Abstract: Tourism is increasingly regarded as a strategic instrument for economic diversification and regional development; however, in many emerging economies, growth in tourist arrivals does not always translate into proportional economic gains. This study examines the sustainable development of domestic tourism in Kazakhstan by analyzing revenue efficiency, structural constraints, and productivity-related factors. Using national statistical data for the period 2014–2024, a log–log regression model estimated by ordinary least squares was applied to assess the elasticity of tourism revenue with respect to tourist flows and investment in tourism-related fixed assets. The results indicate a moderate positive elasticity of tourism revenue with respect to tourist arrivals (0.56), suggesting that increases in visitor numbers lead to relatively modest income growth. In contrast, investment in tourism-related fixed assets exhibits a short-term negative elasticity (0.39), indicating that additional investment does not immediately translate into higher revenue, likely due to adjustment lags. Sectoral analysis shows that tourism revenues are heavily concentrated in transport and accommodation services, while higher value-added activities remain underdeveloped. These findings imply that policy should shift from volume-oriented growth toward diversification, productivity enhancement, and the development of higher value-added tourism activities, thereby strengthening tourism’s contribution to sustainable economic growth in Kazakhstan.

Abstract:

Colon-targeted drug delivery systems are of considerable interest for improving the therapeutic efficacy of anticancer agents while minimizing systemic side effects. In this study, semi-interpenetrating polymer network (semi-IPN) hydrogels based on methacrylated dextran and native inulin were designed as biodegradable carriers for the colon-specific delivery of uracil as a model antitumor compound. The hydrogels were synthesized via free-radical polymerization, using diethylene glycol diacrylate (DEGDA) as a crosslinking agent at varying concentrations (5, 7.5, and 10 wt%), and their structural, thermal, and biological properties were systematically evaluated. Fourier transform infrared spectroscopy (FTIR) confirmed successful crosslinking and physical incorporation of uracil through hydrogen bonding. At the same time, differential scanning calorimetry (DSC) revealed an increase in glass transition temperature (T_g) with increasing crosslinking density (149, 153, and 156 °C, respectively). Swelling studies demonstrated relaxation-controlled, first-order swelling kinetics under physiological conditions (pH 7.4, 37 °C), and high gel fraction values (84.75, 91.34, 94.90%, respectively) indicated stable network formation. All formulations exhibited high encapsulation efficiencies (>86%), which increased with increasing crosslinker content, consistent with the observed gel fraction values. Simulated in vitro gastrointestinal digestion showed negligible drug release under gastric conditions and controlled release in the intestinal phase, primarily governed by crosslinking density. Antimicrobial assessment against Escherichia coli and Staphylococcus epidermidis, used as an initial or indirect indicator of cytotoxic potential, revealed no inhibitory activity, suggesting low biological reactivity at the screening level. Overall, the results indicate that DEGDA-crosslinked dextran/inulin semi-interpenetrating polymer network (semi-IPN) hydrogels represent promising carriers for colon-targeted antitumor drug delivery.

Abstract: We present a self-contained, audit-grade formulation of the Quantum Information Copy-Time (QICT) program as a micro–macro closure framework. The microscopic layer is strictly unitary and localitypreserving (a quantum cellular automaton, QCA), including a gauge-coded code-subspace construction and a continuum Dirac limit as a controlled long-wavelength approximation. The central micro–macro bottleneck is the emergence of diffusion from deterministic unitary dynamics. Rather than overclaiming a resolved theorem where the general problem remains open, we (i) replace informal “fast mixing” language by a structured, measurable spectral criterion in the hydrodynamic sector (SDC), and (ii) provide a quantitative bridge showing how certified second-moment (design-channel) diffusion controls infinite-temperature density correlators whenever a local approximate-design property holds (with explicit error bounds). We supply complementary numerical evidence: exact-unitary diagnostics by ED at L = 12 with an L = 14 cross-check, a max-L certification up to L = 512 at the momentchannel level, including a vanishing ballistic/Drude proxy, and a scalable unitary MPS–TEBD typicality diagnostic with explicit Drude bounds and bond-dimension convergence tests. We then propagate audited parameter intervals through a phenomenological closure map, with an explicit reproducibility contract (JSON, hashes, and PASS/FAIL verifier). All claims are labeled as PROVEN, CERTIFIEDNUMERICAL, EXTERNAL-DATUM, HYPOTHESIS, or CONJECTURE.

Abstract: Fault-tolerant control in safety-critical industrial systems demands adaptive responses to equipment degradation, parameter drift, and sensor failures while maintaining strict operational constraints. Traditional model-based controllers struggle under these conditions, requiring extensive retuning and dense instrumentation. This work presents a safety-aware multi-agent deep reinforcement learning framework for adaptive fault-tolerant control in sensor-lean industrial environments, addressing three critical deployment barriers: formal safety guarantees, simulation-to-reality transfer, and instrumentation dependency. The framework integrates four synergistic mechanisms: (1) multi-layer safety architecture combining constrained action projection, prioritized experience replay, conservative training margins, and curriculum-embedded verification achieving zero constraint violations; (2) multi-agent coordination via decentralized execution with learned complementary policies; (3) curriculum-driven sim-to-real transfer through progressive four-stage learning achieving 85--92\% performance retention without fine-tuning; and (4) offline Extended Kalman Filter validation enabling 70\% instrumentation reduction (91--96\% reconstruction accuracy) while maintaining regulatory compliance. Validated through sustained deployment in commercial beverage manufacturing Clean-In-Place (CIP) systems—a representative safety-critical testbed with hard flow constraints ($\geq$1.5 L/s), harsh chemical environments, and zero-tolerance contamination requirements—the framework demonstrates superior control precision (coefficient of variation: 2.9--5.3\% versus 10\% industrial standard) across three hydraulic configurations spanning complexity range 2.1--8.2/10. Comprehensive validation comprising 37+ controlled stress-test campaigns and hundreds of production cycles (July--December 2025) confirms zero safety violations, high reproducibility (CV variation < 0.3\% across replicates), predictable complexity-performance scaling ($R^2 = 0.89$), and zero-retuning cross-topology transferability. The system has operated autonomously in active production since July 2025, establishing reproducible methodology for industrial reinforcement learning deployment in safety-critical, sensor-lean manufacturing environments.

Abstract:

Additive manufacturing of polymer tools represents a promising alternative to conventional steel tooling for low-force and low-volume sheet metal air bending. However, accurate prediction of sheet springback and the resulting deviation of the bending angle after elastic unloading remains a major challenge. This study presents an integrated experimental–numerical framework for the analysis of air bending with additively manufactured polymer tools, with emphasis on material characterization, springback prediction, and tool angle compensation. The methodology combines uniaxial tensile testing, controlled air-bending experiments, finite element modelling with rigid and deformable tools, and optical 3D scanning for angle measurement. Low-carbon steel DC04 sheets were modeled using an elastoplastic constitutive law, while FDM-printed ABS tools were described by experimentally calibrated material models. Numerical simulations were performed over a range of forming forces to evaluate springback behavior and elastic tool deformation. The results show very good agreement between experiments and simulations. Deviations in bending angle were below 1.5% for metallic tools and below 0.5% for springback compensation, with the smallest discrepancy obtained using a two-dimensional model with deformable tools. Experimental validation with ABS tools confirmed bending accuracy within ±1°. The proposed framework provides a reliable basis for springback prediction and rational design of additively manufactured polymer tools for air-bending applications.

Abstract:

Background: Trained immunity (TRIM) enhances innate immune responses through epigenetic and metabolic reprogramming but can become maladaptive, contributing to chronic inflammation. In people living with HIV (PLWH), maladaptive TRIM has been proposed but remains insufficiently defined. Methods: We examined inflammatory cytokine production in monocyte-derived macrophages (MDMs) obtained from PLWH and age-matched individuals without HIV infection. Baseline cytokine output and responses to Toll-like receptor (TLR) stimulation were measured. We also assessed whether TRIM influenced susceptibility of MDMs to HIV infection. Results: Unstimulated MDMs from male, but not female, PLWH produced significantly higher levels of IL-6 compared with uninfected controls. IL-6 production positively correlated with duration of HIV infection, suggesting cumulative TRIM imprinting. TLR engagement markedly amplified cytokine responses in PLWH-derived MDMs, consistent with a trained phenotype. Despite enhanced inflammatory responsiveness, TRIM did not confer protection from HIV infection of MDMs, indicating functional maladaptation rather than beneficial priming. Conclusions: These findings provide evidence of maladaptive TRIM in PLWH, characterized by persistent inflammation and heightened cytokine responsiveness. The observed sex-specific differences suggest distinct TRIM programming in male and female PLWH. Further studies are needed to elucidate mechanisms driving these disparities and to determine their impact on HIV-associated inflammation and clinical outcomes.

Abstract: This study investigates effective strategies for delivering physiotherapy services in underserved rural settings. It explores the factors influencing the success of public-private partnerships (PPPs) from the perspective of key stakeholders. Through qualitative inquiry in regional Australian towns, the research identifies critical mechanisms that facilitate or hinder the implementation of sustainable physiotherapy services. Findings highlight the importance of resource allocation, stakeholder collaboration, and process optimization in overcoming challenges in remote healthcare delivery.

Abstract:

Adverse childhood experiences (ACEs) prompt parentification, which is related to providing regular caregiving as adults. This study examines the association between the number and types of ACEs and caregiving as adults, and to whom caregiving is extended. Analyses were based on 91,193 adults from 13 states in the U.S. in 2020-2024 and involved binomial and multinomial logistic regression, adjusted for selected covariates. Approximately 21% of participants provided regular care and 66% had ≥1 ACEs. Each of 11 ACEs considered was positively associated with providing regular care. As the number of ACEs increased, the odds of providing regular care increased. The strongest ACE predictor of providing regular care was living with a parent or adult who was depressed, mentally ill, or suicidal, and the weakest was when the parents were divorced, separated, or an unmarried couple. As the number of ACEs increased, providing regular care for a parent significantly decreased, whereas providing regular care for a friend/nonrelative significantly increased. Among those receiving regular care, if the caregiver had more ACEs versus less, they were significantly less likely to care for a parent or grandparent but more likely to care for a spouse, child, friend or non-relative.

Abstract:

Artificial intelligence (AI) based motion capture has revolutionized the field of biomechanics and locomotion analysis by enabling more widespread adoption of the technique. In this realm, the Google based Mediapipe Pose AI motion capture software is a robust platform for close-to-real-time motion capture of many body landmarks stretching from the upper limbs to lower limbs. This preprint reports an attempt to code an in-house Mediapipe Pose based Python motion capture platform useful for upper limb exercise performance analysis, and rehabilitative therapy of upper limbs with dysfunctional muscle control and movement such as in mild stroke patients. Specifically, the software is capable of tracking real-time position and movement of the elbow, wrist, and shoulder joints, and can calculate both the shoulder and elbow joint angle evolution, and angular velocity changes. More importantly, such data are chronicled in both graphs and a frame-by-frame catalogue of joint angle and angular velocity changes, that altogether, serves as useful data for personal evaluation of exercise performance, as well as physiotherapy post-rehab assessment of treatment progress. The software is capable of tracking the full range of motions of the shoulder-elbow movement system, and can be used for a variety of exercise performance tests, as well as for diagnosing and tracking upper limb movement disorders in mild stroke and musculoskeletal dysfunction patients.

Abstract: The current practices of the university technology transfer profession seem to reflect the belief that the chances for success are greatly improved when faculty inventors employ their social capital to facilitate the process. However, this notion has not been extensively investigated directly. There is a gap in the university technology transfer literature regarding our understanding of faculty inventor social capital in the context of the occurrence of technology transfer outcomes. The aim of this study was to understand whether the use of faculty inventor social capital is a causal condition for the occurrence of university technology transfer. This question was examined using a multiple case study approach and the qualitative comparative analysis (QCA) method. The data were generated by collecting information on 21 cases that occurred during or around calendar year 2019 in which a private sector organization considered whether to obtain and assimilate a technology that was created at a university in the United States of America. The results of the study suggest that the use of faculty inventor social capital is not a necessary, sufficient, or INUS condition for the occurrence of university technology transfer.

Abstract: Background: Emerging evidence suggests that lipedema may share hormonal, in-flammatory, and genetic mechanisms with gynecologic diseases, particularly endome-triosis. However, the extent and nature of these interrelationships remain poorly cha-racterized, supporting the need for this scoping review. Objectives: To map and synthesize the available evidence on the clinical, pathophysiological, and epidemiolo-gical interrelationships between lipedema in women, endometriosis, and other gyne-cologic diseases. Methods: Searches were conducted in international and regional health databases, including MEDLINE (PubMed), CINAHL, Scopus, Embase, Web of Science, the Cochrane Library, LILACS/VHL, APA PsycInfo, SciELO, Epistemonikos, and La Referencia, as well as grey literature sources and relevant institutional websites. There were no language restrictions. The search period began in 1940, the year in which li-pedema was first described by Allen and Hines. Study selection followed a two-stage process conducted independently by two reviewers, consisting of title and abstract screening followed by full-text review. Data extraction was performed using a pre-developed and peer-reviewed instrument covering participants, concept, context, study methods, and main findings. The review protocol was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/D65GS). Results: Twenty-five stu-dies from ten countries were included. Synthesis of the available evidence indicates that lipedema is consistent with a systemic condition involving metabolic and hormonal dimensions, characterized by onset related to reproductive milestones, a high frequency of gynecologic and endocrine comorbidities, and molecular features overlapping with steroid-dependent pathologies. These findings reflect a recent shift from a predominantly lymphovascular paradigm toward a more integrated endocrinometabolic framework. Conclusions: The findings indicate that lipedema clusters with hormone-sensitive gynecologic and endocrine features across reproductive life stages.

Abstract: Background: Ductoscopic resolution is insufficient to distinguish the flat lesions and microcalcifications that indicate malignancy in patients with pathologic nipple discharge (PND). This study evaluated the feasibility of imaging intraductal epithelial layers, premalignant, or malignant lesions using catheter-integrated optical coherence tomography (OCT) through the nipple orifices. Methods: Mastectomy specimens were prospectively obtained from patients who had undergone simple or skin-sparing mastectomies for either malignancy (n = 14) or prophylaxis (n = 4). Ductoscopy was used to ensure that the OCT catheter was safely inserted through the nipple orifice of the ex vivo specimens. Cross-sectional OCT scanning of the ductal epithelial layers was performed to acquire high-resolution images of approximately one million pixels. The abnormal lesions identified on the OCT images were evaluated using correlating histopathologic analyses. Results: Fourteen out of 18 mastectomy specimens could be cannulated and distended using ductoscopic instruments and saline. Only 4 out of 18 specimens had presented with clinical PND. To confirm that the ductoscopic trocars were located inside the ducts, 14 specimens were randomly selected and explored with ductoscopy. The OCT catheter was able to insert through the ductoscopic trocars in 10 specimens and revealed one in situ ductal cancer (DCIS) in a cancer-involved specimen and one florid ductal hyperplasia in a prophylactic specimen. Both lesions were confirmed by histopathological correlations. The OCT scanning did not detect malignant lesions in 80% of the specimens without PND; however, the OCT scanning did detect microcalcifications and undefined lesions. Conclusion: This is the first published study to confirm the feasibility of intraductal breast OCT to show millimetric Florid Ductal Hyperplasia and a DCIS in a prophylactic and cancer involved specimen, respectively.

Abstract: Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin condition associated with psychological distress and diminished quality of life (QoL). The complex interplay between anxiety, depression, and multidimensional QoL in adults with AD remains insufficiently understood. This study aimed to examine the relationships and key predictors linking psychological distress and QoL in this population. Methods: In this cross-sectional study, 47 AD participants completed the Hospital Anxiety and Depression Scale (HADS) and World Health Organization Quality of Life (WHOQOL-BREF). Bivariate and multivariate analyses identified associations and predictors among anxiety, depression, and QoL domains. Results: Elevated anxiety (7.91 ± 3.27) and depression (6.28 ± 3.62) scores were observed, with moderate-to-poor QoL across all domains. Anxiety and depression were negatively correlated with all QoL dimensions (p &lt; 0.05). Depression and stress predicted poorer self-perceived QoL (p &lt; 0.001), and inadequate sleep was associated with lower environmental QoL (p = 0.006). Higher AD episode frequency correlated with reduced psychological QoL (p = 0.007). Conclusions: This study highlighted the substantial psychological burden and impaired QoL experienced by adults with AD, with depression, stress, and sleep quality serving as key modifiable factors. Integrated care addressing both physical and psychological factors is recommended to improve outcomes in this population. Future research should prioritize longitudinal designs and AD-specific assessments to further elucidate causal pathways and inform targeted interventions.

Abstract: Artificial intelligence (AI) is increasingly integrated into security operations to support threat detection, alert triage, and incident response. However, miscalibrated trust in AI systems—manifesting as either over-reliance or undue skepticism—can undermine both operational effectiveness and human oversight. This paper presents a conceptual framework for calibrated trust in AI-driven security operations, emphasizing analyst–AI collaboration rather than fully autonomous decision-making. The framework synthesizes key dimensions including transparency, uncertainty communication, explainability, and human-in-the-loop controls to support informed analyst judgment. We discuss how calibrated trust can mitigate automation bias, reduce operational risk, and enhance analyst confidence across common security workflows. The proposed framework is intended to guide the design, deployment, and evaluation of trustworthy AI systems in security operations and to serve as a foundation for future empirical validation.

Abstract:

Ocular hypotony is an uncommon but vision-threatening cause of optic disc oedema. We present a case of a young woman with a complex ophthalmic history, including juvenile idiopathic arthritis (JIA), JIA-associated uveitis, secondary glaucoma, and suspected idiopathic intracranial hypertension, who developed significant hypotony-related optic disc oedema on a background of mild bilateral disc swelling. The case emphasises the importance of recognising hypotony maculopathy as a differential diagnosis for disc swelling, particularly in patients with fluctuating intraocular pressure and coexisting inflammatory eye disease. We discuss the concepts of the translaminar pressure gradient and its role in the development of optic disc oedema in the presence of both ocular hypotony and probable raised intracranial pressure.

Abstract:

Background/Objectives: Accurate preoperative localization of hyperfunctioning parathyroid tissue is essential for minimally invasive parathyroidectomy. Conventional planar dual-phase 99mTc-sestamibi scintigraphy is widely used but shows reduced diagnostic accuracy in patients with thyroid nodules or ectopic glands. Hybrid triple-head SPECT/CT integrates functional and anatomical imaging and may improve lesion detection. This study evaluated the diagnostic performance of triple-head SPECT/CT compared with planar scintigraphy and explored correlations between biochemical markers and imaging positivity. Methods: A retrospective single-center study included 90 adults referred for suspected primary hyperparathyroidism between January 2021 and August 2025. Demographic data, laboratory parameters (PTH, total and ionized calcium, 25-hydroxyvitamin D), and imaging results were collected. Diagnostic accuracy was assessed in patients with surgical confirmation or robust clinical verification. Correlations between biochemical markers and imaging positivity were analyzed using Pearson correlation coefficients. Results: SPECT/CT demonstrated significantly higher sensitivity than planar scintigraphy (62.5% vs. 14.3%) and an excellent negative predictive value (95.1%), whereas planar imaging showed slightly higher specificity (79.5%). Ionized calcium correlated significantly with SPECT/CT positivity (r = 0.39; p = 0.009), while PTH and 25-hydroxyvitamin D showed no significant association. SPECT/CT accurately localized ectopic parathyroid glands and lesions in patients with coexisting thyroid nodularity, overcoming limitations of planar imaging. Several lesions undetected by planar scintigraphy were identified on SPECT/CT, supporting its role in anatomically complex or subtle cases. Conclusions: Triple-head SPECT/CT provided superior diagnostic performance over planar scintigraphy for preoperative localization in primary hyperparathyroidism, particularly in patients with thyroid nodularity or ectopic glands. Ionized calcium may serve as a complementary predictor of lesion detectability. These findings support hybrid SPECT/CT as the preferred first-line imaging modality, facilitating targeted minimally invasive surgery and optimizing surgical planning.

Abstract: To achieve the dual objectives of utilizing agricultural waste and efficiently removing sulfamethoxazole (SMX) from water, this study prepared biochar from corn straw at 700  °C. The biochar was subsequently activated via KOH and H₃PO₄ treatments to produce two types of modified biomass-activated carbon: KOH-C and H₃PO₄-C. Both activated carbons exhibited similar surface functional groups. The adsorption kinetics of SMX were better described by the pseudo-second-order model, while both the Langmuir and Freundlich models provided good fits to the adsorption isotherm data. Characterized by a larger specific surface area and more developed pore structure, KOH-C demonstrated a higher adsorption capacity for SMX than H₃PO₄-C. Therefore, KOH-C was selected for further investigation. A Box-Behnken design combined within response surface methodology was then employed to analyze the factors influencing SMX removal. The results showed that the interactive effects of pH–dosage and pH–temperature were significant (P < 0.05). The main effects of temperature and dosage, along with the quadratic term of dosage, were highly significant (P < 0.01). Lower pH, higher temperature, and larger dosage favored SMX removal. Under the theoretically predicted optimal conditions (pH = 4, temperature = 35  °C, and dosage = 198.4  mg, equivalent to 0.992  g/L), the removal rate of SMX reached 99.9%.

Abstract: Background Transcatheter tricuspid edge-to-edge repair (T-TEER) is a widely available treatment option for patients with tricuspid regurgitation (TR). However, not all patients benefit from T-TEER and may require alternative transcatheter tricuspid valve interventions (TTVI). The aim of the study was to characterize patients with severe TR referred for transcatheter treatment and identify potential candidates for alternative TTVI. Methods The CAPTURE Pilot Study (NCT 06838611) enrolls consecutive patients referred for TR treatment. All patients undergo clinical and echocardiographic assessment to determine eligibility for T-TEER. Those deemed anatomically ineligible or with unsuccessful T-TEER are considered for alternative TTVI. Results 147 patients were enrolled, 77 (52.4%) patients were qualified for T-TEER and the procedure was performed in 71 (48.3%) patients, with successful TR reduction in 55 cases (77.5% of treated patients); a subset of 34 patients (23.1%) was identified as potential candidates for alternative TTVIs. These patients exhibited more advanced TR (torrential TR 76.5% vs. 18.2%; p< 0.001) and right heart failure symptoms (ascites 44.1% vs. 12.7%; < 0.001). Additionally, they had significantly higher bilirubin concentration (1.09 [1.20] mg/dl vs. 0.61 [0.42] mg/dl; p=0.003), lower hemoglobin level (11.8 [1.7] g/dl vs. 12.3 [1.7] g/dl; p=0.017) and platelet count (161.0 [51.0] x 109/L vs. 183.0 [79.0] x 109/L; p=0.015) suggesting an increased bleeding risk. Conclusions In this study, approximately half of patients with severe TR were eligible for T-TEER, while more than 20% may require alternative TTVI. This subgroup exhibits more advanced disease and a higher prevalence of bleeding risk factors, which should be carefully considered during the decision process.

Abstract: Skyline Query, one of the profound tools that holds up tremendously when it comes to extracting valuable insights has witnessed multiple significant evolutions both in application domain and problem complexity over the years. In this SLR (Structural Literature Review), this study has tried to investigate the trends, evolutions of the application domain, and problem complexity from as early as 2008 until now. The authors divided the timespan into three major periods and analyzed 28 Scopus-indexed papers which this study chose using the PRISMA methodology. When looking at insights on application domain evolution, in the early years fundamental algorithmic research was taking place and it gradually shifted towards more specialized applications such as smart cities, IoT, and distributed computing. As the domains evolved, the complexity of the problems also spiked as a need to handle higher dimensionality in data, larger volume, and increased uncertainty became apparent. This paper provides impactful insights into how skyline query research domains have changed and tries to highlight future directions for addressing newer and more complex data management challenges.

Abstract: Human metapneumovirus genotype B (HMPV-B) is an important respiratory pathogen, requiring detailed elucidation of the evolutionary and antigenic features of its fusion (F) gene. Using 500 sequences collected between 1982 and 2024, we investigated the molecular evolution, phylodynamics, and structural epitope landscape of the HMPV-B F gene. Time-scaled phylogeny dated the divergence of sublineages B1 and B2 to around 1938, and Bayesian Skyline Plot analysis showed that these sublineages exhibited distinct demographic trajectories over time. The F gene evolved at a rate of 1.01 × 10⁻³ substitutions/site/year; however, amino acid variation remained limited, consistent with pervasive purifying selection, with 39% of codons under strong negative selection and little consensus evidence for positive selection. Conformational B-cell epitope prediction demonstrated a high degree of conservation across neutralizing antibody binding regions (sites Ø and I–V), and amino acid substitutions occurring within these sites were not predicted to substantially alter epitope architecture. Together, these findings indicate that the HMPV-B F gene evolves under strong evolutionary constraint while maintaining stable antigenic features, supporting the potential for antibody-based strategies that target neutralizing antibody binding regions of the F protein.