Specific Features of Focal Cortical Dysplasia in Tuberous Sclerosis Complex.

Patients with tuberous sclerosis complex present with cognitive, behavioral, and psychiatric impairments, such as intellectual disabilities, autism spectrum disorders, and drug-resistant epilepsy. It has been shown that these disorders are associated with the presence of cortical tubers. Tuberous sclerosis complex results from inactivating mutations in the TSC1 or TSC2 genes, resulting in hyperactivation of the mTOR signaling pathway, which regulates cell growth, proliferation, survival, and autophagy. TSC1 and TSC2 are classified as tumor suppressor genes and function according to Knudson's two-hit hypothesis, which requires both alleles to be damaged for tumor formation. However, a second-hit mutation is a rare event in cortical tubers. This suggests that the molecular mechanism of cortical tuber formation may be more complicated and requires further research. This review highlights the issues of molecular genetics and genotype-phenotype correlations, considers histopathological characteristics and the mechanism of morphogenesis of cortical tubers, and also presents data on the relationship between these formations and the development of neurological manifestations, as well as treatment options.

Major Contribution of c.[1622T>C;3113C>T] Complex Allele and c.5882G>A Variant in ABCA4-Related Retinal Dystrophy in an Eastern European Population.

Inherited retinal diseases (IRDs) constitute a prevalent group of inherited ocular disorders characterized by marked genetic diversity alongside moderate clinical variability. Among these, ABCA4-related eye pathology stands as a prominent form affecting the retina. In this study, we conducted an in-depth analysis of 96 patients harboring ABCA4 variants in the European part of Russia. Notably, the complex allele c.[1622T>C;3113C>T] (p.Leu541Pro;Ala1038Val, or L541P;A1038V) and the variant c.5882G>A (p.Gly1961Glu or G1961E) emerged as primary contributors to this ocular pathology within this population. Additionally, we elucidated distinct disease progression characteristics associated with the G1961E variant. Furthermore, our investigation revealed that patients with loss-of-function variants in ABCA4 were more inclined to develop phenotypes distinct from Stargardt disease. These findings provide crucial insights into the genetic and clinical landscape of ABCA4-related retinal dystrophies in this specific population.

HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?

Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the BRCA status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The BRCA mutational rate was 29% (114/388); 252 samples (65%) were classified as HRD-positive. Our data demonstrate the feasibility of internal HRD testing by the AmoyDx HRD Focus Panel for high-grade serous ovarian cancer (HGSOC), showing results similar to other methods. The HRD rate in the Russian population is very similar to those of other European populations, as is the BRCA mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic BRCA alterations had higher GSS compared with those with monoallelic inactivation, consistent with positive HRD status. The study indicates that grades 1-2 of the pathological response caused by chemotherapy affect HRD scores and suggests controlling for tumor purity of 40% or more as a critical factor for GSS measurement.

Epigenomic Profiling Advises Therapeutic Potential of Leukotriene Receptor Inhibitors for a Subset of Triple-Negative Breast Tumors.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the LTB4R/LTB4R2 genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high LTB4R/LTB4R2 expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the LTB4R and LTB4R2 genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = -0.4, p = 2.6 × 10-6; R = -0.21, p = 0.015) and cg21886367 (R = -0.45, p = 7.3 × 10-8; R = -0.24, p = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan-Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated LTB4R. To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated LTB4R/LTB4R2 genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating LTB4R/LTB4R2 hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents.

Loss of heterozygosity and uniparental disomy of chromosome region 10q23.3-26.3 in glioblastoma.

Glioblastoma is the most frequent and aggressive brain tumor in the adult population. Loss of heterozygosity (LOH) at markers of the long arm of chromosome 10 is the most common genetic alteration in glioblastoma, being detectable in up to 80% of cases. We have tested 124 glioblastoma samples for LOH by microsatellite analysis of the 10q23.3-26.3 region which contains the cancer related genes PTEN, FGFR2, MKI67, and MGMT. Then, a real-time quantitative microsatellite analysis (QuMA) was used to qualitatively estimate the change in copy number of this region in the samples with LOH. LOH was detected in 62.1% of the glioblastoma samples. A total of 64 samples with LOH in this region were examined by QuMA. LOH was attributed to a deletion in 37.5% of cases, and uniparental disomy (UPD) in 25% of cases. In 37.5% of cases, deletion and UPD segments alternated within the region: deletions being more frequent than UPD in its proximal part (encompassing PTEN and FGFR2) and both deletions and UPD occurring at the same frequency in its distal part (MGMT). Thus, we have investigated mechanisms of structural alterations of the chromosome region 10q23.3-26.3 in glioblastoma. In addition to a structural deletion of this region, UPD was identified as a frequent cause of LOH. We resume that more detailed studies of glioblastoma at the molecular genetic level are essential in search for potential markers suitable for predicting the disease outcome and the response to treatment.

Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer.

Prostate cancer (PC) is the most common uro-oncological disease in the global population and still requires a more efficient laboratory diagnosis. Point mutations of oncogenes and tumor sup-pressor genes are the most frequent molecular genetic events in carcinogenesis. The mutations are re-sponsible, to a great extent, for the clonal evolution of cancer and can be considered as primary candi-date molecular markers of PC. Using next-generation sequencing to analyze the mutations in PC, the main molecular PC subtypes were identified, which depended on the presence of fusion genes and FOXA1, CHD1, and SPOP point mutations; other driver mutations responsible for the progression of PC subclones were also characterized. This review summarizes the data on early PC genetic markers (an mtDNA deletion, and TMPRSS2:ERG expression), as well as these somatic mutations at later stages of PC. Emphasis is placed on a switch in AR synthesis to a constitutively active variant and the point muta-tions that facilitate PC transition to a castration-refractory state that is resistant to new AR inhibitors. Based on the current whole-exome sequencing data, the frequencies and localizations of the somatic mu-tations that may provide new genetic diagnostic markers and drug targets are described.

Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice.

INTRODUCTION: We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. CONCLUSION: We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.

The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

Superoleophobic Surfaces Obtained via Hierarchical Metallic Meshes.

Hierarchical metallic surfaces demonstrating pronounced water and oil repellence are reported. The surfaces were manufactured with stainless-steel microporous meshes, which were etched with perfluorononanoic acid. As a result, a hierarchical relief was created, characterized by roughness at micro- and sub-microscales. Pronounced superoleophobicity was registered with regard to canola, castor, sesame, flax, crude (petroleum), and engine oils. Relatively high sliding angles were recorded for 5 µL turpentine, olive, and silicone oil droplets. The stability of the Cassie-like air trapping wetting state, established with water/ethanol solutions, is reported. The omniphobicity of the surfaces is due to the interplay of their hierarchical relief and surface fluorination.

Simple and Efficient Synthesis of Oligoetherdiamines: Hardeners of Epoxyurethane Oligomers for Obtaining Coatings with Shape Memory Effect.

In this work, new polymers with a shape memory effect for self-healing coatings based on oligomers with terminal epoxy groups, synthesized from oligotetramethylene oxide dioles of various molecular weights, were developed. For this purpose, a simple and efficient method for the synthesis of oligoetherdiamines with a high yield of the product, close to 94%, was developed. Oligodiol was treated with acrylic acid in the presence of a catalyst, followed by the reaction of the reaction product with aminoethylpiperazine. This synthetic route can easily be upscaled. The resulting products can be used as hardeners for oligomers with terminal epoxy groups synthesized from cyclic and cycloaliphatic diisocyanates. The effect of the molecular weight of newly synthesized diamines on the thermal and mechanical properties of urethane-containing polymers has been studied. Elastomers synthesized from isophorone diisocyanate showed excellent shape fixity and shape recovery ratios of >95% and >94%, respectively.

Influence of Synthesis Conditions on the Properties of Zinc Oxide Obtained in the Presence of Nonionic Structure-Forming Compounds.

This work investigated the influence of synthesis conditions, including the use of nonionic structure-forming compounds (surfactants) with different molecular weights (400-12,600 g/mol) and various hydrophilic/hydrophobic characteristics, as well as the use of a glass substrate and hydrothermal exposure on the texture and structural properties of ZnO samples. By X-ray analysis, it was determined that the synthesis intermediate in all cases is the compound Zn5(OH)8(NO3)2∙2H2O. It was shown that thermolysis of this compound at 600 °C, regardless of the physicochemical properties of the surfactants, leads to the formation of ZnO with a wurtzite structure and spherical or oval particles. The particle size increased slightly as the molecular weight and viscosity of the surfactants grew, from 30 nm using Pluronic F-127 (MM = 12,600) to 80 nm using Pluronic L-31 (MM = 1100), PE-block-PEG (MM = 500) and PEG (MM = 400). Holding the pre-washed synthetic intermediates (Zn5(OH)8(NO3)2∙2H2O) under hydrothermal conditions resulted in the formation of hexagonal ZnO rod crystal structures of various sizes. It was shown that the largest ZnO particles (10-15 µm) were observed in a sample obtained during hydrothermal exposure using Pluronic P-123 (MM = 5800). Atomic adsorption spectroscopy performed comparative quantitative analysis of residual Zn2+ ions in the supernatant of ZnO samples with different particle sizes and shapes. It was shown that the residual amount of Zn2+ ions was higher in the case of examining ZnO samples which have spherical particles of 30-80 nm. For example, in the supernatant of a ZnO sample that had a particle size of 30 nm, the quantitative content of Zn2+ ions was 10.22 mg/L.

Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary KIT Mutations.

We showed previously that inhibition of KIT signaling in GISTs activates FGFR-signaling pathway rendering cancer cells resistant to receptor tyrosine kinase inhibitor (RTKi) imatinib mesylate (IM) (Gleevec) despite of absence of secondary KIT mutations and thereby illustrating a rationale for the combined (e.g., KIT- and FGFR-targeted) therapies. We show here that long-term culture of IM-resistant GISTs (GIST-R1) with IM substantially down-regulates KIT expression and induces activation of the FGFR-signaling cascade, evidenced by increased expression of total and phosphorylated forms of FGFR1 and 2, FGF-2, and FRS-2, the well-known adaptor protein of the FGF-signaling cascade. This resulted in activation of both AKT- and MAPK-signaling pathways shown on mRNA and protein levels, and rendered cancer cells highly sensitive to pan-FGFR-inhibitors (BGJ 398, AZD 4547, and TAS-120). Indeed, we observed a significant decrease of IC50 values for BGJ 398 in the GIST subclone (GIST-R2) derived from GIST-R1 cells continuously treated with IM for up to 12 months. An increased sensitivity of GIST-R2 cells to FGFR inhibition was also revealed on the xenograft models, illustrating a substantial (>70%) decrease in tumor size in BGJ 398-treated animals when treated with this pan-FGFR inhibitor. Similarly, an increased intra-tumoral apoptosis as detected by immunohistochemical (IHC)-staining for cleaved caspase-3 on day 5 of the treatment was found. As expected, both BGJ 398 and IM used alone lacked the pro-apoptotic and growth-inhibitory activities on GIST-R1 xenografts, thereby revealing their resistance to these TKis when used alone. Important, the knockdown of FGFR2, and, in much less content, FGF-2, abrogated BGJ 398's activity against GIST-R2 cells both in vitro and in vivo, thereby illustrating the FGF-2/FGFR2-signaling axis in IM-resistant GISTs as a primary molecular target for this RTKi. Collectively, our data illustrates that continuous inhibition of KIT signaling in IM-resistant GISTs lacking secondary KIT mutations induced clonal heterogeneity of GISTs and resulted in accumulation of cancer cells with overexpressed FGF-2 and FGFR1/2, thereby leading to activation of FGFR-signaling. This in turn rendered these cells extremely sensitive to the pan-FGFR inhibitors used in combination with IM, or even alone, and suggests a rationale to re-evaluate the effectiveness of FGFR-inhibitors in order to improve the second-line therapeutic strategies for selected subgroups of GIST patients (e.g., IM-resistant GISTs lacking secondary KIT mutations and exhibiting the activation of the FGFR-signaling pathway).

DNA Methylation and Prospects for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy for Triple-Negative and Luminal B Breast Cancer.

Despite advances in the diagnosis and treatment of breast cancer (BC), the main cause of deaths is resistance to existing therapies. An approach to improve the effectiveness of therapy in patients with aggressive BC subtypes is neoadjuvant chemotherapy (NACT). Yet, the response to NACT for aggressive subtypes is less than 65% according to large clinical trials. An obvious fact is the lack of biomarkers predicting the therapeutic effect of NACT. In a search for epigenetic markers, we performed genome-wide differential methylation screening by XmaI-RRBS in cohorts of NACT responders and nonresponders, for triple-negative (TN) and luminal B tumors. The predictive potential of the most discriminative loci was further assessed in independent cohorts by methylation-sensitive restriction enzyme quantitative PCR (MSRE-qPCR), a promising method for the implementation of DNA methylation markers in diagnostic laboratories. The selected most informative individual markers were combined into panels demonstrating cvAUC = 0.83 (TMEM132D and MYO15B markers panel) for TN tumors and cvAUC = 0.76 (TTC34, LTBR and CLEC14A) for luminal B tumors. The combination of methylation markers with clinical features that correlate with NACT effect (clinical stage for TN and lymph node status for luminal B tumors) produces better classifiers, with cvAUC = 0.87 for TN tumors and cvAUC = 0.83 for luminal B tumors. Thus, clinical characteristics predictive of NACT response are independently additive to the epigenetic classifier and in combination improve prediction.

Preparation, Structure and Properties of Urethane-Containing Elastomers Based on Epoxy Terminal Oligomers.

The effect of polyester oligoethylene adipate molecular weight, diisocyanate structure, and chain extender on the properties of epoxyurethane-based oligomer elastomers was studied in this research. Oligoethylene adipates were obtained via polycondensation of adipic acid and ethylene glycol. Epoxyurethane oligomers were synthesized according to a two-step route with an oligodiisocyanate as an intermediate product. The elastomers with hard urethane hydroxyl blocks were synthesized from oligodiisocyanates. The deformation and strength properties of the elastomers were studied.

Synthesis and Study of Physical and Mechanical Properties of Urethane-Containing Elastomers Based on Epoxyurethane Oligomers with Controlled Crystallinity.

The influence of the molecular weight of oligoamine, oligoether, and the type of diisocyanate on the physical and mechanical properties of elastomers with urethane hydroxyl hard segments was studied. For this purpose, oligoetherdiamines with molecular weights ~1008 and ~1400 g mol-1 were synthesized by a three-stage method. Epoxyurethane oligomers were synthesized according to a two-step route with an oligodiisocyanate as an intermediate product. A series of 12 elastomers with controlled crystallinity were synthesized from these elastomers and amines. The deformation and strength properties of the elastomers were studied.

Effect of asymmetric cooling of sessile droplets on orientation of the freezing tip.

HYPOTHESIS: The shape of the "freezing tip" formed by the crystallization of water droplets demonstrated remarkable universality - no dependence on the cooling rate and physico-chemical properties of the substrate has been observed. At the same time, the spatial orientation of the freezing cone may be varied. We hypothesized that the orientation of the freezing tip is determined by the direction of heat flux at the base of the sessile droplet. This direction is expected to be changed when the substrate with a low thermal diffusivity is not cooled uniformly. EXPERIMENTS: We studied the freezing of water droplets placed on the inclined surface of wedges made from a variety of materials (polymers: Polymethylmethacrylate, Polytetrafluoroethylene, Polyurethane and metal: Titanium), which were cooled from below. The shape of the frozen droplets was controlled in situ. COMPUTATIONS: The computational model was suggested for the transient temperature field in the polymer wedge to determine a time variation of the local heat flux under the droplets. A comparison of numerical results and the measurements enabled us to confirm the aforementioned hypothesis relating the orientation of the freezing tips to the direction of the heat flux. FINDINGS: It was established that the orientation of the freezing cone axis depends on the location of the frozen droplet on the inclined surface of the wedge. Calculations of the transient temperature field of the wedge confirmed our hypothesis about the physical reason of the various spatial orientations of the freezing cones.

Pediatric chordoma associated with tuberous sclerosis complex: A rare case report with a thorough analysis of potential therapeutic molecular targets.

Chordoma associated with tuberous sclerosis complex (TSC) is an extremely rare tumor that was described only in 13 cases since 1975. Сhordoma itself is a malignant slow-growing bone tumor thought to arise from vestigial or ectopic notochordal tissue. Chordoma associated with TSC differs from chordoma in the general pediatric population in the median age, where the diagnosis of TSC-associated chordoma is 6.2 months, whereas for chordoma in the general pediatric population it is set to 12 years. The majority of TSC-associated chordomas are localized in skull-based and sacrum regions, and rare in the spine. Chordomas are genetically heterogeneous tumors characterized by chromosomal instability (CIN), and alterations involving PI3K-AKT signaling pathway genes and chromatin remodeling genes. Here we present the 14th case of chordoma associated with TSC in a 1-year-old pediatric patient. Alongside biallelic inactivation of the TSC1 gene, molecular genetic analysis revealed CIN and involvement of epigenetic regulation genes. In addition, we found the engagement of CBX7 and apolipoprotein B editing complex (APOBEC3) genes that were not yet seen in chordomas before. Amplification of CBX7 may epigenetically silence the CDKN2A gene, whereas amplification of APOBEC3 genes can explain the frequent occurrence of CIN in chordomas. We also found that KRAS gene is located in the region with gain status, which may suggest the ineffectiveness of potential EGFR monotherapy. Thus, molecular genetic analysis carried out in this study broadens the horizons of possible approaches for targeted therapies with potential applications for personalized medicine.

Long noncoding RNA landscapes specific to benign and malignant thyroid neoplasms of distinct histological subtypes.

The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma (clPTC and fvPTC), and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour. Specific patterns of lncRNAs involved in the development of clinical and morphological features can be presumed. LncRNA landscapes within distinct benign and malignant histological variants of thyroid neoplasms were not investigated. The aim of the study was to discover long noncoding RNA landscapes common and specific to major benign and malignant histological subtypes of thyroid neoplasms. LncRNA expression in FA, FTC, fvPTC, clPTC and ATC was analysed with comprehensive microarray and RNA-Seq datasets. Putative biological functions were evaluated via enrichment analysis of coexpressed coding genes. In the results, lncRNAs common and specific to FTC, clPTC, fvPTC, and ATC were identified. The discovered lncRNAs are putatively involved in L1CAM interactions, namely, pre-mRNA processing (lncRNAs specific to FTC); PCP/CE and WNT pathways (lncRNAs specific to fvPTC); extracellular matrix organization (lncRNAs specific to clPTC); and the cell cycle (lncRNAs specific to ATC). Known oncogenic and suppressor lncRNAs (RMST, CRNDE, SLC26A4-AS1, NR2F1-AS1, and LINC00511) were aberrantly expressed in thyroid carcinomas. These findings enhance the understanding of lncRNAs in the development of subtype-specific features in thyroid cancer.

Robust icephobic coating based on the spiky fluorinated Al2O3 particles.

Omniphobic and icephobic twin-scale surfaces based on the "urchin"-like fluorinated Al2O3 particles are presented. Combined effect of hierarchical topography and fluorination supplied to the surfaces omniphobic and icephobic properties. The study of the stability of the Cassie wetting state is reported. High apparent contact angles were accompanied with the low contact angle hysteresis and high stability of the Cassie air trapping wetting state. Time delay of the ice crystallization as high as [Formula: see text] min was established when compared to the ice formation on flat aluminum and non-fluorinated "urchin"-like surfaces. Crystallized water droplets formed on the reported nano-structured surfaces were easily blown out by the air jet with the velocity of [Formula: see text] m/s, (which is markedly lower than that common for exploitation of aircrafts and turbines). Heated "urchin"-like surfaces completely restored their omniphobic and icephobic surfaces after thawing. Qualitative analysis of water freezing is supplied.

New Regions With Molecular Alterations in a Rare Case of Insulinomatosis: Case Report With Literature Review.

Insulinomatosis is characterized by monohormonality of multiple macro-tumors and micro-tumors that arise synchronously and metachronously in all regions of the pancreas, and often recurring hypoglycemia. One of the main characteristics of insulinomatosis is the presence of insulin-expressing monohormonal endocrine cell clusters that are exclusively composed of proliferating insulin-positive cells, are less than 1 mm in size, and show solid islet-like structure. It is presumed that insulinomatosis affects the entire population of ß-cells. With regards to molecular genetics, this phenomenon is not related to mutation in MEN1 gene and is more similar to sporadic benign insulinomas, however, at the moment molecular genetics of this disease remains poorly investigated. NGS sequencing was performed with a panel of 409 cancer-related genes. Results of sequencing were analyzed by bioinformatic algorithms for detecting point mutations and copy number variations. DNA copy number variations were detected that harbor a large number of genes in insulinoma and fewer genes in micro-tumors. qPCR was used to confirm copy number variations at ATRX, FOXL2, IRS2 and CEBPA genes. Copy number alterations involving FOXL2, IRS2, CEBPA and ATRX genes were observed in insulinoma as well as in micro-tumors samples, suggesting that alterations of these genes may promote malignization in the ß-cells population.