growth rate of dairy calves, as well as on morphological and biochemical blood parameters and natural resistance of the animal organism. Calves of the I and II experimental groups in addition to the main diet were fed a phyto supplement made of Hungarian sainfoin mixed with concentrates in doses of 150 and 300 g per head per day during 92 days. The use of herbal supplements in feeding calves ensured an increase in live weight in the animals of experimental groups by 11.0 kg (6.55 %) and by 11.7 kg (6.96 %) (p