bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental germline mosaicism in genome-wide phased de novo variants: recurrence risk assessment and implications for precision genetic counselling
Authors: Lecoquierre François , Drouot Nathalie , Coutant Sophie , Quenez Olivier , Fourneaux Steeve , Jumeau Fanny , Rives Nathalie , Charbonier Françoise , Derambure Celine , Boland Anne , Olaso Robert , Meyer Vincent , Deleuze Jean-François , Goldenberg Alice , Guerrot Anne-Marie , Charbonnier Camille , Nicolas Gaël 
Published: August 2024

Abstract

Background:
De novo mutations (DNMs) significantly impact health, particularly through developmental disorders. DNMs occur in both paternal and maternal germlines via diverse mechanisms including parental early embryonic mosaicism, which increases recurrence risk for future pregnancies through germline mosaicism. Embryonic mosaicism is divided based on primordial germ cell specification (PGCS): pre-PGCS events may affect both germline and somatic tissues, while post-PGCS events are only found in the germline. The specific contribution of germline mosaicism to DNMs across the genome is not well defined. We aimed at categorizing DNMs and their recurrence risk by detecting a large set of DNMs followed by systematic deep sequencing of parental blood and sperm DNA.
Methods:
We performed trio-based short-read genome sequencing for initial DNM detection and long-read genome sequencing for phasing, followed by high-depth targeted sequencing of parental blood and paternal sperm to detect germline mosaicism.
Results:
We detected a total of 428 DNMs (on average 85.6 per trio, n = 5 trios), with an expected paternal bias of 80%. Targeted resequencing of parental blood and sperm (depth > 5000x) unveiled 20/334 parental germline mosaics (2–5 per trio) with variant allele fractions (VAFs) ranging from 0.24–14.7%, including 7 that were detected in paternal sperm exclusively (1–2 per trio). We estimate that individual genomes harbour about 2 paternal and 2 maternal pre-PGCS DNMs and 2 paternal post-PGCS DNMs (detectable in sperm only). Due to paternal bias, maternally phased variants appear 3.4x more likely to be mosaic in blood. By using average VAFs in sperm as a direct indicator, we estimate recurrence risk of genome -wide paternally phased de novo variants to be 0.3%, prior to any sperm sequencing assessment. This estimate is an average between a majority of variants with a null recurrence risk and a handful of variants with a high recurrence risk.
Conclusions:
Genetic counselling of DNM may not rely anymore on empirical estimates of recurrence risk. Sperm sequencing may be an effective method to reliably specify the recurrence risk of most individual DNMs. Long-read sequencing, allowing the phasing of DNMs, may also become critical in this process.
Enhanced seismic mitigation through energy management using nonlinear energy sinks with clearance–contacts
Authors: Gzal Majdi O. , Gendelman Oleg V. , Bergman Lawrence A. , Vakakis Alexander F. 
Published: August 2024

Abstract

This study investigates the implementation of non-smooth nonlinear energy sinks, namely with clearance-contacts (CC-NESs), for passive seismic mitigation of a 1D shear frame (primary) structure. To this end, two nonparasitic (in the sense that they do not add extra mass into the structure) local NESs incorporating single-sided clearance contacts are introduced, one at each of the top two stories of the structure. We investigate the nonlinear management of seismic input energy to the primary structure, showcasing the effectiveness of the CC-NESs compared to classical tuned mass dampers (TMDs). Utilizing historical earthquakes scaled for severe excitation, a multi-task optimization approach is employed to determine optimal CC-NESs design parameters, with the main objectives to decrease the input seismic energy and maintain low overall acceleration levels. The results show that the implementation of non-smooth CC-NESs yields significant benefits, exceeding those of TMDs which are linear and narrowband devices. First, due to the action of the CC-NESs a drastic reduction of seismic input energy into the primary structure is achieved compared to that of the corresponding unprotected structure. Second, the CC-NESs facilitate rapid, robust, and irreversible targeted energy transfer (TET) from the primary structure to the local CC-NESs, leading to passive energy confinement and local dissipation. Third, the clearance nonlinearities induce intermodal targeted energy transfer (IMTET) from low to high-frequency structural modes of the primary structure, thereby enhancing energy dissipation performance even during the initial cycles of the structural response, i.e., in the critical highly energetic regime of the seismic response. Remarkably, such enhanced seismic mitigation performance of the CC-NESs is achieved while simultaneously maintaining low acceleration levels. This performance is attributable to the synergy of TET-based NES and IMTET, occurring in the physical and modal spaces, respectively. Lastly, we demonstrate robustness performance of the optimized CC-NESs across a broad spectrum of seismic input energy levels and frequency content, even under severe ground excitations. Further extensions of this methodology to 2D are discussed.
Detection of multi-residue insecticides in bitter gourd using Glutathione-S-Transferase enzyme based different analytical techniques
Authors: Mawtham M. M. , Bhuvaneswari K. , Thirumalairajan S. , Suganthi A. , Kulanthaisami S. , Subramanian K. S. 
Published: August 2024

Abstract

The food safety issues related to the pesticide residues in agricultural produce have increased the demand for instruments that can rapidly, sensitively, and selectively detect pesticide residues in food commodities. This idea served as the impetus for the development of protocols for the detection and quantification of various insecticide residues using GST-based biosensor probes. We demonstrated the effectiveness of GST-based biosensor and compared with analytical methods such as GC-MS/LC-MS for application in detection of multi-residue insecticides viz., synthetic pyrethroid and neonicotinoid in bitter gourd samples. Spectrophotometric analysis was confirmed from Michaelis-Menten constant (Km) and maximum velocity (Vmax) in the range 0.00178–0.00767 M and 0.01519–0.05249 mM/s for six different insecticides. Further, GST-based biosensor for the detection of various insecticides showed good linear curve (R2 > 0.98) in the range from 0.01 to 0.5 mg kg− 1 with LOD and LOQ calculated in 0.01 and 0.05 mg kg− 1. Method validation parameters namely linearity, recovery inhibition were calculated 1.83–65.10%, accuracy (71–100%) and precision (RSD < 6.0%), respectively. Among the 20 farmgate and market samples subjected to different techniques, imidacloprid residues were detected in four bitter gourd samples ranging from 0.042 to 0.099 mg kg− 1 in LC-MS and 0.050–0.10 mg kg− 1 for three samples in GST-based biosensor techniques.
Efficiency of identification of tuberculosis in high-risk groups of the population under extreme conditions conducive to the formation of an epidemic situation
Authors: Kolomietz V. M. 
Published: August 2024

An analytical review of scientific literature, international acts and Russian regulatory documents on the issues of implementation of anti-epidemic actions in tuberculosis among the general population and, on a priority basis, in high-risk groups – migrants (refugees and resettlers) are presented. The review is aimed to raise awareness among readers about the RF regulatory environment on this issue, as well as the results of research on migrants’ access to the measures on early detection, diagnosis, prevention and treatment of tuberculosis in Russia. The features of identification of disease cases among migrants have been determined based on the results of observation of the formation of an epidemic situation in the border region of the Russian Federation under extreme conditions and development of a pandemic. In the period before, during the development and after the pandemic, 2268 newly diagnosed and recurrent tuberculosis patients were followed-up, who were identified using various approaches and diagnostic methods: radiation (fluorography + radiography), bacteriological, molecular and genetic, computed tomography, histological studies. There are interesting data on the use of immunological methods. The conclusions: the created regulatory environment to identify, treat and prevent the spread of tuberculosis in the country, including high-risk groups such as migrants/refugees, among whom there are many children, ensured the implementation of controlled anti-epidemic actions under extreme conditions conducive to the formation of an epidemic situation; extreme conditions, including a pandemic/ epidemic of other etiologies, affected the formation of the epidemic situation of tuberculosis, as well as among children and adolescents, in the region; the efficiency of immunological methods, primarily the recombinant tuberculosis allergen, in the high-risk groups under consideration has been proven.
Endosurgical technologies in the treatment of children with intestinal obstruction
Authors: Korovin S. A. , Dzyadchik A. V. , Donskoy D. V. , Akopyan M. К. , Sokolov Yu. Yu. 
Published: August 2024

Introduction. In recent years there has been an increase in the number of cases of postoperative adhesive intestinal obstruction among children after surgical interventions due to congenital anomalies of the gastrointestinal tract, traumatic injuries and abdominal masses. The laparoscopic technology opportunities are directly related to the type of obstruction and the severity of the patients’ condition on admission. The rationale for laparoscopic technologies will help improve the outcomes of surgical treatment of children with various types of intestinal obstruction.Aim. To evaluate the effectiveness of laparoscopic technologies in a group of children with intestinal obstruction.Materials and methods. The study included 88 patients who underwent surgery for intestinal obstruction from 2008 to 2022 at the age of 1 month up to 18 years (7.75 ± 4.62). The patients were divided into two groups: Group I – obstructive intestinal obstruction (51) and Group II – strangulating intestinal obstruction (37). Methods for personalized evaluation of the options for endosurgical interventions were created based on the coefficients of the Bayesian decision rule characteristics.Results and discussion. The method for personalized evaluation of the options for endosurgical intervention completion in the form of laparoscopic version was proposed on the basis of the analysis of clinical and anamnestic data, outcomes of instrumental approaches to preoperative diagnosis and laparoscopy in a group of patients with intestinal obstruction. Laparoscopic technology has proved to be effective in the groups of patients with obstructive and strangulation intestinal obstruction in 70 and 62.2% of follow-ups, respectively.Conclusion. The effectiveness of laparoscopic technologies in children with intestinal obstruction depends on the patients’ group-specific decision rule characteristics of the method for personalized evaluation of the options for endosurgical interventions and accounts for 66% (Sn – 90%; Se – 85%; ACC – 85.8%). The method for personalized evaluation of the options for endosurgical interventions is a highly informative test for a group of patients with intestinal obstruction (AUC – 92.2%).
A child with diabetes in school and kindergarten: results of the all-russian sociological study “ROSTOK-2023”
Authors: Saverskaya E. N. 
Published: August 2024

Introduction. Type 1 diabetes in children creates difficulties and requires certain conditions for control while attending school/ kindergarten, while children should receive education without any restrictions.Aim. To identify problems and assess the needs of children with type 1 diabetes mellitus and their parents during their stay in preschool and general education organizations.Materials and methods. A sociological online survey of 684 parents of children with diabetes was conducted in September- October 2023 in 8 federal districts of Russia. The electronic questionnaire contained 117 questions on 9 main blocks of studying the problems of children staying in schools/kindergartens.Results. The age of children is from 2 to 18 years (median – 9.9 years); gender of children: female – 50.9%, male – 49.1%; diabetes experience – from 1 month. up to 15 years (median – 3.6 years). Parents consider the main problems to be difficulties with organizing meals (54.7%), administering insulin (52.8%), controlling glycemia (44.9%), their own fear (41.2%), and mistrust of teachers (20.8%) and nurses (11.1%), administrative barriers (29.4%). Teachers do not have sufficient knowledge about diabetes in children (78.5%), teaching aids (53.0%), regulations on their responsibilities when accompanying children (46.0%), 54.8% of them are afraid, 87.9% cannot help a child in an emergency. Parents are concerned about the lack of nurses (80.1%) and a separate room for self-monitoring (47.7%) at school. According to parents, educational organizations need awareness-raising work (85.8%) and support from an assistant/tutor (56.5%) for children with diabetes.Conclusion. It is possible to solve the identified problems through the cooperation of teachers, parents and children, endocrinologists, psychologists, social workers and government authorities who can remove barriers and create conditions for a comfortable stay for children with diabetes in educational organizations.
The effect of cholecalciferol subsidies on the level of pro-inflammatory cytokines in children with bronchial asthma
Authors: Dolbnya S. V. , Tolkunova A. A. , Zakharova I. N. , Ponamaryova V. R. , Klimov L. Ya. , Barycheva L. Yu. , Zaritovskaya N. V. , Kuznetsova V. V. , Enina E. A. 
Published: August 2024

Introduction. Currently, there are insufficient studies to demonstrate the effect of vitamin D status on the production of proinflammatory cytokines in children with allergic diseases, which precipitated this study.Aim. To analyse interferon-γ, interleukin-17A and 33 profiles in children with asthma according to serum calcidiol levels before and during cholecalciferol subsidies.Materials and methods. A total of 71 children aged 3 to 18 years were examined: 51 patients with asthma and 20 children in the control group. A 3-month cholecalciferol course at a prophylactic dose specified in the national program was prescribed to all children. 25(OH)D, interferon-γ, interleukin-17A and 33 levels were twice determined in the examined children.Results and discussion. Median 25(OH)D levels in patients with asthma did not reach the levels of healthy children either before or after cholecalciferol subsidies at prophylactic doses. Vitamin D intake led to a decrease in interferon-γ levels in healthy children from 3.07 [2.29; 4.81] pg/ml to 2.18 [1.74; 3.45] pg/ml (p < 0.05). In patients with asthma, such changes were not detected in the initial population, however, after cholecalciferol subsidies their interferon-γ levels were significantly higher than those in healthy children: 3.11 [0.89; 5.0] pg/ml and 2.18 [1.74; 3.45] pg/ml, respectively (p < 0.05). Assessment results of interleukin-17A levels in children with asthma showed that the median cytokine levels were significantly higher before the cholecalciferol subsidies than after them: 2.03 [0.1; 10.01] pg/ml and 0.96 [0.1; 12.87] pg/ml, respectively (p = 0.03). The median interleukin-17A levels in children with asthma were significantly higher than in healthy children, both before and during the cholecalciferol subsidies. The median interleukin-33 levels were significantly higher in children with asthma as compared to healthy children, both before and during vitamin D subsidies.Conclusion. Our results suggest that cholecalciferol has a modulatory effect on interferon-γ and interleukin-17A in patients with asthma. Interleukin-33 levels did not change significantly in children with asthma on cholecalciferol.
Experience of using a combination of herbal preparations in the treatment of acute rhinosinusitis in children
Authors: Karpishchenko S. A. , Rodneva Iu. A. , Ekushov K. A. 
Published: August 2024

Introduction. Rhinosinusitis, along with adenoiditis, holds leading positions in terms of incidence among adults and children. About 10 million cases of rhinosinusitis per year are reported in Russia.Aim. To study the effectiveness and safety of secretolytic drugs in the treatment of acute rhinosinusitis in different groups of patients, features of the course of rhinosinusitis in patients with concomitant disorders of the immune system.Materials and methods. A total of 98 medical records of children with acute sinusitis that was diagnosed by an otolaryngologist during the initial examination based on complaints, past medical history data and paranasal sinuses x-rays were selected for analysis. Of these, 60 children aged 3 to 15 years (23 girls and 37 boys) were included in Group 1. 38 immunocompromised children aged 3 to 12 years (18 girls and 20 boys) were included in Group 2.Results. In the group of patients without oncohematological diseases (Group 1), the average duration of bacterial sinusitis was from 6 to 12 days, if the standard treatment regimen was ussed; if therapy included Sinupret complex-action herbal medicine, children were ill for an average of 6.46 days, and the average duration of the disease in patients who did not receive the herbal medicine was 3 days longer, totalling to 9.54 days. Patients with various immunocompromising diseases, who received specific immunosuppressive therapy, on average were ill significantly longer – from 8 to 16 days on systemic antibacterial therapy. Moreover, the average duration of sinusitis in patients, who additionally used Sinupret was 7.5 days, which was almost 5 days less (12.4) than in patients, who received treatment without Sinupret herbal medicine. The article also presented the results of treatment of patients receiving several immunosuppressive drugs, who had a graft-versus-host reaction, cytopenia and other unfavorable factors.Conclusion. The inclusion of the herbal medicine with complex action in the treatment regimen significantly improves the positive effect of therapy, reduces the duration and intensity of clinical presentations, even if a patient has immunological diseases and immunocompromising conditions.
Features of the parietal and cavity intestinal microbiota in infants born to mothers with bronchial asthma, depending on the mode of delivery
Authors: Kosenkova T. V. , Novikova V. P. , Boytsova E. A. , Kelmanson I. A. , Zazerskaya I. E. , Lavrova O. V. , Boldyreva M. N. 
Published: August 2024

Introduction. Intestinal microbiota is a complex and unique system in its composition, performing a huge number of diverse functions in the body. Its formation begins in utero.Aim. To study the features of the parietal and cavity intestinal microbiota in children born to mothers suffering from moderate bronchial asthma, depending on the mode of delivery.Material and methods. A prospective longitudinal study was carried out, which included children from the first day of life to 12 months. A total of 68 children at high risk of atopy (HRA) from mothers with asthma were included, of whom 22 were born by cesarean section and 46 were born through the vaginal birth canal. Qualitative and quantitative analysis of GM was carried out by real-time PCR with group- and species-specific primers: in the examined children, the dynamics of 4 phylums including 31 microorganisms was assessed. The child’s feces and brush-biopsy were taken from the rectum at 7 control points of measurement.Results and discussion. The data obtained showed that the method of delivery has an impact on the formation of the intestinal microbiota: in children born by cesarean section, in the parietal microbiota, starting from the age of 1–2 months, and in the cavity microbiota – 3–4 months, representatives of phylum Firmicutes (Clostridium leptum gr m.). In children born through the vaginal birth canal, all the first 8 months of life in the cavity and parietal microbiota were dominated by representatives of phylum Bacteroidetes (Bacteroides spp., Prevotella spp.). Clostridium leptum can be a marker of an inflammatory process in the intestinal mucosa in children at high risk of atopy. The research conducted over the past few years has found that Clostridium leptum promotes the secretion of anti-inflammatory (IL-10 and IL-12) and inhibition of the production of pro-inflammatory (IL-8) cytokines, and also boosts the number of Treg cells.Conclusion. The mode of delivery in children with a high risk of atopy is an additional epigenetic factor that influences the nature of both the parietal and cerebrospinal microbiota.
Diagnostic value of serological markers for celiac disease in children
Authors: Dmitrieva Yu. A. , Zakharova I. N. , Osmanov I. M. , Gostyukhina A. D. , Teslenko S. E. , Radchenko E. R. , Miyanova A. R. , Scorobogatova E. V. 
Published: August 2024

Introduction. Serologic tests are the main tool to screen for celiac disease. The serologic tests for tissue transglutaminase (tTG-IgA) antibodies combined with the assessment of the total serum IgA concentration is recommended as a primary test. Other serological markers, in particular IgA and/or IgG antibodies against deamidated gliadin peptides (DGP-IgG/IgA) and native gliadin (AGA-IgA/IgG), are not recommended for use in diagnosing celiac disease in immunocompetent patients.Aim. To determine the diagnostic value of serological markers during the initial examination for celiac disease in children.Materials and methods. The sensitivity, specificity, positive and negative predictive value of tTG-IgA/IgG, DPG-IgA/IgG, AGA-IgA/IgG were calculated for a group of 1247 children.Results. Celiac disease was diagnosed in 101 patients of the study group. Tissue transglutaminase IgA antibodies demonstrated the highest sensitivity, specificity, positive and negative predictive values of 98.02, 99.48, 94.29 and 99.82%, respectively. DPG-IgA/IgG, AGA-IgA were inferior in sensitivity and specificity to tTG-IgA, the positive predictive value of DGP-IgG and AGA-IgA was 34.62 and 34.21%, respectively. AGA-IgG showed the worst specificity (40.3%) and positive predictive values (12.41%).Discussion The low predictive value of the positive results of AGA IgA and DPG IgG determines the extremely high percentage of false-positive results for these tests. In none of the cases of an isolated elevation in AGA and DPG antibodies the diagnosis of celiac disease was confirmed, if tissue transglutaminase IgA antibody concentrations were normal.Conclusion. The results of our study are fully consistent with the position of modern clinical guidelines, demonstrating the maximum diagnostic value of tissue transglutaminase IgA antibody during examination for celiac disease. Other antibodies are not recommended for use in the screening process to avoid unnecessary referrals of patients for endoscopic examination and to reduce healthcare costs.