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Abstract Nocturnal scratch is one major factor leading to impaired quality of life in atopic dermatitis (AD) patients. Therefore, objectively quantifying nocturnal scratch events aids in assessing the disease state, treatment effect, and AD patients’ quality of life. In this paper, we describe the use of actigraphy, highly predictive topological features, and a model-ensembling approach to develop an assessment of nocturnal scratch events by measuring scratch duration and intensity. Our assessment is tested in a clinical setting against the ground truth obtained from video recordings. The new approach addresses unmet challenges in existing studies, such as the lack of generalizability to real-world applications, the failure to capture finger scratches, and the limitations in the evaluation due to imbalanced data in the current literature. Furthermore, the performance evaluation shows agreement between derived digital endpoints and the video annotation ground truth, as well as patient-reported outcomes, which demonstrated the validity of the new assessment of nocturnal scratch.

Abstract The diagnostic performance of porcine epidemic diarrhea virus (PEDV) IgG and IgA ELISAs was evaluated using paired serum and meat juice samples collected from PEDV-negative (n = 50) and PEDV-inoculated pigs (n = 87). Serum samples were tested by PEDV (IgG, IgA) ELISAs using a procedure performed routinely at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were tested using PEDV serum IgG and IgA ELISA procedures as routinely performed at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were diluted 1:50 and conjugate concentrations were 1/20,000 for IgG and 1/3000 for IgA. Meat juice samples were tested using the serum PEDV IgG and IgA ELISAs, with modifications, i.e., meat juice samples were diluted 1:25 and conjugate concentrations were 1/40,000 for IgG and 1/10,000 for IgA. Receiver operator characteristic (ROC) curve analyses were used to estimate diagnostic sensitivities and specificities over a range of sample-to-positive (S/P) cutoffs. Consistent with previous reports, this study showed that the PEDV IgG and IgA meat juice ELISAs provided excellent diagnostic performance and suggest that meat juice recovered from samples collected at slaughter could be used in routine PEDV surveillance.

African swine fever virus is transmissible through animal consumption of contaminated feed. To determine virus survival during transoceanic shipping, we calculated the half-life of the virus in 9 feed ingredients exposed to 30-day shipment conditions. Half-lives ranged from 9.6 to 14.2 days, indicating that the feed matrix environment promotes virus stability.

The causal effect of an exposure on an outcome of interest in an observational study cannot be estimated directly if the confounding variables are not controlled. Many approaches are available for estimating the causal effect of an exposure. In this manuscript, we demonstrate the advantages associated with using inverse probability weighting (IPW) and doubly robust estimation of the odds ratio in terms of reduced bias. IPW approach can be used to adjust for confounding variables and provide unbiased estimates of the exposure's causal effect. For cluster-structured data, as is common in animal populations, inverse conditional probability weighting (ICPW) approach can provide a robust estimation of the causal effect. Doubly robust estimation can provide a robust method even when the specification of the model form is uncertain. In this paper, the usage of IPW, ICPW, and doubly robust approaches are illustrated with a subset of data with complete covariates from the Australian-based National Bovine Respiratory Disease Initiative as well as simulated data. We evaluate the causal effect of prior bovine viral diarrhea exposure on bovine respiratory disease in feedlot cattle. The results show that the IPW, ICPW and doubly robust approaches would provide a more accurate estimation of the exposure effect than the traditional outcome regression model, and doubly robust approaches are the most preferable overall.

ABSTRACT This study compared the performances of three commercial transmissible gastroenteritis virus/porcine respiratory coronavirus (TGEV/PRCV) blocking enzyme-linked immunosorbent assays (ELISAs) using serum samples (n = 528) collected over a 49-day observation period from pigs inoculated with TGEV strain Purdue (n = 12), TGEV strain Miller (n = 12), PRCV (n = 12), or with virus-free culture medium (n = 12). ELISA results were evaluated both with “suspect” results interpreted as positive and then as negative. All commercial kits showed excellent diagnostic specificity (99 to 100%) when testing samples from pigs inoculated with virus-free culture medium. However, analyses revealed differences between the kits in diagnostic sensitivity (percent TGEV- or PRCV-seropositive pigs), and all kits showed significant (P

[This corrects the article DOI: 10.1371/journal.pone.0194509.].

[This corrects the article DOI: 10.1371/journal.pone.0194509.].

The goal of this study was to evaluate survival of important viral pathogens of livestock in animal feed ingredients imported daily into the United States under simulated transboundary conditions. Eleven viruses were selected based on global significance and impact to the livestock industry, including Foot and Mouth Disease Virus (FMDV), Classical Swine Fever Virus (CSFV), African Swine Fever Virus (ASFV), Influenza A Virus of Swine (IAV-S), Pseudorabies virus (PRV), Nipah Virus (NiV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Swine Vesicular Disease Virus (SVDV), Vesicular Stomatitis Virus (VSV), Porcine Circovirus Type 2 (PCV2) and Vesicular Exanthema of Swine Virus (VESV). Surrogate viruses with similar genetic and physical properties were used for 6 viruses. Surrogates belonged to the same virus families as target pathogens, and included Senecavirus A (SVA) for FMDV, Bovine Viral Diarrhea Virus (BVDV) for CSFV, Bovine Herpesvirus Type 1 (BHV-1) for PRV, Canine Distemper Virus (CDV) for NiV, Porcine Sapelovirus (PSV) for SVDV and Feline Calicivirus (FCV) for VESV. For the remaining target viruses, actual pathogens were used. Virus survival was evaluated using Trans-Pacific or Trans-Atlantic transboundary models involving representative feed ingredients, transport times and environmental conditions, with samples tested by PCR, VI and/or swine bioassay. SVA (representing FMDV), FCV (representing VESV), BHV-1 (representing PRV), PRRSV, PSV (representing SVDV), ASFV and PCV2 maintained infectivity during transport, while BVDV (representing CSFV), VSV, CDV (representing NiV) and IAV-S did not. Notably, more viruses survived in conventional soybean meal, lysine hydrochloride, choline chloride, vitamin D and pork sausage casings. These results support published data on transboundary risk of PEDV in feed, demonstrate survival of certain viruses in specific feed ingredients ("high-risk combinations") under conditions simulating transport between continents and provide further evidence that contaminated feed ingredients may represent a risk for transport of pathogens at domestic and global levels.

Abstract Background The clinical implication of Ras/Raf/ERK pathway activity in breast cancer tissue and its association with response to chemotherapy is controversial. We aimed to explore the value of p90RSK phosphorylation, a downstram molecule of the pathway, in predicting chemotherapy response in breast cancer. Methods The expression of phosphorylated p90RSK (phospho-p90RSK) and chemotherapy response was measured in 11 breast cancer cell lines and 21 breast cancer tissues. The predictive value of phospho-p90RSK was validated in core needle biopsy specimens of 112 locally advanced breast cancer patients who received anthracycline and taxane-based neoadjuvant chemotherapy. Results In 11 breast cancer cell lines, the relative expression of phospho-p90RSK was inversely correlated with cell survival after doxorubicin treatment (p = 0.021). Similar association was observed in fresh tissues from 21 breast cancer patients in terms of clinical response. In paraffin-embedded, formalin-fixed tissues from core needle biopsy tissues from 112 patients, positive phospho-p90RSK expression was associated with greater tumor shrinkage and smaller post-chemotherapy tumor size. The association between phospho-p90RSK expression and chemotherapy response was more evident in estrogen receptor(ER)-positive tumors. The expression of phosphor-p90RSK did not show a significant relationship with the incidence of pCR. P90RSK silencing using siRNA did not affect the cancer cell’s response to doxorubicin, and the expression of phospho-p90RSK was highly correlated with other Ras/Raf/ERK pathway activation. Conclusion Our results suggest that phospho-p90RSK expression, which reflects the tumor’s Ras/Raf/ERK/p90RSK pathway activation can be a potential predictive marker for chemotherapy response in ER-positive breast cancer which needs further independent validation.

Abstract Introduction Disease progression of ankylosing spondylitis has been considered irreversible. However, we report a case of spontaneous regression of syndesmophyte development following allogeneic peripheral blood stem cell transplantation in a patient with acute myeloid leukemia, who was also diagnosed as having ankylosing spondylitis. To the best of our knowledge, this is the first case report presenting the partial radiologic regression of syndesmophytes. Case presentation A 39-year-old man with active ankylosing spondylitis achieved clinical remission and partial radiological regression of cervical spine syndesmophytes following a peripheral blood stem cell transplantation for acute myeloid leukemia. Our patient received an allogeneic peripheral blood stem cell transplantation following a pre-transplantation conditioning regimen of total body irradiation and cyclophosphamide. The donor was a human leukocyte antigen-matched 29-year-old man. Our patient has remained asymptomatic and has received no medication for ankylosing spondylitis for nearly three years. Conclusions Several explanations are proposed for the regression of syndesmophytes and clinical improvement in active ankylosing spondylitis observed in our patient, including changes in bone remodeling and immune reconstitution following stem cell transplantation, the effect of immunosuppressive agents, or fluctuation in the natural course of ankylosing spondylitis although further studies are required. The regression of syndesmophytes in ankylosing spondylitis in this case raises the possibility that stem cell transplantation might contribute to the development of a novel therapeutic strategy for treatment of the disease.

Background: Rheumatoid arthritis (RA) and prolonged high-dose glucocorticoid (GC) treatment are established risk factors for osteoporosis. Objectives: In this study, we aimed to evaluate the therapeutic efficacy of denosumab according to the GC dose considered to increase the risk of glucocorticoid-induced osteoporosis (GIOP) in patients with RA. Design: A retrospective analysis of collected data on RA patients with osteoporosis starting denosumab. Methods: We included 418 patients with RA who were started on denosumab therapy and categorized them into those with and without GC intake ⩾2.5 mg/day for >3 months. The T -score and areal bone mineral density (aBMD) at the lumbar spine, total hip, and femur neck, as well as serum bone turnover markers, were measured at baseline and 12 months. We performed between-group and within-group comparisons of the BMD values at baseline and at 12 months. Results: Denosumab significantly increased the T -scores and aBMD at the lumbar spine, total hip, and femur neck after 12 months, regardless of GC intake. However, apart from the T -score at the lumbar spine, the other parameters did not show significant between-group differences. Similarly, in patients with anti-cyclic citrullinated peptide (CCP) antibody positivity or those treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), although there were significant increases in the T -score and areal BMD at all sites in both groups, there were no significant between-group differences. Conclusion: Our findings suggest that the GC dose considered to increase the risk of GIOP did not significantly attenuate the therapeutic efficacy of denosumab in RA patients, including those positive for anti-CCP antibodies and users of biologic or targeted synthetic DMARDs. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to investigate the insufficiently understood differences in the immune system between anti-citrullinated peptide antibody (ACPA)-positive (ACPA+) and ACPA-negative (ACPA-) early rheumatoid arthritis (eRA) patients. Methods: We performed multiple cytokine assays using sera from drug-naïve ACPA+ and ACPA- eRA patients. Additionally, we conducted single-cell RNA sequencing of CD45+ cells from peripheral blood samples to analyze and compare the distribution and functional characteristics of the cell subsets based on the ACPA status. Results: Serum concentrations of interferon-γ (IFN-γ) and interleukin (IL)-12 were higher in ACPA+ eRA than in ACPA- eRA. Single-cell transcriptome analysis of 37,318 cells identified 17 distinct cell types and revealed the expansion of IL1B+ proinflammatory monocytes, IL7R+ T cells, and CD8+ CCL4+ T cells in ACPA+ eRA. Furthermore, we observed an enrichment of IFN-γ response genes in nearly all monocytes and T cells of ACPA+ eRA subsets. Heightened interactions between IFN-γ and IFN-γ receptors were observed in ACPA+ eRA, particularly between monocytes and T cells. We examined IFITM2 and IFITM3 as potential key markers in ACPA+ eRA given their pronounced upregulation and association with the IFN response. Specifically, the expression of these genes was elevated in IL1B+ proinflammatory monocytes (likely M1 monocytes), correlating with serum IFN-γ levels. Discussion: Compared to ACPA- eRA, ACPA+ eRA showed higher serum IFN-γ and IL-12 levels, upregulated IFN-γ response genes, and enhanced IFN-γ-driven monocyte-T cell interactions. These distinct immune features of the peripheral circulation in ACPA+ eRA suggest a role for type 1 helper T cell-related immunity in its pathogenesis. [ABSTRACT FROM AUTHOR]