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Along with horizontal drilling techniques, multi-stage hydraulic fracturing has improved shale gas production significantly in past decades. In order to understand the mechanism of hydraulic fracturing and improve treatment designs, it is critical to conduct modelling to predict stimulated fractures. In this paper, related physical processes in hydraulic fracturing are firstly discussed and their effects on hydraulic fracturing processes are analysed. Then historical and state of the art numerical models for hydraulic fracturing are reviewed, to highlight the pros and cons of different numerical methods. Next, commercially available software for hydraulic fracturing design are discussed and key features are summarised. Finally, we draw conclusions from the previous discussions in relation to physics, method and applications and provide recommendations for further research.

The aim of the article is to solve the scientific problem of outlining the issue of protection of patent law objects created using artificial intelligence technologies, and to establish whether it is possible to recognize artificial intelligence technologies as inventor at the present stage of development of legal systems. Philosophical, comparative-legal and system-structural methods were used in the research process. Based on the analysis of the European Patent Convention, the main generally accepted conditions of patentability of the invention are determined: novelty, inventive step, industrial applicability. It has been established that inventions created by artificial intelligence technologies will meet such criteria provided that certain requirements are met. In the context of the study, the case of the invention of artificial intelligence «DABUS» is analyzed and the results of its consideration in the European Patent Organization, the United Kingdom and the United States are summarized. In particular, it has been established that artificial intelligence technologies are currently not considered as inventors in either the Romano-Germanic or Anglo-Saxon legal systems.

Nowadays dental caries and periodontal diseases are among the most pressing problems in Paediatric Dentistry. Young patients with psychoneurological disorders are a special category among children with somatic pathology. At the same time, the issue of providing dental care to such children is underrepresented. Today, traditional schemes used for the prevention and treatment of caries and periodontal disease in children with mental retardation requires further improvement taking into account the clinical status of children with particular forms of mental retardation, including oligophrenia. Thus, the aim of our study was to develop and evaluate the effectiveness of a complex of measures to prevent dental caries in children with oligophrenia. To assess the effectiveness of the elaborated preventive complex, 56 children aged 12 years with the diagnosis of oligophrenia of I degree of severity (mild mental backwardness) were under observation during 2 years; 27 children received the complex we developed. The group of comparison included 29 children; caries prevention measures for these children were based on regional protocols (hygienic education, keeping oral hygiene, use of fluoride toothpastes). The effectiveness of the developed preventive complex was evaluated 6, 12 and 24 months after the beginning of its implementation according to the following criteria: the growth of dental caries intensity; reduction in the growth of dental caries intensity; level of oral hygiene (OHI-S index); changes in the biocenosis of the oral cavity (in 1 and 6 months of the observation). The results of the examination after the 6 month observation period have shown the dental caries intensity in children of the main group is 6.65 ± 0.45 teeth that is 1.02 times lower than in the children of the comparison group (6.79 ± 0.26 teeth, p ˃0.05). Thus, the growth of dental caries intensity in the children of the main group is, on average, 0.41 ± 0.05 tooth, which is significantly lower than in children of the comparison group (0.58 ± 0.06 tooth, p

Summary. The aim of the study. To improve the results of patients with tumors and non-neoplastic diseases of the colon treatment, to introduce into clinical practice the original surgical technique and methods of creating of colon anastomoses, which were tested in experiment. Materials and methods. Original methods of invaginational ileo-transverse and colon anastomoses creating were developed in the experiment on rabbits. Taking into account the obtained positive results, the methods of anastomoses formation were transferred to the surgical clinic and patents of Ukraine were obtained. In 2020, ileo-transverse and colonic anastomoses were formed in 134 patients on the basis of Transcarpathian Antitumor Center: one-row invaginational anastomosis according to the developed method in 22 patients (16.4 %), two-row manual — in 58 (43.3 %), circular stapler — in 36 (26.9 %), linear stapler anastomosis — in 4 (3 %), laparoscopic (linear stapler) — in 14 (10.4 %). Results and discussion. The most of complications occurred in the group with manual two-row anastomosis (16), in two cases the anastomotic leakage was recorded. When using a circular stapler suture, anastomotic leakage was observed in 1 patient, and anastomositis — in 4. When using linear stapler anastomoses, postoperative wound suppuration was observed in 1 patient. Conclusions. The most of early postoperative complications was observed after using a two-row manual colonic anastomosis (27.5 %). When using a circular stapler suture, the number of early postoperative complications was less than with a two-row manual anastomosis (22.2 % vs. 27.5 %, respectively). The least number of complications was recorded after the creation of a one-row invaginational anastomosis in the proposed original technique.

ABSTRACT: In this paper we describe various approaches used to capture heterogeneity within the reservoir undergoing hydraulic fracturing treatment and their implication on modelling of fracture propagation. In highly laminated reservoirs with soft and/or weak layers, capturing heterogeneity at an appropriate resolution is the key for successful prediction fracture growth and other crucial treatment parameters. Our focus is on studying several strategies to average fracture toughness and assess their suitability for use in advanced computational methods such as FE/BEM. In practice the well log and petrophysical data deduced from various measurements and observations are upscaled and/or homogenized to the spatial approximation size. The fracture toughness is one of the most delicate physical parameters and application of the homogenization techniques are rather uncertain, hence any proposed averaging will depend on process conditions and the toughness distribution. We propose and analyse a notion of an average toughness and show that it is a process dependent variable and provide some recommendations how to implement the defined measure into the numerical modelling. As an example, we use periodic distributions and consider model without leak off that allows us straightforward handling different regimes (toughness/viscosity). 1. INTRODUCTION Typically, when using computational methods such as Finite Element Method, the well log and petrophysical data obtained from various measurements and observations are upscaled and/or "homogenized" to the element size. From all in-situ parameters, toughness is one of the most delicate physical parameters to handle, as application of the homogenization techniques are rather questionable here as commented on by Caiulo and Kachanov (2010) and Kachanos (1994). Compared to other types of fracture evolution, hydraulic fracturing is probably the most stable crack propagation process and thus, fortunately, some estimates can be provided here. We estimate errors introduced by various strategies to incorporate heterogeneous fracture toughness into numerical modelling (Dontsov and Suarez-Rivera (2021), Da Fies et al. (2021)). We use periodic distributions and consider model without leak off that allows us straightforward handling different regimes (toughness/viscosity). For the simulations, we use an extremely effective in house-built time – space adaptive solver utilizing main ideas from those reported by Wrobel and Mishuris (2015). The solver is capable to compute rather arbitrary distribution of the toughness.

Dutko A. Protection of Family Rights of a Person by a Court / Alyona Dutko // Societas et iurisprudentia. - 2020. - Vol. 8. - No. 4. - Pp. 36-50.

SUMMARY We present unambiguous evidence that the Mahogany salt body, located in the Northern part of the Gulf of Mexico, is seismically anisotropic. Evidence of anisotropy comes from shear wave splitting data obtained from a vertical seismic profile VSP. The data set consists of 48 vertically aligned receivers in a borehole drilled through the salt body. Splitting analysis is performed on shear wave phases that are converted from compressional waves at the top and bottom of the salt body. The phase converted at the top of the salt layer shows a clear signature of seismic anisotropy, while the phase at the base of the salt layer shows negligible splitting. We investigate the possibility of rock salt halite LPO as a cause of the observed anisotropy. A finite element geomechanical salt deformation model of the Mahogany salt body is developed, where deformation history is used as an input to the texture plasticity simulation program VPSC. Assuming a halite salt body, a full elasticity model is then calculated and used to create a synthetic VSP splitting data set. The comparison between the synthetic and real VSP data set shows that LPO of rock salt can explain the observed anisotropy remarkably well. This is the strongest evidence to date of seismic anisotropy in a deforming salt structure. Furthermore, for the first time, we are able to demonstrate clear evidence that deforming halite is the most likely cause of this anisotropy, combining data set analysis and synthetic full wave form modelling based on calculated rock salt elasticities. Neglecting anisotropy in seismic processing in salt settings could lead to potential imaging errors, for example the deformation models show an averaged delta parameter of δ = –0.06, which would lead in a zero offset reflection setting to a depth mismatch of 6.2 per cent. Our work also show how observations of salt anisotropy can be used to probe characteristics of salt deformation.

Objective. To establish the impact of intraintestinal pressure on the intestinal anastomosis integrity and to propose a prophylactic measures of its insufficiency in surgical treatment of the colon diseases. Materials and methods. Intraintestinal pressure was measured in 30 patients, using Waldman method during 72 h postoperatively - before and after the transanal lavage (every 4 h). Primary operation - resection of sigmoid colon with formation of a one-barrel colostomy. The restoration intervention was performed in 3 mo with formation of a large-bowel anastomosis in accordance to the method elaborated (n=17), hand-made two-layered large-bowel anastomosis (n=3), and the apparatus large-bowel anastomosis (n=10). Results. There was noted the intraintestinal pressure raising during first 24 - 36 h up to (5.3 ± 0.1) mm Hg with its further lowering during 12 - 20 h down to (2.1 ± 0.3) mm Hg. In 20 min after the transanal drain lavage the intraintestinal pressure have lowered by (3.0 ± 1.3) mm Hg, and in 3 - 5 h - gradually raised. While application of a hand-made two-layered large-bowel anastomosis its insufficiency was observed (n=1) and anastomositis (n=1); and in the apparatus large-bowel anastomosis formation - anastomositis (n=1). While disorder of the intestinal suture healing the intraintestinal pressure have raised in 16 - 60 h up to (11.4 ± 0.2) mm Hg with peak at (16.3 - 17.1) mm Hg, which persisted 12 -18 h. Prophylactic measures were directed towards lowering of intraintestinal pressure and elimination of unfavorable local and general factors. Conclusion. While persisting noncorrected, the intraintestinal pressure in the 16.3 - 17.1 mm Hg borders during 12 - 18 h leads to complicated course of postoperative period. Direct and nondirect methods of decompression of the interintestinal anastomoses constitutes a basic prophylactic principle for it.

The aim of the article is to describe the principles of cloud technology and the scope of its use at a lesson of the Russian language in a polylingual class. Following the analysis of scientific and methodological literature on digital education, new technologies are suggested which have been introduced in a new type of handbook – a course navigator. The authors present a model to construct a course «Theatrical readings» for primary and secondary schoolchildren. The methodical constructor is oriented not only on reading as a kind of speech activity but also on material visualization and audio perception. The system of tasks reflects the specific nature of teaching Russian by means of fiction texts, teaching reading strategies and fiction understanding with the application of differential, problem search methods of teaching. When constructing the educational navigator the resources of the Google Network were used, which is a useful instrument for a teacher of Russian. This service allows for a favorable combination of various forms of tasks which form a motivation for cognitive activity. The article concludes that cloud technology as an element of digital learning in the modern educational process should emerge as a set of teaching tools to create methodical products contributing to the effective study of Russian linguistic culture.

The contribution describes the peculiarities of the protection of the right to property in the case law of the European Court of Human Rights. It has been found that, given the peculiarities of the legal nature of the right to property, it requires state regulation and may be subject to restriction and interference. Attention is drawn to the predication of any potential interference with the right to property on a general principle, according to which everyone has the right to peacefully enjoy their property. The article further clarifies the forms of interference with the ownership of individuals and legal entities by the state, such as expropriation of property and control over use of property. The triple normative regulation of property relations is investigated, and the elements of the relevant structure were covered in detail. The contents of the three-component test, in particular, its elements, such as the legality of interference with the right to property, the legitimacy of the purpose of such interference, and a fair balance between the interests of protection of the right to property and public interests, are expounded with reference to the awards of the European Court of Human Rights. Particular attention was paid to legality provisions. The contribution further dwells on the conceptual and categorical framework of the terms “general interest” and “public interest.” The authors complete their scientific inquiry with appropriate generalisations and a summary.

Summary. Aim of the study. Development and implementation of colon anastomoses formation method to improve their mechanical strength and biological hermeticity. Materials of the study. A comparative morphological study of the original and traditional two-row colonic anastomoses was performed in the experiment on 18 rabbits, and an assessment of their mechanical strength and biological hermeticity. The assessment of mechanical strength was defined by using a pneumopression technique. The assessment of biological hermeticity was defined by the method of culturing flushing water from the area of the anastomosis to the growth medium, species identification of isolated microorganisms using test systems and calculating the number of colony-forming units by quantitative method. Results of the research. The mechanical strength of one-row manual intra-nodular colonic anastomosis is higher by 66.3–85.4 %, respectively, of the first and seventh day of observations compared with the two-row manual anastomosis. During biological hermeticity assessment in the experimental group, in which colonic anastomosis was performed in the original method, the cultures were sterile at all stages of the sampling, whereas in the control group, where the traditional two-row manual anastomosis was formed, only from the seventh day all the cultures were sterile. Conslusions. The mechanical strength of one-row manual intra-nodular colonic anastomosis using atraumatic suture 4/0 without suturing the mucosa is higher by 66.3-85.4 %, respectively, of the first and seventh day of observations compared with the two-row manual anastomosis. Biological hermeticity of one-row manual intra-nodular colonic anastomosis is 100 % compared with the two-row manual anastomosis (28,5 %).

The legal regime of separation is a complex institute in which establishment entails several legal consequences for both the spouses and other members of the family and concerns both the property and personal non-property rights of the parties. It is characterized by the features common to a particular model of legal regulation of this institute. The purpose of the study is to analyze the characteristics of legal regulation of family relations, which arise out of the establishment, operation, and suspension of spousal separate residence regime in the countries of the European Union and Ukraine and their representation from the perspective of correlation of institutes of separation and divorce. During the study of models of legal regulation of the institute of spousal separate residence, general and special methods of legal phenomena identification were used. In particular, the dialectical method was used to determine the place of the institute of separation in the system of law and its relation with the institute of divorce. The social purpose of this institute was also established. The hermeneutical method helped to interpret the main features inherent in each of the models of legal regulation of separation. Logical-legal and systematic methods were used for the formulation of logically relevant conclusions, and consistent presentation of study materials. The legal comparative method is aimed at comparing the models of legal regulation of the institute of spousal separate residence in the current family law of Ukraine and the legislation of the countries of the European Union. On grounds of a comprehensive analysis of the legislation and practice of its application regarding the legal regime of spousal separate residence in the countries of the European Union and Ukraine, the features of each of the four models for legal regulation are distinguished. Keywords: Divorce, the European Union, separation, spousal separate residence regime, Ukraine.

ImportanceDue to the emergence of highly transmissible SARS-CoV-2 variants, evaluation of boosters is needed.ObjectivesEvaluate safety and immunogenicity of 100-µg of mRNA-1273 booster dose in adults.DesignOpen-label, Phase 2/3 study.SettingMulticenter study at 8 sites in the U.S.ParticipantsThe mRNA-1273 100-µg booster was administered to adults who previously received a two dose primary series of 100-µg mRNA-1273 in the phase 3 Coronavirus Efficacy (COVE) trial, at least 6 months earlier.InterventionLipid nanoparticle containing 100-µg of mRNA encoding the spike glycoprotein of SARS-CoV-2 (Wuhan-HU-1).Main Outcomes and MeasuresSolicited local and systemic adverse reactions, and unsolicited adverse events were collected after vaccination. Primary immunogenicity objectives were to demonstrate non-inferiority of the neutralizing antibody (nAb) response against SARS-CoV-2 based on the geometric mean titer (GMTs) and the seroresponse rates (SRRs) (booster dose vs. primary series in a historical control group). nAbs against SARS-CoV-2 variants were also evaluated.ResultsThe 100-µg booster dose had a greater incidence of local and systemic adverse reactions compared to the second dose of mRNA-1273 as well as the 50-µg mRNA-1273 booster in separate studies. The geometric mean titers (GMTs; 95% CI) of SARS-CoV-2 nAbs against the ancestral SARS-CoV-2 at 28 days after the 100-µg booster dose were 4039.5 (3592.7,4541.8) and 1132.0 (1046.7,1224.2) at 28 days after the second dose in the historical control group [GMT ratio=3.6 (3.1,4.2)]. SRRs (95% CI) were 100% (98.6,100) at 28 days after the booster and 98.1% (96.7,99.1) 28 days after the second dose in the historical control group [percentage difference=1.9% (0.4,3.3)]. The GMT ratio (GMR) and SRR difference for the booster as compared to the primary series met the pre-specified non-inferiority criteria. Delta-specific nAbs also increased (GMT fold-rise=233.3) after the 100-µg booster of mRNA-1273.Conclusions and RelevanceThe 100-µg mRNA-1273 booster induced a robust neutralizing antibody response against SARS-CoV-2, and reactogenicity was higher with the 100-µg booster dose compared to the authorized booster dose level in adults (50-µg). mRNA-1273 100-µg booster dose can be considered when eliciting an antibody response might be challenging such as in moderately or severely immunocompromised hosts.Trial Registration: NCT04927065Key PointsQuestion: What is the safety and immunogenicity of a booster dose of 100 µg of mRNA-1273 in adults who previously received the primary series of mRNA-1273?Findings: In this open-label, Phase 2/3 study, the 100 µg booster dose of mRNA-1273 had a greater incidence of local and systemic adverse reactions compared to a 50 µg booster dose of mRNA- 1273 or after the second dose of mRNA-1273 during the primary series. The 100 µg booster dose of mRNA-1273 induced a robust antibody response against the ancestral SARS-CoV-2 and variants.Meaning: mRNA-1273 100 µg booster dose might be considered when eliciting an antibody response might be challenging, such as in moderately or severely immunocompromised hosts.

Background: Breast cancer is the second most common cancer in women. In 2022, it accounted for 15% of total new cancer cases and is the number four cause of death among all cancer types. To benefit from precision medicine, distinguishing molecular subtypes for prognosis and treatment in a clinical setting is essential. While intrinsic subtype classification from NGS results of patients is well established, the approach has not been comprehensively described for patient-derived xenograft (PDX) models, which have been shown to be powerful in translational research. The National Cancer Institute's Patient-Derived Models Repository (NCI PDMR; https://pdmr.cancer.gov) provides rich information in developing the method. Materials and Methods: Normalized gene expression data of breast cancer PDX and patient specimens (originators) were extracted using tximport and DESeq2 based on RNA-seq analysis. The immunohistochemistry (IHC) was used to determine the status of ER, PR and HER2 receptor expression in these tumor specimens. The PAM50 classification was performed by the R package Genefu. For further analysis, the PAM50 centroids for all 5 subtypes were also obtained from Genefu. Results: Using the RNA-seq data from 43 PDX models (180 PDX samples, 4~6 samples/model), we were able to predict subtypes at the model level based on the PAM50 method: There are 1 Luminal A subtypes, 5 Luminal B; 6 Her2; 30 Basal and 1 Normal, which encompasses the whole spectrum of PAM50. Thirty originators were also included and there are 8 Luminal A, 9 Luminal B, 2 Her2 and 11 Basal. With the matched 11 originators and the PDX models, 91% of their predicted subtypes are identical; 0.80 Cohen’s kappa was obtained, indicating high inter-rater agreement. We also described subsequent analysis with IHC data-based subtypes. For the 10 originators having IHC-based subtypes, 90% agreement was observed; for 24 PDX models with IHC data, 88% was observed. Of all the 180 PDX samples, 33 of the 43 PDX models (77%) have consistent predicted PAM50 molecular subtypes across different passages and lineages. Within the discordant samples, we observed cases such as a mixture of luminal B and Basal, which can be reasonably interpreted by AR positive signal from IHC. The discrepancy encourages further PDX subclassification from the Basal subtype. Conclusions: Using our high-throughput gene expression profiles from many patients and samples from patient derived models, we have demonstrated the feasibility of applying classic PAM50 classification algorithm, which was originally developed with microarray data, to be able to recognize the expression signals from our RNA-seq data. Overall, this study should set a primer for the identification of PDX-based subtypes, starting from breast cancer. Citation Format: Peter I. Wu, Lindsay Dutko, Shahanawaz Jiwani, Li Chen, Biswajit Das, Ting-Chia Chang, Yvonne A. Evrard, Chris A. Karlovich, Alyssa Chapman, Brandie Fullmer, Ashley Hayes, Ruth Thornton, Nikitha Nair, Kelly Benauer, Gloryvee Rivera, Thomas Forbes, John Carter, Suzanne Borgel, Tiffanie Miner, Chelsea McGlynn, Justine Mills, Shannon Uzelac, Tia Shearer, Lauren Hicks, Michelle Norris, Carley Border, Sergio Alcoser, Thomas Walsh, Michael Mullendore, Michelle Eugeni, Dianne Newton, Melinda G. Hollingshead, P. M. Williams, James H. Doroshow. Molecular subclassification of NCI PDMR breast cancer models using PAM50 gene expression signature [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2050.

Introduction: Structural variants (SVs) are a unique class of mutations which have certain therapeutic implications for the tumor. Certain SVs, such as chromosomal aneuploidy, whole-genome doubling (WGD), have specific therapeutic implications. The underlying cellular processes present in the tumor are reflected in mutational signatures. Here, we describe the landscape of chromosomal aneuploidy, WGD and mutational signatures in the National Cancer Institute’s Patient-Derived Models Repository (NCI PDMR) to facilitate the investigation of their roles in therapeutic responses of the preclinical models. Method: Chromosome arm-level aneuploidy was called by scoring at the individual arm level if >90% of the arm copy number (CN) was gained/lost based on whole-exome sequencing (WES) data. Aneuploidy score was defined as number of arms with aneuploidy. WGD was determined by derived allelic specific CN, purity and ploidy from tumor/normal matched samples and permutation test. Mutational signatures (COSMIC v3) including single base substitutions (SBS), doublet base substitutions (DBS), small insertions and deletions (ID) and CN signatures were derived using SigProfiler for specimens with somatic mutations and CNs. Results: A large fraction (85%) of patient-derived xenograft (PDX) models (N=755) have at least one arm -level aneuploidy. Certain chromosomes and arms (7, 8, 17p and 18) are more frequently aneuploid, which might be biased due to the overrepresentation of gastrointestinal cancer in the cohort. Histology specific differences were observed in the frequency of arm level aneuploidies. For example, synovial sarcoma (SYNS) and endometrioid carcinoma (UEC) have much lower level of aneuploidy than non-small cell lung cancer (NSCLC) or clear cell renal carcinoma (ccRCC) models. 61% of PDX models (N=277) have WGD, in which certain histologies have more WGD [NSCLC: 81%, head and neck squamous cell carcinomas (HNSCC): 71%] than others. Samples having WGD have a higher degree of aneuploidy and chromosomal instability. WGD and aneuploidy remain stable along the passages in 78% PDX models. Intra-model heterogeneity of WGD was observed due to lineage difference. Mutational signatures (SBS6,15,20) indicating concurrent DNA polymerase epsilon (POLE) mutation and defective DNA mismatch repair were highly enriched in microsatellite instability-high models (p Conclusion: We have characterized chromosomal aneuploidy, WGD and mutational signatures in NCI PDMR models. The models with SVs can be utilized in preclinical drug studies to understand their role in therapeutic response in patients. Citation Format: Li Chen, Biswajit Das, Ting-Chia Chang, Yvonne A. Evrard, Chris A. Karlovich, Alyssa Chapman, Brandie Fullmer, Ashley Hayes, Ruth Thornton, Nikitha Nair, Shahanawaz Jiwani, Lindsay Dutko, Kelly Benauer, Gloryvee Rivera, Corinne Camalier, John Carter, Suzanne Borgel, Tiffanie Miner, Chelsea McGlynn, Justine Mills, Shannon Uzelac, Tia Shearer, Lauren Hicks, Michelle Norris, Carley Border, Sergio Alcoser, Thomas Walsh, Michael Mullendore, Michelle Eugeni, Dianne Newton, Melinda G. Hollingshead, P. Mickey Williams, James H. Doroshow. Chromosomal aneuploidy, whole-genome doubling and mutational signatures in NCI PDMR models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6072.

The National Cancer Institute’s Patient-Derived Models Repository (NCI PDMR; https://pdmr.cancer.gov) has developed a national repository of Patient-Derived Models (PDMs) comprised of patient-derived xenografts (PDXs), in vitro patient-derived tumor cell cultures (PDCs) and cancer associated fibroblasts (CAFs) as well as patient-derived organoids (PDOrg). These PDMs are clinically annotated with molecular information available in an easily accessible database for the extramural community. A key effort in developing these models is to develop matched models sets allowing for larger scale screening efforts using 2D or 3D models to prioritize selection of PDX models for preclinical translational research. To date, over 220 model sets with a PDX, PDOrg, and PDC from a single patient have been developed; 40 of these have matched CAF models allowing for exploration of research questions focused on tumor microenvironment. The largest model sets are in colorectal cancer (COADREAD, n=76), gynecologic cancers (n=33), pancreatic adenocarcinoma (PAAD, n=29), melanoma (MEL, n=19), and head and neck squamous cell carcinomas (HNSCC, n=17). Every model undergoes several quality control assessments that serve as go/no-go criteria including pathology assessment, STR validation, NGS concordance assessment and for PDXs, human:mouse DNA content assessment. It should be noted that not every model is successful in the development or QC phase so additional model sets with only one or two of the model types are also available for researcher requests, for example there are over 125 PDX/PDOrg matched model sets. The NCI is currently performing parallel preclinical screening of PDXs and PDCs or PDOrgs to determine the ability of the in vitro lines to predict in vivo activity. Genetic and histopathologic assessment of these matched model sets have demonstrated a high degree of stability by somatic mutation, copy number alteration (CNA) and gene expression data. Gene expression correlation analysis shows that mean of Spearman r between PDXs 0.89, between matched PDC/PDXs 0.79, and between matched PDOrg/PDXs 0.82. As expected, some variation at the gene expression level when comparing PDX to in vitro cultures by t-SNE can be observed, likely due to the differences in culture conditions. Funded by NCI Contract No. HHSN261200800001E Citation Format: Yvonne A. Evrard, Li Chen, Sergio Alcoser, Gareth Bliss, Carrie Bonomi, Suzanne Borgel, John Carter, Ting-Chia Chang, Alice Chen, Kevin Cooper, Biswajit Das, Kelly Dougherty, Lindsay Dutko, Marion Gibson, Michelle M. Ahalt-Gottholm, Tara Grinnage-Pulley, Keegan Kalmbach, Chris Karlovich, Kimberly Klarmann, Shahanawaz Jiwani, Tiffanie Miner, Michael Mullendore, Matthew Murphy, Kevin Plater, Gloryvee Rivera, Jessica Steed, Luke Stockwin, Cindy R. Timme, Dianne L. Newton, Paul Mickey Williams, Melinda G. Hollingshead, James H. Doroshow. NCI patient derived models repository: PDX, organoid and cell lines from the same patient - bridging the translational pipeline [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 40.

With the increasing demand for CO 2 storage in the subsurface, it is important to recognize that candidate formations may present complex stress conditions and material characteristics. Consequently, modelling of CO 2 injection requires the selection of the most appropriate constitutive material model for the best possible representation of the material response. The authors focus on modelling the geomechanical behaviour of the reservoir material, coupled with a multiphase flow solution of CO 2 injection into a saline-saturated medium. It is proposed that the SR3 critical-state material model is used, which considers a direct link between strength–volume–permeability that evolves during the simulation; furthermore, the material is considered to yield prior to reaching a peak strength in agreement with experimental observations. Verification of the material model against established laboratory tests is conducted, including multiphase flow accounting for relative permeabilities and fluid densities. Multiphase flow coupled to advanced geomechanics provides a holistic approach to modelling CO 2 injection into sandstone reservoirs. The resulting injection pressures, CO 2 migration extent and patterns, formation dilation, and strength reduction are compared for a range of in situ porosities and incremental material enhancements. This work aims to demonstrate a numerical modelling framework to aid in the understanding of geomechanical responses to CO 2 injection for safe and efficient deployment, and is particularly applicable to CO 2 sequestration in less favourable aquifers with a relatively low permeability, receiving CO 2 from a limited number of injection wells at high flow rates. The proposed framework can also enable additional features to be incorporated into the model such as faults and detailed overburden representation. Thematic collection: This article is part of the Geoscience for CO 2 storage collection available at: https://www.lyellcollection.org/cc/geoscience-for-co2-storage

Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6–8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 (NCT04405076). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.7-fold (95% confidence interval (CI): 1.5, 1.9) higher than those at 28 days after the second injection of the primary series, which met the pre-specified non-inferiority criterion (primary immunogenicity objective) and might indicate a memory B cell response. The nAb titers against the Delta variant (B.1.617.2) (exploratory objective) at 1 month after the booster were 2.1-fold (95% CI: 1.8, 2.4) higher than those at 28 days after the second injection of the primary series. The seroresponse rate (95% CI (four-fold rise from baseline)) was 100% (98.7, 100.0) at 28 days after the booster compared to 98.3% (96.0, 99.4) after the primary series. The higher antibody titers at 28 days after the booster dose compared to 28 days after the second dose in the phase 3 COVE study were also observed in two assays for anti-spike IgG antibody measured by ELISA and by Meso Scale Discovery (MSD) Multiplex. The frequency of solicited local and systemic adverse reactions after the booster dose was similar to that after the second dose in the primary two-dose series of mRNA-1273 (50 µg or 100 µg); no new signals were observed in the unsolicited adverse events; and no serious adverse events were reported in the 1-month follow-up period. These results show that a booster injection of mRNA-1273 more than 6 months after completing the primary two-dose series is safe and elicited nAb titers that were statistically significantly higher than the peak titers detected after the primary vaccination series, suggesting that a booster dose of mRNA-1273 might result in increased vaccine effectiveness against infection and disease caused by SARS-CoV-2.

Мета роботи: покращення результатів лікування хворих із хірургічною патологією ободової кишки шляхом розпрацювання і впровадження патогенетично обґрунтованого алгоритму лікування та техніки створення анастомозу, спрямованого на зниження частоти післяопераційних ускладнень. Матеріали і методи. В групі з 30 пацієнтів вимірювали внутрішньокишковий тиск (ВКТ) у післяопераційному періоді. Під час операції, крім трансанального дренажу, який заводили вище анастомозу на 5–10 см, проводили трубку діаметром 0,5 см, кінець якої встановлювали на рівні товстокишкового анастомозу (ТКА). Вимірювання тиску проводили методом Вальдмана протягом 72 год із моменту операції, кожні 4 години. При цьому виконували 2 вимірювання – до і після промивання трансанального дренажу. При виконанні відновного втручання ТКА за розробленою методикою виконали – 17, ручний дворядний ТКА – 3, апаратний ТКА – 10 хворим. Результати досліджень та їх обговорення. Встановлено, що в післяопераційному періоді в ободовій кишці спостерігається зростання ВКТ (Р) протягом перших 24–36 год (t) в середньому до (5,3 ± 0,1) мм рт. ст., з подальшим зниженням цього рівня протягом наступних 12–20 год до (2,1 ± 0,3) мм рт. ст. Через 20 хв після промивання трансанального дренажу і відходження “промивних вод” рівень ВКТ знижується в середньому на (3,0 ± 1,3) мм рт. ст. Це зниження утримувалося протягом 3–5 год, після чого відбулося поступове зростання рівня ВКТ. При застосуванні традиційного дворядного анастомозу у 2 хворих відмічено в одному спостереженні неспроможність ТКА, у другому – анастомозит. ТКА розробленим способом виконано 17 хворим, апаратний ТКА – 10 хворим, анастомозит розвинувся в одного пацієнта. Ускладнення траплялися переважно при застосуванні ручного традиційного шва (10 %). У всіх хворих з розвиненими порушеннями загоєння анастомозу спостерігається підвищення ВКТ через 16–60 год до (11,4 ± 0,2) мм рт. ст., з піком близько (16,3–17,1) мм рт. ст., що спостерігалось аж до розвитку неспроможності анастомозу, з наступним різким зниженням ВКТ. При анастомозиті подібного зниження ВКТ не було. Мало значення не тільки стійке підвищення ВКТ з критичним рівнем до 16,3–17,1 мм рт. ст., а й тривалість впливу його протягом 12–18 год.

In recent years, digital communications have rapidly entered the lives of modern people. Globalization of digital technologies is solved in Russia at the state level – Federal programs of digitalization are created and implemented. They are aimed at the inclusion a person in the virtual space since the very childhood which undoubtedly affects many aspects of the human life. Thus, children developing in the context of the global spread of digital technologies have been called “generation Z”. Of course, this category of children could not go unnoticed by many domestic and foreign scientists. In this article, the authors provide an overview of studies devoted to the study of the “digital generation”.

The aim of this article is to analyze the capabilities of Google services and their combination with traditional approaches to studying the novel by L.N. Tolstoy’s “War and Peace”. Based on the generalization of the experience of teachers, school practice, the author proposes a model of an educational navigator, which is used in the study of a voluminous epic work – the novel “War and Peace”. Particular attention in the article is paid to ways of introducing students to reading and methods of working with the text of the novel using Google-services. The expediency and efficiency of using this resource for organizing the activities of students in the lesson and in extracurricular activities have been revealed. To build an educational navigator, it is relevant to turn to Google services: electronic encyclopedias, numerous Internet resources, multimedia tools (video encyclopedias, e-books, etc.). Separately, the specifics of the use of Google services in guiding students’ independent work through a specially organized interactive educational and information environment, which saves educational time, ensures long-term memorization of educational material, contributes to the development of the necessary reading skills of students, creates conditions for differentiated learning. The didactic capabilities of Google services are demonstrated using the example of different types of the educational navigator content. The article describes individual navigator modules. Based on the study, it was concluded that the Google services in the modern educational space should become a didactic toolkit for developing methodological recommendations and organizing a system for working with the text of a literary work, aimed at developing the reading activity of schoolchildren, their independence and creativity, and personal growth.

Prevention of hard dental tissue diseases and periodontal diseases in children is one of the urgent issues of pediatric dentistry. This is especially true for the category of children with psychoneurological pathology. Due to the high prevalence of dental diseases, decreased immunity, and sometimes difficult assess to dental care for children with mental retardation, dental disease prevention is the most effective measure to maintain the normal functioning of the dentofacial apparatus. The results obtained by examining the children with oligophrenia allowed us to work up an algorithm for therapeutic and preventive measures aimed at preventing the development of oral tissue diseases in these children. The algorithm included measures for primary and secondary prevention of periodontal diseases. To assess the efficacy of the algorithm, the study involved a group of 55 mentally impaired children. The control group consisted of 50 children with oligophrenia, who were treated by traditional methods. Taking into account the burdened mental status of the children when developing the individual hygiene regimens, a motivational approach was worked out in co-operation with a psychiatrist and a paediatrician. Evaluation of treatment outcomes in the groups was performed in 1 month after the completion of the full course of treatment and prevention and in long-term intervals, in 6 and 12 months. Clinical evaluation of treatment efficacy was performed according to the following criteria: "normalization", "improvement", "progression". In one month following the regimen proposed, the "normalization" of the affected tissues was diagnosed in 40 children of the main group (72,73 ± 6,06%), p