Abstract: Black pepper (Piper nigrum L.) faces challenges related to irregular flowering, which compromises crop productivity. Gibberellic acid (GA₃) is a plant growth regulator known for its role in inducing reproductive processes, although its effects on this species are not yet fully understood. This study aimed to evaluate the influence of different GA₃ doses on flowering and vegetative growth in black pepper plants. The experiment was conducted with black pepper seedlings of the Bragantina cultivar in a randomized block design, with four doses of GA₃ (0, 10, 20, and 30 mg L⁻¹) and six replications, using eight-month-old plants grown in pots under full sun. GA₃ applications were performed in two floral induction cycles. Variables related to flowering, chlorophyll a fluorescence, vegetative growth, biomass allocation, and carbohydrate distribution were evaluated. The data were subjected to analysis of variance, regression, mean grouping test, and principal component analysis. The results showed that inter-mediate doses (10 and 20 mg L⁻¹) significantly stimulated flowering at early developmental stages, whereas the 30 mg L⁻¹ dose enhanced vegetative growth while reducing floral induction. Additionally, GA₃ affected physiological parameters by increasing photosynthetic efficiency and altering carbohydrate balance, with higher accumulation of soluble sugars in leaves and reduced starch content in roots. It is concluded that GA₃ application is a promising strategy to modulate reproductive transition in black pepper, with 10 to 20 mg L⁻¹ doses recommended to promote flowering without compromising plant development.

Abstract: This study investigated the effects of dietary nano-antimicrobial peptides (NAPs) on the microbial communities and metabolic profiles in Tibetan sheep. Using 16S rRNA gene high-throughput sequencing and non-targeted metabolomics, the contents of the small intestine, rumen, and rectum were systematically analyzed in a control group (Group A) and a NAP-supplemented group (Group B). Multi-omics integration methods, including O2PLS and Pearson correlation analysis, were employed to explore the association between microbial communities and metabolites. Alpha and beta diversity analyses revealed significant differences (P < 0.05) in the microbial community structure of the small intestine between the two groups. In contrast, the rumen and rectal microbiota remained relatively stable, indicating that the regulatory effects of NAPs on the intestinal microecology are site-specific. In the small intestine, NAPs altered the composition of dominant functional microbiota and the abundance of taxa related to energy metabolism. Metabolomic analysis identified significant shifts in metabolic profiles, specifically within the bile acid, fatty acid, and phospholipid pathways (P < 0.05). Group A exhibited baseline steady-state characteristics (e.g., cholic acids and phospholipids), whereas Group B showed activation of unsaturated fatty acids and related metabolites. Multi-omics integration revealed a stable systematic association between intestinal microbial genera and metabolites. Specifically, bile acid and prostaglandin metabolites were negatively correlated with Firmicutes-related taxa, suggesting a potential role for bile acid metabolism in regulating intestinal microecology and host immunity. These findings suggest that NAP supplementation may contribute to maintaining host energy metabolism and intestinal homeostasis by regulating intestinal microecology.

Abstract: Special and general relativity (SR/GR) work for observers, but they do not provide diagrams of nature that work for all observers. This is because there is no concept of absolute space in SR/GR, where all action is due to an absolute parameter. We show: Euclidean relativity (ER) achieves precisely that. ER describes a mathematical Master Reality, which is absolute 4D Euclidean space (ES). All objects move through ES at the dimensionless speed C. There is no time coordinate in ES. All action in ES is due to an absolute, external evolution parameter θ. In addition, ER describes an observer’s physical reality. He experiences two projections of ES as space and time. The axis of his current 4D motion is his proper time τ. Three orthogonal axes make up his 3D space x₁, x₂, x₃. Without gravity, his physical reality is a Minkowskian reassembly of his axes x₁, x₂, x₃, τ. In this “τ-based Minkowskian spacetime” (τ-MS), τ is the time coordinate and θ converts to parameter time ϑ. Minkowski spacetime and τ-MS are mathematically identical. Thus, ER retains the SR formalism. ER also retains the GR formalism, but only in a specific reference frame defined by τ. The Einstein field equations hold true in this specific frame, but not in ES. ER reproduces both the Lorentz factor and gravitational time dilation. ER rejects cosmic inflation, expanding space, dark energy, and non-locality. And yet, ER predicts time’s arrow, galactic motion, the Hubble tension, and entanglement. Thus, ER significantly improves cosmology and quantum mechanics. We conclude: ER is indispensable for unifying physics.

Abstract: This study examines how the adoption of artificial intelligence (AI) and the implementation of policies shape inclusive educational outcomes for marginalized learners in Bangladesh, using evidence from Sherpur Sadar Upazilla. A convergent mixed-methods design integrated a student survey (N = 213; seven institutions; March–September 2024) with qualitative data from 37 stakeholders (teachers and policymakers) collected through semi-structured interviews and focus group discussions. Quantitative findings show that AI tool adoption was the strongest predictor of a composite educational outcome score (β = 0.38, p < 0.001), followed by institutional support (β = 0.25, p = 0.01). In contrast, the policy implementation gap—defined as the mismatch between policy intent and on-the-ground delivery—was negatively associated with outcomes (β = −0.12, p = 0.04). Digital infrastructure quality was positively associated with the outcome but was not statistically significant in the multivariable model (β = 0.17, p = 0.12). The model demonstrated strong explanatory power (R² = 0.67; F(4, 208) = 42.3; p < 0.001). Disparity analyses revealed persistent urban–rural inequities in reliable internet access (94.6% vs. 69.7%) and device readiness, with tablet access emerging as a key enabler of advanced AI-supported learning. Qualitative results corroborated three binding constraints: limited teacher AI preparedness, affordability barriers, and trust concerns related to privacy and algorithmic bias. Building on these findings, the paper proposes a policy–innovation framework centered on localized AI toolkits, sustained teacher upskilling, device-access interventions, and enforceable fairness and transparency safeguards to advance equitable learning opportunities.

Abstract: Milk production in dairy cattle is increasingly challenged by thermal variability. This underscores the need for reliable assessment of microclimatic conditions and their interaction with animal- and management-related factors to ensure sustainable dairy production. The aim of this study was to evaluate the effects of thermal variability and selected environmental and biological factors on key milk production traits in dairy cattle. The influence of fixed factors related to production conditions and microclimatic variability, including the Temperature–Humidity Index (THI), on daily milk yield (MY), milk fat content (MF), and milk protein content (MP) was assessed. The study used a dataset covering two observation periods of daily milk production traits in cows of different breeds (Simmental, Holstein-Friesian, Red Holstein, and Brown Swiss) reared in three regions of the Republic of Serbia (Mačva, Podunavlje, and Šumadija), enabling an assessment of thermal variability under diverse production and microclimatic conditions. The expression and variability of the investigated traits were determined using the PROC FREQ and PROC MEANS procedures, while the effects of individual factors were analysed using general linear and regression models, with results expressed as least squares means. All examined factors showed a highly significant effect on MY, MF, and MP (p < 0.0001). Although the overall level of heat stress was moderate, milk production was highest within the THI range of 51–60. These findings demonstrate that thermal variability significantly influences milk production and composition and highlight the importance of integrating microclimatic indicators into sustainability-oriented dairy management and breeding strategies.

Abstract: Since the pioneering work of Dean P. M. and Matthew E. K. (1970), four decades have elapsed without any consensus on the mechanism responsible for the oscillations of the plasma membrane voltage exhibited by pancreatic β-cells stimulated by glucose. In this review, the different hypothesis dealing with the cause of voltage oscillations that lead to insulin secretion pulsatility will be commented. The earliest explanation attributed the voltage oscillations (bursting) to glycolytic oscillations, taking as a reference skeletal muscle glycolysis oscillations. Later, the scientific interest moved to glucose oxidation after discovering that some mitochondrial parameters also oscillated in synchrony with membrane voltage oscillations. As [Ca2+]cyt increases resultant from membrane depolarization oscillated in synchrony with membrane bursting, it competed with metabolic oscillations (e.g. cytosolic ATP/ADP) for being the cause or the effect of insulin pulsatility; it was demonstrated that metabolic oscillations preceded [Ca2+]cyt oscillations. We are contributing with the hypothesis attributing the cause of voltage oscillations to a sequential competition of two β-cell plasma membrane channels: K+ATP channel and Cx36 hemichannel (Cx36H). Whereas increased glucose metabolism (increased ATP/ADP) closures K+ATP channels and depolarizes the plasma membrane (active phase of a bursting), Cx36Hs are opened and repolarize the membrane potential with a certain delay by inhibiting glucose metabolism (silent phase of a bursting). Repolarization, in turn, closes Cx36H and allows the recovery of glucose oxidation and beginning of a new active phase.

Abstract: In 1916, A. Einstein developed a model of the absorption and emission of radiation from which he derived M. Planck’s radiation law. He postulated light-induced (stimulated) emission, because within the framework of classical physics an oscillator can, depending on the phase difference, both extract energy from the electromagnetic field and transfer energy to it. In a non-coherent field, α = β should hold, where α denotes the kinetic constant of absorption and β that of stimulated emission. This assumption is indispensable for deriving the radiation law from his model. In this context, it is problematic that a certain degree of field coherence follows necessarily from his model, which implies that α ≠ β. Moreover, the model cannot readily be generalised to fields of arbitrary coherence. An alternative model for the absorption and emission of radiation by matter is therefore developed here. On the one hand, it is based on the assumption that, within a blackbody, quanta of different energies may recombine freely; on the other hand, it employs the “pairwise interference model of quantum theory” (PIMOQ). The alternative model of the interaction between light and matter allows the radiation law to be derived for thermal equilibrium in a non-coherent field, under which conditions, according to the model, no stimulated emissions occur. It also describes the behaviour of systems with a coherent field (interference experiment, laser). Furthermore, considerations are presented regarding the energy distribution within a blackbody and the explanatory scope of A. Einstein’s model in this respect.

Abstract: Aquaculture plays a strategic role in food security and rural development in coastal regions. However, structural, economic, and institutional constraints affect small-scale producers in heterogeneous ways. This study analyzes how small-scale aquaculture producers in Manabí (Ecuador) perceive the main challenges affecting their activity, based on a typology comprising three production systems: Backyard, Transitional, and Commercial. A structured questionnaire was administered to 98 producers, including 20 variables assessed using a five-point Likert scale. The analysis combined non-parametric univariate tests (Kruskal–Wallis with Dunn post-hoc comparisons) and multivariate techniques to identify statistically significant differences and structured perception patterns across production systems. Significant differences were detected in variables related to biological input supply, market conditions, and structural production constraints. In particular, larvae and fingerling supply, selling prices, buyer availability, and pond surface area showed differentiated perception patterns across systems. Most differences occurred between Backyard farms and the other two production systems, while Transitional and Commercial farms displayed more similar perception profiles. Transversal constraints shared across systems included high feed costs, energy expenditure, and regulatory requirements. Principal Component Analysis identified two main perception gradients related to market and input constraints and to structural and managerial limitations. Discriminant analysis further confirmed the ability of these dimensions to differentiate production systems. These findings highlight the multidimensional nature of constraints affecting small-scale aquaculture and suggest that production systems are better interpreted as gradients of pressures rather than strictly discrete categories. The results underline the need for adaptive governance approaches combining transversal measures with system-specific interventions. Overall, the study provides empirical evidence to support the design of differentiated and context-sensitive policies aimed at strengthening the sustainable development of small-scale aquaculture in Manabí and similar territories.

Abstract: Transarterial chemoembolization (TACE) is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC), yet nearly half of treated patients fail to achieve durable benefit, and reliable biomarkers enabling early therapeutic stratification are still lacking. Treatment response is typically assessed by imaging one month after TACE and at three-month intervals, potentially delaying timely access to alternative therapies in non-responding patients. Circulating microRNAs (miRNAs) represent promising biomarkers due to their stability in body fluids and ease of detection. Here, we evaluated circulating miR-22 as an early predictor of TACE response and as a mechanistically relevant therapeutic target. Circulating miR-22 levels were measured by microarray and quantitative RT–PCR in three independent cohorts of early-to-intermediate stage HCC patients undergoing TACE. Circulating miR-22 increased significantly in non-responders as early as 48 h after treatment, and fold changes consistently predicted treatment failure across two independent validation cohorts. Mechanistically, we identified the G2/M checkpoint kinase WEE1 as a direct functional target of miR-22. Modulation of the miR-22/WEE1 axis affected cell-cycle progression, proliferation, apoptosis, and DNA damage response in HCC cell lines and xenograft models. Under hypoxia-mimicking conditions combined with doxorubicin exposure, pharmacological inhibition of WEE1 induced mitotic catastrophe in highly proliferative miR-22–silenced cells. Collectively, these findings identify early post-TACE elevation of circulating miR-22 as a biomarker of non-response and highlight the miR-22/WEE1 axis as a potential target for precision treatment strategies in HCC.

Abstract:

In Cambodia, farmers construct artificial household bat roosts to collect and sell guano as fertilizer. We investigated farming practices and attendant spillover risks using: 1) surveys on guano production; 2) estimating bat population size and species present using carcasses, visual identification, and audio recordings; 3) surveying guano-producing and neighbor households on water, sanitation, and hygiene practices; and 4) testing guano and household food, water and surfaces for coronaviruses by PCR. Bat roosts are constructed using dried palm leaves with coconut tree and/or steel/concrete supports. Roosting areas ranged from 42-327 m², bat abundance varied from 0-11,187, guano production was 5-120 kg/week, guano yields were 0.15-0.4 kg/m2/week, and farmers earned ~100-200 USD/household/month. Higher guano production in peak (normally wet) season was associated with greater bat abundance (p=0.016). The lesser Asiatic yellow house bat (Scotophilus kuhlii) was the only bat species identified. Roosts were <20 m from guano-producing households. Neighbors and households’ hygiene risks included not having handwashing stations and not covering food in storage/while drying. Alphacoronaviruses or Infectious Bronchitis Virus were found in 14.6%, 17.3%, 2.9%, 1.4%, and 0.0% of guano, urine, surface, food, and water samples, respectively. While guano farming offers economic benefits, spillover risks exist. Safe guano collection and storage, handwashing, and food covering in guano-producing communities are necessary to mitigate spillover risks.

Abstract: We pose the Typhoon Engulfment Grand Challenge: determine whether any physically realizable feedback control law can guarantee the safe flight and landing of a commercial aircraft under all extreme, physically admissible typhoon wind fields—or prove that such a guarantee is mathematically impossible. The problem is formulated as a two-player zero-sum differential game between an autopilot (the minimizer, seeking survival) and an adversarial but physics-constrained typhoon (the maximizer, seeking to force the aircraft outside its safe operating envelope). We detail the coupled nonlinear dynamics, define the safe operating set in the airspeed–load-factor plane, and identify four interlocking barriers—high-dimensional Hamilton–Jacobi–Isaacs equations, PDE-constrained adversarial disturbances, hybrid structural failure dynamics, and imperfect observations—that place this problem beyond the reach of any existing mathematical framework. This article serves as a formal statement of the challenge, provides accessible explanations for researchers across disciplines, and charts concrete research directions for communities spanning control theory, aerospace engineering, applied mathematics, machine learning, fluid dynamics, structural mechanics, formal verification, operations research, signal processing, meteorology, and independent researchers worldwide.

Abstract:

The green peach aphid, Myzus persicae (Sulzer), is a globally important agricultural pest whose management is increasingly challenged by widespread insecticide resistance, prompting interest in alternative and sustainable control strategies such as endophytic fungi. This study evaluated the effects of two endophytic fungi, Trichoderma harzianum and Chaetomium cupreum, applied individually or as a 1:1 mixture, on the population ecology of M. persicae feeding on capia-type red pepper (Capsicum annuum L.). Aphid development, survival, and reproduction were assessed using age-stage, two-sex life table analysis. Contrary to expectations, T. harzianum significantly enhanced aphid population growth, resulting in a higher intrinsic rate of increase (r = 0.42 d^-1), finite rate of increase (λ = 1.52 d^-1), and net reproductive rate (R₀ = 87.67 offspring) compared to the control (r = 0.32 d^-1, λ = 1.37 d^-1, R₀ = 42.90 offspring). The mixture treatment also increased population parameters, whereas C. cupreum showed limited effects on aphid life table traits. Population projections indicated that T. harzianum treatment could produce aphid populations approximately 380 times larger than the control after 60 days. These results suggest that T. harzianum may improve host plant quality in ways that indirectly favor M. persicae. The findings highlight the importance of evaluating plant–fungus–herbivore interactions before incorporating endophytic fungi into integrated pest management programs.

Abstract: Scaling generalist GUI agents is hindered by the data scalability bottleneck of expensive human demonstrations and the ``distillation ceiling'' of synthetic teacher supervision. To transcend these limitations, we propose UI-Oceanus, a framework that shifts the learning focus from mimicking high-level trajectories to mastering interaction physics via ground-truth environmental feedback. Through a systematic investigation of self-supervised objectives, we identify that forward dynamics, defined as the generative prediction of future interface states, acts as the primary driver for scalability and significantly outweighs inverse inference. UI-Oceanus leverages this insight by converting low-cost autonomous exploration, which is verified directly by system execution, into high-density generative supervision to construct a robust internal world model. Experimental evaluations across a series of models demonstrate the decisive superiority of our approach: models utilizing Continual Pre-Training (CPT) on synthetic dynamics outperform non-CPT baselines with an average success rate improvement of 7% on offline benchmarks, which amplifies to a 16.8% gain in real-world online navigation. Furthermore, we observe that navigation performance scales with synthetic data volume. These results confirm that grounding agents in forward predictive modeling offers a superior pathway to scalable GUI automation with robust cross-domain adaptability and compositional generalization.

Abstract: The present study examines the effects of ICT education on the competency development of 600 trainee teachers in Sri Lanka's National Institutes of Education (NIE). With respect to ICT tools and their interfaces in relation to digital literacy, teaching, and overall facilitator effectiveness, the author presents a discrete quantitative, cross-sectional ICT study. The sample was made up of 300 teachers educated in ICT and 300 teachers educated in traditional (non-ICT) methods. The study utilized a self-administered questionnaire. The author applied and described ICT, regression, and correlation analyses and integrated the ICT variable with effectiveness and competency development in Sri Lanka. The author observed that ICT educators had a higher self-efficacy and ICT tool usage and demonstrated improvements in digital literacy and pedagogy compared to non-ICT educators. A lack of integration of supplemental education technology to support teaching baseline ICT competencies was noted. A holistic approach to teacher training was advocated based on the integrated train of constructivist learning theory and TPACK framework. This study advances the empirical support of ICT and its contribution to the Sustainable Development Goal (SDG) 4, Quality Education, by demonstrating the increased value of educator competencies. The study offers actionable insights to enhance ICT training within the teacher education curricula in Sri Lanka, with the aim of equipping teachers to tackle the challenges of the digital era.

Abstract: This paper addresses the critical communication barrier experienced by deaf and hearing-impaired individuals in the Arab world through the development of an affordable, video-based Arabic Sign Language (ArSL) recognition system. Designed for broad accessibility, the system eliminates specialized hardware by leveraging standard mobile or laptop cameras. Our methodology employs Mediapipe for real-time extraction of hand, face, and pose landmarks from video streams. These anatomical features are then processed by a hybrid deep learning model integrating Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs), specifically Bidirectional Long Short-Term Memory (BiLSTM) layers. The CNN component captures spatial features, such as intricate hand shapes and body movements, within individual frames. Concurrently, BiLSTMs model long-term temporal dependencies and motion trajectories across consecutive frames. This integrated CNN-BiLSTM architecture is critical for generating a comprehensive spatiotemporal representation, enabling accurate differentiation of complex signs where meaning relies on both static gestures and dynamic transitions, thus preventing misclassification that CNN-only or RNN-only models would incur. Rigorously evaluated on the author-created JUST-SL dataset and the publicly available KArSL dataset, the system achieved 96% overall accuracy for JUST-SL and an impressive 99% for KArSL. These results demonstrate the system’s superior accuracy compared to previous research, particularly for recognizing full Arabic words, thereby significantly enhancing communication accessibility for the deaf and hearing-impaired community.

Abstract: Brucellosis is an important infectious disease affecting livestock worldwide, causing reproductive losses in small ruminant production systems and representing a persistent challenge for animal health and public health under a One Health perspective. Despite its importance, epidemiological information on ovine brucellosis in Ecuador remains scarce. This cross-sectional study aimed to estimate the seroprevalence of Brucella spp. infection in sheep at both the individual and herd levels and to identify potential risk factors associated with infection. This study represents the largest epidemiological investigation conducted to date on ovine brucellosis in Ecuador, covering the main sheep-producing regions of the country (more than 95% of the national sheep population). Between 2024 and 2025, a total of 970 sheep from 385 farms were sampled. Serum samples were analyzed using a commercial ELISA assay, and epidemiological information was obtained through structured farm surveys. Statistical analyses included bivariate tests and a multivariable model using Generalized Estimating Equations (GEE). The overall individual seroprevalence was 5.1% (49/970), while herd-level prevalence reached 7.5% (29/385). Multivariable analysis identified abortion rate (OR = 1.045; 95% CI: 1.016–1.074) and isolation of sick animals (OR = 2.843; 95% CI: 1.150–7.027) as factors associated with seropositivity, whereas access to technical advisory services was identified as a protective factor. These findings provide essential epidemiological evidence to support surveillance programs and improve biosecurity and veterinary extension strategies in Ecuadorian sheep production systems.

Abstract: Background:Transcrestal maxillary sinus floor elevation (TSFE) is a key technique for posterior maxillary bone deficiency in implantology, with sinus membrane perforation as the main complication. Accurate risk assessment is critical for improving surgical success and implant survival rates. Findings:TSFE surgical risk is determined by six core factors: bone defect type, elevation height, sinus floor morphology, sinus membrane status, ostium patency, and immediate implant placement. Surgical difficulty can be stratified into Easy/Moderate/Difficult, with matching technical strategies to reduce risks. Conclusions: and RelevanceMultidimensional risk stratification and targeted technique selection effectively control TSFE risks. Surgeons with lateral window technique experience are recommended for TSFE, and multidisciplinary collaboration is advised for high-difficulty cases, providing precise guidance for clinical implant practice.

Abstract: This study presents a distribution-optimized mesostructure estimation method for modeling near-surface aggregate size distributions in concrete by optimizing the spatial arrangement of polydisperse spherical aggregates with respect to formwork boundaries. The approach is based on minimizing the deviation between a generated cumulative aggregate volume function and an idealized linear target function corresponding to a constant area fraction along the specimen depth. To enable efficient computation for systems containing a large number of aggregates, grain size classes derived from the grading curve are represented using symmetric Beta distributions, allowing each group to be described by a single shape parameter. The resulting optimization problem is solved using a derivative-free Powell algorithm. The method inherently captures wall effects, leading to a migration of smaller aggregates toward the specimen boundaries to compensate for geometric constraints of bigger aggregates. Experimental validation was performed by determining the depth-dependent mean bulk density of a concrete cube using incremental surface grinding combined with high-resolution 3D laser scanning. The optimized mesostructure shows strong agreement with measured density profiles, significantly improving over a non-optimized distribution. Furthermore, increasing aggregate volume fractions intensify near-surface accumulation of fine particles. The proposed method provides a computationally efficient framework for incorporating wall effects into mesoscale concrete models.

Abstract:

Background/Objectives: Trigeminal neuralgia (TN) is a debilitating neurological condition characterized by recurrent, severe pain linked to peripheral and central sensitization within trigeminal pathways. Although current pharmacologic treatments are limited by inadequate efficacy or dose-limiting side effects, botulinum neurotoxin type A (BoNT/A) has emerged as a viable option. However, its potential use in the management of TN is hampered by methodological limitations in existing studies and a lack of pivotal clinical trials. This study investigated the efficacy, optimal treatment site, preventive utility, and duration of effect of incobotulinumtoxinA (Inco/A), a BoNT/A, in a model of TN. Methods: An infraorbital nerve chronic constriction injury model was used to induce mechanical allodynia in male Sprague–Dawley rats, reproducing the trigeminal sensitization seen in TN. The effects of subcutaneous Inco/A (1, 2, and 4U) were measured using the mechanical sensitivity (von Frey) test to evaluate the dose response, effect of injection location, potential preventive nature of treatment, and duration of benefit. Results: Inco/A produced a robust, dose-dependent reduction in mechanical allodynia, predominantly via a local mechanism of action. Both preventive and therapeutic administration of Inco/A was efficacious, with significant reduction of allodynia even when administered up to 28 days before nerve injury. The anti-allodynic effect persisted up to 56 days post-injection. Conclusions: Inco/A is highly effective in alleviating mechanical allodynia in a validated rat model of TN. The findings highlight Inco/A as a promising candidate for clinical translation in TN and related neuropathic pain syndromes and support systematic investigation in well-controlled human trials.

Abstract: Predicting profitable entry signals in Bitcoin markets remains challenging due to price volatility, the absence of fundamental valuation frameworks, and methodological pitfalls that are common in the literature. In this study, we evaluate five machine learning classifiers using a 37-feature hierarchical multi-timeframe pipeline with price-level-agnostic normalisation across four temporal resolutions (15-minute, 4-hour, daily, and 3-day), spanning January 2020 to November 2025. Binary training labels were generated via majority-vote aggregation across 54 stop-loss/take-profit combinations, producing 6,951 balanced samples (48.5% positive class). Five algorithms --- Logistic Regression, Decision Tree, Random Forest, XGBoost, and LightGBM --- are compared using expanding-window TimeSeriesSplit validation (5 folds). Random Forest achieved the highest cross-validated ROC-AUC (0.6086), with all models showing modest but consistent discriminative ability (range 0.57--0.61). Feature importance analysis identifies 4-hour Bollinger Band position and RSI as dominant predictors, with all timeframes contributing meaningfully. A true out-of-sample holdout on 1,136 independently generated 2025 samples confirms generalisation, with Logistic Regression achieving 0.6087 ROC-AUC. A subtle multi-timeframe look-ahead bias in higher-timeframe data alignment is identified and corrected, which inflated performance by approximately 0.20 ROC-AUC points before correction. Event-driven backtesting on 2025 out-of-sample data yields a gross upper-bound return of +35.97% (185 trades, SL=1%, TP=2%, threshold=0.7, Sharpe=0.14) before transaction costs; after realistic round-trip fees, net returns are likely negligible. The central finding is that models with ROC-AUC $\approx$ 0.60 cannot reliably generate economically significant returns once transaction costs are accounted for. The methodology provides a reproducible framework for ML-based binary classification studies requiring transparent, bias-corrected validation across diverse market regimes.