Search Results (233)

This review explores the hypothesis that schizophrenic symptoms may be understood not as isolated deficits, but as interconnected manifestations of a structural reorganization of consciousness. The premises of this work are grounded in a comparative matrix that suggests an underlying “consanguinity” between the philosopher’s voluntary epoché—the suspension of the natural attitude performed to study the inner workings of consciousness—and the involuntary “unworlding” passively experienced in schizophrenia. By exploring this shared ontological ground, the text suggests how specific phenomenological shifts, such as the collapse of the “vital drive,” may manifest as clinical markers; this process may eventually lead to an involuntary “transcendental reduction” where the mind’s internal machinery becomes an object of forced awareness. Building on these premises, the review tentatively outlines several key achievements. It addresses the substrate-subjectivity gap by linking biological sensory-binding failures to the onset of involuntary hyper-reflexivity. Regarding structural loss and gain of function, it suggests that the psychotic transition involves a simultaneous erosion of common-sense coherence and an intensified receptivity to unfiltered perceptual fragments, which may trigger a search for metaphysical meanings. In terms of a therapeutic synthesis, it proposes exploring the conversion of “artless decentering” into a manageable, strategic distance through mindfulness and person-centered position-taking. Finally, it discusses a potential nosographic evolution, advocating for future diagnostic classifications that prioritize the experiencing self and qualitative insights to support a more translational and empathetic approach to psychiatry. Full article

Astrocytes are now recognized as active and essential participants in neural circuit function, extending far beyond their traditional roles as passive support cells. Emerging evidence highlights their critical involvement in synaptic modulation, information processing, and complex behaviors, making them key targets for understanding cognitive dysfunction in psychiatric disorders. This narrative review synthesizes current findings from rodent models to elucidate the relationship between astrocytic networks and multidomain cognitive performance. We first outline the morphological and physiological features of astrocytes, followed by a comprehensive overview of the modern experimental toolkit, including observational markers and advanced interventional strategies. Next, we evaluate commonly used behavioral assays that capture distinct cognitive domains, ranging from basic spatial and recognition memory to higher-order executive functions, cognitive flexibility, and social cognition. By integrating recent experimental evidence, we detail the specific mechanistic pathways, such as intracellular calcium signaling, gliotransmission, and neuroinflammatory reactivity, through which astrocytes directly govern these cognitive processes. Finally, we highlight critical knowledge gaps stemming from methodological limitations, arguing for the integration of more ethologically relevant, high-throughput behavioral tasks alongside highly specific targeting tools to better capture the functional heterogeneity of astrocytes in cognitive health and disease. Full article

Background/Objectives: Accurate intraoperative tumour localisation remains challenging in minimally invasive colorectal surgery, where conventional tattooing methods suffer from marker migration, tissue diffusion, and potential allergic reactions. Radio frequency identification (RFID) technology offers a promising alternative through implantable passive transponders detectable via electromagnetic coupling, eliminating ionising radiation exposure. Methods: This preclinical feasibility study evaluated three RFID frequency bands for surgical tumour marking: 134 kHz (low frequency, LF), 13.56 MHz (high frequency, HF), and 868 MHz (ultra-high frequency, UHF). Finite element electromagnetic simulations characterised antenna field distributions, while experimental validation employed glass-encapsulated transponders in air and tissue-simulating saline (0.9% NaCl, σ ≈ 1.5 S/m). Detection ranges were measured across 28 angular configurations with expanded measurement uncertainty (k = 2) ranging from ±0.9 to ±3.2 mm. Results: Maximum detection distances in air were 25.0 ± 0.9 mm (LF), 23.0 ± 1.1 mm (HF), and 68.0 ± 2.3 mm (UHF). In saline, ranges decreased to 22.5 ± 1.0 mm, 20.7 ± 1.2 mm, and 18.0 ± 1.4 mm, respectively, demonstrating tissue attenuation of 10% at LF/HF vs. 74% at UHF. Angular characterisation revealed 64–70% range reduction at orthogonal orientation for LF/HF systems. Computational–experimental correlation yielded r² = 0.975 across 154 paired observations. Conclusions: The 13.56 MHz HF band emerges as the optimal candidate for clinical translation, offering adequate tissue penetration (20.7 mm), superior antenna miniaturisation potential (5 mm diameter), established biocompatibility pathways, and mature near-field communication ecosystem support. Future development should address angular sensitivity through multi-axis antenna configurations and validation in anatomically realistic tissue phantoms. This study establishes the electromagnetic evidence base for clinical system development; translation to clinical practice requires sequential preclinical and clinical evaluation. Full article

Wastewater surveillance emerged as a critical public health tool during the COVID-19 pandemic, enabling early detection of community-level pathogen circulation independent of clinical testing. Its ability to capture signals from both symptomatic and asymptomatic individuals highlighted the importance of optimizing sampling methodologies to improve sensitivity and reliability. A key question is whether the several-fold increase in SARS-CoV-2 detectability observed when using passive tampon swab sampling compared with paired grab samples also applies to other respiratory viruses, including influenza A (including its avian influenza H5N1 subtype), influenza B, and respiratory syncytial virus (RSV). We collected 24 h passive swab samples with same-day grab samples from Detroit sewersheds, concentrated and purified nucleic acids, and using RT-ddPCR, quantified respiratory syncytial virus, SARS-CoV-2, influenza A, influenza B, and H5N1 influenza A viruses using markers RSV, SC2, InfA, InfB, and H5, respectively. Samples testing positive for H5 (marker for H5N1 influenza A) were further analyzed by targeted PCR and amplicon sequencing. Across three sites, median 24 h swab:grab ratios of virus copies were 7.0 for RSV, 9.2 for SC2, 9.9 for InfA, and 3.6 for InfB. A 239 bp hemagglutinin sequence from a sample with a strong H5 signal (795 copies/10 mL) had 100% identity to avian influenza viruses from Canada geese. Twenty-four-hour swab sampling greatly improves viral detectability across diverse targets and enabled the first confirmed detection of H5 in Detroit wastewater. Combined with magnetic bead purification, the overall sensitivity gain over conventional PEG-NaCl-Qiagen methods is approximately 36-fold, enabling earlier warning of community pathogens than grab samples. By integrating 24 hour passive swab sampling with high-efficiency nucleic acid purification, we expand the sensitivity of wastewater surveillance to enable detection and confirmation of low-abundance pathogens like avian influenza (H5). Full article

Background: The estimation of the postmortem interval (PMI) remains a complex challenge in forensic medicine. While macroscopic, biochemical, and molecular methods are well-documented, postmortem functional approaches at the organ level are largely underexplored. This pilot study investigated the feasibility of utilizing an isolated ex vivo kidney perfusion model to assess residual postmortem renal function—specifically glomerular filtration and tubular solute handling—as a potential chronological marker for PMI. Methods: Sixteen adult New Zealand rabbits were euthanized and randomly assigned to four postmortem interval groups (1, 5, 10, and 15 h). An unoxygenated, room-temperature crystalloid perfusion system was established to mimic natural postmortem decay. Initially, 32 kidneys were perfused; two were excluded due to anuria, resulting in 30 successfully analyzed kidneys. To strictly eliminate pseudoreplication bias, bilateral functional data were mathematically aggregated at the subject level, establishing the individual rabbit (n = 16) as the statistical unit. Results: Following statistical adjustment at the subject level, none of the measured functional parameters exhibited statistically significant chronological variation across the postmortem intervals (all p > 0.05; statistical significance defined as p < 0.05). Glomerular filtration was profoundly depressed across all groups, with adjusted inulin clearance ranging between 0.0031 and 0.0086 mL/min/g (peaking nonsignificantly at 10 h). Furthermore, active tubular reabsorption was virtually nonexistent; calculated reabsorbed loads for evaluated solutes, particularly potassium and sodium, yielded predominantly negative values. This phenomenon indicates a complete absence of physiological active reabsorption, reflecting instead a massive passive leakage of intracellular electrolytes into the tubular fluid due to cellular autolysis. Conclusions: Within this specific experimental setup, the isolated kidney perfusion model failed to demonstrate reproducible, time-dependent renal function useful for PMI estimation. These findings indirectly suggest that, unlike the prolonged supravital physiological resilience observed in skeletal muscle, highly metabolically active renal tissue rapidly loses its complex functional capacity following somatic death. Future studies exploring supravital renal function should consider targeting the immediate early postmortem period (0–1 h) or integrating advanced organ preservation techniques to unmask residual cellular capabilities. Full article

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43 hemichannels), and osteocyte paracrine mediators (extracellular vesicles and senescence-associated factors), and examine how each axis modulates tumor cell dormancy, osteolysis, or osteoblastic progression. We then review translational strategies targeting osteocytes, recent preclinical and clinical insights. Emerging biomarkers (e.g., serum sclerostin, DKK1, bone turnover markers) and immune–skeletal imaging approaches are also considered. Controversies, including the paradoxical effects of sclerostin blockade and the identity of in vivo RANKL sources, are discussed. Finally, we outline key knowledge gaps and propose endpoints for future trials. In summary, an osteocyte-centric perspective reveals novel targets and strategies for managing bone metastases, guiding future translational research. Full article

Acute pulmonary embolism (PE) is increasingly managed as a dynamic risk continuum in which imaging findings guide therapeutic escalation rather than merely confirm diagnosis. The principal challenge still remains normotensive patients with intermediate–high-risk features, where early right ventricular (RV) dysfunction may precede overt hemodynamic collapse. New trends focus on a trajectory-based model by integrating clinical, laboratory, and standardized imaging parameters into severity categorization. This review critically examines how imaging-derived markers influence risk stratification, escalation timing, and endovascular decision pathways in contemporary PE management. A structured narrative review was conducted focusing on the literature published between January 2020 and January 2026. PubMed/MEDLINE, Scopus, and Web of Science were searched for studies addressing imaging-based risk assessment, catheter-based reperfusion strategies, randomized trials, prospective registries, and guideline documents. Contemporary data consistently demonstrate that catheter directed therapies (CDTs) lead to rapid improvement in RV imaging surrogates and hemodynamic parameters. However, short-term mortality differences are uncommon in predominantly normotensive cohorts. Clinically meaningful signals instead emerge in the reduction in early clinical deterioration, the need for rescue escalation, bleeding optimization, and healthcare resource utilization. Imaging, as standardized reporting of RV strain on computed tomography pulmonary angiography and echocardiography, should be further embedded into escalation algorithms. In modern PE care, imaging functions as a trigger for escalation within multidisciplinary pathways rather than as a passive prognostic marker. CDTs should be interpreted as tools for trajectory modulation in selected intermediate-risk patients rather than mortality-reduction strategies. Future research should integrate imaging phenotyping, dynamic reassessment models, and organizational variables to refine patient selection and optimize outcome-relevant endpoints. Full article

Arterial stiffness has traditionally been interpreted as a marker of vascular ageing and cumulative blood pressure exposure. Increasing evidence, however, indicates that it should be viewed as an active determinant of cardiovascular loading conditions rather than a passive epiphenomenon. By accelerating pulse wave velocity and altering the timing of wave reflection, large artery stiffening increases central systolic pressure, augments late systolic load, and facilitates the transmission of pulsatile energy to the microcirculation. These hemodynamic alterations shape ventricular remodeling, influence ventricular–vascular coupling, and contribute to organ vulnerability even when brachial blood pressure appears adequately controlled. In this review, population-based observations and mechanistic human studies are integrated to position arterial stiffness as a stage-dependent dimension of cardiovascular disease. Community data illustrate its association with different blood pressure phenotypes and early cardiac structural changes, whereas evidence from advanced heart failure settings helps contextualize arterial stiffness within states of marked autonomic activation. Taken together, this perspective suggests that arterial stiffness is not merely a marker of cumulative damage, but a mediator that contributes to disease progression across clinical stages and, in practical terms, a phenotyping dimension along the trajectory from hypertension to heart failure. Full article

Background: Older adults are particularly vulnerable to heat related illness due to impaired thermoregulatory responses. Heat acclimation (HA) strategies can mitigate the negative impacts of high environmental temperatures on physiological and perceptual responses. Whilst active HA strategies may prove problematic for older adults, passive approaches such as hot water immersion (HWI) may be more feasible. Methods: This study investigated the effects of four consecutive days of HWI on physiological and perceptual markers in individuals aged over 65 years during moderate exercise. Nine healthy, recreationally active participants (76 ± 5 years) completed two 30 min cycling bouts at 75–80% age predicted HR_max pre- and post-four days of HWI at 40 °C. Measures of average HR, gastrointestinal temperature, skin temperature, thermal sensation, thermal comfort, rate of perceived exertion, power output, and distance covered were recorded during both exercise bouts. Results: Results showed a significant increase in exercise capacity as measured by power output (p < 0.05, 7.45 W) post-intervention, despite no change in ratings of perceived exertion, and reductions in average heart rate (112 ± 3 vs. 109 ± 4 bpm). There were no alterations in gastrointestinal or skin temperature, and ratings of thermal comfort and sensation remained unchanged post-intervention. Conclusions: These preliminary findings provide important new evidence that four days of passive HWI may be a practical and effective method of inducing physiological adaptations in older individuals, which may be of use in interventions to mitigate the negative impact of high environmental temperatures in this population. Full article

Background/Objectives: Diagnosing anterior cruciate ligament (ACL) insufficiency, particularly partial tears, remains challenging with standard static imaging. This study introduces a novel conceptual approach: assessing the dynamic kinematics of the infrapatellar fat pad (IPFP) as an indirect marker of ACL deficiency. Methods: In this biomechanical proof-of-concept study, dynamic ultrasound tracked IPFP kinematics in eight cadaveric knees evaluated in intact (Control), Sham, and Torn ACL states during passive flexion. The primary endpoints were (i) the absolute anteroposterior position at 90° (y₂ − y₁) and (ii) the posterior displacement during the 60–90° flexion arc (ΔY 60–90°). Results: ACL deficiency significantly altered deep-flexion IPFP kinematics. For ΔY 60–90°, the Torn ACL group demonstrated a substantial loss of posterior excursion compared to the Control group (Mean ± SD: −0.25 ± 1.03 vs. 2.88 ± 1.29 mm; Welch’s p < 0.001; Hedges’ g = 2.54, 95% CI: 1.18 to 3.89) and the Sham group (3.46 ± 1.63 mm; p < 0.001; g = −2.57, 95% CI: −3.90 to −1.25). Consequently, for y₂ − y₁ at 90°, the Torn ACL group remained abnormally anterior versus Control (p = 0.003; g = −1.97) and Sham (p < 0.001; g = −1.82). Conclusions: ACL deficiency induces a distinct reduction in posterior IPFP displacement. While these massive effect sizes establish a strong biomechanical rationale, this study serves as a foundational proof-of-concept. Large-scale in vivo clinical trials are strictly required to validate its diagnostic utility before clinical implementation. Full article

Ammopiptanthus nanus (Fabaceae) is a Class II nationally protected endangered evergreen shrub in China and is endemic to the arid regions of Central Asia. To assess how contrasting ex situ management histories are associated with sequence-variant retention at an ecologically relevant gene, we analyzed a 594 bp coding fragment of the antifreeze protein gene (AnAFP) in one wild population and two ex situ collections maintained under active versus passive management contexts. Only two variable sites were detected across 75 individuals, both represented by single-base indels near the 5′ end of the coding region. The wild population contained both rare variants, the actively managed ex situ collection retained one of them at low frequency, and the passively maintained collection was monomorphic across the analyzed fragment. Rarefaction analysis indicated that the absence of variation in the passive collection is unlikely to be explained by sample-size disparity alone at this targeted locus. Because only one locus was analyzed, these results are interpreted as locus-specific patterns rather than evidence of genome-wide diversity change. Nevertheless, the observed pattern is consistent with reduced retention of rare sequence variants in the passive ex situ collection and with the possibility that a narrow founder base, together with the absence of subsequent genetic supplementation, contributed to this outcome. These results support the view that ex situ conservation of A. nanus may benefit from maximizing founder representation, maintaining sufficiently large managed collections, and combining neutral marker approaches with targeted monitoring of ecologically relevant loci. Targeted loci such as AnAFP should, however, be regarded as complementary indicators rather than stand-alone proxies for broader genetic diversity or adaptive potential. Full article

Oxidative stress is no longer viewed as a random imbalance between reactive oxygen species and antioxidants, but as a failure of an integrated redox network that connects metabolism, immunity, and metal homeostasis. Classical markers such as malondialdehyde and 4-hydroxynonenal define oxidative damage, yet they cannot explain how redox adaptation occurs or fails. Over the past decade, the discovery of regulated cell-death pathways (ferroptosis, cuproptosis) and emerging metabolic signals has revealed a new generation of adaptive redox mediators—including itaconate, nitro-fatty acids, reactive sulfur species and succinate—that act as electrophilic or persulfidating regulators rather than passive by-products of oxidation. This review integrates mechanistic, biochemical and clinical evidence to define how these mediators remodel the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1, nuclear factor kappa-light-chain-enhancer of activated B cells, and hypoxia-inducible factor 1-alpha axes, coordinate lipid–metal–sulfur cross-talk, and shape vulnerability or resistance to ferroptosis and cuproptosis. By combining deep molecular research with translational perspectives, we propose a unifying framework for predictive redox medicine based on composite biomarker panels and AI-assisted phenotyping. Understanding and quantifying these next-generation mediators will open new avenues for precision nutrition, drug development, and disease prevention—transforming oxidative-stress biology from a descriptive field into an actionable platform for human health. Full article

This study proposes a non-invasive, simplified muscle force estimation model (NSMFEM) designed for elderly individuals and stroke patients under slow walking conditions. The model estimates lower limb muscle forces dynamically using only kinematic parameters—with real-time muscle fiber length as the key variable—thus avoiding the limitations of traditional surface electromyography (sEMG)-based approaches such as environmental interference, signal noise, and difficulty in obtaining deep muscle sEMG. A personalized Digital Twin Musculoskeletal Model (DTMSM) was constructed by scaling a reference kinematic model and calibrating muscle origin/insertion markers based on individual anthropometry. Muscle architecture indices were derived from a multiple regression model with publicly available anatomical data. Twelve elderly subjects (eight healthy ESND and four post-stroke ESP) were evaluated at varying walking speeds. Results at slow speeds (X-slow and slow) show strong Pearson correlations between NSMFEM predictions and reference data for the majority of nine representative lower limb muscles (e.g., TFL, Iliacus, Pectineus, Tib_Ant, Soleus); passive forces of TFL, Iliacus, and Vas_Int also correlate strongly. As speed rises, correlations for some muscles (e.g., Vas_Int, Tib_Post) decline, reflecting the growing influence of segmental acceleration and muscle activation—factors omitted in the model. For stroke patient gait (ESP), Spearman analysis indicates maintained strong correlations for affected side muscles Glut_Max1, TFL, Pectineus, and Soleus, supporting the model’s utility in stroke rehabilitation assessment. Overall, NSMFEM offers a practical, sEMG free method for non-invasive dynamic muscle force estimation in slow walking elderly and post-stroke populations, aiding functional assessment and personalized rehabilitation planning. Future efforts will aim to incorporate muscle activation corrections to extend the model to faster walking speeds. Full article

Background: This study aims to systematically analyze the structural transition of AI in mental health, differentiating between passive tools and autonomous agents, and to propose a governance framework to facilitate responsible integration or mitigate integration risks. Methods: Employing a semi-systematic approach, we screened records from IEEE Xplore, PubMed, and ACM DL, ultimately analyzing 61 included studies. We track the transition from the first paradigm, AI-as-Tool (AI-T) to the second paradigm, AI-as-Agent (AI-A). Results: Early empirical evidence suggests that AI-A systems may assist in fostering preliminary working alliances and demonstrate potential for symptom reduction in controlled settings; however, their efficacy cannot currently be equated with, nor serve as a replacement for, standard low-intensity clinical care. Conclusions: To mitigate these risks, we propose the Tiered Human–AI Healing Ecosystem (THHE) for mental health. This framework utilizes dynamic autonomy modulation—automatically restricting AI agency based on real-time risk markers—to manage transitions between AI-led support and human-led care, promoting clinical safety. Full article

The Carpathian Basin is a coherent biogeographic unit whose wildlife populations and pathogen dynamics are increasingly reshaped by administratively fragmented governance, land-use change and linear infrastructure. This review synthesizes evidence that the permeability patterns governing host movement also structure the transboundary exchange of genes and infections, creating a connectivity substrate for conservation genetics and One Health risk. Focusing on wild boar (Sus scrofa), red deer (Cervus elaphus), roe deer (Capreolus capreolus), fallow deer (Dama dama) and the expanding golden jackal (Canis aureus), we integrate population genetic inferences with wildlife epidemiology to examine how highways, border fences and asymmetric management (e.g., supplemental, feeding practices, hunting pressure and surveillance regimes) can generate biological asymmetries across boundaries. We highlight African swine fever as an emblematic disturbance in wild boar populations, discuss cervid risks including tick-borne pathogens and chronic wasting disease (CWD) preparedness and evaluate zoonotic threats associated with carnivore expansion (e.g., Echinococcus spp.). We propose a Carpathian Basin-level monitoring and data-sharing architecture, coupling harmonized passive surveillance, strategic active surveillance for priority pathogens, and standardized genetic marker panels supported by interoperable metadata. A Basin-scale One Health approach is a pragmatic prerequisite for the coordinated prevention, early detection and resilient management of cross-border epizootics and zoonotic threats. Full article