Search Results (202)

Background: Members of the virus family Herpesviridae are among the most successful pathogen groups in evolutionary history. They not only pose a serious public health threat to humans but also cause significant economic losses in the global livestock industry. The primary immunological challenge in developing sterilizing vaccines is the lifelong latency of herpesviruses in the nervous system or lymphoid tissues. Methods: This analysis compares the vaccine strategies designed against the five most important Alphaherpesvirinae pathogens: HSV-1/2, PRV, BHV-1, EHV-1/4, and FHV-1. The contrast between the globally licensed veterinary vaccines and the relative stagnation in the field of human HSV vaccines is stark. However, there are notable success stories regarding the implementation of ‘Marker Vaccines’ (DIVA strategies) in veterinary medicine. This review examines various vaccine modalities, assessing their potential to mitigate clinical outbreaks and their shortcomings in preventing viral shedding and establishing latency. Results: This study reveals common technical bottlenecks across species, attributed to immune evasion mechanisms such as the downregulation of MHC I, TAP inhibition, the failure to induce robust mucosal IgA, and safety concerns regarding the recombination of live vectors. Conclusions: This review highlights several promising avenues that could lead to enhanced herpesvirus vaccines and recommends the rational design of T-cell epitopes alongside innovative mucosal adjuvants. Furthermore, it bridges the gap between veterinary and human vaccinology from a One Health perspective, suggesting that lessons learned from veterinary practices could facilitate necessary breakthroughs in human medicine. Full article

The scorpion genus Hottentotta Birula, 1908 is widely distributed across Africa and the Middle East, extending to Pakistan, India and Sri Lanka. The processes which resulted in their evolution and diversification across this vast area are poorly understood. The present study investigated the phylogeny and historical biogeography of the genus in the Iranian Plateau and the Zagros Mountains based on nuclear and mitochondrial DNA sequences from four African species, an Arabian species and eight species from the Middle East, most of which are endemic to Iran. Phylogenetic analyses confirmed the monophyly of all species included in the analysis and recovered a clade comprising Iranian and Afro-Arabian species. S-DIVA and BBM analyses demonstrated that the species of Hottentotta occurring in the Iranian Plateau and the Zagros Mountains originated from an African ancestor and then dispersed to their current geographical ranges. Further divergence coincided with the orogeny of the Zagros Mountains and climatic changes during the Miocene epoch. The results support the hypothesis that the Zagros Mountains formed a geographical barrier which promoted vicariance and diversification on the Iranian Plateau. Full article

Background/Objectives: Cancer cachexia is a wasting syndrome with significant loss of body weight and muscle mass caused by inflammation and abnormal metabolism in advanced cancers. Despite its detrimental effects on patients, no standard treatment has been established for this syndrome. Thus, finding new treatments will broaden the remedy for cancer cachexia, resulting in increased survival in patients with terminal cancer. Methods: In this study, we assessed the therapeutic effects of the natural compound polydatin on cancer cachexia in vitro and in vivo using C2C12 myoblasts and CT26-bearing mice to elucidate the mechanisms of how it ameliorates muscle atrophy. At the same time, molecular docking analysis of polydatin with the IL6/STAT3 signaling pathway was conducted to demonstrate their interaction. Results: Our data showed that polydatin treatment at 100 mg/kg could attenuate symptoms of cancer cachexia including body weight loss, muscle strength and severe inflammation. Muscle mass reduction—with the shrinking of muscle fibers, an increase in the expression levels of two E3 ubiquitin ligases (MuRF1 and Atrogin-1) and interleukin-6, and a downregulation of MyHC—observed in CT26-bearing mice was reversed by polydatin at 100 mg/kg. On C2C12 myotubes, polydatin also ameliorated muscle atrophy induced by the CT26 conditioned medium and suppressed STAT3 phosphorylation at the concentration of 200 µM. Structural features of polydatin in the proteins in the STAT3 pathway were identified through molecular docking simulations. Conclusions: Taken together, polydatin significantly attenuated muscle atrophy in a cancer cachexia model by inhibiting the STAT3 signaling pathway; thus, it might be a promising compound in the development of drug candidates for cancer cachexia therapy. Full article

Bluetongue (BT) is a noncontagious, arthropod-borne viral disease of domestic and wild ruminants caused by bluetongue virus (BTV), an arbovirus of the Orbivirus genus within the Sedoreoviridae family. At least 36 serotypes have been identified globally; recurrent circulation of BTV-1, -4, and -8, along with the recent emergence of BTV-3 in northern Europe, underscores a persistent incursion risk for Mediterranean herds. Key drivers include climate-driven expansion of Culicoides vector niches, windborne dispersal, animal movements, and subclinical reservoirs in cattle and goats. As no specific treatment is currently available, control of bluetongue disease still relies largely on vaccination. Live-attenuated vaccines and inactivated vaccines have reduced incidence, but important limitations persist: risk of reversion and the possibility of reassortment for LAVs; requirement for multiple doses and limited cross-protection for inactivated products; and the absence of DIVA capability for both. As an alternative, next-generation platforms are under active evaluation. Subunit formulations, often VP2 combined with VP5 and/or NS1/NS2 virus-like particles (VLPs), and viral-vectored constructs demonstrate favorable safety, strong humoral and cellular responses, inherent or engineered DIVA compatibility, and potential for rapid updating against emergent serotypes. This review synthesizes recent bluetongue activity across the Mediterranean Basin and provides a critical assessment of both existing and emerging vaccine strategies, with a focus on recommending next-generation platforms that emphasize DIVA-compliant, multiserotype, and adaptable vaccination approaches, supported by integrated surveillance and vector control in the region. Full article

Avian influenza (AI), particularly highly pathogenic avian influenza (HPAI), represents a serious and growing threat to global poultry production, international trade, and human health security. Control of AI is complicated by the high evolutionary rate of influenza A viruses, which drives antigenic diversity and ongoing emergence of novel strains. Effective surveillance and disease management therefore depend on timely and accurate diagnostics. While conventional methods—including virus isolation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assays (ELISAs)—remain effective and widely used, they are limited by long turnaround times, the need for specialized equipment, and reliance on highly trained personnel. In addition, strict state and federal regulatory requirements restrict testing to a limited number of authorized laboratories. Although these regulations are essential for maintaining diagnostic accuracy and quality assurance, they place substantial strain on laboratory capacity during outbreaks and delay actionable results. The need for rapid, on-site decision making has driven interest in alternative diagnostic approaches, including biosensor technologies. A major limitation of current diagnostic strategies is the lack of robust DIVA (Differentiating Infected from Vaccinated Animals) capability. In countries such as the United States, where poultry vaccination against AI is not routinely practiced, the absence of DIVA-compatible diagnostics has hindered adoption of vaccination as a disease management tool, as seropositive birds and products face significant trade restrictions. Biosensor platforms capable of enabling DIVA strategies offer a potential pathway to support vaccination while preserving surveillance integrity. This review examines the current landscape of AI and HPAI diagnostics, emphasizing the limitations of traditional approaches and the opportunities presented by biosensor platforms. We evaluate electrochemical, optical, piezoelectric, and nucleic-acid-based biosensors, with particular attention to biorecognition strategies, performance metrics, field deployability, and applications supporting subtype discrimination, DIVA implementation, and One Health surveillance. Full article

Background and Clinical Significance: Furuncular myiasis is a tropical parasitic skin infestation caused by dipterous fly larvae, most commonly affecting travellers to endemic regions. While returning travellers typically present with one or few lesions, extensive parasitism is rare. Increased global mobility and expanding ecological range of myiasis-causing species underscores the need for clinicians in endemic and non-endemic regions to recognise, diagnose, and manage this condition promptly. Awareness of exposure risks—including soil contact, infested clothing, and poor living conditions—is essential to reducing morbidity and preventing complications like secondary bacterial infection. Case Presentation: A healthy male in his forties returned to the UK after a month-long visit to rural Ethiopia, during which he slept on dirt floors and hung his washing on a line. He developed pruritic papular lesions that progressed to erythematous furuncles with central puncta and purulent discharge, accompanied by sensations of movement. The patient self-extracted 12 larvae in Ethiopia and subsequently sought local medical attention, receiving Albendazole, after which emerging larvae were non-motile. On UK presentation, he had 27 lesions at varying stages, 3 with signs of secondary infection. Laboratory investigations revealed elevated inflammatory markers, and wound swabs grew scanty Streptococcus pyogenes. Management included wound occlusion and systemic antibiotics. No further larvae were retrieved, precluding definitive speciation. All lesions improved over subsequent reviews. Conclusions: This case illustrates an unusually extensive presentation of presumed Cordylobia spp. myiasis in a returning traveller, highlighting potential complications following larvicidal therapy. Clinicians should maintain a high index of suspicion for myiasis in patients with compatible cutaneous lesions and relevant history. Increasing travel and shifting vector distributions make familiarity with tropical dermatoses and provision of effective safety measures essential in clinical practice. Full article

The integration of the Internet of Things (IoT) and edge computing is transforming healthcare by enabling real-time acquisition, processing, and exchange of sensitive patient data close to the data source. However, the distributed nature of IoT-enabled smart healthcare systems exposes them to severe security and privacy risks during health information exchange (HIE). This study proposes an edge-enabled hybrid encryption framework that combines elliptic curve cryptography (ECC), HMAC-SHA256, and the Advanced Encryption Standard (AES) to ensure data confidentiality, integrity, and efficient computation in healthcare communication networks. The proposed model minimizes latency and reduces cloud dependency by executing encryption and verification at the network edge. It provides the first systematic comparison of hybrid encryption configurations for edge-based HIE, evaluating CPU usage, memory consumption, and scalability across varying data volumes. Experimental results demonstrate that the ECC + HMAC-SHA256 + AES configuration achieves high encryption efficiency and strong resistance to attacks while maintaining lightweight processing suitable for edge devices. This approach provides a scalable and secure solution for protecting sensitive health data in next-generation IoT-enabled smart healthcare systems. Full article

Infection of susceptible horses with Streptococcus equi subspecies equi (S. equi), the causative agent of strangles, is associated with commingling. Exposure may occur among horses at equestrian events, sales, or horses moved among different equine stabling environments. Strangles can affect all horses on a farm, leading to the death of up to 10% of cases depending on their immunity status at the time of infection, the development of complications, the success of biosecurity measures, and the use of vaccination. The current retrospective study used ELISAs to measure the exposure of horses to S. equi at a farm that experienced an outbreak of strangles shortly after the introduction of a new horse on the same day that the majority of the 17 resident horses were vaccinated with Strangvac for the first time. One vaccinated horse, which subsequently tested positive for S. equi and EHV-4, developed a cough, elevated body temperature, and nasal discharge 11 days after the first vaccination. Two other horses developed fever for one day at 22 days post-first vaccination, but only one had serological evidence of exposure to S. equi. All vaccinated horses had high antibody titres to vaccine components, whilst 7 of the 17 resident horses, and the new arrival, tested seropositive for exposure to S. equi. Although 3 out of the 17 vaccinated horses developed mild signs of disease before second vaccination, serological data support the effectiveness of vaccination in resident populations of horses to minimise the risk of strangles following the introduction of a new horse. Full article

Piscine orthoreovirus genotype 1 (PRV-1) is an emerging viral pathogen in salmon aquaculture that causes Heart and Skeletal Muscle Inflammation (HSMI), with high prevalence in salmon-producing countries such as Chile. A significant obstacle in PRV-1 vaccine development is the inability to culture the virus in vitro, which limits the scalability and production of traditional inactivated or DNA-based vaccine strategies. This study describes the development of a novel virus-like particle (VLP)-based vaccine against PRV-1. Recombinant VLP were produced by co-expressing the six structural proteins of PRV-1 (λ1, λ2, μ1, σ1, σ2, σ3) using a baculovirus-based expression system in insect cells. In addition, to enable differentiating infected from vaccinated animals (DIVA) strategies, the σ1 protein was modified by adding of a cmyc epitope tag. The results demonstrated that the native VLP vaccine (VLP6n) significantly reduced viral loads in Atlantic salmon challenged with PRV-1. Moreover, in rainbow trout, the cmyc-tagged VLP-like vaccine (VLP6c) elicited a specific antibody response against the cmyc epitope, allowing differentiation between vaccinated and naturally infected fish. Overall, this VLP-based vaccine platform represents a promising strategy for controlling PRV-1 prevalence in salmon-producing counties, supporting the implementation of serological surveillance programs. Full article

In recent years, deep learning networks have demonstrated remarkable progress in the semantic segmentation of historical documents. Nonetheless, their limited explainability remains a critical concern, as these models frequently operate as black boxes, thereby constraining confidence in the trustworthiness of their outputs. To enhance transparency and reliability in their deployment, increasing attention has been directed toward explainable artificial intelligence (XAI) techniques. These techniques typically produce fine-grained attribution maps in the form of heatmaps, illustrating feature contributions from different blocks and layers within a deep neural network (DNN). However, such maps often closely resemble the segmentation outputs themselves, and there is currently no consensus regarding appropriate explainability metrics for semantic segmentation. To overcome these challenges, we present SegClarity, a novel workflow designed to integrate explainability into the analysis of historical documents. The workflow combines visual and quantitative evaluations specifically tailored to segmentation-based applications. Furthermore, we introduce the Attribution Concordance Score (ACS), a new explainability metric that provides quantitative insights into the consistency and reliability of attribution maps. To evaluate the effectiveness of our approach, we conducted extensive qualitative and quantitative experiments using two datasets of historical document images, two U-Net model variants, and four attribution-based XAI methods. A qualitative assessment involved four XAI methods across multiple U-Net layers, including comparisons at the input level with state-of-the-art perturbation methods RISE and MiSuRe. Quantitatively, five XAI evaluation metrics were employed to benchmark these approaches comprehensively. Beyond historical document analysis, we further validated the workflow’s generalization by demonstrating its transferability to the Cityscapes dataset, a challenging benchmark for urban scene segmentation. The results demonstrate that the proposed workflow substantially improves the interpretability and reliability of deep learning models applied to the semantic segmentation of historical documents. To enhance reproducibility, we have released SegClarity’s source code along with interactive examples of the proposed workflow. Full article

Magnesium (Mg²⁺) is the fourth most abundant cation in the human body and a critical cofactor in hundreds of enzymatic reactions that regulate energy metabolism, neuromuscular function, cardiovascular health, bone integrity, immune defense, and psychological well-being. Despite its essential roles, magnesium deficiency remains common worldwide, driven by inadequate dietary intake, chronic diseases, medication use, and lifestyle factors. Low magnesium status is associated with hypertension, type 2 diabetes, osteoporosis, migraines, depression, and chronic inflammation, whereas sufficient intake supports cardiometabolic resilience, skeletal strength, neurological stability, and healthy aging. This review synthesizes current evidence on magnesium metabolism, physiological functions, and the health consequences of deficiency, and it summarizes global status with attention to biomarker limitations, widespread suboptimal intake, and key demographic and lifestyle determinants. It also discusses dietary sources, supplementation, and innovative approaches such as food fortification, personalized nutrition, and improved diagnostic strategies. The evidence highlights magnesium as a modifiable factor with potential to lessen the burden of chronic diseases. Recognizing magnesium deficiency as a pressing but underappreciated public health issue, this article underscores the need for integrated strategies to optimize magnesium balance at both individual and population levels. Full article

Senecavirus A (SVA) causes a vesicular disease in pigs with clinical signs indistinguishable from those of other swine vesicular diseases. To enable serological differentiation infected from vaccinated animals (DIVA), we developed indirect ELISAs (iELISAs) based on recombinant non-structural proteins (NSPs). A His-tagged tandem antigen, r3AB-3C, was designed by integrating immunodominant B-cell epitopes from 3AB and 3C proteins, and was successfully expressed in Escherichia coli (E. coli) and purified alongside the individual r3AB and r3C proteins. Serological evaluation results showed that the immunoreactivity of the r3AB-3C iELISA was superior to that of r3AB, which in turn was better than r3C. The r3AB-3C and r3AB iELISAs were subsequently validated. The cut-off values were established at sample-to-positive (S/P) ratios of ≥0.2635 for the r3AB-3C iELISA and ≥0.5775 for the r3AB iELISA. The r3AB-3C iELISA demonstrated higher sensitivity for detecting infection-induced antibodies than the r3AB iELISA, despite the later seroconversion of anti-NSP antibodies compared to neutralizing antibodies. In a serosurvey, the r3AB-3C iELISA revealed seropositivity rates of 35.2% in 2023 and 22.3% in 2024. In conclusion, the r3AB-3C iELISA is a valuable serological tool for monitoring SVA infection, effectively supporting DIVA strategies. Full article

Background/Objectives: Classical swine fever (CSF) is listed by the World Organisation for Animal Health as a highly devastating and contagious pig disease, causing severe economic losses to the swine industry. In spite of the successful elimination of CSF in Taiwan, preparedness against potential reintroduction remains essential. The live attenuated vaccines have been effective in disease control, but are not capable of a viable strategy that differentiates infected from vaccinated animals (DIVA). Subunit vaccines are recognized for their safety and ability to induce protective immunity against infectious diseases. Methods: In this study, the recombinant CSF virus (CSFV) E2 proteins were formulated with a CpG motif as an adjuvant to produce the E2-CpG subunit vaccine. Its efficiency in specific-pathogen-free (SPF) pigs was compared with a commercially available E2 subunit vaccine (Bayovac^® CSF-E2; Bayer Taiwan Co., Ltd., Taipei City, Taiwan). Results: Significantly higher titers of anti-E2 antibodies were induced in pigs immunized with a single dose of the E2-CpG vaccine, particularly the reduced E-0.5A formulation, than those immunized with a dose of the commercialized E2 subunit vaccine adjusted to double dosage. This designed subunit vaccine showed high efficacy in protection against clinical symptoms and significant pathological alterations in pigs after a highly virulent CSFV (genotype 1.1) challenge. Viral shedding was not detected in vaccinated pigs before completion of the challenge study, and the viral load in their spleens remained undetectable. Conclusions: These results could support the potential of the E2-CpG vaccine as a cost-effective, single-dose subunit vaccine capable of inducing robust CSFV-specific immunity and providing 100% protection against lethal CSFV challenges. Full article

Introduction/Background: Rift Valley fever virus (RVFV) and peste des petits ruminants virus (PPRV) are significant pathogens affecting small ruminants, causing substantial economic losses in the affected regions. The development of effective vaccines against both viruses is crucial for disease control. Recombinant viruses expressing heterologous antigens have shown promise as multivalent vaccine candidates. Unlike conventional PPRV vaccines, our recombinant RVFV-vectored vaccines offer a novel dual-protection strategy against RVF and PPR, combining safety, immunogenicity, and a DIVA strategy. Methods: Recombinant RVFVs (ZH548 strain) were generated to express either the hemagglutinin (H) or fusion (F) proteins from the PPRV strain Nigeria 75/1. The stability of these recombinant viruses was assessed through consecutive passages in cell culture. Immunogenicity studies were carried out in both mice and sheep to assess the induction of cellular and humoral immune responses capable of providing protection against RVFV and PPRV. These studies included intracellular cytokine staining (ICS), IFN-γ ELISAs, standard ELISAs for antibody detection, and virus neutralization assays. Results: The recombinant RVFVs expressing PPRV H or F proteins demonstrated stability in cell culture, maintaining high viral titers and consistent transgene expression over four passages. Immunization of mice resulted in the production of serum antibodies capable of neutralizing both RVFV and PPRV in vitro as well as cell-mediated immune responses specific to PPRV and RVFV antigens. In mice vaccinated with a high dose (10⁵ pfu), RVFV neutralizing titers reached ≥1:160 and PPRV neutralizing titers ranged from 1:40 to 1:80 by day 30 post-immunization. In sheep, neutralizing antibody titers against RVFV exceeded 1:160 as early as 2 days post-inoculation, while PPRV-specific neutralization titers reached up to 1:80 by day 21 in responsive individuals. In mice, administration of rZH548ΔNSs:F_PPRV elicited a detectable CD8+ IFNγ+ T-cell response against PPRV, with levels ranging from 1.29% to 1.56% for the low and high doses, respectively. In sheep, rZH548ΔNSs:F_PPRV also induced a robust IFNγ production against PPRV at 14 and 21 days post-infection (dpi). Conclusions: The successful generation and characterization of recombinant RVFVs expressing PPRV antigens demonstrate the potential of using rationally attenuated RVFV as a vector for multivalent vaccine development. Notably, the strategy proved more effective for the recombinant virus expressing the F protein, as it consistently induced more robust cellular and humoral immune responses. These results suggest that this approach could be a viable strategy for simultaneous immunization against Rift Valley fever and other prevalent ruminant diseases, such as peste des petits ruminants. Even though challenge studies were not performed in target species, the strong immune response observed supports including them in future studies. Full article

Background/Objectives: This narrative review addresses ongoing controversies and advancements concerning ultrasound-guided peripheral intravenous (IV) catheter insertion, and the impact of ultrasound guidance on success rate, procedural time, patient and staff experience, complications and costs, as well as requirements for its use. Methods: A literature review was conducted. Results: Growing evidence suggests that ultrasound-guided insertion of peripheral IV catheter represents a superior technique across various patient populations, particularly those presenting with difficult IV access (DIVA). Key findings highlight significant improvements in first-attempt success rates, reduction of procedural complications, and enhanced patient comfort. Ultrasound-guided insertion is also associated with an increase in catheter dwell time, a reduction in repeat procedures and in central line placements, leading to improved resource utilization and the potential for substantial long-term cost-effectiveness, despite the cost of initial investment and training. However, obtaining these improvements involves a critical importance for standardized training, adherence to rigorous aseptic techniques, and generalization of the transformative impact of ongoing technological advancements in ultrasound devices. Conclusions: The collective body of evidence supports the widespread adoption of ultrasound-guided peripheral IV cannulation as an evidence-based best practice in modern healthcare. Full article