Search Results (167)

Background/Objectives: Caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis, is difficult to control on goat farms because of subclinical infection, abscess rupture, environmental contamination, and repeated herd-level exposure. This study evaluated a Korean inactivated CLA vaccine under commercial goat farm conditions and combined vaccination outcomes with farm-level bacteriological profiling. Methods: Goats from three commercial farms were allocated according to baseline CLA serostatus and vaccination status into seropositive vaccinated, seronegative vaccinated, seropositive non-vaccinated, and seronegative non-vaccinated control groups. Vaccinated goats received two intramuscular doses at weeks 0 and 4. Clinical signs, external abscess occurrence, growth performance, CLA-specific antibody responses, and abscess bacterial loads were monitored. Farm-level microbial profiles were assessed using culture, MALDI-TOF MS, and targeted PCR. Results: Baseline antibody classification showed strong agreement between the commercial CLA ELISA and the in-house whole-bacterial IgG ELISA, with a Spearman’s rho of 0.89 (p < 0.001) and 96.7% classification agreement. Vaccination induced CLA-specific antibody responses in both assays and was not associated with a persistent reduction in growth performance. External abscesses were observed only in baseline seropositive goats. Abscesses occurred in 1/30 vaccinated and 2/15 non-vaccinated seropositive goats, but the difference was not statistically significant (p = 0.254). Microbial profiling showed farm-dependent detection patterns. Conclusions: The vaccine induced CLA-specific antibody responses (immunogenicity) with acceptable tolerability. The exploratory abscess endpoint was underpowered, and clinical protection was not confirmed; larger studies are needed. Full article

Background: SARS-CoV-2 infection may impair functional capacity in athletes, while prior vaccination status may be associated with post-infection functional status. However, evidence comparing objective post-infection exercise responses according to vaccination status in elite athletes remains limited. Methods: This study included a total of 220 male athletes with PCR-confirmed SARS-CoV-2 infections: 101 unvaccinated and 119 vaccinated with two doses prior to infection. Cardiopulmonary exercise testing (CPET) was performed 14 ± 1 days after confirmation of SARS-CoV-2 infection and before the athletes returned to full training. A two-way ANOVA was conducted for each CPET variable, using vaccination status and sport as fixed factors. Results: After accounting for the type of sport, vaccinated athletes showed significantly higher VO₂max, VO₂ at VT1, oxygen pulse, heart rate at VT1, and heart rate at VT2, as well as lower VE/VCO₂ values. No significant differences were found for VEmax, HRmax, or heart rate during recovery. The interaction between vaccination status and sport was not significant for the main CPET outcomes, indicating a similar pattern in both sports. Conclusions: These findings suggest that prior vaccination is associated with a more favorable early post-infection physiological profile in professional team-sport players. Full article

Background: Pediatric pleural empyema is a major complication of community-acquired pneumonia and remains associated with substantial morbidity despite advances in vaccination, antimicrobial therapy, and supportive care. Intrapleural fibrinolytic therapy has become an important minimally invasive treatment for complicated parapneumonic effusions and empyema, but uncertainty persists regarding the optimal fibrinolytic agent, treatment protocols, patient selection, and indications for surgical intervention. Methods: A narrative review of the literature was conducted to summarize current evidence on the use of intrapleural fibrinolytic therapy in pediatric pleural empyema. Experimental studies, randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international clinical practice guidelines were critically reviewed. Particular attention was paid to the biological rationale for fibrinolysis, pharmacological characteristics of available agents, comparative effectiveness with video-assisted thoracoscopic surgery (VATS), practical treatment protocols, safety, and future research priorities. Results: Intrapleural fibrinolysis effectively improves pleural drainage by lysing fibrin septations during the fibrinopurulent stage of empyema and is associated with shorter hospitalization compared with chest-tube drainage alone. Urokinase remains the fibrinolytic agent supported by the highest-quality pediatric randomized evidence, whereas alteplase has demonstrated favorable outcomes in observational studies and randomized comparisons with VATS. Current evidence indicates comparable clinical outcomes between fibrinolysis and primary VATS in appropriately selected children, although fibrinolysis is generally associated with lower treatment costs and avoidance of surgery in most patients. Conventional-dose fibrinolytic therapy has an acceptable safety profile, with clinically significant bleeding reported only rarely. Current pediatric evidence does not support the routine addition of DNase to tissue plasminogen activator. Conclusions: Intrapleural fibrinolytic therapy represents a safe, effective, and minimally invasive first-line treatment for most children with complicated parapneumonic effusions and pleural empyema requiring drainage. Management should be individualized within a multidisciplinary framework, integrating timely diagnosis, image-guided pleural drainage, appropriate antimicrobial therapy, and selective surgical intervention. Future multicenter studies are needed to optimize fibrinolytic protocols, validate predictive biomarkers, and further standardize clinical management. Full article

Background: Black adults are frequently portrayed as uniformly vaccine-hesitant, obscuring heterogeneity in the attitudes, beliefs, and decision-making processes that shape vaccine decisions. Methods: Guided by the socioecological and 5C frameworks, a latent profile analysis was conducted to identify distinct and meaningful profiles of vaccine decision-making among Black adults in South Central Los Angeles, a historically disinvested and medically underserved community (N = 203). Results: Three profiles emerged: Empowered and Engaged Trusters (52.0%), Unempowered and Unengaged Noncommitters (32.2%), and Empowered and Engaged Skeptics (15.8%). Subsequent analyses identified healthcare utilization, age, and voting affiliation as predictors of profile membership. Additionally, profile membership was associated with five vaccination outcomes in expected directions, with Trusters reporting higher vaccination intentions and past uptake than both Noncommitters and Skeptics. Conclusions: Study findings underscore the heterogeneity in vaccine decision-making among Black adults and offer insight into the within-group diversity in vaccine acceptance beyond hesitancy. Findings have implications for tailored interventions that maintain confidence, overcome apathy, and reduce skepticism to better promote vaccine acceptance and uptake in Black disinvested communities. Full article

Background: People living with human immunodeficiency virus (HIV) (PLWH) remain at increased risk of severe COVID-19 outcomes; however, conflicting evidence exists regarding the seroconversion rates of COVID-19 vaccines in this population. Methods: A systematic review and meta-analysis were conducted on studies reporting seroconversion outcomes following COVID-19 vaccination in PLWH. Results: Forty-four studies (5391 PLWH) were included in the meta-analysis. The overall pooled seroconversion proportion was 93.5%. Bootstrap analysis confirmed robustness (92.8%). Subgroup analyses revealed significantly higher seroconversion rates for mRNA vaccines (98.2%) compared to non-mRNA vaccines (80.5%). CD4 count demonstrated a graded association: <200 cells/mm³ (53.8%), 200–500 cells/mm³ (86.2%), and >500 cells/mm³ (93.5%). Prior COVID-19 infection (99.1% vs. 89.5%) and antiretroviral therapy (ART) status (93.5% vs. 49.6%) were significant determinants. Safety data demonstrated a favorable profile, with predominantly mild-to-moderate local (injection-site pain: 23.8%) and systemic (headache: 12.95%, fatigue: 6.4%) adverse events; serious adverse events were rare and no consistent association with HIV disease progression was observed. Conclusions: COVID-19 vaccination induces high seroconversion rates in PLWH, particularly among those receiving mRNA vaccines, with preserved CD4 counts, on ART, or with prior infection. Full article

Breast cancer remains one of the most prevalent malignancies affecting women worldwide and continues to be a leading cause of cancer-related morbidity and mortality. Patients may present with either localized or advanced disease, with clinical outcomes increasingly influenced by molecular subtype and genetic profile. This review highlights the key genetic factors involved in breast cancer, current diagnostic and therapeutic strategies, and promising emerging approaches that may shape future clinical management. Breast cancer diagnosis typically involves clinical breast examination, imaging techniques such as mammography and ultrasound, and confirmatory biopsies. Genetic mutations in specific genes are strongly linked to the development, progression, and metastasis of the disease. Treatment options for localized breast cancer continue to include surgery (lumpectomy or mastectomy) and radiotherapy, combined with systemic therapies tailored to tumor biology, such as endocrine therapy, human epidermal growth factor receptor 2 (HER2)-targeted therapy, and cyclin-dependent kinase (CDK)4/6 inhibitors. For advanced or metastatic breast cancer, recent therapeutic advances include the use of immunotherapy (e.g., immune checkpoint inhibitors), Poly (ADP-ribose) polymerase (PARP) inhibitors for Breast Cancer gene (BRCA)-mutated cancers, antibody–drug conjugates, and novel targeted agents, which have significantly improved patient outcomes in selected populations. Recent findings in breast cancer genetics have highlighted the critical role of germline and somatic mutations, particularly in genes such as BRCA1, BRCA2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and TP53, in driving tumor initiation, progression, and therapeutic response. Molecular profiling and next-generation sequencing technologies have enabled more precise tumor classification and facilitated the development of personalized treatment strategies. Despite these advances, treatment resistance and disease recurrence remain major challenges, particularly in aggressive subtypes such as triple-negative breast cancer. Consequently, ongoing research is exploring alternative and complementary approaches, including nanotechnology-based drug delivery systems, gene editing techniques such as clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9) (CRISPR-Cas9), cancer vaccines, and the integration of traditional and plant-derived compounds. These strategies aim to enhance therapeutic efficacy, reduce systemic toxicity, and overcome resistance mechanisms. Full article

Patients with multiple myeloma (MM) exhibit profound immune dysregulation, predisposing them to severe outcomes following SARS-CoV-2 infection. Current evidence highlights shared immunopathological mechanisms linking MM and COVID-19, with particular emphasis on the interleukin-6 (IL-6) axis as a shared amplifier of inflammation rather than the sole driver of disease. MM is characterized by a baseline pro-inflammatory milieu, in part mediated by IL-6, which is further amplified during SARS-CoV-2 infection, resulting in cytokine escalation, complement activation, coagulopathy, and multi-organ injury. This amplification operates within a broader, redundant network that also includes T-cell exhaustion, NK-cell dysfunction, checkpoint signaling, complement and endothelial injury, and treatment-induced immune defects. This overlap provides a mechanistic basis for the disproportionately high morbidity and mortality observed in this population. Even with advancements in vaccination, antiviral therapy, and clinical practice, patients with MM who exhibit impaired vaccine responses, active disease, or treatment-related immune dysfunction continue to experience considerable vulnerability to COVID-19. In addition, MM patients demonstrate suboptimal vaccine-induced immune responses, contributing to persistent vulnerability to severe and breakthrough infections. Modern MM therapies, including anti-CD38 antibodies, BCMA-directed agents, and bispecific T-cell redirecting antibodies, further reshape antiviral immunity by reducing NK cells, inducing plasma cell aplasia, causing hypogammaglobulinemia, and impairing T-cell function. Emerging treatment approaches targeting this shared pathway have been explored, with a focus on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). EVs exhibit multimodal properties, including suppression of pro-inflammatory cytokines, restoration of immune homeostasis, inhibition of viral entry, and promotion of tissue repair and regeneration. Early clinical experience in severe COVID-19 populations suggests a favorable short-term safety profile; reported efficacy, however, derives from small, largely uncontrolled or early-phase studies, and the single randomized trial reporting a mortality benefit did so only in an exploratory post hoc subgroup, with its pre-specified primary endpoint not met. Overall, EVs constitute a biologically plausible but as yet unproven adjunctive strategy that warrants further investigation. Critically, no MM patient has ever been enrolled in an EV trial; current rationale for EV use in MM is therefore extrapolated entirely from non-MM populations, and no MM-specific data exist. Difficulties such as EV heterogeneity, manufacturing variability, uncertain pharmacokinetics, limited targeting efficiency, and potential prothrombotic effects must be resolved before their application in MM-specific clinical settings. Full article

Background/Objectives: We describe the rationale, design and evaluation of a novel feline combination vaccine (Nobivac^® NXT HCPChFeLV) incorporating RNA particle technology against feline leukemia virus (FeLV) alongside live attenuated components for feline herpesvirus-1 (FHV), feline calicivirus (FCV), feline panleukopenia (FPL) and Chlamydia felis. Efficacy and safety outcomes from laboratory and field studies are presented. Methods: Nobivac NXT HCPChFeLV is a 0.5 mL, non-adjuvanted, lyophilized vaccine containing live attenuated FHV, FCV, FPL, and C. felis strains, and an alphavirus replicon-derived RNA particle expressing FeLV envelope glycoprotein (gp85). The primary vaccination schedule involved subcutaneous vaccination at 8–9 weeks of age with a booster 4 weeks later. Onset-of-immunity studies were performed 1 week post primary vaccination. Duration-of-immunity studies evaluated challenge both at 1 year and 3 years after primary vaccination with a booster at 1 year (FHV, FCV, FeLV); FPL duration was assessed at 3 years after primary vaccination; C. felis duration was assessed at 1 year. Clinical signs of disease, survival, leukopenia (FPL) and pathogen excretion were assessed. Safety was assessed in laboratory overdose/repeat-dose studies and in a field study comparing concurrent (non-mixed) use with rabies vaccination vs a positive control regimen. Results: Vaccination significantly reduced clinical disease following FHV, FCV and C. felis challenge and reduced FHV-associated mortality. Vaccinated cats were protected from FPL clinical disease, mortality, leukopenia, and FPL excretion. Persistent FeLV antigenemia was significantly prevented after primary vaccination and in 1-year-duration-of-immunity studies and was reduced 3 years after revaccination. The excretion of FHV, FCV and C. felis was significantly reduced in vaccinates vs controls. No serious adverse events were observed in laboratory studies; field vaccination was well tolerated with no injection-site reactions reported. Conclusions: Nobivac NXT HCPChFeLV provides robust, long-lasting protection against multiple feline pathogens, reduced pathogen shedding and demonstrated a favorable safety profile, supporting its use in feline preventive healthcare. Full article

COVID-19, influenza, and respiratory syncytial virus are leading causes of severe acute respiratory infection (SARI). As viral dynamics shift post-pandemic, comparing their clinical profiles is essential for optimizing management and vaccination strategies. We conducted a retrospective observational study of adults hospitalized with PCR-confirmed COVID-19, influenza, or RSV over three consecutive seasons (2021–2024). We compared clinical features, comorbidities and outcomes, including mortality, intubation rates and respiratory deterioration. Multivariable analyses were performed where virus was the independent variable and respiratory deterioration, intubation rate and mortality, Charlson Comorbidity Index, smoking status and pneumonia were co-variates. 263 patients were analyzed. Key findings revealed distinct clinical profiles: influenza patients were significantly younger, while COVID-19 was the predominant cause of viral pneumonia. RSV patients presented with the most severe oxygenation deficit upon admission and experienced the highest rate of respiratory deterioration (28%). Logistic regression analyses demonstrated that pneumonia [OR 2.81, 95% Confidence Interval (CI): 1.23–6.43, p = 0.01] and RSV (OR 2.8, 95% CI: 1.16–6.63, p = 0.02) were independently associated with respiratory deterioration. Similarly, pneumonia (OR 4.86, 95%CI: 1.62–17.36, p < 0.01] and RSV (OR 4.67, 95%CI: 1.5–14.34, p < 0.01) were independently associated with high risk of intubation. Among patients hospitalized because of COVID-19, RSV and Influenza, pneumonia and RSV were linked with respiratory deterioration and increased risk of intubation but not with death. Full article

Anesthetic agents are widely used in aquaculture to facilitate handling, transport, surgery, vaccination, tagging, and other husbandry procedures. However, most previous reviews have primarily focused on induction time, recovery duration, and welfare outcomes, with comparatively limited emphasis on blood physiology as an indicator of systemic anesthetic safety. The present review synthesizes current evidence regarding hematological, hemato-biochemical, blood gas, and immunohematological alterations induced by major anesthetic classes in aquaculture species. Literature published between 2000 and 2026 was retrieved from Scopus, Web of Science, Google Scholar, PubMed, ScienceDirect, and Springer Nature databases, with approximately 150 studies included following structured screening. Available evidence indicates that anesthetic exposure frequently alters erythrocyte and leukocyte profiles, cortisol secretion, glucose and lactate metabolism, hepatic enzyme activity, electrolyte balance, acid–base regulation, and blood oxygen transport. Respiratory depression, hypercapnia, hypoxemia, and transient metabolic acidosis were recurrent consequences of deep anesthesia, particularly during prolonged exposure or unfavorable environmental conditions. Several anesthetics also modulated innate immune responses through alterations in complement activity, respiratory burst function, cytokine signaling, and leukocyte redistribution. Collectively, the review highlights blood physiology as an essential framework for evaluating anesthetic safety and improving welfare-oriented aquaculture practices. Full article

Therapeutic cancer vaccines have emerged as a promising approach in cancer immunotherapy, aiming to stimulate the immune system to recognize and eliminate malignant cells. Despite this potential, clinical efficacy has remained variable across multiple vaccine platforms. This review synthesizes completed clinical trials evaluating major therapeutic cancer vaccine modalities, including peptide-based, nucleic acid--based, dendritic cell, whole cell, and viral and bacterial vector--based vaccines, with a focus on safety, immunogenicity, and clinical outcomes for diverse tumor types. Overall, these vaccines demonstrate a favorable safety profile; however, clinical efficacy as monotherapy has been limited. Clinical outcomes vary by platform and tumor type and are influenced by factors such as antigen selection, tumor heterogeneity and immunosuppressive tumor microenvironment (TME). Recent advances in antigen design, vaccine technologies, and combination strategies are redefining the role of therapeutic cancer vaccines in oncology. Future progress will depend on optimizing their integration with standard treatment modalities, particularly immune checkpoint inhibitors. Full article

Secondary dengue infections are often linked to more severe clinical outcomes, yet pre-existing antibodies may exert either protective or pathogenic effects. To evaluate the role of acute-phase dengue antibodies in pediatric dengue, we analyzed clinical and laboratory features, viremia, and antibody profiles in children infected with DENV-1. We conducted a retrospective study of patients under 18 years diagnosed with DENV-1 in Salta, Argentina. Viremia was quantified by real-time RT-PCR; acute-phase IgG antibodies (within 7 days from symptom onset) against DENV, DENV-1, and DENV-NS1 were measured by immunoassays, and neutralizing antibodies by plaque reduction neutralization tests. Among 151 patients (median age 12 years), 62% presented dengue with warning signs and one case progressed to severe dengue. Viremia was higher in probable primary infections than in probable secondary infections and did not correlate with disease severity. Probable secondary infections were characterized by acute-phase antibody profiles that did not associate with DENV viremia. Age-stratified analyses revealed that adolescents exhibited higher viremia levels than younger children in probable primary infections, while viremia levels were comparable across age groups in probable secondary infections. Furthermore, children younger than 10 years displayed acute-phase antibody levels similar to those of adolescents. In adolescents with probable secondary infections, anti-DENV and anti-DENV-1 IgG were inversely correlated with platelet counts, whereas neutralizing and anti-DENV-NS1 antibodies showed no association. Collectively, these findings indicate that probable secondary DENV infections in our pediatric cohort were characterized by acute-phase antibodies that were not associated with viremia control, and that in adolescents, anti-DENV and anti-DENV-1 IgG antibodies likely associated with platelet depletion. These results highlight important implications for vaccine design, underscoring the need for vaccines that elicit strong neutralizing responses while minimizing cross-reactivity and the risk of antibody dependent enhancement. Full article

Seasonal influenza remains an important public health concern worldwide, and pregnant women represent a particularly vulnerable population due to physiological and immunological changes associated with gestation. Influenza infection during pregnancy has been associated with adverse maternal, fetal and neonatal outcomes. This narrative review summarizes current evidence regarding maternal influenza infection and influenza vaccination during pregnancy. A structured literature search was conducted using PubMed, Embase and Cochrane Library databases. Studies published between 2020 and 2025 addressing maternal influenza infection, pregnancy outcomes and influenza vaccination were reviewed. Current evidence suggests that maternal influenza infection is associated with increased risks of spontaneous abortion, preterm birth, hospitalization and congenital malformations, especially neural tube defects and congenital heart defects when infection occurs during the first trimester. In contrast, evidence regarding long-term neurodevelopmental outcomes remains inconsistent. Influenza vaccination during pregnancy demonstrates moderate-to-high effectiveness in preventing maternal and neonatal influenza infection and shows a favorable safety profile. Available evidence also suggests that neuraminidase inhibitors, particularly oseltamivir, can be used safely during pregnancy without increasing the risk of congenital malformations or adverse neonatal outcomes. Influenza vaccination during pregnancy should continue to be promoted as a safe and effective public health strategy to protect both mothers and infants. Full article

Leishmaniasis, a neglected tropical disease endemic to 98 countries, affects more than 300 million people worldwide. The disease is transmitted through the bite of infected female phlebotomine sand flies harboring Leishmania parasites. Although infection initiates at the cutaneous inoculation site, Leishmania species exhibit distinct tissue tropisms, resulting in three primary clinical manifestations: cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL). The initial stage of infection involves the engulfment of metacyclic promastigotes (MPs) by host phagocytes, a process mediated by early interactions between the MP flagellum and the host cell surface. This study investigates how species-specific MP-flagellar proteomic profiles dictate unique interactions with host cell populations, thereby driving divergent pathogenic outcomes. To address this, we conducted a comparative quantitative proteomic analysis of flagella from Leishmania species representing each clinical form. Our analysis revealed distinct flagellar proteomic signatures that differentiate the VL-causing species, L. infantum, from others. Notably, we identified five virulence factor families that were differentially expressed: amastins, cysteine peptidases, heat shock proteins, promastigote surface antigens, and leishmanolysins. These findings link flagellar surface composition to species-specific pathogenicity, providing molecular insights into early infection dynamics and identifying potential antigenic targets for developing species-specific vaccines and therapeutics. Full article

This study introduces a Caputo fractional-order version of the SEIRS-V model to investigate the spreading dynamics of worms within wireless sensor networks. Traditional integer-order worm propagation models describe the instantaneous evolution of network states; however, they do not adequately account for memory and hereditary characteristics that may influence the transmission dynamics. Consequently, their ability to represent realistic network behavior can be limited in systems where past states affect current propagation patterns. The framework divides sensor nodes into susceptible, exposed, infectious, recovered, and vaccinated classes, while explicitly incorporating worm transmission rates, temporary loss of immunity, and the impact of preventive security measures under limited resource conditions. A detailed theoretical examination is performed, covering the existence, boundedness, and uniqueness of solutions of the fractional-order system. The coupled nonlinear fractional system is solved semi-analytically by means of the Fractional Reduced Differential Transform (FRDT) technique. To confirm accuracy and robustness, the identical system is also discretized and solved using the finite difference scheme (FDS). Unlike previous studies on worm propagation models in wireless sensor networks, which are mainly limited to equilibrium point analysis and qualitative investigations without deriving explicit solutions, the present work develops an approximate semi-analytical solution for the fractional-order SEIRS-V system using the FRDTM. Comparisons between the two solution sets demonstrate excellent agreement and high precision. Numerical outcomes are presented through a series of 2D graphical profiles that illustrate the time-dependent behavior of each compartment and reveal the sensitivity of worm propagation and suppression to variations in the fractional order and key model parameters. The integrated theoretical and computational findings underscore the strong protective role of vaccination in mitigating worm outbreaks and offer valuable guidelines for strengthening cybersecurity measures in wireless sensor networks. Full article