Search Results (188)

This article examines a hybrid generation of cryptographic keys, whose novelty lies in the fusion of a multiscale subkey generation with prime sieve and subkeys inspired by quantum mechanics. It combines number theory with techniques emulated and inspired by quantum mechanics, also based on two demons capable of dynamically modifying the cryptographic model. The integration is structured through the JDL. In fact, a specific information fusion model is used to improve security. As a result, the resulting key depends not only on the individual components, but also on the fusion path itself, allowing for dynamic and cryptographically agile configurations that remain consistent with quantum mechanics-inspired logic. The proposed approach, called quantum and prime information fusion (QPIF), couples a simulated quantum entropy source, derived from the numerical solution of the Schrödinger equation, with a multiscale prime number sieve to construct multilevel cryptographic keys. The multiscale sieve, based on recent advances, is currently among the fastest available. Designed to be compatible with classical computing environments, the method aims to contribute to cryptography from a different perspective, particularly during the coexistence of classical and quantum computers. Among the five key generation algorithms implemented here, the ultra-optimised QRNG offers the most effective trade-off between performance and randomness. The results are validated using standard NIST statistical tests. This hybrid framework can also provide a conceptual and practical basis for future work on PQC aimed at addressing the challenges posed by the quantum computing paradigm. Full article

We propose Observer-Linked Branching (OLB), a mathematically rigorous extension of quantum theory in which an observer’s cognitive commitment actively modulates collapse dynamics at macroscopic scales. The OLB framework rests on four axioms, employing a norm-preserving nonlinear Schrödinger evolution and Lüders-type projection triggered by crossing a cognitive commitment threshold. Our expanded formalism provides five main contributions: (1) deriving Lie symmetries of the observer–environment interaction Hamiltonian; (2) embedding OLB into the Consistent Histories and path-integral formalisms; (3) multi-agent network simulations demonstrating intentional synchronisation toward shared macroscopic outcomes; (4) detailed statistical power analyses predicting measurable biases (up to ~5%) in practical experiments involving traffic delays, quantum random number generators, and financial market sentiment; and (5) examining the conceptual, ethical, and neuromorphic implications of intent-driven reality selection. Full reproducibility is ensured via the provided code notebooks and raw data tables in the appendices. While the theoretical predictions are precisely formulated, empirical validation is ongoing, and no definitive field results are claimed at this stage. OLB thus offers a rigorous, norm-preserving and falsifiable framework to empirically test whether cognitive engagement modulates macroscopic quantum outcomes in ways consistent with—but extending—standard quantum predictions. Full article

Background: Recurrent aphthous stomatitis (RAS) has been recognized as a pathology characterized by ulcerations of the oral mucosa with a wide cross-prevalence in the general population. The aim of the present investigation was to investigate a new gel formulation for the treatment of minor oral ulcers after 2 weeks of treatment. Materials and Methods: A randomized triple-blinded controlled trial was designed for the present purpose. A total of two different study groups was conceptualized: group I (placebo) and group II (active treatment). After the enrolment process, the subjects were included in a domiciliary treatment and evaluated by a blinded operator to clinical scoring and thermography assessment at the baseline, after 1 week, and 2 weeks. Results: A total of 60 patients were observed and treated in the present study. The mean age of the patients was 34.91 ± 7.27 years old for a total of 38 females and 22 males. At 1 and 2 weeks, a significant difference in clinical scoring was observed comparing group I and group II (p < 0.05). A significant reduction in pain score was detected in group II patients (p < 0.05) after the topical gel administration. Conclusions: According to the findings of this randomized trial, the gel treatment showed a significant decrease in the signs and symptoms of oral ulcerations and could be considered useful to ameliorate the clinical course of the disease. Full article

Background/Objectives: Despite 50 years of research, there is still no consensus on whether burnout and depression are distinct constructs within the domain of occupational psychopathology. The overarching aim of this study was to address the question of whether burnout and depression represent manifestations of the same phenomenon, based on data collected from a sample of police officers working in Central Europe. Methods: The participants included a representative group of Polish police officers. They were selected using a probabilistic (random) sampling method. Correlational analyses were conducted to examine the relationships between burnout (including the dimensions of exhaustion and disengagement) and depression. Results: The results indicated that although burnout and depression are closely related, they are not identical phenomena. This conclusion was further supported by the results of confirmatory factor analyses (CFAs), which demonstrated that the dimensions of disengagement and exhaustion did not overlap with the construct of depression. Conclusions: As psychiatrists have observed, individuals diagnosed with burnout often also meet criteria for mental disorders such as somatoform, affective, or anxiety disorders. As psychologists, we may continue to debate whether burnout and depression are conceptually equivalent; however, it remains equally important to provide support to police officers experiencing burnout and/or depression. Full article

Background: High-grade gliomas (HGGs), particularly glioblastoma (GBM), are associated with exceptionally high mortality and inevitable recurrence. In considering novel treatment options for these devastating diseases, immunotherapies represent promising candidates. Immunotherapies have demonstrated efficacy for several advanced tumors outside the central nervous system, highlighting a potential role for these agents in treating HGGs. However, multiple challenges to immunotherapy efficacy have tempered therapeutic benefit in practice, including local and systemic immunosuppression, intratumoral heterogeneity, and various mechanisms of intrinsic and acquired resistance. In the past 30 years, diverse immunotherapeutic subclasses have been assessed for benefit against HGGs. Methods: We performed a PubMed search for randomized clinical trials performed within the last 30 years evaluating the following immunotherapy agents for high-grade gliomas: immune checkpoint inhibitors, vaccines, oncologic viruses, cytokines, and CAR T-cells. The present review offers a critical analysis of key pre-clinical and clinical trials that have shaped the immunotherapy landscape for high-grade gliomas over the past two decades. Results/Conclusions: Across the different immunotherapeutic methods and modalities explored thus far, a recurring theme emerges: while therapeutic strategies with a compelling conceptual basis are continually under development and even demonstrate a benefit in preclinical and early-phase trials, larger and later-phase trials consistently fail to produce concordantly significant outcomes. To date, no large-scale clinical trial has demonstrated a benefit of sufficient consequence to change practice. Continued critical appraisal of the strengths and pitfalls of prior investigative work, optimization of treatment development and delivery, and innovative approaches to combination therapy design will collectively be integral to future therapeutic advancement. Full article

Despite the significant progress made in the development of epigenetic age (eAge) clocks designed to estimate the various aspects of aging, currently available models, generated using large DNA methylation microarray datasets, still cannot fully address the issues of batch effects and technical variation. This hinders the use of the publicly available eAge clocks in routine laboratory practice, and it motivates the development of cost-effective, custom epigenetic clocks that are tailored to the given biological subjects and research methods. In this study, we analyzed the local DNA methylation of mesenchymal stem cell samples during culture expansion using high-throughput targeted bisulfite sequencing (BS-seq). Using the obtained data, we trained a minimized eAge model based on a Random Forest Regression with Leave-One-Out Cross-Validation, which determines cell passage with good performance (MAE 1.094 and R² 0.897) and which is comparable to previous solutions. Using the advantage of BS-seq to analyze consecutive CpGs methylation patterns, we demonstrated that combining the analysis of average DNA methylation levels with local methylation heterogeneity scores—thereby reflecting stochastic DNA methylation dynamics—can improve the quality of the epigenetic clock models. Therefore, we propose a research strategy for creating customized epigenetic clocks using targeted BS-seq and provide a mechanistic conceptualization of how information on longitudinal changes in DNA methylation patterns can potentially be used for the assessment of specific aging aspects. Full article

Surface runoff change is significantly influenced by both human activities and climate change. Decoupling their respective contributions to runoff change represents a critical frontier in hydrological research and a pressing challenge for water resource management. This study focuses on the Dawen River Basin, a strategic area for ecological conservation and high-quality development in the lower Yellow River region. By integrating three methodological approaches—empirical models (Precipitation–Runoff Double Mass Curve), conceptual models (elasticity coefficient methods), and hydrological models (Soil and Water Assessment Tool, SWAT)—we systematically quantify the impacts of climate change and human activities on runoff change. A correlation analysis was first applied to screen independent runoff drivers and basin characteristic factors, followed by a random forest algorithm to rank their relative importance. This process informed the establishment of a comprehensive framework for runoff attribution analysis. Results demonstrate that hydrological modeling (SWAT) is the most appropriate method for the Dawen River Basin, revealing human activities as the dominant driver of runoff changes, accounting for 70% to 82%. These findings provide critical insights for guiding sustainable water resource planning and management in anthropogenically stressed basins under a changing environment. Full article

Mammalian fertilization depends on sperm successfully navigating a spatially and chemically complex microenvironment in the female reproductive tract. This process is often conceptualized as a competitive race, but is better understood as a collective random search. Sperm within an ejaculate exhibit a diverse distribution of motility patterns, with some moving in relatively straight lines and others following tightly turning trajectories. Here, we present a two-state random walk model in which sperm switch from high-persistence-length to low-persistence-length motility modes. In reproductive biology, such a switch is often recognized as “hyperactivation”. We study a circularly symmetric setup with sperm emerging at the center and searching a finite-area disk. We explore the implications of switching on search efficiency. The first proposed model describes an adaptive search strategy in which sperm achieve improved spatial coverage without cell-to-cell or environment-to-cell communication. The second model that we study adds a small amount of environment-to-cell communication. The models resemble macroscopic search-and-rescue tactics, but without organization or networked communication. Our findings provide a quantitative framework linking sperm motility patterns to efficient search strategies, offering insights into sperm physiology and the stochastic search dynamics of self-propelled particles. Full article

The global aging trend increases chronic diseases and lowers quality of life. Exercise is vital for physiological, cognitive, and mental health, countering age-related decline. Outdoor multidomain interventions enhance adherence, motivation, and resilience, supporting independence and well-being. Objectives: This paper aimed to apply an outdoor exercise protocol for middle-aged and older people and to study its preliminary effects on cognitive state, body composition, cardiovascular health, physical fitness, physiological function, physical activity, frailty, incidence of sarcopenia, and satisfaction with life. Methods: This protocol describes an eighteen-week, two-pronged, parallel, single-blind randomized controlled trial. This paper complies with the Consort and SPIRIT guidelines. A cohort comprising a minimum of fifty-two older adults from the University for Seniors program will be equally allocated to a multidomain training group (TG) and a passive control group (CG). Intervention: The TG will follow a multidomain outdoor intervention twice a week for a complete duration of 18 weeks, with recommendations for additional autonomous cardiorespiratory training. The supervised sessions will be divided into a 10-min warm-up session focusing on activation and joint mobility, followed by 40 min of resistance training, cardiorespiratory training, and balance and coordination; and it concludes with a 10-min cool-down featuring flexibility, relaxation, and playful emotional intelligence tasks. Cognitive training will be integrated across different parts of the session. Conclusions: This preliminary study aims to explore the feasibility and potential effectiveness of outdoor multidomain training in improving the health of older adults. Importantly, by including late middle-aged adults from the age of 55, this study also aims to explore the potential of preventive strategies initiated before reaching old age. This reflects a broader conceptualization of healthy aging as a lifelong process, where early interventions may help mitigate decline and extend independence into later life. The partnership between health professionals and physical activity fosters independence for older adults, addressing the increasing burden on health services. Full article

Background: Recent systematic reviews report a limited number of return-to-work (RTW) interventions for individuals touched by cancer (ITBC), with many falling short in effectiveness and lacking an integrated work-health approach. In response, iCanWork—a theoretically informed, multidisciplinary RTW intervention integrating vocational rehabilitation (VR) and occupational therapy (OT)—was conceptualized and developed to address the gap identified in recent reviews for robust, work-health-focused RTW interventions. Methods: A pilot randomized controlled trial was conducted to explore the feasibility, acceptability, and preliminary work-related outcomes of the iCanWork intervention among 23 ITBC participants randomized to either the intervention or control group. Feasibility was assessed through recruitment, retention, and engagement benchmarks; acceptability was measured using a participant satisfaction survey. Preliminary work-health-related outcomes included RTW status, work ability index (WAI) scores, and health-related quality of life (QoL) domains. Results: Feasibility benchmarks were achieved, with 92% recruitment, 83% retention, and 100% completing at least one VR session. Adherence to the session delivery benchmarks was met by 75% of participants before RTW and 41.7% after RTW. Participants rated the intervention highly for its tailored and supportive approach. Compared to the control group, the iCanWork group showed modest improvements in RTW status, WAI scores (mean change: +2.54), and QoL domains, including fatigue, social roles, and pain interference. Given the small sample size, these exploratory findings should be interpreted as preliminary signals to inform outcome selection for a future trial. Conclusions: iCanWork is a feasible and acceptable RTW intervention for ITBC with early indications of benefit. These findings inform the design and outcome selection for a future, larger trial aimed at evaluating the intervention’s potential to improve RTW outcomes for ITBC. Full article

The present Perspective analyzes the remarkable evolution of the Amyloid Cascade Hypothesis 2.0 (ACH2.0) theory of Alzheimer’s disease (AD) since its inception a few years ago, as reflected in the diminishing role of amyloid-beta (Aβ) in the disease. In the initial iteration of the ACH2.0, Aβ-protein-precursor (AβPP)-derived intraneuronal Aβ (iAβ), accumulated to neuronal integrated stress response (ISR)-eliciting levels, triggers AD. The neuronal ISR, in turn, activates the AβPP-independent production of its C99 fragment that is processed into iAβ, which drives the disease. The second iteration of the ACH2.0 stemmed from the realization that AD is, in fact, a disease of the sustained neuronal ISR. It introduced two categories of AD—conventional and unconventional—differing mainly in the manner of their causation. The former is caused by the neuronal ISR triggered by AβPP-derived iAβ, whereas in the latter, the neuronal ISR is elicited by stressors distinct from AβPP-derived iAβ and arising from brain trauma, viral and bacterial infections, and various types of inflammation. Moreover, conventional AD always contains an unconventional component, and in both forms, the disease is driven by iAβ generated independently of AβPP. In its third, the current, iteration, the ACH2.0 posits that proteolytic production of Aβ is suppressed in AD-affected neurons and that the disease is driven by C99 generated independently of AβPP. Suppression of Aβ production in AD seems an oxymoron: Aβ is equated with AD, and the later is inconceivable without the former in an ingrained Amyloid Cascade Hypothesis (ACH)-based notion. But suppression of Aβ production in AD-affected neurons is where the logic leads, and to follow it we only need to overcome the inertia of the preexisting assumptions. Moreover, not only is the generation of Aβ suppressed, so is the production of all components of the AβPP proteolytic pathway. This assertion is not a quantum leap (unless overcoming the inertia counts as such): the global cellular protein synthesis is severely suppressed under the neuronal ISR conditions, and there is no reason for constituents of the AβPP proteolytic pathway to be exempted, and they, apparently, are not, as indicated by the empirical data. In contrast, tau protein translation persists in AD-affected neurons under ISR conditions because the human tau mRNA contains an internal ribosomal entry site in its 5′UTR. In current mouse models, iAβ derived from AβPP expressed exogenously from human transgenes elicits the neuronal ISR and thus suppresses its own production. Its levels cannot principally reach AD pathology-causing levels regardless of the number of transgenes or the types of FAD mutations that they (or additional transgenes) carry. Since the AβPP-independent C99 production pathway is inoperative in mice, the current transgenic models have no potential for developing the full spectrum of AD pathology. What they display are only effects of the AβPP-derived iAβ-elicited neuronal ISR. The paper describes strategies to construct adequate transgenic AD models. It also details the utilization of human neuronal cells as the only adequate model system currently available for conventional and unconventional AD. The final alteration of the ACH2.0, introduced in the present Perspective, is that AβPP, which supports neuronal functionality and viability, is, after all, potentially produced in AD-affected neurons, albeit not conventionally but in an ISR-driven and -compatible process. Thus, the present narrative begins with the “omnipotent” Aβ capable of both triggering and driving the disease and ends up with this peptide largely dislodged from its pedestal and retaining its central role in triggering the disease in only one, although prevalent (conventional), category of AD (and driving it in none). Among interesting inferences of the present Perspective is the determination that “sporadic AD” is not sporadic at all (“non-familial” would be a much better designation). The term has fatalistic connotations, implying that the disease can strike at random. This is patently not the case: The conventional disease affects a distinct subpopulation, and the basis for unconventional AD is well understood. Another conclusion is that, unless prevented, the occurrence of conventional AD is inevitable given a sufficiently long lifespan. This Perspective also defines therapeutic directions not to be taken as well as auspicious ways forward. The former category includes ACH-based drugs (those interfering with the proteolytic production of Aβ and/or depleting extracellular Aβ). They are legitimate (albeit inefficient) preventive agents for conventional AD. There is, however, a proverbial snowball’s chance in hell of them being effective in symptomatic AD, lecanemab, donanemab, and any other “…mab” or “…stat” notwithstanding. They comprise Aβ-specific antibodies, inhibitors of beta- and gamma-secretase, and modulators of the latter. In the latter category, among ways to go are the following: (1) Depletion of iAβ, which, if sufficiently “deep”, opens up a tantalizing possibility of once-in-a-lifetime preventive transient treatment for conventional AD and aging-associated cognitive decline, AACD. (2) Composite therapy comprising the degradation of C99/iAβ and concurrent inhibition of the neuronal ISR. A single transient treatment could be sufficient to arrest the progression of conventional AD and prevent its recurrence for life. Multiple recurrent treatments would achieve the same outcome in unconventional AD. Alternatively, the sustained reduction/removal of unconventional neuronal ISR-eliciting stressors through the elimination of their source would convert unconventional AD into conventional one, preventable/treatable by a single transient administration of the composite C99/iAβ depletion/ISR suppression therapy. Efficient and suitable ISR inhibitors are available, and it is explicitly clear where to look for C99/iAβ-specific targeted degradation agents—activators of BACE1 and, especially, BACE2. Directly acting C99/iAβ-specific degradation agents such as proteolysis-targeting chimeras (PROTACs) and molecular-glue degraders (MGDs) are also viable options. (3) A circumscribed shift (either upstream or downstream) of the position of transcription start site (TSS) of the human AβPP gene, or, alternatively, a gene editing-mediated excision or replacement of a small, defined segment of its portion encoding 5′-untranslated region of AβPP mRNA; targeting AβPP RNA with anti-antisense oligonucleotides is another possibility. If properly executed, these RNA-based strategies would not interfere with the protein-coding potential of AβPP mRNA, and each would be capable of both preventing and stopping the AβPP-independent generation of C99 and thus of either preventing AD or arresting the progression of the disease in its conventional and unconventional forms. The paper is interspersed with “validation” sections: every conceptually significant notion is either validated by the existing data or an experimental procedure validating it is proposed. Full article

A novel approach to the quantum version of $\kappa$-entropy that incorporates it into the conceptual, mathematical and operational framework of quantum computation is put forward. Various alternative expressions stemming from its definition emphasizing computational and algorithmic aspects are worked out: First, for the case of canonical Gibbs states, it is shown that $\kappa$-entropy is cast in the form of an expectation value for an observable that is determined. Also, an operational method named “the two-temperatures protocol” is introduced that provides a way to obtain the $\kappa$-entropy in terms of the partition functions of two auxiliary Gibbs states with temperatures $\kappa$-shifted above, the hot-system, and $\kappa$-shifted below, the cold-system, with respect to the original system temperature. That protocol provides physical procedures for evaluating entropy for any $\kappa$. Second, two novel additional ways of expressing the $\kappa$-entropy are further introduced. One determined by a non-negativity definite quantum channel, with Kraus-like operator sum representation and its extension to a unitary dilation via a qubit ancilla. Another given as a simulation of the $\kappa$-entropy via the quantum circuit of a generalized version of the Hadamard test. Third, a simple inter-relation of the von Neumann entropy and the quantum $\kappa$-entropy is worked out and a bound of their difference is evaluated and interpreted. Also the effect on the $\kappa$-entropy of quantum noise, implemented as a random unitary quantum channel acting in the system’s density matrix, is addressed and a bound on the entropy, depending on the spectral properties of the noisy channel and the system’s density matrix, is evaluated. The results obtained amount to a quantum computational tool-box for the $\kappa$-entropy that enhances its applicability in practical problems. Full article

Uncertainty quantification in cloud models requires simultaneous characterization of fuzziness (via Entropy, En) and randomness (via Hyper-entropy, He), yet existing similarity measures often neglect the stochastic dispersion governed by He. To address this gap, we propose HECM-Plus, an algorithm integrating Expectation (Ex), En, and He to holistically model geometric and probabilistic uncertainties in cloud models. By deriving He-adjusted standard deviations through reverse cloud transformations, HECM-Plus reformulates the Hellinger distance to resolve conflicts in multi-expert evaluations where subjective ambiguity and stochastic randomness coexist. Experimental validation demonstrates three key advances: (1) Fuzziness–Randomness discrimination: HECM-Plus achieves balanced conceptual differentiation (δC₁/C₄ = 1.76, δC₂ = 1.66, δC₃ = 1.58) with linear complexity outperforming PDCM and HCCM by 10.3% and 17.2% in differentiation scores while resolving He-induced biases in HECM/ECM (C₁–C₄ similarity: 0.94 vs. 0.99) critical for stochastic dispersion modeling; (2) Robustness in time-series classification: It reduces the mean error by 6.8% (0.190 vs. 0.204, *p* < 0.05) with lower standard deviation (0.035 vs. 0.047) on UCI datasets, validating noise immunity; (3) Design evaluation application: By reclassifying controversial cases (e.g., reclassified from a “good” design (80.3/100 average) to “moderate” via cloud model using HECM-Plus), it resolves multi-expert disagreements in scoring systems. The main contribution of this work is the proposal of HECM-Plus, which resolves the limitation of HECM in neglecting He, thereby further enhancing the precision of normal cloud similarity measurements. The algorithm provides a practical tool for uncertainty-aware decision-making in multi-expert systems, particularly in multi-criteria design evaluation under conflicting standards. Future work will extend to dynamic expert weight adaptation and higher-order cloud interactions. Full article

This study analyzes human sleep disorders using non-contact approaches. The proposed approach analyzes periodic limb movement disorder (PLMD) under sleep conditions. This was conceptualized as data capture using a non-contact approach with ultrasonic sensors. The model was designed to estimate PLMD and classify it using real-time sleep data and a machine learning-based random forest classifier. Hardware schemes play a vital role in capturing sleep data in real time using ultrasonic sensors. A field-programmable gate array (FPGA)-based accelerator for a random forest classifier was designed to analyze PLMD. This is a novel approach that aids subjects in taking further medications. Verilog HDL was used for PLMD estimation using a Xilinx Vivado 2021.1 simulation and synthesis. The proposed method was validated using a Xilinx Zynq-7000 Zed board XC7Z020-CLG484. Full article

Modern organizations operate not only through formal structures but also through informal networks, which play a critical role in fostering a resilient organization. This study focused on informal advice networks within organizations as a key mechanism for strengthening contextual resilience, one of the core components of organizational resilience. By analyzing the activation of informal advice networks, this study conceptualized advice-seeking networks as a critical informal system that enhances contextual resilience and examined the individual, structural, and attitudinal factors influencing their formation. Specifically, we hypothesized that employees with higher levels of Machiavellianism are more likely to engage in advice-seeking behaviors, whereas the relationship between Machiavellianism and advice-seeking behaviors is moderated by betweenness centrality and organizational commitment, such that the positive effect of Machiavellianism on advice-seeking is weaker when betweenness centrality or organizational commitment is high. To empirically test these hypotheses, we conducted a network survey of employees at the headquarters of a life insurance company in Seoul, South Korea, and analyzed the data using an Exponential Random Graph Model (ERGM). The findings provide empirical support for all hypotheses. Based on these results, we discussed the theoretical contributions and practical implications of the study, along with its limitations. Full article