Molecular Subgroups of HRD Positive Ovarian Cancer and Their Prognostic Significance.

Homologous recombination repair deficiency (HRD) is involved in the development of high-grade serous ovarian carcinoma (HGSOC) and its elevated sensitivity to platinum-based chemotherapy. To investigate the heterogeneity of the HRD-positive HGSOC we evaluated the HRD status, including BRCA mutations, genomic scar score, and methylation status of genes in 352 HGSOC specimens. We then divided the HRD-positive cohort into three molecular subgroups, the BRCA mutation cohort (BRCA+), BRCA1 methylation cohort (Meth+), and the rest of the HRD+ cohort (HRD+BRCA-Meth-), and evaluated their first-line chemotherapy response, benefit from olaparib, and progression-free survival (PFS).

Observation of nonlinear fractal higher order topological insulator.

Higher-order topological insulators (HOTIs) are unique materials hosting topologically protected states, whose dimensionality is at least by 2 lower than that of the bulk. Topological states in such insulators may be strongly confined in their corners which leads to considerable enhancement of nonlinear processes involving such states. However, all nonlinear HOTIs demonstrated so far were built on periodic bulk lattice materials.

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 genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes.

Observation of π solitons in oscillating waveguide arrays.

Floquet systems with periodically varying in time parameters enable realization of unconventional topological phases that do not exist in static systems with constant parameters and that are frequently accompanied by appearance of novel types of the topological states. Among such Floquet systems are the Su-Schrieffer-Heeger lattices with periodically-modulated couplings that can support at their edges anomalous π modes of topological origin despite the fact that the lattice spends only half of the evolution period in topologically nontrivial phase, while during other half-period it is topologically trivial. Here, using Su-Schrieffer-Heeger arrays composed from periodically oscillating waveguides inscribed in transparent nonlinear optical medium, we report experimental observation of photonic anomalous π modes residing at the edge or in the corner of the one- or two-dimensional arrays, respectively, and demonstrate a new class of topological π solitons bifurcating from such modes in the topological gap of the Floquet spectrum at high powers.

Observation of nonlinear disclination states.

Introduction of controllable deformations into periodic materials that lead to disclinations in their structure opens novel routes for construction of higher-order topological insulators hosting topological states at disclinations. Appearance of these topological states is consistent with the bulk-disclination correspondence principle, and is due to the filling anomaly that results in fractional charges to the boundary unit cells. So far, topological disclination states were observed only in the linear regime, while the interplay between nonlinearity and topology in the systems with disclinations has been never studied experimentally.

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 status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens.

The Charge Distribution, Seebeck Coefficient, and Carrier Concentration of CuCrLnS (Ln = Dy-Lu).

The atom oxidation states were determined using the binding energies of the core S2p-, Cu2p-, Cr2p-, and Ln3d-levels in CuCrLnS (Ln = Dy-Lu) solid solutions. The charge distribution on the matrix elements (Cu, Cr, and S) remained unaffected after cationic substitution. The sulfur atoms were found to be in the S oxidation state, the copper-Cu, and the chromium-Cr.

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.

Observation of Linear and Nonlinear Light Localization at the Edges of Moiré Arrays.

We observe linear and nonlinear light localization at the edges and in the corners of truncated moiré arrays created by the superposition of periodic mutually twisted at Pythagorean angles square sublattices. Experimentally exciting corner linear modes in the femtosecond-laser written moiré arrays we find drastic differences in their localization properties in comparison with the bulk excitations. We also address the impact of nonlinearity on the corner and bulk modes and experimentally observe the crossover from linear quasilocalized states to the surface solitons emerging at the higher input powers.

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson's Disease at the Prodromal Stage.

Parkinson's disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD.

Charge Distribution in Layered Lanthanide-Doped CuCrLnS (Ln = Pr-Tb) Thermoelectric Materials.

The charge distribution study of metal atoms in CuCrLnS (Ln = Pr-Tb) solid solutions was carried out using X-ray photoelectron spectroscopy (XPS). The analysis of the binding energy of S2p, Cu2p, Cr2p, Ln3d and Ln4d levels allows one to determine the oxidation state of atoms. Copper atoms were found to be monovalent.

[Enhanced Natural Killers with CISH and B2M Gene Knockouts Reveal Increased Cytotoxicity in Glioblastoma Primary Cultures].

In an experimental study using the CRISPR/Cas9 system, "enhanced" NK cell lines with knockout of CISH, the gene for the CIS protein (a negative regulator of NK cytotoxicity), as well as two lines with a knocked-out β2-microglobulin gene, which provides membrane exposure of MHC class I, were obtained from two parental lines of human natural killers (YT wild type and YT-VAV1^(+) overexpressing the VAV1 cytotoxicity enhancing protein). The knockout efficiency was determined by real-time PCR as well as by flow cytometry with specific antibodies. The resulting CISH^(-/-) or B2M^(-/-) knockout lines were tested for cytotoxicity in primary monolayer cultures of human glioblastoma multiforme.

Time-domain Hong-Ou-Mandel interference of quasi-thermal fields and its application in linear optical circuit characterization.

We study temporal correlations of interfering quasi-thermal fields, obtained by scattering laser radiation on a rotating ground glass disk. We show that the Doppler effect causes oscillations in the temporal cross correlation function. Furthermore, we propose how to use Hong-Ou-Mandel interference of quasi-thermal fields in the time domain to characterize linear optical circuits.

Observation of nonlinearity-controlled switching of topological edge states.

We report the experimental observation of the periodic switching of topological edge states between two dimerized fs-laser written waveguide arrays. Switching occurs due to the overlap of the modal fields of the edge states from topological forbidden gap, when they are simultaneously present in two arrays brought into close proximity. We found that the phenomenon occurs for both strongly and weakly localized edge states and that switching rate increases with decreasing spacing between the topological arrays.

New facets of nanozyme activity of ceria: lipo- and phospholipoperoxidase-like behaviour of CeO nanoparticles.

Cerium dioxide nanoparticles have a special place among engineered nanomaterials due to the wide range of their enzyme-like activities. They possess SOD-, catalase- and peroxidase-like properties, as well as recently discovered phosphatase-, photolyase-, phospholipase- and nuclease-like properties. Advancing biomedical applications of CeO-based nanozymes requires an understanding of the features and mechanisms of the redox activity of CeO nanoparticles when entering the vascular bed, especially when interacting with lipid-protein supramolecular complexes (biomembranes and lipoproteins).

Observation of Edge Solitons in Topological Trimer Arrays.

We report the experimental observation of nonlinear light localization and edge soliton formation at the edges of fs-laser written trimer waveguide arrays, where transition from nontopological to topological phases is controlled by the spacing between neighboring trimers. We found that, in the former regime, edge solitons occur only above a considerable power threshold, whereas in the latter one they bifurcate from linear states. Edge solitons are observed in a broad power range where their propagation constant falls into one of the topological gaps of the system, while partial delocalization is observed when considerable nonlinearity drives the propagation constant into an allowed band, causing coupling with bulk modes.

Parental Origin of the Gene Mutations in Families with Low Penetrance Hereditary Retinoblastoma.

Our aim was to identify alterations causing hereditary low penetrance retinoblastoma and to evaluate how the parental origin of an mutation affects its phenotypic expression. By NGS and MLPA, mutations were found in 191 from 332 unrelated retinoblastoma patients. Among patients with identified mutations but without clinical family history of retinoblastoma, 7% (12/175) were found to have hereditary disease with one of the parents being an asymptomatic carrier of an mutation.

Mutations in Epigenetic Regulation Genes in Gastric Cancer.

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority ( = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority ( = 41), in histone modifier genes, among which mutations were most commonly found in and .

Valence band structure and charge distribution in the layered lanthanide-doped CuCrLnS (Ln = La, Ce) solid solutions.

The comprehensive study of the electronic density distribution of CuCrLnS (Ln = La, Ce) solid solutions was carried out using both X-ray photoelectron and emission spectroscopy. It was found that cationic substitution of chromium with lanthanum or cerium atoms does not significantly affect the atomic charges of the matrix elements (Cu, Cr, S) in the lanthanide-doped solid solutions. The copper atoms in the composition of CuCrS-matrix and the lanthanide-doped solid solutions were found to be in the monovalent state.

Crystal-Chemical and Thermal Properties of Decorative Cement Composites.

The advanced tendencies in building materials development are related to the design of cement composites with a reduced amount of Portland cement, contributing to reduced CO emissions, sustainable development of used non-renewal raw materials, and decreased energy consumption. This work deals with water cured for 28 and 120 days cement composites: Sample A-reference (white Portland cement + sand + water); Sample B-white Portland cement + marble powder + water; and Sample C white Portland cement + marble powder + polycarboxylate-based water reducer + water. By powder X-ray diffraction and FTIR spectroscopy, the redistribution of CO, SO, SiO, AlO, and OH (as O-H bond in structural OH anions and O-H bond belonging to crystal bonded water molecules) from raw minerals to newly formed minerals have been studied, and the scheme of samples hydration has been defined.

[Development of early diagnosis of Parkinson's disease and comprehensive economic analysis of the effect of its implementation].

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost.

Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer.

Cell transmembrane receptors and extracellular matrix components play a pivotal role in regulating cell activity and providing for the concerted integration of cells in the tissue structures. We have assessed DNA methylation in the promoter regions of eight integrin genes, two nidogen genes, and the dystroglycan gene in normal breast tissues and breast carcinomas (BC). The protein products of these genes interact with the basement membrane proteins LAMA1, LAMA2, and LAMB1; abnormal hypermethylation of the LAMA1, LAMA2, and LAMB1 promoters in BC has been described in our previous publications.

[Development of early diagnosis of Parkinson's disease based on the search for biomarkers such as premotor symptoms and changes in blood].

Objective: To determine changes in the chemical composition of blood plasma in subjects at risk of Parkinson's disease (PD) at the prodromal stage compared with age control.

Material And Methods: Subjects at risk were selected for the presence of characteristic premotor symptoms, including impairments of sleep, olfaction and constipation.The risk group included 12 people, the control group - 8 people.

Analysis of miRNA Expression in Patients with Rheumatoid Arthritis during Olokizumab Treatment.

Rheumatoid arthritis (RA) is the most common autoimmune disease worldwide. Epigenetic alternations of microRNAs (miRNAs) can contribute to its pathogenesis and progression. As the first line therapy with DMARDs is not always successful, other drugs and therapeutic targets should be applied.

Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study).

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group).