Identification of a Novel Indel Variant in the DARS2 Gene in Russian Patients with Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation.

BACKGROUND: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is an inherited disease caused by pathogenic biallelic variants in the gene DARS2, which encodes mitochondrial aspartyl-tRNA synthetase. This disease is characterized by slowly progressive spastic gait, cerebellar symptoms, and leukoencephalopathy with brainstem and spinal cord involvement. CASE PRESENTATION: Peripheral blood samples were collected from four patients from four unrelated families to extract genomic DNA. All patients underwent partial exon analysis of the DARS2 gene using Sanger sequencing, which detected the c.228-21_228-20delinsC variant in a heterozygous state. Further DNA from three patients was analyzed using a next-generation sequencing-based custom AmpliSeq™ panel for 59 genes associated with leukodystrophies, and one of the patients underwent whole genome sequencing. We identified a novel pathogenic variant c.1675-1256_*115delinsGCAACATTTCGGCAACATTCCAACC in the DARS2 gene. Three patients (patients 1, 2, and 4) had slowly progressive cerebellar ataxia, and two patients (patients 1 and 2) had spasticity. In addition, two patients (patients 2 and 4) showed signs of axonal neuropathy, such as decreased tendon reflexes and loss of distal sensitivity. Three patients (patients 1, 2, and 3) also had learning difficulties. It should be noted the persistent presence of characteristic changes in brain MRI in all patients, which emphasizes its importance as the main diagnostic tool for suspicion and subsequent confirmation of LBSL. Conclusions: We found a novel indel variant in the DARS2 gene in four patients with LBSL and described their clinical and genetic characteristics. These results expand the mutational spectrum of LBSL and aim to improve the laboratory diagnosis of this form of leukodystrophy.

Effectiveness of Photodynamic Therapy as Antiseptic Measure for Oral Cavity and Pharynx: A Systematic Review.

BACKGROUND: The complex traditional treatment of inflammation diseases in oral cavity includes the prescription of antibiotic and antiseptic therapy. This systematic review aims to evaluate the effect of photodynamic therapy as a part of management of inflammatory diseases in oral cavity; Methods: The study is presented in accordance with the preferred reporting points for systematic reviews and meta-analyses (PRISMA). This systematic review was conducted using electronic databases such as Medline PubMed, Scopus and the Cochrane Central Register of Controlled Trials. All the studies in this systematic review, were randomized, the risk of bias 2 (ROB 2) were assessed; Results: Considering the inclusion and exclusion criteria, we included 10 randomized clinical trials, published up to 2023 investigating the application of photodynamic therapy as a part of management of inflammatory diseases in oral cavity. The diode laser was used in the oral cavity in the zone of inflammatory process (gingivitis, mucositis, periimplantitis, marginal periodontitis, abscess, periostitis, osteomyelitis etc.) in nine studies or in the zone before surgical procedures in one study; Conclusion: Based on the results of clinical studies, it can be stated that photodynamic therapy shows good results for operations performed in the oral cavity and pharynx.

Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies.

Here we present a patient with a cranioectodermal phenotype associated with pathogenic variants in the IFT140 gene. Most frequently, pathogenic variants in IFT140 correspond to the phenotype of Mainzer-Saldino syndrome. Only four patients have previously been described with this cranioectodermal phenotype and variants in IFT140. In comparison to other IFT140-cranioectodermal patients, our proband had similar skeletal features among with early onset end-stage renal failure that required kidney transplantation but did not have common ophthalmological features such as retinopathy, optic nerve atrophy, or nystagmus. Following exome sequencing, a splicing variant and exons 27-30 tandem duplication were suspected and further validated. The two other patients with Mainzer-Saldino syndrome that we described displayed a typical clinical picture but a special diagnostic journey. In both cases, at first only one pathogenic variant was detected following panel or exome NGS sequencing. Further WGS was performed for one of them where tandem duplication was found. Screening the third patient for the same tandem duplication was successful and revealed the presence of this duplication. Thus, we suggest that the description of the clinical feature polymorphism in a rare IFT140-cranioectodermal phenotype is extremely important for providing genetic counseling for families, as well as the formation of the correct diagnostic path for patients with a variant in IFT140.

Dynamics of liquids with high viscosity contrast in unevenly rotating Hele-Shaw cell.

The paper is devoted to the experimental study of the dynamics of an interface between two liquids with high viscosity contrast filling a vertical, circular narrow gap rotating about a horizontal axis at a speed modulated by librations. The equilibrium shape and stability of the interphase boundary are considered. In the absence of librations, under the action of the centrifugal force the boundary has an axisymmetric shape. At librations, at certain frequency ratios, the interface loses its axisymmetric position: in the cavity reference frame, it is displaced in the radial direction. It is theoretically shown that the discovered phenomenon is explained by the average action of gravity; the results of experiments and theory are consistent. The experiments reveal that with an increase in the modulation amplitude the circular interface loses stability in a threshold manner: an azimuthally periodic relief, quasi-stationary in the cavity frame, emerges. This is associated with the Kelvin-Helmholtz instability due to tangential oscillations of the less viscous liquid near the interface. A dimensionless parameter that determines the stability of the interface is obtained in the limit of high dimensionless libration frequency. The stability threshold increases with the decrease in the dimensionless frequency. This article is part of the theme issue 'New trends in pattern formation and nonlinear dynamics of extended systems'.

Previously Undescribed Gross HACE1 Deletions as a Cause of Autosomal Recessive Spastic Paraplegia.

Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS, OMIM 616756) is a rare genetic disease caused by biallelic pathogenic variants in the HACE1 gene. Originally, these mutations have been reported to be implicated in tumor predisposition. Nonetheless, via whole exome sequencing in 2015, HACE1 mutations were suggested to be the cause of a new autosomal recessive neurodevelopmental disorder, which is characterized by spasticity, muscular hypotonia, and intellectual disability. To date, 14 HACE1 pathogenic variants have been described; these variants have a loss-of-function effect that leads to clinical presentations with variable severities. However, gross deletions in the HACE1 gene have not yet been mentioned as a cause of spastic paraplegia. Here, we report a clinical case involving a 2-year-old male presenting with spasticity, mainly affecting the lower limbs, and developmental delay. Exome sequencing, chromosomal microarray analysis, and mRNA analysis were used to identify the causative gene. We revealed that the clinical findings were due to previously undescribed HACE1 biallelic deletions. We identified the deletion of exon 7: c.(534+1_535-1)_(617+1_618-1)del (NM_020771.4) and the gross deletion in the 6q16.3 locus, which affected the entire HACE1 gene: g.105018931_105337494del, (GRCh37). A comprehensive diagnostic approach for the patients with originally homozygous mutations in HACE1 is required since false homozygosity results are possible. More than 80% of the described mutations were reported to be homozygous. Initial hemizygosity is hard to detect by quantitative methods, and this may challenge molecular diagnostic identification in patients with spastic paraplegia.

Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel.

Hearing loss is one of the most genetically heterogeneous disorders known. Over 120 genes are reportedly associated with non-syndromic hearing loss (NSHL). To date, in Russia, there have been relatively few studies that apply massive parallel sequencing (MPS) methods to elucidate the genetic factors underlying non-GJB2-related hearing loss cases. The current study is intended to provide an understanding of the mutation spectrum in non-GJB2-related hearing loss in a cohort of Russian sensorineural NSHL patients and establish the best diagnostic algorithm. Genetic testing using an MPS panel, which included 33 NSHL and syndromic hearing loss (SHL) genes that might be misdiagnosed as NSHL genes, was completed on 226 sequentially accrued and unrelated patients. As a result, the molecular basis of deafness was found in 21% of the non-GJB2 NSHL cases. The total contribution pathogenic, and likely pathogenic, variants in the genes studied among all hereditary NSHL Russian patients was 12%. STRC pathogenic and likely pathogenic, variants accounted for 30% of diagnoses in GJB2-negative patients, providing the most common diagnosis. The majority of causative mutations in STRC involved large copy number variants (CNVs) (80%). Among the point mutations, the most common were c.11864G>A (p.Trp3955*) in the USH2A gene, c.2171_2174delTTTG (p.Val724Glyfs*6) in the STRC gene, and c.107A>C (p.His36Pro) and c.1001G>T (p.Gly334Val) in the SLC26A4 gene. Pathogenic variants in genes involved in SHL accounted for almost half of the cases with an established molecular genetic diagnosis, which were 10% of the total cohort of patients with non-GJB2-related hearing loss.

Agro-industrial and fishery complex of the Russian Far East: Data on investment projects and transport connectivity.

In the article, the authors identified the most attractive areas for investment in the Far Eastern Federal District based on statistical data on the agriculture and processing industry. The authors presented a set of secondary data from the Federal State Statistics Service and the Investment Projects Digital Platform, which reflect the cost of implementing projects in the Far Eastern Federal District. These data were presented to characterize the region as deeply diversified, with a predominance of the livestock and fishing sectors. The authors identified the most promising investment projects in various regions of the Far Eastern Federal District and assessed their attractiveness in terms of accessibility to transportation. The result was a map of the implementation of the main areas of investment activity, taking into account transport connectivity. In addition, recommendations have been drawn for the development of agriculture in the Far Eastern Federal District. These recommendations deserve the attention not only of government specialists but also of all stakeholders involved in agricultural production.

Crop production in Russia 2030: Alternative data of the development scenarios.

This article reveals the main indicators of scientific and technological development (gross yield, yield, acreage and average annual prices for crop products) of the crop industry in the long term. Using these indicators, two development scenarios "Technological adaptation" and "Technological breakthrough" of the crop production sector until 2030 were identified. Scenarios for the development of the crop production industry in Russia until 2030 were constructed by means of a correlation and regression analysis. The objectivity of using the obtained regression equations is confirmed by the strong relationship between factors and gross yield. These factors are the basis for determining the gross yield of each crop in 2030. The article also presents the forecast of export volumes of agricultural crops in Russia. Predicted indicators of the Russian crop industry indicate an increase in the volume of seed and organic products.

Crop production in Russia 2030: Scenarios based on data from the scientific and technological development of the sector.

A feature of modern crop production is the acute need to accelerate its scientific and technological development, on the basis of innovative processes. The sector of crop production has an essential dependence on external factors and the modern directions in its scientific and technological development should also reduce dependence on external factors and to improve controllability by reducing the uncertainty of responses to external influences. The methodology of scenario forecasting, adapted to the crop production gives the opportunity to answer the questions such as, for example as: How the determinants of the development of the crop sector will change? What future bifurcation points may occur? What strategic decisions can be made? What consequences these decisions will bring in future? Among the stages of long-term forecasting, the special part is assigned to development of scenarios of development. Scenario prediction allows, based on the available data, to suppose the development and behavior of the object under study in the future. As a result, it becomes possible to develop strategic and tactical solutions based on the implementation of the proposed scenarios. The peculiarity of this method is that it is applicable in situations of uncertainty of the object's reactions to various external influences. The development of scenarios allows to surmount the stochastic nature of the processes occurring in the scientific and technological sphere, to expose large-scale scientific and technological breakthroughs that can significantly change the crop sector. Scenario approach as much as possible forces out uncertainty of choice space between scenarios.