cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.11811672
title: Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease

description: The aim of this study was to determine pathological features of T peripheral helper (Tph)-like (PD-1<sup>+</sup>CXCR5<sup>−</sup>CD4<sup>+</sup> T) cells in IgG4-related disease (IgG4-RD). Tph-like cells in the blood and submandibular glands (SMGs) from IgG4-RD patients were analyzed by flow cytometry. Correlations between level of a Tph-like cell subset and clinical parameters of IgG4-RD were investigated. The cytotoxic capacity of Tph-like cells was also examined. Expression profiles of a molecule related to a Tph-like cell subset in IgG4-RD SMGs were assessed by immunohistochemistry. Tph-like cells from IgG4-RD patients highly expressed a fractalkine receptor, CX3CR1. Percentages of circulating CX3CR1<sup>+</sup> Tph-like cells were significantly correlated with clinical parameters including IgG4-RD Responder Index, number of involved organs, and serum level of soluble IL-2 receptor. CX3CR1<sup>+</sup> Tph-like cells abundantly possessed cytotoxic T lymphocyte-related molecules such as granzyme A, perforin, and G protein-coupled receptor 56. Functional assays revealed their cytotoxic potential against vascular endothelial cells and ductal epithelial cells. Immunohistochemistry showed that fractalkine was markedly expressed in vascular endothelial cells and ductal epithelial cells in IgG4-RD SMGs. CX3CR1<sup>+</sup> Tph-like cells are thought to contribute to persistent tissue injury in IgG4-RD and are a potential clinical marker and/or therapeutic target for inhibiting progression of IgG4-RD.
DOI: 10.6084/m9.figshare.12038712.v1
title: Clinical aspects in patients with rheumatoid arthritis complicated with lymphoproliferative disorders without regression after methotrexate withdrawal and treatment for arthritis after regression of lymphoproliferative disorders

description: To identify predictive factors for lymphoproliferative disorders (LPDs) that persist after methotrexate (MTX) withdrawal (Persistent-LPD) and the optimal treatment for rheumatoid arthritis (RA) after LPD regression. Among 3666 patients with RA treated with MTX in our department from 2006 to 2017, 26 cases of LPD that regressed after MTX withdrawal (Regressive-LPD) and 25 cases of Persistent-LPD were compared. Multivariate logistic analysis was performed to identify predictive factors for Persistent-LPD. Retention rates of biological disease-modifying antirheumatic drugs (bDMARDs) were calculated using the Kaplan–Meier Method. In Persistent-LPD, the incidence of diffuse large B-cell lymphoma was higher (76%). The overall 2-year survival rate was 83.9%: 95.8% for Regressive-LPD and 71.0% for Persistent-LPD. The International Prognostic Index (IPI) risk classification was useful for predicting Persistent-LPD. bDMARDs were introduced in 38 RA patients after LPD regression. Unadjusted retention rate of bDMARDs in the 51 LPD patients was significantly lower than that in the 1668 non-LPD RA patients in our bDMARD cohort (controls) (<i>p</i> = 0.029). The 1-year retention rates for bDMARDs were 69% and 64% for tocilizumab and abatacept, respectively vs. 46% for TNF-inhibitor (TNFi). Risk assessment using IPI predicted Persistent-LPD. After LPD regression, non-TNFi tended to have higher retention rates.
DOI: 10.6084/m9.figshare.11811672.v1
title: Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease

description: The aim of this study was to determine pathological features of T peripheral helper (Tph)-like (PD-1<sup>+</sup>CXCR5<sup>−</sup>CD4<sup>+</sup> T) cells in IgG4-related disease (IgG4-RD). Tph-like cells in the blood and submandibular glands (SMGs) from IgG4-RD patients were analyzed by flow cytometry. Correlations between level of a Tph-like cell subset and clinical parameters of IgG4-RD were investigated. The cytotoxic capacity of Tph-like cells was also examined. Expression profiles of a molecule related to a Tph-like cell subset in IgG4-RD SMGs were assessed by immunohistochemistry. Tph-like cells from IgG4-RD patients highly expressed a fractalkine receptor, CX3CR1. Percentages of circulating CX3CR1<sup>+</sup> Tph-like cells were significantly correlated with clinical parameters including IgG4-RD Responder Index, number of involved organs, and serum level of soluble IL-2 receptor. CX3CR1<sup>+</sup> Tph-like cells abundantly possessed cytotoxic T lymphocyte-related molecules such as granzyme A, perforin, and G protein-coupled receptor 56. Functional assays revealed their cytotoxic potential against vascular endothelial cells and ductal epithelial cells. Immunohistochemistry showed that fractalkine was markedly expressed in vascular endothelial cells and ductal epithelial cells in IgG4-RD SMGs. CX3CR1<sup>+</sup> Tph-like cells are thought to contribute to persistent tissue injury in IgG4-RD and are a potential clinical marker and/or therapeutic target for inhibiting progression of IgG4-RD.
DOI: 10.6084/m9.figshare.12444812
title: Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis

description: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (<i>n</i> = 26) or teriparatide (TPTD) (<i>n</i> = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, <i>T</i>-scores of the lumbar spine [LS] − 2.7 and femoral neck [FN] − 2.2) were switched to either (1) raloxifene (RAL) (<i>n</i> = 13) or BP [(2) weekly or monthly BP (wmBP) (<i>n</i> = 29) or (3) zoledronate (ZOL) (<i>n</i> = 11)], based on each physician’s decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. Changes in LS BMD at 1.5 years after final DMAb administration were −2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (<i>p</i> = .31 between groups), and in FN BMD were −3.8%, −0.8%, and 1.8%, respectively (<i>p</i> = .02 between the RAL and ZOL; <i>p</i> = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (<i>p</i> = .048 between the RAL and ZOL; <i>p</i> = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.
DOI: 10.6084/m9.figshare.12850811
title: Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan

description: We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. We included 123 courses of 107 patients (RTX <i>n</i> = 14, IS <i>n</i> = 64, GC <i>n</i> = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (<i>p</i> = .122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. RTX maintenance therapy could be effective and safe in Japanese GPA patients.
DOI: 10.6084/m9.figshare.12444812.v1
title: Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis

description: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (<i>n</i> = 26) or teriparatide (TPTD) (<i>n</i> = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, <i>T</i>-scores of the lumbar spine [LS] − 2.7 and femoral neck [FN] − 2.2) were switched to either (1) raloxifene (RAL) (<i>n</i> = 13) or BP [(2) weekly or monthly BP (wmBP) (<i>n</i> = 29) or (3) zoledronate (ZOL) (<i>n</i> = 11)], based on each physician’s decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. Changes in LS BMD at 1.5 years after final DMAb administration were −2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (<i>p</i> = .31 between groups), and in FN BMD were −3.8%, −0.8%, and 1.8%, respectively (<i>p</i> = .02 between the RAL and ZOL; <i>p</i> = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (<i>p</i> = .048 between the RAL and ZOL; <i>p</i> = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.
DOI: 10.6084/m9.figshare.12326285.v1
title: Prevalence of anti-cyclic citrullinated peptide antibodies in patients with spondyloarthritis: A retrospective study

description: Anti-cyclic citrullinated peptide (CCP) antibodies are frequently detected in the sera of patients with rheumatoid arthritis (RA). However, recent studies have revealed a potentially high prevalence rate of these antibodies in patients with other rheumatic disorders, causing confusion while diagnosing RA. Therefore, this study aimed to evaluate the positive rate of anti-CCP antibodies in other chronic arthritis diseases focusing on patients with spondyloarthritis (SpA). A total of 109 patients who were diagnosed with SpA at Yukioka Hospital from 1993 to 2018 were included in this retrospective analysis, including patients with ankylosing spondylitis (AS); psoriatic arthritis (PsA); synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (SAPHO); undifferentiated spondyloarthritis (uSpA); reactive arthritis (ReA); and inflammatory bowel disease-associated SpA (IBD). Overall, 15.3% (16/109) of patients with SpA were positive for anti-CCP antibodies, including 2.3% (1/43) in AS, 23.1% (3/13) in SAPHO, 35.0% (7/20) in PsA, 14.8% (4/27) in uSpA, 0% (0/3) in ReA, and 33.3% (1/3) in IBD. PsA patients have a significantly higher prevalence rate of positive anti-CCP antibodies among SpA patients, and the positive rates in SAPHO and uSpA were also high. These findings provide insight into the heterogeneity of SpA with relevance for RA differential diagnosis.
DOI: 10.6084/m9.figshare.12326285
title: Prevalence of anti-cyclic citrullinated peptide antibodies in patients with spondyloarthritis: A retrospective study

description: Anti-cyclic citrullinated peptide (CCP) antibodies are frequently detected in the sera of patients with rheumatoid arthritis (RA). However, recent studies have revealed a potentially high prevalence rate of these antibodies in patients with other rheumatic disorders, causing confusion while diagnosing RA. Therefore, this study aimed to evaluate the positive rate of anti-CCP antibodies in other chronic arthritis diseases focusing on patients with spondyloarthritis (SpA). A total of 109 patients who were diagnosed with SpA at Yukioka Hospital from 1993 to 2018 were included in this retrospective analysis, including patients with ankylosing spondylitis (AS); psoriatic arthritis (PsA); synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (SAPHO); undifferentiated spondyloarthritis (uSpA); reactive arthritis (ReA); and inflammatory bowel disease-associated SpA (IBD). Overall, 15.3% (16/109) of patients with SpA were positive for anti-CCP antibodies, including 2.3% (1/43) in AS, 23.1% (3/13) in SAPHO, 35.0% (7/20) in PsA, 14.8% (4/27) in uSpA, 0% (0/3) in ReA, and 33.3% (1/3) in IBD. PsA patients have a significantly higher prevalence rate of positive anti-CCP antibodies among SpA patients, and the positive rates in SAPHO and uSpA were also high. These findings provide insight into the heterogeneity of SpA with relevance for RA differential diagnosis.
DOI: 10.6084/m9.figshare.12850811.v1
title: Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan

description: We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. We included 123 courses of 107 patients (RTX <i>n</i> = 14, IS <i>n</i> = 64, GC <i>n</i> = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (<i>p</i> = .122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. RTX maintenance therapy could be effective and safe in Japanese GPA patients.
DOI: 10.6084/m9.figshare.14559756
title: health management

description: 3scales
DOI: 10.5519/qd.dux0xk3b
title: Query on the Natural History Museum Data Portal (data.nhm.ac.uk) (53 records)
DOI: 10.6084/m9.figshare.12909880
title: Correlation intensity index: mathematical modeling of cytotoxicity of metal oxide nanoparticles

description: Metal oxide nanoparticles (MO-NPs) have unique structural characteristics, exceptionally high surface area, strong mechanical stability, catalytic activities, and are biocompatible. Consequently, MO-NPs have recently attracted considerable interest in the field of imaging-guided therapeutic and biosensing applications. This study aims to develop Quantitative Structure–Activity Relationships (QSAR) for the prediction of cell viability of MO-NPs. The QSAR model based on the so-called optimal descriptors which calculated with a simplified molecular input-line entry system (SMILES). The Monte Carlo technique applied to calculate correlation weights for SMILES fragments. Factually, the optimal descriptor for SMILES is the summation of the correlation weights. The model of cytotoxicity is one variable correlation between cytotoxicity and the above optimal descriptor. The Correlation Intensity Index (CII) is a possible criterion of the predictive potential of the model. Applying the CII as a component of the target function in the Monte Carlo optimization routine, employed by the CORAL program, that is designed to find a predictive relationship between the optimal descriptor and cytotoxicity of MO-NPs, improves the statistical quality of the model. The significance of different eclectic features, in terms of whether they increase/decrease cell viability, i.e. decrease or increase cytotoxicity, is also discussed. Numerical data on 83 experimental samples of MO-NPs activity under different conditions taken from the literature are applied for the “nano-QSAR” analysis.
DOI: 10.6084/m9.figshare.12909880.v1
title: Correlation intensity index: mathematical modeling of cytotoxicity of metal oxide nanoparticles

description: Metal oxide nanoparticles (MO-NPs) have unique structural characteristics, exceptionally high surface area, strong mechanical stability, catalytic activities, and are biocompatible. Consequently, MO-NPs have recently attracted considerable interest in the field of imaging-guided therapeutic and biosensing applications. This study aims to develop Quantitative Structure–Activity Relationships (QSAR) for the prediction of cell viability of MO-NPs. The QSAR model based on the so-called optimal descriptors which calculated with a simplified molecular input-line entry system (SMILES). The Monte Carlo technique applied to calculate correlation weights for SMILES fragments. Factually, the optimal descriptor for SMILES is the summation of the correlation weights. The model of cytotoxicity is one variable correlation between cytotoxicity and the above optimal descriptor. The Correlation Intensity Index (CII) is a possible criterion of the predictive potential of the model. Applying the CII as a component of the target function in the Monte Carlo optimization routine, employed by the CORAL program, that is designed to find a predictive relationship between the optimal descriptor and cytotoxicity of MO-NPs, improves the statistical quality of the model. The significance of different eclectic features, in terms of whether they increase/decrease cell viability, i.e. decrease or increase cytotoxicity, is also discussed. Numerical data on 83 experimental samples of MO-NPs activity under different conditions taken from the literature are applied for the “nano-QSAR” analysis.
DOI: 10.6084/m9.figshare.12936731
title: Evaluation of the skin-sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold

description: Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl<sub>3</sub>) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 µg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl<sub>3</sub> then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group – simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure.
DOI: 10.6084/m9.figshare.12850883
title: Sex differences in the acute and subchronic lung inflammatory responses of mice to nickel nanoparticles

description: Nickel nanoparticles (NiNPs) are increasingly used in nanotechnology applications, yet information on sex differences in NiNP-induced lung disease is lacking. The goal of this study was to explore mechanisms of susceptibility between male and female mice after acute or subchronic pulmonary exposure to NiNPs. For acute exposure, male and female mice received a single dose of NiNPs with or without LPS by oropharyngeal aspiration and were necropsied 24 h later. For subchronic exposure, mice received NiNPs with or without LPS six times over 3 weeks prior to necropsy. After acute exposure to NiNPs and LPS, male mice had elevated cytokines (CXCL1 and IL-6) and more neutrophils in bronchoalveolar lavage fluid (BALF), along with greater STAT3 phosphorylation in lung tissue. After subchronic exposure to NiNPs and LPS, male mice exhibited increased monocytes in BALF. Moreover, subchronic exposure of male mice to NiNP only induced higher CXCL1 and CCL2 in BALF along with increased alveolar infiltrates and CCL2 in lung tissue. STAT1 in lung tissue was induced by subchronic exposure to NiNPs in females but not males. Males had a greater induction of IL-6 mRNA in liver after acute exposure to NiNPs and LPS, and greater CCL2 mRNA in liver after subchronic NiNP exposure. These data indicate that susceptibility of males to acute lung inflammation involves enhanced neutrophilia with increased CXCL1 and IL-6/STAT3 signaling, whereas susceptibility to subchronic lung inflammation involves enhanced monocytic infiltration with increased CXCL1 and CCL2. STAT transcription factors appear to play a role in these sex differences. This study demonstrates sex differences in the lung inflammatory response of mice to NiNPs that has implications for human disease.
DOI: 10.6084/m9.figshare.12850883.v1
title: Sex differences in the acute and subchronic lung inflammatory responses of mice to nickel nanoparticles

description: Nickel nanoparticles (NiNPs) are increasingly used in nanotechnology applications, yet information on sex differences in NiNP-induced lung disease is lacking. The goal of this study was to explore mechanisms of susceptibility between male and female mice after acute or subchronic pulmonary exposure to NiNPs. For acute exposure, male and female mice received a single dose of NiNPs with or without LPS by oropharyngeal aspiration and were necropsied 24 h later. For subchronic exposure, mice received NiNPs with or without LPS six times over 3 weeks prior to necropsy. After acute exposure to NiNPs and LPS, male mice had elevated cytokines (CXCL1 and IL-6) and more neutrophils in bronchoalveolar lavage fluid (BALF), along with greater STAT3 phosphorylation in lung tissue. After subchronic exposure to NiNPs and LPS, male mice exhibited increased monocytes in BALF. Moreover, subchronic exposure of male mice to NiNP only induced higher CXCL1 and CCL2 in BALF along with increased alveolar infiltrates and CCL2 in lung tissue. STAT1 in lung tissue was induced by subchronic exposure to NiNPs in females but not males. Males had a greater induction of IL-6 mRNA in liver after acute exposure to NiNPs and LPS, and greater CCL2 mRNA in liver after subchronic NiNP exposure. These data indicate that susceptibility of males to acute lung inflammation involves enhanced neutrophilia with increased CXCL1 and IL-6/STAT3 signaling, whereas susceptibility to subchronic lung inflammation involves enhanced monocytic infiltration with increased CXCL1 and CCL2. STAT transcription factors appear to play a role in these sex differences. This study demonstrates sex differences in the lung inflammatory response of mice to NiNPs that has implications for human disease.