Rare Mendelian disorders affect 300-400 million people globally. Although genetic testing has become widely adopted, gene-specific evidence for tailored variant interpretation remains scattered across resources. We present Gene Portals, a framework for gene-centered multimodal knowledge bases that co-localize expert-harmonized clinical data, functional assays, population variation, structural annotations and gene-specific ACMG/AMP specifications within a single resource. A modular interface integrates this unified evidence with VCEP-refined ACMG specifications to enable automated gene-specific variant classification, infer molecular mechanisms, and support cross-gene analyses. We demonstrate the framework's utility across five Gene portals spanning eleven neurodevelopmental disorder-associated genes, integrating data from 4,423 individuals with 2,838 unique variants, 36,149 ClinVar submissions, and 1,044 expert-curated molecular readouts. By organizing evidence that is otherwise dispersed across multiple sources into a unified, queryable framework, the SCN, GRIN, CACNA1A, SATB2 and SLC6A1 Gene Portals became widely used community resources and provide an extensible template for standardized rare-disease variant interpretation and mechanism-aware discovery.

Ideally, educators should use the best available evidence to make decisions about their practices as teachers, scholars, and policymakers. However, the rapid increase of scholarly literature in medical education poses a major challenge. Knowledge syntheses (aka reviews), which contextualize and integrate information into a single resource, have become essential tools for navigating this information overload. This article presents an overview of knowledge synthesis in medical education, starting by defining it and providing an overview of the general steps. It then examines four key types of syntheses: systematic reviews, scoping reviews, meta-reviews, and realist reviews, providing examples of each type and, when possible, pointing to reporting guidelines and resources for conducting the type. The article then addresses common methodological pitfalls, including inadequate time planning, limited collaboration with end-users, insufficiently actionable findings, and narrow search strategies. The article concludes by presenting emerging innovations, such as artificial intelligence-supported methodologies, living reviews, and alternative knowledge translation activities.

Medical clearance considerations for medically complex adult patients.

As the use of functional tonality diminished in the twentieth century, composers searched for new means by which to create momentum and articulate form. This article examines some of these explorations as found in the works of Roger Smalley (1943–2015). In Smalley’s two percussion-only works, Ceremony I (1987), for percussion quartet and Music for An Imaginary Ballet (1994), for percussion soloist, momentum is often driven by processes of expansion and contraction. The use of unpitched percussion in these works elevates the importance of Smalley’s use of these processes when determining durations, tempos, density, dynamics and spatial separation. In each of these fields, expansion and contraction play important generative roles and drive the momentum. This article will also discuss their less obvious, but equally important, application in the pitch domain. To articulate large-scale form, Smalley experimented with single (or highly restricted) timbral resources within individual movements. Although each movement was thereby restricted in its timbral variety, the juxtaposition of movements with highly contrasting timbres proved to be a highly successful articulator of form.

Under the background of digital economy and highly coordinated tourism service chain, overbooking strategy, as a core means for enterprises to balance resource utilization and revenue, has been widely applied in aviation, hotel and other industries. However, overbooking of a single resource is likely to trigger chain reactions in the multi-resource network, restricting the sustainable operation of the industry. Taking the aviation industry as a research case, this paper focuses on the overbooking problem in multi-resource network, constructs a theoretical analysis framework of "upstream triggering-inventory substitution-downstream spillover", analyzes the operation mechanism and multiple impacts of network overbooking, and focuses on exploring the transmission path of overbooking risks in the tourism service chain and its comprehensive effects on customer experience, enterprise operation and industry development. On this basis, from four dimensions of information synchronization, benefit distribution, passenger service and environmental protection-cost balance, this paper proposes a multi-subject collaborative overbooking optimization strategy, which provides theoretical reference and practical path for airlines and related enterprises in the tourism service chain to improve overbooking management level, balance benefits and public interests, and helps the industry transform from "scale priority" to "quality priority".

Assessment practices in secondary science and physics classrooms often emphasize scoring rather than generating actionable evidence of students’ understanding. This challenge becomes more urgent under the Merdeka Curriculum, which positions assessment as an integral component of learning. To address this need, this study aimed to develop and validate a teacher guide module for UbD (Understanding by Design)-based science assessment for junior and senior secondary levels by operationalizing backward design and the six facets of understanding into practical procedures, templates, and worked examples. Using a research and development approach with the 4D model (Define–Design–Develop–Disseminate), the module was produced through needs analysis, curriculum and literature review, and iterative drafting. Content validation was conducted by three validators using a four-point relevance scale, analyzed with feasibility percentages and Aiken’s V complemented by Score (Wilson) confidence intervals. Practicality was examined through a limited pilot involving three science teachers who applied the module and completed a five-point response questionnaire. The results showed high feasibility across usefulness, practicality, conceptual accuracy, and language/visual design. At the same time, item-level content validity was strong (Aiken’s V = 0.78–1.00) with conservative lower confidence bounds indicating at least moderate validity for all items. Teachers reported uniformly positive perceptions, with perceived usefulness rated highest (M = 4.83), although implementation of the Explanation facet was relatively more challenging (lowest item mean, M = 3.67). This study’s novelty lies in providing a step-by-step, facet-based assessment design guide that explicitly links learning objectives, acceptable evidence, and analytic rubrics within a single teacher-ready resource. In conclusion, the validated module is feasible and practically promising as an evidence-centered tool to strengthen alignment between curriculum outcomes and assessment in secondary science. The module contributes to physics education by supporting teachers to design authentic, rubric-based assessments that better capture students’ scientific reasoning and conceptual understanding.

Beyond the breast: Mammographic manifestations of systemic disease.

Destructive tests are widely used in the industry to determine the mechanical properties of materials. However, they are usually time-consuming, expensive, and can cause damage to the materials. In this context, nondestructive ultrasound tests emerge as a viable alternative to determine mechanical properties without harming the material. The main objective of this study was to determine the Poisson coefficient of aluminum samples, using nondestructive ultrasound testing. Additionally, a metrological approach was implemented to assess the quantities, and their respective measurement uncertainty was presented, showing a high confidence level in the results. The study also highlighted the economic viability of nondestructive ultrasound testing, as it does not cause damage to the materials and allows for the evaluation of multiple mechanical properties in a single test, saving time and resources. Furthermore, the test contributes to quality control in the manufacturing and service of materials, by detecting flaws and variations in their mechanical properties. In this work, the Poisson modulus was determined as 0.3488 and associated with a measurement uncertainty of 0.0133. The results demonstrated that the Poisson modulus determined in this work, following the resources on ultrasound tests, was consistent with literature data and technical standards. Therefore, it is reinforced that nondestructive ultrasound testing is reliable, safe, and efficient in characterizing the Poisson modulus, providing compliance and safety in using materials.

The research examines the impact of MERN and MEAN full-stack technologies and automation tools on software development processes. It analyzes case studies from 2019 to 2024 and finds that these technologies lead to significant improvements in productivity and shorter development times. They are 25-35% faster than other development approaches due to their modularity and integrated design approaches. React's reusable bits, Angular's two-way data binding, and Node.js's asynchronous processing help teams work together. Automation tools like Jenkins, Selenium, Docker, and Kubernetes manage testing and deployment, achieving a 40% decrease in next deployment time and a 50% reduction in defect rate. Cost efficiency can reach 20% to 40% due to single development practices and optimal resource use. However, challenges like high-slope learning and initial configuration difficulties remain. These can be addressed through training programs, community support, and partnering tools with project needs. The integration of MERN and MEAN stacks with automation tools provides a strong foundation for software development, promoting efficiency, better quality, and less expense.

The study is devoted to the topical issue of digitalization of communications in the sports sector, using futsal clubs as an example. With the growing popularity of futsal and the expansion of youth leagues, high-quality information support is becoming particularly important, as it ensures timely information, interactive communication with fans, and effective management of club activities. The lack of a single resource for combining communication channels often leads to fragmentation, inconsistency, and delays in the dissemination of data about matches, events, and news, which negatively affects the development of clubs and their competitiveness. The purpose of the article is to create a minimum viable digital solution (MVP) in the form of a web resource that provides a systematic approach to communication with fans, promotes loyalty, and opens opportunities for further commercialization. The methodological basis is a combination of the Lean Model Canvas, or Lean Model Canvas (LM) for identifying key elements of the business model and the Customer Journey Map (CJM) for researching user experience at all stages of interaction with the club. The methodology is based on systematic, analytical, and comparative approaches. Methods of theoretical analysis, modeling, observation, and expert assessment were used to provide a comprehensive view of the futsal club’s digital communication and scientific justification for the proposed solutions. The developed MVP was implemented using the Weblium platform. The website contains structured sections (“Home”, “About the Club”, ‘Partnership’, “Contacts”), provides responsive design, integration with social networks, and a convenient navigation system. Particular attention was paid to the intuitiveness of the interface, visual style, and interactive elements that increase audience engagement. Internal testing confirmed positive user perception: informativeness, ease of use, and potential for further improvement were noted. The scientific novelty lies in the comprehensive application of the LM and CJM methods to form a digital development strategy for a futsal club. The practical significance of the development is evident in the creation of a core digital ecosystem capable of scaling through the integration of additional services (online ticket sales, Customer Relationship Management (CRM), analytical modules). The conclusions emphasize that the MVP website performs not only an informational but also a communicative function, strengthening the club’s brand and forming the basis for further digital transformation. The proposed solution can be adopted by other sports organizations, which increases its significance in the broader context of sports development in the digital age.

Reactome is the most comprehensive, open source, open access biological pathway knowledgebase, widely used in the research community. To ensure the highest quality of its content, human pathway data in Reactome is manually curated. However, manual curation is labor-intensive, time-consuming, and increasingly difficult to keep up with the ever-growing biomedical literature. Large language model (LLM)–driven artificial intelligence (AI) technologies are transforming many fields, including bioinformatics resource development. Applying LLM/AI technologies in Reactome may offer a powerful way to scale curation and consolidate pathway-related data into a single resource. This manuscript describes the first stage of our attempt to adopt LLM/AI technologies for Reactome manual curation. We developed an LLM workflow that can assist curators in adding new genes to existing pathways and refining the functional annotations of existing ones. The workflow predicts pathways in which genes are likely to function, identifies PubMed-indexed literature that may support these predictions, generates text summaries describing potential molecular mechanisms, and extracts functional relationships among biological entities from full-text PDF papers. To validate the workflow output, we used a computational approach based on semantic similarity between LLM workflow-generated summaries and Reactome manual annotations. The results show significant enrichment of high-similarity matches. Manual evaluation of 19 genes indicated that more than half of the outputs are useful for supporting curation. Based on these results, we developed an enhanced workflow that incorporates protein-protein interaction data, facilitating Reactome’s reaction-based annotation. In summary, our initial adoption of LLM/AI technologies produced encouraging results and provides a practical framework for integrating AI-assisted methods into Reactome’s curation pipeline. The strategies described here may be broadly applicable to community knowledgebases in general.

The role of AI for improved management of breast cancer: Enhanced diagnosis and health disparity mitigation.

Introduction: Viral vector systems are crucial in delivering therapeutic genetic material for gene and cell therapy in clinical settings. With new progress in viral vector-based gene therapies, healthcare professionals and pharmacists must stay informed and apply appropriate biosafety precautions when handling these products. Comprehensive guidelines covering biosafety measures for every viral vector-based gene therapy, including storage, preparation, administration, and disposal, remain scarce. As viral vector-based gene therapy advances rapidly, it is critical to equip healthcare professionals with the expertise to safely manage these agents in a clinical setting. Methods: As gene therapies become more integrated into mainstream medicine, with 43 cell and gene therapy products approved as of 2025, pharmacists, nurses, and caregivers face new safety challenges when handling these therapies. While guidelines such as United States Pharmacopeia (USP) 797 and USP 800 provide a foundation for handling viral vector-based gene therapies, no single resource consolidates all biosafety considerations for healthcare professionals. This review provides an overview of the viral vector-based gene therapy landscape. It compiles best practices from various sources to establish a potential standardized approach to guide safe handling procedures for viral vector systems in a healthcare setting. Discussion: By adopting the biosafety strategies outlined in this article, healthcare staff and pharmacists can safely manage viral vectors while developing standard operating procedures tailored to their specific clinical environments. Implementing these measures will support the continued advancement of gene therapy while ensuring the safety of healthcare providers, patients, and the environment.

Genes influencing opioid use disorder (OUD) biology have been identified via genome-wide association studies (GWAS), gene expression, and network analyses. These discoveries provide opportunities to identifying existing compounds targeting these genes for drug repurposing studies. However, systematically integrating discovery results and identifying relevant available pharmacotherapies for OUD repurposing studies is challenging. To address this, we’ve constructed a framework that uses existing results and drug databases to identify candidate pharmacotherapies. For this study, two independent OUD related meta-analyses were used including a GWAS and a differential gene expression (DGE) study of post-mortem human brain. Protein-Protein Interaction (PPI) sub-networks enriched for GWAS risk loci were identified via network analyses. Drug databases Pharos, Open Targets, Therapeutic Target Database (TTD), and DrugBank were queried for clinical status and target selectivity. Cross-omic and drug query results were then integrated to identify candidate compounds. GWAS and DGE analyses revealed 3 and 335 target genes (FDR q < 0.05), respectively, while network analysis detected 70 genes in 22 enriched PPI networks. Four selection strategies were implemented, which yielded between 72 and 676 genes with statistically significant support and 110 to 683 drugs targeting these genes, respectively. After filtering out less specific compounds or those targeting well-established psychiatric-related receptors (OPRM1 and DRD2), between 2 and 329 approved drugs remained across the four strategies. By leveraging multiple lines of biological evidence and resources, we identified many FDA approved drugs that target genes associated with OUD. This approach a) allows high-throughput querying of OUD-related genes, b) detects OUD-related genes and compounds not identified using a single domain or resource, and c) produces a succinct summary of FDA approved compounds eligible for efficient expert review. Identifying larger pools of candidate pharmacotherapies and summarizing the supporting evidence bridges the gap between discovery and drug repurposing studies.

The variable character of aquatic systems forces organisms to constantly adjust to their changing environment. We investigated how resource availability shapes the temperature sensitivity of growth for the freshwater phytoplankton species Scenedesmus armatus (Chodat). We used a gradient design of light and nutrients, to assess their interdependent effects on numerous thermal traits, determined from thermal performance curves (TPCs). Building on previous studies that demonstrated resource-dependent temperature sensitivity in growth for a single resource type, we advance this understanding by revealing the interdependent effects of multiple resources on thermal traits, using response surfaces. We showed that most resource effects on thermal traits highly depend on the availability of other resource that can even change the direction of the effect, and that thermal traits can differ in their resource dependence. Our study provides important knowledge of how organisms cope in their changing and multifactorial environment, especially in the face of climate warming.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-27601-w.

Foreign direct investment (FDI) is a significant phenomenon in the modern globalized economy. In simple terms, it assists nations to develop through enhancement of their economies, the introduction of new technologies and employment opportunities. The world is striving towards achieving the Sustainable Development Goals (SDGs) of the UN, and it is becoming evident that FDI is playing a major role in ensuring that sustainable future becomes a reality. This paper gives a further examination of how FDI leads to sustainable development in both the developed and developing nations, and how it impacts on the economic, social, and environmental environments of the nations. This essay will look at how Foreign Direct Investment (FDI) has influenced sustainable development compared to the effects in the developed and developing nations. Even though FDI has been noted to be one of the major drivers of economic growth, the extent to which it will contribute to sustainability in terms of economic, environmental, and social aspects differs significantly depending on the level of economic development and the institutional framework of the host country. In the developed countries, FDI is mostly recognized with technological, infrastructural, and social wellbeing progress, specifically with high technology industries and with energy production that is renewable. Conversely, in developing nations, FDI has been very instrumental in industrialization and provision of employment. It is however associated with undesirable side effects like environmental degradation, resource depletion, pollution and social inequalities especially in single resource intensive industries like mining and agriculture. This paper assumes a comparative approach to discuss the various results of FDI in different geographic areas, in this case, studies of the European Union, Africa, and Southeast Asia. The discussion shows that governance systems, regulatory frameworks and institutional capabilities can play a key role in influencing the contribution of FDI to sustainable development. It is based on these understandings that the paper presents a policy recommendation that can help to make certain that FDI can help in the long-term sustainability objectives. It proposes policies to both the developed and developing countries that would help to align FDI to economic, social, and environmental sustainability. The results underscore the need to enhance the regulatory frameworks and promote the process of corporate social responsibility (CSR) within developing nations to diminish the negative effects of FDI. Furthermore, the paper indicates the future research opportunities, in particular, the investigation of the role of CSR and longitudinal studies to get a better idea about the long-term impacts of FDI on sustainability.

In the digital era, users’ information needs are increasingly characterized by diversity and personalization. Traditional library communication models, constrained by limitations such as single resource carriers, delayed service responses, and restricted spatial coverage, can no longer meet these evolving demands. The rapid advancement of artificial intelligence (AI) and big data technologies has provided strong technical support for the transformation of library communication. Through methods such as literature analysis and logical reasoning, this study explores the technological foundations of AI and big data–empowered integrated communication in libraries. It constructs an innovative three-dimensional model of integrated communication across resources, services, and spaces; analyzes the coordination mechanisms between technologies and stakeholders; identifies existing challenges in technological adaptation, data security, and personnel capacity; and proposes targeted optimization strategies. This research aims to offer theoretical guidance for libraries to enhance their communication capabilities and improve service efficiency.

TargetPair: A Single Cell-omics Resource of Clinical Trials-derived Therapeutical Target Combinations for Cancer Therapy.

Abstract In support of the renovation wave, the European Union (EU) has proposed Digital Building Logbooks (DBLs) as central repositories for all relevant building data to foster informed decision-making and better information sharing in the construction sector. A DBL records details such as energy performance certificates, smart readiness indicators, and energy consumption data, all of which may be sensitive personal information under regulations like the General Data Protection Regulation (GDPR). Consequently, concerns over privacy, confidentiality, and data control might limit DBLs market adoption. DBLs should allow secure user control while permitting regulated third-party access. The Social Linked Data (Solid) specification is an emerging initiative in decentralized data stores that gives users control over their data and its usage, enabling reuse across competing applications. This study explores integrating DBLs with the Solid specification, focusing on technical bottlenecks, GDPR compliance, and the data management burden on building owners. It outlines several configuration options; from using a single resource for the entire DBL within the Solid Pod to treating each piece of information as a separate resource. Each option has distinct implications for privacy and data management, and trade-offs must be evaluated based on specific requirements.

Australia’s renewable energy transition will be dominated by solar and wind power, yet their contrasting variability necessitates hybrid integration with storage to ensure reliability. This study uses Australian reanalysis data, BARRA (Bureau of Meteorology Atmospheric High-Resolution Regional Reanalysis for Australia), to quantify solar (global horizontal irradiance, GHI) and wind (wind power density, WPD) resources by examining their availability, variability, synergy, episode length, and lulls. The novelty of this work is the use of rarely examined metrics such as variability, availability, episode length, and extended lull events (Dunkelflaute) with a high-resolution and 29-year duration reanalysis dataset. The results show that solar is the more reliable resource, with high daytime availability and relatively short lulls. Wind, despite being abundant in coastal regions, is highly intermittent, characterized by a skewed distribution, low availability, and extended periods of lulls. Synergy metrics demonstrate significant complementarity, with combined solar–wind synergy reducing deficits in single resources, while joint non-synergy events define critical system vulnerabilities. Importantly, hybrid systems limit maximum joint lulls, which are far shorter than wind-only extremes, thereby reducing the scale of long-duration storage required. These findings underscore that, while solar provides a stable baseline supply and wind contributes spatial diversity, hybrid systems supported by batteries offer a resilient pathway. Synergy and non-synergy statistics provide essential parameters for optimally sizing storage to withstand rare but severe shortfalls, ensuring a reliable, utility-scale renewable future for Australia.