Search Results (5,225)

Heart rate variability (HRV) is an established biomarker of autonomic nervous system activity, yet its profile in miniature cattle remains poorly understood despite their growing importance in sustainable farming. This study compared HRV parameters between miniature and Holstein cows and assessed the influence of age on these profiles. Eighty clinically healthy female cattle (40 miniature, 40 Holstein), aged 2 to 8 years, were evaluated under field conditions using a Polar H10 heart rate monitor. RR intervals were analyzed using Kubios HRV software to obtain time- and frequency-domain indices. Miniature cows exhibited significantly lower heart rates and higher time-domain measures (RMSSD and SDNN) compared to Holsteins, while frequency-domain analysis revealed significant differences in LF, HF, and LF/HF ratio, suggesting group-associated differences in proportional autonomic balance. Age-stratified analysis revealed that these physiological distinctions were more pronounced in older cows (6–8 years). However, given the observational cross-sectional design of this study, confounding factors—specifically the different farm environments, management systems, and the active lactation status of the Holstein group—preclude attributing these differences solely to breed or body size. Therefore, these results suggest an associative physiological pattern rather than a definitive autonomic adaptation. Despite these limitations, portable HRV monitoring proved feasible under farm conditions, providing valuable preliminary baseline data that can inform future controlled studies on bovine cardiovascular welfare. Full article

Background/Objectives: Although vascular mechanisms are increasingly implicated in the etiology of sudden sensorineural hearing loss (SSNHL), the inability to directly visualize the labyrinthine artery remains a diagnostic obstacle. Sharing embryological and physiological parallels with the inner ear, the eye represents an accessible surrogate organ capable of reflecting systemic microvascular status. This study aimed to evaluate the diagnostic value of ocular hemodynamic and structural parameters in patients with acute unilateral idiopathic SSNHL. Methods: This prospective, comparative, cross-sectional study enrolled 30 patients with acute unilateral idiopathic SSNHL and 25 age and sex matched healthy controls. Three groups were defined: the affected eye, the contralateral eye, and the control eye. Retrobulbar hemodynamics (PSV, EDV, RI, PI) were assessed by color Doppler imaging; peripapillary choroidal thickness, RNFL, GCC+, and macular thickness by swept-source OCT; and macular microvascular perfusion by OCT angiography. Results: End diastolic velocity in the posterior ciliary arteries was significantly reduced in both patient eye groups relative to controls (p < 0.001), while RI and PI were significantly elevated (p = 0.001 and p = 0.004, respectively). Comparable hemodynamic impairment was observed in the ophthalmic artery. Peripapillary choroidal thickness was bilaterally reduced in the inferior and temporal quadrants in both patient groups (p = 0.003 and p = 0.010). No significant difference was detected between affected and contralateral eyes in any parameter. RNFL, GC+, and macular thickness remained comparable across all groups. Conclusions: The bilateral symmetry of hemodynamic impairment and choroidal thinning suggests that SSNHL arises against a background of systemic microvascular disease. The combined use of OCT and color Doppler ultrasonography holds clinical potential as a non-invasive biomarker panel for defining the vascular phenotype of the condition. Full article

Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article

Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial hemodynamics and may provide additional information for perioperative risk assessment. In this prospective single-center observational study, 108 patients aged >70 years scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Patients who had pre-existing neurological disease, had a pathological carotid Doppler ultrasound, underwent emergency surgery, or were unable to undergo delirium screening were excluded. Preoperative bilateral TCD of the middle cerebral arteries was performed using an automated WAKIe R3 system. POD was assessed on postoperative days 1–3 using the CAM-ICU. The primary endpoint was the occurrence of POD. Twenty-one patients were excluded, leaving 87 patients for analysis. POD occurred in 14 patients (16%). All patients who developed POD had pathological preoperative TCD findings, whereas no POD occurred among patients with normal TCD examinations. Overall, 82 patients (94%) demonstrated pathological intracranial hemodynamic findings despite normal carotid Doppler ultrasound. In multivariable Firth logistic regression adjusted for age and sex, pathological TCD findings remained associated with POD; however, interpretation was limited by the small number of outcome events and quasi-complete separation. In elderly patients undergoing cardiac surgery with cardiopulmonary bypass, pathological preoperative TCD findings were frequently observed and may be associated with an increased risk of postoperative delirium. The marked discrepancy between normal carotid ultrasound and abnormal intracranial hemodynamics suggests that TCD may provide complementary information regarding cerebrovascular function. Given the limited sample size and event rate, these findings should be considered exploratory and require confirmation in larger multicenter studies. Full article

Intestinal fungal overgrowth (IFO) is an increasingly recognized yet underexplored component of gut dysbiosis with potential implications for gastrointestinal and systemic disease. While bacterial microbiota have historically garnered research attention, recent advances in sequencing technologies have highlighted the importance of the gut mycobiome in maintaining intestinal homeostasis. Disruption of fungal–bacterial balance, particularly involving Candida albicans, C. tropicalis, and C. glabrata, may contribute to symptom generation through immune activation, epithelial barrier dysfunction, biofilm formation, and the production of toxic metabolites such as acetaldehyde and candidalysin. Emerging clinical evidence suggests that IFO is associated with persistent gastrointestinal symptoms, including bloating, abdominal discomfort, and altered bowel habits, particularly in patients who do not respond to conventional therapies targeting bacterial overgrowth. Furthermore, fungal dysbiosis involving Malassezia restricta and Saccharomyces cerevisiae has been associated with inflammatory bowel disease, metabolic disorders, and systemic immune dysregulation; however, the nature and directionality of these relationships remain incompletely understood. Despite increasing recognition, the diagnosis of IFO remains challenging due to a lack of standardized criteria and validated non-invasive tools. Therapeutic strategies, including antifungal agents such as fluconazole and nystatin, as well as microbiome-targeted interventions, show promise but require further validation. This review provides a comprehensive synthesis of current evidence regarding the epidemiology, pathophysiology, clinical manifestations, diagnostic challenges, and therapeutic implications of IFO, with particular emphasis on species-specific mechanisms. Recognition of the intestinal mycobiome as a potentially important component of gut health may provide new perspectives for understanding gastrointestinal disorders and inform future precision medicine approaches. Full article

Background: Cancer pain affects approximately 44.5% of all patients with malignancy and up to 55–65% of those with advanced or metastatic disease; a substantial proportion remain inadequately controlled with conventional pharmacological approaches alone. Peripheral nerve stimulation (PNS), a minimally invasive neuromodulatory strategy, has emerged as a potential opioid-sparing analgesic option for the perioperative management of oncologic surgical patients. Objectives: This narrative review synthesizes current evidence on the application, mechanisms, clinical efficacy, safety, and integration of temporary and permanent PNS systems in cancer patients, with specific focus on cancer-specific pain syndromes, key clinical studies, opioid-sparing immunological implications, evidence quality, and directions for future research. Methods: As a narrative review, this work was structured in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) to ensure methodological transparency. A focused, non-systematic literature search of PubMed/MEDLINE, Embase, and the Cochrane Library was performed from database inception through March 2026, supplemented by hand-searching of reference lists and targeted retrieval of clinical practice guidelines. Sources were selected on the basis of relevance to PNS or closely analogous peripheral neurostimulation modalities in oncologic, perioperative, or chronic pain contexts. Evidence was synthesized narratively, with each cited study graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 Levels of Evidence framework to enable transparent calibration of confidence. Results: Available preliminary and largely extrapolated evidence supports PNS as a promising but not yet established useful adjunct in oncologic perioperative care; because cancer-specific data rest substantially on a single pilot study (n = 12), one retrospective review (n = 15), and extrapolation from non-cancer populations, these conclusions should be regarded as hypothesis-generating. Randomized controlled trial data from non-cancer cohorts demonstrate opioid consumption reductions of approximately 80–90% in the PAINfRE trial, while the post-amputation trial demonstrated ≥50% pain-relief responder rates and reductions in pain interference, with clinically meaningful improvements in pain and function. Oncologic-specific pilot and retrospective evidence confirms feasibility and a 58–67% success rate across diverse cancer pain subtypes. Conclusions: The opioid-sparing properties of PNS carry additional biological plausibility for preserving perioperative antitumor immune function. High-quality prospective trials specifically designed for oncologic surgical populations remain needed to establish evidence-based recommendations. Full article

Arthropathies are a major global health challenge because of their high prevalence, chronic progression, and significant impact on quality of life and health systems. Therefore, prompt and accurate diagnosis is critical for slowing disease progression and improving outcomes. Traditional imaging modalities, such as ultrasound and magnetic resonance imaging, suffer from significant limitations, including operator dependence, limited accessibility, high cost, and limited reproducibility. Infrared thermography has become a promising non-invasive imaging technique for identifying thermal variations linked to inflammatory and metabolic processes. Advances in quantitative thermography, automated segmentation, and artificial intelligence have greatly enhanced its clinical applicability. This review summarizes recent advances in thermography-based biomarkers, including region-of-interest-derived metrics, asymmetry indices, hotspot burden, spatial and texture descriptors, and composite thermographic scores. It discusses the role of machine learning and deep learning in prediction, phenotyping, and multimodal integration with clinical, laboratory, and imaging data. Heterogeneity of protocols, variability in measurements, domain shift, validation design, overfitting, and reporting quality are also addressed. Overall, thermography combined with AI is highly promising as an adjunct to early diagnosis, assessment of disease activity, and follow-up in arthropathies. However, clinical application at a large scale requires strict standardization, external validation, transparent reporting, and well-elucidated, reproducible analytical processes. Full article

Accurate assessment of winding condition for power transformers is critical for ensuring the stable operation of modern power systems. Vibration signal has been regarded as an effective and promising evaluator for winding diagnosis. While on-line vibration monitoring offers the continuous, non-invasive and in-service assessment for winding condition, establishing precise correlations between the variable vibration patterns and specific winding condition remains challenging. To this end, an off-line vibration response analysis (VRA) technique was presented in the paper. Specifically, vibration frequency response (VFR) curves, indicating the winding response, were first obtained when the transformer was excited by the developed vibration response testing system, consisting of constant current variable-frequency power supply, intermediate transformer, accelerometers, data acquisition, control and analysis system. The VFR curves were then quantitatively and comprehensively described through four kinds of correlation indices. Finally, hierarchical integration strategy was proposed to aggregate those indices into quantitative criterion for condition assessment. The proposed method was validated on a real transformer under both normal and fault conditions, demonstrating superior performance. Notably, a 10% decrease in the evaluation criterion indicates an incipient winding looseness, while a reduction of 25% or more suggests severe looseness, prompting timely maintenance recommendations. Full article

Head and neck squamous cell carcinoma (HNSCC) remains one of the most aggressive and heterogeneous malignancies worldwide, characterized by high rates of locoregional recurrence, metastatic dissemination, and therapeutic resistance. Angiogenesis plays a central role in tumor progression by supporting vascular remodeling, hypoxia adaptation, invasion, immune evasion, and metastatic spread. In HNSCC, angiogenic activation is regulated through complex interactions involving hypoxia-inducible factors, vascular endothelial growth factor (VEGF) signaling, stromal remodeling, inflammatory pathways, and epigenetic mechanisms within the tumor microenvironment. Recent evidence has also highlighted the role of non-coding RNAs, particularly microRNAs, and exosome-mediated communication in modulating angiogenic and immune-related signaling pathways. Although antiangiogenic therapies, including monoclonal antibodies and tyrosine kinase inhibitors, have demonstrated biological activity in HNSCC, their clinical efficacy remains limited by tumor heterogeneity, adaptive resistance mechanisms, toxicity, and the lack of validated predictive biomarkers. Several emerging therapeutic strategies are under preclinical or early clinical investigation in HNSCC, including miRNA-based approaches, nanoparticle-assisted delivery systems, vascular normalization concepts, and combinations with immune checkpoint inhibitors; however, robust clinical evidence for most of these strategies remains limited, and their translation to routine practice requires further validation. This review provides a comprehensive overview of the molecular mechanisms regulating angiogenesis in HNSCC and critically discusses current and emerging pharmacological strategies targeting these pathways. Particular emphasis is placed on VEGF/VEGFR signaling, the integration of miRNA and exosome biology, resistance mechanisms, and translational perspectives for biomarker-guided personalized therapy. The novelty of this review lies in the systematic integration of miRNA- and exosome-mediated angiogenic regulation, therapeutic resistance pathways, and precision medicine strategies into a unified pharmacological framework, addressing gaps not fully covered by prior reviews focused primarily on VEGF-targeted agents. Full article

With increasing constraints on extensive farming—including soil degradation, salinisation and more frequent climatic anomalies—the development of ‘smart’ agriculture requires the integration of affordable, non-invasive methods for monitoring the physiological state of plants. A key indicator for assessing productivity and the early detection of stress is the rate of photosynthetic CO₂ assimilation (A); however, widely available commercial gas analysers are characterised by high cost, technical complexity and considerable weight, which limits their use in large-scale field studies. Here, a new handheld system for measuring assimilation was developed and tested, based on the accumulative principle of recording changes in CO₂ concentration using simple infrared sensors and without maintaining a constant air flow around the leaf. A comparison was carried out between a prototype of the developed system and a commercial gas analyser when measuring leaf assimilation under irrigation and simulated drought conditions. The results demonstrated the consistency of the readings from the two systems. The developed system is characterised by its compact size, low cost, and the absence of moving parts and consumables. The proposed system has the potential to be effective for large-scale screening tasks and rapid diagnosis of stress-induced changes; it represents a promising, affordable tool for addressing applied tasks in precision agriculture, environmental monitoring and physiological research. Full article

Objective: This study aims to investigate the acute effects of transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic nervous system (ANS) regulation and spasticity in children with spastic cerebral palsy (SCP). Methods: This preliminary study includes 20 children aged 2–15 years diagnosed with SCP. Participants undergo a single session of taVNS. Spasticity is assessed using the Modified Ashworth Scale, and autonomic regulation is evaluated through heart rate variability (HRV) parameters measured before and immediately after stimulation. Results: Following taVNS, spasticity scores decrease significantly (Modified Ashworth Scale: pre 2.00 ± 0.64 vs. post 1.60 ± 0.52; p = 0.004). Significant reductions are also observed in mean heart rate (pre 98.60 ± 16.32 bpm vs. post 91.25 ± 20.22 bpm; p = 0.022), LF/HF ratio (pre 2.22 ± 2.22 vs. post 1.12 ± 0.84; p = 0.006), and LF power (p = 0.009). No significant changes are detected in RMSSD, pNN50, or HF power (all p > 0.05). No adverse events are reported. Conclusions: This preliminary study suggests that a single session of taVNS may be associated with acute changes in autonomic regulation and reductions in spasticity in children with SCP. The observed shifts in HRV parameters indicate a modulation of sympathovagal balance. These findings support the feasibility of taVNS as a non-invasive neuromodulatory approach and warrant further large-scale, controlled studies with longer follow-up. Because of the small sample size, the absence of a control or sham group, and the short (1-min) HRV recording window, these results should be regarded as preliminary and hypothesis-generating, and they require confirmation in larger, randomised, sham-controlled studies. Clinical Trial Registration: This study was registered at ClinicalTrials.gov (Identifier: NCT06880887) on 10 March 2025. The study was conducted between January 2025 and March 2025; registration on 10 March 2025 therefore occurred during the enrolment and data-collection period rather than prior to it. This retrospective registration is acknowledged as a limitation. Full article

The growing need for sustainable wastewater treatment highlights the importance of low-energy solutions such as horizontal subsurface flow constructed wetlands (HSSF CWs). While effective, these systems often face clogging issues that reduce performance and lifespan. This study investigates clogging dynamics in a Water Treatment Plant (Lleida, Spain) using a multidisciplinary approach. Non-invasive geophysical methods such as Electrical Resistivity Tomography (ERT) and Induced Polarization (IP) were combined with high-resolution drone imagery to characterize surface and subsurface indicators of clogging. Drone data captured surface anomalies, while geophysical measurements revealed subsurface obstructions. The integrated analysis identifies clogged zones and shows a strong spatial correlation between surface features and geophysical anomalies. These results validate the use of drone imagery as a rapid, non-invasive diagnostic tool and demonstrate the effectiveness of combining remote sensing with geophysical techniques for wetland assessment. This approach supports improved monitoring, targeted maintenance, and optimized long-term performance of HSSF CWs. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most prevalent and biologically aggressive subtype of renal cell carcinoma, characterized by pronounced immunogenicity and extensive remodeling of the tumor microenvironment. Chronic inflammation and dysregulated cytokine signaling contribute substantially to tumor progression. Signal transducer and activator of transcription 3 (STAT3) represents a central molecular hub integrating cytokine- and hypoxia-driven pathways. This review aims to summarize current evidence on the cytokine–STAT3 signaling axis in ccRCC and to evaluate its translational relevance for biomarker development. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science databases. Experimental, translational, and clinical studies addressing cytokine signaling, STAT3 activation, tumor microenvironment interactions, and biomarker development in ccRCC were evaluated. Particular attention was given to studies analyzing cytokine profiles in tumor tissue, plasma, and urine, as well as their associations with STAT3 activation and clinicopathological parameters. Results: Accumulating evidence indicates that ccRCC exhibits a complex, compartment-specific cytokine signature involving interleukins, chemokines, and tumor necrosis factor (TNF)-related cytokines. Among these mediators, IL-6, IL-8, and selected chemokines such as CXCL10 appear particularly relevant due to their associations with tumor progression, immune modulation, and clinical outcome. Many of these mediators converge on persistent STAT3 activation, which promotes tumor cell survival, angiogenesis, immune suppression, and metastatic potential. Tissue-based analyses demonstrate correlations between altered cytokine expression and STAT3 activation, while urinary cytokine profiles reflect tumor-associated inflammatory processes in a non-invasive manner. Plasma cytokines appear to capture broader systemic inflammatory responses. Conclusions: The cytokine–STAT3 axis represents a biologically plausible signaling network associated with tumor progression and immune modulation in ccRCC. By integrating evidence from cytokine profiling in tumor tissue, plasma, and urine with current knowledge of STAT3 signaling, this review highlights the importance of compartment-specific inflammatory signatures in understanding ccRCC biology and their potential relevance for biomarker discovery. Integrative approaches combining cytokine profiling with functional assessment of STAT3 activation may improve disease characterization and support the development of diagnostic and prognostic biomarkers, although rigorous clinical validation remains necessary. Full article

Smart contact lens sensors integrate biochemical sensing elements, flexible electronics, power modules, and wireless readout components onto optically transparent contact lens platforms, enabling non-invasive and potentially continuous analysis of tear-derived biomarkers and ocular physiological signals. This review focuses on the translation pathway from contact lens materials and fabrication methods to sensing mechanisms, tear biomarker interpretation, and clinical deployment. We synthesize recent progress in substrate engineering, manufacturing processes, power delivery, and representative sensing strategies for intraocular pressure, glucose, electrolytes, pH, cortisol, cholesterol, and inflammatory cytokines. Instead of treating these systems as isolated examples, we compare optical/colorimetric, electrochemical, field-effect transistor, microfluidic, and wireless resonant approaches in terms of sensitivity, response time, power/readout requirements, and clinical relevance. Finally, we discuss persistent barriers, including biocompatibility, interface stability, tear-sample variability, calibration, sterilization, regulatory validation, data privacy, and compatibility with commercial contact lens manufacturing. Full article

Background/Objectives: Ketogenic diets induce profound metabolic reprogramming; however, their impact on systemic metabolism in patients with hepatic fibrosis remains insufficiently characterized. This study aimed to investigate serum metabolic changes induced by Very Low Energy Ketogenic Therapy (VLEKT) and to assess the influence of hepatic fibrosis development on these metabolic adaptations. Methods: Fifty serum samples from 25 obese patients were analyzed using 1D 1H CPMG NMR spectroscopy at baseline (T0) and after 8 weeks of VLEKT (T1). Patients were stratified according to the FIB-E fibrosis index into a low-risk group (LR; FIB-E < 8) and an intermediate-high-risk group (IHR; FIB-E ≥ 8) for hepatic fibrosis onset. Results: An integrated approach combining NMR-based metabolomics and pathway enrichment analysis revealed a marked metabolic shift following VLEKT, characterized by increased ketone bodies (including β-hydroxybutyric acid and acetone), together with changes in amino acids and lipid-related signals. Among these, acetone provided a robust and quantifiable NMR signal, consistent with enhanced ketogenesis. Stratified analysis indicated differential metabolic flexibility: LR patients exhibited enhanced modulation of tricarboxylic acid (TCA) cycle-related metabolites, whereas IHR patients showed persistent alterations in aromatic amino acids and lipid signals. Significant correlations between tyrosine and β-alanine with clinical biochemical markers further supported the presence of a fibrosis-dependent metabolic signature. Conclusions: These findings highlight the potential of circulating metabolites as sensitive and non-invasive indicators of hepatic vulnerability and determinants of metabolic adaptability to VLEKT. Moreover, the study underscores the value of NMR-based metabolomics as an innovative tool for improving the non-invasive assessment of metabolic and hepatic health. Full article