Abstract: The paper shows how the ideas of Archimedes about integrating “mechanical methods” and formal reasoning can be connected with the modern-day use of three computer programs – Wolfram Alpha, Maple, and Excel – in exploring topics from elementary theory of numbers. Explorations deal with subsequences of integer sequences through step-by-step elimination of every other term obtained on the previous step. This process, resembling the sieve of Eratosthenes, is applied to tetrahedral numbers appearing in the social context of the family therapy triangulation method. It is demonstrated that symbolic computations of Wolfram Alpha enable generalization in the construction of the sieves that is confirmed by Maple and a spreadsheet. The paper addresses one of the aims of the special issue by demonstrating the duality of mathematics and technology in the sense that whereas the latter facilitates new approaches to knowledge acquisition, the former can be used to improve the efficiency of computations by reflecting on the results made possible by those approaches. The activities advocate for the value of integrating ancient ideas, digital tools, and elementary number theory in the education of mathematics teachers. Reflective comments by teacher candidates are included as appropriate.

Abstract: Background: Common Variable Immunodeficiency (CVID), a heterogeneous syndrome characterized by hypogammaglobulinemia and defective humoral immunity, is the most prevalent symptomatic primary immunodeficiency. CVID-8 is a monogenic variant due to bi-allelic mutation in the LRBA gene. Individuals carrying a single mutated LRBA allele are considered phenotypically healthy. However, immune dysregulation may arise in certain heterozygous carriers likely via haploinsufficiency or dominant-negative activity. LRBA critically regulates CTLA-4 recycling, directly linking this deficiency to immune checkpoint biology. Case Presentation: We report a 7-year-old female, born to consanguineous Lebanese parents, with a family history of thrombocytopenia, presented with chronic refractory ITP first diagnosed at age 2. The patient was resistant to multiple sequential therapeutic interventions including immunosuppressive agents and splenectomy. Whole exome sequencing (WES) detected compound heterozygous LRBA variants c.7937T>G (p.Ile2646Ser) and c.7046T>A p.Leu2349*, the former is pathogenic associated with CVID-8. Immunological assessment revealed hypogammaglobulinemia with suppressed IgG1, IgG3, IgA and IgM levels. Her latest hospitalization was marked by abdominal pain, impaired consciousness, acute liver injury, coagulopathy, peripheral leukocytosis, and lung infiltrates on imaging, suggesting autoimmune enteropathy complicated by infection. Conclusion: This report raises important questions regarding the clinical impact of heterozygous LRBA variant. It highlights the diagnostic value of WES in refractory cytopenias and inherited immune deficiencies. Abatacept, a CTLA-4-Ig fusion protein, is a promising targeted therapy for LRBA deficiency cases; yet its unavailability in Lebanon impeded its use, emphasizing the critical gap in access to targeted biologics in the MENA region.

Abstract: Rapid detection and localization of liquid fuel spills is critical for first responders assessing fire and health hazards, yet current methods require ground-based sampling or specialized instrumentation, limiting their practicality for wide-area emergency response. We present a drone-based passive colorimetric sensor system using test strips impregnated with Nile red, similar to colored confetti. Nile red is a solvatochromic dye that undergoes distinct visible color transitions upon exposure to different liquids. The dye is embedded within a polymer matrix that minimizes leaching while providing high optical contrast between dry, water-exposed, and fuel-exposed states. The sensor strips exhibit solvent-specific colorimetric responses within one minute of exposure, readily detectable by standard RGB cameras mounted on unmanned aerial vehicles (UAV) at altitudes up to 50 m. Automated classification was validated at 20 m altitude, enabling remote surveillance of contaminated surfaces without specialized equipment. Color-corrected image analysis using Calibrite ColorChecker calibration ensures reliable interpretation under variable field illumination (625–77,000 lux). Systematic laboratory evaluation of twelve fossil and bio-derived fuels revealed characteristic hue shifts that clearly discriminate ethanol-containing gasoline blends from diesel-range fuels. Field validation confirmed localization and classification of fuel-exposed sensors, achieving F1 scores of 0.94 for gasoline and 0.98 for diesel detection with no false positives in the tested scenarios. This cost-effective and scalable approach provides actionable information on both contamination location and fuel type, crucial for rapid hazard assessment in emergency response scenarios.

Abstract: Metabolic syndrome (MetS) is highly prevalent in people living with HIV (PLHIV), but whether their intestinal microbiota differs from that of HIV negative individuals with MetS remains unclear. We conducted a cross-sectional study including 30 virologically suppressed PLHIV with MetS and 30 HIV-negative individuals with MetS. Fecal microbiota composition was assessed by 16S rRNA gene sequencing, and predicted functional profiles were inferred using PICRUSt2 and MetaCyc. PLHIV with MetS exhibited markedly reduced alpha diversity and a clearly distinct beta diversity profile compared with HIV negative MetS, indicating a remodeled community structure. Differential abundance analysis showed enrichment in PLHIV + MetS of Prevotella, Selenomonas, Odoribacter, Christensenellaceae R-7 group, and uncultured Lachnospiraceae, whereas Subdoligranulum and the Ruminococcus gauvreauii group were relatively more abundant in HIV negative MetS. Functional predictions revealed higher representation in PLHIV + MetS of Gram-negative cell envelope and lipopolysaccharide-related pathways, amino acid degradation, and ppGpp biosynthesis, while HIV negative MetS showed comparatively greater saccharolytic potential. Carbohydrate related pathways correlated positively with adiposity and blood pressure, and Prevotella correlated positively with BMI only in PLHIV + MetS. These findings support MetS in chronic treated HIV as a distinct dysbiotic and metabolically adverse intestinal phenotype and highlight the intestinal microbiota as a potential target for microbiome-oriented interventions in this population.

Abstract:

This review provides a comprehensive overview of the genetic diversity and epidemiological potential of Yersinia pestis in Kazakhstan’s natural plague foci, emphasizing the link between genotypic variation and outbreak capacity. Integrating historical epidemiological records with contemporary microbiological and genomic data (including PCR, VNTR/MLVA, SNP analysis, and whole-genome sequencing), we evaluate core and accessory genome variations. The data reveal substantial regional heterogeneity. High-risk desert foci (Caspian and Aral regions) are dominated by the Medievalis biovar, including atypical genovariants lacking canonical markers. Conversely, high-mountain foci (Sarydzhaz, Talas) harbor Antiqua and Talas biovars primarily linked to enzootic circulation. Notably, the Ili River focus exhibits extreme genomic variability, featuring strains with plesiomorphic traits. Furthermore, the widespread distribution of mobile elements like the cryptic plasmid pCKF suggests significant horizontal transfer contributing to pathogen adaptation. Ultimately, Central Asian plague dynamics are driven by complex evolutionary and ecological interactions. Given climate change and expanding human-wildlife interfaces, continuous genomic and ecological surveillance is essential for the early detection of high-risk Y. pestis genovariants and improving public health preparedness.

Abstract: Rational use of medicines (RUM) is a cornerstone of safe, effective, and affordable health care. In Nepal, irrational medicine use-particularly of antibiotics-remains widespread, driven by self-medication, over-the-counter (OTC) sales without prescription, inappropriate prescribing practices, weak regulatory enforcement, and commercial influences. These practices contribute directly to the growing burden of antimicrobial resistance, increased adverse drug reactions (ADR), and avoidable economic costs for households and the health system. This perspective article synthesizes recent evidence from knowledge, attitude, and practice (KAP) studies, national policy experiences, and global trends from the past five years to examine the magnitude and drivers of irrational medicine use in Nepal. Ensuring RUM is a shared responsibility involving individuals, communities, health professionals, regulators, policymakers, pharmaceutical industries, and the media. Strengthening RUM in Nepal requires coordinated regulatory enforcement, antimicrobial stewardship, and community-level behavior change.

Abstract: This paper presents the design, implementation, and evaluation of Shine Bright Like Silver, a mobile application developed for PIOP's Silversmithing Museum in Ioannina, Greece, to document, simulate, and present the sand casting and filigree silversmithing techniques. The proposed solution integrates semantic knowledge graphs, an interactive crafting simulation, and gamified learning elements to externalize and operationalize the implicit procedural knowledge involved in the craft. A user study was conducted with n=26 museum visitors to assess the system's effectiveness in terms of usability, learning outcomes, and early indicators of craft valorization. The findings suggest that combining semantic representation with interactive simulation, embedded within a museum context, offers a scalable and replicable framework for the digital preservation of heritage crafts. The work contributes to the broader discourse on technology-mediated craft education by illustrating how tacit knowledge can be systematically captured and transmitted through mobile digital environments, and by positioning visitor-facing tools within a broader reenactable preservation infrastructure.

Abstract: The proliferation of digital content platforms has rendered personalized recommendation systems a foundational component of modern information retrieval. Classical Matrix Factorization (MF) methods, while computationally tractable, are fundamentally constrained by the linearity of the inner product operator, which prevents them from capturing the non-linear, higher-order dependencies characteristic of real-world user–item interaction spaces. This paper presents a complete end-to-end system embodying Neural Collaborative Filtering (NCF), wherein a Generalized Matrix Factorization (GMF) module and a Multi-Layer Perceptron (MLP) are fused to model both linear and non-linear latent factors simultaneously. Two fully isomorphic implementations are developed: a pedagogical NumPy-based version featuring hand-derived backpropagation, and an optimized PyTorch version leveraging Apple Silicon MPS acceleration. Empirical evaluation on the MovieLens dataset demonstrates that both implementations converge to equivalent final Binary Cross-Entropy losses (0.2257 and 0.2307, respectively), while the PyTorch variant achieves a 3.39× speedup in total training time (3,295 s versus 972 s over 20 epochs). Peak recommendation quality, measured by Hit Ratio at cutoff 10 (HR@10), reaches 0.615 for the PyTorch implementation. The system is deployed as a production-grade microservices architecture comprising a FastAPI gateway, a dedicated PyTorch inference server, a PostgreSQL persistence layer, and a Netflix-style frontend with TMDB poster integration. A hybrid cold-start module supplements the NCF core for new users and items. The findings validate the feasibility of bridging rigorous algorithmic pedagogy with industry-standard deployment practices.

Abstract: Public sector organizations face growing pressure to modernize service delivery through digitalization while ensuring transparency, interoperability, and citizen trust. Although blockchain technology offers promising capabilities for addressing these challenges, the absence of clear architectural guidelines for public sector contexts limits effective adoption. This study proposes BRA-PS, a Blockchain Reference Architecture for Public Sector Citizen-Centric Applications, developed from a realworld digitalization project in Quebec, Canada. The architecture organizes components into six layers (presentation, business, communication, smart contract, blockchain, and data) with cross-cutting concerns addressing governance, access control, security, and monitoring. A key design principle is the publicprivate workflow separation, which enables inter-organizational collaboration while preserving each organization’s operational autonomy and data confidentiality. We validated the architecture through a case study involving a vehicle registration process between two public agencies, supported by a proof-of-concept implementation using Hyperledger Fabric. An Architecture Tradeoff Analysis Method (ATAM) evaluation, conducted with a panel of five domain experts, identified six architectural risks, including IPFS confidentiality exposure and smart contract inflexibility, six non-risks, six sensitivity points, and six trade-offs across three key quality attributes: autonomy, collaboration, and functional suitability. The results confirm that BRA-PS effectively guides implementation decisions and stakeholder alignment. Practical recommendations derived from the evaluation provide actionable guidance for blockchain adoption in public sector services.

Abstract: A function-based definition of a living individual as a central element and specially distinguished level of the phenomenon of life is proposed. According to this definition a living individual is a causally-closed network of five types of subordinate functions: p-processes (Ps), signals (Ss), feedbacks (Fs), re-writing (R(s)) and decoding (D(s)), directed recursively on the superior function: survival and proliferation (copying of its own identity in a possibly large number of copies possibly similar to the original), being self-dependent and self-sufficient in the realization of this purpose in its environment/ecological niche. This definition separates univocally living phenomena from inanimate processes in the case of the contemporary terrestrial life, origin of life on our planet, spontaneously-originated alien life in the universe, artificial and virtual life. According to this definition, life originated in the moment of formation of the first genetic code, including the “key” to this code coupling autocatalytic cycles of proteins (with random amino-acid sequences and divers catalytic abilities) and RNA (R), supported by and supporting proto-metabolism (P) and embedded in coacervate-like bubbles, into hypercycles of proteins and RNA (D) (“everything first” hypothesis). It clearly distinguishes the living individual from other levels of the organization of biological systems, such as living cells and organs, populations, ecosystems and the whole biosphere. Finally, it clearly decides whether such phenomena of doubtful status as viruses and viroids, plasmids, retrotransposons, chromosomes B, prions, cancer cells, mutualistic symbionts, mitochondria, colonial coelenterates, slime molds and eusocial insect(s) (colonies) are living individuals or not, and to what degree.

Abstract: Virtual currencies have become an increasingly prominent feature of the modern financial system, yet their public perception and adoption remain insufficiently understood. This study examines the perception and use of virtual currencies in Slovakia. Its primary objective is to assess public awareness, attitudes, and patterns of use. Data were collected through a structured questionnaire covering knowledge, perception, and engagement with virtual currencies. The responses were analysed using graphical methods and statistical techniques, including the t-test and Pearson’s chi-square test of independence, which were also employed to test the proposed hypotheses. The findings indicate high levels of awareness among younger respondents, but also a limited understanding of the underlying technologies and broader potential of virtual currencies. The results further suggest that many individuals hold only one virtual currency, reflecting either insufficient information or uncertainty about these assets. On the basis of these findings, the study proposes measures to improve the current situation, including targeted educational initiatives, investment in research and development, wider practical applications, enhanced security and trust, and continuous monitoring of market trends. The study offers evidence-based insights into the Slovak context and may also inform policymakers, educators, and financial institutions seeking to promote informed and responsible engagement with virtual currencies.

Abstract: Smallholder aquaculture communities at Musangezhi and Chisola Dams in Kalumbila District, Zambia, face escalating, poorly characterised water-quality threats from the adjacent Trident copper mine, yet no real-time monitoring infrastructure exists at either site. This paper presents the design, deployment, and empirical evaluation of the Resilient AI-Enhanced IoT (RAEI) framework a seven-node, solar-powered LoRaWAN sensor network coupled with a comparative machine-learning suite comprising Random Forest, XGBoost, Long Short-Term Memory (LSTM), and CNN-LSTM Hybrid models—trained on 3,551 ICP-OES heavy-metal observations covering copper (Cu), cobalt (Co), iron (Fe), and lead (Pb). XGBoost achieved the highest predictive performance across all four metals and all four-evaluation metrics, attaining a mean R2 of 0.515 and a mean MAPE of 35.89%, with lead prediction reaching R2 = 0.673. A TinyML-quantised LSTM on ESP32 microcontrollers ensured on-device anomaly alerting despite the loss of cloud connectivity. A 14-day trial field test achieved a composite resilience score of 7.5/10 (Technical: 7.4; Data: 8.3; Operational: 6.8). Desire to adopt the community was 73.3%, with cooperative membership (OR = 3.12, p < 0.001) and mobile-money use (OR = 2.67, p = 0.004) being the most significant factors. The RAEI framework detected 97.9% of contamination events missed by the prevailing quarterly manual-monitoring regime. These results confirm the RAEI framework as a technically viable, economically justified, and community-compatible solution for mining-proximate aquaculture surveillance across sub-Saharan Africa.

Abstract: Background: The number of elderly patients with hepatocellular carcinoma (HCC) has been increasing worldwide. This study aimed to evaluate the clinical outcomes of stereotactic body radiation therapy (SBRT) for patients aged ≥80 years with solitary HCC. Methods: This retrospective study included 117 patients with solitary HCC treated with SBRT between January 2019 and June 2025 at eight institutions in Japan. Patients were categorized into the very elderly group (≥80 years, n = 41) and the control group (<80 years, n = 76). Overall survival (OS), local tumor progression (LTP), and treatment-related toxicities were evaluated. Propensity score matching (PSM) was performed to minimize baseline imbalances between the two groups. Results: The median age was 84 years in the very elderly group and 74 years in the control group. The 3-year OS rates were 79.0% in the very elderly group and 62.8% in the control group, with no statistically significant difference observed (crude cohort, p = 0.072; PSM cohort, p = 0.114). The 3-year LTP rates were 18.9% in the very elderly group and 15.6% in the control group, without significant intergroup differences. Acute toxicities were numerically more frequent in the very elderly group; however, no grade ≥3 toxicities or treatment-related deaths were observed. Changes in ALBI score did not differ significantly between groups (p = 0.785). Conclusions: SBRT may represent a feasible treatment option with an acceptable safety profile in carefully selected very elderly patients with solitary HCC. It may be a reasonable option for this growing patient population.

Abstract: Background: Finerenone is associated with a lower, yet clinically relevant, risk of hyperkalemia compared with steroidal mineralocorticoid receptor antagonists in diabetic kidney disease (DKD) trials. However, real-world data on hyperkalemia and its associated factors are lacking. Methodology: FINE-TURK is a national, observational cohort of DKD patients who were initiated on finerenone. Eligible adults were included; demographic, clinical, and laboratory data were evaluated. The primary outcome (PO) was hyperkalemia risk signal (potassium ≥ 5.0 mEq/L), and the secondary outcome (SO) was clinically meaningful hyperkalemia (potassium ≥ 5.5 mEq/L). Multivariate logistic regression (LR) was used to define features associated with both PO and SO. LR, random forest (RF), gradient boosting, and CatBoost classifiers were used to define important features associated with the PO. Results: 699 patients were included. 259 (37.1%) reached the PO, and 51 (7.3%) reached the SO. Baseline potassium and estimated glomerular filtration rate (eGFR) were the most important variables associated with both outcomes and were consistently identified as the top features across all models. Thiazide use, presence of diabetic retinopathy, and diabetes duration were also associated with the PO. LR demonstrated the highest recall; random forest achieved the highest precision in performance. Discussion: Real-world data suggest that the risk of clinically meaningful hyperkalemia is similar to that in the clinical trials. In parallel with the safety analysis of clinical trials, baseline potassium and eGFR were consistently the most important factors associated with hyperkalemia risk.

Abstract: Cognitive impairment (CI) is prevalent among heart failure (HF) patients. Although the brain injury in HF is multifactorial, oxidative stress and neuroinflammation are common pathological features of neurological disorders and are increasingly recognized as key underlying mechanisms of CI. The role of extracellular vesicles (EVs) as effective communicators of biological signaling in myocardial function has been extensively investigated. EVs are well-known to transport a variety of microRNAs (miRNAs), however, it is unclear if myocardial injury alters the miRNA profiling of brain EVs which may contribute to CI by disrupting brain homeostasis. Using a rodent myocardial infarction (MI) model, we isolated brain EVs, and characterized their miRNA profiling by small RNA sequencing. Our results demonstrate that miRNA profiling in brain EVs varies with the progression of HF. Only three miRNAs were significantly changed at 3wks post-MI, thirty-two miRNAs demonstrate significant changes at 6wks post-MI, and sixty-five miRNAs show significant alterations at 12wks post-MI. Bioinformatic analysis suggests that some miRNAs against oxidative stress and inflammation were downregulated in brain EVs following 6wks post-MI, whereas several miRNAs responsible for oxidative stress and neuroinflammation were significantly increased, which may be cardiac in origin following MI. Collectively, cardiac EVs may contribute to the miRNA alterations in brain EVs, potentially contributing to CI by disrupting brain homeostasis.

Abstract: Background/Objectives: Household poverty is a known risk factor for early childhood development. However, the extent to which caregiver education can mitigate these risks remains underexplored in Southeast Asian contexts. This study investigates whether caregiver educational attainment buffers the negative impact of low household income on child-rearing environments and early developmental outcomes in Indonesia. Methods: This study utilized cross-sectional data from Indonesian caregivers. To maximize statistical power, analyses of the home environment (Index of Child Care Environment) full sample (N = 933). Analyses of developmental outcomes (Early Childhood Development Index) were restricted to the validated age cohort of 3- and 4-year-old children (N = 355). General Linear Models (GLM) were conducted, controlling for child age and sex. Results: For the home environment, both household income (p = .042) and caregiver education (p = .021) were independent, significant predictors, with no significant interaction. However, for actual developmental outcomes, a highly significant interaction between income and education emerged (p < .001). Conclusions: While education and income independently improve the home environment, caregiver education acts as a robust protective buffer for actual child development, mitigating the risks typically associated with low-income households. Interventions targeting socioeconomic disparities should prioritize parenting and caregiver education.

Abstract: This paper introduces the radius of integrability, a quantitative invariant that transforms the qualitative ϵ-δ formulation of Riemann integration into a measurable property of function spaces. For a Riemann integrable function and a prescribed accuracy ϵ, the radius identifies the largest partition mesh δ that guarantees every tagged Riemann sum approximates the integral within the specified error. The framework is developed for both compact domain intervals, via pointwise and uniform radii, and unbounded intervals, through the tail integrability radius which quantifies the necessary truncation window for improper integrals. Key theoretical results include the establishment of a bottleneck identity relating local and global mesh requirements and a structural theorem showing that for C1 integrands, the radius is asymptotically governed by the inverse of the function’s total variation. Furthermore, this work completes a hierarchical program of regularity radii—encompassing convergence, continuity, and differentiability—by revealing a dimensional progression of geometric anchors. We demonstrate that while continuity is anchored at a point and differentiability at a line, integrability is anchored at a two-dimensional region. The theory is illustrated through explicit computations for several classical functions, including the normal density, the stretched exponential, and the Thomae function, providing a new quantitative lens for classifying integrable functions based on their partition sensitivity and tail decay regimes.

Abstract: Blood can clot into anomalous, fibrinolysis-resistant forms that arise from prothrombotic seeding areas, including damaged cellular debris and membrane-derived surfaces, giving rise to what we have termed fibrinaloid microclot complexes (colloquially: microclots).Their proteolytic resistance is due to the fact that they are amyloid in nature, and they can also entrap inhibitors of proteolysis. They consist of a variety of proteins besides the expected fibrin, and are highly enriched for other amyloidogenic proteins (in contrast to normal clots, whose proteome largely reflects the soluble plasma proteome). They also contain DNA in the form of neutrophil extracellular traps (NETs). Importantly, fibrinaloid microclot complexes are heterogeneous structures comprising multiple phenotypic forms, including those that nucleate and grow on cellular debris such as damaged membranes, microparticles, and immune-derived material. These debris-associated complexes act as catalytic scaffolds that recruit fibrin(ogen) and inflammatory molecules, thereby amplifying amyloidogenic transformation and prothrombotic activity. Fibrinaloid microclot complexes have been reported in a widening range of chronic inflammatory and thrombo-inflammatory diseases in which they have been sought, and are highly enriched for amyloidogenic proteins. Additionally, the thrombi extracted from ischaemic stroke also contain proteins in an amyloid form, implying that such macroclots can form via the accretion of microclots that already contain amyloid. We here show that these microclots exhibit a classical ‘apple-green’ birefringence when stained with the dye Congo red. The urgent task now is to find means of inhibiting the transition to amyloid forms during the clotting process.

Abstract: Emerging technologies and cyber-physical systems have led to the development of complex mathematical models described by differential equations with multiple fractional orders. In this regard, this paper investigates the stability of control systems for this class of models, defined by state equations with multiple fractional orders ranging between 0 and 1. Matrix criteria and comparison principle for linear and nonlinear autonomous systems of different fractional orders are developed based on generalized Lyapunov functions for differential equations with multi-order fractional exponents. The results are extended to non-autonomous linear or with nonlinear components systems of different fractional orders. The application of the Yakubovich-Kalman-Popov lemma, adapted for this class of systems, allows us to obtain new stability criteria presented as frequency criteria and represented graphically by familiar frequency plots similar those of the Nyquist or Popov type. Numerical applications illustrate these results such as models of complex human-machine systems described by state equations of multivariable fractional orders. An analysis of the advantages of the proposed methods compared to procedures and techniques used in other papers regarding the study of multi-order fractional exponent systems is presented. It is demonstrated that the proposed methods minimize the computational effort required for stability criteria.

Abstract: The association of a major aortopulmonary collateral artery (MAPCA) with simple trans-position of the great arteries (TGA) is uncommon. Such high-flow lesions in the postoper-ative period following arterial switch operation (ASO) may lead to pulmonary hyperten-sion, pulmonary hemorrhage, heart failure (HF), failure to thrive and prolonged mechan-ical ventilation. We report a neonate who developed pulmonary overcirculation and HF in the early postoperative period due to a hemodynamically significant MAPCA. Although the association of MAPCA with simple TGA is infrequent, such lesions should be considered in cases of unexplained cardiovascular compromise following ASO. Fol-lowing transcatheter occlusion of the MAPCA with a vascular coil, rapid hemodynamic stabilization and subsequent extubation of the patient were achieved.