Search Results (6,245)

Polycyclic aromatic hydrocarbons (PAHs) are produced primarily by incomplete combustion of organic materials, including biomass burning, vehicle exhaust, and forest fires. Exposure to PAHs can induce reactive oxygen species (ROS) and oxidative stress, leading to lipid peroxidation and DNA damage. Biomass burning is a major environmental and public health problem in Chiang Mai province, containing particulate matter linked with respiratory and cardiovascular diseases. This prospective observational study aimed to evaluate the association between oxidative stress biomarkers and PAH exposure. A total of 152 participants comprised healthy controls (88), diabetes patients (35), hypertension patients (15) and diabetes + hypertension patients (14). Only participants aged more than 18 years were included. Participants who had acute respiratory infection or malignancies were excluded. This study was conducted in the pre-burning (December) and post-burning (May) periods by measuring biomarkers such as 1-OHP, MDA and 8-OHdG. Urinary 1-OHP increased significantly in the post-burning period from 0.21 ± 0.50 to 0.87 ± 1.25 μmol/mol creatinine (p < 0.001). Serum 8-OHdG increased significantly in all participants from 51.04 ± 24.90 to 66.08 ± 27.82 pg/mL (p < 0.001) and increased significantly in the diabetic and hypertension group. Serum MDA did not show any significant change post-burning (6.09 ± 3.71 to 6.00 ± 3.71 nmol/mL; p = 0.825), but MDA significantly decreased in the diabetic group (p = 0.017). 8-OHdG tended to increase in all clinical groups in the post-burning season compared to the pre-burning season, indicating oxidative DNA damage. 8-OHdG was found to be a sensitive biomarker of oxidative stress, suggesting its potential as an early indicator in haze season in vulnerable populations. Full article

Background/Objectives: Hypercapnic respiratory failure (HRF) is a serious complication of chronic obstructive pulmonary disease (COPD) and is associated with increased morbidity, mortality, and healthcare utilisation. National HRF trends among patients with COPD remain poorly characterised in Lithuania, and the knowledge of prehospital emergency-care professionals regarding oxygen therapy and hypercapnia has not been evaluated. Methods: This study comprised two components. First, a cross-sectional online survey assessed knowledge of COPD, hypercapnia, and oxygen therapy among prehospital emergency-care professionals (EMS physicians, emergency nurses, EMS paramedics, and paramedics); three questionnaire items whose designated correct answers could not be unambiguously supported were excluded from the knowledge score, and the original 10-item score was retained as a sensitivity analysis. Second, nationwide electronic health record data from the Lithuanian national health record system (ESPBI IS, 2020–2023) were analysed retrospectively: patients with COPD and concomitant chronic HRF were identified using ICD-10-AM diagnostic codes, and the number of patients with a recorded J96.11 diagnosis irrespective of underlying disease was obtained as a national denominator. Proportions are reported with 95% confidence intervals and temporal trends as absolute changes in percentage points; multivariable logistic regression was used to estimate odds ratios adjusted for age group and sex. Between-year differences were tested using the χ² test with Holm-adjusted pairwise comparisons, and the association between sex and chronic HRF was expressed as an odds ratio. All tests were two-sided, and p < 0.05 was considered significant. Results: Among the 65 prehospital emergency-care professionals surveyed, knowledge of hypercapnia was relatively high: 78.5% (95% CI 67.0–86.7) correctly defined it and 72.3% (95% CI 60.4–81.7) identified its symptoms, whereas 58.5% (95% CI 46.3–69.6) identified the recommended SpO₂ target range of 88–92%. Respondents answered a median of 5 of the 7 scored knowledge items correctly (IQR 4–6). Total knowledge scores differed by professional role (p = 0.034) but not by years of experience, sex, or frequency of COPD contact; the sensitivity analysis using the original 10-item score gave the same pattern (p = 0.006). In the national electronic health record data, the COPD population increased from 27,239 to 32,446 (+19.1%) between 2020 and 2023, while the number of COPD patients with a recorded chronic HRF diagnosis rose from 160 to 291 (+81.9%). The proportion rose from 0.59% (95% CI 0.50–0.69) to 0.90% (95% CI 0.80–1.01), an absolute increase of 0.31 percentage points (95% CI 0.17–0.45; risk ratio 1.53, 95% CI 1.26–1.85). Men had higher odds than women after adjustment for age (adjusted OR 1.55, 95% CI 1.28–1.88), and adjusted odds were lowest in patients aged 80 years or older. Across the four annual cross-sections, COPD accounted for 41.5% of patient-year observations with a recorded J96.11 diagnosis nationally. Conclusions: Knowledge of COPD, hypercapnia, and oxygen therapy varied among the prehospital emergency-care professionals surveyed, with one of the lowest proportions of correct responses observed for the recommended target oxygen saturation range. National electronic health record data showed an increase in the proportion of patients with COPD who had a recorded diagnosis of chronic HRF between 2020 and 2023. These components were analysed independently, and no relationship between professional knowledge and temporal trends in recorded diagnoses was assessed. The electronic health record findings support continued monitoring and recognition of chronic HRF in COPD, whereas the survey findings support further evaluation of targeted education on oxygen therapy in the prehospital setting. Full article

Colorectal cancer (CRC) remains a major global health concern. Marine by-products are increasingly recognized as promising sources of functional ingredients with diverse bio-activities. This study investigated the effects of sea cucumber viscera hydrolysates prepared by protease hydrolysis (SVH) and further fermented with Cordyceps militaris (FSVH) on cellular function and energy metabolism in HCT116 cells. Cell viability, apoptosis, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and Transwell assays. Cellular energy metabolism was assessed by measuring glucose uptake, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR). The results showed that SVH and FSVH exhibited distinct biological activity profiles in HCT116 cells. Both SVH and FSVH induced apoptosis and inhibited the migration and invasion of HCT116 cells. Both treatments affected glucose metabolism and mitochondrial respiratory function, including glucose uptake, lactate production, mitochondrial respiration, and glycolytic activity. SVH exhibited stronger inhibitory effects on glycolysis-related parameters, whereas FSVH showed greater effects on mitochondrial respiratory capacity. These findings indicate that C. militaris fermentation modified rather than simply enhanced the biological properties of sea cucumber viscera hydrolysates, resulting in distinct effects on cellular function and energy metabolism. This study highlights the potential application of sea cucumber viscera hydrolysates for the value-added utilization of marine processing by-products. Full article

Backgorund/Objectives: Respiratory diseases represent a substantial global health burden and require effective localised pulmonary delivery strategies, particularly for poorly water-soluble therapeutic molecules. Nanoparticle-based drug delivery systems, especially those manufactured using microfluidics, have emerged as promising approaches to overcome pulmonary barriers, enhance local drug retention, and reduce systemic side effects. Among these nanocarriers, solid lipid nanoparticles (SLNs) and solid hybrid nanoparticles (SHNs) combine biocompatibility with controlled release and improved formulation stability. Methods: In this study, SLNs and lipid–chitosan SHNs were developed using microfluidic technology as candidate platforms for pulmonary drug delivery, with Cyclosporine A (CyA) used as a model hydrophobic cyclic peptide. Nanocarriers were produced using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol as lipids, with low-molecular-weight chitosan incorporated to obtain hybrid systems. Physicochemical properties were evaluated using dynamic light scattering (DLS) and ζ potential measurements, while morphology and structural organisation were investigated using transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Results: The microfluidic approach enabled the production of nanoparticles with controlled sizes below 200 nm, narrow size distributions, and good reproducibility. In addition, the SHNs exhibited a positive surface charge, high encapsulation efficiency (~80%), and good colloidal and thermal stability. In vitro release studies showed an initial burst release followed by sustained CyA release, reaching approximately 94% cumulative release within 6 h. The Korsmeyer–Peppas model was used as the standard kinetic model. No blank nanoparticles were used as controls in the EE and release assay. Conclusions: Overall, these findings support further investigation of microfluidic-produced lipid and hybrid nanoparticles as candidate platforms for pulmonary drug delivery. Full article

Welding technology, extensively utilized in modern industry, poses significant health risks due to metal dust exposure, which can lead to respiratory discomfort, neurological issues, and an increased risk of lung cancer and pneumoconiosis. Enhancing ventilation within factory buildings has proven to be an economical approach to mitigating these risks. This study employs computational fluid dynamics (CFD) to model the airflow and dust transport within a large welding workshop measuring 300 m in length, 28 m in width, and 21 m in height. The impact of the exhaust-to-supply air ratio (ESR) and the height of the side exhaust port (SEP) on dust removal efficiency is investigated. Comparative analysis of transport dynamics between low-density aluminum alloy welding fume and high-density carbon steel welding fume reveals optimal dust exhaust designs. The study identifies two peaks in workshop air velocity at 0–2 m and 8–12 m above the ground, with the top exhaust port (TEP) outperforming the SEP in dust removal. An increased ESR accelerates the upward migration of welding fume, reducing lateral dispersion. An improperly set SEP height can lead to airflow short-circuiting or excessive lateral dispersion, hindering effective dust removal. Optimal SEP height for aluminum alloy and carbon steel dust are determined to be 5 m and 6 m, respectively. Full article

Air quality in equestrian facilities is an important factor affecting equine respiratory health. This study evaluated particulate matter (PM), gaseous pollutants, and microclimatic parameters in a stable, an indoor riding arena, and an outdoor riding arena, and estimated the potential inhaled dust dose in horses under different exposure scenarios. Nine independent measurements were conducted at a height of 1.5 m in three locations. Concentrations of PM₁, PM_2.5, PM₁₀, respirable dust, total dust, and selected gaseous pollutants were measured. Four exposure scenarios combined 18 or 20 h spent in the stable with 4 or 6 h spent in the indoor or outdoor riding arena. Measurements were performed during summer under normal operating conditions at a university equestrian centre in Slovakia. The outdoor riding arena exhibited the highest concentrations of all PM fractions, whereas the indoor riding arena showed the lowest values (p < 0.05). Ammonia concentrations were higher in the stable than in the indoor riding arena, while the remaining gaseous pollutants showed only minor differences between facilities. Spatial mapping identified localized areas of elevated PM_2.5 and PM₁₀ concentrations, and exposure modelling demonstrated higher estimated inhaled mass of total and respirable dust for scenarios involving outdoor training. The results indicate that particulate matter, rather than gaseous pollutants, was the main factor affecting air quality. Reducing dust generation through appropriate riding surface management, regular maintenance, and air quality monitoring may help minimize inhalation exposure and improve the respiratory environment for horses. Full article

The case of common ragweed (Ambrosia artemisiifolia) stands as a prime example of an invasive plant that links global change, biological invasion, aeroallergen exposure, and allergic airway disease. However, evidence remains fragmented across invasion biology, aerobiology, molecular allergology, and respiratory medicine. By separating plant occurrence, pollen abundance, molecular allergen dose, sensitisation, and airway disease, this review develops an integrated invasion–exposure–disease logic for interpreting ragweed-related health risk. We examine how climate change, land-use disturbance, repeated introductions, rapid adaptation, and air pollution influence plant distribution, flowering phenology, pollen production, airborne allergen load, and respiratory outcomes. Attention is given to Amb a 1 as the principal marker of genuine ragweed sensitisation, cross-reactivity with Artemisia and other weed pollens, allergen-bearing respirable particles, and the diagnostic limitations of extract-based immunoglobulin E (IgE) testing. The literature indicates that ragweed sensitisation follows a pronounced hotspot–gradient pattern in Europe, whereas patterns in other invaded regions remain more heterogeneous and incompletely characterised. Clinically relevant exposure depends not only on pollen concentration but also on airborne allergen load, pollen allergen potency, atmospheric transport, respirable particle fractions, meteorological conditions, and pollution. Ragweed-related airway disease is mediated by IgE-dependent type 2 immunity and amplified by epithelial danger signals, oxidative stress, protease activity, and innate immune pathways. Based on current evidence, we propose that an integrated surveillance framework linking plant distribution, pollen and airborne-allergen exposure, molecular sensitisation, symptoms, lung function, and asthma outcomes could strengthen risk forecasting, source attribution, prevention, and invasion control of the common ragweed. Full article

Water and wastewater workers encounter complex occupational exposures, but evidence on related injuries and adverse health outcomes remains fragmented. We systematically searched PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase on 23 April 2026 and synthesized evidence using a Population–Exposure–Outcome framework and PRISMA 2020. Two reviewers independently screened and extracted data. Methodological quality was evaluated with design-specific Joanna Briggs Institute tools, and certainty for prevention measures was assessed using a GRADE-informed narrative approach. Seventy studies published from 1940 to 2025 were included; most were cross-sectional. The most reproducible findings concerned respiratory effects from bioaerosols, endotoxins, and hydrogen sulfide, musculoskeletal morbidity (12-month low-back-pain prevalence up to 72.8%), and severe acute hazards during chemical handling and confined-space entry. Infectious findings, including hepatitis A/E, Helicobacter pylori, and intestinal parasites, were heterogeneous and particularly vulnerable to confounding by community background prevalence. Employment duration, inadequate personal protective equipment, insufficient training, and unsafe facility design amplified risk. Meta-analysis was precluded by heterogeneity, and confidence was limited by cross-sectional designs and inconsistent adjustment. The review was not registered and received no external funding. Engineering controls, confined-space safeguards, and task-specific protective equipment are priority measures, although intervention-effectiveness evidence remains low or very low certainty. Full article

Respiratory diseases in chickens are a major concern in poultry production, as they adversely affect animal health and production efficiency. Chicken vocalizations often contain important acoustic cues associated with respiratory conditions. However, conventional sound classification methods typically rely on predefined categories, limiting their ability to capture complex acoustic patterns. To address this limitation, this study introduces an audio captioning framework for the analysis of chicken respiratory sounds and proposes a model termed FeeCLAP for generating descriptive text from chicken vocalizations. The proposed model maps acoustic signals into natural language descriptions of sound quality, rhythm, and related attributes, thereby enabling semantic-level representation of vocal patterns. Built upon the baseline EnCLAP framework, a dataset of chicken respiratory sound descriptions with medically relevant semantic styles was constructed. An Acoustic Token Adapter (ATA) module was then introduced between discrete acoustic tokens and the text encoder to enhance the temporal modeling of acoustic features. In addition, a CLAP (Contrastive Language-Audio Pretraining)-aware semantic alignment mechanism was incorporated to improve consistency between acoustic representations and the semantic space. During inference, a CLAP-based similarity re-ranking strategy was further applied to improve the quality of generated descriptions. Experiments showed that FeeCLAP outperformed existing methods, achieving Consensus-based Image Description Evaluation (CIDEr), Semantic Propositional Image Caption Evaluation (SPICE), and SPIDEr scores of 0.423, 0.202, and 0.313, respectively, with generated descriptions approaching human-annotated references. Overall, the proposed approach demonstrated its effectiveness in generating semantic descriptions of chicken respiratory sounds under the experimental conditions used in this study. These findings suggest its potential to support respiratory health assessment in poultry; however, further validation under commercial poultry production conditions is required before the method can be considered a reliable tool for practical intelligent monitoring or early detection of respiratory abnormalities. Full article

Background: β-lactam/β-lactamase inhibitor combinations (BL/BLIs) and siderophore cephalosporin serve as critical polymyxin alternatives for carbapenem-resistant Pseudomonas aeruginosa (CRPA). However, systematic multicenter clinical data from China and the resistance mechanisms underlying non-susceptibility to these agents remain poorly defined. Methods: We collected 442 CRPA isolates from 10 hospitals across eight Chinese provinces (2017–2025), determined minimum inhibitory concentrations (MICs) for cefiderocol (FDC), ceftazidime–avibactam (CZA), imipenem–relebactam (IMR), and ceftolozane–tazobactam (CT) through broth microdilution, and performed whole-genome sequencing. Resistance genes, virulence factors, and sequence types (STs) were identified. A chromosomal co-selection score (eight non-mobile resistance genes) was constructed. Multivariable regression and receiver operating characteristic (ROC) analysis identified predictors of non-susceptibility. Results: Carbapenemase genes were detected in only 33 isolates (7.5%): metallo β lactamase (MBL) genes in 28, bla_KPC-2 in 2, and bla_{GES 5/14} in 3; the ST463 clone was absent. MBL producers were resistant to CZA, IMR, and CT (0–4% susceptible) but 100% susceptible to FDC. KPC 2 and GES producers were CZA-susceptible (100%) but IMR- and CT-resistant. Among 127 CZA non-susceptible isolates, 99 (78%) lacked carbapenemase genes; ST270 (from a single center) accounted for 64.6% of these. The chromosomal score independently predicted MIC (ρ: CT 0.64, FDC 0.59, IMR 0.50, CZA 0.25—largely attributable to ST270; all p < 0.001). ExoU positive isolates had lower MICs (FDC median 0.12 vs. 0.25 mg/L, p < 0.001). FDC remained active against 97.3% of all isolates and 100% of carbapenemase-positive ones. Genotype-based prediction yielded area under the ROC curve (AUC) values of 0.86 (CT) and 0.80 (CZA). Conclusions: Mechanisms other than acquired carbapenemases—consistent with chromosomal determinants—accounted for most non-susceptibility in this predominantly northern Chinese respiratory tract CRPA collection. Carbapenemase types determine distinct drug susceptibility patterns. Routine carbapenemase detection fails to identify most CZA-resistant strains. FDC retained the broadest in vitro activity and is a reliable therapeutic option pending clinical outcome data, and ST270-associated resistance deserves continuous surveillance. Full article

Human respiratory viruses represent a major global health burden, causing millions of severe infections and deaths annually. Despite the central role of vaccines in prevention, their limitations, such as incomplete coverage, waning immunity, and vulnerability to viral evolution, underscore the urgent need for effective antiviral therapeutics. This review examines the principles and applications of target-based antiviral drug development against human respiratory viruses, emphasizing the identification and exploitation of conserved viral and host targets. Key viral proteins, including RNA-dependent RNA polymerases, proteases, and fusion glycoproteins, are analyzed across major virus families such as coronaviruses, paramyxoviruses, and adenoviruses, highlighting their structural features, functional constraints, and therapeutic potential. We further explore the integration of high-throughput screening and rational drug design, supported by advances in structural biology, cryo-electron microscopy, and computational approaches, including artificial intelligence-driven drug discovery. These methodologies collectively enhance the precision and efficiency of antiviral development. However, significant challenges remain, particularly the conflict between viral mutation and target conservation, the rapid emergence of drug resistance, and the safety limitations of host-targeted therapies. Finally, we discuss emerging strategies to overcome these barriers, including combination therapies and the development of broad-spectrum antivirals targeting conserved molecular mechanisms. This paper highlights a framework for the rational design of durable antiviral interventions capable of addressing both existing and emerging respiratory viral threats. Full article

Background: Long-acting monoclonal antibodies have become an important strategy for preventing respiratory syncytial virus (RSV) disease in infants. Nirsevimab is the first product for which substantial post-licensure implementation data are available, whereas real-world evidence on clesrovimab remains limited. Although nirsevimab has demonstrated high efficacy, its uptake varies considerably across countries, healthcare systems, delivery settings, and population subgroups. This World Association for Infectious Diseases and Immunological Disorders (WAidid) consensus document examines the policy, organizational, economic, and equity-related determinants that shape real-world implementation of long-acting monoclonal antibodies for infant RSV prevention. Methods: This study was conducted as a structured narrative review and WAidid expert consensus document. A structured literature search was performed in PubMed and Embase for English-language publications relevant to nirsevimab uptake and implementation, complemented by targeted review of surveillance reports, policy documents, and public health guidance from the ECDC, UKHSA, and CDC, as well as reference lists of selected publications. Eligible sources included observational and real-world implementation studies, systematic reviews and meta-analyses, economic evaluations, guidelines, policy statements, surveillance reports, and relevant narrative reviews. Evidence was synthesized qualitatively according to policy frameworks, financing and reimbursement, delivery pathways, demographic and socioeconomic determinants, and healthcare-system factors influencing uptake. No statistical software was used because no quantitative re-analysis or meta-analysis was performed. Results: Nirsevimab uptake was strongly influenced by national RSV prevention policies, particularly whether countries adopted universal infant monoclonal antibody programs, maternal RSV vaccination strategies, dual maternal–infant approaches, or targeted risk-based models. Universal, publicly funded programs integrated into neonatal care achieved the highest and most homogeneous coverage, especially when administration occurred before hospital discharge and was supported by registry-based recall systems for infants born outside the RSV season. In contrast, fragmented, outpatient-only, insurance-dependent, or partially reimbursed models were associated with lower, delayed, or more variable uptake. Additional determinants included product cost, reimbursement pathways, provider practices, caregiver awareness and health literacy, insurance status, income, race and ethnicity, geographic deprivation, and access to primary pediatric care. Most available evidence comes from high-income countries, limiting generalizability to low- and middle-income settings, where RSV burden is greatest and implementation constraints may differ. Conclusions: Successful implementation of long-acting monoclonal antibodies for infant RSV prevention requires more than regulatory approval and demonstrated efficacy. Equitable uptake depends on clear national recommendations, sustainable public financing, reliable product supply, integration into neonatal and primary pediatric care, proactive identification and recall of eligible infants, and targeted strategies to reduce socioeconomic and geographic disparities. Although many determinants identified in high-income settings are likely relevant globally, their feasibility, relative importance, and impact require dedicated evaluation in low- and middle-income countries. Full article

Background: Children with Down syndrome often have co-occurring physical conditions affecting well-being, and respiratory issues remain a leading cause of hospitalization and death among people with Down syndrome. Parents of children with Down syndrome experience stressors associated with respiratory illness and challenges navigating healthcare access. No prior qualitative study has examined parental perspectives on respiratory health specifically among children with Down syndrome. Identifying parental concerns can help in the development of strategies to mitigate respiratory ailments in children with Down syndrome. Methods: One-hour, semi-structured interviews were conducted among 24 families of children with Down syndrome to understand respiratory concerns. Findings were identified through codebook thematic analysis. Results: The themes identified included persistent concerns about respiratory health, repeated impact from acute and chronic respiratory issues, a rapid and unexpected decline in health during respiratory illness, insurance coverage concerns, and a lack of confidence in assessing air quality which could impact respiratory health. Conclusions: Insights gained from interviews of parents of children with Down syndrome can help policy makers identify opportunities to prevent and mitigate respiratory health problems. Findings underscore the importance of clinician responsiveness to parental concern about rapid deterioration and suggest that insurance coverage policies for this high-risk population warrant further research and policy consideration. Full article

Microplastics and nanoplastics (MNPs) have emerged as widespread environmental contaminants, with increasing evidence suggesting that chronic exposure may adversely affect human health. Experimental and emerging human studies indicate that MNPs can interact with multiple biological systems and trigger a range of mechanisms, including oxidative stress, mitochondrial dysfunction, cellular injury, barrier disruption, and immune and inflammatory responses. These effects may involve direct interactions with tissues and cells as well as indirect pathways, including alterations in gut microbial and intestinal homeostasis. In turn, persistent inflammatory and metabolic disturbances may contribute to tissue dysfunction and the development or progression of chronic diseases. This narrative review summarizes current evidence on the biological effects of MNP exposure, focusing on the mechanisms linking environmental exposure to chronic inflammation and disease. We discuss their potential involvement in cardiovascular, liver, kidney, respiratory, and neurological diseases, while highlighting the emerging role of the gut microbiota and intestinal barrier as potential modulators of these effects. Given the limitations of current human evidence and the heterogeneity of experimental models, we also discuss major knowledge gaps and the need for further mechanistic and epidemiological studies to clarify the clinical relevance of chronic MNPs exposure. Full article

Highly pathogenic avian influenza H5N1 virus (H5N1 HPAIV) has long circulated in wild waterfowl and poultry and continues to cross species barriers, posing sustained threats to livestock productivity and public health. The 2024 outbreak of H5N1 HPAIV in dairy cattle across multiple U.S. states represents the first recognized large-scale transmission event of this virus in ruminants, reshaping our understanding of its host range and transmission ecology. This review summarizes recent advances in the epidemiology, virological characteristics, transmission, pathogenesis, surveillance, and control of dairy cattle-associated H5N1. The initial multistate outbreak was dominated by clade 2.3.4.4b genotype B3.13, whereas subsequent independent introductions of genotype D1.1 demonstrated that repeated avian-to-cattle spillover also contributes to the evolving outbreak ecology. A defining feature is efficient replication in bovine mammary epithelial cells, resulting in high viral titers in milk, supporting milk-associated exposure and milking-related contamination as plausible components of transmission, although the relative contribution of different routes remains unresolved. Infected cattle typically show reduced feed intake, a marked decline in milk production, abnormal milk, and mild systemic signs, whereas severe respiratory disease and mortality are uncommon. Mutations such as PB2-M631L, PA-K497R, and changes in NP and NS1 may promote replication and immune evasion in bovine cells, while genotype-specific PB2 adaptations highlight the potential for further mammalian adaptation. Human infections reported to date have been predominantly mild and associated with occupational exposure, with no evidence of sustained human-to-human transmission. Experimental vaccine studies have begun to demonstrate immunogenicity in cattle, although protection against mammary infection, viral shedding, and transmission remains to be established. Future priorities include clarifying mammary tropism and transmission dynamics, while strengthening diagnostics, farm biosecurity, vaccination, evaluating cattle vaccination strategies, and integrated One Health surveillance. Full article