Abstract: Background: Pharmaceutical innovation plays a vital role in advancing global health. This study evaluates the landscape of pharmaceutical innovation in the European Union (EU) over the 2011-2020 decade. Methods: A retrospective analysis was performed on new medicinal products containing new active substances (NAS) authorized between 2011 and 2020 through the centralized procedure. Products were categorized in first-in-class, advance-in-class, and addition-to-class. Trends in therapeutic areas (ATC codes), orphan designation, technology platforms etc), administration routes, and dosage forms were analyzed. Results: Across the decade, 357 new medicinal products received authorization. Of these, 56% were designated as first in class and 28% as advance in class, indicating that 84% of new products contributed substantive therapeutic innovation. Small molecules remained the predominant technology (63.5%), yet the decade also wit-nessed a pronounced expansion in monoclonal antibodies and the introduction of cell and gene therapies (Advanced Therapy Medicinal Products, ATMPs). The increased use of subcutaneous delivery systems, particularly for monoclonal antibodies, suggests a broad-er move toward patient centered administration routes. Conclusion: Between 2011 and 2020, pharmaceutical innovation in the EU was distinguished by a high rate of break-through innovation and a transition to more sophisticated biologic therapies. EU could boost innovation further by refining expedited approval pathways (e.g., PRIME).

Abstract: We present a geometric charge–lattice framework for describing the internal structure of the proton and neutron. In this approach, nucleons are represented as stable 3 × 3 arrangements of discrete positive and negative charge units. The proton corresponds to a lattice containing five positive and four negative charges, reproducing its observed net charge and characteristic size scale. The neutron is described as a closely related charge–rebalanced configuration of the same geometric form. We show that linear projections of these charge lattices naturally generate effective charge patterns consistent with quark–like signatures observed in high–energy scattering experi- ments. Within this interpretation, fractional charge responses arise as geometric averages of integer charge units distributed across the lattice, without requiring independently existing fractional–charge constituents. The charge–lattice representation provides a concrete spatial interpretation of nucleon charge organization that remains compatible with established experimental phenomenology. The framework leads to testable implications for nucleon charge form factors and motivates further investigation through precision scattering and spatial distribution measurements.

Abstract: The prevalence of microalgae as a food source is challenged by the consumers disliking the organoleptic traits mainly due to the intense green color and bitter taste associated with the high chlorophyll content. The eukaryotic microalgae Chlorella vulgaris can grow under heterotrophic conditions providing the opportunity to cultivate chlorophyll-less strains. In this work we applied random mutagenesis for breeding chlorophyll deficient C. vulgaris strains. Wild type strain was UVC-radiated, and 12 colonies with changed pigmentation were selected. Based on phenotypic stability two mutants, M6 and M11, were selected for characterization of growth, pigment- and biomass accumulation. Cultivation under photo-, mixo-, and heterotrophic conditions revealed distinct phenotypes for the two mutants. M6 remained chlorophyll deficient in all cultivation conditions tested, while limited amounts of chlorophyll were observed in M11 when grown in light. At heterotrophic and mixotrophic growth conditions, both mutants were chlorophyll defi-cient while biomass productivity and protein content and amino acid composition were not significantly different from wild type. Characterization of the cellular ultrastructure of the wild type and mutants using cryo Focused Ion-Beam Scanning Electron Microscopy revealed that functional chloroplasts and thylakoid membranes were absent in the mu-tants. Our work demonstrates how a simple approach using UV mutagenesis and visual screening can provide novel strains of C. vulgaris with traits for improved consumer acceptance, without compromising the use of the algae biomass as a protein-rich food source.

Abstract: This paper introduces a production-grade smart-routing gate-way that boosts permission results by ranking acquirer terminals witha two-stage AI pipeline: a static sieve that enforces business rules andforecasts gateway downtime, followed by a dynamic scorer that computesdecay-weighted, real-time success features and infers per-terminal winprobabilities. The system blends time-window and event-window teleme-try with adaptive half-life revisions and a random-forest classifier, thenorchestrates retries to the next-best route on failure, delivering 4–6%success-rate lift across cards, net-banking, and UPI at Internet scale.Deployed inline at a payment processor, it shows flexible and adaptivepayment processing and gateway choice with explainable signals, lowlatency, and continuous feedback learning.

Abstract: Entrepreneurial branding on Instagram has emerged as a strategic practice through which entrepreneurs construct, communicate, and reinforce their professional identities while engaging directly with audiences. This study examines the psychological motivations that drive entrepreneurs to invest in personal branding activities on Instagram and the mechanisms through which these motivations shape user engagement. Drawing on theories of self-presentation, intrinsic and extrinsic motivation, and social identity, the paper explores how needs for autonomy, competence, recognition, and social belonging influence branding behaviors such as content curation, storytelling, authenticity signaling, and interaction patterns. The analysis further considers how psychological drivers affect engagement outcomes, including likes, comments, shares, and follower loyalty, by shaping perceived credibility and emotional connection. By synthesizing insights from entrepreneurship research, psychology, and digital marketing, the study provides a conceptual understanding of why entrepreneurs engage intensively with Instagram branding and how psychological motivations translate into sustained audience engagement. The findings offer implications for entrepreneurs seeking to align branding strategies with authentic psychological drivers, as well as for scholars examining the human factors underlying digital entrepreneurial activity.

Abstract: Minesweeper has been a traditional puzzle game based on numeric patterns to indicate the presence of hidden mines. Despite being a game with simple gameplay patterns, its algorithmic structure has been well defined in terms of a set of predefined rules to deduce safe and harmful cells. This research aims to perform an algorithmic analysis of Minesweeper instead of being a traditional game analysis approach. Several player-based tests have been developed for evaluating the algorithmic performance in different sizes of game boards. Black-box and user-based testing techniques have been employed in this research as used in traditional game analysis frameworks. The experiment outcomes indicate good algorithmic performance for smaller game boards but poor performance for larger boards under conditions of uncertain game data.

Abstract: By using Littlewood's oscillatory theorem and a result of Fujii we disprove the Riemann hypothesis.

Abstract: The object of research in the scientific article is the process of converting wind flow energy into mechanical energy. The process of converting wind energy into mechanical energy is carried out by two counter-rotating wind wheels. And into electrical energy in the generator, with the armature and inductor rotating in opposite directions. The purpose of the scientific article is to study and develop an efficient power supply system for autonomous consumers based on a wind power plant of a special design with an increased wind energy utilization coefficient. In the course of the work, the main parameters of a special-designed wind turbine with counter-rotating wind wheels were determined and the process of electric generation was modeled on the principle of counter-rotation of the armature and generator inductor; a physical model of a special-designed wind turbine based on a two-wheeled system located in the same wind flow and providing rotation of the armature and generator inductor individually from each wind wheel in the opposite direction was developed; a design documentation on the basis of which the experimental design sample was made; experimental studies of the experimental design sample of a wind turbine were conducted to determine its main parameters for the purpose of efficient power supply to autonomous consumers. Main design and technical and economic indicators: optimization of wind power plant parameters, dimensions of wind wheels, their relative location, as well as generator power depending on the expected wind speed. The degree of implementation lies in the fact that a wind generator with variable torque of a wind wheel is patented (patent for invention of the Republicof Kazakhstan No. 36903; Eurasian patent for invention No. 047230). The effectiveness of the research lies in the application of technical solutions patented by the authors in practice, which makes it possible to increase the energy efficiency of wind turbines. Scope of application of the developed wind turbine of special design in the field of alternative energy and decentralized agricultural consumers.

Abstract: Galaxy evolution models usually treat environment as a driver of quenching and morphological transformation, but less often as a regulator of how systems retain or erase long-term memory of past conditions. This paper uses the homeostatic potential framework $\hat{\phi}$ to ask a focused question: once a galaxy has crossed the structural ``stability gate'', how much additional leverage does environment still have on its chemical memory?Using SDSS DR8 and GAMA DR4 as low-redshift benchmarks, and the EAGLE RefL0100N1504 simulation as a controlled comparison, galaxies are split into structurally ``infant'' and ``adult'' regimes by the stability proxy $\hat{S}$. For each regime, the dispersion of the metallicity-based memory proxy $\hat{M}$ is measured as a function of local density and group-scale environment (k-nearest-neighbour density, projected surface density, and host-group halo mass). The same diagnostics are then applied to the TNG suite to test whether the infant/adult environmental contrast is a robust feature of hydrodynamical models with different feedback prescriptions. A MaNGA pilot sample provides an independent sanity check that $\hat{S}$ behaves as a structural maturity indicator rather than a data-quality or environment artefact. In SDSS, metallicity scatter rises with local density for structurally infant galaxies, but remains lower and only weakly environment-dependent for adults at fixed mass and stability. In GAMA, the scatter is nearly flat across four decades in projected density once $\hat{S}$ is fixed, with only a mild broadening in the highest-density adult bin. In EAGLE, the dependence of scatter on host halo mass is similarly weak at fixed structural state. TNG runs show very weak correlations between the homeostatic components and local density once mass selection is imposed, indicating that the stability gate is not simply a field--cluster split in disguise. The MaNGA pilot confirms that the entropy-like component $\hat{S}$ correlates strongly with galaxy size but only weakly with S/N, behaving as a structural maturity coordinate. Together, these results support a simple picture: environment acts as a strong modulator of homeostatic potential before the stability gate is crossed, but mainly tunes residual variance once galaxies have internalised their history into a stable configuration. Environment is a modulator of memory, not its primary container.

Abstract: Post-transcriptional regulation of gene expression is influenced by RNA-binding proteins (RBPs) and small non-coding RNAs which bind to conserved mRNA sequences to modulate mRNA processing. These regulatory molecules effect the structural conformation of mRNAs, creating formations like G-quadruplexes (G4s) which alter translation initiation and regulatory factor site accessibility. Recent studies have highlighted Nuclear factor erythroid 2-related factor 2 (NRF2) as a key regulator of cellular redox homeostasis and cellular response to oxidative stress. An intriguing feature of NRF2 is the structural formation of its 5’ untranslated region (UTR) which may promote or inhibit translation initiation depending on the cellular context. In this study with mini genes, we provide evidence of RNA G4s in NRF2 mRNA’s 5’ UTR regions under basal (no stress) conditions in vitro through EMSA and fluorescence spectra in the presence of pyridostatin. Understanding how structural motifs within NRF2’s 5’UTR regions influence mRNA function provides insights into a common molecular mechanism underlying diseases where NRF2 is dysregulated, like cancers, cardiovascular disease, and neurodegeneration, and highlights potential therapeutic avenues through regulation of NRF2.

Abstract: Remote sensing semantic segmentation encounters several challenges, including scale variation, the coexistence of class similarity and intra-class diversity, difficulties in modeling long-range dependencies, and shadow occlusions. Slender structures and complex boundaries present particular segmentation difficulties, especially in high-resolution imagery acquired by satellite and aerial cameras, UAV-borne optical sensors, and other imaging payloads. These sensing systems deliver large-area coverage with fine ground sampling distance, which magnifies domain shifts between different sensors and acquisition conditions. This work builds upon DeepLabV3+ and proposes complementary improvements at three stages: input, context, and decoder fusion. First, to mitigate the interference of complex and heterogeneous data distributions on network optimization, a feature-mapping network is introduced to project raw images into a simpler distribution before they are fed into the segmentation backbone. This approach facilitates training and enhances feature separability. Second, although the Atrous Spatial Pyramid Pooling (ASPP) aggregates multi-scale context, it remains insufficient for modeling long-range dependencies. Therefore, a routing-style global modeling module is incorporated after ASPP to strengthen global relation modeling and ensure cross-region semantic consistency. Third, considering that the fusion between shallow details and deep semantics in the decoder is limited and prone to boundary blurring, a fusion module is designed to facilitate deep interaction and joint learning through cross-layer feature alignment and coupling. The proposed model improves the mean Intersection over Union (mIoU) by 8.83% on the LoveDA dataset and by 6.72% on the ISPRS Potsdam dataset compared to the baseline. Qualitative results further demonstrate clearer boundaries and more stable region annotations, while the modifications to the baseline are minimal and easy to integrate into camera-based remote sensing pipelines and other imaging-sensor systems.

Abstract: In the transition towards digitalization and automation of mining processes, high vol-umes of data are generated, including data from distributed sensor and actuator networks, voice communications, videos and vehicle telemetry data. This generated data is prepro-cessed on-site and subsequently transferred not only to headquarters for detailed analysis but also between mining machines and vehicles in case of automation or autonomous mining. Stable and efficient communication in the mining industry and particularly in underground environments is essential for increasing safety and productivity, support fast and secure transportation and facilitate logistical processes, ensuring continuous and smooth operations. Several different communication technologies and protocols exist related to the mining field, each with its unique characteristics, advantages, or limitations. This article focuses on two essential technologies that, despite their shared goal of enhancing communication networks, exhibit notable contrasts in some of their characteristics: Long Range (LoRa) as an existing technology in the industry since years and the technology of the fifth genera-tion (5G) of cellular network will be presented and discussed in this article, highlighting the significant differences in their properties and applications. This provides an important basis for understanding the limits and possible trade-offs of the wireless communication technologies required in the mining industry for large scale sensor networks.

Abstract: High pressure processing (HPP) and ultrasound assisted extraction (UAE) can effectively shorten extraction time and increase extraction efficiency of cold brew (CB). however, their application in CB citri reticulatae pericarpium (CRP) and the underlying mechanisms of flavor modulation remain poorly understood. In this study, CB-CRP beverage was prepared with HPP-assisted, UAE-assisted and HPP-UAE-assisted extraction from 1, 3, 5, and 10 years CRP. Results revealed that the total soluble solids (TSS), total sugars, flavonoids, polyphenols, and volatile organic compounds (VOCs) and antioxidant activity of CB-CRP increased after assisted extraction. The combined application of HPP and HPP-UAE assisted extraction exhibited the most pronounced effects. The kinds and total content of VOCs of CB beverage prepared from 10-year-aged CRP increased from 45 to 81, and from 2.44 to 5.98 μg/mL resectively. Moreover, the combined HPP-UAE extraction promoted the enrichment of fatty and woody aroma-related compounds, which drove a shift in the flavor profile from fresh to a richer woody type. And this endowed the CB-CRP water with a more complex and multidimensional aroma profile.

Abstract: The Qinghai–Tibet Plateau and surrounding montane valleys comprise one of the world’s most pronounced freshwater environmental gradients, where cold, intense UV radiation, variable dissolved oxygen, and heterogeneous hydrodynamics interact with drainage reorganization and connectivity constraints. Schizothoracinae are among the most representative endemic lineages in these systems, combining exceptional lineage diversity with pervasive polyploid genomic backgrounds. Here we synthesize schizothoracine research through an “environment–evolution–conservation” framework, linking (i) taxonomic and phylogenetic foundations under pervasive convergence, cryptic diversity, and hybridization; (ii) geologic history and drainage evolution as drivers of radiation and gene exchange; (iii) polyploidy, post-WGD structural remodeling, and early rediploidization as a testable process rather than a static ploidy fact; and (iv) omics resources and analytical pipelines that enable verifiable evidence chains across comparative genomics, population genomics, and tissue-level stress responses. Across major stressors, recurrent molecular themes emerge for cold-associated metabolic remodeling and UV-associated DNA repair and genome maintenance, whereas hypoxia-related signals are often inconsistent, plausibly reflecting strong spatiotemporal heterogeneity and multi-route physiological accommodation. We further connect molecular candidates to functional outcomes using reusable phenotypic evidence streams, including geometric morphometrics, high-throughput phenotyping, otolith microchemistry, and age–growth life-history syndromes of slow growth and longevity. Finally, we translate population structure into operational MU/ESU delineation and propose an auditable, iterative management checklist centered on MU-aligned stocking, connectivity performance metrics during critical seasonal windows, and quantified habitat restoration targets. We conclude by outlining priorities to raise evidentiary strength across basins: chromosome-level genomes across lineages, systematic SV/TE comparisons, standardized stressor–phenotype–transcriptome designs, and intensified sampling in geomorphic transition zones and putative hybrid regions to enable cumulative, decision-ready synthesis.

Abstract: Postoperative aneurysm sac enlargement is a significant clinical issue in endovascular aortic aneurysm repair that is potentially associated with impaired microcirculation in the aneurysmal wall. We developed centimeter-long, fiber-shaped aggregates of human bone marrow-derived mesenchymal stromal cells (HMSC fiber) to function as a scaffold-free cellular construct applicable to endovascular treatment. HMSC fibers were fabricated using a cell self-aggregation technique and optimized by controlling the cell number per unit length to preserve cellular viability and mechanical stability. The resulting fibers retained mesenchymal stromal cell characteristics and endogenous extracellular matrix, facilitating smooth handling and intraluminal delivery without structural collapse. After transcatheter administration into a swine aortic aneurysm model, HMSC fiber-induced fibroconnective tissue formation stimulated neovascularization within the aneurysm cavity. These findings demonstrate the feasibility of HMSC fiber as a controllable and stable platform for localized endovascular cell delivery. Furthermore, this study established their potential utility as a regenerative adjunct to current endovascular treatment for aortic disease.

Abstract: Introduction: Despite improved health service accessibility, neonatal mortality in Ethiopia remains high at 33 per 1,000 live births. Thus, improving health facilities’ readiness across infrastructure, basic amenities, equipment, medications, laboratory services, Kangaroo Mother Care, infection prevention and control, staffing, and guidelines availability is critical for improving the quality of neonatal care and improving survival. Objective: To evaluate the readiness of Ethiopian hospitals to provide services to small and sick newborns. Methods: A cross-sectional study including 208 hospitals across four regions in Ethiopia in 2021–2024, prior to the phased implementation of the Saving Little Lives program. Data were collected using an adapted World Health Organization’s Service Availability and Readiness Assessment tool and are presented using composite scores. Results: The mean composite readiness score for the 208 hospitals for providing services to small and sick newborns in labour and delivery wards was 59%, with domain-specific scores of 47% for basic amenities, 56% for essential neonatal care, and 74% for newborn resuscitation. Significant variation was seen across hospital levels, and basic amenities were available in 68%, 49%, and 43%, essential neonatal care in 68%, 81%, and 71%, and newborn resuscitation in 68%, 66%, and 50% of referral, general, and primary hospitals, respectively. The mean composite readiness score to provide newborn care in the neonatal care units was 57%. Scores varied by hospital levels, with scores of 73%, 64%, and 50% for referral, general, and primary hospitals, respectively. Domain-specific scores were 63% for basic amenities, 65% for equipment, 67% for medications, 63% for laboratory services, 25% for Kangaroo Mother Care, 68% for infection prevention and control, 55% for staffing, and 51% for guidelines. Functional bCPAP machines were available in 14% of labour and delivery wards and in 35% of neonatal care units. Conclusion: There is a substantial gap in readiness to provide care for small and sick newborns, and significant variations across hospital levels. Immediate actions must be taken to address the observed gaps to reach the sustainable development goal of reducing neonatal mortality to at least 12 per 1,000 live births by 2030.

Abstract: Charles Bonnet syndrome (CBS) is characterized by complex visual hallucinations in visually impaired individuals who maintain intact cognitive function. Despite significant progress in understanding this condition, the precise neural mechanisms underlying CBS remain incompletely understood. This review synthesizes current evidence regarding the pathophysiology of CBS, with particular emphasis on emerging neurobiological models that extend beyond simple cortical hyperexcitability. Recent neuroimaging, neurophysiological and computational modeling studies suggest that CBS hallucinations may arise from complex interactions between deafferentation-induced neural plasticity, neurotransmitter imbalances and altered functional connectivity within visual processing hierarchies. The evidence increasingly points toward a model involving desynchronization between bottom-up and top-down visual processing pathways, rather than mere hyperexcitability of deafferented visual cortex. This integrated perspective has important implications for both theoretical understanding of visual perception and the development of targeted therapeutic interventions.

Abstract: Asymmetry Theory (AT) is a unified mathematical framework that derives both classical and relativistic phenomena from a single empirically validated principle: light propagates at constant speed c from its emission origin. By retaining classical time and space, while introducing observer-dependent light velocity, AT bridges the conceptual divide between classical mechanics and relativistic physics, providing a common mathematical foundation that encompasses both regimes within a coherent structure.From this single principle, AT derives: (1) a light observed velocity formula explaining the Sagnac effect, GPS one-way light speed measurements, stellar aberration, and optical clock variation; (2) a unified formula encompassing both classical and relativistic Doppler effects, cosmological redshift, and Cherenkov radiation; (3) electrodynamics equations addressing particle acceleration, mass-energy equivalence, and matter waves; (4) an observer-frame formulation of Maxwell's equations that directly yields Doppler and Sagnac effects as solutions.AT reproduces all validated predictions of Special Relativity (STR) when the observer’s motion is perpendicular to the “source-observer” line, while preserving classical time synchronization and causality and naturally handling non-inertial frames.AT maintains consistency with all established empirical evidence: Michelson-Morley, optical cavity resonators, Hafele-Keating, optical clock, Ives-Stilwell spectroscopy, particle accelerators, muon decay, nuclear reactions and GPS Sagnac corrections. It also reconciles with the contested Gezari lunar ranging and Thim microwave. We demonstrate that the extensive empirical evidence traditionally cited as validating STR equally supports AT - a unified framework based on classical spacetime.To distinguish from STR, AT is empirically testable with novel predictions: (1) Sagnac phase shift Δt = 2vL/c² in inertial frame; (2) momentum asymmetry for parallel acceleration versus deceleration. A motion-controlled interferometer with first order sensitivity detecting two-way light speed deviation is proposed for the confirmative test of AT.

Abstract: Theoretical background: Occupational burnout remains a key organizational challenge, while the phenomenon of quiet quitting (QQ - conscious limitation of effort to formal requirements) gains significance in contemporary workplaces. However, existing literature lacks frameworks for distinguishing deliberate disengagement from unintentional, apathetic withdrawal. To address this gap, the concept of passive quitting (PQ - apathetic withdrawal from exhaustion and loss of meaning) is introduced and both mechanisms' unique contributions to explaining burnout are examined.Purpose of the article: To determine the impact of quiet quitting and passive quitting phenomena on occupational burnout and empirically assess their unique contributions within a single coherent latent model.Research methods: Cross-sectional CAWI study on a nationwide sample of Polish employees (N = 1040). QQ and PQ were measured using validated scales, burnout was assessed with the OLBI questionnaire. Covariance-based structural equation modeling (CB-SEM) was employed to test hypotheses assuming both phenomena as significant predictors of occupational burnout.Main findings: Passive quitting is a strong and significant predictor of occupational burnout (β = 0.475, p < 0.001), while quiet quitting shows virtually no relationship (β = 0.0012, p > 0.001). The most influential factors were items related to loss of job satisfaction and meaning (PQS6, PQS7), distinguishing apathetic withdrawal from conscious boundary-setting. PQ may serve as a practical early warning indicator, while QQ behaviors alone do not increase burnout risk when PQ is controlled for.

Abstract: Hierarchical triple systems (HTSs), composed of an inner compact binary and a distant tertiary companion, can undergo secular interactions that induce Kozai–Lidov (KL) oscillations. These oscillations can drive the inner binary to high eccentricities, substantially enhancing its gravitational wave (GW) emission. In this work, we simulate the evolution of such systems using the N-body integrator REBOUND, selecting astrophysical models from constrained parameter spaces that are likely to exhibit KL dynamics. To assess detectability, we employ tools such as EccentricFD to model GW signals from these eccentric binaries, varying mass ratios and eccentricities across detectors, including LIGO, LISA, and LGWA. Our results highlight the influence of general relativistic corrections at 1PN order on the suppression or modulation of KL cycles and suggest the existence of an additional dynamical constraint governing HTS stability. We find that GW signals from such systems are within the sensitivity range of both current and future detectors. This study underscores the role of three-body dynamics in shaping GW observables and provides a foundation for the development of waveform templates for eccentric sources.