Search Results (247)

Perceptual Control Theory (PCT) and the Free Energy Principle (FEP) are two foundational, principle-based frameworks originally developed to explain brain function. However, since their initial proposals, both frameworks have been generalized to account for the behavior of living systems more broadly. Despite their conceptual overlap and practical successes, a mathematical comparison of the two frameworks has yet to be undertaken. In this article, we briefly introduce and compare the philosophical foundations underlying PCT and FEP. We then introduce and compare their experimental and mathematical foundations concretely in the context of bacterial chemotaxis. With these foundations in place, we can use tools from category theory to argue that PCT can be formally understood as a subset of the FEP framework; however, it is worth noting that the mathematical machinery unique to FEP is not required to successfully model bacterial chemotaxis. Finally, we conclude with a proposal for a mathematical synthesis where each framework plays an orthogonal yet complementary role. Full article

SARS-CoV-2 variants have demonstrated distinct epidemiological patterns and clinical presentations throughout the COVID-19 pandemic. Understanding variant-specific differences at the respiratory epithelium is crucial for understanding their pathogenesis. Here, we utilized human nasal organoid air–liquid interface (HNO-ALI) cell cultures to compare the viral replication kinetics, innate immune response, and epithelial damage of six different strains of SARS-CoV-2 (B.1.2, WA, Alpha, Beta, Delta, and Omicron). All variants replicated efficiently in HNO-ALIs, but with distinct replication kinetic patterns. The Delta variant exhibited delayed replication kinetics, achieving a steady state at 6 days post-infection compared to 3 days for other variants. Cytokine analysis revealed robust pro-inflammatory and chemoattractant responses (IL-6, IL-8, IP-10, CXCL9, and CXCL11) in WA1, Alpha, Beta, and Omicron infections, while Delta significantly dampened the innate immune response, with no significant induction of IL-6, IP-10, CXCL9, or CXCL11. Immunofluorescence and H&E analysis showed that all variants caused significant ciliary damage, though WA1 and Delta demonstrated less destruction at early time points (3 days post-infection). Together, these data show that, in our HNO-ALI model, the Delta variant employs a distinct “stealth” strategy characterized by delayed replication kinetics and epithelial cell innate immune evasion when compared to other variants of SARS-CoV-2, potentially explaining a mechanism that the Delta variant can use for its enhanced transmissibility and virulence observed clinically. Our findings demonstrate that variant-specific differences at the respiratory epithelium could explain some of the distinct clinical presentations and highlight the utility of the HNO-ALI system for the rapid assessment of emerging variants. Full article

While having or raising a child with a neurodivergence can be rewarding and life-enhancing, a diagnosis may trigger stress as people adapt to and navigate a new “assumptive world”. The purpose of this paper is to draw on the Attention Deficit Hyperactivity Disorder (ADHD) literature and explore it using grief theory as a conceptual framework, so as to understand parents’ and adults’ potential reactions to a diagnosis of ADHD. A narrative review of the ADHD literature suggests that adapting to a diagnosis can be understood as a process, which can occur in decisions to seek, and in reactions to, a diagnosis. For some, diagnostic work can be abrupt and unexpected, a life-changing moment when one receives an initial diagnosis. For others, diagnostic work begins pre-diagnosis. Either way, the diagnostic process requires an adjustment. This adaptation, like grief, can be ongoing and can involve a psychosocial transition. Rather than traditional models of grief (e.g., Freud and Kübler-Ross), contemporary views of grief such as the Dual Process Model and Meaning Making enable us to understand the meaning-making that is central to diagnostics work. Pre-diagnostically, people must become aware that something is different than previous expectations, in order to seek a diagnosis. Exposure to ADHD knowledge and stigma is influential pre-diagnostically. Post-diagnostically, people encounter a range of emotions which they need to process, such as grief for the past, making decisions (e.g., treatment), worries for the future, and reconstructing identity. The neurodiversity paradigm poses opportunities and challenges for people within this meaning-making process. This paper identifies implications for practice, particularly around pre- and post-diagnostic support, and directions for future research. Full article

Tin phthalocyanine (SnPc) nanoprobes with strong reverse saturable absorption (RSA) are extremely needed for photoacoustic (PA) molecular imaging. The optical properties and dynamics of SnPc nanoprobes by pulse trains were studied. During the propagating of pulse trains in SnPc, the electronic structure of SnPc is simplified to the five-state energy model. The pulse train contains 25 subpulses with space 13 ns, and the widths of subpulses were set as $3.5$ ps, 35 ps, 350 ps, $3.5$ ns, 10 ns, 20 ns, 35 ns and 100 ns, respectively. In this work, we solved two-dimensional paraxial field coupled with rate equations employing the Crank–Nicholson numerical method. The results reveal the unique optical properties and outstanding optical limiting (OL) effects of SnPc nanoprobes, indicating huge application potential as optical limiters, sensors and switches. Full article

Background: The global rise in the aging population presents significant challenges to healthcare systems, especially with increasing rates of chronic illnesses, mental health issues, and functional decline among older adults. In response, holistic and tech-driven approaches, such as telehealth and remote virtual interactive agents (VIAs), are potential emerging solutions to support the physical, cognitive, and emotional well-being of older adults. VIAs are multimodal digital tools that provide interactive and immersive experiences to users. Despite its promise, gaps still exist in the insights that explore ways of delivering geriatric healthcare remotely. Objective: This systematic review examines the existing literature on remote virtual interventions for older adults, focusing on bibliometrics, study purposes, outcomes, and network analysis of studies extracted from major databases using selected keywords and managed using the Covidence application. Methods and Results: Following five stages, namely, problem identification, a literature search, data evaluation, data analysis, and presentation, the review found that the studies on remote VIAs for older adults (2013–2025) were mostly from a positivist perspective, multi-authored, and U.S.-led, mainly showing positive outcomes for most studies (n = 13/15) conducted in home settings with healthy older participants. The dominance of positivist, US-led studies reflect an epistemological stance that emphasizes objectivity, quantification, and generalizability. VIAs, often pre-programmed and internet-based, supported health promotion and utilized visual humanoid avatars on personal devices. Keyword and network analysis additionally revealed four themes resulting from the review: Health and Clinical, Holistic and Cognitive, Home and Caring, and Hybrid and Connection. Conclusions: The review provides innovative insights and illustrations that may serve as a foundation for future research on VIAs and remote healthcare delivery for older adults. Full article

Despite considerable effort and analysis over the last two to three decades, no integrated scenario yet exists for data quality frameworks. Currently, the choice is between several frameworks dependent upon the type and use of data. While the frameworks are appropriate to their specific purposes, they are generally prescriptive of the quality dimensions they prescribe. We reappraise the basis for measuring data quality by laying out a concept for a framework that addresses data quality from the foundational basis of the FAIR data guiding principles. We advocate for a federated data contextualisation framework able to handle the FAIR-related quality dimensions in the general data contextualisation descriptions and the remaining intrinsic data quality dimensions in associated dedicated context spaces without being overly prescriptive. A framework designed along these lines provides several advantages, not least of which is its ability to encapsulate most other data quality frameworks. Moreover, by contextualising data according to the FAIR data principles, many subjective quality measures are managed automatically and can even be quantified to a degree, whereas objective intrinsic quality measures can be handled to any level of granularity for any data type. This serves to avoid blurring quality dimensions between the data and the data application perspectives as well as to support data quality provenance by providing traceability over a chain of data processing operations. We show by example how some of these concepts can be implemented at a practical level. Full article

In this paper, we study direct and inverse problems for a spatial-fractional Black–Scholes equation with space-dependent volatility. For the direct problem, we provide CN-WSGD (Crank–Nicholson and the weighted and shifted Grünwald difference) scheme to solve the initial boundary value problem. The latter aims to recover the implied volatility via observable option prices. Using a linearization technique, we rigorously derive a mathematical formulation of the inverse problem in terms of a Fredholm integral equation of the first kind. Based on an integral equation, an efficient numerical reconstruction algorithm is proposed to recover the coefficient. Numerical results for both problems are provided to illustrate the validity and effectiveness of proposed methods. Full article

The arithmetic average of the first n primes, ${\overline{p}}_n={\displaystyle \frac{1}{n}}{\sum }_{i=1}^n{p}_i$, exhibits very many interesting and subtle properties. Since the transformation from $p_n\to {\overline{p}}_n$ is extremely easy to invert, $p_n=n{\overline{p}}_n-(n-1){\overline{p}}_{n-1}$, it is clear that these two sequences $p_n⟷{\overline{p}}_n$ must ultimately carry exactly the same information. But the averaged sequence ${\overline{p}}_n$, while very closely correlated with the primes, (${\overline{p}}_n\sim {\displaystyle \frac{1}{2}}{p}_n$), is much “smoother” and much better behaved. Using extensions of various standard results, I shall demonstrate that the prime-averaged sequence ${\overline{p}}_n$ satisfies prime-averaged analogues of the Cramer, Andrica, Legendre, Oppermann, Brocard, Fourges, Firoozbakht, Nicholson, and Farhadian conjectures. (So these prime-averaged analogues are not conjectures; they are theorems). The crucial key to enabling this pleasant behaviour is the “smoothing” process inherent in averaging. While the asymptotic behaviour of the two sequences is very closely correlated, the local fluctuations are quite different. Full article

Background/Objectives: Many Canadians experience challenges navigating the healthcare system during their cancer care. Nurse navigators are uniquely positioned to support patients with their clinical expertise in oncology and patient care, but they have not been widely implemented. This study aimed to examine the impact of nurse navigators and barriers to successful implementation of a nurse navigator program. Methods: MEDLINE, EMBASE, and Web of Science databases were searched for articles examining the role of nurse navigators in cancer care. The data was extracted on study design, patient characteristics, nurse navigators’ responsibilities, outcomes, barriers to success, and recommendations for implementing nurse navigator programs. Content analysis was used to identify common themes. Results: Of 1787 articles identified, 44 articles met the inclusion criteria and underwent data extraction. Nurse navigator responsibilities included patient education, psychosocial support, clinical assessment, care coordination, patient advocacy, and improving workflows. Most studies reported significant benefits from nurse navigator programs, including patient-centered care, satisfaction with the healthcare system, reduced patient distress, healthcare provider support, and enhanced patient monitoring. Barriers included a lack of understanding of the role, overwhelmed nurse navigators, and inefficient healthcare system workflows. Recommendations for future nurse navigator programs include providing personalized support to patients, encouraging integrated healthcare teams, and permanent funding. Conclusions: Nurse navigator programs improve cancer patients’ experiences and the efficiency of cancer care delivery. Implementation necessitates integration into the healthcare team and longitudinal financial and professional support of nurse navigators. Full article

In carbazole-substituted phthalocyanine complexes 2,3,9,10,16,17,23,24-octakis-(3,6-dibromo-9Hcarbazol) phthalocyaninato zinc(II) (Pc 2) and 2,3,9,10,16,17,23,24-Octakis-(9H-carbazol-9-yl) phthalocyaninato zinc(II) (Pc 4) and their conjugated complexes to graphene quantum dots (GQDs), we studied the nonlinear absorption and propagating of picosecond pulse trains. Each pulse train contains 25 subpulses with width 100 ps seperated by space 13 ns. During the interaction with pulse trains, the structures of Pcs can be simplified to the five-state energy model. In our calculations, the coupled rate equations and two-dimensional paraxial field were solved using the Crank–Nicholson numerical method. The effects of substituted carbazoles and conjugated GQDs were investigated. Pcs and their conjugated complexes with GQDs exhibit optical limiting (OL) properties, and GQDs could decrease the OL of Pcs. One-photon absorption cross section ${\sigma }_{S_0{S}_1}$ or ${\sigma }_{T_1{T}_2}$ is the critical factor to determine the limiting value of energy transmittance in weak- or strong-intensity regions, respectively. The two-step two-photon absorption (TPA) tunnel $(S_0\to S_1)\times (T_1\to T_2)$ is the main absorption mechanism; therefore, the effective population transfer time ${\tau }_{ST}$ from $S_0$ to $T_1$ is another critical factor that is determined by one-photon absorption cross section ${\sigma }_{S_0{S}_1}$ and intersystem crossing time ${\tau }_{isc}$. Through further exploration it is found that a high incident intensity will lead to an asymmetric shape of output intensity due to different absorption mechanisms in the front and latter subpulses of the pulse train. Full article

Natural and human-made disasters, community violence, climate change, and political instability engender mental health problems worldwide. Childhood traumas, now recognized as commonplace and global in nature, augment the urgent need for mental health interventions that are accessible and scalable. The World Health Organization has called for innovative strategies that extend beyond traditional cognitive approaches. Biologically based methods are gaining recognition for their significant role in affect regulation and wellness promotion. This paper explores the potential for interventions focusing on interoceptive awareness, or noticing sensations arising from the body, to address mental health challenges, especially relevant for populations affected by trauma. The Community Resiliency Model (CRM)^®, a low-intensity, body-based intervention that cultivates interoceptive awareness, is described and compared to other well-being interventions. Available research studies, program evaluations and anecdotal reports are presented in addition to CRM’s biological and theoretical underpinnings. The neurobiology of trauma, interoception research, and the concept of neural synchrony are briefly introduced, further explaining the likely mechanism of action and an underlying rationale for the reported improvements in well-being and resilience among individuals and communities who learn CRM body awareness techniques. Given increasing global demand and limited access to conventional mental health services, CRM and the six core skills that are taught in this model offer a promising, transferable, self-care strategy. Community dissemination has the potential to expand access in underserved populations. This review concludes by suggesting future research directions, such as the exploration of biophysical outcomes, intra- and interpersonal synchrony, and evaluation of interoceptive training for emotional regulation and populations affected by trauma or violence. Full article

Traumatic injury leads to an extension of the half-life of circulating neutrophils. However, how quickly neutrophil apoptosis is delayed post-injury is currently unknown, as are the underlying mechanisms and factors that promote this extension of lifespan. During the ultra-early (≤1 h) and acute (4–12 and 48–72 h) post-injury phases, we collected blood samples from 73 adult trauma patients. Following ex vivo culture, neutrophil apoptosis was measured, alongside caspase-3 activation and expression of the anti-apoptotic protein Mcl-1. To identify factors that may promote neutrophil survival post-trauma, neutrophils from healthy controls (HCs) were cultured with mitochondrial-derived damage-associated molecular patterns (mtDAMPs) or mitochondrial DNA (mtDNA). Accompanied by reduced mitochondrial membrane depolarisation, delayed Mcl-1 turnover, and reduced caspase-3 activation, the ex vivo lifespan of neutrophils from trauma patients was significantly enhanced in a protein synthesis-independent manner within minutes to hours after injury. Neutrophils from HCs exhibited delayed apoptosis when cultured in media supplemented with trauma patient serum, which occurred alongside stabilisation of Mcl-1. Culturing HCs neutrophils with mtDAMPs or mtDNA significantly delayed apoptosis rates, promoted stabilisation of Mcl-1, and reduced caspase-3 activation. The release of mtDAMPs from damaged tissue may drive post-trauma immune dysregulation by promoting the survival of dysfunctional neutrophils. Full article

A novel electromyography (EMG)-based wheelchair interface was developed that uses contractions from the temporalis muscle to control a wheelchair. To aid in the training process for users of this interface, a serious training game, Limbitless Journey, was developed to support patients. Amyotrophic Lateral Sclerosis (ALS) is a condition that causes progressive motor function loss, and while many people with ALS use wheelchairs as mobility devices, a traditional joystick-based wheelchair interface may become inaccessible as the condition progresses. Limbitless Journey simulates the wheelchair interface by utilizing the same temporalis muscle contractions for control of in-game movements, but in a low-stress learning environment. A usability study was conducted to evaluate the serious-game-based training platform. A major outcome of this study was qualitative data gathered through a concurrent think-aloud methodology. Three cohorts of five participants participated in the study. Audio recordings of participants using Limbitless Journey were transcribed, and a sentiment analysis was performed to evaluate user perspectives. The goal of the study was twofold: first, to perform a think-aloud usability study on the game; second, to determine whether accessible controls could be as effective as manual controls. The user comments were coded into the following categories: game environment, user interface interactions, and controller usability. The game environment category had the most positive comments, while the most negative comments were primarily related to usability challenges with the flexion-based controller. Interactions with the user interface were the main topic of feedback for improvement in future game versions. This game will be utilized in subsequent trials conducted at the facility to test its efficacy as a novel training system for the ALS population. The feedback collected will be implemented in future versions of the game to improve the training process. Full article

Fluorescent cholesterol probes are indispensable tools for studying membrane structure, dynamics, and trafficking. To better understand the structure–function relationship of fluorescent cholesteryl probes, we developed a series of five new modular naphthalimide-containing cholesteryl probes (CND15–CND19). These probes incorporate an L-lysine linker between the cholesterol moiety and the fluorophore, along with a series of distinct head groups. We conducted extensive biophysical characterizations of these probes, including the determination of their solvatochromic properties and lipid partitioning behavior using giant unilamellar vesicles. Molecular dynamics simulations were employed to identify key molecular interactions of these probes within model lipid membranes. Furthermore, live-cell imaging in 3T3 fibroblasts demonstrated the potential applications of these analogs in live-cell imaging, measuring cellular membrane dynamics and studying cholesterol-related processes. The results of this study underscore the critical role of the linker and head group in designing fluorescent cholesterol-mimicking probes. These findings provide valuable insights into optimizing probe designs for future cholesterol and membrane biology research. Full article

TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24–27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule. Full article