bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using granuated buckwheat husks in urban surface runoff treatment
Authors: Samodolova Olesya A. , Ulrikh Dmitrii V. , Lonzinger Tatiana M. 
Published: April 2023

In recent years, the Russian Federation has paid more attention to protecting the environment from the negative impact of various pollutants. The goal of the Closed Loop Economy federal project, for example, was to stimulate the use of recyclable material. The agro-industrial complex produces a huge amount of waste during the processing of crops. One of these wastes is buckwheat husk. There are a number of studies proving the application of buckwheat husks in large quantities as a sorbent for certain wastewater treatment methods. However, the low strength of husk leads to a number of technological difficulties in operation.
The goal of this study is to increase the performance of buckwheat husks through granulation and evaluate the sorption capacity of granulated buckwheat husks when treating urban surface runoff. In this study we used granulated buckwheat husks produced in a method analogous to fuel pellets. Tests were run on real runoff collected from storm sewers in Chelyabinsk. We determined that granulated buckwheat husks effectively remove pollutants from runoff.
In static conditions at a temperature of 10C to 20C, aluminum was most effectively sorbed upon contact with the sorbate over 168 hours (94.12%). At 0C, slightly less aluminum was sorbed (82.35%). Cobalt, chromium, copper, and zinc are completely extracted from runoff after 3 hours of sorption, regardless of temperature changes.In dynamic test conditions, we determined that the buckwheat husk granules totally extract heavy metals (cobalt, chromium, copper) from storm drain runoff. The concentration of aluminum cations was reduced to 68%. Lower concentrations of sodium and silicon cations were also noted.
Hereditary lung diseases and modern possibilities of genetic testing
Authors: Avdeev S. N. , Kondratyeva E. I. , Namazova-Baranova L. S. , Kutsev S. I. 
Published: April 2023

The European Respiratory Society website gives the following criterion for the disease to be classified as rare (orphan) - the disease occurs in 1 person per 2 000. One of the well-studied rare lung diseases is cystic fibrosis (CF), which is often considered a medical care model for patients with other orphan diseases. However, effective diagnostics and therapies have not yet been developed for many other rare diseases. Moreover, their true prevalence remains unknown because these diseases often go undiagnosed. One of the problems in diagnosing rare diseases is the lack of knowledge among physicians.The aim of this review is to provide a brief clinical and genetic description of rare hereditary lung diseases and to show modern genetic diagnostics to raise awareness among physicians. Data from 95 articles on hereditary lung diseases were used.Results. The results of the analysis of lung diseases associated with bronchiectasis, fibrosis, pneumothorax, and hereditary storage diseases are presented. Genetics and diagnostics, including the three-step molecular genetic testing for cystic fibrosis, are considered in detail. The diagnosis has been developed for both neonatal screening and clinical manifestations. The emergence of targeted therapy based on genetic diagnosis makes neonatal screening even more relevant and leads to an increase in life expectancy. A patient registry was established within 10 years. A detailed analysis of the diagnosis of primary ciliary dyskinesia (PCD) is given, taking into account the absence of a single “golden” standard for the diagnosis of PCD. The genetic basis of the most common hereditary diseases and modern possibilities of their diagnosis are discussed, including sequencing of genes responsible for the development of orphan diseases using standard Sanger sequencing methods and next-generation sequencing, and creating multigene panels.Conclusion. New molecular diagnostic methods will help to understand the nature of orphan lung diseases, study their epidemiology, and develop new diagnostic algorithms. The study of the genetic causes of rare diseases may serve as a basis for the development of targeted therapy.
Russian registry of patients with cystic fibrosis: lessons and perspectives
Authors: Kondratyeva E. I. , Voronkova A. Yu. , Kashirskaya N. Yu. , Krasovsky S. A. , Starinova M. A. , Amelina E. L. , Avdeev S. N. , Kutsev S. I. 
Published: April 2023

A registry of patients with cystic fibrosis (CF) of the Russian Federation has been compiled annually since 2011. Analysis of the national registry with large amounts of clinical and laboratory data helps understand changes in demographic indicators, plan measures to improve the quality of medical care and evaluate their effectiveness.Aim. To analyze health status of patients with cystic fibrosis in the Russian Federation and the dynamics of key clinical and laboratory parameters from 2011 to 2021. Methods. The health status of CF patients was assessed using the registry data from 2011 to 2021.Results. The analysis revealed an increase in the total number of patients from 1,026% in 2011 to 3,969 in 2021, in the number of patients identified by neonatal screening from 28.8% to 53.5%, and in coverage by genetic testing from 91.8 to 93.6%. At the same time, the number of mutations detected dropped from 80 to 90.5% and the number of patients with unidentified mutations decreased from 9.5 to 3.2%. The mean age at diagnosis of cystic fibrosis did not change (3.3 ± 5.5 in 2011 and 3.1 ± 6.2 in 2021) despite an increase in the number of patients diagnosed through neonatal screening. There was a difference in M ± SD age from 2011 to 2021 (11.5 ± 8.9 in 2011 and 14 ± 9.8 in 2021). The proportion of adult patients was 24.95% in 2011 and 27.4% in 2021. The therapy changed over 11 years - the number of courses of intravenous therapy decreased from 70.9 to 36.4%, the number of patients using inhaled antipseudomonal therapy expanded to 45%, the number of patients using hypertonic sodium chloride solution expanded from 8.7 to 70.7%, the use of glucocorticoids decreased. The targeted therapy was introduced in 2018, and the number of patients receiving pathogenetic drugs is growing.Conclusion. The observed changes are indicative of the health status of Russian patients with cystic fibrosis. Analysis of registries helps improve the organization of medical care, predict and implement sanitary and epidemic measures, plan therapy, and assist the regions in organizing outpatient monitoring and microbiological control. The registry is analyzed to organize health care for adult patients.
Function of ion channels of epithelial cells in cystic fibrosis
Authors: Melyanovskaya Yu. L. , Kondratyeva E. I. , Budaeva A. M. 
Published: April 2023

Cystic fibrosis is a systemic hereditary disease caused by mutations in the CFTR gene, which regulates the transport of electrolytes (mainly chloride) across the membranes of the epithelial cells that line excretory ducts of exocrine glands. Dysfunction of the CFTR protein reduces passage of chloride ions through cell membranes and disrupts the passage of sodium ions, bicarbonate ions, and water.The aim of the study was to analyze comprehensively functioning of chloride and alternative (sodium and calcium) channels in the epithelium of patients with cystic fibrosis in relation to the age using functional tests in vitro.Methods. We used data from medical histories of patients with cystic fibrosis and intestinal current measurements.Results. The function of the calcium channel decreased with age in people without cystic fibrosis and carriers of “severe” genotypes. The function of sodium, chloride, and calcium channels was lower in all age groups of patients with cystic fibrosis compared to controls (p < 0.05). When comparing groups of patients with “severe genotype” and “mild genotype”, statistically significant differences were found in response to forskolin (p < 0.05). Patients with “mild” genotypes had a residual function of the CFTR channel which decreased with age.Conclusion. For the first time, the functioning of chloride and alternative channels in cystic fibrosis have been described in relation to the age and the genotype of patients.
Efficacy of CFTR modulators in clinical practice (6-month follow-up)
Authors: Kondratyeva E. I. , Odinaeva N. D. , Zhekaite E. K. , Pasnova E. V. , Fatkhullina I. R. , Maksimycheva T. Yu. , Sherman V. D. , Kutsev S. I. 
Published: April 2023

Pathogenetic therapy for the treatment of cystic fibrosis (CF) has been developed that modulates the CFTR protein and restores its activity as a chloride channel. This treatment is represented by CFTR modulators for various genotypes covering 85 - 90% of patients with CF.The aim was to analyze the efficacy of two targeted drugs in patients aged 6 - 18 years with CF in clinical practice during a 6-month follow-up.Methods. The study was conducted based on the analysis of the database “CF Patient Registry of the Russian Federation” for 2021 - 2022. The study included 178 patients receiving lumacaftor/ivacaftor and 158 patients receiving elexacaftor/tezacaftor/ivacaftor. Respiratory function indicators (FEV1, FVC), sweat test, and anthropometric data were analyzed.Results. In the group of children treated with lumacaftor/ivacaftor, Me (Q1 - Q3) body weight (kg) increased at 6-month follow-up from 40.0 (28.9 - 48.0) to 44.9 (29.3 - 50.8), p < 0.001, and the height (cm) increased from 156.0 (140.0 - 161.0) to 158.0 (143.0 - 162.0),p < 0.001. Me (Q1 - Q3) FEV1 improved from 63.5 (42.3 - 84.8) to 72.0 (56.9 - 82.4) %,p < 0.045. Sweat test (mmol/l) decreased Me (Q1 - Q3) from 115 (101.0 - 123.0) to 86.5 (79.0 - 103.0), p < 0.001. During therapy with elexacaftor/tezacaftor/ ivacaftor, Me (Q1 - Q3) body weight (kg) increased at 6-month follow-up from 44.4 (36.8 - 50.0) to 49.3 (44.1 - 51.9),p < 0.001, and Me (Q1 -Q3) height (cm) increased from 160.5 (152.3 - 165.1) to 163.0 (155.5 - 166.9),p < 0.001. Me (Q1 - Q3) FVC and FEV1 improved: FVC from 78.5 (60.9 - 91.0) to 90.5 (76.8 - 106.8) %,p < 0.001, FEV1 from 73.5 (60.5 - 82.1) to 95.0 (65.3 - 107.0) %,p < 0.001. Sweat test (mmol/l) decreased from 119 (108 - 126) to 75.5 (65.3 - 88);р < 0.001.Conclusion. Health status indicators of of children with CF aged 6 - 18 years were analyzed for 6 months of targeted therapy (lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor). Positive changes were observed in weight, height, respiratory function, and sweat test.
Characteristics of patients with primary ciliary dyskinesia
Authors: Nikolaeva E. D. , Ovsyannikov D. Yu. , Strel’nikova V. A. , Polyakov D. P. , Tronza T. V. , Karpova O. A. , Fatkhullina I. R. , Bragina Е. E. , Shchagina O. A. , Starinova M. A. , Krasovskiy S. А. , Kyian T. A. , Zhekaite E. K. 
Published: April 2023

Primary ciliary dyskinesia (PCD) (Online Mendelian Inheritance in Man - OMIM - #242650) is a rare hereditary disease, which is based on a defect in the ultrastructure of the cilia epithelium of the respiratory tract which leads to the motor function disorder. Data about health characteristics of patients with PCD in the Russian Federation are incomplete.The aim of the study was to investigate the clinical, laboratory, and instrumental characteristics of patients with PCD.Methods. The data of 90 patients (22 adults (24.4%) and 68 children (75.6%)) from several medical centers were studied. The following methods were used: medical history, spirometry, microbiological examination of the respiratory tract, video microscopic analysis of the functional activity of the nasal mucosa ciliated epithelium, transmission electron microscopy of the ciliated epithelium, and DNA testing.Results. The median age at diagnosis was 17.0 years for adults and 5.0 years for children. Kartagener syndrome was detected in 23 (27%) people, including 6 (26.0%) adults. Hearing loss was noted in 5 (26.3%) adult patients and 15 (26.8%) children. Light microscopy of the ciliated epithelium was performed in 14 (82.3%) children and 3 (17.7%) adults. In 12 patients, cilia motor activity was not registered at each of the magnifications (x 100, x 400, x 1,000). Transmission electron microscopy showed that absence ofinternal and external dynein handles (51%) and absence of internal dynein handles (17.9%) were the most common disorders. DNA testing was performed in 55 (61.2%) patients: 16 (29.1%) adults and 38 (70.9%) children. The most common genetic variants were found in the DNAH5 and HYDIN genes. Lung function was reduced in both adults and children, but a significant decrease was noted in adult patients. P. aeruginosa predominated in the culture and accounted for 21.3% (intermittent detection in 13.2%, persistent detection in 9%). It has increased resistance to antibiotics.Conclusion. The results correlate with the European data. Infection caused by P. aeruginosa with the increased resistance to antibiotics was prevalent in patienths with PCD.
Ciliated cell cultures for diagnosis of primary ciliary dyskinesia
Authors: Demchenko A. G. , Smirnikhina S. A. 
Published: April 2023

Primary ciliary dyskinesia (PCD) is a hereditary autosomal recessive disease that results in a defect in the ultrastructure of epithelial cilia. To date, there is no single diagnostic test for PCD, so the diagnosis is based on the results of multiple tests, such as DNA diagnostics, assessment of nasal nitric oxide levels, ciliary beat frequency (CBF) in nasal biopsy, ciliary ultrastructure, etc. Diagnosis of PCD can be difficult due to secondary damage to the airway epithelium, leading to undiagnosed or false positive cases.The aim of this work was to review studies on the cultivation of human nasal epithelial cells and subsequent differentiation into ciliated cells for the diagnosis of PCD.Conclusion. In vitro ciliogenesis helps to make a correct diagnosis of PCD while avoiding false positives. There are three different methods of ciliogenesis in vitro: the suspension culture method, the ALI culture method, and the organoid culture method. Each method of ciliogenesis has its own advantages and disadvantages. The ALI culture method is the most widely used. It produces a sufficient number of ciliated cells for diagnosis, which can be maintained in culture for a long time. The obtained cultures of nasal epithelial ciliated cells allow to analyze the ultrastructure of cilia, to evaluate CBF and localization of ciliary proteins, which helps in the diagnosis of PCD.
Randu - Osler - Weber disease (or hereditary hemorrhagic teleangectasia) with respiratory involvement
Authors: Mizernitskiy Yu. L. , Shatokha P. A. , Sokolova L. V. 
Published: April 2023

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominantly inherited disease characterized by various vascular defects, including nosebleeds, dilation of blood vessels (telangiectasias), and arteriovenous malformations (AVMs) in the lungs and other internal organs. Pulmonary AVMs are observed in 15 - 50% of patients with HHT. The disease manifests in childhood, with the severity of clinical manifestations increasing throughout the patient’s life. The eponymous name of Randu - Osler - Weber disease comes from the surnames of the physicians who first described it in the mid-19th century. Despite some progress in understanding its etiology and pathogenesis, treatment tactics remains incomplete.The aim of this review is to systematize information on the etiology, diagnosis, and treatment of HHT. This review presents the current status of the problem, lists the main diagnostic tests and the principles of pharmacological and surgical treatment.Conclusion. The polyorganic lesions in HHT require an interdisciplinary approach to the management of these patients both in childhood and in adulthood. With the discovery of the genetic basis of the disease, pathogenetic therapy with humanized monoclonal antibodies seems promising. However, this therapy requires further research.
Description of the clinical picture and assessment of functional activity of the CFTR channel in a patient with a complex allele [S466X; R1070Q]
Authors: Krasnova M. G. , Melianovskaya Yu. L. , Krasovskiy S. A. , Bulatenko N. V. , Efremova A. S. , Bukharova T. B. , Goldshtein D. V. 
Published: April 2023

The presence of pathogenic variants in the CFTR gene causes cystic fibrosis (CF) through various molecular mechanisms that affect the formation and functional activity of the CFTR chloride channel. An important factor affecting the phenotypic manifestations of CF and the effectiveness of targeted therapy is the presence of complex alleles with > 2 consecutive mutations per 1 allele, or in the cis position. The influence of complex alleles on the manifestations of CF has not been sufficiently studied globally due to the small number of studies.The aim of the study was to investigate the influence of the complex allele [S466X; R1070Q] on the phenotypic manifestations of CF and the effectiveness of targeted therapy in a model of intestinal organoids from a patient with [S466X; R1070Q]/CFTRdele2,3 genotype.Methods. We used medical history data, intestinal current measurement, intestinal organoid method, and forskolin test.Results. The progressive nature of the disease with a clear degradation of lung function was established. The ICM method showed absent chloride channel function. The tests on the culture of organoids obtained from the intestinal tissue indicated a complete loss of the chloride channel function. In addition, the complex allele [S466X; R1070Q] was insensitive to all targeted drugs tested.Conclusion. The complex allele [S466X; R1070Q] causes a complete loss of the functional CFTR protein and is not sensitive to any of the approved targeted drugs.
Primary ciliary dyskinesia in a young woman: case report with challenged transition from pediatrics to adult network
Authors: Zinchenko A. V. , Gembitskaya T. E. , Bondarenko I. B. 
Published: April 2023

Primary ciliary dyskinesia (PCD) is a rare genetic autosomal recessive disease associated with a defect in the ultrastructure of epithelial cilia. Currently, there is no standard method for diagnosing PCD, so the diagnosis is based on the clinical picture and the results of tests, such as DNA diagnostics, nasal nitric oxide measurements, ciliary beat frequency in a nasal biopsy, ciliary ultrastructure, etc. Diagnosis of PCD can be difficult due to secondary damage to the respiratory epithelium, which often results in undiagnosed or false positive cases. Differential diagnosis with diseases forming widespread bronchiectasis (BE) and upper respiratory tract lesions, especially with cystic fibrosis (CF), is necessary.The aim of this paper is to introduce the difficulties of diagnosis, the appropriate level of detail of the clinical, laboratory and instrumental characteristics over a long period of time, and the organization of care for a patient with PCD. This article describes a clinical case of PCD in a young woman, diagnosed at the age of 17, presents the difficulties and typical mistakes in the management of such patients, and the lack of succession of pediatrician-pulmonologist care.Conclusion. The presented clinical case demonstrates how difficult the diagnosis of PCD is. Such patients need a complex examination, a thorough differential diagnosis to exclude other diseases with a similar clinical picture. Long-term follow-up is carried out by a multidisciplinary team with mandatory microbiological monitoring. The organized care for patients should begin in early childhood and continue in adulthood with proper succession of care and follow-up by of pulmonologist, preferably in specialized centers.
A rare variant of primary ciliary dyskinesia in combination with hereditary hemorrhagic telangiectasia type 1: a case from practice
Authors: Shatokha P. A. , Novak A. A. , Shudueva A. R. , Mizernitskiy Yu. L. , Groznova O. S. 
Published: April 2023

Primary ciliary dyskinesia (PCD) is a rare genetic disease belonging to the group of ciliopathies. The disease develops because a defect in the ultrastructure of the epithelial cilia in the respiratory tract and similar structures (sperm flagella, villi of the fallopian tubes, ventricular ependyma, etc.) disturbs their motor function. Currently, various clinical and genetic variants of the disease are distinguished, increasing the effectiveness of dynamic examination and treatment.Aim. In this article, we describe a patient with a rare variant of PCD that we identified in combination with a mutation in the ENG gene responsible for the development of hereditary hemorrhagic telangiectasia type 1 (HHT-1). HHT-1 is a rare hereditary disease that manifests as various vascular dysplasias, including arteriovenous malformations (AVM) in the lungs, which can significantly worsen the course of the disease and be a predictor of an unfavorable outcome.Conclusion. The presented case demonstrates a combination of two rare genetic diseases in a child. The uniqueness of the case also lies in the fact that the identified rare mutation in the DRC1 gene responsible for the development of PCD is not associated with a loss of motility of the cilia of the ciliated epithelium, which makes the testing and the correct diagnosis even more difficult.
Primary ciliary dyskinesia in a child with type II Simpson -Golabi - Bemel syndrome due to OFD1 gene mutation
Authors: Strelnikova V. A. , Tsverava A. G. , Ovsyannikov D. Yu. , Zhekaite E. K. , Kondakova O. B. , Berejansky P. V. , Savostyanov K. V. , Gorev V. V. , Airapetyan M. I. , Topilin O. G. 
Published: April 2023

Primary ciliary dyskinesia (PCD) is an orphan disease associated with mutations in several genes. It is a ciliopathy, an abnormality of the cilia and flagella. Ciliopathies include the extremely rare Simpson - Golabi - Bemel syndrome (SSGB) type II.The aim of this article is to familiarize the reader with the possibility of simultaneous presence of type II SSGB and PCD in a patient with bronchiectasis (BE).Results. The first clinical observation in the Russian literature is presented withhistory, physical examination, including clinical and morphologic examination, results of additional investigations and initiation of therapy. The case describes a 15-year-old patient with BE and other lesions typical of PCD confirmed on the basis of structural changes in the cilia of the respiratory epithelium of the trachea detected by transmission electron microscopy. The patient had a pathogenic mutation of the OFD1 gene responsible for the development of both type II SSGB and PCD.Conclusion. Several variants of ciliopathies may occur in one patient, and PCD may present as a syndrome.
Clinical case of a patient with Prader - Willi syndrome
Authors: Nuralieva G. S. , Kryuchkova K. Yu. , Anokhina V. M. , Bolotskaya A. A. , Kozhevnikova M. M. , Avdeev I. S. , Nekludova G. V. , Gaynitdinova V. V. , Khaziakhmetova M. R. , Avdeev S. N. 
Published: April 2023

Prader — Willi syndrome (PWS) is a rate multisystem disease caused by a developmental disorder of the nervous system. The syndrome is associated with an imprinting defect, i.e. lack of expression of paternal genes on chromosome 15 q11.2q13.1. This genetic defect leads to cognitive and behavioral disorders; hypothalamic dysfunction; endocrine, cardiovascular, musculoskeletal, respiratory, and other disorders. PWS is the most frequent cause of hereditary obesity. In turn, the obesity causes the obesity-hypoventilation syndrome and respiratory failure.The aim of this article was to describe a clinical case of 28-year-old female who presented with acute hypercapnic respiratory failure.Conclusion. The patient was treated with respiratory support (non-invasive ventilation). The timely diagnosis and treatment of respiratory failure is important for the outcome as it can improve the patient’s quality of life and the life expectancy.