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Article
Medicine and Pharmacology
Dentistry and Oral Surgery

Ece Selen Koçar

,

Kıvanç Akça

Abstract: Centric relation (CR) is a reproducible mandibular reference position that plays a critical role in complex prosthodontic cases. With the advent of digital jaw tracking devices, CR can now be recorded with greater precision through fully digital methods. This study aimed to compare pati-ent-reported outcome measures (PROMs) for the recording of CR determined with conventional and digital techniques. Patients requiring occlusal rehabilitation due to bilateral loss of posterior support in the maxilla were included. Two different jaw relation recording techniques were ap-plied: conventionally determined CR and digitally determined CR. The former was determined using bimanual manipulation, while the latter through multiple mandibular closure recordings performed with an anterior plateau using a jaw-tracking device. PROMs were assessed using Visual Analog Scale (VASs) to evaluate patient experience during jaw relation recording and comfort during restoration try-in. The recording time for both techniques was documented, and the correlation between recording time and VAS scores related to the recording procedure was analyzed. Statistical analyses were performed using the Wilcoxon signed-rank test and Spear-man correlation analysis (α=0.05). Twelve patients were included. No statistically significant difference was found between the two methods in VAS scores assessing patient-reported com-fort and experience. Recording time was significantly shorter for the recording of conventionally determined CR (p=0.002). No statistically significant correlation was found between recording time and patient-reported experience for both techniques (p>0.05). Despite the need for clinician experience and patient compliance, PROMs for digitally determined CR were comparable to those of conventionally determined CR.

Article
Social Sciences
Religion

Bupinder Singh Bali

Abstract: This article examines Sikhism's principle of Vand Chakna (sharing one's earnings) and its institutional manifestation in Langar (community kitchen) as distinctive configurations of religious giving that challenge dominant anthropological frameworks. Drawing on gift theory, moral economy, and comparative religious ethics, the analysis demonstrates how Sikh practices resist the hierarchical asymmetries and moral accounting that structure charitable systems. Rather than framing giving as oriented toward reciprocity, merit, or obligation, Vand Chakna positions sharing as a constitutive condition of collective life, grounded in relational ontology and enacted through embodied practice. Langar functions as an "ethical infrastructure"—a material, spatial, and institutional arrangement that stabilizes egalitarian ethics through routine participation. Comparative analysis with Hindu dāna and Islamic zakāt clarifies how Sikh ethics diverge from merit-accumulation and purification-oriented giving. The concept of ethical infrastructure proves analytically valuable for understanding how religious practices materialize moral orientations while negotiating persistent social hierarchies. This theoretical framework invites future ethnographic research on how egalitarian principles operate in lived contexts marked by caste, class, and gender inequalities.

Article
Biology and Life Sciences
Life Sciences

Marissa Cervantes-Llamas

,

Tania Judith Hernández-López

,

Juana María Coronado-Blanco

,

Jacinto Treviño-Carreón

Abstract:

Species of the Orchidaceae family, as floristic members of the ecosystems they inhabit, are of great importance. However, many of them have been categorized as at risk because of the low rate of seed production. For this reason, knowledge of the biology of pollination of species at risk is vital for their conservation. Studies conducted in this area are scarce; thus, the objective of this research was to determine the mechanism of pollination for reproductive success in a wild population of Cyrtopodium macrobulbon La Llave & Lex. The study was conducted in the ejido Gallos Grandes, Tula, Tamaulipas, Mexico. We selected 23 Cyrtopodium macrobulbon individuals in the flowering stage and described the morphology of the flowers and inflorescences, as well as the adult individuals. To determine their mechanisms of pollination, five treatments were set up. The fruits produced by everyone were collected and we obtained their fructification percentage and seed mass. The data were analyzed using SAS 9.0. The percentage of fructification was higher in the control treatment, while the seed mass was significantly higher in the treatment of cross pollination. This study determined effective pollination mechanisms that guarantee reproductive success and that can be considered in conservation plans for the species C. macrobulbon.

Short Note
Chemistry and Materials Science
Organic Chemistry

Andrej Bogataj

,

Luka Ciber

,

Nejc Petek

,

Franc Požgan

,

Jurij Svete

,

Bogdan Štefane

,

Uroš Grošelj

Abstract: An alkene-tethered enaminone was synthesized in four steps from bromoacetic acid and 3,3-dimethylallyl alcohol. The enaminone was fully characterized, including UV-Vis spectra. TBADT-catalyzed HAT of the alkene-tethered enaminone initiated a fragmentation that yielded the literature-known phenylacetone-derived enaminone.

Article
Medicine and Pharmacology
Endocrinology and Metabolism

Rajashekar Korutla

,

Tanisha Garg

,

Michael P Wilczek

,

Elsie G Ross

,

Saeed Amal

Abstract: Peripheral artery disease (PAD) is a global health burden affecting over 200 million individuals and is frequently complicated by limb-threatening ischemia, leading to major amputations. Despite known clinical risk factors, the genetic basis underlying amputation risk in PAD remains poorly defined. In this study, we performed a multi-pronged genome-wide association study (GWAS) to identify genetic variants associated with lower extremity amputation in patients with PAD, using data from the All of Us Research Program. Two analytical strategies were employed: a targeted GWAS using ClinVar variants on the full cohort and a comprehensive genome-wide association study using Allele Count/Allele Frequency (ACAF) data on a balanced subset. The ClinVar analysis of 118,871 variants in 14,771 PAD patients (613 with amputation, 14,158 without) identified 3 suggestive associations with a genomic inflation factor of 1.046. The ACAF analysis of 7,784,837 quality-controlled variants in 804 balanced samples (399 cases, 405 controls) yielded 35 suggestive associations (p < 1×10⁻⁵) with a genomic inflation factor of 1.017. No variants achieved suggestive significance in both analyses. These findings highlight candidate loci for further validation and may inform future development of risk prediction tools and targeted interventions to reduce limb loss in PAD.

Article
Engineering
Safety, Risk, Reliability and Quality

Abeer K. Jameel

,

Zaineb Mossa Jasim

Abstract: Speed management plays a critical role in road safety; however, conventional speed limits are determined based on geometry and traffic characteristics, with limited consideration of pavement structural condition and surface distress. This study proposes an integrated mechanistic–quantitative framework that links pavement distress and road safety indicators to the selection of speed limits. A flexible pavement section on Highway No. 80 in Iraq is analyzed as a case study. Mechanistic pavement analysis using KENPAVE is employed to estimate critical strains based on field traffic data and Equivalent Single Axle Loads (ESAL). The rate of failure is estimated by comparing the ESAL and the allowable load repetitions. Safety-related constraints are then derived to quantify hydroplaning risk, braking performance through stopping sight distance, and the vertical shock criterion. The results indicate that the existing pavement structure is marginal, with a high probability of fatigue failure and sensitivity to rutting under traffic growth. The integrated safety analysis yields a critical wet-weather speed of approximately 67–70 km/h, while localized settlements exceeding 10 mm require speed reductions to 50–60 km/h to maintain vehicle stability. The proposed framework demonstrates that pavement condition directly influences safe speed and provides a rational basis for safety-oriented speed management.

Article
Public Health and Healthcare
Public Health and Health Services

Leon Wreyford

,

Raj Gururajan

,

Xujuan Zhou

,

Niall Higgins

Abstract: Background: Documentation in oncologist Electronic Health Records (EHRs) plays a critical role in communication, shared decision-making, and the detection of adverse effects all of which influence treatment concordance and adherence. However, narrative content is often incomplete, delayed, or written in formal styles that obscure patient priorities. Methods: Following PRISMA-ScR guidelines, we conducted a scoping review of studies published between 2013 and early 2024 that used natural language processing (NLP) or text mining on oncologist notes, or qualitatively examined EHR use in oncology. Data were charted by topic (e.g., adverse effects, note style, stigma, workflow burden) and synthesized using discourse analysis. Results: Twenty-three studies met inclusion criteria. Four clinician-side themes emerged: (1) compliance-oriented EHR design; (2) incomplete or delayed documentation of adverse effects, pain, and social determinants of health (SDOH); (3) formal or stigmatizing language; and (4) time and cognitive burden limiting person-centred narratives. These factors hinder concordance documentation and communication transparency. Conclusions: Improvements in EHR design, including person-centred prompts, plain-language templates, and audit-log-informed workflow changes, may enhance adherence by supporting better documentation and communication. Nursing and service leaders can implement these changes to promote trust, engagement, and continuity of care. Registration: Not registered

Article
Medicine and Pharmacology
Neuroscience and Neurology

Andreea Bianca Dabu

,

Dana Craiu

,

Cristina Pomeran

,

Diana Barca

,

Cristina Motoescu

,

Carmen Sandu

,

Alice Dica

,

Catrinel Iliescu

,

Alexandru-Ștefan Niculae

Abstract: Background: Autoimmune encephalitis (AE) is an increasingly well recognized disorder in the past decade both in adults and in children, yet pediatric data are still limited. A full peripheral blood cell count is a routine examination that provides valuable information regarding the immune system. Thus, there are peripheral blood cell count (PBCC)- derived ratios that reflect systemic inflammatory activity and have been associated with disease severity in adults: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratios (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI). Methods: This study is a retrospective chart review of children under 18 years diagnosed with definite or probable AE and treated in our institution from January 1, 2018 until December 1, 2025. Only patients with available PBCC results prior to any immunomodulatory therapy were included. An age-matched control group was created by selecting results of PBCC of patients presenting for routine pediatric follow-ups with normal inflammatory and hematologic parameters. Group means were compared using independent samples t-test or the Mann Whitney U test for non-normally distributed data. Analysis of the receiver operating characteristics curve (ROC curve) was conducted followed by the area under the curve ROC curve (AUC). Results: 45 children with AE and 150 controls were included in the study. NLR, PLR, SII, SIRI and AISI values were significantly higher in AE patients compared with controls, suggesting an overall pro-inflammatory profile at presentation. Concerning the platelet indices, a trend tower higher medium platelet volume and platecrit was observed in the AE group. These findings point to distinct peripheral immune alterations in pediatric AE, consistent with reports in adult patients. Conclusions: Our results suggest that at the time of the initial hospitalization, children with AE already show altered peripheral immune cell profiles compared to their age-matched peers The high specificity and the low sensitivity of the inflammatory indices make them more suitable for supporting the AE diagnosis in suggestive clinical circumstances, but not for screening. These results represent a foundation for further investigating the roles that these indices have both as diagnostic and prognostic factors for these children.

Article
Computer Science and Mathematics
Applied Mathematics

Tatsuya Sekiguchi

,

Hiroyuki Hamada

,

Masahiro Okamoto

Abstract: Parameter estimation for biochemical reaction networks is computationally demanding, especially for systems with oscillatory nonlinear dynamics, where standard iterative optimization strategies, including genetic algorithms, often struggle with prohibitive computational costs. We introduce an efficient parameter estimation framework that combines a real-coded genetic algorithm with a novel adaptive simulation termination strategy. This strategy defines a time-dependent termination boundary based on population quantiles, which is permissive during early transients and becomes progressively stricter as simulations advance, explicitly accounting for the temporal structure of oscillatory behavior. Crucially, this mechanism facilitates the efficient identification and early simulation termination of poor parameter candidates, thus avoiding the computational expense of full-horizon simulations. The framework further integrates global exploration with the modified Powell method for rapid local refinement. Numerical experiments on two benchmark oscillatory models—the Lotka–Volterra and Goodwin oscillators—demonstrate that the framework reduces computational cost by approximately 30%–50% compared to a baseline GA without this strategy. For the parameter-sensitive Goodwin model, the framework efficiently identifies candidates evolving toward damped oscillations caused by subtle parameter variations. Sensitivity analysis also confirms robustness across diverse hyperparameter settings, indicating that adaptive simulation termination provides a practical acceleration mechanism for inverse problems in systems biology where iterative objective-function evaluation dominates runtime.

Article
Environmental and Earth Sciences
Water Science and Technology

Xiaolin Li

,

Hongjin Zhao

,

Haoran Wang

,

Ziheng Zhou

,

Zhihua Sun

,

Chun Zhao

,

Hongyv Lu

,

Yusheng Sun

Abstract: To address the feasible issues in water treatment facilities such as low particle removal and overuse of chemical in flocculation-sedimentation treatment of complex sediment-laden particles in snowmelt and high-intensity rainfall water, this research presents a new multi-layered separation tank. Combining a multi-layer structural design and a synergistic enhancement mechanism flocculation-centrifugation it is possible to engineer the tank to achieve a great improvement in the coexistence. This study methodically examines the impact of the agitator speed, agitator height and the number of blades on the flow field qualities and the effectiveness of the agitator in removing particles in the multi-layer separation tank. Computational fluid dynamics (CFD) simulation validation, comparison with hydro-calculations and laboratory experiments are used in a combined method. Findings show that there is strong agreement between numerical representation and experimental values in determining the optimal conditions of operation and the exact rate of dosage of polyaluminum chloride (PAC) and polyacrylamide (PAM). At these optimised conditions, the system magnetises at a 75.25 percent removal rate of particles whose size ranges are 20–50 μm and turbidity of the effluent decreases to 10.6 NTU in 30 minutes of settling time. The proposed technology is more efficient than conventional coagulation processes in that effluent turbidity is reduced by 22.1% with same dosages of chemical additive indicating a higher performance of the proposed technology.

Article
Physical Sciences
Particle and Field Physics

Dimitris Mastoridis

,

Konstantinos Kalogirou

,

Panos Razis

Abstract: We present a non-supersymmetric Grand Unified Theory based on the gauge group U(4) that offers a unified origin for the electroweak scale, the strong interactions, the hierarchy of fermion masses, and the confinement of color. We propose that the symmetry breaking pattern SU(4) → SU(2)H is radiatively selected, partitioning the vacuum into a standard gluon sector and a new topological "Warden" sector. We identify the excitations of this new sector (the Wardens) not as simple gauge bosons, but as Hopf solitons (Hopfons) formed by the scalar Goldstone degrees of freedom. Crucially, we employ the Cho-Duan-Ge decomposition to separate the gauge potential into a topological ’restricted’ mode and dynamical valence gluons. We demonstrate that the transverse valence modes acquire a large constituent mass from the magnetic background and effectively decouple from the renormalization group flow, leaving the evolution dominated by the scalar topological degrees of freedom. Furthermore, we show that the fermionic statistics of the Warden fields are not a violation of quantum field theory but a rigorous consequence of the Finkelstein-Rubinstein mechanism, where the non-trivial Hopf invariant (QH = 1) induces a geometric Berry phase that mandates Fermi-Dirac quantization to preserve S-matrix unitarity. This topological identification resolves the spin-statistics tension and justifies the use of scalar beta-function coefficients, leading to a precise three-loop unification of gauge couplings at MGUT ≈ 3.2 × 1016 GeV. The theory posits a "Tilted Universe" mechanism wherein the electroweak scale is generated by a geometric misalignment between the Higgs vacuum and the rigid Warden condensate. The misalignment angle is dynamically locked to the flavor sector, predicting a fundamental stiffness scale of FUV ≈ 1.1 TeV. We demonstrate that this high-energy stiffness generates a lower dynamical confinement scale via dimensional transmutation, ΛIR ≈ 330 MeV, which correctly predicts the scalar glueball mass (MGB ≈ 1699 MeV) and string tension (√σ ≈ 440 MeV) from first principles. In the matter sector, a single flavor-democratic Yukawa coupling at the GUT scale is shown to deterministically evolve into the observed 17-order-of-magnitude hierarchy of quark and charged lepton masses. The model resolves the flavor puzzle by predicting a hierarchical CKM matrix for quarks and, via a non-universal "Hopf Portal," an anarchic PMNS matrix for leptons. The framework makes two sharp, falsifiable predictions: the absolute stability of the proton, and the existence of a heavy topological resonance at 8.2 ± 0.4 TeV, accessible at future hadron colliders. The proposed model, along with its associated phenomenological effects and searches for new particles within the emergent "Warden" sector, accurately derives from first principles the Top Quark mass (172.68(22) GeV), the Weak Mixing Angle ( sin2 θW = 0.23125), and other experimentally derived quantities with high accuracy. It can be examined at current and upcoming high energy physics experiments focused on Beyond the Standard Model (BSM) physics, such as at the High Luminosity LHC at CERN and the Future Circular Collider (FCC).

Article
Computer Science and Mathematics
Data Structures, Algorithms and Complexity

Frank Vega

Abstract: We present the Hvala algorithm, an ensemble approximation method for the Minimum Vertex Cover problem that combines graph reduction techniques, optimal solving on degree-1 graphs, and complementary heuristics (local-ratio, maximum-degree greedy, minimum-to-minimum). The algorithm processes connected components independently and selects the minimum-cardinality solution among five candidates for each component. \textbf{Empirical Performance:} Across 233+ diverse instances from four independent experimental studies---including DIMACS benchmarks, real-world networks (up to 262,111 vertices), NPBench hard instances, and AI-validated stress tests---the algorithm achieves approximation ratios consistently in the range 1.001--1.071, with no observed instance exceeding 1.071. \textbf{Theoretical Analysis:} We prove optimality on specific graph classes: paths and trees (via Min-to-Min), complete graphs and regular graphs (via maximum-degree greedy), skewed bipartite graphs (via reduction-based projection), and hub-heavy graphs (via reduction). We demonstrate structural complementarity: pathological worst-cases for each heuristic are precisely where another heuristic achieves optimality, suggesting the ensemble's minimum-selection strategy should maintain approximation ratios well below $\sqrt{2} \approx 1.414$ across diverse graph families. \textbf{Open Question:} Whether this ensemble approach provably achieves $\rho < \sqrt{2}$ for \textit{all possible graphs}---including adversarially constructed instances---remains an important theoretical challenge. Such a complete proof would imply P = NP under the Strong Exponential Time Hypothesis (SETH), representing one of the most significant breakthroughs in mathematics and computer science. We present strong empirical evidence and theoretical analysis on identified graph classes while maintaining intellectual honesty about the gap between scenario-based analysis and complete worst-case proof. The algorithm operates in $\mathcal{O}(m \log n)$ time with $\mathcal{O}(m)$ space and is publicly available via PyPI as the Hvala package.

Review
Medicine and Pharmacology
Pharmacy

Omolayo Tinuke Umaru

,

Adebowale Sylvester Adeyemi

,

Olajumoke Aderonmu

,

Balyodh Singh Bhangu

,

Harjot Singh Dhaliwal

,

Hae Lim

,

Taiwo Opeyemi Aremu

Abstract: Pharmaceutical regulation and healthcare governmental agencies are central to protecting public health by governing clinical trials, market authorization, and post-market safety monitoring of medicinal products worldwide. Although substantial literature describes major established systems, particularly the United States Food and Drug Administration (FDA), Japan's Pharmaceuticals and Medical Devices Agency (PMDA), and the European Union regulatory network coordinated by the European Medicines Agency (EMA) together with national competent authorities, comparative analysis that integrate both established and emerging regulatory authorities remain limited. This review examines the core functions of regulatory affairs across the product life cycle and compares key features of global regulatory frameworks, including approval pathways, evidentiary expectations, data transparency, and pharmacovigilance approaches. It emphasizes the need for systems thinking to balance innovation with safety, efficacy, and quality, while anticipating unintended consequences of new therapies. This evaluation also highlights how region‑specific constraints and enabling infrastructures, such as national drug‑utilization registries in parts of Europe, can shape regulatory decision‑making and post‑market evaluation. Finally, this paper discusses opportunities for stronger international alliances and greater harmonization to improve efficiency, support timely patient access to essential therapies, strengthen risk management, and reinforce global health security in an increasingly interconnected healthcare environment.

Article
Arts and Humanities
Other

Qianyu Wang

,

Wenjie Liu

Abstract: Intangible cultural heritage (ICH) is a cornerstone of national identity, driving economic development and social cohesion globally. Yangliuqing New Year Woodblock Paintings, a representative Chinese national ICH, face development bottlenecks due to insufficient internal innovation and ineffective external interventions, with existing research lacking holistic analysis of its historical evolution and contemporary challenges. This study aims to establish a dynamic framework for its innovative development. It first identifies cultural ecological factors via representative case analysis, then employs an integrated EWM-DEMATEL-ISM model to quantify these factors, determine their core components, and map their influence relationships. The results reveal that technical factors, cultural merit, and resource factors constitute the core cultural ecology of Yangliuqing New Year Paintings, with cultural merit as the deep-layer cultural gene, technical factors as the intermediate maintenance force, and resource factors as the surface-level interface. Three feasible innovative development paths are proposed, centered on activating cultural merit, upgrading technical factors, and optimizing resource allocation. This research provides a new analytical perspective for Yangliuqing New Year Paintings and offers insights for the sustainable development of other ICH categories by integrating historical context with future-oriented strategies.

Article
Physical Sciences
Astronomy and Astrophysics

Huang Hai

Abstract:

This paper proposes an extremely simple logarithmically modified gravitational potential, whose most prominent feature is the cross-scale unity from black hole "singularities" to galactic dynamics: through the sign reversal of the gravitational potential at the microscale (r<r*≈8.792×10-11m), dynamics avoids any matter collapsing into "singularities". Under this mechanism, the angular diameter of black hole shadows and the orbital velocities of high-speed stars orbiting them can be a priori predicted without introducing any free parameters (such as spin, eccentricity, etc.), and finally extended to explain galactic rotation dynamics. By analyzing the mathematical asymptotic behavior of all dark matter halo models, we obtain a core finding: adding a simple logarithmic correction term to the original Newtonian gravitational potential: \( Φ(r)=-\frac{GM}{r}-\frac{(kG_h M^2 (ln⁡r+1))}{r} \) a possible framework that avoids collapse to (eliminates) singularities and explains the flattening of galaxy rotation curves under the same physical mechanism can be obtained. Among them, the logarithmic term " " is the key to realizing the cross-scale effect of "repulsion at short distances and attraction at long distances". Without introducing additional free parameters (such as spin), we a priori predict black hole shadows (Sgr A*, M87*) that are consistent with EHT observations; then, based on the same physical mechanism, a priori calculate the "perihelion" velocities of high-speed stars (S4714, S62) orbiting black holes, which are consistent with observations; finally, through this mechanism, we posteriori fit galaxy rotation curve data (Milky Way, Andromeda Galaxy, NGC2974) and other cross-scale verifications (spanning nearly 30 orders of magnitude from black hole singularities to galaxies), initially proving that the framework shows a high degree of observational consistency in both strong gravitational fields (black holes) and weak gravitational fields (galaxies) (especially the a priori prediction of black hole shadows). Based on this, we further provide almost unique quantitative a priori predictions for the angular diameters of six candidate black hole shadows (such as NGC4261, M84, etc.) that have not been observed by EHT under this theoretical mechanism (unable to adjust spin α and inclination i to match observations), as observable predictions awaiting future verification (e.g., NGC4261 is predicted to have a shadow angular diameter of 5.9 ~6.3μas, M84 is predicted to have a shadow angular diameter of 9.8 ~10.7μas, etc.). Core feature: The logarithmic correction is not introduced to address any single phenomenon. It originates from the universal result of the asymptotic mass distribution \( ρ(r)∼r^{-3} \) of dark matter halos, and is consistently reflected in: 1) the regularization of the central gravitational potential; 2) the formation of black hole shadows; 3) the dynamics of high-speed stars; 4) galactic rotation curves. These manifestations form an inseparable whole. This framework not only achieves, for the first time, a unified description of gravity from the microscopic to the macroscopic scale (requiring only ordinary matter mass) but also provides an observable and reproducible empirical framework for quantum gravity theory, potentially freeing it from the long-standing research method of pure mathematical modeling (distant from actual observations) and transitioning to physical verification.

Article
Medicine and Pharmacology
Oncology and Oncogenics

Ramona Abrudan

,

Luca Abrudan

,

Andreea Cămărășan

,

Ovidiu Camarasan

,

Corina Florica Ioniță

,

Luca Vilceanu

,

Ovidiu Laurean Pop

Abstract: Colorectal cancer is a heterogeneous malignancy characterized by alterations in onco-genic signaling pathways and epigenetic mechanisms involved in gene regulation. Ab-errant activation of the Wnt/β-catenin pathway represents a central molecular event in colorectal tumorigenesis, while histone-associated epigenetic modifications may contribute to tumor progression and variability. This study aimed to investigate the relationship between Wnt pathway activation and histone H3 lysine 27 trimethylation in colorectal cancer and to examine their associations with clinicopathological and molecular characteristics. A retrospective observational study was performed on 83 colorectal adenocarcinoma cases using immunohistochemical evaluation of nuclear β-catenin and H3K27me3 expression in formalin-fixed, paraffin-embedded tumor samples, together with molecular analysis of KRAS, NRAS, and BRAF mutations and microsatellite instability status. Nuclear β-catenin expression was observed in 39.8% of cases, while H3K27me3 exhibited negative, mosaic, or diffuse nuclear staining pat-terns. Nuclear β-catenin expression was significantly associated with patient sex and age, whereas H3K27me3 expression patterns were significantly associated with tumor location, histological grade, disease stage, and metastatic status. These results indicate that Wnt pathway activation and H3K27me3-associated epigenetic alterations fre-quently coexist in colorectal cancer and support the value of integrated molecular and epigenetic assessment.

Brief Report
Biology and Life Sciences
Neuroscience and Neurology

Javed Akram

,

Muhammad A. Usmani

,

Amama Ghaffar

,

Usman Shareef

,

Asma Ali Khan

,

Zubair M. Ahmed

,

Sheikh Riazuddin

,

Saima Riazuddin

Abstract: After following up of more than 9 years, we report three affected male siblings from a consanguineous family (PKSOK) in rural Baluchistan, Pakistan, presenting with a novel, levodopa/carbidopa-responsive Nocturnal Akinesia Syndrome (NAS). Clinical features include nocturnal hypotonia, developmental delay, mild intellectual disability, speech impairment, and psychomotor delay without classical metabolic crises or spasticity. Exome sequencing identified a predicted pathogenic homozygous missense variant [c.313G>A; p.(Gly105Ser)] in the Isovaleryl-CoA dehydrogenase (IVD) gene, traditionally associated with Isovaleric Acidemia (IVA). However, the clinical phenotype of affected individuals of family PKSOK deviates from classical IVA, exhibiting unique levodopa-responsive motor symptoms rather than metabolic decompensation. Protein-protein interaction analyses predicted IVD interactions with dopamine receptors DRD1 and DRD4, suggesting a functional link between metabolic enzymes and dopaminergic neurotransmission and circadian rhythm. The potential involvement of GABAergic pathways may further explain the motor phenotype and therapeutic responsiveness. This study expands the phenotypic spectrum of IVD variants, highlighting new mechanisms underlying movement disorders and offering important implications for diagnosis and targeted treatment in similar rare neurometabolic syndromes.

Article
Engineering
Transportation Science and Technology

Hyun Kim

,

Branislav Dimitrijevic

Abstract: Extensive research has been conducted to develop technologies that enable paratransit systems to operate autonomously, including advanced sensing technologies and associated software. However, there remains a significant gap in research addressing the development of adaptive operational algorithms for such systems in urban environments. Autonomous Shuttles (AS) represent an emerging technology that has gained attention from industry, government, and academia as a novel public transit solution. AS hold the potential to enable Ride-shared Autonomous Mobility on Demand (RAMoD), which can improve accessibility and service equity in transportation-disadvantaged populations across urban and surrounding regions. To address this gap, this study applies an imitation-learning-assisted Deep Reinforcement Learning (DRL) approach to develop a routing method for AS under stochastic and dynamic passenger demand conditions. The proposed framework integrates Generative Adversarial Imitation Learning with Proximal Policy Optimization to enable real-time pickup and drop-off decision-making without centralized re-optimization. The DRL agent was trained over approximately 1.5 million training steps and evaluated across twenty episodes with stochastic passenger generation. Its performance was benchmarked against a deterministic Dial-a-Ride Problem (DARP) solver implemented using Google’s OR-Tools, which employs a Cheapest Insertion heuristic with Local Search refinement. Comparative analysis showed median percentage differences of 37%, –6%, 20%, and 44% in passenger wait time, in-vehicle time, total service time, and episode completion time relative to the DARP baseline. The OR-Tools implementation was selected as a benchmark due to the lack of established step-wise evaluation methods for dynamic routing optimization in simulation environments. These findings demonstrate the potential of learning-based routing policies to support scalable, demand-responsive autonomous mobility services and future smart urban transportation systems.

Article
Chemistry and Materials Science
Paper, Wood and Textiles

Tadeáš Zachara

,

Přemysl Šedivka

,

Vlastimil Borůvka

,

Kryštof Kubista

,

Tomáš Holeček

,

Martin Lexa

,

Lukáš Sahula

,

Adam Sikora

Abstract: This study investigates the valorization of post-consumer and post-industrial recycled cotton fibers from textile waste into porous fiber-based insulation composites using a lowenergy cold-pressing process and a water-borne hybrid binder based on polyvinyl acetate (PVAc) and modified cornstarch. Insulation boards were produced with target densities ranging from 300 to 340 kg·m⁻³, achieved by systematically adjusting the percentage weight fractions of recycled cotton fibers and binder components. The influence of board density on microstructure, inter-fiber bonding, and structure-property relationships was evaluated. The resulting boards exhibited thermal conductivity values between 0.0710 and 0.0739 W·m⁻¹·K⁻¹. Compressive strength measured at 10% relative deformation of the specimen thickness ranged from 46 to 162 kPa, while internal bond strength varied between 2 and 6 kPa. Water absorption decreased by approximately 18% with increasing density, indicating improved binder distribution and reduced open porosity. The PVAc–starch binder system enabled effective inter-fiber bonding without formaldehyde-based resins or energy-intensive curing, supporting a low-energy and circular processing concept for textile waste valorization. Overall, the results demonstrate that recycled cotton fibers represent a viable feedstock for porous insulation composites combining balanced thermal, mechanical, and moisture-related performance with reduced environmental impact.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Ana M. González de Miguel

,

Antonio Sarasa-Cabezuelo

Abstract: The development and operation of cooperative Digital Library Systems face management problems that do not always have a complete solution. These cooperative systems currently need to incorporate new Artificial Intelligence solutions to develop intelligent services for decision-making and recommendation mechanisms for which there is not an integral management solution. Indeed, the management of these intelligent services is outside the scope of traditional management systems for digital collections. This paper proposes using an Intelligent Management Framework to address these issues. Basically, we use a top-down design approach based on six abstractions and four refinement techniques to design a management model that integrates suitable cooperative models, system behaviours, software architecture and processes to manage cooperative Digital Library Systems that incorporate intelligent services. The approach is evaluated designing an Intelligent Management Framework for cooperative, intelligent Digital Library Systems used in a government organization for current digital transformations. Finally, a qualitative analysis methodology is used with this case study, collecting relevant data with a questionnaire, and showing and discussing these results.

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