Endogenous Regeneration of Alveolar Bone by Decellularized Tooth Matrix.

The efficiency of bone tissue regeneration by decellularized tooth matrix, demineralized tooth matrix, and commercial xenograft Bio-Oss Spongiosa was compared on the model of a critical-size circular defect in the alveolar bone of the upper jaw of adult Wistar rats. The defect healing dynamics was assessed using histological, histomorphometrical, and immunohistochemical methods on days 30 and 60. In contrast to demineralized matrix and commercial xenograft, decellularized matrix induces the formation of the new bone tissue by day 60. Decellularized matrix can be considered as a biomaterial for cell-free tissue engineering for alveolar bone restoration in dentistry and maxillofacial surgery.

Identification of Chimeric NTRK3 Genes in Papillary Thyroid Cancer Cells by Analyzing the Imbalance of the Expression of 5' and 3' mRNA Fragments.

The standard for detecting chimeric genes of neurotrophic receptor tyrosine kinases (NTRK) is next generation sequencing (NGS). However, this analysis is expensive and takes several days. As a rapid screening method for the detection of NTRK3-dependent papillary thyroid cancer, an analysis of the expression imbalance between 5' and 3' NTRK3 mRNA fragments was used (5'/3' RT-PCR). The reference method for detection of NTRK3 rearrangements was fluorescent in situ hybridization (FISH), and the most frequent rearrangements in papillary thyroid cancer were tested using reverse transcription PCR (RT-PCR). Using 5'/3' RT-PCR, 18 samples of papillary thyroid cancer carrying chimeric transcripts of NTRK3 mRNA were detected. The sensitivity of the developed technique was 88.9% and specificity was 99.3%. Thus, a fast and cost-effective method of screening samples of papillary thyroid cancer in paraffin blocks is proposed with acceptable sensitivity and specificity.

Differences in Transcriptomic Profiles of Brain and Thyroid Tumors with NTRK Gene Rearrangement.

For tumors with chimeric NTRK genes, entrectinib and larotrectinib can be prescribed regardless of tumor localization. We compared changes in the transcriptional activity of genes in brain tumors (BT) and thyroid cancer (TC) with rearrangement (NTRK+) and without rearrangement (NTRK-) of the NTRK genes using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We revealed an increase in the transcription of the JUN gene in NTRK+ samples in comparison with NTRK- samples: by 1.6 times for BT (p=0.239) and by 2.5 times for TC (p=0.003). The transcription of eight HOX genes in NTRK+ BT samples was also increased (by 85-725 times, p<0.05) in comparison with NTRK-. In NTRK+ TC samples, the level of miR-31 and miR-542 was statistically significantly higher (by 3 and 2.5 times, respectively) than in NTRK-samples. For the NTRK+ BT samples, the levels of miR-10b, miR-182, and miR-21 more than 5-fold surpassed the corresponding values in NTRK-samples (p<0.05). These findings reflect differences in activation of gene transcription resulting from NTRK gene rearrangement in BT and TC.

Histological Variants of Papillary Thyroid Cancer in Relation to Clinical and Morphological Parameters and Prognosis.

The correlation of histological features of papillary thyroid cancer with clinical and morphological prognostic factors and cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center (25 cases with lethal outcome and 64 follow-up controls). Significant variability was revealed in the histological structure of papillary thyroid cancer with the prevalence of classic (62%) and less frequent follicular (19%), tall cell (8%), and solid (7%) variants. In comparison with the classic variant, the solid variant was more often associated with male sex and large tumor size; follicular and tall cell variant was associated with more frequent metastases to regional lymph nodes; follicular and solid variants were associated with an increased proportion of cases with disease stages III-IV. The main differences reflecting the effect of histological factor on the disease outcome were associated with the solid variant of papillary thyroid cancer that was detected in 21% of lethal cases and only in 2% of control subjects. The detection of this variant can be of importance as an additional prognostic factor of the postoperative survival in papillary thyroid cancer.

Infrared Thermometry for Acute Radiation Syndrome in Mice.

Experiment on female ICR CD-1 mice showed that non-contact infrared thermometry can be used for short-term and medium-term prognosis of animal death during the development of acute radiation syndrome. In mice irradiated with X-rays in a dose of 7.25 Gy (LD100/30), the body temperature 1 and 5 days before death was below the normal limit (<36.4°C) in 90 and 50% cases, respectively. The decrease in body temperature closely correlated with a decrease in the mean body weight in irradiated animals (from 24 to 19 g).

[Epithelial-stromal interactions in pancreatic adenocarcinoma: the role of stroma in disease progression]. / Epitelial'no-stromal'nye vzaimodeistviya v adenokartsinome podzheludochnoi zhelezy: rol' stromy v progressirovanii zabolevaniya.

Pancreatic ductal adenocarcinoma (PDAC) is the most common and difficult to treat form of pancreas cancer. PDAC and other solid cancers contain both tumor cells and normal connective tissue cells called stromal cells, which are responsible for the excess production of extracellular matrix. It is known that in more than 90% of PDAC tumors and in many other types of cancer, mutations of the KRAS gene are observed, the reciprocal signaling of which has been shown between tumor and stromal cells in vitro. Pancreatic stromal stellate cells are considered precursors of activated or tumor-associated fibroblasts (CAFs), which are an increasing population of cells that proliferate in situ or are recruited into the tumor. CAFs are a heterogeneous population of stromal fibroblasts with different molecular profiles that change during tumorigenesis. Both immunosuppressive and immunosuppressive subsets of CAFs can coexist in the stroma of a single tumor. Based on the heterogeneity of the intertumor stroma, attempts are being made to classify PDAC and predict the course of the disease.

Solidification of ternary melts with a two-phase layer.

This review is concerned with the nonstationary solidification of three-component systems in the presence of two moving phase transition regions-the main (primary) and cotectic layers. A non-linear moving boundary problem has been developed and its analytical solutions have been defined. Namely, the temperature and impurity concentration distributions were determined, the solid phase fractions in the phase transition regions and the laws of motion of their boundaries were found. It was shown that variations in the initial impurity concentration affect significantly the ratio between the lengths of the two-phase layers. A non-linear liquidus surface equation is theoretically taken into account as well.

Prediction of EVT6-NTRK3-Dependent Papillary Thyroid Cancer Using Minor Expression Profile.

Solid tumors resulting from oncogenic stimulation of neurotrophin receptors (TRK) by chimeric proteins are a group of rare tumors of various localization that respond to therapy with targeted drugs entrectinib and larotrectinib. The standard method for detecting chimeric TRK genes in tumor samples today is considered to be next generation sequencing with the determination of the prime structure of the chimeric transcripts. We hypothesized that expression of the chimeric tyrosine kinase proteins in tumors can determine the specific transcriptomic profile of tumor cells. We detected differentially expressed genes allowing distinguishing between TRK-dependent tumors papillary thyroid cancer (TC) from other molecular variants of tumors of this type. Using PCR with reverse transcription (RT-PCR), we identified 7 samples of papillary TC carrying a EVT6-NTRK3 rearrangement (7/215, 3.26%). Using machine learning and the data extracted from TCGA, we developed of a recognition function for predicting the presence of rearrangement in NTRK genes based on the expression of 10 key genes: AUTS2, DTNA, ERBB4, HDAC1, IGF1, KDR, NTRK1, PASK, PPP2R5B, and PRSS1. The recognition function was used to analyze the expression data of the above genes in 7 TRK-dependent and 10 TRK-independent thyroid tumors obtained by RT-PCR. On the test samples from TCGA, the sensitivity was 72.7%, the specificity - 99.6%. On our independent validation samples tested by RT-PCR, sensitivity was 100%, specificity - 70%. We proposed an mRNA profile of ten genes that can classify TC in relation to the presence of driver NTRK-chimeric TRK genes with acceptable sensitivity and specificity.

[Is there a claudin-low phenotype of breast cancer?] / Sushchestvuet li «nizkoklaudinovyi¼ fenotip raka molochnoi zhelezy?

The novel molecular subtype of breast cancer (BC), named "claudin-low", was described in 2007. It was characterized by the consistently low expression of genes involved in the formation of epithelial tight junctions in combination with the high activation of genes associated with the epithelial-to-mesenchymal transition, as well as tumor stem cell markers. The similar claudin- low subtype was later identified at the transcriptional level in bladder cancer, gastric cancer, and serous ovarian cancer. However, only in relation to BC, attempts were made to create a surrogate panel for immunohistochemical identification of this subtype in a manner like the intrinsic molecular BC subtypes identified using three main markers, such as ER, PR, and HER-2. At the same time, the ambiguity in the expression of claudins among the subtypes of BC, which is defined by various authors at the immunohistochemical level, as well as the absence of both the confirmed set of immunohistochemical criteria and a unified approach to their assessment, complicate these efforts. The purpose of the review is to show that the immunohistochemical identification of claudin-low subtype of BC is a separate problem that has significant limitations, needs standardization and has not yet reached diagnostic value.

DNA Damage in Splenocytes of Mice Exposed to Secondary Radiation Created by 650 MeV Protons Bombarding a Concrete Shielding Barrier.

The proportion of splenocytes with a high level of DNA double-strand breaks was determined in mice exposed to primary and secondary radiation created by bombarding of a concrete barrier (thickness 20, 40, and 80 cm) by 650 MeV protons. The proportion of splenocytes with a high level of DNA double-strand breaks was assessed by flow cytometric analysis of γH2AX+ and TUNEL+ cells. It is shown that concrete barrier can significantly reduce primary proton radiation; the severity of negative biological effects in mice irradiated in the center of the proton beam decreased with increasing the thickness of this barrier. However, the spectrum of secondary radiation changes significantly with increasing the barrier thickness from 20 to 80 cm and the distance from central axis of the beam from 0 to 20 cm, and the proportion of the neutron component increases, which also causes negative biological effects manifesting in a significant (p<0.05) increase in the percentage of splenocytes with a high level of DNA damage in mice irradiated at a distance of 20 cm from the center of the proton beam and receiving relatively low doses (0.10-0.17 Gy).

[Endovascular treatment of extracranial dissecting aneurysms of cervical arteries]. / Vnutrisosudistoe lechenie ekstrakranial'nykh dissektsionnykh anevrizm brakhiotsefal'nykh arterii.

BACKGROUND: Dissecting aneurysms of extracranial cervical arteries are a rare vascular pathology. To date, there is no consensus on the choice of optimal surgical approach for these aneurysms. OBJECTIVE: To evaluate the effectiveness of endovascular treatment of various extracranial dissecting aneurysms. MATERIAL AND METHODS: There were 19 patients with 21 extracranial dissecting aneurysms for the period from January 1, 2013 to October 19, 2020. Clinical examination, ultrasound and neuroimaging data were considered to determine surgical intervention. RESULTS: Nineteen patients underwent 20 intravascular interventions: aneurysm embolization with detachable coils with stent-assistance (n=9), flow-diverting stent implantation (n=5), arterial reconstruction with a stent for carotid stenting (n=3), aneurysm embolization with balloon assistance (n=1), aneurysm embolization with detachable coils without assistance (n=2). There were no complications. All patients were discharged without neurological impairment after 1-5 days. Long-term results of control angiography were analyzed within 1-19 months in 12 patients. All aneurysms were completely occluded. Asymptomatic occlusion of flow-diverting stent together with aneurysm occurred in 1 patient with low compliance to antiplatelet therapy. Other 6 patients are scheduled for elective angiography. CONCLUSION: Extracranial dissecting aneurysms of cervical arteries require vigilance due to their rare occurrence and risk of severe complications. In our opinion, intravascular interventions are advisable for these patients as effective and safe procedures.

Rat Blood Leukocytes after Intravenous Injection of Magnetoliposomes on the Basis of Nanomagnetite.

The structure of blood neutrophils, eosinophils, monocytes, and lymphocytes and differential white blood count in adult rats were studied over 120 days after a single intravenous injection of magnetoliposomes based on nanomagnetite. Magnetoliposomes had no effect on the structure of neutrophils, eosinophils, monocytes, and lymphocytes. At the same time, injection of a suspension of magnetoliposomes based on magnetite nanoparticles led to a decrease in lymphocyte count and an increase in the count of monocytes and band and segmented neutrophils in the blood. These changes were transient and the parameters returned to normal by day 40-60 after injection.

[The first experience of endovascular treatment of chronic subdural hematomas with non-adhesive embolization materials of various viscosities: Squid 12 and 18]. / Pervyi opyt endovaskulyarnogo lecheniya khronicheskikh subdural'nykh gematom neadgezivnymi emboliziruyushchimi materialami razlichnoi vyazkosti SQUID 12 i 18.

Chronic subdural hematomas (CSH) usually require surgical evacuation via a burr hole or craniotomy. Certain incidence of recurrent postoperative CSH is known. Middle meningeal artery (MMA) embolization has been described as an alternative surgery for new or recurrent CSH or as a preventive measure to reduce the risk of postoperative recurrence. The authors report successful MMA embolization with 2 non-adhesive embolic agents of various viscosities (SQUID 12 and SQUID 18, Balt USA, Irvine, CA, USA) for recurrent postoperative CSH in a 44-year-old woman.

Multimodal nonlinear-optical imaging of nucleoli.

Multimodal nonlinear microscopy combining third-harmonic generation (THG) with two- and three-photon-excited fluorescence (2PEF and 3PEF) is shown to provide a powerful resource for high-fidelity imaging of nucleoli and nucleolar proteins. We demonstrate that, with a suitably tailored genetically encoded fluorescent stain, the 2PEF/3PEF readout from specific nucleolar proteins can be reliably detected against the extranucleolar 2PEF/3PEF signal, enabling high-contrast imaging of the key nucleolar ribosome biogenesis components, such as fibrillarin. THG is shown to provide a versatile readout for unstained nucleolus imaging in a vast class of biological systems as different as neurons in brain slices and cultured HeLa cells.

Local electronic structure rearrangements and strong anharmonicity in YH3 under pressures up to 180 GPa.

The discovery of superconductivity above 250 K at high pressure in LaH10 and the prediction of overcoming the room temperature threshold for superconductivity in YH10 urge for a better understanding of hydrogen interaction mechanisms with the heavy atom sublattice in metal hydrides under high pressure at the atomic scale. Here we use locally sensitive X-ray absorption fine structure spectroscopy (XAFS) to get insight into the nature of phase transitions and the rearrangements of local electronic and crystal structure in archetypal metal hydride YH3 under pressure up to 180 GPa. The combination of the experimental methods allowed us to implement a multiscale length study of YH3: XAFS (short-range), Raman scattering (medium-range) and XRD (long-range). XANES data evidence a strong effect of hydrogen on the density of 4d yttrium states that increases with pressure and EXAFS data evidence a strong anharmonicity, manifested as yttrium atom vibrations in a double-well potential.

Osteogenic Potential of Decellularized Tooth Matrix.

We studied the possibility of using decellularized tooth matrix as a scaffold to restore bone tissue. It was found that mesenchymal stem cells underwent spontaneous osteogenic differentiation on the decellularized tooth matrix, which makes it possible to use it as a natural allograft in the treatment of resorption of alveolar bone tissue.

Behavioral Responses and Immune and Cytogenetic Parameters of Food-Restricted Mice.

The experiments on mice showed that subchronic food restriction to 40 and 8% of unrestricted ration is a strong stressor inducing devastation of lymphoid organs, primarily the thymus and spleen. The mice in the group with severe food restriction (8% of normal ration) demonstrated increased front paw grip force. We also observed an increase in spontaneous motor activity in these animals correlated with food restriction. Food deprivation led to inhibition of proliferative activity of the bone marrow cells and suppression of erythropoiesis. Moreover, severe food restriction was accompanied by a decrease in the number of double-strand DNA breaks evaluated by the release of γH2AX+-cells and the ratio of polychromatophilic erythrocytes.

The Relationship of Immunoexpression of Ki-67 and Hsp70 with Clinical and Morphological Parameters and Prognosis of Papillary Thyroid Cancer.

We studied the correlations of the expression of Ki-67 proliferation marker and localization of heat shock protein Hsp70 in tumor cells of papillary thyroid cancer with some clinical and morphological parameters and a 10-year survival prognosis. High variability of the proliferative activity (by Ki-67 index) of tumor cells was revealed. It was found that Hsp70 protein has different localization in tumor cells: cytoplasmic, nuclear, nucleolar, and mixed. Nuclear translocation of the Hsp70 protein correlated with the stage of the process and the prognosis of the disease, but did not correlate with sex, tumor size, capsule invasion, and lymph node metastasis. Ki-67 index of tumor cells correlated with sex, stage of the process, size of tumor formation and prognosis, but did not correlated with age, invasion into the capsule and metastasis to the lymph nodes. Depending on the variants of Hsp70 and Ki-67 co-expression, three molecular types of papillary thyroid cancer can be distinguished: favorable, intermediate, and poor prognosis.

Update of ion-optical system of neutral beam of Tokamak à Configuration Variable.

An injector of fast deuterium atoms for plasma heating was designed and installed at the Tokamak à Configuration Variable (TCV). The neutral beam can deliver 1 MW power to the plasma in 2 s pulses. An ion beam of the injector is formed by a triode multislit ion-optical system with spherical electrodes which provide ballistic focusing. Tests at TCV revealed that the total angular divergence of the neutral beam across the slits exceeded the expected value more than twice. It was finally established that this increase in divergence was caused by the asymmetry of the chamfers at the slit edges of the plasma electrode. The redesigned shape of the slits of the plasma grid together with precise machining significantly improved the beam quality. Experimental testing proved that the neutral beam profile in the direction across the grid slits became very close to the expected value.

Cell-specific three-photon-fluorescence brain imaging: neurons, astrocytes, and gliovascular interfaces.

We present brain imaging experiments on rat cortical areas, demonstrating that, when combined with a suitable high-brightness, cell-specific genetically encoded fluorescent marker, three-photon-excited fluorescence (3PEF), enables subcellular-resolution, cell-specific 3D brain imaging that is fully compatible and readily integrable with other nonlinear-optical imaging modalities, including two-photon-fluorescence and harmonic-generation microscopy. With laser excitation provided by sub-100-fs, 1.25-µm laser pulses, cell-specific 3PEF from astrocytes and their processes detected in parallel with a three-photon-resonance-enhanced third harmonic from blood vessels is shown to enable a high-contrast 3D imaging of gliovascular interfaces.