Search Results (119)

Background and Objectives: Coronavirus disease 2019 (COVID-19) is characterized by excessive inflammatory responses, including the so-called cytokine storm, which contributes substantially to morbidity and mortality in hospitalized patients. The vagus nerve, through the cholinergic anti-inflammatory pathway, represents a theoretically attractive therapeutic target for modulating systemic inflammation. Vagus nerve stimulation (VNS) has emerged as a potential adjunctive treatment for COVID-19, with several randomized controlled trials (RCTs) investigating its efficacy on inflammatory biomarkers and clinical outcomes. The quality of this evidence base has not been rigorously evaluated. This systematic review critically appraises all available RCT evidence for VNS in hospitalized COVID-19 patients. Materials and Methods: We systematically searched PubMed, Scopus, Cochrane (CENTRAL), and Web of Science from database inception to January 2026, for RCTs evaluating any form of VNS (invasive, non-invasive, cervical, or auricular) in hospitalized patients with confirmed acute COVID-19. Two reviewers independently screened titles, abstracts, and full texts according to pre-specified eligibility criteria. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, with assessments initially performed using multiple artificial intelligence tools and subsequently validated by the authors in accordance with PRISMA 2020 guidelines. Given substantial heterogeneity and high risk of bias, narrative synthesis was performed rather than meta-analysis. Also, GRADE assessment was performed. Results: From 437 records identified, six RCTs comprising 221 patients met the inclusion criteria. Five trials (83%) were rated as high risk of bias, primarily due to inadequate blinding, substantial baseline imbalances, significant missing data and extensive multiple testing without statistical correction. The single double-blind trial with a credible sham control (Rangon et al.) found null results across all outcomes, including clinical progression, ICU transfer, and mortality, while the five “high” risk-of-bias trials generally reported positive findings on various inflammatory markers and clinical outcomes. One trial (Corrêa et al.) measured heart rate variability as a direct indicator of vagal activation and found no change despite claiming anti-inflammatory effects, contradicting the proposed mechanism of action. Significant cognitive findings from an interim analysis (Uehara et al., n = 21) disappeared in the larger completed trial (Corrêa et al., n = 52), providing empirical demonstration of false positive findings in small, underpowered studies. Conclusions: Currently available evidence supporting the use of VNS for acute COVID-19 remains scarce; however, the physiological rationale remains sound, although the absence of reliable target engagement markers in the included studies limits confidence in this treatment method. Large-scale, double-blind, sham-controlled trials are required before VNS can be firmly recommended for COVID-19 management. Full article

Transcutaneous electrical nerve stimulation techniques (TENS) are rapidly gaining attention for their potential in various clinical applications. One such technique is transcutaneous auricular vagus nerve stimulation (taVNS), and it involves delivering nerve stimulation through the skin of the external ear. However, taVNS relies on electrodes that must conform to the complex anatomy of the ear while maintaining stable electrical performance. Conventional taVNS electrodes, typically rigid metal or adhesive pads, are uncomfortable, difficult to position, prone to drying, and costly to produce. Here, we present and evaluate two complementary fabrication approaches for soft dry electrodes suitable for taVNS, which are compliant with curved anatomical features and can be operated without gel. The first employs wet spinning of a conductive elastomer into fibers, while the second extends this method to create hollow cylindrical geometries. The resulting spongy polymer composite electrodes exhibit tunable geometry, high conductivity, mechanical resilience under strain and compression, and low material impedance confirmed through bench and human testing, even under dry conditions. These properties are critical for in-ear and broader transcutaneous stimulation applications, highlighting the potential of these fabrication methods for next-generation soft bioelectronic interfaces. Full article

Determining an appropriate sequence of interrelated activities is one of the keys to developing a complex product. One of the approaches used to sequence activities consists of solving the feedback length minimization problem (FLMP). Several metaheuristic algorithms for this problem have been reported in the literature. However, they suffer from high computational costs when dealing with large-scale problem instances. To address this research gap, we propose a fast hybrid heuristic for the FLMP, which integrates the simulated annealing (SA) technique with the variable neighborhood search (VNS) method. The local search component of VNS relies on a fast insertion neighborhood exploration procedure performing only $O\left(1\right)$ operations per move. Using rigorous statistical tests, we show that the SA-VNS hybrid is superior to both SA and VNS applied individually. We experimentally compare SA-VNS against the insertion-based simulated annealing (ISA) heuristic, which is the state-of-the-art algorithm for the FLMP. The results demonstrate the clear superiority of SA-VNS over ISA. The SA-VNS hybrid technique produces equally good or better results across all tested problem instances. In particular, SA-VNS is able to find better solutions than ISA on all instances of size 150 or more. Moreover, SA-VNS requires two orders of magnitude less CPU time than the ISA algorithm. Thus, SA-VNS achieves excellent performance regarding solution quality and running time. Full article

Background/Objectives: Migraine is a complex neurological headache disorder, and transcutaneous auricular vagus nerve stimulation (taVNS) can effectively relieve headache symptoms, but its mechanism of effect is still unclear. This study aimed to explore the regulatory effects of taVNS on the locus coeruleus (LC) and the norepinephrine (NE) system in migraine mice. Methods: C57/BL6 mice were randomly assigned to four experimental groups: the control group, model group, taVNS group, and sham taVNS group. A migraine model was established by administration of nitroglycerin. Headache behaviors were assessed using the orofacial stimulation test (OST) and the mouse grimace scale (MGS). Immunofluorescence staining was conducted to evaluate the expression of NE neurons in the LC, while Western blotting was used to determine the expression levels of α-2A adrenergic receptors in the spinal trigeminal nucleus caudalis (Sp5C). Additionally, fiber-optic recording was employed to monitor the real-time dynamics of NE release in Sp5C. Results: After taVNS intervention, the drinking time of OST in the model mice was significantly prolonged(p < 0.05), and facial expression scores were reduced (p < 0.05). TaVNS increased the number of NE neurons in the LC (p < 0.05), promoted the release of NE in Sp5C (p < 0.05), and upregulated the expression of α-2A adrenergic receptors in Sp5C (p < 0.05). Conclusions: The analgesic effects of taVNS are related to the activation of the LC-NE system and the inhibition of the decrease in Sp5C in migraine mice. Full article

Background: Although antivenom is the standard treatment for snakebite envenoming, its efficacy may be impacted by geographic variation in venom composition, emphasizing the need for region-specific antivenom development. Methods: We report a case of snakebite envenoming, in which the patient was bitten on the hand by a captive Malayan pit viper (Calloselasma rhodostoma) with typical clinical manifestations following. Antivenom (produced in Thailand) was administered at 33 and 39 h post-bite. Venom from the causative individual snake was collected for compositional analysis via SDS-PAGE. Enzymatic activity of the venom was evaluated through the degradation of casein and phospholipid substrates, along with the assessment of enzymatic inhibition by two regionally specific antivenoms produced in Vietnam (AV. Cr. VN.) and Thailand (AV. Cr. TL.). Results: The patient showed good recovery, with complete normalization by day 7. SDS-PAGE profiling of the venom revealed five major enzymes, with SVSP, SVMP and PLA₂ being the most abundant (16.7%, 40.11% and 26.11%, respectively). Antivenom inhibition tests revealed remaining casein percentages of 67.43% (AV. Cr. VN) and 59.35% (AV. Cr. TL). Blood agar assays indicated that phospholipase activity was reduced to 21.01% by AV. Cr. VN. and 23.30% by AV. Cr. TL. Conclusions: Our results show that the Vietnamese antivenom generated greater inhibitory activity against proteinases compared to the Thai product, underscoring the importance of using regionally specific antivenoms that are more effective against the venom profiles of locality-matched snake populations. Full article

Background/Objectives: Tinnitus lateralization, a perceptual characteristic often neglected in clinical assessment, may reflect underlying auditory plasticity. This study aimed to investigate whether changes in tinnitus lateralization following a multimodal neuromodulation protocol are associated with improved clinical outcomes, particularly regarding tinnitus severity and discomfort. Methods: A retrospective interventional study was conducted with 104 adults diagnosed with chronic tinnitus. All participants underwent a combined protocol involving transcutaneous auricular vagus nerve stimulation (taVNS), cervical transcutaneous electrical nerve stimulation (TENS), and photobiomodulation (PBM) targeting auditory pathways. Clinical assessments included the Tinnitus Handicap Inventory (THI), Visual Analog Scales (VAS) for loudness and discomfort, and lateralization reports before and after treatment. Lateralization patterns were categorized and compared using ANOVA and Kruskal–Wallis tests. Linear models explored demographic and clinical predictors of symptom change. Results: Substantial changes in lateralization were observed post-treatment. Participants who shifted from bilateral to unilateral tinnitus or from unilateral to non-perception showed the greatest symptom reductions (p < 0.001). The Bilateral → Unilateral group presented the most marked THI reduction (−20.82 ± 7.12), while minimal changes were observed in the Bilateral → Bilateral group. Loudness and discomfort improvements followed similar trends. No significant influence of age or sex on clinical response was identified, whereas longer tinnitus duration showed a modest positive association with symptom improvement. Conclusions: Perceptual reorganization of tinnitus lateralization may serve as a clinical marker of response to neuromodulation. Tracking lateralization could provide a simple, cost-effective adjunct to outcome monitoring in tinnitus management. Full article

The flexible job shop scheduling problem (FJSP) becomes significantly more complex when real-world factors such as due dates, sequence-dependent setup times, and processing times are considered as multiple criteria. This study presents a hybrid scheduling approach that combines a genetic algorithm (GA) and variable neighborhood search (VNS), where several dispatching rules are used to create the initial population and improve exploration. The multiple objectives are to minimize makespan, total tardiness, and total setup time while improving overall production efficiency. To test the proposed approach, standard FJSP datasets were extended with due dates and setup times for two different environments. Due dates were generated using the Total Work Content (TWK) method. This study also introduces a dynamic scheduling framework that addresses dynamic events such as machine breakdowns and new job arrivals. A rescheduling strategy was developed to maintain optimal solutions in dynamic situations. Experimental results show that the proposed hybrid framework consistently performs better than other methods in static scheduling and maintains high performance under dynamic conditions. The proposed method achieved 6.5% and 2.59% improvement over the baseline GA in two different environments. The results confirm that the proposed strategies effectively address complex, multi-constraint scheduling problems relevant to Industry 4.0 and smart manufacturing environments. Full article

Aim: To investigate the vestibulosympathetic reflex (VSR) in humans by comparing the hemodynamic responses to air-conducted sound stimulus (ACSS) of the vestibular system between healthy individuals and participants with vestibular neuritis (VN). Methods: Twenty-one healthy controls and seven participants with VN were enrolled. Each autonomic test was first conducted without and then with ACSS of the vestibular system. The following autonomic tests were performed: heart rate response to Valsalva maneuver; heart rate response to deep breathing; and heart rate and blood pressure response to a supine position, passive tilt, and active standing. Results: In healthy participants, there was a difference between respiratory sinus arrhythmia values without and with otolithic stimulation (26.63 ± 6.16 vs. 24.67 ± 7.34, p = 0.02). During passive tilt, the average heart rate throughout ACSS was lower than immediately before ACSS (88.63 ± 14.68 vs. 90.96 ± 14.93, p = 0.001). In participants with VN, no such differences were observed. Conclusions: This study demonstrated a significant effect of otolithic stimulation with ACSS on heart rate during passive tilt in healthy participants. These findings suggest that ACSS of the vestibular system could be a valuable method for future research on the VSR. Full article

The Fraser Valley of British Columbia, Canada is among the top ten blueberry producing regions globally. Viral diseases are established in the region and significantly reduce average yields. While testing for two viruses is routine, characterization of all the viruses present in the region is incomplete. We used high-throughput sequencing to obtain an unbiased overview of RNA viruses present in 97 plants collected across the region. In addition to known viruses, we identified four luteoviruses previously unidentified in the region. Two of them matched the blueberry virus L (BlVL) and blueberry virus M (BlVM). recently found in the USA, while the third constitutes a new major variant of BlVM (BlVM-2), and the fourth a new luteovirus, which we named blueberry virus N (BlVN). The genome sequences were ~5 kbp long and contained four open-reading frames similar to other luteoviruses. PCR screening revealed that these luteoviruses are widespread in the region, and that plants typically harbour more than one of these luteoviruses. While luteoviruses are typically vectored by aphids, they were also present in nursery stock, indicating that spread also occurs via vegetative propagation. Full article

Kapton and Mylar film materials are used to manufacture space inflatable antenna reflectors; therefore, their mechanical characteristics are considered important parameters for the design of inflatable antenna reflectors. This paper mainly introduces a series of experiments on the mechanical properties of Kapton VN and Kapton HN, and Mylar I and II film specimens, including film tensile tests, film seam tests with tape bonding and glue bonding, and skirt edge joint tests. Therefore, failure modes, stress versus strain curves, ultimate tensile strength, and extension at break are obtained for these specimens of Kapton VN and Kapton HN and Mylar I and II films. Based on these measured data, stress conditions of models with 12 and 18 sections using ANASYS are compared to identify the effect of different sections and pressures on the force of inflatable antenna reflectors. Full article

Vanadium nitride (VN) ceramic layers were deposited on 304L stainless steel specimens by direct current (DC) magnetron sputtering in an Ar/N₂ gas mixture at substrate temperatures of 250 °C, 300 °C, and 350 °C. The obtained films were evaluated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). The results showed the existence of VN and V₂N phases in the as-deposited coatings. It was found that the surface roughness parameter (Ra = 10 nm) decreased with increasing substrate temperatures up to 350 °C. The highest hardness (10.6 GPa) was achieved in the layer produced at 300 °C. The low values of plastic and elastic deformation, as well as a low friction coefficient (0.38), led to an enhancement in the coatings’ tribological properties. The film’s thickness increased with increasing temperature due to the presence of nucleation centers in the films. The highest thickness (557 nm) was achieved in the layer deposited at 350 °C. The electrochemical tests exhibited reliable protection against corrosion in strongly aggressive electrolytes. It has been proven that the temperature significantly affects the ceramic coatings’ structural, morphological, tribological, and corrosion properties. Full article

This study tackles scheduling challenges in multi-product assembly within distributed manufacturing, where components are produced simultaneously at dedicated factories (single capacity per site) and assembled centrally upon completion. To minimize makespan and maximum tardiness, we design a symmetry-exploiting enhanced Non-dominated Sorting Genetic Algorithm II (NSGA-II) integrated with Q-learning. Our approach systematically explores the solution space using dual symmetric variable neighborhood search (VNS) strategies and two novel crossover operators that enhance solution-space symmetry and genetic diversity. An ε-greedy policy leveraging maximum Q-values guides the symmetry-aware search toward optimality while enabling strategic exploration. We validate an MILP model (Gurobi-implemented) and present our symmetry-refined algorithm against six heuristics. Multi-scale experiments confirm superiority, with Friedman tests demonstrating statistically significant gains over benchmarks, providing actionable insights for efficient distributed manufacturing scheduling. Full article

Antibody titer testing can be useful in controlling successful puppy immunization and can reduce unnecessary vaccinations in adult dogs. We evaluated three commercially available point-of-care tests (POCTs) for detecting antibodies against canine parvovirus (CPV-2), canine distemper virus (CDV) and canine adenovirus (CAV-1 and/or -2), comparing them to the reference virus neutralization (VN) assay. Sera from 200 client-owned dogs (13 healthy, 63 chronically diseased, 124 acute) and 60 specific pathogen-free (SPF) dogs, including 20 sera with maternally derived antibodies (MDA), were tested. All three POCTs demonstrated high sensitivity (79.0–100%) and specificity (97.8–100%) for CPV-2. In contrast, specificity for CDV and CAV was lower with POCT-1 (43.5% and 55.3%) and POCT-2 (42.4% and 79.2%), despite high sensitivity (CDV in both POCTs 98.7%; CAV POCT-1: 99.4%, POCT-2: 90.8%). POCT-3, by comparison, showed high specificity (CDV: 94.1%; CAV: 84.4%) but very low sensitivity (CDV: 17.4%; CAV: 33.1%). Only POCT-1 for CPV-2 detected MDA reliably, whereas the other two POCTs, and POCT-1 for CDV and CAV, did not. When compared to VN, the agreement in vaccination recommendations was 82% for POCT-1 and POCT-2, and 62% for POCT-3. In conclusion, all three POCTs reliably detected antibodies against CPV-2, including MDA with POCT-1. However, the lower specificity for CDV and CAV antibody detection in POCT-1 and POCT-2 raises concerns about misclassifying unprotected dogs as immune, while false-negatives with POCT-3 could lead to unnecessary vaccinations. Further optimization of all three POCTs for CDV and CAV is recommended. Full article

The Volumetric Neutron Source (VNS) is a pivotal facility proposed for advancing fusion nuclear technology, particularly for the qualification of breeding blanket systems, a key component of DEMO and future fusion reactors. This study focuses on the design and optimisation of the VNS Thermal Shield, adopting a multidisciplinary approach to address its thermal and structural behaviours. The Thermal Shield plays a crucial role in protecting superconducting magnets and other cryogenic components by limiting heat transfer from higher-temperature regions of the tokamak to the cryostat, which operates at temperatures between 4 K and 20 K. To ensure both thermal insulation and structural integrity, multiple design iterations were conducted. These iterations aimed to reduce electromagnetic (EM) forces induced during magnet charge and discharge cycles by introducing strategic cuts and reinforcements in the shield design. The optimisation process included the evaluation of various aluminium alloys and composite materials to achieve a balance between rigidity and weight while maintaining structural integrity under EM and mechanical loads. Additionally, an integrated thermal study was performed to ensure effective temperature management, maintaining the shield at an operational temperature of around 80 K. Cooling channels were incorporated to homogenise temperature distribution, improving thermal stability and reducing thermal gradients. This comprehensive approach demonstrates the viability of advanced material solutions and design strategies for thermal and structural optimisation. The findings reinforce the importance of the VNS as a dedicated platform for testing and validating critical fusion technologies under operationally relevant conditions. Full article

Introduction: Masseter vestibular evoked myogenic potentials (M-VEMPs) are a recent tool for assessing a vestibulo-trigeminal pathway departing from the saccule, similarly to cervical VEMPs (C-VEMPs), that evaluate saccular function via the sternocleidomastoid muscle. M-VEMPs may offer a complementary diagnostic value in vestibular neuritis (VN). Methods: This retrospective study analysed M-VEMPs and C-VEMPs in 28 monolateral patients and 1 bilateral (30 ears) diagnosed with VN between 2023 and 2024. Diagnostic evaluation included video head impulse tests (VHIT), caloric tests, ocular VEMPs, and, in a few cases, electromyography (EMG) of the sternocleidomastoid muscle. M-VEMPs were elicited using 500 Hz tone bursts at 97 dB nHL. Results were compared based on the topography of vestibular involvement and muscle response concordance. Results: M-VEMPs were always present in patients with superior VN and intact saccular function, showing consistent results with normal C-VEMPs. In some cases, with saccular dysfunction, M-VEMPs were preserved despite the absence of C-VEMPs, suggesting greater robustness. One patient with herpes zoster (HZ) involving both the VIII and trigeminal nerves showed absent M-VEMPs, indicating trigeminal pathway involvement. Edentulous patients showed reduced or absent M-VEMPs due to compromised masseter muscle electromyography activity. Conclusions: M-VEMPs are reliable and often concordant with C-VEMPs in VN but may reveal additional diagnostic information in discordant or complex cases. They are particularly useful in identifying trigeminal involvement but are limited in patients with poor masseter muscle function. Further studies are needed to clarify their full diagnostic potential. Full article