Standard Format Research Articles

Introducing GWAStic: A user-friendly, cross-platform solution for genome-wide association studies and genomic prediction

Abstract Motivation Advances in genomics have created an insistent need for accessible tools that simplify complex genetic data analysis, enabling researchers across fields to harness the power of genome-wide association studies and genomic prediction. GWAStic was developed to bridge this gap, providing an intuitive platform that combines artificial intelligence with traditional statistical methods, making sophisticated genomic analysis accessible without requiring deep expertise in statistical software. Results We present GWAStic, an intuitive, cross-platform desktop application designed to streamline genome-wide association studies and genomic prediction for biological and medical researchers. With a user-friendly graphical interface, GWAStic integrates machine learning and traditional statistical approaches to support genetic analysis. The application accepts inputs from standard text-based Variant Call Formats and PLINK binary files, generating clear graphical outputs, including Manhattan plots, quantile-quantile plots, and genomic prediction correlation plots, to enhance data visualization and analysis. Availability and implementation Project page: https://github.com/snowformatics/gwastic_desktop GWAStic documentation: https://snowformatics.gitbook.io/product-docs PyPI: https://pypi.org/project/gwastic-desktop/

The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity.

The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7000 publications for >15000 traits, from which more than 625000 lead associations have been curated. Additionally, 85 000 full genome-wide summary statistics datasets-containing association data for all variants in the analysis-are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.

The effect of inverting decades and units on the retention of two-digit numbers in working memory: a matter of the output mode.

Number-word structure affects transcoding and relates to working memory capacity (WMc). We tested the relationship between the structure of number-words (inverted "Units-Decades (UD) format" or not "Decades-Units (DU) format") and performance on the digit span task for recalling two-digit number-words presented verbally, using two modes of output. University students, native speakers of Arabic, who were also highly proficient in Hebrew, and native speakers of Hebrew, were asked to response by typing Arabic digits or recalling numbers verbally. Arabic and Hebrew speakers were equal in WMc for one-digit numbers in the two modes. However, when inversion was presented, performance was related to output and participants habits. In the typing response, both groups showed better performance for the DU format. In the native language (standard format), Arabic speakers (UD) remembered fewer numbers than Hebrew speakers (DU). Arabic speakers show inversion errors even in the noninverted format. For verbal responses, there were no differences between the groups in their standard format, and native speakers of Arabic weren't affected by the format, while Hebrew speakers still preferred the DU format. Experience with inverted and noninverted language affected WMc but is also related to the output demands.

Security-Diplomacy Nexus: Nature of Bilateral Cooperation in Kenya - India Military Diplomatic Relations Since 1963

Bilateral and multilateral agreements have been one of the mechanisms through which growth and development have taken place. The newly created independent states of the Cold War period presented a major paradigm shift in international cooperation to include military diplomacy. Kenya and India being among these newly created states have had their cooperation where by the two countries have used their good diplomatic relations to bolster one another's military capabilities. The current study sought to put into perspective the conduct of bilateral relations between Kenya and India. The objective of this study was to examine the nature of bilateral cooperation in enhancing Kenya-India military-diplomatic relations since 1963. The study was anchored on power theory. The study adopted a descriptive research design. The study was carried out in Nairobi County, Kenya with a specific focus on the Ministry of Foreign Affairs, Defence Ministry, and Indian High Commission. The target population was 2500. The sample size for the study was determined using Yamane's (1967) formula to calculate the sample size, which was 250 Qualitative data obtained from interviews were analysed using narrative reports using thematic techniques. Quantitative data from the questionnaires was edited, coded, and entered into a computer spreadsheet in a standard format to allow descriptive statistics analysis. Statistical Packages for Social Sciences (SPSS) edition 24 and Microsoft Office Excel 2013 were used for the quantitative data. The findings of the study revealed that the nature of Kenya-India military diplomatic relations manifested in various forms including through High-profile visits by Kenyan and Indian officials to both states as a way of strengthening bilateral relations. Technological transfer was another way through which these two nations shaped their diplomatic relationship, particularly in information and communication technology (ICT). Additionally, Defense trade and trade agreements, Security Partnerships, Counterterrorism activities, Maritime Safety, and Peacekeeping missions were common areas of cooperation between Kenya and India. The study concludes that bilateral cooperation between Kenya and India has been instrumental in enhancing their military-diplomatic relations since 1963. The study recommends that, to better understand the nature of bilateral cooperation, Kenya and India should establish a permanent joint military commission to oversee and coordinate defense initiatives.

Generating Ontology-Learning Training-Data through Verbalization

Ontologies play an important role in the organization and representation of knowledge. However, in most cases, ontologies do not fully cover domain knowledge, resulting in a gap. This gap, often expressed as a lack of concepts, relations, or axioms, is usually filled by domain experts in a manual and tedious process. Utilizing large language models (LLMs) can ease this process; a fine-tuned LLM could receive as input up-to-date and reliable domain knowledge natural text and output a structured graph in OWL RDF/Turtle format, which is the standard format of ontologies. Thus, to fine-tune a model, text-owl sentence pairs that constitute such a dataset must be acquired. Unfortunately, such a dataset does not exist in the literature or within the open-source community. Therefore, this paper introduces our LLM-assisted verbalizer to create such a data set by converting OWL statements from existing ontologies into natural text. We evaluate the verbalizer on 322 classes from four different ontologies using two different LLMs, achieving precision and recall as high as 0.99 and 0.96, respectively.

The Proteomics Standards Initiative Standardized Formats for Spectral Libraries and Fragment Ion Peak Annotations: mzSpecLib and mzPAF.

Mass spectral libraries are collections of reference spectra, usually associated with specific analytes from which the spectra were generated, that are used for further downstream analysis of new spectra. There are many different formats used for encoding spectral libraries, but none have undergone a standardization process to ensure broad applicability to many applications. As part of the Human Proteome Organization Proteomics Standards Initiative (PSI), we have developed a standardized format for encoding spectral libraries, called mzSpecLib (https://psidev.info/mzSpecLib). It is primarily a data model that flexibly encodes metadata about the library entries using the extensible PSI-MS controlled vocabulary and can be encoded in and converted between different serialization formats. We have also developed a standardized data model and serialization for fragment ion peak annotations, called mzPAF (https://psidev.info/mzPAF). It is defined as a separate standard, since it may be used for other applications besides spectral libraries. The mzSpecLib and mzPAF standards are compatible with existing PSI standards such as ProForma 2.0 and the Universal Spectrum Identifier. The mzSpecLib and mzPAF standards have been primarily defined for peptides in proteomics applications with basic small molecule support. They could be extended in the future to other fields that need to encode spectral libraries for nonpeptidic analytes.

In-vitro and In-silico evaluation of antimicrobial and antibiofilm effect of Neem oil and Calcium hydroxide nanoparticles against Mutans Streptococci and Enterococcus faecalis isolated from endodontic infections

Different Streptococcal species including Streptococcus mutans, Streptococcus sobrinus and Enterococcus faecalis are commonly isolated in root canal infections including refractory, recurrent, and persistent cases. Calcium hydroxide (Ca (OH)2) has been widely used in endodontics as an intracanal medicament. However, using new antimicrobial herbal alternatives offers promising potentials which can be additionally enhanced by using nanoparticles (NPs). In this study, we evaluate the antimicrobial efficacy and antibiofilm effect of Neem oil including its NPs preparations and we compare the effect of conventional Ca (OH)2 to Ca (OH)2 NPs using standard disc diffusion method and quantitative microtitre dish biofilm formation assay against common pathogens isolated from root canal samples. Molecular docking was used to test the binding of 10 Streptococcal macromolecules to 5 candidate neem active constituents. Neem NPs 0.125 mg/ml showed better antibacterial effect than both Neem 15 mg/ml and Neem 0.15 mg/ml. Ca (OH)2 NPs 0.125 mg/ml also showed better antibacterial effect than each of Ca (OH)2 10 mg/ml and Ca (OH)2 0.1 mg/ml. Best biofilm mass inhibition was achieved by Neem oil 0.15 mg/ml at 74.55% ( IQ: 67.36–87.65) and Neem NPs 0.0125 mg/ml at 59.33% (IQ: 51-–75.27). For Ca (OH)2, the best biofilm mass inhibition was observed with Ca (OH)2 NPs 0.125 mg/ml at 54.7% (IQ: 42.37– 77.25). Both neem oil and neem NPs show promising antibacterial and antibiofilm potential against Mutans Streptococci group at low concentrations and hence are good candidates for use as endodontic medications. In silico analysis shows that both Sitosterol and Gedunin appear to be important active constituents of neem and possible drug candidates. Additionally, Ca (OH)2 NPs showed significantly higher antimicrobial effect against Mutans streptococci group than conventional Ca (OH)2 preparations.

Development of conceptual provisions for implementing innovative technologies to quality standards of public passenger transport

This paper reports a study of the main principles for the formation of public passenger transport service quality standards. The object of the research is public passenger transport services. The task of the study is the development of conceptual foundations for the formation of quality standards using modern innovative technologies. It has been established that the main factor in achieving the quality of public passenger transport services is taking into account innovative technologies and compliance with the criteria and norms of EU standards. Features in the functioning of public passenger transport in the world have been studied, including the use of information platforms for tracking the movement of transport routes, Internet applications, ensuring safety and compliance with environmental requirements. The criteria that serve as indicators of improving the efficiency of the quality of services have been defined, among the main ones are the availability of transportation, comfort, frequency of traffic, and waiting time, quality of service, as well as safety. A system of forming the quality of public passenger transport services has been proposed, which involves determining the needs and requirements of consumers of public passenger transport services, ensures the development of measures to improve the quality of services and their certification. A comprehensive approach to the formation of the quality of public passenger transport services based on the introduction of innovative technologies has been formed, which could make it possible to determine the level of their innovative development, as well as ways to improve it. This approach takes into account the relationship between implemented measures, measuring the level of service quality and the distribution of obligations to ensure the level of services determined by quality criteria. This makes it possible to determine the required level of quality of public passenger transport services and to form a relationship between the level of innovative technologies and the stages of the approach. The practical significance of the results is the design of tools that would ensure the improvement of the quality of public passenger transport services.

Chemical thermodynamics of biomass, cellulose, and cellulose derivatives: A review

This article provides a review of the research on the chemical thermodynamics and thermochemistry of biomass, cellulose, and its derivatives such as ethers, esters, and oxycelluloses. For diverse biomass types, gross and net heating values were studied. It has been established that these energetical characteristics of biomass can be calculated using a superposition of the energetical characteristics of the main components of biomass such as cellulose, hemicelluloses, lignin, lipids, proteins, etc. The pelletization of biomass improves its fuel performance. It was shown that, if the ultimate goal is to generate the maximum amount of thermal energy, then it is more profitable to directly burn the initial biomass in the form of pellets than to burn the amount of solid or liquid biofuel that can be extracted from this biomass. After the cellulose study, the direct and exact thermochemical method for determining the crystallinity degree of this biopolymer was proposed. In addition, the standard combustion and formation enthalpies of various cellulose samples were studied. As a result, the thermodynamic characteristics of four crystalline allomorphs of cellulose, CI, CII, CIII, and CIV, were obtained and their thermodynamic stability was evaluated. The thermochemistry of enzymatic hydrolysis of cellulose was studied. In addition. The thermodynamical characteristics of various cellulose derivatives were determined, and the thermochemistry of the reactions of cellulose alkalization, etherification, esterification, and oxidation was studied.

Investigating immersion and migration decisions for agent-based modelling: Acautionary tale.

Agent-based modelling provides an appealing methodological choice for simulating human behaviour and decisions. The currently dominant approaches based on static transition rates or unverified assumptions are restrictive, and could be enhanced with insights from cognitive experiments on actual decision making. Here, one common concern is that standard surveys or experiments may lack ecological validity, limiting the extent to which research findings can be generalised to real-life settings. For complex, highly emotive decision-making scenarios, such as those related to irregular migration, the typically used short, methodical survey questions may not appropriately map onto complex real-world decisions of interest. Immersive contexts may offer more accurate representations of reality, potentially enhancing the usefulness of experimental information in multi-disciplinary modelling endeavours. This preregistered study, aimed directly at examining the effect of immersion on risk-taking in the context of migration decisions, and indirectly at informing a multi-disciplinary construction of an agent-based model of migration, presents a choice-based interactive fiction game in which players make migration decisions to advance through a story. (N = 1000 Prolific users) took part in one of four experimental conditions, three involving different renditions of the game attempting to create immersion, with the last condition presenting the decisions in standard survey format. Although addressing the lack of ecological validity in survey data is important for improving agent-based modelling methodology, the experimental design used to tackle this issue, while responding directly to modelling needs, proved too complex. The created experimental conditions ended up too distinct from each other, involving stimuli that differed in quantity and content. This introduced several unintended and uncontrolled confounds, making it impossible to meaningfully interpret the results of this experiment on its own. Our results act as a cautionary tale for agent-based modellers, highlighting that the modelling needs should not override the principles of experimental design, and provide motivation for more rigorous research on this topic.

Geospatial tools and data for health service delivery: opportunities and challenges across the disaster management cycle.

As extreme weather events increase in frequency and intensity, the health system faces significant challenges, not only from shifting patterns of climate-sensitive diseases but also from disruptions to healthcare infrastructure, supply chains and the physical systems essential for delivering care. This necessitates the strategic use of geospatial tools to guide the delivery of healthcare services and make evidence-informed priorities, especially in contexts with scarce human and financial resources. In this article, we highlight several published papers that have been used throughout the phases of the disaster management cycle in relation to health service delivery. We complement the findings from these publications with a rapid scoping review to present the body of knowledge for using spatial methods for health service delivery in the context of disasters. The main aim of this article is to demonstrate the benefits and discuss the challenges associated with the use of geospatial methods throughout the disaster management cycle. Our scoping review identified 48 articles employing geospatial techniques in the disaster management cycle. Most of them focused on geospatial tools employed for preparedness, anticipatory action and mitigation, particularly for targeted health service delivery. We note that while geospatial data analytics are effectively deployed throughout the different phases of disaster management, important challenges remain, such as ensuring timely availability of geospatial data during disasters, developing standardized and structured data formats, securing pre-disaster data for disaster preparedness, addressing gaps in health incidence data, reducing underreporting of cases and overcoming limitations in spatial and temporal coverage and granularity. Overall, existing and novel geospatial methods can bridge specific evidence gaps in all phases of the disaster management cycle. Improvement and 'operationalization' of these methods can provide opportunities for more evidence-informed decision making in responding to health crises during climate change.

Evaluation of the accuracy of digital impressions with different scanning strategies: An in vitro study

ObjectivesTo evaluate the effects of three different scanning strategies on the trueness and precision of optical impressions obtained with four intraoral scanners (IOSs). MethodsThe reference maxillary dental arch model was fabricated using Telio CAD, and the reference digital reference cast was obtained using a computer numerical control machine and an optical scanner (E4, 3Shape, Copenhagen, Denmark). Test scans were performed with four different IOSs (TRIOS3, MEDIT i700, CS 3600, and iTero Element 5D) by an experienced operator and three different scanning strategies (S1: manufacturer-recommended, S2: optimal per previous literature, and S3: experimental). The scan duration was recorded for each scan. All scans were converted to standard tessellation language format and imported into Geomagic Control X. The accuracy was measured by absolute deviation/distance between aligned surfaces. Data of trueness and precision of each IOS and scan duration were statistically compared using analysis of variance for repeated measures and Bonferroni post-hoc test (p < .05). ResultsNo significant differences in trueness were found among strategies (S1: 9.98 µm, S2: 11.93 µm, S3: 8.84 µm; p = .388) in Trios 3 and iTero Element 5D (S1: 12.24 µm, S2: 11.53 µm, S3: 10.71 µm; p = p = .279). Scanning strategy S3 with MEDIT i700 achieved greater trueness (7.33 µm) than S2 (16.33 µm, p < .05), while no significant difference was noted between S1 (10.44 µm) and S3 (p = .291). S3 showed the highest trueness (16.28 µm) compared to S2 (24.05 µm) and S1 (24.78 µm, p < .001) for CS 3600, with no difference between S1 and S2 (p = .457). Trios 3 had higher precision with S2 (22.46 µm) than S3 (31.69 µm, p < .05), and no significant differences between S1 (25.67 µm) and S2/S3 (p > .05). MEDIT i700 with S3 (29.52 µm) was more precise than both S1 (39.52 µm) and S2 (46.24 µm) (p < .001) with no difference between the last two (p = .302). S2 yielded the highest precision (44.93 µm) compared to S3 (61.81 µm) and S1 (76.53 µm) (p < .001) for CS 3600, with S3 more precise than S1 (p < .001). Similarly, iTero Element 5D showed S2 as the most precise (30.19 µm) compared to S3 (42.80 µm) and S1 (44.45 µm) (p < .05), with no difference between S1 and S3 (p = .472).Scan durations were shorter for S3 and S1 compared to S2 in Trios 3 (p < .001), and S3 was faster than S1 and S2 for MEDIT i700 (p < .001). CS 3600 scans with S1 were quicker than S2 and S3 (p < .001). For iTero Element 5D, no significant differences were found between S1 and S3 (p = .511), but S2 was slower than both (p < .001). ConclusionsScanning strategies significantly affect the accuracy and scan duration of optical impressions. Specifically, S3 provided the best trueness with both the MEDIT i700 and the CS 3600 while the S2 strategy demonstrated the highest precision for most scanners. Overall, the S1 and S3 strategies resulted faster than S2 among the devices evaluated. Clinical SignificanceThe results suggest that the experimental scan strategy may optimize the use of intraoral scanners in clinical practice, potentially leading to more accurate and time-efficient dental impressions.

Data ecosystem using smart home technology to support healthy aging

Abstract Background Smart home technology has been widely used to mitigate the challenges that population aging brings. However, the lack of a centralized data ecosystem has prevented these technologies from realizing their full potential. This project aimed to construct a data ecosystem compatible with smart home sensors to monitor healthcare for seniors, improving their quality of life. Methods The infrastructure was constructed using a user-centered design approach, allowing smart devices such as motion, temperature sensors to operate independently and communicate through a Wi-Fi mesh network. API technology provides a reliable channel for real-time data collection. To ensure data privacy and security, extracted data is hosted in a cloud environment that provides comprehensive data protection, and cloud computing is utilized for high-performance computation tasks. Analytical models such as Machine Learning can be implemented to recognize indoor activities, achieving the goal of remote monitoring. Results This data ecosystem advances in privacy and security, interoperability, accessibility, and data-sharing. Unified authentication mechanism ensures data is transmitted among heterogeneous devices with minimal vulnerability. Additionally, the common communication protocol provides the foundation of interoperability between devices. With unobtrusive devices, inhabitants are not burdened with operation, ensuring their accessibility and improving their user experience. Lastly, the data is exchanged in a standardized JSON data format, enabling efficient data-sharing board data integration. Conclusions This project developed a data ecosystem based on existing smart home environments. The ecosystem is compatible with smart devices that families already have, effectively reducing additional healthcare costs. Implications of this study include helping health policy and decision makers to adopt more smart home ecosystems to keep older people healthy at home. Key messages • Study constructed a data ecosystem compatible with smart home sensors, achieving remote monitoring of indoor activities and improving the quality of life for seniors. • The developed ecosystem offers promotion in privacy and security, interoperability, accessibility, and efficient data-sharing, reducing healthcare costs.

A Data Model for Unrecognised Historical Neighbourhood (Case study: Telukbetung, Indonesia)

Abstract. Unrecognised Historical places, which are locations with history but lacking official recognition, particularly prevalent in Southeast Asia, often face a dearth of accessible historical information. To tackle this challenge, there is an urgent need to commence the collection and documentation of historical data concerning Unrecognised Historical places. This initiative aims to prevent the loss of history, given that such sites are frequently subjected to rapid development and commercialization. To date, City Geography Markup Language (CityGML), an Open Geospatial Consortium (OGC) standard 3D data format, has been developed for presenting city models along with semantic data and is often used in the heritage domain for preservation. It aids in digital infrastructure development and the conservation of urban elements. Furthermore, it provides a mechanism to extend the standard data model to meet the requirements of various purposes. While several CityGML extensions tailored to the documentation of Cultural Heritage already exist, there is currently no extension specifically designed to address the requirements of Unrecognised Historical places. The aim of this paper is to identify a suitable approach for developing a new standardised data model that integrates geometric and semantic information, which is demonstrated for the modelling of Telukbetung, an old city in Bandar Lampung through time.

Event log extraction methodology for Ethereum applications

The adoption of smart contracts in decentralized blockchain-based applications enables reliable and certified audits. These audits allow the extraction of valuable information from blockchains, which can be used to reconstruct the execution of the application and facilitate advanced analyses. One of the most commonly used techniques in this context is process mining, which leverages event logs to trace and accurately represent the process execution of applications. However, extracting execution data from blockchains poses significant challenges, and the current methodologies developed have some limitations. Most approaches are tailored to specific use cases, requiring that analysis techniques are defined during the smart contract’s development. Other techniques are applied a posteriori, relying on blockchain events that often lack a standardized format. This absence of standardization requires complex processing steps to correlate logs with the executed actions and such approaches are not universally applicable to all smart contracts on the blockchain, further limiting their scope. Lastly, none of the existing techniques can extract information from event logs embedded in internal transactions of smart contracts.To address these limitations, we propose EveLog an application-agnostic methodology that can be applied to any EVM-compatible application without predefined constraints. Its primary goal is to extract information from smart contracts, capturing both public and internal transactions, and organizing the results into a structured XES event log. The EveLog methodology consists of five key steps: (i) extraction of data from smart contract transactions, (ii) decoding raw data, (iii) selection of sorting criteria, (iv) construction of traces, and (v) generation of the XES event log. EveLog has been implemented in a client–server application and tested on existing solutions, specifically the CryptoKitties application, a blockchain-based game on the Ethereum blockchain. The study was conducted using 12,996 blocks, including over 8000 real transactions from the Ethereum mainnet.

Maximizing the "Functional" in the Functional External Memory Aid Tool for Patient-Centered Treatment Planning in Mild Cognitive Impairment.

The Functional External Memory Aid Tool (FEMAT) is an 11-item performance-based measure that simulates everyday tasks (e.g., medication management) to measure one's use of compensation (e.g., pill organizer). The FEMAT is not a norm-referenced diagnostic tool; rather, it is designed to provide clinicians with information about a patient's function and compensation in a standardized format. To provide further evidence for validity of the FEMAT, the purpose of this study was to conduct a mixed-methods analysis of FEMAT responses to operationalize the types of behaviors elicited during test administration. We adopted an embedded single-case study design to analyze the FEMAT administrations of 12 community-dwelling female participants, ages 73-90 years, who met criteria for mild cognitive impairment. These participants were part of the original validation sample during which they completed the FEMAT (Version 1.0) in a single session with an assessor. Sessions were video-recorded and transcribed. We analyzed the data qualitatively in two phases using theme and subtheme codes and then quantitatively analyzed the data for response trends. Our thematic analysis revealed four themes to operationalize participants' verbal and behavioral FEMAT responses: (a) used an external memory aid (EMA), (b) described using a strategy, (c) discussed memory and comprehension, and (d) discussed functional information. While completing the FEMAT, most participants described using a strategy (85%) and discussed their self-perceived memory and comprehension (33%). Several subthemes also emerged within each theme (e.g., self-perceived memory strengths and barrier). Our analysis suggests that beyond a 4-point item score, the FEMAT elicits behavioral (e.g., used an EMA) and verbal (e.g., discussion of health information) content that may be useful for person-centered treatment planning. This study is part of a comprehensive research agenda establishing the evidence for the validity of the FEMAT to support its use to inform person-centered treatment approaches.

A First-Passage Model of Intravitreal Drug Delivery and Residence Time-Influence of Ocular Geometry, Individual Variability, and Injection Location.

Standard of care for various retinal diseases involves recurrent intravitreal injections. This motivates mathematical modeling efforts to identify influential factors for ocular drug residence time, aiming to minimize administration frequency. We sought to describe the vitreal diffusion of therapeutics in nonclinical species frequently used during drug development assessments. In human eyes, we investigated the impact of variability in vitreous cavity size and eccentricity, and in injection location, on drug disposition. Using a first-passage time approach, we modeled the transport-controlled distribution of two standard therapeutic protein formats (Fab and IgG) and elimination through anterior and posterior pathways. Anatomical three-dimensional geometries of mouse, rat, rabbit, cynomolgus monkey, and human eyes were constructed using ocular images and biometry datasets. A scaling relationship was derived for comparison with experimental ocular half-lives. Model simulations revealed a dependence of residence time on ocular size and injection location. Delivery to the posterior vitreous resulted in increased vitreal half-life and retinal permeation. Interindividual variability in human eyes had a significant influence on residence time (half-life range of 5-7days), showing a strong correlation to axial length and vitreal volume. Anterior exit was the predominant route of drug elimination. Contribution of the posterior pathway displayed a 3% difference between protein formats but varied between species (10%-30%). The modeling results suggest that experimental variability in ocular half-life is partially attributed to anatomical differences and injection site location. Simulations further suggest a potential role of the posterior pathway permeability in determining species differences in ocular pharmacokinetics.

Архитектура создания самообучающегося колледжа

The competence approach has firmly gained its place in the world educational paradigm, distinguishing rigid (professional) and flexible (supra professional) skills. But the high speed of technological changes will significantly transform the landscape of the modern labor market, when within the next decades up to a quarter of traditional professions will disappear, and hard skills will be significantly transformed after them. The most important competitive advantage will be the speed of perception and translation of new knowledge, as well as competencies formed on their basis. The key competences for continuous development will be flexible competences (soft skills), some of which will be enriched with basic hard skills. The traditional conservatism of the educational system, the long period of formation of educational standards of training becomes a certain brake on the training of specialists of the future. If rigid skills can be formed based on the existing production base (jobs of the future, which do not exist yet), flexible skills can be formed now. This actualizes the idea of creating self-learning spaces in secondary vocational education institutions. Copying Chris Argyris' idea will not find a positive response, given our realities and the specifics of the Millennial generation, Z generation and later α generation, it will be a good idea to create self-learning spaces in secondary vocational education institutions. The author's developments on the implementation of approaches to the formation of the model of a self-learning college in the institution of secondary vocational education are presented. This approach can be useful for secondary vocational education organizations developing educational, managerial and financial strategies in order to unpack the expertise of the teaching community.

Modeling Enzyme Kinetics: Current Challenges and Future Perspectives for Biocatalysis.

Biocatalysis is becoming a data science. High-throughput experimentation generates a rapidly increasing stream of biocatalytic data, which is the raw material for mechanistic and novel data-driven modeling approaches for the predictive design of improved biocatalysts and novel bioprocesses. The holistic and molecular understanding of enzymatic reaction systems will enable us to identify and overcome kinetic bottlenecks and shift the thermodynamics of a reaction. The full characterization and modeling of reaction systems is a community effort; therefore, published methods and results should be findable, accessible, interoperable, and reusable (FAIR), which is achieved by developing standardized data exchange formats, by a complete and reproducible documentation of experimentation, by collaborative platforms for developing sustainable software and for analyzing data, and by repositories for publishing results together with raw data. The FAIRification of biocatalysis is a prerequisite to developing highly automated laboratory infrastructures that improve the reproducibility of scientific results and reduce the time and costs required to develop novel synthesis routes.

Evolution of social standards and guarantees in the legal system of Ukraine: current challenges and development prospects

The study is devoted to the evolution of social standards and guarantees in the legal system of Ukraine, the analysis of modern challenges in the field of social protection and the determination of prospects for their further development. In the conditions of economic and political transformations, ensuring the appropriate level of social standards is an urgent task. The article examines the historical development of social standards from the Soviet period to the modern stage of Ukraine’s integration into the European legal space. The impact of international law, in particular the European Social Charter and ILO conventions, on the formation of social standards is analyzed. The importance of adapting national legislation to international standards for increasing the level of social protection and bringing Ukrainian policy closer to European standards is emphasized. The influence of economic and social factors, such as crises, demographic changes, social inequality and migration processes, which create serious challenges for the state, is considered. Special attention is paid to social guarantees for vulnerable population groups, such as pensioners, people with disabilities, internally displaced persons and combatants. The main problems of these groups in the realization of the rights to social protection were identified and recommendations were given for improving the mechanisms of social support. The author emphasizes the need to reform social policy to create a more effective and fair system of social protection. Contemporary challenges in the implementation of social standards are explored, including economic instability, demographic changes, military conflict, inefficiency of public administration, and corruption. Emphasis is placed on a comprehensive approach to overcoming them, increasing the financial stability of the social system, improving legal regulation and cooperation with international organizations. Prospects for the development of social standards depend on the state’s ability to ensure the sustainability of social policy, adapt legislation to international standards, and increase the availability of social services. The successful implementation of these measures will contribute to Ukraine’s integration into the European legal space, which is strategically important for the country’s development. The article offers a comprehensive analysis of the evolution of social standards in the legal system of Ukraine, identifies the main challenges and provides recommendations for the further development of social policy.