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The prevalence of hepatitis E virus (HEV) genotype 3 infections in the English population (including blood donors) is unknown, but is probably widespread, and the virus has been detected in pooled plasma products. HEV-infected donors have been retrospectively identified through investigation of reported cases of possible transfusion-transmitted hepatitis E. The frequency of HEV transmission by transfusion and its outcome remains unknown. We report the prevalence of HEV RNA in blood donations, the transmission of the virus through a range of blood components, and describe the resulting morbidity in the recipients. From Oct 8, 2012, to Sept 30, 2013, 225 000 blood donations that were collected in southeast England were screened retrospectively for HEV RNA. Donations containing HEV were characterised by use of serology and genomic phylogeny. Recipients, who received any blood components from these donations, were identified and the outcome of exposure was ascertained. 79 donors were viraemic with genotype 3 HEV, giving an RNA prevalence of one in 2848. Most viraemic donors were seronegative at the time of donation. The 79 donations had been used to prepare 129 blood components, 62 of which had been transfused before identification of the infected donation. Follow-up of 43 recipients showed 18 (42%) had evidence of infection. Absence of detectable antibody and high viral load in the donation rendered infection more likely. Recipient immunosuppression delayed or prevented seroconversion and extended the duration of viraemia. Three recipients cleared longstanding infection after intervention with ribavirin or alteration in immunosuppressive therapy. Ten recipients developed prolonged or persistent infection. Transaminitis was common, but short-term morbidity was rare; only one recipient developed apparent but clinically mild post-transfusion hepatitis. Our findings suggest that HEV genotype 3 infections are widespread in the English population and in blood donors. Transfusion-transmitted infections rarely caused acute morbidity, but in some immunosuppressed patients became persistent. Although at present blood donations are not screened, an agreed policy is needed for the identification of patients with persistent HEV infection, irrespective of origin, so that they can be offered antiviral therapy. Public Health England and National Health Service Blood and Transplant.

Background:Abnormal autoimmunity occur before the onset of clinical rheumatoid arthritis(RA)[1]. Soluble interleukin-2 receptor (sIL-2R) is an indicator of immune activation in the body, which may be related to the activity, prognosis, and response to treatment of the disease[2, 3]. Early identification in the undifferentiated arthritis(UA) is crucial for precision therapy. In order to explore the predictive value of sIL-2R for the development of patients with UA.Objectives:We included seropositive patients (ACPA positive with or without RF positive) with undifferentiated arthritis (UA, n=27), early RA patients (Ea-RA, n=40), newly diagnosed RA patients (new RA, n=60), and patients who had been treated were readmitted due to disease activity (Relapsed RA, Re-RA, n=50). 45 healthy controls(HC) matched by sex and age were also included. Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α were detected by magnetic bead multiplex immunofluorescence assay using human Th1/Th2/Th17 subsets detection kit. The level of sIL-2R was analyzed by ELISA.Methods:We included seropositive patients with undifferentiated arthritis (UA, n=27), early RA patients (Ea-RA, n=40), newly diagnosed RA patients (new RA, n=60), and patients who had been treated were readmitted due to disease activity (Relapsed RA, Re-RA, n=50). 45 healthy controls(HC) matched by sex and age were also included. Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α were detected by magnetic bead multiplex immunofluorescence assay using human Th1/Th2/Th17 subsets detection kit. The level of sIL-2R was analyzed by ELISA.Results:The results showed that the serum levels of IL-2, IL-4 and IL-17 in UA, Ea-RA, New RA and Re-RA groups were significantly higher than those in HC, and the levels of IL-4 in Ea-RA and New-RA groups were increased than those in Re-RA. Moreover, the levels of IL-10, IFN-γ and TNF-α in Ea-RA, New-RA and Re-RA groups were elevated, while UA group showed no statistical difference, while the levels of IL-6 in New-RA and Re-RA groups were significantly higher than those in healthy controls. Additionally, the level of sIL-2R in the UA group was not significantly higher than that in the healthy control group, while the Ea-RA, New-RA and Re-RA groups were significantly higher than that in the HC and the UA group. In order to further assess predictive value in UA and early RA, we conducted ROC curve analysis, with an area under the curve (AUC) of 0.7952, (95% CI 0.6820 to 0.9084, p<0.0001). The cutoff value was 429 pg/ml, with a sensitivity of 70% and specificity of 73.08%. In UA, there were a total of 7 cases with sIL-2R levels greater than 429, among which 4 cases with normal ESR accounted for 57%, but had suspicious joint pain or morning stiffness symptoms, and the remaining 3 cases with elevated ESR accounted for 43%.Conclusion:Elevated levels of sIL-2R in the undifferentiated stage of arthritis may indicate the possibility of progression, which has reference value for guiding treatment.REFERENCES:[1] van Steenbergen HW, Cope AP, van der Helm-van Mil AHM.Rheumatoid arthritis prevention in arthralgia: fantasy or reality? Nat Rev Rheumatol.2023;19(12): 767-777.[2] Damoiseaux J.The IL-2 - IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor. Clin Immunol.2020;218:108515.[3] van Steenbergen HW, van Nies JA, Ruyssen-Witrand A, Huizinga TW, Cantagrel A, Berenbaum F, et al.IL2RA is associated with persistence of rheumatoid arthritis. Arthritis Res Ther.2015;17(1): 244.Figure 1.Comparison of serum cytokines in all groups.(UA(n=27), Early-RA(n=40), New-RA(n=60), ReRA(n=60),Control(n=45)).*p<0.05,**p<0.001,***p<0.0001.Figure 2.The predictive value of sIL-2R for the development of UA into early RA; A: Receiver operating curve of sIL-2R for predicting early onset of RA; B: Proportion of normal and elevated ESR in patients with sIL-2R levels greater than 429 pg/ml.Acknowledgements:NIL.Disclosure of Interests:None declared.

Myopericarditis after vaccination has been sporadically reported in the medical literature. Here, we present a thorough descriptive analysis of reports to a national passive vaccine safety surveillance system (VAERS) of myopericarditis after vaccines licensed for use in the United States. We identified U.S. reports of myopericarditis received by VAERS during 1990–2018 that met a published case definition for myopericarditis or were physician-diagnosed. We stratified analysis by age group (<19, 19–49, ≥50 years), describing reports by serious/non-serious status, sex, time to symptom onset after vaccination, vaccine(s) administered, and exposure to other known causes of myopericarditis. We used Empirical Bayesian data mining to detect disproportionate reporting of myopericarditis after vaccination. VAERS received 620,195 reports during 1990–2018: 708 (0.1%) met the case definition or were physician-diagnosed as myopericarditis. Most (79%) myopericarditis reports described males; 69% were serious; 72% had symptom onset ≤ 2 weeks postvaccination. Overall, smallpox (59%) and anthrax (23%) vaccines were most commonly reported. By age, among persons aged < 19 years, Haemophilus influenzae type b (22, 22%) and hepatitis B (18, 18%); among persons aged 19–49 years smallpox (387, 79%); among persons aged ≥ 50 years inactivated influenza (31, 36%) and live attenuated zoster (19, 22%) vaccines were most commonly reported. The vaccines most commonly reported remained unchanged when excluding 138 reports describing other known causes of myopericarditis. Data mining revealed disproportionate reporting of myopericarditis only after smallpox vaccine. Despite the introduction of new vaccines over the years, myopericarditis remains rarely reported after vaccines licensed for use in the United States. In this analysis, myopericarditis was most commonly reported after smallpox vaccine, and less commonly after other vaccines.

The underlying cause of autoimmune diseases is not known,infections, especially viral infections, is thought to be a possible reason[1].Disorder of CD4+T cells have been linked to autoimmunity, they are key players in various autoimmune diseases but are also crucial for immunity against different infections[2]. However, the immune response status of different types of infections in the context of autoimmune diseases is poorly understood. To evaluate the differences of lymphocyte subsets in connective tissue disease(CTD) with different types of pathogen bloodstream infections. We analyzed 40 CTD patients with bloodstream infections, including 11 with virus infections,7 with fungal infections,13 with Gram negative bacteria infections(G- infection), 9 with Gram positive bacteria infections(G+infection), and 10 newly diagnosed CTD patients without co-infection were included as controls.The percentage and absolute numbers of lymphocyte phenotypes and CD4+ T subsets in peripheral blood were examined by flow cytometry. There were no significant difference in the percentage and absolute value of T,B,NK,CD4+T,CD8+T cells in different types of infection groups and no-infection group. Among comparison of the CD4+T subsets, the percentage of Th2 in the fungal infection was decreased than G- infection group and no-infection group,while the G- infection was increased than G+infection,and the virus infection was increased than fungal infection. The percentage of Th1,Th17 and Treg had no significant difference between different groups. Whereas for the absolute value comparison, the absolute value of Treg cells in the virus infection was higher than the fungal infection,G- infection and G+ infection, meanwhile the the fungal infection was obvious lower than no infection group. But there was no significant difference in Th1 and 17 among all groups. Different types of pathgen blood may lead to development of specific immunological dysbalance,especially in the case of autoimmune disease hosts. CTD patients with fungal infection had lower Th2 response, higher Treg cells may be a characteristic of CTD combined with virus infection compare with other types of infection. [1]Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, Elledge SJ, Niebuhr DW, Scher AI, Munger KL, Ascherio A. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022 Jan 21;375(6578):296-301. [2]Quaglia M, Merlotti G, De Andrea M, Borgogna C, Cantaluppi V. Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story. Viruses. 2021,13(2):277. None declared [Display omitted]

The precise depth measurement of common structural defects, such as bulging, delamination, and spalling, is paramount in building condition assessment. This paper presents an efficient and portable parallel laser line‐camera system designed for accurately reconstructing defect depth profiles from projected laser stripes. The system features a telescopic design to enhance the measurement range and operational flexibility. Central to its efficacy is a machine learning–aided image processing algorithm that facilitates both robust and highly accurate depth measurements. Specifically, advanced deep learning techniques are applied to detect and segment laser stripes from background interference. A novel hypothesis optimization (HO) algorithm, grounded in a three‐layer backpropagation (BP) neural network, is proposed to reduce errors in laser baseline recovery caused by image distortion further. Comprehensive laboratory and field experiments validate the measurement accuracy and superior noise suppression capabilities of the system. Additionally, the paper studies potential errors that could emerge during field operations, thereby confirming the practical utility of the device. The proposed system quickly generates surface profiles in a single shot, making it a valuable tool for monitoring uneven objects.

MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French–American–British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1 . The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.

The seismic performance of steel reinforced engineered cementitious composite (RECC) short columns was investigated in this study. RECC columns with various shear span-to-depth ratios, axial load levels and transverse reinforcement ratios, together with one control reinforced concrete (RC) short column, were tested under the combined action of constant axial loading and reversed cyclic lateral loading. Test results indicate that RECC columns are superior to RC columns in terms of ductility, energy dissipation capacity and damage tolerance. The control RC column and the RECC column with the smallest shear span-to-depth ratio (of 1.42) were found to fail in shear. All other RECC columns, with higher shear span-to-depth ratios, including one RECC column without stirrups, failed in a flexure-dominated manner. Furthermore, theoretical flexural strength and shear strength expressions of RECC columns were derived and validated by the test results.

Background:Mixed connective tissue disease (MCTD) with a range of clinical manifestations and is recognized as an independent disease with similarities to systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), or as an early manifestation of these conditions. In SLE, there is an imbalance in Th1/Th2 and Th17/Treg[1,2], activation of B cells in CD4+T cell subsets[3], and abnormal activation of CD4+T cells, as well as skin tissue infiltration and Th2/Th17 immune bias in SSc[4]. However, there is limited research on CD4+T cell subsets in MCTD, and the characteristics of these subsets are not well understood. Furthermore, cytokines such as IL-10 have been found to be closely associated with MCTD and play a significant role in its onset and progression.Objectives:We conducted an analysis of the peripheral blood lymphocyte subsets, CD4+T cell subsets, and related cytokines in these three disease groups and healthy controls in order to uncover the immune differences and characteristics between MCTD and SLE, SSc. Furthermore, we aimed to explore the relationship between the related cytokines IL-2 and IL-10 and MCTD.Methods:48 patients with MCTD, 51 patients with SLE, 35 patients with SSc and 49 with HCs were enrolled in this research. The absolute counts of peripheral blood lymphocyte subsets and CD4+T cell subsets were examined using flow cytometry, and serum cytokine levels were measured using flow cytometry microbead arrays.Results:Absolute counts of T cells, CD4+T cells, CD8+T cells, NK cells, Th1 cells, Th2 cells, and Treg cells were decreased in the MCTD group compared to the HC group (P<0.05). The absolute counts of CD4+T cells, Th1 cells, and Th2 cells were reduced in the MCTD group compared to the SSc group (P<0.05), and there was no significant difference compared to the SLE group. Cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α) levels were significantly higher in the MCTD group compared to the HC group and the SSc group (P<0.05), and there was no significant difference in cytokines compared to the SLE group. Further analysis revealed that cardiac enzymes (CK, CK-MB, AST, α-HBDH, LDH) were positively correlated with cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α) in MCTD (P<0.05). In addition, we found that IL-2 was associated with disease activity in MCTD and IL-10 was associated with myoinflammatory symptoms in MCTD, the area under the ROC curve (AUC) was 0.745 (95% CI 0.576-0.915, P=0.0116).Conclusion:Our investigation uncovered immunological variances in peripheral blood lymphocyte subgroups, CD4+T cell subgroups, and cytokines among MCTD, SLE, SSc, and healthy controls. Furthermore, we emphasized that cytokines in MCTD are linked with cardiac enzymes, and IL-2 is correlated with disease activity. IL-10 can serve as an autonomous risk factor and predictor of myoinflammatory symptoms in MCTD, laying the groundwork for further exploration into the potential pathogenesis of MCTD.REFERENCES:[1] Shan J, Jin H, Xu Y. T Cell Metabolism: A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus [J]. Front Immunol, 2020, 11: 1027.[2] Dolff S, Bijl M, Huitema M G, et al. Disturbed Th1, Th2, Th17 and T(reg) balance in patients with systemic lupus erythematosus [J]. Clin Immunol, 2011, 141(2): 197-204.[3] Long D, Yang B, Yang M, et al. Bach2 in CD4(+) T cells from SLE patients modulates B-cell differentiation and IgG production [J]. Eur J Immunol, 2023, 53(4): e2250109.[4] Maehara T, Kaneko N, Perugino C A, et al. Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis [J]. Journal of Clinical Investigation, 2020, 130(5): 2451-2464.Acknowledgements:NIL.Disclosure of Interests:None declared.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by small-vessel vasculitis and systemic autoimmune inflammatory response [1, 2]. Although AAV is rare, the condition of AAV is relatively severe. The clinical manifestations of patients with AAV are different [3], ranging from mild non-specific symptoms to severe life-threatening organ involvement. Therefore, the clinical need to achieve accurate and quick identification for the high-risk groups of organ involvement in early-stage AAV remains strong. There is no study to identify the high-risk patients with organ involvement of early-stage of AAV. We aimed to develop a model to identify those high-risk patients at an early stage. The data of the 74 new-onset patients with AAV (61 of whom had definite organ involvement) was collected in our retrospective study. The predictor variables for organ involvement in AAV were assessed by the logistic regression analysis. We developed the risk stratification model by nomogram. And the model was validated by concordance index, calibration curve, and decision curve analysis. The logistic regression analysis showed that BVAS, IL-17 and Treg cells were the predictor variables for organ involvement in AAV (Figure 1). We constructed a nomogram model consisting of BVAS, Treg cells and IL-17 (Figure 2A). In the nomogram, the value of each predictor was assigned a certain number of points, and the sum of the points for each predictor corresponded to the risk of organ involvement in AAV. Then we evaluated the nomogram model. The calibration curve in 1000 bootstrap replications revealed a good predictive accuracy between the predicted probability and observed probability of the nomogram model with a concordance index (C-index) of 0. 957 (95% CI = 0. 694–0.960) and bias-corrected C-index of 0. 937 (Figure 2B). And the chi-squares of Hosmer–Lemeshow test was 0.37(P = 0.83) indicating a good fitness of the model. Next, the receiver operating characteristic (ROC) curve of the model (Figure 2C) yielded the AUC of the curve was 0.9571 (95%CI =0.9124–1.000) showing it had a great ability for discriminating organ involvement in AAV. The decision curve analysis (DCA) showed a positive net benefit for patients with organ involvement (Figure 2D), which suggested that patients with organ involvement could benefit from interventions. And the clinical impact curve (Figure 2E) showed that the risk of organ involvement predicted by the nomogram model under threshold probability (red curve) was close to the actual value of organ involvement events under each threshold probability (blue curve). The risk stratification nomogram model was effective to identify the high-risk patients of organ involvement in early-stage AAV, and it was validated with good discrimination, calibration as well as great application value in clinical. [1]Kitching AR, Anders H-J, Basu N, Brouwer E, Gordon J, Jayne DR et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020, 6(1):71. [2]Nakazawa D, Masuda S, Tomaru U, Ishizu A. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nat Rev Rheumatol. 2019, 15(2). [3]Yaseen K, Mandell BF. ANCA associated vasculitis (AAV): a review for internists. Postgrad Med. 2022. NIL. None Declared. [Display omitted] [Display omitted]

Rockburst is a sudden and violent failure of rocks and it often occurs in hard rocks in highly stressed ground. Strainburst is classified as one type of rockburst and it often occurs in rocks near or at the excavation boundary. Deep insight into the strainburst phenomenon is essential for safe underground construction at depth. In this paper, an experimental laboratory study on the strainburst behavior of Beishan granite is presented. Based on in-situ stress measurement data from the Beishan area in China, a series of tests under different unloading rates were performed to investigate the strainburst process using a true-triaxial strainburst test system which was equipped with an acoustic emission (AE) monitoring system. In addition, a high-speed video camera was used to record and visualize the initiation and ejection of rock fragments as well as the sudden dynamic failure (strainburst) of the test samples. AE characteristics associated with the cumulative energy and frequency–amplitude distributions were analyzed. Characteristics of the microscopic structure of a fragment generated from one test were observed using a scanning electron microscope. The experimental results indicate that the degree of violence during failure and the associated AE energy release in the strainburst process are dependent on the unloading rate. When the unloading rate is high, the rock is prone to strainburst. On the other hand, as the unloading rate decreases, the failure mode changes from strainburst to spalling. In addition, the cumulative AE energy is not sensitive to unloading rates greater than 0.05 MPa/s. When the unloading rate is less than 0.05 MPa/s, the cumulative AE energy shows a marked decreasing trend during rock failure.