64 research outputs found

    Macrophage-Specific Chemokines Induced via Innate Immunity by Amino Acid Copolymers and Their Role in EAE

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    The random amino acid copolymer poly(Y,E,A,K)n (Copaxone®) is widely used in multiple sclerosis treatment and a second generation copolymer poly(Y,F,A,K)n with enhanced efficacy in experimental autoimmune encephalomyelitis in mice has been described. A major mechanism through which copolymers function to ameliorate disease is the generation of immunosuppressive IL-10-secreting regulatory T cells entering the CNS. In addition, the antigen presenting cell to which these copolymers bind through MHC Class II proteins may have an important role. Here, both CCL22 (a Th2 cell chemoattractant) in large amounts and CXCL13 in much smaller amounts are shown to be secreted after administration of YFAK to mice and to a smaller extent by YEAK parallel to their serum concentrations. Moreover, bone marrow-derived macrophages secrete CCL22 in vitro in response to YFAK and to higher concentrations of YEAK. Strikingly, these chemokines are also secreted into serum of MHC Class II −/− mice, indicating that an innate immune receptor on these cells also has an important role. Thus, both the innate and the adaptive immune systems are involved in the mechanism of EAE amelioration by YFAK. The enhanced ability of YFAK to stimulate the innate immune system may account for its enhanced efficacy in EAE treatment

    Azimuthal single- and double-spin asymmetries in semi-inclusive deep-inelastic lepton scattering by transversely polarized protons

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    A comprehensive set of azimuthal single-spin and double-spin asymmetries in semi-inclusive leptoproduction of pions, charged kaons, protons, and antiprotons from transversely polarized protons is presented. These asymmetries include the previously published HERMES results on Collins and Sivers asymmetries, the analysis of which has been extended to include protons and antiprotons and also to an extraction in a three-dimensional kinematic binning and enlarged phase space. They are complemented by corresponding results for the remaining four single-spin and four double-spin asymmetries allowed in the one-photon-exchange approximation of the semi-inclusive deep-inelastic scattering process for target-polarization orientation perpendicular to the direction of the incoming lepton beam. Among those results, significant non-vanishing cos (phi-phi(S)) modulations provide evidence for a sizable worm-gear (II) distribution, g(1T)(q) (x, p(T)(2)). Most of the other modulations are found to be consistent with zero with the notable exception of large sin (phi(S)) modulations for charged pions and K+

    Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

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    Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

    Pathologist-like explainable AI for interpretable Gleason grading in prostate cancer

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    The aggressiveness of prostate cancer is primarily assessed from histopathological data using the Gleason scoring system. Conventional artificial intelligence (AI) approaches can predict Gleason scores, but often lack explainability, which may limit clinical acceptance. Here, we present an alternative, inherently explainable AI that circumvents the need for post-hoc explainability methods. The model was trained on 1,015 tissue microarray core images, annotated with detailed pattern descriptions by 54 international pathologists following standardized guidelines. It uses pathologist-defined terminology and was trained using soft labels to capture data uncertainty. This approach enables robust Gleason pattern segmentation despite high interobserver variability. The model achieved comparable or superior performance to direct Gleason pattern segmentation (Dice score: 0.713±0.0030.713±0.003{0.713}_{\pm 0.003} vs. 0.691±0.0100.691±0.010{0.691}_{\pm 0.010}) while providing interpretable outputs. We release this dataset to encourage further research on segmentation in medical tasks with high subjectivity and to deepen insights into pathologists’ reasoning
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