Search Results (640)

Physicians routinely operate in environments that require the rapid processing of complex and dynamic visual information to diagnose patient conditions, communicate effectively, and make informed decisions. Despite the central role of visual attention in clinical practice, these processes are rarely conceptualized or systematically measured in medical education research. In other professional domains, such abilities are described as professional vision (PV)—the situated capacity to selectively attend to relevant cues and interpret them considering domain-specific knowledge. Although the term professional vision foregrounds visual attention, we use it here to cover the multimodal clinical perception in which visual cues are typically embedded—predominantly visual, but in many tasks also auditory and verbal—with visual attention as the analytic anchor. This paper introduces a cognitive process model of professional vision for medical education (PV-CP) that specifies the perceptual and cognitive subprocesses underlying how physicians perceive and interpret clinically relevant information. Building on this model, we propose a theory-driven framework for the measurement of professional vision using multimodal indicators. Central to our argument is the assumption that professional vision represents a latent, temporally unfolding construct that cannot be validly captured through single behavioral metrics or outcome measures. Instead, robust measurement requires the coordinated analysis of gaze-based indicators of visual attention and cognitive indicators of reasoning, each reflecting distinct subprocesses of professional vision. By systematically linking families of indicators to specific subprocesses and clarifying their respective inferential strengths and limitations, the PV-CP model advances a process-oriented approach to studying professional vision in medical education. The framework provides a conceptual basis for integrating multimodal data sources and supports more precise interpretations of gaze and reasoning data in expertise research. In doing so, the model contributes to the theoretical refinement of professional vision and offers a structured foundation for future empirical research and the design of learning environments aimed at fostering clinically relevant perceptual–cognitive skills. Full article

Plasminogen activator inhibitor-1 (PAI-1), encoded by SERPINE1, is the principal physiological inhibitor of tissue-type and urokinase-type plasminogen activators and a central regulator of fibrinolysis. Beyond its canonical hemostatic role, PAI-1 has emerged as a pleiotropic mediator of tissue remodeling, fibrosis, metabolic dysfunction, cancer progression, cellular senescence, and age-associated immune dysregulation. A central argument of this review is that PAI-1 should be understood not only as a downstream biomarker of aging-associated pathology, but also as an active effector linking senescence-associated secretory phenotype (SASP) signaling, chronic low-grade inflammation, impaired immune surveillance, fibrotic extracellular matrix remodeling, and a prothrombotic state. In this framework, PAI-1 may function as an immune-aging checkpoint: a molecular node through which senescent, stromal, malignant, and inflammatory cells reinforce immune evasion and tissue dysfunction. Structure-guided drug discovery has enabled the development of small-molecule PAI-1 inhibitors, including TM5275, TM5441, TM5509, and TM5614. Among these, TM5614 is an orally available investigational compound that has progressed to clinical evaluation. Preclinical studies support anti-thrombotic, anti-fibrotic, anti-inflammatory, anti-senescent, and tumor-microenvironment-modulating effects of PAI-1 inhibition, while early clinical studies have evaluated TM5614 in chronic myeloid leukemia, immune-checkpoint-refractory malignant melanoma, non-small-cell lung cancer, and COVID-19-associated pneumonia. This review summarizes the biology of PAI-1, expands the discussion of immunoaging, reviews representative preclinical and clinical data, compares available PAI-1 inhibitors, and discusses the translational opportunities and safety considerations for TM5614 and related compounds. Full article

In her final novel, Daniel Deronda (1876), George Eliot (1819–1880) repeatedly stages moments in which gentile characters project expectations onto Jewish women, drawing on inherited cultural representations from literature, history, and the performing arts. These moments reveal how limited their real-world knowledge of Jews—particularly Jewish women—was, and how readily they relied on cultural templates rather than lived experience. George Eliot herself, however, had undertaken extensive study of Jewish history, religion, and culture in preparation for the novel, including research into the Talmud, Mishna, kabbalah, and halacha (Jewish law). Yet this knowledge is purposefully not afforded to her characters. This article examines George Eliot’s increasing understanding of Jewish society, and her shifting attitudes towards Judaism, and explores how allusions to Jewish women in history, literature, and performance shape the gentile characters’ othering of Mirah Lapidoth, a young Jewish woman fleeing enforced familial exploitation, whom Daniel rescues from drowning in the Thames. Two significant conceptual terms underpin my argument. Objectification refers here not only to eroticisation or aestheticisation, but to the broader process by which Mirah is perceived as a symbolic figure—as an image, a type, or role—rather than a fully realised person. Othering denotes the interpretative habit by which gentile characters position Mirah through pre-existing stereotypes or literary precedents, instead of understanding her as a subject with her own history and interiority. Rescue describes the narrative mechanisms by which Mirah is brought into focus, first through Daniel’s intervention, then through her placement within the Meyrick household, and finally through marriage, though always within structures that continue to idealise, discipline, or contain her. I argue that George Eliot’s deployment of familiar stereotypes does not reinforce them; instead, she exposes them as cultural constructions that must be deconstructed or exorcised before she reconstructs her own version of Jewish culture and identity, which she referred to as “the inner life of modern Judaism” in her notebooks. I also argue that Daniel’s rescue of Mirah, rather than an act of pure benevolence, becomes a further site of objectification, othering her as an idealised model of Jewish womanhood rather than acknowledging her as an autonomous individual. Full article

Background: Hypoplastic left heart syndrome (HLHS) is defined as “a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch”. Without treatment, HLHS is usually lethal in the neonate. Many hypotheses have been advanced to explain the etiology of HLHS; however, no single theory appears to fully explain the phenotypic variability seen in HLHS. Furthermore, many of these theories offer no explanations regarding the precipitating events which lead to the development of HLHS. Objective: This review considers and critically evaluates the strengths and weaknesses of the leading theories proposed to explain the pathogenesis of HLHS—including hemodynamic disturbances, primary myocardial structural defects, valvar malformations, and genetic or epigenetic alterations that may provoke developmental and anatomic abnormalities. After presenting each model, we propose a novel, comprehensive, and data-driven framework which may assist researchers in developing models for the pathogenesis of the various subtypes of HLHS. Methods: Key findings from human fetal imaging, histopathology, genetic studies, and animal models were considered, as well as the hypothetical contribution of each in observed HLHS phenotypes. The rationales for these findings as causal factors initiating individual HLHS patterns, as well as how they might contribute to HLHS in general, were critically analyzed. Results: The flow theory is strongly supported by animal models and in utero interventions that demonstrate the impact of altered hemodynamics on cardiac morphogenesis. However, the flow theory fails to identify initial causes of disturbed flow or related histological features of HLHS like endocardial fibroelastosis. The myocardial and valve-first models suggest an important role in developmental defects, but do not necessarily have a strong experimental basis that provides explanations for how they mediate HLHS. Genetic studies in patients with HLHS have identified several candidate causal mutations. However, such genetic causes of HLHS exhibit incomplete phenotypic penetrance and clinical impact. A multifactorial framework attempts to integrate these diverse mechanisms and may provide the most coherent explanation that can accommodate the heterogeneity and variable presentation of HLHS. Such a framework may identify multiple forces that drive disease but does not provide useful pathways for future research about HLHS. Conclusions: No single hypothesis has fully explained how HLHS is initiated, progresses, and presents with the clinical conditions that are encountered by cardiac surgeons and cardiologists. The most current models suggest that the spectrum of HLHS reflects acomplex interaction between genetic susceptibility, flow-dependent cardiac remodeling, and environmental factors in utero. A multifactorial model integrates these diverse mechanisms and may provide the most coherent explanation for the various phenotypic variations in HLHS. Based on our analysis of the most current data and the strengths and weaknesses of the current theoretical frameworks, we propose a novel research strategy aimed at identifying specific cardiac progenitor cell populations whose dysregulation may represent a unifying explanation for the etiology of the various phenotypes of HLHS. Based on the arguments made throughout this manuscript that evaluate the various genetic, structural, and hemodynamic models of initiation of disease, we believe that the significant phenotypic variability across the spectrum of HLHS (i.e., the different anatomic subtypes for “classic” HLHS) most likely reflects different underlying etiologies and mechanisms. At the very least, it is very likely that the timing of the insult is critical in determining anatomic subtype. Based on the published data and the arguments within this manuscript, it seems naive to think that there is a single unifying mechanism explain all forms of HLHLS. Full article

This paper re-examines the problem of free will in light of both deterministic and indeterministic assumptions about the structure of the world. On the philosophical side, it analyzes van Inwagen’s arguments that free will is incompatible with determinism—because our actions would then be fixed by a remote past and the laws of nature—and with indeterminism, on the grounds that indeterministic outcomes reduce to mere chance. On the neuroscientific side, it revisits Libet-style experiments, often interpreted as showing that unconscious brain activity initiates voluntary actions before conscious intention, and critically reviews recent reinterpretations of the readiness potential and the limitations of such paradigms for assessing free will. The paper then diagnoses a shared structure in these challenges: they presuppose a strict dichotomy between Laplacean determinism and a thin, law-governed conception of chance that leaves no conceptual space for non-chance indeterminism or for agent-level causal contributions. A simple quantum thought experiment is used to show how microscopic indeterminism can have direct macroscopic effects, undermining the assumption that the macroworld is effectively deterministic. Finally, the implications of computational and dynamical models of cognition are considered, arguing that their built-in constraints should be read as limits of the models rather than as metaphysical results. The conclusion advocates a naturalistic agnosticism: current physics, neuroscience, and cognitive science neither establish nor refute free will, but underdetermine its status while still placing substantive constraints on any viable theory of it. Full article

We examine factors that allow higher status people to steal credit from lower status people. Drawing on opportunity hoarding research and status characteristics and expectation states theory, we develop the concept of status hoarding: the use of one’s status position to accumulate more status through illegitimate means. Compared to similar concepts such as the Matthew Effect, which do not offer a mechanism by which benefits disproportionately accumulate, status hoarding explains how group structures give rise to perceptions of competence and reward deservingness among group members, which facilitate higher status actors’ ability to steal credit and thus increase their status. We use two survey experiments to test our arguments on the role of expectations and referential structures in both assigning credit to higher status actors and inhibiting lower status actors from reporting theft of their ideas. In study one, we find that participants were more likely to assign credit for a valued task contribution to a higher status actor, and these effects were mediated by expectations for reward and competence. In study two, we find that people perceive higher status actors as more likely to report credit stealing to their supervisors, but these effects were not mediated by expectations in the way that we predicted. We conclude with a general discussion of the broader implications of status hoarding and directions for future research. Full article

This paper examines the transhumanist prospect of abolishing death and argues that technological immortality would undermine the conditions that make meaning and philosophy possible. Mortality is a biological limit but also the existential horizon against which identity, value, and narrative coherence are constituted. If death were eliminated, the structures that orient personhood, ethics, and motivation would be destabilized, along with the urgency and depth that characterize human life. The argument directly relates to current debates in AI ethics, bioethics, and technoethics, as the pursuit of digital or biotechnological immortality raises questions about personhood, embodiment, responsibility, and the moral limits of technological intervention. The central claim is that the very practice of philosophy presupposes mortality as its constitutive horizon, such that removing it would deprive philosophy of its central subject matter. The argument unfolds in three steps. First, it shows that life’s narrative coherence depends on finitude, for without an end, a life cannot take shape. Second, it claims that moral and communal values such as legacy, sacrifice, and generational concern rest on mortality. Third, it considers how the scarcity of time gives urgency to reasoning and commitment. Without temporal limits, projects can always be deferred, eroding their significance. Philosophy has long drawn its seriousness from the confrontation with death, from Platonic Socrates’ practice to modern existentialism. I conclude that transhumanist immortality would not extend philosophy but radically transform or undermine it, since the existential tension supplied by mortality has been indispensable to philosophy. Full article

This paper addresses the existence of mild solutions and the approximate controllability of a class of higher-order Hilfer fractional semi-linear neutral stochastic differential equations with non-instantaneous impulses in Hilbert spaces. The system is driven by both fractional Brownian motion and Poisson jumps, thereby capturing long-range dependence as well as random discontinuities. By combining techniques from fractional calculus, stochastic analysis, and operator theory, we establish sufficient conditions for the existence of mild solutions. The analysis is carried out through the construction of suitable solution operator families and the application of Sadovskii’s fixed point theorem in an appropriate phase space framework. In addition, we investigate the controllability properties of the system and derive criteria ensuring approximate controllability of the underlying fractional neutral dynamics. The proposed approach relies on the structural properties of the higher-order Hilfer fractional derivative, estimates for stochastic integrals with respect to fractional Brownian motion, and compactness arguments adapted to non-instantaneous impulsive effects. The inclusion of Poisson jumps and neutral terms introduces significant analytical difficulties, which are overcome using refined resolvent operator techniques and fractional power estimates. An illustrative example is presented to demonstrate the applicability of the theoretical results. The results obtained generalize and unify several recent developments in the theory of fractional stochastic systems and provide a flexible framework for analyzing controlled dynamical models with memory, randomness, and impulsive behavior. Full article

We study the center problem for polynomial maps $y=f\left(x\right)=-x-{\displaystyle \sum _{n=1}^{\infty }}{a}_n{x}^{n+1},$ arising from homogeneous algebraic curves $x+y+{\displaystyle \sum _{i=0}^n}{\alpha }_{n-i,i}{x}^{n-i}{y}^i=x+y+H_n(x,y)=0.$ While explicit conditions were previously known only for low even degrees $n=2,4,6,8,10$, their general structure remained conjectural. In this paper we resolve the case $n=12$ and prove that for all even degrees $n=2k$, the center condition is completely characterized by two families of algebraic relations: mirror symmetry conditions and alternating-sum conditions. The proof combines algebraic methods with a direct structural argument. In particular, the necessity part is established without relying on explicit formulas for focus quantities, instead, we make use of the involutive property of the associated map and analyze the symmetric difference $H_n(x,f\left(x\right))-H_n(f\left(x\right),x),$ which leads to a simple and rigorous characterization of the center condition. This provides a complete and conceptually transparent solution of the homogeneous center problem for polynomial maps. Full article

This article reexamines Liang Fa’s Riji Yanxing (Record of Words and Deeds, 1830) from the perspective of narrative structure rather than solely as a historical missionary document. Previous scholarship has shown that the diary was produced within the institutional framework of the London Missionary Society and functioned primarily as a record of early Protestant evangelization in China. Building on these studies, this article argues that the diary simultaneously records missionary work and narrates the formation of Christian faith. Through close readings of Liang Fa’s reflections, prayers, and recorded dialogues with potential converts, the study demonstrates how an institutional testimonial text develops a narrative configuration shaped by Christian theology. Within this framework, missionary responsibility, anxiety over divine judgment, and reflections on death and salvation form recurring cycles of crisis, repentance, and renewed commitment. Dialogues with potential converts further dramatize this theological logic by transforming doctrinal arguments into scenes of spiritual confrontation and hesitation. Although Riji Yanxing was not originally composed as a literary work, it reveals the emergence of a new mode of Christian narrative in Chinese writing. The diary thus illustrates how Christian concepts of sin, redemption, and judgment reshaped narrative consciousness in early nineteenth-century China. Full article

The rapid growth of prosperity-oriented Pentecostalism in the Global South has renewed debate about the relationship between religion and economic life. Revisiting Weberian concerns with the moral organization of economic conduct, this paper offers a neo-Weberian comparative interpretation of how prosperity-oriented Pentecostal practices can shape entrepreneurial orientation under conditions of institutional constraint and economic uncertainty. Focusing on Brazil and Nigeria, the research identifies four mechanisms through which these religious formations could serve as cultural accelerators of entrepreneurial activity: moral legitimation of entrepreneurial striving, disciplined self-transformation, congregational network support, and theological framing of risk and uncertainty. The argument is not monocausal but instead suggests that prosperity-oriented Pentecostalism interacts with broader structural conditions—including inequality, informality, and economic insecurity—to initiate, normalize, and sustain entrepreneurial action. By distinguishing prosperity-oriented currents from Pentecostalism as a whole, the research also emphasizes theological and organizational diversity, as well as the importance of mediating factors such as gender and national context. It concludes that the cultural accelerator is best understood as a bounded analytical framework for interpreting the religion-economy relationship rather than as a general theory of development. Full article

We construct three new families of asymmetric quantum MDS codes from nested Hermitian self-orthogonal generalized Reed–Solomon and extended generalized Reed–Solomon codes over ${\mathbb{F}}_{q^2}$. The construction is developed in three settings: affine partitions of ${\mathbb{F}}_{q^2}$, projective norm partitions of ${\mathbb{F}}_{q^2}^{*}$, and extended affine configurations obtained by adjoining the point at infinity. In each case, the Hermitian orthogonality conditions are reduced to explicit linear systems over ${\mathbb{F}}_q$, whose solvability follows from structured moment identities and Vandermonde-type arguments. This yields nested classical MDS codes satisfying the Hermitian dual-containment condition required in the Hermitian construction of asymmetric quantum codes. As a consequence, we obtain three explicit families of asymmetric quantum MDS codes with fully determined lengths, dimensions, and asymmetric distances $d_z$ and $d_x$. Our results show that affine and projective partition techniques provide a natural and effective framework for constructing optimal asymmetric quantum codes with flexible parameters. Full article

This article outlines the life of James Clerk Maxwell (1831–1879) and presents some aspects of his philosophy of science. It describes the influence of the philosopher Sir William Hamilton on Maxwell’s general thinking. It considers Maxwell’s view that the boundary conditions of science (the ultimate origin of matter, the ultimate origin of the logic of the universe, and the initial characteristics of fundamental entities) appear to point to a Creator. It sets these issues within their historical context. Full article

In contemporary scholarship, pilgrimage is increasingly analysed as a practice associated with personal transformation, spiritual reflection, and psychological well-being. Among the most popular contemporary pilgrimage routes, the Camino de Santiago attracts hundreds of thousands of participants each year, many of whom describe their journey in explicitly therapeutic terms. This article examines the Camino experience through the theological category of penance understood as a form of spiritual therapy within the Christian tradition. The main argument of the study is that the early Christian understanding of penance as spiritual medicine provides a meaningful interpretative framework for analysing the therapeutic experiences reported by contemporary pilgrims. Early Christian authors such as Hermas, Tertullian, and Cyprian described sin as a spiritual illness and penance as a process of healing and restoration. Within this perspective, practices involving physical effort, repentance, prayer, and moral transformation functioned as forms of spiritual therapy (gr. θεραπεία). The article combines theological and empirical approaches. Analyses the concept of penance as spiritual healing in early Christian sources and traces its historical connection with penitential pilgrimage. Presents qualitative research based on semi-structured interviews conducted with pilgrims on the Camino de Santiago. While the participants rarely framed their experiences explicitly in penitential terms, their testimonies reveal recurring themes of inner purification, emotional reconciliation, coping with illness or personal crisis, and the search for meaning. The findings suggest that these experiences can be meaningfully interpreted through the lens of the Christian understanding of penitential practice, particularly as a process of transformation and restoration. Rather than demonstrating a direct continuity, the study proposes an interpretative perspective that highlights structural similarities between historical theological models and contemporary experiential narratives. By integrating theological reflection with empirical data, the article contributes to debates on how historical religious concepts can illuminate contemporary experiences of healing, meaning, and well-being. Full article

This paper presents a unified analytical and computational framework for the study of typhoid fever transmission dynamics governed by a Caputo fractional-order compartmental model of order $\kappa \in (0,1]$. The population is stratified into five epidemiological classes, namely susceptible $\left(\mathcal{S}\right)$, asymptomatic $\left(\mathcal{A}\right)$, symptomatic $\left(\mathcal{I}\right)$, hospitalised $\left(\mathcal{H}\right)$, and recovered $\left(\mathcal{R}\right)$, and the governing system explicitly incorporates asymptomatic transmission, treatment dynamics, and temporary immunity with waning. The use of the Caputo fractional derivative is motivated by the well-documented existence of chronic asymptomatic Salmonella Typhi carriers, whose heavy-tailed sojourn times in the carrier state are naturally encoded by the Mittag–Leffler waiting-time distribution arising from the fractional operator. A complete qualitative analysis of the fractional system is carried out: the basic reproduction number ${\mathcal{R}}_0$ is derived via the next-generation matrix method; local and global asymptotic stability of both the disease-free equilibrium ${\mathcal{E}}_0$ (when ${\mathcal{R}}_0\le 1$) and the endemic equilibrium ${\mathcal{E}}^{*}$ (when ${\mathcal{R}}_0>1$) are established using fractional Lyapunov theory and the LaSalle invariance principle; and the normalised sensitivity indices of ${\mathcal{R}}_0$ are computed to identify transmission-amplifying and transmission-suppressing parameters. Existence, uniqueness, and Ulam–Hyers stability of solutions are established via Banach and Leray–Schauder fixed-point arguments. To complement the analytical results, a fractional physics-informed neural network ($\mathcal{PINN}$) framework is developed to simultaneously reconstruct compartmental trajectories and identify unknown biological parameters from sparse synthetic observations. $\mathcal{PINN}$ embeds the L1-Caputo discretisation directly into the training residuals and employs a four-stage Adam–L-BFGS optimisation strategy to recover five trainable parameters $\mathbf{\Theta }$ = $\{\varphi ,\mu ,\sigma ,\psi ,\beta \}$ across three fractional orders $\kappa \in \{1.0,0.95,0.9\}$. The estimated parameters show strong agreement with the true values at the classical limit $\kappa =1.0$ ($\mathrm{MAPE}=2.27\%$), with the natural mortality rate $\mu$ recovered with $\mathrm{APE}\le 0.51\%$ and the transmission rate $\beta$ with $\mathrm{APE}\le 3.63\%$ across all fractional orders, confirming the structural identifiability of the model. Pairwise correlation analysis of the learned parameters establishes the absence of equifinality, validating that $\beta$ can be reliably included in the trainable set. Noise robustness experiments under Gaussian perturbations of $1\%$, $3\%$, and $5\%$ demonstrate graceful degradation ($\mathrm{MAPE}$: $0.82\%\to 3.10\%\to 7.31\%$), confirming the reliability of the proposed framework under realistic observational conditions. Full article