Untapped Potential of Poly(ADP-Ribose) Polymerase Inhibitors: Lessons Learned From the Real-World Clinical Homologous Recombination Repair Mutation Testing.

Background: Testing for homologous recombination deficiency (HRD) mutations is pivotal to assess individual risk, to proact preventive measures in healthy carriers and to tailor treatments for cancer patients. Increasing prominence of poly(ADP-ribose) polymerase (PARP) inhibitors with remarkable impact on molecular-selected patient survival across diverse nosologies, ingrains testing for BRCA genes and beyond in clinical practice. Nevertheless, testing strategies remain a question of debate.

Diagnosis of Familial Hypercholesterolemia in Children and Young Adults.

The early detection and treatment of familial hypercholesterolemia (FH) in childhood and adolescence are critical for increasing life expectancy. The purpose of our study was to investigate blood lipid parameters, features of physical signs of cholesterol accumulation, and a personal and family history of premature cardiovascular diseases in children and young adults when FH is diagnosed. The analysis included patients under 18 years of age (n = 17) and young adults (18-44 years of age; n = 43) who received a diagnosis of FH according to clinical criteria.

[The relationship between the relative length of leukocyte telomeres and mtDNA copy number and acute coronary syndrome in a 15-year follow-up.].

to study the association of relative leukocyte DNA telomere length with death from natural causes during a 15-year follow-up in a middle-aged and elderly Siberian population. Study of the association of the relative length of leukocyte telomeres (LTL) with fatal outcomes during a 15-year follow-up of a random population sample formed in 2003-2005 (n=9 360, 45-69 years old, Novosibirsk, HAPIEE project). The main group included the persons died from natural causes (except external) without a previous history of CVD and cancer (n=609); controls were stratified by sex and age (n=799).

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis.

Background: A socioeconomic crisis in Russia lasted from 1991 to 1998 and was accompanied by a sharp drop in the birth rate. The main factor that influenced the refusal to have children during this period is thought to be prolonged social stress.

Methods: comparing frequencies of common gene variants associated with stress-induced diseases among generations born before, after, and during this crisis may show which genes may be preferred under the pressure of natural selection during periods of increased social stress in urban populations.

Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet.

In animals, obesity caused by consumption of a sweet-fat diet (SFD) is the most adequate mouse model of human diet-induced obesity. Fibroblast growth factor 21 (FGF21) reduces body weight, beneficially affects taste preferences, and corrects glucose metabolism in obese mice. Sex is known to influence FGF21 effects in different models of diet-induced and hereditary obesity.

Association of Common Variants of , , and the 9p21.3 Chromosomal Region with the Risk of Myocardial Infarction: A Prospective Study.

The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors. This study was aimed at analyzing possible associations of several genetic factors with the risk of myocardial infarction (MI). For our study, we selected genes that have been significantly associated with MI in meta-analyses: the chromosomal region 9p21.

The Relationship between All-Cause Natural Mortality and Copy Number of Mitochondrial DNA in a 15-Year Follow-Up Study.

We explored the relationship between the copy number of mitochondrial DNA (mtDNA-CN) and all-cause natural mortality. We examined a random population sample in 2003/2005 ( = 9360, men/women, 45-69, the HAPIEE project) and followed up for 15 years. Using a nested case-control design, we selected non-external deaths among those free from baseline cardiovascular diseases (CVD) and cancer ( = 371), and a sex- and age-stratified control ( = 785).

The Mutation Spectrum of Rare Variants in the Gene of Adenosine Triphosphate (ATP)-Binding Cassette Subfamily C Member 8 in Patients with a MODY Phenotype in Western Siberia.

During differential diagnosis of diabetes mellitus, the greatest difficulties are encountered with young patients because various types of diabetes can manifest themselves in this age group (type 1, type 2, and monogenic types of diabetes mellitus, including maturity-onset diabetes of the young (MODY)). The MODY phenotype is associated with gene mutations leading to pancreatic-β-cell dysfunction. Using next-generation sequencing technology, targeted sequencing of coding regions and adjacent splicing sites of MODY-associated genes (, , , , , , , , , , , , , and ) was carried out in 285 probands.

Prevalence of Common Alleles of Some Stress Resilience Genes among Adolescents Born in Different Periods Relative to the Socioeconomic Crisis of the 1990s in Russia.

Social stress is common among people and is considered one of the causes of the declining birth rate. Predisposition to stress and stress-induced disorders is largely determined genetically. We hypothesized that due to differences in stress resistance, carriers of different genetic variants of genes associated with stress resilience and stress-induced diseases may have dissimilar numbers of offspring under conditions of long-term social stress.

[The relationship between the relative length of leukocyte telomeres and mtDNA copy number and acute coronary syndrome in a 15-year follow-up.].

We studied the relationship between the leucocyte telomere length (LTL) and the copy number of mitochondrial DNA (CNmtDNA) and the development of acute coronary syndrome during 15 years of follow-up. A random population sample was examined at baseline in 2003-2005 (n=9 360, men and women 45-69 years old, Novosibirsk, the HAPIEE project) and followed-up for 15 years. In the frame of nested case-control design, we selected cases - incident myocardial infarction/acute coronary syndrome (MI/ACS) among those free from baseline CVD (n=256) and sex- and age-stratified control among those free from baseline CVD and cancer and alive by the end of follow-up (n=799).

Associations of Gene Variants rs429358 and rs7412 with Parameters of the Blood Lipid Profile and the Risk of Myocardial Infarction and Death in a White Population of Western Siberia.

The present study aimed to analyze possible associations of rs7412 and rs429358 of the gene with lipid profile parameters, the risk of myocardial infarction, and death in the mostly white population of Western Siberia (Russia). The study population was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 subjects, age 53.8 ± 7.

Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia).

The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the promoter and exons.

A.Eye Drive: Gaze-based semi-autonomous wheelchair interface.

Existing wheelchair control interfaces, such as sip & puff or screen based gaze-controlled cursors, are challenging for the severely disabled to navigate safely and independently as users continuously need to interact with an interface during navigation. This puts a significant cognitive load on users and prevents them from interacting with the environment in other forms during navigation. We have combined eyetracking/gaze-contingent intention decoding with computer vision context-aware algorithms and autonomous navigation drawn from self-driving vehicles to allow paralysed users to drive by eye, simply by decoding natural gaze about where the user wants to go: A.

Data on the morphology and chemical state of coatings based on TiN obtained by condensation with ion bombardment on various substrates.

This article presents the effect of the substrate on the morphology and chemical composition of titanium nitride coatings formed using the condensation with ion bombardment method. Various steels, sintered hard alloy (tungsten carbide - 92%, cobalt - 8%) and titanium-based alloy were used as substrates. The paper presents the XPS data obtained at various depths from the surface.

Association of RS708272 ( Gene Variant) with Lipid Profile Parameters and the Risk of Myocardial Infarction in the White Population of Western Siberia.

The B (rs708272) single-nucleotide variant, i.e., the +279 G/A substitution in intron 1 of the gene, is actively investigated as a risk factor of lipid metabolism disorders.

[Mitochondrial DNA copy number of leucocytes as ageing marker and risk factors for age-related diseases in human.].

We used quantitative real-time PCR method to analyse mtDNA copy number in a random subsample (n=996; 358 men aged 66,31±7,24 years; 468 women aged 67,62±7,1 years) selected from a population cohort (n=9 630) examined at baseline in international project HAPIEE in Novosibirsk, Russia, in 2003-2005. The participants were re-examined after 12 years in 2015-2017. The average relative number of mtDNA copies in peripheral blood leukocytes was greater in women than in men, independently of age and smoking (p=0,001).

Analysis of Polymorphism rs1333049 (Located at 9P21.3) in the White Population of Western Siberia and Associations with Clinical and Biochemical Markers.

The 9p21.3 chromosomal region is a marker of the risk of cardiovascular diseases. The aim of this study was to analyze single-nucleotide polymorphism rs1333049 (chr9:22125504) in the population of Western Siberia (Russia) and possible associations with clinical and biochemical parameters.

Leukocyte telomere length and risk of coronary heart disease and stroke mortality: prospective evidence from a Russian cohort.

Previous studies suggest that reduced leukocyte telomere length (LTL) is related to higher risk of mortality and several chronic conditions, including coronary heart disease (CHD) and stroke. However, the consistency of this association differs across populations. We investigated the relationship of LTL with CHD, stroke and all-cause mortality together with non-fatal CHD and stroke events in a Russian cohort with a mean age of 58 years at baseline.

Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia.

Objective: Earlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia.

A Case of Maturity Onset Diabetes of the Young (MODY3) in a Family with a Novel HNF1A Gene Mutation in Five Generations.

Diabetes mellitus with autosomal dominant inheritance, i.e., maturity-onset diabetes of the young (MODY), is a genetic form of diabetes mellitus.

Association of Polymorphism in SCN5A, GJA5, and KCNN3 Gene with Sudden Cardiac Death.

We studied association of single-nucleotide SCN5A (rs1805124), GJA5 (rs35594137), and KCNN3 (rs13376333) polymorphisms and sudden cardiac death. Humans died suddenly from cardiac causes (N=379) and unrelated sex- and age-matched control subjects were genotyped. No significant intergroup differences were found in the frequency of rs1805124 and rs13376333 genotypes and alleles.