Abstract: Pathogenicity islands (PAIs) are regions of bacterial genomes that harbor genes encoding virulence factors. Identifying molecules that enhance pathogenicity is crucial for understanding the mechanisms pathogens employ to cause disease and their evolution. Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a pathogenic micro-organism that causes caseous lymphadenitis (CLA) in sheep and goats. Despite its prevalence in Mexico, its genetic material has not been analyzed for virulence factors acquired through horizontal gene transfer. Therefore, the objective of this study was to analyze the complete genome of C. pseudotuberculosis strains of Mexican origin to identify genes hosted in PAIs. Seventeen genomes were sequenced using Illumina technology. GIPSY software was used to identify the coordinates of the PAIs, and a positive selection analysis was performed. All genomes corresponded to C. pseudotuberculosis biovar ovis, and fourteen regions harboring virulence factors were identified. Additionally, five coding sequences with mutations under positive selection were identified. A comparative genetic study was conducted between the new Mexican strains and previously reported strains, using whole-genome multilocus sequence typing (wgMLST) to determine phylogenetic relationships. This work provides the complete genetic repertoire of 17 new strains and identifies 51 genes that could serve as targets in future studies.

Abstract: The coagulation cascade depends on the active participation of several elements present in the blood as well as signals arising from the endothelial cells. A platelet plug is a temporary, fast-response seal formed by platelets at the site of a damaged blood vessel to initiate hemostasis. It acts as the first step in primary hemostasis, where platelets stick to exposed collagen, activate, and aggregate to create a plug that temporarily prevents blood loss. Among changes platelets undergo is the degranulation step. Platelet degranulation is the process where activated platelets release stored chemical mediators from their internal alpha and dense granules into the bloodstream to promote hemostasis and immune responses. Platelet degranulation results in the release of substances like ADP, serotonin, fibrinogen, and zinc. In the present work we provide evidence that the high local concentration of zinc is intended to target junctional adhesion molecule A (JAM-A) that remains inactive (inhibited cell-adhesion and cytoskeleton dynamics) when coagulation is not needed and platelets move through the blood stream as single units. Zinc-activated JAM-A leads the platelets to aggregate. Our experimentation includes work with platelets, and a synthetic biology small peptide to quench the effects of zinc. We suggest that further exploring this mechanism of zinc-activated JAM-A can be advantageous for better understanding hemostasis, its role in antithrombotic therapy, coagulation inhibition, or thrombosis prevention.

Abstract: Financial crises are usually identified through drawdowns, volatility and changes in returns, but these indicators do not fully describe changes in the underlying dynamical structure of markets. This study tests whether Laminarity, a measure derived from Recurrence Quantification Analysis, can provide a complementary indicator of financial market stress during the COVID-19 shock. Daily data for the Dow Jones Industrial Average, S&P 500 and NASDAQ Composite from 2018 to 2022 are analyzed using adjusted prices and log returns. Rolling-window Recurrence Quantification Analysis is applied across alternative window lengths and recurrence thresholds, and the resulting Laminarity measures are compared with conventional benchmarks including drawdown and rolling volatility. The results confirm that the COVID-19 crisis is clearly identified by conventional risk indicators, while Laminarity provides a more nuanced and parameter-sensitive signal. Price-based Laminarity generally increases during the COVID-19 stress period, suggesting a more persistent crisis trajectory, whereas return-based Laminarity produces mixed evidence, including some cases of Laminarity loss depending on index and window length. The findings indicate that Laminarity should not be interpreted as a universal or mechanical crash-warning signal, but as a complementary diagnostic measure that can help describe changes in market-regime structure during periods of acute stress.

Abstract: Background/Objectives: There are well-established sex differences in the epidemiology of stroke, but current data does not provide a clear mechanism to explain this phenomenon. This study asked if relationships between circulating sex hormone levels and stroke incidence could explain the sex differences in stroke rates. Methods: 393,158 participants from the UK Biobank aged were followed for a mean duration of 13.2 years. The incidence of ischemic stroke (IS) and intracerebral haemorrhage (ICH) was analysed in relation to baseline and changing levels of testosterone, sex hormone binding globulin (SHBG) and oestradiol. Results: A total of 3,844 participants experienced an IS and/or ICH, with incidence higher in men than women. In both sexes, a U-shaped association between total testosterone and ICH was found, independent of common cerebrovascular disease risk factors (P=0.006). Higher SHBG levels were associated with higher risk of IS (Q4 hazard ratio=1.18; P<0.001) in both men and women, independent of common cerebrovascular risk factors. No significant associations were observed between oestradiol levels and stroke events after making demographic adjustments. Conclusions: These data highlight the nuanced roles that sex hormones play in the epidemiology of stroke between sexes. Whilst sex hormones are implicated in modulating stroke risk, this study demonstrated the complexity of this relationship.

Abstract: Differential Causal Networks (DCNs) were introduced to represent changes between two causal networks inferred under different conditions. In their original use, however, DCNs remain pairwise objects: each differential graph summarizes rewiring within a single system, while common differential structures shared across many systems remain implicit. We introduce a methodological framework for the local alignment of DCNs aimed at detecting recurrent rewiring motifs, that is, small directed differential subnetworks that reappear across multiple systems under the same contrast. The proposed framework transforms each system-specific comparison into a signed directed differential graph, preserves both edge direction and change type, and searches for approximate local correspondences rather than enforcing a full-network mapping. The method consists of four steps: construction of signed DCNs, extraction of differential seeds, pairwise local alignment by seed-and-extend, and progressive multiple alignment to build consensus motifs. We define a score that combines node compatibility, differential-edge conservation, directional consistency, and recurrence support, and we complement the alignment procedure with null-model testing and robustness analysis. The result is a collection of consensus local differential modules ranked by recurrence, confidence, and statistical significance. In this formulation, DCNs become comparable units in a higher-order analysis whose goal is not merely to describe pairwise causal change, but to identify the same local rewiring logic reused across multiple systems.

Abstract: A multi-analytical study was conducted to investigate the deterioration mechanisms affecting the stone materials of the Arca di Cansignorio della Scala (Verona, Italy) and to identify the residual traces of polychromy and gilding. The investigation combined macroscopic mapping, stratigraphic sampling, optical microscopy (OM), environmental scanning electron microscopy (ESEM) coupled with energy-dispersive spectroscopy (EDXS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and ion chromatography (IC). The monument, mainly carved in Candoglia marble, exhibits three principal weathering typologies: (i) meteoric washing associated with marble decohesion, (ii) grey deposits (dirt accumulation areas); and (iii) sulphation-related black crust formation (dirt wetting areas). In addition, severe mechanical damage is as-sociated with early 20th-century structural consolidation using embedded iron bars, whose corrosion-induced volumetric expansion generated vertical fissures. Strati-graphic analyses revealed the presence of original azurite-based polychrome, proteina-ceous and lipidic binders, lead white preparatory layers, and multiple gold leaf applica-tions of gold leaf. The study highlights the interaction between environmental exposure, atmospheric pollution, material incompatibility resulting from past restorations cam-paigns, and the preservation state of the surviving decorative painted layers.

Abstract: Lithium-ion batteries (LIBs) are widely used across a range of applications; however, they degrade over time due to various factors, including repeated charge–discharge cycling, material aging, and environmental conditions. Degradation models play a crucial role in predicting the lifespan of LIBs and in optimizing their design and opera-tional strategies. This paper presents a comprehensive review of state-of-the-art deg-radation models for LIBs. The reviewed models primarily address key degradation mechanisms, including solid electrolyte interphase (SEI) formation, lithium plating, and particle fracture. For each mechanism, the underlying modeling approaches, their development, advantages, limitations, and associated challenges are critically dis-cussed. Finally, this review identifies existing gaps in battery degradation modeling and proposes the Unified Mechanics Theory (UMT), which is the unification of laws of Newton and the second law of thermodynamics, and uses entropy as a degradation metric, as a promising alternative framework for capturing the coupled and multifac-eted nature of battery degradation processes.

Abstract: Functional fermented beverages represent promising dietary tools for modulating nutrient-responsive pathways and intestinal homeostasis. The probiotic strain Lacticaseibacillus paracasei subsp. paracasei F19 (F19) has demonstrated exceptional resilience in technologically harsh environments, including high-hopped beers, acidic dairy matrices, and polyphenol-rich fruit substrates. Evidence from multi-omics analyses indicates that F19 activates hop- and acid-resistance systems while maintaining metabolic functions responsible for folate biosynthesis, short-chain fatty acid production, and the generation of bioactive volatiles. These metabolites participate in host-directed mechanisms, including the upregulation of the vitamin D receptor (VDR), modulation of autophagy-related genes such as ATG16L1, and attenuation of inflammatory signaling. Complementary studies using red pitaya (Hylocereus sp.) fermented with F19 and Bifidobacterium animalis subsp. lactis BB-12 further demonstrate increased VDR and CAMP expression, reduced CYP24A1, and the enrichment of anti-inflammatory flavonoids such as rutin and quercetin. Collectively, these findings support the concept of a probiotic paradox, in which environmental stressors do not suppress probiotic function but instead enhance genetic, metabolic, and host-interactive capacities. F19 thus emerges as a compelling candidate for the development of functional fermented foods aimed at improving epithelial barrier integrity, modulating immune responses, and supporting microbiota equilibrium, with translational potential for managing inflammatory and nutrient-responsive intestinal disorders.

Abstract: Background: Pirtobrutinib has recently emerged as a promising first-line treatment option for chronic lymphocytic leukemia (CLL). Unlike currently established regimens, which are generally based on doublet combinations, pirtobrutinib can be administered as monotherapy. Because no head-to-head trials comparing pirtobrutinib with contemporary first-line combinations are currently available, indirect comparative evidence may help define its potential role. Methods: A non-anchored indirect comparison based on reconstructed individual patient data (IPD) was conducted using published Kaplan-Meier curves from randomized controlled trials evaluating first-line treatments for CLL. Progression-free survival (PFS) was the endpoint of interest. Reconstructed IPD were generated using WebPlotDigitizer and the IPDfromKM algorithm. Pirtobrutinib monotherapy was compared indirectly with acalabrutinib plus obinutuzumab, venetoclax plus obinutuzumab, and venetoclax plus ibrutinib. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using univariate Cox models. Results: The analysis included four randomized trials. Compared with pirtobrutinib monotherapy, HRs for PFS were 0.5544 (95%CI, 0.2696-1.1397) versus venetoclax plus obinutuzumab, 0.4583 (95%CI, 0.2066-1.0200) versus venetoclax plus ibrutinib, and 1.4453 (95%CI, 0.6684-3.1240) versus acalabrutinib plus obinutuzumab. Confidence intervals were wide and crossed unity in all comparisons, indicating substantial statistical uncertainty. Visual inspection of reconstructed Kaplan-Meier curves did not suggest inferior PFS for pirtobrutinib relative to established doublet regimens. Conclusions: This exploratory non-anchored analysis suggests that pirtobrutinib monotherapy may provide PFS outcomes broadly comparable to current first-line combination regimens for CLL. Given the methodological limitations inherent to indirect comparisons, prospective head-to-head studies are needed to clarify the optimal positioning of pirtobrutinib in treatment-naïve CLL.

Abstract: This study examines the role of agricultural and tourism entrepreneurship in reducing rural poverty through community empowerment within a place-based development framework. Using data from 400 respondents in Jambi Province, Indonesia, and employing Partial Least Squares Structural Equation Modeling (PLS-SEM) combined with the Analytical Hierarchy Process (AHP), the results reveal that agricultural entrepreneurship (β = 0.482, p < 0.001) and tourism entrepreneurship (β = 0.361, p < 0.001) significantly enhance community empowerment. In turn, community empowerment has a strong negative effect on poverty (β = -0.533, p < 0.001). The mediation analysis confirms that empowerment fully mediates the relationship between entrepreneurship and poverty reduction. Furthermore, AHP results indicate that community empowerment is the highest policy priority (44.2%), followed by agricultural entrepreneurship (33.8%) and tourism entrepreneurship (22.0%). This study contributes to the literature by integrating dual-sector entrepreneurship and identifying empowerment as a key mechanism in sustainable and inclusive rural development.

Abstract: The calibrated model reproduced the overall trend of specimen-to-specimen mechanical variation observed experimentally. Predicted stiffness values were in reasonable agreement with measured data. Fracture force predictions showed moderate agreement for dynamically tested specimens (R² = 0.60), which improved to R² = 0.88 after exclusion of one statistically identified outlier. Compared with a purely linear elastic formulation, the proposed viscoelastic model demonstrated modest improvement in stiffness prediction and more substantial improvement in fracture force prediction. These findings indicate that incorporating density-dependent viscoelastic effects improves representation of vertebral mechanical behavior, particularly at higher loading rates. Owing to its simplicity and computational efficiency, the proposed model requires only limited imaging input and may be useful for future biomechanical investigations, rapid screening, and injury risk prediction.

Abstract: Purpose: Next-generation sequencing (NGS) is routinely used in the diagnostic workup of neurological diseases, enabling systematic screening for SMA with tailored bioinformatic tools, further enhancing diagnostic speed and accuracy. Methods: We leveraged SMNCopyNumberCaller, SMAca, and SMAFinder in our NGS cohort (n = 3493), including 74 MLPA-validated SMA cases (one compound heterozygous) in the exome dataset. Putative SMA cases were validated using PCR-RFLP and MLPA. Results: With default settings of SMA Finder in exome cohort (n = 2437), 16.4% of samples were uncallable including 40 known SMA cases. Lowering read thresholds markedly improved callability and identified 71/73 known SMA cases, two cases remaining uncallable. SMAca correctly detected 73/73 SMA cases. Both tools had a positive predictive value of 100% and identified two missed cases (DM1, MND), subsequently molecularly confirmed. After inclusion of correction value to scale factor, SMAca showed high concordance with MLPA for SMN2 copy number estimation in SMA cases. Carrier frequencies were estimated as 1:36 and 1:47, in genome and exome respectively. Using SMNCopyNumberCaller, we provided detailed SMN profiling in a Turkish genome cohort (n = 1056). Conclusions: NGS-based SMN analysis enables robust detection of SMA and supports systematic cohort screening to identify missed cases.

Abstract: This study investigates the regularity of the three-dimensional (3D) incompressible Navier-Stokes equations (NSE) for plane Couette flow, a canonical shear-driven flow model with a well-defined laminar-turbulent transition threshold. Employing Sobolev space theory and the Energy-Velocity Monotonicity Principle (EVMP), we rigorously prove that no global smooth solutions exist as the Reynolds number exceeds the critical value \( Re_{cr} \). Prior studies have revealed that a zero velocity gradient on the velocity profile is the necessary and sufficient condition for turbulence generation in 3D plane Couette flow, yet they lack mathematical theoretical proof from the perspective of partial differential equation framework. This study fills this gap via velocity decomposition and singularity analysis. We show that nonlinear disturbance amplification induces local cancellation of mean and disturbance velocity gradients, triggering finite-time singularity formation in flow field, which leads to the breakdown of regularity of the 3D NSE and thus the non-existence of global smooth solutions. It is emphasized that the non-existence of smooth solutions is due to the local regularity breakdown of solutions instead of the velocity blow-up. Further, it is important that the critical condition for regularity breakdown obtained through Sobolev space analysis accords with the critical condition for turbulence onset obtained through experiments and simulations.

Abstract: Partial metrics have shown to be useful dissimilarity measures when incomplete information, partial states, or inherent uncertainty is involved. The main characteristic of this kind of distances is allowing non-zero self-distances. This distinctive property makes them particularly appropriate for applications to computer science, artificial intelligence, pattern recognition and bioinformatics. Nevertheless, in these fields it is often more relevant to quantify the amount of shared information between objects rather than their dissimilarity. In this context, similarity metrics have proven to be a valuable tool. The literature has suggested the existence of a duality relationship between partial metrics and similarity metrics. In this paper we investigate such a relationship. Specifically, we focus on identifying the properties of functions that induce a similarity metric from a partial metric in the sense of O’Neill. We provide a characterization of these functions, showing that they coincide with the class of strictly decreasing and convex functions on the set of non-negative real numbers. We also show that these functions preserve the topology and the partial order, that is, the partial order and topology generated by the induced similarity metric and by the original partial metric are the same. Besides, we characterize the class of functions capable of generating an O’Neill partial metric from a similarity metric showing that such a class is formed by strictly decreasing and concave functions on the set of real numbers. In this case we also show that the partial orders and the topologies generated by the induced partial metric and by the original similarity metric coincide. The results are supported and clarified by appropriate examples.

Abstract: Nano-engineering strategies have been increasingly applied to enhance the biological performance of calcium silicate–based materials; however, the optimal concentration of nano-hydroxyapatite (HANP) remains unclear. This study evaluated the bone-healing response to different concentrations of HANP incorporated into mineral trioxide aggregate (MTA) and bioceramic (BC) sealers in an experimental rabbit model. Thirty adult New Zealand white rabbits were allocated into two experimental groups according to sealer type: HANP-modified MTA and HANP-modified BC (n = 15 each). Two standardized circular intrabony defects were created bilaterally in the maxillary diastema of each rabbit. In the MTA group, the right-side defects were filled with 2% and 4% HANP-modified MTA, while on the left side one defect received 6% HANP-modified MTA and the adjacent defect was left as control. The same protocol was followed for the BC group using corresponding HANP concentrations. Five rabbits per group were sacrificed at 2, 4, and 8 weeks postoperatively for histopathological hematoxylin and eosin (H&E) and Masson trichrome staining. The results demonstrated significant differences among groups at all-time points, with 4% HANP showing the most favorable biological response, including reduced inflammatory cell infiltration, increased new bone formation, and improved collagen organization compared with lower and higher concentrations. Pairwise comparisons at matched HANP concentrations revealed no statistically significant differences between HANP-modified MTA and BC groups. These findings indicate that HANP incorporation enhances the biological performance of calcium silicate–based sealers in a concentration-dependent manner, with 4% representing an optimal formulation for promoting bone regeneration.

Abstract: Additive manufacturing is moving towards the use of machines with five or more axes but is limited by the inability to easily generate print paths. This usually requires the creation of custom G-code in order to utilize five-axis printing. However, as additive manufacturing begins to utilize five-axis printing for scenarios such as repair, modification, or composite printing, the existing print surfaces become potential obstacles that need to be accounted for in path planning. This paper shows a novel way of expanding the capabilities for printing on complex, concave parts, in order to prevent collisions between the printer and the part. This is achieved through two main steps: Area Refinement, and Angle Determination. During Area refinement, the proposed print area is altered based on the geometry of the print surface, along with printer parameters. This results in a print region that is feasible with the given machine configuration and geometry, that will not attempt to print too close to any existing surface in the presence of concavities. During Angle Determination, the finalized print paths are adjusted to set a nozzle orientation that prevents the machine from colliding with the part. In this paper, we present the algorithmic details behind these approaches and show computational results for two complex concave geometries.

Abstract: This study introduces new classes of fuzzy open sets, namely (p,q)-FΩ-open (resp. (p,q)-FΩP open, (p,q)-FΩS-open, (p,q)-FΩα-open, and (p,q)-FΩγ-open) sets in double fuzzy topological spaces (DFTSs) in view of Šostak. We conduct a detailed investigation of the relationships among these classes of open sets, supported by carefully constructed illustrative examples. Furthermore, we propose and characterize the associated DFΩ-interior and DFΩ-closure operators. Subsequently, we define and analyze new classes of fuzzy functions based on (p,q)-FΩ-open sets, referred to as DFΩ-continuous and DFΩ-irresolute functions within the framework of DFTSs (S,ϑ,ϑ^∗) and (Z,ζ,ζ^∗). We also introduce the notions of DFΩP-continuous, DFΩS-continuous, DFΩα continuous, and DFΩγ-continuous functions, which constitute weaker forms of DFΩ-continuity. As an application, we demonstrate that these newly defined continuity concepts generalize, extend, and unify several existing results in the theory of DFTSs. Finally, we propose and discuss the concepts of DFAΩ-continuity and DFWΩ-continuity as additional weaker variants of DFΩ-continuity. Moreover, we establish new separation axioms, termed (p,q)-FΩ-normal and (p,q)-FΩ-regular spaces, formulated via (p,q)-FΩ-closed sets.

Abstract:

Background: The local twitch response (LTR) elicited during ultrasound-guided fascial hydrorelease (FHR) is conventionally attributed to dysfunctional motor endplates. However, in a related observational paper under concurrent submission, 89/89 evaluable archived LTR events were observed within stacking fascia at sites incompatible with direct endplate excitation. Hypothesis: We propose the Fascial Capacitor Model: stacking fascia functions as a multilayer biological capacitor in which collagen sublayers act as electrodes and the interposed densified hyaluronic-acid (HA)-rich loose layer acts as the dielectric, with the LTR reinterpreted as a transient electrophysiological discharge when a needle bridges its layers. This biophysical model is explicitly grounded in the established molecular and histological architecture of human deep fascia. Supporting evidence: Each premise is independently supported by primary literature from at least eight research lines spanning roughly seventy years. Voltage gap: The apparent gap between estimated bulk discharge voltages and motor neuron threshold is resolved by reconsidering needle-tip geometry and stimulation modality, anchored by the ±6 V triboelectric measurements of Ouyang et al. (2022). Implications: The model is the immediate-phase complement to the Fascial Memory Reset Hypothesis (Int J Mol Sci 2026, 27, 3720), explains intra-procedural symptom relief, and yields falsifiable predictions. A direct empirical validation programme using insulating-needle SEA recording is in preparation at the corresponding author’s institution.

Abstract: This paper examines whether digital skill requirements in educational job postings are associated with higher advertised salaries in the labor markets of Almaty and Astana, Kazakhstan, and whether the observed salary gap reflects genuine skill valuation or employer heterogeneity. Using 794 vacancies collected via the HH.kz API, we construct an analytical sample of 755 observations after data cleaning. A seven-category dictionary-based skill extraction pipeline is implemented and its integral lexical consistency is evaluated against a TF-IDF+Logistic Regression baseline (5-fold CV: F1=0.755, AUC=0.928). Vacancies specifying at least one digital requirement carry a median advertised salary that is 18.2% higher than non-digital postings. OLS with HC3- robust standard errors and occupational and city controls yields a coefficient of 0.200 (SE = 0.039, p< 0.001, approximately +22.2%). Adding an employer-type proxy reduces this estimate to +15.2% (p < 0.001). In the Almaty subsample, the effect is no longer statistically significant (p = 0.075). Part of the observed premium reflects a measurement problem. Higher-paying employers are also more likely to specify digital requirements, inflating the estimated association. The design does not identify firm effects and supports only an associational interpretation. Quantile regression shows that the salary-digital gradient increases from +15.0% at Q25 to +44.4% at Q90. This pattern is consistent with labor market segmentation rather than a uniform skill premium.

Abstract: In this study the development of sustainable electrocatalysts for clean energy by modifying biomass-derived activated carbon with nitrogen and transition metals is presented. Activated carbon (AWC) was synthesized using alder wood char as a precursor, while nitrogen and cobalt or copper nanoparticles were incorporated with the aim to create efficient materials for hydrazine oxidation (HzOR) and direct hydrazine-hydrogen peroxide fuel cells (DHHPFC, N2H4–H2O2). The composition, structure, and surface morphology of the created catalysts were examined using inductively coupled plasma optical emission spectroscopy (ICP-OES), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and scanning electron microscopy and energy dispersive X-ray analysis (SEM/EDX). The activity of the AWC, AWC–Co–N, and AWC–Cu–N catalysts for HzOR was evaluated by cyclic voltammetry (CV) and linear sweep voltammetry (LSV). N2H4–H2O2 fuel cell tests were carried out by employing the catalysts both as the anode and cathode. It was found that all materials retained a hierarchical porous carbon framework, while metal incorporation altered surface compactness Cobalt doping produced well-dispersed Co nanoparticles and abundant Co–N–C coordination sites, whereas Cu introduction resulted in moderately compact structures with uniformly distributed Cu-based nanoparticles. Electrochemical measurements demonstrated that both metal dopants enhanced HzOR activity, with the catalytic performance following the order AWC–Co–N &gt; AWC–Cu–N &gt; AWC. Fuel-cell testing further confirmed this trend: AWC–Co–N achieved the highest maximum power density (30.4 mW cm–2), outperforming AWC–Cu–N (17.7 mW cm–2). These results identify AWC–Co–N as a highly effective bifunctional electrocatalyst for DHHPFCs.