IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in ankylosing spondylitis (AS). Blocking IL-17A is expected to inhibit ...bony ankylosis. Here, we investigated the effects of anti IL-17A agents in AS.
TNFα, IL-17A, and IL-12/23 p40 levels in serum and synovial fluid from patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), osteoarthritis (OA), or healthy controls (HC) were measured by ELISA. Bone tissue samples were obtained at surgery from the facet joints of ten patients with AS and ten control (Ct) patients with noninflammatory spinal disease. The functional relevance of IL-17A, biological blockades, Janus kinase 2 (JAK2), and non-receptor tyrosine kinase was assessed in vitro with primary bone-derived cells (BdCs) and serum from patients with AS.
Basal levels of IL-17A and IL-12/23 p40 in body fluids were elevated in patients with AS. JAK2 was also highly expressed in bone tissue and primary BdCs from patients with AS. Furthermore, addition of exogenous IL-17A to primary Ct-BdCs promoted the osteogenic stimulus-induced increase in ALP activity and mineralization. Intriguingly, blocking IL-17A with serum from patients with AS attenuated ALP activity and mineralization in both Ct and AS-BdCs by inhibiting JAK2 phosphorylation and downregulating osteoblast-involved genes. Moreover, JAK2 inhibitors effectively reduced JAK2-driven ALP activity and JAK2-mediated events.
Our findings indicate that IL-17A regulates osteoblast activity and differentiation via JAK2/STAT3 signaling. They shed light on AS pathogenesis and suggest new rational therapies for clinical AS ankylosis.
Calcium oxide (CaO) is an important construction material, used as expansive agent, alkaline activator, and repairing material for historical structures. In this study, the dissolution and subsequent ...hydration of CaO, with or without the polycarboxylate ether (PCE)-based superplasticizer, were investigated to elucidate the complex crystallization process of calcium hydroxide (Ca(OH)2). On contact with pure water, CaO particles began to hydrate within a few minutes, while releasing a significant amount of heat. Adding superplasticizer slowed such rapid heat evolution by forming a dormant period and significantly affected the crystallinity of the hydration product. The dormant period was controllable by the amount of added superplasticizer. Moreover, as a result of early nucleation of Ca(OH)2, the formation of 10–100-nm spherical nanoparticles was observed via an in-situ transmission electron microscope, which completely differed from the final crystal shape of the hydration product.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Carbon microcoils (CMCs) were formed on stainless steel substrates using C
H
+ SF
gas flows in a thermal chemical vapor deposition (CVD) system. The manipulation of the SF
gas flow rate and the SF
...gas flow injection time was carried out to obtain controllable CMC geometries. The change in CMC geometry, especially CMC diameter as a function of SF
gas flow injection time, was remarkable. In addition, the incorporation of H
gas into the C
H
+ SF
gas flow system with cyclic SF
gas flow caused the formation of the hybrid of carbon nanofibers-carbon microcoils (CNFs-CMCs). The hybrid of CNFs-CMCs was composed of numerous small-sized CNFs, which formed on the CMCs surfaces. The electromagnetic wave shielding effectiveness (SE) of the heating film, made by the hybrids of CNFs-CMCs incorporated carbon paste film, was investigated across operating frequencies in the 1.5-40 GHz range. It was compared to heating films made from commercial carbon paste or the controllable CMCs incorporated carbon paste. Although the electrical conductivity of the native commercial carbon paste was lowered by both the incorporation of the CMCs and the hybrids of CNFs-CMCs, the total SE values of the manufactured heating film increased following the incorporation of these materials. Considering the thickness of the heating film, the presently measured values rank highly among the previously reported total SE values. This dramatic improvement in the total SE values was mainly ascribed to the intrinsic characteristics of CMC and/or the hybrid of CNFs-CMCs contributing to the absorption shielding route of electromagnetic waves.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Differentiating inflammatory bowel disease (IBD) from other inflammatory diseases is often challenging. Programmed cell death protein-1 (PD-1) is expressed in T cells and is an indicator of their ...exhaustion. The role of PD-1 expression in diagnosing IBD and predicting the response of biologic agents remains inconclusive. In this study, endoscopic biopsy samples of 19 patients diagnosed with IBD, intestinal tuberculosis, and intestinal Behcet's disease were analyzed using multiplexed immunohistochemistry. Additionally, a separate "vedolizumab (VDZ) cohort" established in ulcerative colitis patients who underwent endoscopic biopsy before VDZ administration was analyzed to predict response to VDZ. In the immunohistochemistry analysis, the cell density of T cell subsets, including PD-1 + cells, was investigated and compared between IBD and other inflammatory diseases (OID). Cell densities of PD-1 + cells (p = 0.028), PD-1 + helper T cells (p = 0.008), and PD-1 + regulatory T cells (p = 0.024) were higher in IBD compared with OID. In the VDZ cohort, patients with a 14-week steroid-free clinical response had higher levels of PD-1 + cells (p = 0.026), PD-1 + helper T cells (p = 0.026), and PD-1 + regulatory T cells (p = 0.041) than the no response group. PD-1 + immune cells may contribute to the diagnosis of IBD and could be used to predict response to VDZ in ulcerative colitis patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The prognostic nutritional index (PNI) has been reported to be associated with postoperative complications and prognosis in cancer surgery. However, few studies have evaluated the association between ...preoperative PNI and postoperative acute kidney injury (AKI) in colorectal cancer patients. This study evaluated association of preoperative PNI and postoperative AKI in patients who underwent colorectal cancer surgery. This study retrospectively analyzed 3543 patients who underwent colorectal cancer surgery between June 2008 and February 2012. The patients were classified into four groups by the quartile of PNI: Q1 (≤43.79), Q2 (43.79–47.79), Q3 (47.79–51.62), and Q4 (≥51.62). Multivariate regression analysis was performed to assess the risk factors for AKI and 1-year mortality. AKI was defined according to Kidney Disease Improving Global Outcomes classification (KDIGO) criteria. Additionally, we assessed surgical outcomes such as hospital stay, ICU admission, and postoperative complications. The incidence of postoperative AKI tended to increase in the Q1 group (13.4%, 9.2%, 9.4%, 8.8%). In the multivariate analysis, high preoperative PNI was significantly associated with low risk of postoperative AKI (adjusted odds ratio OR: 0.96, 95% confidence interval CI: 0.93–0.99, p = 0.003) and low 1-year mortality (OR: 0.92, 95% CI: 0.86–0.98, p = 0.011). Male sex, body mass index, diabetes mellitus, and hypertension were risk factors for AKI. The Q1 (≤43.79) group had poor surgical outcomes, such as postoperative AKI (OR: 1.52, 95% CI: 1.18–1.95, p = 0.001), higher rates of ICU admission (OR: 3.13, 95% CI: 1.82–5.39, p < 0.001) and higher overall mortality (OR: 3.81, 95% CI: 1.86–7.79, p < 0.001). In conclusion, low preoperative PNI levels, especially in the Q1 (≤43.79), were significantly associated with postoperative AKI and surgical outcomes, such as hospital stay, postoperative ICU admission, and mortality.
Objective
To investigate the accuracy of automated identification of cephalometric landmarks using the cascade convolutional neural networks (CNN) on lateral cephalograms acquired from nationwide ...multi‐centres.
Settings and sample population
A total of 3150 lateral cephalograms were acquired from 10 university hospitals in South Korea for training.
Materials and Methods
We evaluated the accuracy of the developed model with independent 100 lateral cephalograms as an external validation. Two orthodontists independently identified the anatomic landmarks of the test data set using the V‐ceph software (version 8.0, Osstem, Seoul, Korea). The mean positions of the landmarks identified by two orthodontists were regarded as the gold standard. The performance of the CNN model was evaluated by calculating the mean absolute distance between the gold standard and the automatically detected positions. Factors associated with the detection accuracy for landmarks were analysed using the linear regression models.
Results
The mean inter‐examiner difference was 1.31 ± 1.13 mm. The overall automated detection error was 1.36 ± 0.98 mm. The mean detection error for each landmark ranged between 0.46 ± 0.37 mm (maxillary incisor crown tip) and 2.09 ± 1.91 mm (distal root tip of the mandibular first molar). A significant difference in the detection accuracy among cephalograms was noted according to hospital (P = .011), sensor type (P < .01), and cephalography machine model (P < .01).
Conclusion
The automated cephalometric landmark detection model may aid in preliminary screening for patient diagnosis and mid‐treatment assessment, independent of the type of the radiography machines tested.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Silica fume (SF) is a key ingredient in the production of ultra-high performance fiber-reinforced concrete (UHPFRC). The use of undensified SF may have an advantage in the dispersion efficiency ...inside cement-based materials, but it also carries a practical burden such as high material costs and fine dust generation in the workplace. This study reports that a high strength of 200 MPa can be achieved by using densified SF in UHPFRC with Portland limestone cement. Additionally, it was experimentally confirmed that there was no difference between densified and undensified SFs in terms of workability, compressive and flexural tensile strengths, and hydration reaction of the concrete, regardless of heat treatment, because of a unique mix proportion as well as mixing method for dispersing agglomerated SF particles. It was experimentally validated that the densified SF can be used for both precast and field casting UHPFRCs with economic and practical benefits and without negative effects on the material performance of the UHPFRC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Endoscopic sampling is essential for tissue diagnosis of cholangiocarcinoma (CCA). To evaluate and compare the diagnostic sensitivities of endoscopic retrograde cholangiopancreatography-guided brush ...cytology biopsy, and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with CCA. A comprehensive literature search through multiple databases was conducted for articles published between January 1995 and August 2020. The pooled rates of sensitivity for the diagnosis of CCA and of adverse events were compared among brushing, biopsy, brushing & biopsy, and EUS-FNA. In total, 1123 patients with CCA (32 studies), 719 patients (20 studies), 358 patients (13 studies), and 422 patients (17 studies) were tested by brushing, biopsy, brushing & biopsy, and EUS-FNA, respectively. The pooled diagnostic sensitivity was 56.0% (95% confidence interval (CI) 48.8–63.1%,
I
2
= 83.0%) with brushing, 67.0% (95% CI 60.2–73.5%,
I
2
= 72.5%) with biopsy, 70.7% (95% CI 64.1–76.8%,
I
2
= 42.7%) with brushing & biopsy, and 73.6% (95% CI 64.7–81.5%,
I
2
= 74.7%) with EUS-FNA. The diagnostic sensitivity was significantly lower for brushing than for biopsy, brushing & biopsy, or EUS-FNA. No significant difference was noted in diagnostic sensitivities among biopsy, brushing & biopsy, and EUS-FNA. Adverse events were comparable between the groups. Intraductal biopsy, brushing & biopsy, and EUS-FNA had comparable efficacy and safety for the diagnosis of CCA. Brushing was the least sensitive diagnostic tool compared with intraductal biopsy or EUS-FNA. Given the modest diagnostic sensitivities of intraductal biopsy and EUS-FNA in the diagnosis of CCA, further studies for complementing these techniques with biomarkers may be needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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