Search Results (148)

Botulism is a neuroparalytic disease caused by exposure to botulinum neurotoxins produced by anaerobic spore-forming bacteria of the genus Clostridium. This disease occurs in both humans and wild and domestic animals, and is currently becoming an increasingly serious problem worldwide due to high animal mortality and economic losses. The clinical signs observed during the progression of botulism are nonspecific and difficult to unequivocally associate with this disease entity. The aim of this study is to present laboratory diagnostics of suspected botulism cases reported in Poland in 2022–2024, as well as to present the challenges encountered during laboratory investigations. The material for the study consisted of samples of liver, serum, digestive tract, feed, feces, straw, and water from drinking lines, sent to the National Veterinary Research Institute (NVRI) in relation to thirteen suspected cases of botulism, predominantly reported in poultry, but also in mink and cattle farms. The samples were analyzed using a mouse bioassay and conventional culture methods, as well as real-time PCR methods aimed at detecting the ntnh and bont genes, which determine the production of botulinum neurotoxins. Of the thirteen suspected cases analyzed, ten were confirmed by the detection of botulinum toxin (BoNTs) and/or the presence of the ntnh and bont genes in the tested material. Based on the results obtained, it was concluded that botulinum toxin type C was the etiological factor of botulism poisoning in most of the analyzed cases. In one case reported in cattle, poisoning occurred as a result of the mosaic variant of BoNT D/C. Due to the nonspecific signs of botulism and the time required for them to appear, laboratory diagnostics play a key role in detecting the disease. However, this process is complicated due to the high heterogeneity observed among Clostridium spp. strains, as well as difficulties encountered during the isolation of the microorganism and the possibility of loss of toxin-producing capacity at later stages of analysis. Full article

Background/Objectives: Mucuna pruriens (Linn.) DC. var. pruriens is a leguminous plant whose seeds have been used in traditional medicine, including for the enhancement of sexual function. However, scientific evidence regarding its toxicological safety remains limited. Accordingly, the present study aimed to investigate the acute and chronic oral toxicity of the ethanolic seed extract of M. pruriens var. pruriens in Sprague–Dawley rats. Methods: Acute oral toxicity was assessed in female rats following a single oral administration of the ethanolic seed extract of M. pruriens var. pruriens at a dose of 5000 mg/kg body weight, with animals monitored for general behavior, clinical signs, and mortality over a 14-day period. Chronic oral toxicity was evaluated in female and male rats administered the ethanolic seed extract of M. pruriens var. pruriens at doses of 100, 500, and 2500 mg/kg body weight daily for 270 days. Animals were monitored for general behavior, clinical signs, and health status throughout the study. Hematological, blood chemistry, gross pathological, and histopathological assessments were conducted at study termination. Results: In the acute oral toxicity study, no mortality or treatment-related behavioral abnormalities or clinical signs were observed in female rats receiving the ethanolic seed extract of M. pruriens var. pruriens, and findings were comparable to those of the control group. In the chronic oral toxicity study, no mortality occurred in any treatment group. Although statistically significant increases or decreases were observed in certain body weight, organ weight, hematological, and blood biochemical parameters compared with the control group, all values remained within established reference ranges. When considered together with the absence of abnormal behavioral changes, clinical signs, and gross pathological or histopathological alterations in major organs, these findings indicate that long-term oral administration of the ethanolic seed extract of M. pruriens var. pruriens did not result in chronic toxicity. Conclusions: The ethanolic seed extract of M. pruriens var. pruriens did not produce acute or chronic oral toxicity in Sprague–Dawley rats. Nevertheless, further clinical investigations are recommended to confirm its long-term safety for human use. Full article

Reliable traffic sign detection is essential for the safety of autonomous driving systems. However, manually annotating large-scale datasets for this task is resource-intensive, making semi-supervised learning (SSL) a vital alternative. Despite their potential, current SSL methods often struggle with unreliable pseudo-label filtering and limited detection accuracy. To address these limitations, we propose a novel framework integrating a Dual Confidence Fusion (DC-Fusion) module and a Structured Block-Regularized Neck (SBR-Neck). The former improves pseudo-label reliability by combining classification and localization confidence scores, while the latter optimizes feature representation through multi-scale fusion and block-wise regularization. To preserve high-frequency spatial details, SBR-Neck incorporates Spatial-Context-Aware Upsampling (SCA-Upsampling), which utilizes multi-granularity feature decomposition. Experimental results on a proprietary traffic sign dataset demonstrate that our method achieves ${\mathrm{mAP}}_{50}$ scores of 10.4%, 17.8%, 23.7%, and 32.1% using 1%, 2%, 5%, and 10% labeled data, respectively. These results surpass the “Efficient Teacher” baseline by margins ranging from 3.07% to 11%, confirming the framework’s ability to provide robust detection in complex traffic scenarios. Full article

Squirrel-cage induction generators often perform better without a mechanical speed sensor. Eliminating an encoder or resolver removes one of the most fragile and failure-prone components, while modern control algorithms can estimate speed with sufficient accuracy. Shaft-mounted sensors are vulnerable to heat, vibration, dust, moisture, and electrical noise; they require precise mounting and additional cabling and typically fail long before the machine itself. In many industrial and marine applications, unplanned shutdowns are more often caused by damaged sensors or cables than by the generator. Unlike sensorless speed-detection methods developed for motoring operation, the proposed approach targets the generator mode, where both phase currents and the DC-link voltage are measured. It uses two indicators: the magnitude and sign of the active current, and the instantaneous rise in DC-link voltage when the converter output frequency matches the machine’s shaft speed. Because active current remains negative over a wide frequency range during start-up, its sign change alone cannot uniquely identify the synchronization point. In generator operation, however, the DC-link capacitor voltage provides an additional criterion: the speed at which power reverses sign, indicated by a change in the sign of the DC-voltage derivative. As the inverter frequency approaches the machine rotational frequency from below, the DC voltage increases, reaches a maximum at maximum slip, and then decreases once the inverter frequency exceeds the machine speed. The article demonstrates how these signals can be used in practice to identify the rotational speed of a squirrel-cage generator. Full article

Deep learning-based sign language recognition plays a pivotal role in facilitating communication for the deaf community. Current approaches, while effective, often introduce redundant information and incur excessive computational overhead through global feature interactions. To address these limitations, this paper introduces a Deformable Correlation Network (DCA) designed for efficient temporal modeling in continuous sign language recognition. The DCA integrates a Deformable Correlation (DC) module that leverages spatio-temporal driven offsets to adjust the sampling range adaptively, thereby minimizing interference. Additionally, a multi-scale local sampling strategy, guided by motion prior, enhances temporal modeling capability while reducing computational costs. Furthermore, an attention-based Correlation Matrix Filter (CMF) is proposed to suppress interference elements by accounting for feature motion patterns. A long-term temporal enhancement module, based on spatial aggregation, efficiently leverages global temporal information to model the performer’s holistic limb motion trajectories. Extensive experiments on three benchmark datasets demonstrate significant performance improvements, with a reduction in Word Error Rate (WER) of up to 7.0% on the CE-CSL dataset, showcasing the superiority and competitive advantage of the proposed DCA algorithm. Full article

Novel adjuvants are key to making allergen-specific immunotherapy (AIT) safer and more effective. Their development is crucial for moving AIT into a new generation of precision medicine. N-glycosylation of protein antigens plays a pivotal role in modulating innate immune responses through enhanced recognition by pattern recognition receptors. New AIT vaccine strategies aim to exploit this by using innate-targeting adjuvants, modifying allergen structures, and routing early responses toward tolerance. Thus, we engineered five distinct N-glycosylated adjuvant configurations, composed of the receptor-binding domain of hemagglutinin (H1s) and Der p 2 (D2) allergen, to explore how glycan profile affects innate immune response for the application in therapeutic strategies for Type 1 hypersensitivity. Glycoengineered proteoforms produced in Pichia pastoris were structurally verified by mass spectrometry. Using M0 and M2 THP-1-derived macrophages, binding of all H1sD2 proteoforms to DC-SIGN was confirmed via confocal microscopy and flow cytometry. Stimulation of PBMCs with these proteoforms led to increased IL-10 and IFN-γ levels, indicating a shift toward regulatory immune responses. Notably, the M2 glycovariant elicited the strongest immunomodulatory signature, suggesting significant promise as a therapeutic candidate. These findings support the potential of glycoengineered allergen-adjuvant proteoforms to fine-tune innate immunity and improve the safety and efficacy of AIT. Full article

Background: Temporomandibular disorders (TMDs) are increasingly understood within the biopsychosocial framework, which highlights the interplay of biological, psychological, and social factors in their onset and persistence. Within this context, orofacial myofunctional disorders (OMDs) represent a significant biological component, reflecting structural and functional disturbances of the orofacial system that may contribute to temporomandibular dysfunction. Objectives: This pilot study evaluated the effectiveness of orofacial myofunctional therapy (OMT) in improving functional parameters and reducing pain in adults with myogenous TMD accompanied by OMDs. Methods: In this prospective single-arm pilot study, twenty-five adults (aged 25–39 years) with myogenous TMD and coexisting OMDs, diagnosed according to DC/TMD criteria by a dentist trained in DC/TMD assessment and referred for the intervention, completed three biweekly OMT sessions. The therapy comprised myofascial release, oromotor exercises, functional retraining of breathing, chewing, and swallowing, as well as mandibular stabilization and dissociation exercises, complemented by home-based practice. Functional parameters—maximum mouth opening (MAX) and tongue mobility (TRMR-TIP, TRMR-LPS)—were measured before and after each session. Pain intensity (VAS) and quality of life (SF-36) were assessed at baseline and post-intervention. Data were analyzed using the Shapiro–Wilk test, paired t-test, and Wilcoxon signed-rank test. Results: Statistically significant improvements (p < 0.001) were observed across all evaluated parameters. Participants demonstrated increased maximum mouth opening and tongue mobility, along with decreased pain intensity and improved quality of life following the intervention. Conclusions: This pilot study provides preliminary evidence that short-term OMT can yield measurable functional improvements and pain reduction in adults with TMD and associated OMDs. These findings underscore the relevance of addressing orofacial myofunctional impairments as part of the biological dimension within the biopsychosocial model and support the integration of OMT into interdisciplinary TMD management. Full article

Background: Posturography is a diagnostic method used to evaluate postural stability by recording body sway and the distribution of pressure on the ground. Temporomandibular disorders (TMDs) involve musculoskeletal and neuromuscular dysfunctions affecting the temporomandibular joint, masticatory muscles, and associated structures. Given the anatomical and functional connections between the stomatognathic system and postural control mechanisms, this study aimed to assess whether TMDs influence body posture and balance as measured by posturographic parameters. Methods: 75 volunteers, aged 19–48, were included. The TMD group (n = 45) was diagnosed based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), and the control group (n = 30) showed no signs of TMD. All participants underwent posturographic assessment and jaw opening range measurement. Posturography was performed using a pressure platform that recorded the center of pressure (COP) in static conditions. Postural stability was assessed using the Romberg test with eyes open and closed. Results: No statistically significant differences were found between the TMD and control groups in COP parameters, including ellipse area (EA) and total load distribution. Within both groups, COP sway increased significantly in the eyes-closed (EC) condition, as reflected by a greater unsteadiness length (UL). In contrast, EA was larger in the eyes-open (EO) condition in both groups, indicating a wider but more controlled spatial dispersion of COP. Intra-group analysis further revealed a significantly higher load on the left side in the control group only. Conclusions: The results do not support a significant postural imbalance in individuals with TMD compared to healthy controls. However, increased sway with eyes closed suggests that visual input plays a key role in postural control, regardless of TMD status. Full article

Objective: Monosodium urate (MSU) crystallization in human joints is poorly understood. This study aimed to investigate whether the length of MSU crystals varies in relation to organized ultrasound deposits, which may lead to longer crystals. Methods: Observational, cross-sectional study analyzing MSU crystals from synovial fluid samples of patients with crystal-proven gout. Using light microscopy, we measured crystal lengths (in µm) and noted the presence of long crystals, defined by cutoffs at the 66th, 75th, and 90th percentiles. We evaluated their association with two ultrasound-defined crystal deposition models: (1) grade 2–3 double-contour (DC) sign, tophi, and/or aggregates; and (2) grade 2–3 DC sign and/or tophi. Results: In a total of 1076 MSU crystals from 28 joints, median length was 23.3 µm (95% confidence interval 22.1–24.5). MSU crystal length was similar regardless of ultrasound deposition: in model 1 (20 joints, 71.4%), 22.5 µm in joints with deposits vs. 21.7 µm without; p = 0.42; in model 2 (15 joints, 53.6%), 22.8 µm vs. 21.2 µm, respectively; p = 0.12. Joints fulfilling model 2 criteria had more long crystals (>66th percentile), both in absolute and relative terms. Long crystals mildly correlated with serum urate levels and were numerically more frequent in patients with tophaceous gout. Conclusions: Most MSU crystals in synovial fluid gathered around a common length, regardless of ultrasound deposition. Long crystals were more common in joints with DC signs or tophi. Our finding is in keeping with two different mechanisms of MSU crystallization in humans. Full article

Vaccine adjuvants play a crucial role in the field of vaccinology, yet they remain one of the least developed and poorly characterized components of modern biomedical research. The limited availability of clinically approved adjuvants highlights the urgent need for new molecules with well-defined mechanisms and improved safety profiles. Hemocyanins, large copper-containing metalloglycoproteins found in mollusks, represent a unique class of natural immunomodulators. Hemocyanins serve as carrier proteins that help generate antibodies against peptides and hapten molecules. They also function as non-specific protein-based adjuvants (PBAs) in both experimental human and veterinary vaccines. Their mannose-rich N-glycans allow for multivalent binding to innate immune receptors, including C-type lectin receptors (e.g., MR, DC-SIGN) and Toll-like receptor 4 (TLR4), thereby activating both MyD88- and TRIF-dependent signaling pathways. Hemocyanins consistently favor Th1-skewed immune responses, which is a key characteristic of their adjuvant potential. Remarkably, their conformational stability supports slow intracellular degradation and facilitates dual routing through MHC-II and MHC-I pathways, thereby enhancing both CD4+ and CD8+ T-cell responses. Several hemocyanins are currently being utilized in biomedical research, including Keyhole limpet hemocyanin (KLH) from Megathura crenulata, along with those from other gastropods such as Concholepas concholepas (CCH), Fissurella latimarginata (FLH), Rapana venosa (RvH), and Helix pomatia (HpH), all of which display strong immunomodulatory properties, making them promising candidates as adjuvants for next-generation vaccines against infectious diseases and therapeutic immunotherapies for cancer. However, their structural complexity has posed challenges for their recombinant production, thus limiting their availability from natural sources. This reliance introduces variability, scalability issues, and challenges related to regulatory compliance. Future research should focus on defining the hemocyanin immunopeptidome and isolating minimal peptides that retain their adjuvant activity. Harnessing advances in structural biology, immunology, and machine learning will be critical in transforming hemocyanins into safe, reproducible, and versatile immunomodulators. This review highlights recent progress in understanding how hemocyanins modulate mammalian immunity through their unique structural features and highlights their potential implications as potent PBAs for vaccine development and other biomedical applications. By addressing the urgent need for novel immunostimulatory platforms, hemocyanins could significantly advance vaccine design and immunotherapy approaches. Full article

Objective: This cross-sectional study analyzed the relationship between maxillary incisor inclination and sagittal condylar guidance in patients with and without temporomandibular disorders (TMD) across different skeletal malocclusions, aiming to enhance orthodontic diagnosis and treatment. Materials and Methods: A total of 154 patients from a private clinic with various skeletal malocclusions were consecutively enrolled in this study. Mandibular kinematics were recorded using Modjaw^® and TMD signs and symptoms were evaluated using the DC-TMD questionnaire. Pearson’s correlation was applied to assess relationships between incisor inclination (U1–NA, U1–APog, U1–PP) and condylar guidance (right and left). Results: TMD signs or symptoms were present in 31.8% of patients. A weak negative correlation was observed between incisor inclination and sagittal condylar guidance for patients with positive overjet and overbite values. Retroclined maxillary incisors were weakly associated with a steeper condylar path (correlation values between R = −0.122 and R = 0.177). No significant relation was found between maxillary incisors’ inclination and the presence of TMD (p > 0.05). No significant association was found between TMD prevalence and skeletal or dental classifications (p > 0.05). Conclusions: Although some correlations reached statistical significance, their magnitude was below the accepted threshold for small effects (r ≥ 0.30), indicating negligible clinical impact. These findings suggest that maxillary incisor inclination does not meaningfully influence condylar guidance and should not be considered a primary determinant in treatment planning. Instead, it should be integrated only as a contextual variable within a multifactorial functional assessment. Full article

Background/Objectives: Hip-level amputees face ambulatory challenges due to the lack of a lower limb and prosthetic hip power. Some hip-level amputees restore mobility by using a prosthesis with hip, knee, and ankle joints. Powered prosthetic joints contain an actuator that provides external flexion-extension moments to assist with movement. Powered knee and powered ankle-foot units are on the market, but no viable powered hip unit is commercially available. This research details the development of a novel powered four-bar prosthetic hip joint that can be integrated into a full-leg prosthesis. Methods: The hip joint design consisted of a four-bar linkage with a harmonic drive DC motor placed in the inferior link and an additional linkage to transfer torque from the motor to the hip center of rotation. Link lengths were determined through engineering optimization. Device strength was demonstrated with force and finite element analysis and with ISO 15032:2000 A100 static compression tests. Walking tests with a wearable hip-knee-ankle-foot prosthesis simulator, containing the novel powered hip, were conducted with three able-bodied participants. Each participant walked back and forth on a level 10 m walkway. Custom hardware and software captured joint angles. Spatiotemporal parameters were determined from video clips processed in the Kinovea software (ver. 0.9.5). Results: The powered hip passed all force and finite element checks and ISO 15032:2000 A100 static compression tests. The participants, weighing 96 ± 2 kg, achieved steady gait at 0.45 ± 0.11 m/s with the powered hip. Participant kinematic gait profiles resembled those seen in transfemoral amputee gait. Some gait asymmetries occurred between the sound and prosthetic legs. No signs of mechanical failure were seen. Most design requirements were met. Areas for powered hip improvement include hip flexion range, mechanical advantage at high hip flexion, and device mass. Conclusions: The novel powered four-bar hip provides safe level-ground walking with a full-leg prosthesis simulator and is viable for future testing with hip-level amputees. Full article

Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress. We have recently demonstrated that functional nanoparticles, including ∼4 nm quantum dots and varying sized gold nanoparticles (GNPs), densely glycosylated with various natural mono- and oligo- saccharides, are powerful biophysical probes for MLGIs. Using two important viral receptors, DC-SIGN and DC-SIGNR (together denoted as DC-SIGN/R hereafter), as model multimeric lectins, we have shown that α-mannose and α-manno-α-1,2-biose (abbreviated as Man and DiMan, respectively) coated GNPs not only can provide sensitive measurement of MLGI affinities but also reveal critical structural information (e.g., binding site orientation and mode) which are important for MLGI targeting. In this study, we produced mannuronic acid (ManA) coated GNPs (GNP-ManA) of two different sizes to probe the effect of glycan modification on their MLGI affinity and antiviral property. Using our recently developed GNP fluorescence quenching assay, we find that GNP-ManA binds effectively to both DC-SIGN/R and increasing the size of GNP significantly enhances their MLGI affinity. Consistent with this, increasing the GNP size also significantly enhances their ability to block DC-SIGN/R-augmented virus entry into host cells. Particularly, ManA coated 13 nm GNP potently block Ebola virus glycoprotein-driven entry into DC-SIGN/R-expressing cells with sub-nM levels of EC₅₀. Our findings suggest that GNP-ManA probes can act as a useful tool to quantify the characteristics of MLGIs, where increasing the GNP scaffold size substantially enhances their MLGI affinity and antiviral potency. Full article

Background/Objective: A growing body of international research continues to show evidence of worsening youth mental health since the beginning of the COVID-19 global pandemic, yet very little research in this area has included young children under 6 years. Given the potential impact of early life stress during this critical period of development, it is crucial to better understand the effects on this age group. The objective of this study was to better understand the impact of the COVID-19 pandemic on the emotional health of very young children. Methods: This study utilized retrospective chart review of primary care records to compare the prevalence of markers of stress in two cohorts of children under the age of 6 years, comparing children presenting for care prior to the pandemic (1 April 2019–31 March 2020; control period) with those presenting for care during the first year of the pandemic (1 April 2020–31 March 2021; study period) in a large pediatric primary care clinic in Washington, DC, USA. Based on power calculations, charts of 200 patients from each cohort were reviewed and prevalence of stress markers were summarized using counts and percentages and compared between groups using chi-squared tests. Multivariable logistic regression models were also conducted for each domain adjusting for age, gender, and insurance type. Results: Overall, sleep difficulties were significantly more prevalent during the pandemic period compared to the control period (14% vs. 6.5%, p = 0.013). In addition, signs of stress presented differently across age groups. For example, during the pandemic period toddlers (13–35 months) were 13 times more likely (OR = 13, 95% CI [2.82, 60.4], p < 0.001) and preschool-aged children (36–71 months) were 18.5 times more likely (OR = 18.5, 95% CI [4.0, 86], p < 0.001) than infants to present with behavior problems, indicating substantially higher risk of externalizing symptoms in older children compared to infants. Toddlers were less likely than infants to present with mood changes (e.g., fussiness or crying) (OR = 0.15, 95% CI [0.03, 0.65], p = 0.011). In addition, toddlers (OR = 0.55, 95% CI [0.31, 0.97], p = 0.038) and preschool-aged children (OR = 0.15, 95% CI [0.06, 0.4], p < 0.001) were also less likely to present with feeding difficulties compared to infants. Conclusions: One of the very few studies of young children under 6 years (including infants) during the COVID-19 pandemic, this study found that even very young children experienced stress during the pandemic. Signs of emotional stress were identified in a primary care office during routine care, highlighting an important opportunity for early intervention and/or prevention, such as counseling and resources for caregivers, in settings where young children are already presenting for routine care. Full article

Background/Objectives: This study aimed to explore the functional implications of occlusal changes during clear aligner treatment (CAT) to (a) analyze occlusal changes throughout CAT and the extent of post-treatment occlusal recovery; (b) assess the relationship between post-treatment occlusion and masticatory performance; (c) investigate whether case complexity, facial biotype, and type of malocclusion influence occlusal adaptation and functional outcomes; and (d) evaluate the presence and progression of signs or symptoms of TMDs in patients undergoing CAT. Methods: This longitudinal cohort pilot study included 42 individuals who underwent CAT. Occlusion was evaluated at three timepoints: before treatment (T0), at treatment completion (T1), and three months after with night-only aligner use (T2). Masticatory performance was assessed using a two-colored chewing gum test analyzed through colorimetric software. TMD signs/symptoms were assessed using the Diagnostic Criteria for TMD [DC/TMD]. Statistical analysis used non-parametric tests. Results: A significant decrease in occlusal contact area was observed during active CAT [p = 0.016], which partially recovered at follow-up. Individuals with normal facial proportions (normodivergent) showed more anterior contacts at T1 compared to hyperdivergent individuals [p = 0.013]. Masticatory performance remained stable between T1 and T2 [p = 0.528]. A weak negative correlation was found between posterior contact number and performance score at T1 [r = −0.378, p < 0.05], suggesting that more contacts may be linked to better chewing. No TMD signs or symptoms were detected at any timepoint. Conclusions: Although CAT temporarily reduces occlusal contact area, it does not negatively impact chewing efficiency or trigger TMD symptoms. These findings support the functional safety of CAT when treatment is properly planned and monitored. Full article