Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry; it is a globally prevalent multifactorial infection primarily caused by viral and bacterial coinfections. In China, Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens associated with BRD. Our previous study attempted to combine the two vaccines and conducted a preliminary investigation of their optimal antigenic ratios. Based on this premise, the research extended its investigation by administering varying vaccine doses in a rabbit model to identify the most effective immunization dosage. After immunization, all rabbits in other immunization dose groups had a normal rectal temperature without obvious clinical symptoms. Furthermore, assays performed on the samples collected from immunized rabbits indicated that there were increased humoral and cellular immunological reactions. Moreover, the histological analysis of the lungs showed that immunized rabbits had more intact lung tissue than their unimmunized counterparts after the challenge. Additionally, there appears to be a positive correlation between the protective efficacy and the immunization dose. In conclusion, the different immunization doses of the attenuated and marker M. bovis HB150 and BoHV-1 gG-/tk- combined vaccine were clinically safe in rabbits; the mix of 2.0 × 108 CFU of M. bovis HB150 and 2.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its highest humoral and cellular immune responses and a more complete morphology of the lung tissue compared with others. These findings determined the optimal immunization dose of the attenuated and marker M. bovis HB150 and BoHV-1 gG-/tk- combined vaccine, laying a foundation for its clinical application.

Despite the fact that pneumonia remains a leading cause of mortality and morbidity in pre-weaned calves, relatively little is known regarding the effects of the concurrent administration of intranasal pneumonia virus vaccines, particularly in calves with high levels of maternally derived antibodies. The objective of this study was to use a cohort of 40 dairy and dairy-beef female and male calves (27 females and 13 males) to determine serological responses to concurrent administration at 3 weeks of age (22 ± 4.85 days) of two commercially available intranasal (IN) vaccines for the viruses: bovine respiratory syncytial virus (BRSV), bovine herpes virus 1 (BoHV-1), and parainfluenza-3-virus (PI3-V). The study groups were as follows: (i) Bovilis IBR Marker Live only® (IO), (ii) Bovilis INtranasal RSP Live® only (RPO), (iii) Concurrent vaccination with Bovilis IBR Marker Live® & Bovilis Intranasal RSP Live® (CV), and (iv) a control group of non-vaccinated calves (CONT). The calves\' serological response post-IN vaccination, clinical health scores, rectal temperatures, and weights were measured. Data were analyzed in SAS using mixed models and logistic regression. The CV calves had an average daily weight gain (ADG) of 0.74 (±0.02) kg, which was similar to CONT (0.77 ± 0.02 kg). Despite no significant differences in the antibody levels between study groups 3 weeks post-IN vaccination, following the administration of subsequent parenteral injections in the form of Bovilis Bovipast RSP®(antigens; inactivated BRSV, inactivated PI3-V, inactivated Mannheimia haemolytica) and Bovilis IBR Marker Live®, the antibody levels of the BRSV and PI3-V increased in both the CV and RPO study groups. Concurrent vaccination resulted in no increase in fever and no difference in health scores when compared to CONT.

Despite significant advances in vaccination strategies and antibiotic therapy, bovine respiratory disease (BRD) continues to be the leading disease affecting the global cattle industry. The etiology of BRD is complex, often involving multiple microbial agents, which lead to intricate interactions between the host immune system and pathogens during various beef production stages. These interactions present environmental, social, and geographical challenges. Accurate diagnosis is essential for effective disease management. Nevertheless, correct identification of BRD cases remains a daunting challenge for animal health technicians in feedlots. In response to current regulations, there is a growing interest in refining clinical diagnoses of BRD to curb the overuse of antimicrobials. This shift marks a pivotal first step toward establishing a structured diagnostic framework for this disease. This review article provides an update on recent developments and future perspectives in clinical diagnostics and prognostic techniques for BRD, assessing their benefits and limitations. The methods discussed include the evaluation of clinical signs and animal behavior, biomarker analysis, molecular diagnostics, ultrasound imaging, and prognostic modeling. While some techniques show promise as standalone diagnostics, it is likely that a multifaceted approach-leveraging a combination of these methods-will yield the most accurate diagnosis of BRD.

Bovine respiratory disease (BRD) is a global prevalent multifactorial infection primarily caused by viral and bacterial coinfections. In China, Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the predominant pathogens associated with BRD. Our previous study involved the development of attenuated M. bovis HB150 and BoHV-1 gG-/tk- vaccine strains, which were thoroughly assessed for their safety profiles and protective efficacy in cattle. In this study, we applied a combination of vaccines in varying ratios and used a rabbit model to determine the safety and protective efficacy. We used PCR/RT-PCR to detect the postimmunization and challenge shedding of M. bovis and BoHV-1. Additionally, we measured antibody titers and the expression of IFN-β and TNF-α to evaluate the humoral and cellular immune responses, respectively. Furthermore, we performed a histopathological analysis to assess lung damage. Our study provides evidence of the safety and effectiveness of the bivalent M. bovis-BoHV-1 vaccine in rabbits, particularly when applying a combination of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 of the BoHV-1 gG-/tk- strain. The bivalent vaccine significantly enhanced both the long-term antibody immune response and cellular protection against the M. bovis and BoHV-1 challenge. These findings provide a valuable model for the potential application in cattle.

NUT midline carcinoma is a rare malignancy most commonly seen in adolescents and young adults. The disease presents most often in the lung or head and neck area but can be seen occasionally elsewhere. The diagnosis can be difficult and requires a high degree of suspicion with demonstration of the classic fusion rearrangement mutation of the NUTM1 gene with one of a variety of partners by immunohistochemistry, fluorescent in situ hybridization, or genomic analysis. Survival is usually only a number of months with few long-term survivors. Here we report one of the longest-known survivors of this disease treated with surgery and radiation without additional therapy. Systemic treatment approaches including the use of chemotherapy and BET and histone deacetylase inhibitors have yielded modest results. Further studies of these, as well as p300 and CDK9 inhibitors and combinations of BET inhibitors with chemotherapy or CDK 4/6 inhibitors, are being evaluated. Recent reports suggest there may be a role for immune checkpoint inhibitors, even in the absence of high tumor mutation burden or PD-L1 positivity. RNA sequencing of this patient\'s tumor demonstrated overexpression of multiple potentially targetable genes. Given the altered transcription that results from the causative mutation multi-omic evaluation of these tumors may uncover druggable targets for treatment.

UNASSIGNED: Bovine respiratory disease (BRD) has a significant impact on the health and welfare of dairy calves. It can result in increased antimicrobial usage, decreased growth rate and reduced future productivity. There is no gold standard antemortem diagnostic test for BRD in calves and no estimates of the prevalence of respiratory disease in seasonal calving dairy herds.
UNASSIGNED: To estimate BRD prevalence in seasonal calving dairy herds in Ireland, 40 dairy farms were recruited and each farm was visited once during one of two calving seasons (spring 2020 & spring 2021). At that visit the prevalence of BRD in 20 calves between 4 and 6 weeks of age was determined using thoracic ultrasound score (≥3) and the Wisconsin respiratory scoring system (≥5). Hierarchical Bayesian latent class analysis was used to estimate the calf-level true prevalence of BRD, and the within-herd prevalence distribution, accounting for the imperfect nature of both diagnostic tests.
UNASSIGNED: In total, 787 calves were examined, of which 58 (7.4%) had BRD as defined by a Wisconsin respiratory score ≥5 only, 37 (4.7%) had BRD as defined by a thoracic ultrasound score of ≥3 only and 14 (1.8%) calves had BRD based on both thoracic ultrasound and clinical scoring. The primary model assumed both tests were independent and used informed priors for test characteristics. Using this model the true prevalence of BRD was estimated as 4%, 95% Bayesian credible interval (BCI) (1%, 8%). This prevalence estimate is lower or similar to those found in other dairy production systems. Median within herd prevalence varied from 0 to 22%. The prevalence estimate was not sensitive to whether the model was constructed with the tests considered conditionally dependent or independent. When the case definition for thoracic ultrasound was changed to a score ≥2, the prevalence estimate increased to 15% (95% BCI: 6%, 27%).
UNASSIGNED: The prevalence of calf respiratory disease, however defined, was low, but highly variable, in these seasonal calving dairy herds.

UNASSIGNED: Bovine Respiratory Disease (BRD) is a leading cause of morbidity and mortality in preweaned dairy calves. Early detection and therefore treatment are essential to minimize animal welfare concerns, particularly given that recent research also demonstrates that BRD is painful. Veterinarians are essential to ensuring calves with BRD receive appropriate treatment, but little to no research exists regarding veterinarians\' perspectives about BRD detection and treatment in dairy calves. This is a critical step to determine education and outreach needs that can target BRD treatment to improve calf welfare. Thus, the objectives of the current study were to describe US veterinarians\' current detection methods and treatment practices for BRD in preweaned dairy calves, understand veterinarians\' rationale for treatment decisions, and identify gaps in knowledge regarding treatment and management of calf BRD.
UNASSIGNED: An online survey was sent to two veterinarian-focused list-serves and newsletter. Final responses (n = 47) were analyzed using qualitative and quantitative analyses.
UNASSIGNED: On-farm necropsy was the diagnostic tool most considered \"extremely important\" (26, 55.3%). All veterinarians indicated that BRD was at least mildly painful. However, only 53% of veterinarians (n = 25) assess pain in preweaned calves with BRD in order to make treatment decisions. Furthermore, of the veterinarians that assessed pain, 40% (n = 10) reported that their knowledge of pain assessment and treatment was adequate, but most (n = 24) considered a calf\'s pain-level at least \"moderately important\" to make BRD treatment decisions. The most important ancillary therapy for antimicrobials were NSAIDs (21, 44.7%). The ancillary therapy most often considered \"extremely important\" for treating BRD was NSAIDs. Qualitative analysis identified the following as factors that influenced veterinarians\' willingness to provide analgesia: the farm\'s willingness to administer drugs, clinical signs, perceived severity of pain, the need for anti-inflammatories, and the presence of fever and comorbidities.
UNASSIGNED: This study included a small sample size and an extremely low response rate; results should therefore be interpreted with caution. Despite this limitation, important gaps in knowledge were identified, including pain assessment and consideration when making treatment decisions, and diagnostic tools. Addressing these needs in future research and outreach efforts could help ensure appropriate and timely treatment of calf BRD, including pain mitigation.

Bovine herpesvirus 1 (BoHV-1), is associated with several clinical syndromes in cattle, among which bovine respiratory disease (BRD) is of particular significance. Despite the importance of the disease, there is a lack of information on the molecular response to infection via experimental challenge with BoHV-1. The objective of this study was to investigate the whole-blood transcriptome of dairy calves experimentally challenged with BoHV-1. A secondary objective was to compare the gene expression results between two separate BRD pathogens using data from a similar challenge study with BRSV. Holstein-Friesian calves (mean age (SD) = 149.2 (23.8) days; mean weight (SD) = 174.6 (21.3) kg) were either administered BoHV-1 inoculate (1 × 107/mL × 8.5 mL) (n = 12) or were mock challenged with sterile phosphate buffered saline (n = 6). Clinical signs were recorded daily from day (d) -1 to d 6 (post-challenge), and whole blood was collected in Tempus RNA tubes on d six post-challenge for RNA-sequencing. There were 488 differentially expressed (DE) genes (p < 0.05, False Discovery rate (FDR) < 0.10, fold change ≥2) between the two treatments. Enriched KEGG pathways (p < 0.05, FDR <0.05); included Influenza A, Cytokine-cytokine receptor interaction and NOD-like receptor signalling. Significant gene ontology terms (p < 0.05, FDR <0.05) included defence response to virus and inflammatory response. Genes that are highly DE in key pathways are potential therapeutic targets for the treatment of BoHV-1 infection. A comparison to data from a similar study with BRSV identified both similarities and differences in the immune response to differing BRD pathogens.

Bovine respiratory disease (BRD) is considered a major cause of morbidity and mortality in young calves and is caused by a range of infectious agents, including viruses and bacteria. This study aimed to determine the frequency of viral and bacterial pathogens detected in calves with BRD from high-production dairy cattle herds and to perform the molecular characterization of N and S1 genes in identified bovine coronavirus (BCoV) strains. Nasal swabs were collected from 166 heifer calves, namely, 85 symptomatic and 81 asymptomatic calves aged between 5 and 90 days, from 10 dairy cattle herds. Nasal swabs were evaluated using molecular techniques for the identification of viruses (BCoV, bovine alphaherpesvirus 1, bovine viral diarrhea virus, bovine parainfluenza virus 3, and bovine respiratory syncytial virus) and bacteria (Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, and Mycoplasma bovis). In addition, five and two BCoV-positive samples were submitted to N and S1 gene amplification and nucleotide sequencing, respectively. The frequency of diagnosis of BCoV was higher (56%, 93/166) than the frequency of P. multocida (39.8%, 66/166) and M. haemolytica (33.1%, 55/166). The three microorganisms were identified in the calves of symptomatic and asymptomatic heifer calve groups. All other pathogens included in the analyses were negative. In the phylogenetic analysis of the S1 gene, the Brazilian strains formed a new branch, suggesting a new genotype, called # 15; from the N gene, the strains identified here belonged to cluster II. This study describes high rates of BCoV, P. multocida, and M. haemolytica in heifer calves from high-production dairy cattle herds with BRD. Additionally, the molecular characterization provides evidence that the circulating BCoV strains are ancestrally different from the prototype vaccine strains and even different BCoV strains previously described in Brazil.