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Species of Penicillium are among the most important fungal pathogens responsible for postharvest diseases of agricultural crops worldwide. This review provides an overview of five economically important Penicillium spp., namely P. expansum, P. digitatum, P. italicum, P. citrinum, and P. oxalicum. Emphasis is placed on P. expansum, P. digitatum, and P. italicum which are the main causal agents of blue mold and green mold rots in pome fruits and citrus, commodities that dominate global fresh produce trade and long-term storage. While studies on plant-pathogenic Penicillium are mainly focused on these hosts, this review highlights reports of infections in other crops across diverse geographic regions, highlighting the broader host range of these species. The main aspects highlighted include host specificity and diversity, production of mycotoxins and other secondary metabolites, current management and control strategies, and the potential influence of climate change on disease incidence and severity. Understanding the biology and epidemiology of plant-pathogenic Penicillium species is essential, as several species are both pathogens and producers of mycotoxins, leading to quality deterioration and nutrient depletion resulting in economic losses.

Background/Objectives: Vaccination against respiratory viruses-such as respiratory syncytial virus (RSV), pneumococcal disease, influenza, and COVID-19-may reduce the risk of adverse outcomes in older adults with cardiovascular disease. This study conducted a scoping review of the effects of respiratory vaccines in older adults with cardiovascular disease. Methods: We included studies evaluating adults aged ≥ 60 years with cardiovascular disease who received different types of respiratory vaccines. Eligible designs comprised clinical trials, observational cohort studies, and other relevant studies. Editorials, commentaries, and non-original publications were excluded. A comprehensive and targeted literature search was conducted in PubMed, Scopus, EMBASE, and Web of Science from database inception through January 2026. Results: A total of 25 studies were included, encompassing 1,782,787 adults aged ≥ 60 years with cardiovascular disease who received various respiratory vaccines. RSV vaccines were associated with a lower incidence of cardiorespiratory hospitalization and stroke among vaccinated individuals. Pneumococcal vaccines showed that sequential dual vaccination strategies were associated with a lower risk of cardiovascular events. Influenza vaccination was associated with improved cardiovascular outcomes, lower mortality, and reduced adverse events. COVID-19 vaccines were associated with reductions in mortality and hospitalizations. These benefits are particularly relevant in an older population with a high burden of comorbidities; therefore, complete vaccination schedules, including booster doses, should be considered a central strategy for prevention and comprehensive management in this high-risk group. Conclusions: Vaccination against respiratory viruses in older adults with cardiovascular disease demonstrates an overall favorable/acceptable profile of efficacy and safety, with reductions in mortality, hospitalizations, and cardiovascular events, without a significant increase in serious adverse events.

The steady increase in allergic diseases among children has coincided with increased global vaccination coverage and the expansion of routine childhood immunization programs. This has contributed to the widespread belief that there is a possible link between immunoprophylaxis and allergic diseases. However, a number of scientific studies have demonstrated the protective effect of early neonatal immunization on the development of nonspecific immunological protection against infections. This is believed to be due to a shift in the immune response from the Th2 type, traditionally predominant in newborns, to the Th1 type, which reduces the risk of developing allergic diseases. This prospective cohort study analyzed the medical records of 2279 children born between 2018 and 2022 to evaluate the impact of neonatal BCG-M and hepatitis B (HepB) vaccination on the incidence of atopic dermatitis (AD) by 36 months of age. Factors analyzed included family history of allergy, cesarean section, prematurity, delayed initiation of breastfeeding, maternal antibiotic use during pregnancy, and antibiotic use in the child during the first three years of life. The cumulative incidence of AD by 36 months of age was 19.9%. Timely neonatal vaccination coverage was 76.2% for BCG-M and 69.2% for HepB; by 12 months of age, these rates increased to 90.2% and 88.5%, respectively. A full-term birth demonstrated a significant protective effect (OR 0.52; 95% CI 0.30-0.93). A positive family history of allergy was the strongest predictor of AD (OR 21.49; 95% CI 14.4-32.9). Cesarean section was also significantly associated with AD (OR 1.30; 95% CI 1.01-1.65). AD incidence was comparable between vaccinated (20.5%) and non-vaccinated (17.5%) children (chi-squared with Yates' correction, p = 0.192), indicating no statistically significant overall impact of immunization on AD risk. The development of AD is primarily driven by hereditary predisposition and specific perinatal factors rather than by routine immunization. These findings confirm that neonatal BCG-M and HepB vaccination does not increase the risk of AD, providing a scientific basis to address vaccine hesitancy.

Bispecific antibodies (BsAbs) have emerged as a powerful therapeutic modality with the ability to simultaneously engage two distinct targets, enabling novel mechanisms of action that traditional monoclonal antibodies cannot achieve. This dual-targeting capability offers significant advantages in treating complex diseases such as cancer, autoimmune disorders, and infectious diseases by enhancing specificity, improving immune engagement, and reducing resistance mechanisms. The development of BsAbs has been driven by innovations in antibody engineering platforms, including BiTE, TriTAC, CrossMAb, XmAb, Fcab, and κλ-body technologies. These platforms allow the construction of diverse BsAb formats, ranging from compact single-chain variable fragments (scFvs) to full-length IgG-like molecules, each optimized for specific pharmacokinetic and pharmacodynamic profiles. Clinical candidates such as blinatumomab, HPN328, and XmAb14045 demonstrate the therapeutic potential and versatility of BsAbs, several of which have progressed to advanced stages of clinical trials or received regulatory approval. However, BsAb development poses unique challenges, including molecular heterogeneity, complex manufacturing processes, and the need for precise functional characterization. Emerging technologies such as high-resolution mass spectrometry, surface plasmon resonance (SPR), hydrogen‑deuterium exchange (HDX-MS), and AI-assisted modeling are increasingly being adopted to overcome these hurdles. As the field evolves, BsAbs are redefining therapeutic strategies by offering multi-functional approaches within a single molecule. Their ability to orchestrate complex biological interactions with high specificity positions them at the forefront of next-generation biologic. This article explores the technical advancements and clinical milestones that underscore the rising impact of BsAbs in modern medicine.

The potential of Trichoderma nordicum (Hypocreales, Ascomycota), a recently described species, for antagonism and use in the biocontrol of oomycete-caused plant diseases is unknown. Trichoderma is a well-known genus for containing microbial antagonists and biocontrol agents. The T. nordicum in this study was isolated from decomposing wood, and rpb2 and tef1 barcode sequencing demonstrated that the isolates were a match to the reference T. nordicum and T. nigricans strains. Since T. nordicum was described before T. nigricans, the isolates were assigned to T. nordicum, although taxonomic uncertainty between these species requires future clarification. In dual-culture confrontation assays, T. nordicum overgrew five economically important oomycete plant pathogens (Phytophthora capsici, P. sojae, Pythium aphanidermatum, P. myriotylum, and Globisporangium ultimum). The inability to recover viable P. aphanidermatum and P. capsici from the parts of the plate overgrown by T. nordicum, coupled with protease and endo-cellulase activities, correlates with T. nordicum having antagonistic abilities. Inoculation with T. nordicum preventively reduced the levels of cucumber seedling damping-off caused by P. aphanidermatum by up to 70%. The T. nordicum biocontrol effects against pepper blight caused by P. capsici were greater than 80%, compared to an autoclaved T. nordicum spore control. T. nordicum could also significantly promote the growth of pepper, with plant weight increased by up to 40%, compared to an autoclaved-spore control. In contrast, T. nordicum could not be used to control Pythium soft rot of ginger caused by P. myriotylum, even though P. myriotylum was overgrown by T. nordicum, suggesting host- or pathosystem-specific factors influence biocontrol efficacy. In summary, T. nordicum is a promising biocontrol agent for use in the control of pepper blight caused by P. capsici, and also has potential for use in the control of other oomycete-caused plant diseases in vegetable production systems.

As a non-invasive mucosal immunization strategy, intranasal vaccines are highly promising for preventing respiratory infectious diseases. Among them, recombinant subunit vaccines represent a safe and ideal option, as they induce targeted mucosal immunity without the safety risks associated with live-vectored or nucleic acid vaccines. However, nasal mucosal defenses rapidly clear antigens before immune activation, limiting protective efficacy. Therefore, intranasal vaccine adjuvants-key regulators of immune response intensity, duration, and type-are essential to overcome mucosal tolerance and improve immunogenicity. Based on a systematic search and analysis of 127 peer-reviewed articles (2010-2026) in PubMed, Web of Science, and Embase, this study comprehensively summarizes the mechanisms, applications, and limitations of existing and candidate adjuvants for intranasal vaccines. This review systematically categorizes and discusses the nasal mucosal barrier, major adjuvant types (e.g., pattern recognition receptor agonists, cytokine adjuvants, and carrier adjuvants), and their mechanisms of action. It also identifies key bottlenecks: insufficient mucosal targeting, inconsistent global safety evaluation standards for adjuvants, and interference from pre-existing antibodies in humans. Furthermore, this review highlights future development directions, including biomimetic adjuvants, pH-responsive nanoadjuvants, and thermostable vaccine formulations. This systematic review clarifies key scientific and technical barriers in intranasal vaccine adjuvant development. The findings provide valuable references for advancing the translation of intranasal vaccines from emergency countermeasures to routine, accessible preventive tools for respiratory infectious diseases.

Nursing homes are congregate settings for elderly individuals where infectious diseases can easily spread. The elderly are at high risk of contracting and dying from influenza, and the most effective way to prevent this is to receive the influenza vaccine. This study conducted a cross-sectional survey of elderly people in nursing homes to investigate the occurrence of influenza symptoms during the 2024-2025 flu season, as well as vaccination status and reasons for receiving or not receiving the vaccine. Bivariate logistic regression was used to determine the factors influencing the vaccination rate. Of the 1024 elderly people who participated in the survey, 25.39% reported experiencing flu-related symptoms in the previous flu season. While 16.21% of the elderly expressed willingness to receive vaccination, only 5.57% actually received it. Influenza vaccination was positively correlated with educational attainment (aOR 3.800, 95% CI 1.480-9.758 for middle school; aOR 5.138, 95% CI 1.738-15.191 for high school), monthly household income (aOR 0.216, 95% CI 0.072-0.644 for >8000), ability for self-care (aOR 0.269, 95% CI 0.123-0.591), and the scale of the nursing home (aOR 9.033, 95% CI 1.531-53.305 for 151-299; aOR 2.629, 95% CI 1.359-5.084 for ≥300). Willingness to receive the influenza vaccination was positively correlated with an unhealthy health status (aOR 0.398, 95% CI 0.204-0.779), symptoms of influenza (aOR 2.730, 95% CI 1.861-4.007), nursing home location (aOR 1.537, 95% CI 1.099-2.941 for outer suburbs), and the scale of the nursing home (aOR 1.991, 95% CI 1.154-3.435 for 151-299; aOR 2.158, 95% CI 1.374-3.390 for ≥300). Most elderly people who received the vaccine believed that vaccination could effectively prevent flu and that it could reduce the risk of complications, the rest were not vaccinated due to concerns about adverse reactions, mobility issues, or the distance to vaccination sites. Low awareness of flu vaccines and physical inability to travel to vaccination sites may be potential barriers to receiving the flu vaccine. It is worrying that the influenza vaccination rate is low among the elderly in nursing homes in Shanghai. As a result, it is crucial to prioritize targeted monitoring and intervention strategies for vulnerable populations living in collective institutions.

Background: Childhood vaccination remains the cornerstone of public health strategies, substantially reducing global morbidity and mortality, yet suboptimal uptake persists in many settings. In South Africa, the challenge is evident, with persistent outbreaks of vaccine-preventable diseases. Addressing localised immunisation shortfalls requires elucidating the complex interplay of factors beyond conventional access barriers. This qualitative study provides context-specific insights into the behavioural and social drivers influencing childhood vaccination uptake among caregivers in Cape Town, South Africa. Methods: Utilising an exploratory qualitative research design, thematic analysis was applied to interview data (n = 25 caregivers) collected via a purposive sampling strategy designed to capture maximum variation in experiences within targeted low-uptake subdistricts. Interpretation of the data was systematically guided by the World Health Organization's Behavioural and Social Drivers (BeSD) framework. The latter consists of four domains, namely, "Thinking and Feeling", "Social Processes", "Motivation", and "Practical Factors". Findings: Analysis across BeSD domains reflected a pattern of the intention-behaviour gap, where caregivers are motivated for vaccination but face structural and practical barriers affecting timely uptake. In the Thinking and Feeling domain, widespread conviction regarding the vital benefits of vaccination co-existed with significant anxiety concerning minor side effects (e.g., pain and fever), which sometimes precipitated missed subsequent appointments. Caregivers frequently accept immunisation as a social routine despite having limited knowledge of the diseases it prevents. Social Processes demonstrated that while decision-making authority rested primarily with mothers, compliance relied on the delegation of logistical responsibilities to extended family members. Critically, reports of poor communication, judgment, or negative attitudes among healthcare workers undermined trust and acted as barriers to sustained engagement. Within the Practical Factors domain, structural constraints frequently overshadowed high intent, with pervasive issues such as long waiting times and financial costs cited as the main reasons for missed appointments. Conclusions: Participants generally expressed strong acceptance of vaccination, but attainment of optimal coverage is constrained by systemic failures in patient-provider communication and persistent logistical barriers within the public healthcare delivery system. Strategic public health interventions must therefore move beyond addressing only attitudinal opposition to prioritise targeted efforts that mitigate structural constraints and reinforce personalised, empathetic communication to sustain caregiver confidence and adherence.

Aspergillosis is a group of different invasive and non-invasive diseases affecting the lung and other organs, caused by species of the genus Aspergillus. Additionally, complications associated with treatment and the increasing emergence of antifungal-resistant strains of Aspergillus spp. are high-impact problems. For these reasons, a combined approach of diagnostic tests is necessary to reach an accurate and timely diagnosis. This review aims to describe some biomarkers and their usefulness for the diagnosis of aspergillosis. Among the findings obtained in different studies, the nature, analytical performance and usefulness for diagnosis in different clinical forms of this disease are described. Currently, the main biomarkers used in the diagnosis of Aspergillus disease fall into three categories: membrane components, specific DNA sequences and metabolic products. The detection of biomarkers is one of the most important innovations of recent decades in the field of medical mycology, as it is a diagnostic aid that allows the timely detection of infections and decreases the time of administration of antifungal therapy.

Background/Objective: The emergence of the COVID-19 pandemic has raised significant concerns regarding its impact on immune-mediated diseases, particularly with respect to disease induction and exacerbation. We aimed to investigate the potential association between SARS-CoV-2 infection and COVID-19 vaccination and the development of Psoriatic Arthritis (PsA). Methods: A retrospective nested case-control study in a cohort of 3,122,602 adults without a diagnosis of PsA was conducted using a database of a large health care provider. Newly diagnosed patients with PsA aged 18 years and older were identified from the database between 1 January 2021 and 30 June 2022 and were matched by age and sex to 10 non-PsA controls. Patients were tracked to assess their exposure to SARS-CoV-2 within six months prior to diagnosis (inception date). The primary outcome of exposure to SARS-CoV-2 was compared in the cases and controls. Univariate and multivariate conditional logistic regression analyses were performed, adjusting for Body Mass Index (BMI), smoking, socioeconomic status (SES), the Charlson comorbidity index, ethnicity, psoriasis and COVID-19 vaccination status within six months. Results: Overall, 718 patients had a new diagnosis of PsA and were matched with 7180 controls. SARS-CoV-2 exposure among PsA cases was (N = 88/718, 12.3%) compared to controls (N = 755/7180, 10.5%), the difference was not statistically significant (p = 0.115). No statistically significant association was found between SARS-CoV-2 infection and PsA development after adjusting for all confounders (OR = 1.08, 95% CI [0.76-1.54], p = 0.652). COVID-19 vaccination was also not associated with PsA development (OR = 1.10, 95% CI [0.86-1.41], p = 0.45). Conclusions: This study found no statistically significant association between SARS-CoV-2 exposure or COVID-19 vaccination and PsA development within six months post-exposure; however, small differences cannot be excluded.

Respiratory infections remain a leading cause of morbidity and mortality worldwide, highlighting the urgent need to better understand host defense mechanisms in the respiratory tract. Recent advances in sequencing technologies have challenged the traditional view of the lungs as sterile organs and revealed the presence of a distinct, low-biomass microbial community known as the lung microbiota. These microbial populations interact closely with airway epithelial cells and immune cells to maintain respiratory homeostasis and regulate host immune responses. In healthy lungs, microbial communities dominated by Firmicutes, Bacteroidetes, and Proteobacteria contribute to immune regulation through interactions with innate and adaptive immune pathways. Microbiota-derived signals are detected by pattern recognition receptors, activating signaling pathways that regulate cytokine production, immune cell recruitment, and T-cell differentiation. In the respiratory mucosa, microbial stimulation can also induce epithelial and antigen-presenting cells to produce B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), which promote immunoglobulin A (IgA) class-switch recombination and support mucosal antibody responses. During pulmonary infection, disruption of microbial communities can lead to dysbiosis that amplifies inflammatory responses, impairs epithelial barrier integrity, and increases susceptibility to secondary bacterial infections. In addition to local microbial interactions, the gut-lung axis represents a key communication pathway linking intestinal microbiota with respiratory immunity through microbial metabolites such as short-chain fatty acids (SCFAs) and immune signaling networks. This review summarizes current insights into microbiota-immune crosstalk in the lung during pulmonary infection and discusses how these interactions may inform mucosal vaccine development. A deeper understanding of host-microbiota interactions may enable microbiome-informed vaccines and therapeutic strategies to improve protection against respiratory diseases.

Astragalus membranaceus suffers severe yield and quality losses due to root rot caused by Fusarium solani. To address this, we analyzed the root-associated microbial communities of healthy and diseased plants in northwest China using high-throughput sequencing. Combining community analysis with pot experiments and transcriptomic profiling, we elucidated the molecular mechanisms by which the biocontrol fungus Purpureocilliu lilacinum BP2-7 suppresses root rot. Root rot reshaped root-associated microbial structure, affecting fungal diversity more than bacterial diversity. The antagonistic effect of P. lilacinum BP2-7 against F. solani reached 71.43% in plate assays and 63.7% control efficacy in pot experiments, representing the first report of P. lilacinum application for managing root rot in A. membranaceus. Transcriptomic analysis revealed that P. lilacinum BP2-7 promotes the transition of plants from a damaged to a recovering state by modulating translation and metabolic processes, and enhancing protein homeostasis, while moderately downregulating defense-related responses to alleviate pathogen-induced excessive defense mechanisms. Additionally, twenty candidate genes involved in the direct inhibition of F. solani were identified, suggesting a role in enhancing host resistance. This study supports eco-friendly biocontrol strategies and advances understanding of plant-microbe interactions for managing soil-borne diseases in other important crops.

Rice sheath blight caused by Rhizoctonia solani is one of the most destructive diseases of rice. Bixafen has been proposed as a promising control agent with moderate resistance risk; however, its cellular mode of action remains unclear. Therefore, this study investigated the antifungal mechanism of bixafen from the perspective of programmed cell death (PCD). Bioassays showed that bixafen strongly inhibited R. solani, with a median effective concentration (EC50) of 1.16 μg/mL. Morphologically, bixafen induced hyphae collapse, vacuolization, chromatin aggregation, and mitochondrial disruption. Transcriptome analysis further revealed that bixafen significantly altered the expression of genes involved in the tricarboxylic acid cycle and PCD pathways. In addition, bixafen, at the concentration of EC50, triggered ROS accumulation accompanied by increased malondialdehyde (MDA) levels. These oxidative effects led to mitochondrial damage, characterized by loss of membrane potential, reduced Tomm20 expression, and decreased Aco-2 activity. Subsequently, bixafen activated apoptosis, as evidenced by induction of the mitochondria-associated inducer of death (AMID), down-regulation of Bcl-2, and DNA fragmentation. Moreover, bixafen also induced autophagy by reducing p62 and increasing Beclin-1 expression, which suggests the clearance of damaged mitochondria. Collectively, these results demonstrated that bixafen induced mitochondrial-dependent apoptosis and autophagy in R. solani, which provided novel insights into its cellular antifungal mechanism and supported its potential as a PCD-targeted fungicide.

Background: Patients with kidney failure requiring dialysis experience a high burden of vaccine-preventable diseases, and vaccine hypo-responsiveness is a key contributor. Uraemic toxins and gut dysbiosis are potential causes of hypo-responsiveness. Aim: This study aimed to determine whether uraemic toxin concentrations or gut dysbiosis are associated with vaccine response in haemodialysis patients. Methods: This was a single centre, observational cohort study of maintenance dialysis patients receiving a conventional 2-dose primary COVID-19 vaccination course. Demographic, clinical and vaccination data were collected from the eMR. Vaccine response (Elecsys Anti-SARS-CoV-2 immunoassay), serum uraemic toxin concentrations (indoxyl sulphate, p-cresyl sulphate, and trimethylamine N-oxide by liquid chromatography), and stool microbiome (16S rRNA gene sequencing) were measured 8 weeks after the second dose of vaccine. Results: Forty participants (43% female, mean age 66 years; 59% Caucasian) were included, 70% of whom were classified as a vaccine responder. Antibiotic exposure, prednisolone use and lymphopenia were significantly associated with hypo-responsiveness. Microbiome profiling identified differences in beta diversity between responders and non-responders, positively correlated with short-chain fatty acid producers (Parabacteriodes) and negatively with pathobionts (Escherichia/Shigella). Differential abundance analysis identified lower levels of Tyzzerella, Gemmiger, and Hungatella and higher levels of Turicibacter in vaccine responders. Total uraemic toxin burden and individual toxin concentrations did not differ between responders and hypo-responders (all p > 0.05). Stratification by low versus high/very high toxin burden groupings was not associated with response (p > 0.99). Conclusions: Differences in gut microbial composition were observed between vaccine responder groups, while uraemic toxin concentrations were not associated with vaccine responsiveness. These findings suggest gut microbiota composition may contribute to vaccine hypo-responsiveness in individuals receiving dialysis and warrant further investigation in larger mechanistic studies.

Insecticides in various formulations are indispensable for agricultural pest control and the prevention of vector-borne diseases. Piperonyl butoxide (PBO) is a synergist widely used to enhance the effectiveness of insecticides, notably pyrethroids, by inhibiting the detoxifying cytochrome P450 enzymes, thus reducing the capacity of insects to metabolize and resist insecticides. Recent studies have revealed an unexpectedly weak enhancement of pyrethroid efficacy by PBO, which may have serious implications for insect control. The underlying mechanism of this effect remains unclear. Here, we demonstrate that the PBO-induced inhibition of cytochrome P450 impedes the effect of deltamethrin by mainly affecting its interaction with the inactivated state of voltage-gated sodium channels (Nav). We describe a new octopamine-dependent regulatory mechanism involving Gαs, PKA, DARPP-32, and PP1-2A, which affect the cytochrome P450 conformation, thus limiting the effect of PBO and modulating the Nav gating. As a result, deltamethrin cannot reach its final binding site in the fenestration to exert its full effect. We confirmed in vivo that the octopamine level is elevated in insects under the treatment with a chemical stressor, which decreases the deltamethrin efficacy. Our findings reveal a novel adaptive mechanism that increases insect survival by reducing insecticide efficacy, underscoring the need to develop more effective formulations and technologies for pest and vector control.

In Croatia, the European Viper Venom Antiserum®, produced by the Institute of Immunology Zagreb, was the only antiserum used to treat Vipera ammodytes envenomation. When production of the Zagreb antivenom ceased, three other antivenoms, Viperfav®, BulBio®, and Viekvin®, replaced it in clinical practice at the Department of Infectious Diseases, University Hospital Split. This study includes 34 patients envenomed by Vipera ammodytes during the period between 2020 and 2025: 24 (71%) suffered grade 2a envenomation, nine (26%) grade 2b, and one grade 3 (severe envenomation). None were admitted to the Intensive Care Unit. All patients received antivenom: 16 received Viperfav®, 17 BulBio®, and one Viekvin®. All grade 2a patients were treated with a single dose of antivenom. Among grade 2b patients, four received one dose and two received two doses of Viperfav®, while one received one dose and two received two doses of BulBio®. The grade 3 patient received two doses of BulBio®. In all cases, treatment was successful and patients were discharged from hospital after an average of 3.97 days. Patients with pronounced neurotoxic signs did not require treatment with multiple doses of antivenom. All antivenoms proved effective. No adverse reactions or fatalities were observed.

Background: Coxsackievirus B2 (CVB2) causes a range of diseases, including hand, foot, and mouth disease; myocarditis; acute flaccid paralysis; meningitis; and encephalitis. However, no specific antiviral drugs or vaccines are currently available for CVB2. Methods: We used plaque purification, virus titre determination, and serial passaging to screen and identify an inactivated CVB2 vaccine candidate strain, KM31-C05, which exhibited high viral titres and good genetic stability. Comprehensive biological characterization of this candidate strain was performed, including phylogenetic analysis, virulence assessment in BALB/c mice, one-step growth curve analysis, optimization of the multiplicity of infection, as well as determination of viral load, pathological evaluation, and immunohistochemical analysis in tissues of BALB/c suckling mice post-challenge. An experimental inactivated vaccine was prepared using KM31-C05 to evaluate its immunogenicity and protective efficacy. Results: The viral titres of KM31-C05 reached 108 CCID50/mL. After 20 serial passages, only three amino acid mutations were identified (VP3-G165V, VP1-N84K, and VP1-D129N). Although the two VP1 mutations were located in surface-exposed loops, the strain maintained high neutralizing titres across passages, indicating good genetic stability. However, whether these sites affect virulence and replication requires further investigation. Phylogenetic analysis revealed that this strain belonged to genotype C, which is consistent with the strains circulating in mainland China in recent years. The experimental inactivated vaccine prepared from KM31-C05 induced effective neutralizing antibodies (1:128-1:256) in BALB/c mice and provided complete protection to suckling mice against lethal challenge with this CVB2 strain in maternal antibody protection experiments. Conclusions: KM31-C05 demonstrates potential as a CVB2 vaccine candidate in China and provides a theoretical basis for the development of a CVB2 vaccine.

Background/Objectives: Allergen immunotherapy (AIT), involving subcutaneous (SCIT) or sublingual (SLIT) administration of the culprit allergen, is the only treatment capable of modifying the natural course of allergic diseases, and provides lasting benefits in terms of symptom reduction and medication use. AIT for allergic rhinitis is acknowledged as safe and effective in both adults and children; however, no studies have comprehensively evaluated the safety and efficacy of AIT in these populations, integrating results from randomized controlled trials (RCTs) and real-world evidence (RWE). Methods: We evaluated data in the literature including studies from RCTs and RWE in which the safety and efficacy of AIT in both children and adults have been analyzed. A narrative literature search was conducted in PubMed up to January 2026 using the following keywords for the search string: "allergen immunotherapy," "AIT," "safety," "efficacy," "clinical outcome," and "clinical evaluation." Results: RCTs and meta-analyses showed that both SCIT and SLIT significantly reduced allergic symptoms and medication use and improved quality of life (QoL). Large SLIT tablet trials have confirmed its efficacy in adults and children, whereas RWE supports its effectiveness in broader populations. Safety data indicated that SCIT carries a small but higher risk of systemic reactions than SLIT, which mainly causes mild local effects. Conclusions: AIT was effective and safe for treating allergic rhinitis across RCT and RWE studies. Integrating RWE with RCT findings is essential for guideline development, particularly for capturing long-term outcomes and real-world applications.

Background: Disseminated coccidioidomycosis (DCM) often requires prolonged antifungal therapy (AFT). Real-world data on AFT duration in DCM are limited. We evaluated time to AFT discontinuation among patients with DCM in the United States clinical practice. Methods: This retrospective, longitudinal study used STATinMED data (2016-2024). Patients had ≥1 International Classification of Diseases, Tenth Revision (ICD-10) code for DCM (B38.3, B38.4, B38.7, B38.81) during January 2017-December 2023, ≥1 claim for a triazole or amphotericin B within 21 days of the DCM diagnosis (index date), and continuous medical/pharmacy coverage during the 6-month baseline period. Discontinuation was defined as a ≥21-day gap without AFT. Antifungal agent/formulation switches were not considered discontinuations unless accompanied by a qualifying gap. The Kaplan-Meier methods were used to estimate time to discontinuation. Results: We identified 991 patients with DCM. Median age was 52 years (IQR 36, 65); 60.0% were men. Most resided in California (42.8%) or Arizona (33.6%). Initial AFT consisted predominantly of triazoles (96.8%), primarily fluconazole (83.2%). Discontinuation occurred in 27.6%, 40.0%, 54.2%, and 68.0% of patients by 3, 6, 12, and 36 months. Median AFT duration was 9.9 months. Conclusions: In a large US claims cohort, there was substantial variability in AFT duration in routine practice. Many patients had AFT durations under the lower limit of guideline recommendations for DCM, suggesting potential under-treatment, though appropriate clinical justifications may have existed.