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Abstract Background Fat infiltration in muscle, called ‘myosteatosis’, precedes muscle atrophy, which subsequently results in sarcopenia. Myosteatosis is frequently observed in patients with nonalcoholic fatty liver disease (NAFLD). We have previously reported that retinoic acid receptor‐related orphan receptor‐α (RORα) regulates mitochondrial dynamics and mitophagy in hepatocytes, resulting in an alleviation of NAFLD. In this study, we aimed to investigate the role of RORα in skeletal muscle and to understand molecular mechanisms by which RORα controls mitochondrial capacity, using an NAFLD‐associated myosteatosis mouse model. Methods To establish a myosteatosis model, 7‐week‐old C57BL/6N mice were fed with high‐fat diet (HFD). After 15 weeks of diet feeding, an adeno‐associated virus vector encoding RORα (AAV‐RORα) was injected to gastrocnemius (GA) muscles, or after 7 weeks of HFD feeding, JC1‐40, an RORα agonistic ligand, was administered daily at a dose of 5 mg/kg/day by oral gavage for 5 weeks. Histological, biochemical and molecular analyses in various in vivo and in vitro experiments were performed. Results First, the number of oxidative MyHC2a fibres with intensive lipid infiltration increased by 3.8‐fold in the red region of the GA of mice with myosteatosis (P

Background: Abnormal new bone formation can occur not only in the vertebral body but also can occur in facet, costovertebral, and costotransverse joints in radiographic axial spondyloarthritis (r-axSpA) patients. Little is known about the association between syndesmophyte progression and paravertebral joint ankylosis in r-axSpA. Objectives: Costotransverse joint ankylosis in r-axSpA patients was measured. Furthermore, the association between syndesmophyte progression for 2 years assessed by computed tomography syndesmophyte score (CTSS) and facet, costovertebral, and costotransverse joints ankylosis were evaluated. Design: Single-center, prospective, cohort study. Methods: Whole spine CT images taken at baseline and 2-year follow-up were used to calculate the CTSS of the vertebral body. In addition, ankylosis of the facet/costovertebral/costotransverse joints was scored. CTSS (range, 0–552) and facet joint ankylosis (range, 0–46) were assessed at 23 vertebral units. Costovertebral joints at T1–T12 (range, 0–48) and costotransverse joints at T1–T10 (range, 0–20) were also assessed by independent two readers. Intraclass correlation coefficients (ICC) were calculated to determine inter-reader reliability. Odds ratios (OR) were calculated to identify the associations between syndesmophyte progression and the baseline status of facet, costovertebral, and costotransverse joints. Results: In all, 50 patients with r-axSpA were included. Readers 1 and 2 identified C7–T3 (facet joints), T5–T7 and T12 (costovertebral joints), and T8–T9 (costotransverse joints), as common sites of ankylosis at baseline and at 2-year follow-up. The ICCs for the facet, costovertebral, and costotransverse joints at baseline were 0.876, 0.952, and 0.753, respectively. OR of baseline costovertebral and costotransverse joint ankylosis for predicting syndesmophyte progression of the vertebral body was 4.644 [95% confidence interval (CI), 2.295–9.398] and 1.524 (95% CI, 1.036–2.244), respectively. Conclusion: Costotransverse joint ankylosis in r-axSpA patients can be measured semi-quantitatively on whole spine CT, and ankylosis of the costotransverse and costovertebral joints predicts the progression of syndesmophytes. Trial registration: Not applicable.

Background/Aims We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP). Methods Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined. Results A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern. Conclusions NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.

Solar radiation, particularly ultraviolet radiation (UVR, 280–400 nm), is known to play a significant role in driving primary production in marine ecosystems. However, our understanding of the specific effects of UVR on the primary production of natural phytoplankton communities is still limited. We utilized the 13C stable isotope to quantify primary production and conducted experiments using different types of incubation bottles (polycarbonate and quartz bottles) to compare the primary production in the absence and presence of UVR. Although we observed a weak inhibitory effect at the surface of the water column, UVR exposure resulted in an approximately 1.5-fold increase in primary production over the euphotic zone. The enhanced primary production during the study period can be attributed to the combined effect of low UVB (280–320 nm) dose and abundant nutrient conditions. Notably, our size-fractionated measurements revealed that UVR exposure led to a two-fold increase in primary production in large cells (>2 μm) compared to the exposure of solely photosynthetically active radiation (PAR). In contrast, there was no significant difference in the primary production of small cells (

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan–Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p

A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule. Compressive neuropathy caused by a ganglion cyst is rarely reported, with the majority of documented cases involving peroneal nerve palsy. To date, cases demonstrating both peroneal and tibial nerve palsies resulting from a ganglion cyst forming on a branch of the sciatic nerve have not been reported. In this paper, we present the case of a 74-year-old man visiting an outpatient clinic complaining of left-sided foot drop and sensory loss in the lower extremity, a lack of strength in his left leg, and a decrease in sensation in the leg for the past month without any history of trauma. Ankle dorsiflexion and great toe extension strength on the left side were Grade I. Ankle plantar flexion and great toe flexion were Grade II. We suspected peroneal and tibial nerve palsy and performed a screening ultrasound, which is inexpensive and rapid. In the operative field, several cysts were discovered, originating at the site where the sciatic nerve splits into peroneal and tibial nerves. After successful surgical decompression and a series of rehabilitation procedures, the patient’s neurological symptoms improved. There was no recurrence.

Abstract Background As significant advances in the field of treatment for rheumatoid arthritis (RA), there is a great need to identify the healthcare outcomes such as treatment satisfaction and health-related quality of life (HRQoL) of patients with various treatment options. This study aims to identify the difference in the treatment satisfaction and HRQoL of patients with RA using different treatment options, by comparing the treatment satisfaction and HRQoL in patients with RA treated with tofacitinib and adalimumab in real-world settings in Korea, using propensity score methods. Methods In this non-interventional, multicenter, cross-sectional study (NCT03703817), a total of 410 patients with RA diagnosis were recruited in 21 university-based hospitals throughout Korea. The treatment satisfaction and HRQoL were assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) and EQ-5D questionnaires self-reported by the patients. This study compared outcomes between two drug groups in unweighted, greedy matching, and stabilized inverse probability of treatment weight (IPTW) samples using propensity score. Results In all three samples, tofacitinib group showed higher convenience domain of TSQM than that in the adalimumab group, but not effectiveness, side effects, and global satisfaction domains. Multivariable analysis using the covariates of demographic and clinical characteristics of the participants also showed consistent results in TSQM. No statistical difference in EQ-5D-based HRQoL was identified between two drug groups in all three samples. Conclusions This study identified that tofacitinib shows higher treatment satisfaction in the convenience domain of TSQM rather than adalimumab, suggesting that various factors such as drug formulation, route or frequency of administration, and storage can have an impact on the treatment satisfaction, especially the convenience domain. These findings may be useful to patients and physicians when determining treatment options. Trial registration ClinicalTrials.gov, NCT03703817.

Abstract The CT syndesmophyte score (CTSS) can evaluate spinal progression more precisely than mSASSS in ankylosing spondylitis (AS); however, it is complex and time consuming. Here, we propose a simplified CTSS (sCTSS) for measuring spinal structural changes in AS. Patients with AS were recruited from a single tertiary hospital. Baseline and 2-year follow-up whole spine CT images were used to calculate CTSS and sCTSS. The sCTSS used the anterior and posterior vertebral corners, and ranged 0–184. Intraclass correlation coefficients (ICC) were calculated, as well as the smallest detectable changes. Fifty AS patients were included. For reader 1, the mean sCTSS at baseline and 2-year follow-up were 11.7 ± 14.6 and 15.8 ± 16.1, whereas those for reader 2 were 12.0 ± 12.5 and 15.8 ± 15.7, respectively. The ICCs for CTSS at baseline and at 2-year follow-up were 0.97 (95% confidence interval [CI] 0.96–0.99) and 0.98 (0.97–0.99), respectively, and that for changes over the 2 years was 0.48 (95% CI 0.23–0.67). For sCTSS, the ICCs were 0.96 (95% CI 0.92–0.97), 0.97 (95% CI 0.94–0.98), and 0.58 (95% CI 0.36–0.74), respectively. Detection rates for syndesmophyte progression were comparable between CTSS and sCTSS. The detection rate for syndesmophytes on only lateral side was 13.2 and 11.4%, and 11.4 and 15.2% at baseline and 2-year follow-up (reader 1 and 2). sCTSS and CTSS showed similar detection rates for syndesmophyte progression. sCTSS may be a reliable method for evaluating spinal structural damage in AS.

Over the past two decades, the environmental characteristics of the northern East China Sea (NECS) that make it a crucial spawning ground for commercially significant species have faced substantial impacts due to climate change. Protein (PRT) within phytoplankton, serving as a nitrogen-rich food for organisms of higher trophic levels, is a sensitive indicator to environmental shifts. This study aims to develop a regional PRT algorithm to characterize spatial and temporal variations in the NECS from 2012 to 2022. Employing switching chlorophyll-a and particulate organic nitrogen algorithms, the developed regional PRT algorithm demonstrates enhanced accuracy. Satellite-estimated PRT concentrations, utilizing data from the Visible Infrared Imaging Radiometer Suite (VIIRS), generally align with the 1:1 line when compared to in situ data. Seasonal patterns and spatial distributions of PRT in both the western and eastern parts of the NECS from 2012 to 2022 were discerned, revealing notable differences in the spatial distribution and major controlling factors between these two areas. In conclusion, the regional PRT algorithm significantly improves estimation precision, advancing our understanding of PRT dynamics in the NECS concerning PRT concentration and environmental changes. This research underscores the importance of tailored algorithms in elucidating the intricate relationships between environmental variables and PRT variations in the NECS.

Abstract The present study evaluated the predictive role of baseline radiographic change and disease activity on drug retention and clinical response in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitor (TNFi). Korean Observational Study Network for Arthritis (KORONA) registry was evaluated to identify RA patients treated with a TNFi. Disease activity score-28 (DAS28) was evaluated at baseline and 1 year after TNFi initiation or at termination of TNFi due to inefficacy (within 1 year). The retention rate of TNFi was compared in patients with and without bony erosions. The hazard ratio (HR) for drug retention was evaluated by Cox regression analysis, as was the odds ratio (OR) for achieving remission (DAS28

Abstract Herein, we investigated the effect of DJ-1 on helper T cell differentiation, fibroblast-like synoviocyte (FLS) activation, and osteoclastogenesis in rheumatoid arthritis (RA). Serum and synovial fluid (SF) of RA and osteoarthritis (OA) patients were collected, and DJ-1 and H2O2 levels were investigated. CD4+ cells from peripheral blood mononuclear cells (PBMCs) were cultured under type 17 helper T cell (Th17) polarization conditions, and CD4+ T cell differentiation, pro-inflammatory cytokine levels, and soluble receptor activator of nuclear factor kappa-Β ligand (RANKL) were assessed. RA-FLSs were stimulated with 50 μM H2O2, and DJ-1 (10, 50, 100 ng/mL) to evaluate MMP-9, VEGF, TNF-α, and sRANKL production, while RANKL+ FLSs were assessed using flow cytometry. Monocytes were cultured with RANKL or IL-17A with or without DJ-1 and H2O2-pretreated RA-FLS, and tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR of osteoclast-related genes were performed. The levels of DJ-1 and H2O2 in serum and SF of RA patients were higher than those of OA patients. Under Th17-polarizing conditions, CD4+RANKL+ and CD4+CCR4+CCR6+CXCR3- T cells decreased, whereas CD4+CD25highFoxp3+ T cell increased after DJ-1 administration. Additionally, IL-17A, TNF-α, and sRANKL levels decreased in DJ-1-treated groups. DJ-1 lowered MMP-9, VEGF, TNF-α, and sRANKL levels, and RANKL+ FLS in ROS-stimulated RA-FLS. Both RANKL and IL-17A stimulated osteoclast differentiation, DJ-1 decreased TRAP+ cell count, and the expression levels of TRAP, ATP6v0d2, NFATc1, and CTSK. These findings were also observed in in vitro osteoclastogenesis with DJ-1 pretreated RA-FLS. As DJ-1 regulates Th17/Treg imbalance, pro-inflammatory cytokine production, RA-FLS activation, and osteoclastogenesis, it holds potential for RA therapy.

OBJECTIVES This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA). METHODS We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups. RESULTS Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups. CONCLUSIONS In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.

Abstract Rheumatoid arthritis (RA) is a systemic inflammatory arthritis in which primary prevention is key. However, the impact of lifestyle and comorbidities on RA development is unknown. Data from the Korean National Health Insurance Service (NHIS)-national sample cohort from 2002 to 2016 were used. At baseline, demographic characteristics, socioeconomic status, type of residential area, lifestyle behaviours (including exercise), and comorbidities (including the Charlson Comorbidity Index, CCI) were included. Cox regression analysis and Kaplan–Meier curves were used to evaluate the impact of lifestyle and comorbidities on seropositive RA occurrence. A total of 517,053 participants were included in the analysis for seropositive RA occurrence. Mean follow up duration was 71.5 and 142.3 person-month for seropositive RA occurrence group and non-occurrence group, respectively. Seropositive RA was diagnosed in 1,948 participants (0.37%) during follow-up. Cox regression analysis revealed that being aged between 40 and 79, a higher CCI, and hyperlipidemia resulted in elevated hazard ratios (HRs) for seropositive RA, whereas male gender, city residence, moderate alcohol consumption, high regular exercise and a BMI between 23 and 34.9 kg/m2 resulted in lower HRs. Using Korean NHIS data, the present study demonstrates that high-intensity regular physical exercise and moderate alcohol consumption are negatively associated with seropositive RA occurrence, which are modifiable lifestyle habits that might aid the primary prevention of seropositive RA.

Each phytoplankton species has intrinsic pigments, which result in different photophysiological characteristics in response to natural light conditions. Therefore, phytoplankton pigments provide important information on the photosynthetic activity that produces the basic food source for marine ecosystems. This study addresses the challenge of accurately measuring pigment production rates in phytoplankton communities. Two strategies are proposed for improving measurement sensitivity. Firstly, increasing the injection of 13C substrate into incubation bottles up to 15% of the total dissolved inorganic carbon is recommended, with minimal impact on pigment production rate determinations. Secondly, optimizing sample injection volume for high-performance liquid chromatography balances analysis time and dilution effects. The in situ field experiments conducted in this study for pigment production measurements revealed diminished activity of photoprotective mechanisms involving zeaxanthin and diatoxanthin during the study period. Furthermore, the results showed that the notable production rates of chl-b (0.069–0.105 ng C L–1 h–1, 74–89% of total accessary pigment production rates), an accessory pigment mainly attributed to prasinophytes, potentially due to restricted light availability. Prioritization of chl-b production over primary production (negative correlation between primary and chl-b production; R2 = 0.6662) highlights the potential impact of compensatory pigment-related activities on overall phytoplankton productivity. In conclusion, this study underscores the significance of directly quantifying pigment production rates to enhance our comprehension of phytoplankton photophysiology and the production mechanisms specific to various pigments.

Various approaches have been applied to red tide monitoring in Korea since reliable information on phytoplankton communities is crucial. In this study, we employed a high-performance liquid chromatography (HPLC) method to analyze two types of red tide, Mesodinium rubrum and Margalefidinium polykrikoides (also known as Cochlodinium polykrikoides), along the southern coasts of Korea. During the M. rubrum red tide on 8 August 2022, an unusual dominance of cryptophytes was observed, being the most dominant phytoplankton group. A significant positive correlation was found between alloxanthin concentrations, a marker pigment of cryptophytes, and M. rubrum cell numbers (p < 0.01, r = 0.830), indicating that HPLC-derived alloxanthin concentrations can serve as a valuable indicator for identifying red tides caused by M. rubrum and estimating cell numbers. However, it is crucial to consider the temporal dynamics of the prey–predator relationship between cryptophytes and M. rubrum. Further investigation is required to understand the environmental conditions that promote cryptophyte predominance and their role in M. rubrum red tide development. In the second field campaign on 29 August 2022, we observed a significant correlation between the concentration of peridinin, a marker pigment for dinoflagellates, and M. polykrikoides cell numbers (p < 0.01, r = 0.663), suggesting that peridinin can serve as a reliable indicator of M. polykrikoides red tides. In conclusion, HPLC-derived pigments, namely alloxanthin and peridinin, can be used to effectively monitor red tides caused by M. rubrum and M. polykrikoides, respectively. However, to overcome certain methodological limitations of HPLC, future studies should explore additional markers or analytical techniques capable of differentiating M. polykrikoides from other coexisting dinoflagellate species. Furthermore, the broad applicability of our method requires thorough investigation in diverse ecosystems to fully comprehend its scope and limitations. Future research should focus on evaluating the method’s efficacy in different contexts, accounting for the distinct traits of the ecosystems under consideration.

Understanding of the primary production of phytoplankton in the Kara Sea (KS), the Laptev Sea (LS), and the East Siberian Sea (ESS) remains limited, despite the recognized importance of phytoplankton in the Arctic Ocean. To address this knowledge gap, we conducted three NABOS (Nansen and Amundsen Basins Observational System) expeditions in 2013, 2015, and 2018 to measure in situ primary production rates using a 13C-15N dual-tracer method and examine their major controlling factors. The main goals in this study were to investigate regional heterogeneity in primary production and derive its contemporary ranges in the KS, LS, and ESS. The daily primary production rates in this study (99 ± 62, 100 ± 77, and 56 ± 35 mg C m−2 d−1 in the KS, LS, and ESS, respectively) are rather different from the values previously reported in each sea mainly because of spatial and regional differences. Among the three seas, a significantly lower primary production rate was observed in the ESS in comparison to those in the KS and LS. This is likely mainly because of regional differences in freshwater content based on the noticeable relationship (Spearman, rs = −0.714, p < 0.05) between the freshwater content and the primary production rates observed in this study. The contemporary ranges of the annual primary production based on this and previous studies are 0.96–2.64, 0.72–50.52, and 1.68–16.68 g C m−2 in the KS, LS, and ESS, respectively. Further intensive field measurements are warranted to enhance our understanding of marine microorganisms and their community-level responses to the currently changing environmental conditions in these poorly studied regions of the Arctic Ocean.

We investigated the spatio-temporal variations in three key biomolecular compounds (carbohydrates, proteins, and lipids) in particulate organic matter (POM) in the Yellow Sea (YS), South Sea of Korea (SS), East China Sea (ECS), and East Sea (Sea of Japan; ES) in order to estimate the regional annual calorie production rates based on the seasonal data obtained in each region. Carbohydrates were found to be most dominant, followed by lipids across all seas. The euphotic-integral calorie contents of POM during the study period were determined as 53.5 ± 12.6 Kcal m−2 in the YS; 54.2 ± 7.5 Kcal m−2 in the SS; 35.7 ± 9.2 Kcal m−2 in the ECS; and 58.7 ± 6.2 Kcal m−2 in the ES. Utilizing seasonal carbon conversion factors and primary production rates, we estimated the annual calorie productions, which were highest in the ES (1705 Kcal m−2 y−1) and lowest in the ECS (403 Kcal m−2 y−1). This can be attributed to the significantly higher energy efficiency of phytoplankton and faster turnover rate of calorie content. However, caution must be taken when comparing these estimates regionally, considering potential variations in developmental phases among the four regions during the sampling period in 2018. The calorie production rates in this study provide valuable insights into the physiological condition of phytoplankton within specific regions.

Abstract The clinical data on the biologic disease-modifying antirheumatic drug (bDMARD) use in late-onset ankylosing spondylitis (LOAS) is limited. Thus, this study aimed to evaluate the drug efficacy and retention rate of bDMARDs in LOAS and compare it to young-onset ankylosing spondylitis (YOAS). Data of patients with AS receiving bDMARDs were extracted from the Korean College of Rheumatology Biologics and Targeted Therapy registry. Patients whose age of onset was > 50 years and ≤ 50 years were classified as having LOAS and YOAS, respectively. Their baseline characteristics and disease-associated parameters were evaluated. Drug efficacy [Ankylosing Spondylitis Disease Activity Score (ASDAS)-clinically important improvement (CII), ASDAS-major improvement (MI), Assessment of SpondyloArthritis International Society (ASAS) 20, and ASAS 40] at 1-year follow-up and drug retention rates were assessed. A total of 1708 patients (comprising 1472 patients with YOAS and 236 patients with LOAS) were included in this analysis. The LOAS group had a lower prevalence among males, lower HLA-B27 positivity and a higher prevalence of peripheral arthritis. Patients with LOAS were more likely to have higher disease-associated parameters (inflammatory reactants, patient global assessment, ASDAS-erythrocyte sedimentation rate, and ASDAS-C-reactive protein). LOAS was negatively associated with achieving ASDAS-CII, ASAS 20, and ASAS 40. The drug retention rate was lower in LOAS; however, the propensity score-matched and covariate-adjusted hazard ratios for bDMARD discontinuation were comparable to YOAS. There were no differences in the drug retention rates based on the type of bDMARD used in LOAS. Inferior clinical efficacy and shorter drug retention time were found in patients with LOAS receiving bDMARDs using real-world nationwide data. There were no differences among each bDMARD type.

Abstract Background Dysbiosis of ulcerative colitis (UC) has been frequently investigated using readily accessible stool samples. However, stool samples might insufficiently represent the mucosa-associated microbiome status. We hypothesized that luminal contents including loosely adherent luminal bacteria after bowel preparation may be suitable for diagnosing the dysbiosis of UC. Methods This study included 16 patients with UC (9 men and 7 women, mean age: 52.13 ± 14.09 years) and 15 sex- and age-matched healthy individuals (8 men and 7 women, mean age: 50.93 ± 14.11 years). They donated stool samples before colonoscopy and underwent luminal content aspiration and endoscopic biopsy during the colonoscopy. Then, the composition of each microbiome sample was analyzed by 16S rRNA-based next-generation sequencing. Results The microbiome between stool, luminal contents, and biopsy was significantly different in alpha and beta diversities. However, a correlation existed between stool and luminal contents in the Procrustes test (p = 0.001) and Mantel test (p = 0.0001). The stool microbiome was different between patients with UC and the healthy controls. Conversely, no difference was found in the microbiome of luminal content and biopsy samples between the two subject groups. The microbiome of stool and lavage predicted UC, with AUC values of 0.85 and 0.81, respectively. Conclusion The microbiome of stool, luminal contents, and biopsy was significantly different. However, the microbiome of luminal contents during colonoscopy can predict UC, with AUC values of 0.81. Colonoscopic luminal content aspiration analysis could determine microbiome differences between patients with UC and the healthy control, thereby beneficial in screening dysbiosis via endoscopy. Trial registration: This trial was registered at http://cris.nih.go.kr . Registration No.: KCT0003352), Date: 2018–11-13.

Abstract Background Patients with rheumatoid arthritis (RA) have increased levels of interleukin-18 (IL-18) and decreased levels of IL-18 binding protein (IL-18BP) in the serum and synovial fluid (SF) compared to those in patients with osteoarthritis (OA) or in healthy controls. In this study, we evaluated the effects of IL-18BP on osteoclastogenesis and T cell differentiation in RA in vitro. Methods Serum and SF of patients with RA and OA were collected to compare IL-18 and IL-18BP levels by the enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) and SF mononuclear cells (SFMCs) of RA patients were cultured under type 17 helper T cell (Th17) polarisation conditions with or without IL-18BP. In addition, PBMCs were cultured in the presence of receptor activator of nuclear factor kappa-Β ligand (RANKL) or IL-17A with or without IL-18BP, and tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative polymerase chain reaction for expression levels of osteoclast-related genes were performed. Results IL-18 levels were higher in the serum and SF of patients with RA, whereas IL-18BP was lower in the SF of patients with RA than in the control group. Treatment of patients’ PBMCs with IL-18BP decreased the differentiation of CD4+ IL-17A+ and CD4+ RANKL+ T cells, whereas the differentiation of CD4+CD25highFOXP3+ T cell population increased in a dose-dependent manner. These changes in CD4+ T cell differentiation were also observed in the SFMCs of patients with RA. The levels IL-17A and soluble RANKL in the culture medium were significantly decreased by IL-18BP. IL-18BP administration decreased TRAP+ cell counts in a dose-dependent manner on the background of stimulation with RANKL-and IL-17A. In addition, expression levels of TRAP, NFATC1, CTSK, and TNFRSF11A (RANK) genes were lower in the IL-18BP treated cells. Conclusion We showed that IL-18BP can rectify the Th17/Treg imbalance and decrease IL-17-induced osteoclastogenesis in PBMCs from patients with RA. Therefore, IL-18BP may have therapeutic potential for RA treatment.

Abstract Background Cardiovascular diseases (CVDs) are the leading cause of death in patients with rheumatoid arthritis (RA). Coronary artery calcium (CAC) score quantifies the severity of atherosclerosis. We estimated CVD risk using several methods and compared these with the CAC score to identify the most suitable CVD risk calculator in RA patients. Methods We recruited RA patients, and the 10-year CVD risk was assessed using various tools, viz. Framingham risk score, Systemic Coronary Risk Evaluation (SCORE), Atherosclerotic Cardiovascular Disease (ASCVD) risk estimator plus, QRISK3, Expanded Risk Score in Rheumatoid Arthritis (ERS-RA), and Reynolds risk score. Computed tomography was used to determine the CAC score of each patient. Correlation analysis and linear regression analysis between the CAC score and CVD risk score was performed. Results In total, 54 RA patients were enrolled. ERS-RA showed the highest correlation coefficient (r = 0.430, P = 0.001). In multivariate linear regression analysis, ERS-RA (β = 10.01, 95% confidence interval 3.78–16.23) showed a positive association with the CAC score in RA patients. Conclusions The ERS-RA method was highly correlated with the CAC score in RA patients. Therefore, the application of the ERS-RA method may be suitable for predicting subclinical atherosclerosis and CVD risk in RA patients.

Interstitial pneumonia with autoimmune feature (IPAF) is a recently established disease entity that is comprised of interstitial lung diseases with evidence of autoimmune features but that does not fulfill the criteria for definite autoimmune rheumatic diseases. The classification criteria for IPAF were defined by the European Respiratory Society and American Thoracic Society in 2015. However, further studies to establish IPAF subgroups and treatment modalities for each subgroup are still needed. In this review, we discuss recent advances regarding IPAF and raise critical points for the diagnosis and management of patients with IPAF from the perspective of rheumatologists.

Abstract Background In the pathogenesis of rheumatoid arthritis (RA), the role of mast cells has not been revealed clearly. We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-α, IL-1β, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FcεR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase− and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-α, IL-1β, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions IL-33 increased inflammatory and tissue-destructive cytokines by activation of mast cells. Mast cells stimulated osteoclast differentiation in monocytes. Mast cells could stimulate osteoclastogenesis indirectly through production of tissue-destructive cytokines and directly through stimulation of osteoclast precursors.

Dietary habits and inter-specific differences in resource use among six commercial fish species, Chelidonichthys spinosus, Cleisthenes pinetorum, Glyptocephalus stelleri, Hexagrammos otakii, Lophius litulon, and Sebastes schlegelii, collected from the southern coast of the East Sea, Korea, were analyzed using stomach content and stable isotope analyses. Teleosts were the main prey items for C. pinetorum and L. litulon, while both crabs and teleosts contributed to the diets of C. spinosus and S. schlegelii. Glyptocephalus stelleri mainly consumed polycheates and carid shrimps, and H. otakii mostly ingested crabs. The composition of prey items was significantly different in the diets of the six fish species. Further, carbon (δ13C) and nitrogen (δ15N) stable isotope values were significantly different among the six species, indicating different trophic positions. L. litulon, C. pinetorum, and S. schlegelii had narrow niches, whereas C. spinosus, G. stelleri, and H. otakii had relatively wider niches. This study demonstrated differences in patterns of food resource use among the six fish species that were categorized into two patterns of resource use according to their main prey items: diet diversity, trophic niche width, and trophic position. These results could contribute to the understanding of trophic relationships among fish species inhabiting the East Sea, Korea.

Background: To compare the incidences of aortic regurgitation, atrial fibrillation (AF), and atrioventricular (AV) block II–III between radiographic axial spondyloarthritis (r-axSpA) patients and the general population (GP). Methods: National Health Insurance Services data were used. R-axSpA patients ( N = 8877) and the age- and sex-matched GP ( N = 26,631) were followed from August 2006 to December 2019. Incidence rates and standardized incidence ratios (SIRs) of aortic regurgitation, AF, and AV block II–III were compared between these groups. Ten-year incidence rates and hazard ratios (HRs) were calculated by the Kaplan–Meier method and Cox regression analysis. Results: Incidence rates of aortic regurgitation, AV block II–III, and AF in the r-axSpA group were 0.42, 0.21, and 4.0 per 1000 person-years (PYs), respectively. In the r-axSpA group, the SIR for aortic regurgitation was highest among 40- to 49-year-old men (4.11). Incidence rates of aortic regurgitation and AF were higher in the r-axSpA group than in the GP group (0.42 versus 0.18 per 1000 PYs 4.00 versus 3.13 per 1000 PYs, both p

Abstract Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, and synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis. Results Serum and synovial IL-25 levels in RA were upregulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers. Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthritis, and the complex interaction and activation of innate and adaptive immune cells are involved in RA pathogenesis. Mast cells (MCs) are one of the tissue-resident innate immune cells, and they contribute to RA pathogenesis. In the present review, the evidence of the pathologic role of MC in RA is discussed based on human and animal data. In addition, the potential role of MC in RA pathogenesis and the research area that should be focused on in the future are suggested.

Background/Aims The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Abstract Background The inflammatory cascade in the rheumatoid arthritis (RA) synovium is modulated by a variety of cytokine and chemokine networks; however, the roles of IL-26, in RA pathogenesis, are poorly defined. Here, we investigated the functional role of interleukin-26 (IL)-26 in osteoclastogenesis in RA. Methods We analyzed levels of IL-20 receptor subunit A (IL-20RA), CD55, and receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs) using confocal microscopy. Recombinant human IL-26-induced RANKL expression in RA-FLSs was examined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Additionally, osteoclastogenesis was evaluated by monocytes co-cultured with IL-26-prestimulated FLSs. Results The expression of IL-20RA in RA-FLSs was higher than that in osteoarthritis-FLSs. Additionally, in IL-26-pretreated RA-FLSs, the expression of IL-20RA (but not IL-10 receptor subunit B) and RANKL increased in a dose-dependent manner, with IL-26-induced RANKL expression reduced by IL-20RA knockdown. Moreover, IL-26-induced RANKL expression was significantly downregulated by inhibition of signal transducer and activator of transcription 1, mitogen-activated protein kinase, and NF-κB signaling. Furthermore, IL-26 promoted osteoclast differentiation from peripheral blood monocytes in the presence of low dose of RANKL, with IL-26 exerting an additive effect. Furthermore, co-culture of IL-26-pretreated RA-FLSs with peripheral blood monocytes also increased osteoclast differentiation in the absence of addition of RANKL. Conclusions IL-26 regulated osteoclastogenesis in RA through increased RANKL expression in FLSs and direct stimulation of osteoclast differentiation. These results suggest the IL-26/IL-20RA/RANKL axis as a potential therapeutic target for addressing RA-related joint damage.

This paper proposes an algorithm that improves ship detection accuracy using preprocessing and post-processing. To achieve this, high-resolution electro-optical satellite images with a wide range of shape and texture information were considered. The developed algorithms display the problem of unreliable detection of ships owing to clouds, large waves, weather influences, and shadows from large terrains. False detections in land areas with image information similar to that of ships are observed frequently. Therefore, this study involves three algorithms: global feature enhancement pre-processing (GFEP), multiclass ship detector (MSD), and false detected ship exclusion by sea land segmentation image (FDSESI). First, GFEP enhances the image contrast of high-resolution electro-optical satellite images. Second, the MSD extracts many primary ship candidates. Third, falsely detected ships in the land region are excluded using the mask image that divides the sea and land. A series of experiments was performed using the proposed method on a database of 1984 images. The database includes five ship classes. Therefore, a method focused on improving the accuracy of various ships is proposed. The results show a mean average precision (mAP) improvement from 50.55% to 63.39% compared with other deep learning-based detection algorithms.

Targeting specific pathologic pro-inflammatory cytokines or related molecules leads to excellent therapeutic effects in inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Most of these agents, known as biologic disease-modifying anti-rheumatic drugs (bDMARDs), are produced in live cell lines and are usually monoclonal antibodies. Several types of monoclonal antibodies target different pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-17A, IL-6, and IL-23/12. Some bDMARDs, such as rituximab and abatacept, target specific cell-surface molecules to control the inflammatory response. The therapeutic effects of these bDMARDs differ in different forms of inflammatory arthritis and are associated with different adverse events. In this article, we summarize the therapeutic utility and adverse effects of bDMARDs and suggest future research directions for developing bDMARDs.

Little information on the phytoplankton community in the Yellow Sea (YS)—especially size-fractionated phytoplankton—is currently available, in comparison to the various physicochemical studies in the literature. Using high-performance liquid chromatography (HPLC), size-fractionated phytoplankton communities were seasonally investigated in the YS in 2019. In the study period, diatoms (55.0 ± 10.2%) and cryptophytes (16.9 ± 9.3%) were the dominant groups. Due to the recent alteration in inorganic nutrient conditions reported in the YS, the contribution of diatoms was lower than in previous studies. The large-sized phytoplankton group (>20 µm) was dominated mostly by diatoms (89.0 ± 10.6%), while the small-sized phytoplankton group (

Abstract Although extra‐glomerular involvement of microscopic polyangiitis is not regarded as a characteristic finding of the disease, tubulointerstitial nephritis should be considered as a new subclass of renal involvement.

Background/Aims Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI. Methods MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and three had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by two blinded readers according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on Haavardsholm’s tenosynovitis score. Results The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected. Conclusions This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice.

Abstract Background To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). Methods This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. Results A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). Conclusions Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. Trial registration ClinicalTrials.gov, NCT02715908. Registered 22 March 2016.

Background/Aims This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). Methods After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4+ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. Results When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14+ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4+ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. Conclusions NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.

A pleasant and quiet cabin in driving a car is one of the most critical factors affecting a customer’s choice in a market. As the traditional noise sources such as power trains become less, the relative contribution of aerodynamic noise to the interior noise of a road vehicle becomes even more critical. In this study, a high-fidelity numerical methodology is developed for the reliable prediction and analysis of the interior transmitted noise due to external flow disturbance. The developed numerical methodology is based on the sequential application of the high-resolution LES technique, wavenumber–frequency transform, and vibroacoustic model. First, the compressible LES techniques with high-resolution grids are employed to accurately predict the external turbulent flow and aeroacoustic fields due to the turbulent flow, at the same time, of a vehicle running at a speed of 110 km/h. Second, surface pressure fluctuations on the front windshield and side windows, obtained from the LES simulation, are decomposed into incompressible and compressible ones using the wavenumber–frequency transform. Lastly, the interior sound pressure levels are predicted using the vibroacoustic model, which consists of the finite element (FE) and statistical energy analysis (SEA) methods. For the efficient computation of the vibroacoustic interaction between the vibration of the vehicle windows and the acoustic field inside the cabin room, the FE and SEA methods are applied in low- and high-frequency ranges, respectively. The predicted interior sound pressure spectral levels agree well with the measured ones. In addition, although the magnitudes of the compressible pressure components are generally lower than those of the incompressible ones, the compressible field is found to contribute more to the interior noise in high-frequency bands. The physical mechanism of the higher transmission is shown to be related to the coincident effect between the compressible pressure field and the structural vibration of the vehicle window.

Background/Aims The present study aimed to investigate whether tocotrienol regulates interleukin 17 (IL-17)-induced osteoclastogenesis in rheumatoid arthritis (RA). Methods We evaluated the effect of tocotrienol on IL-17-induced receptor activator of nuclear factor kappa B ligand (RANKL) production using RA fibroblast-like synoviocyte (FLS), together with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Osteoclast differentiation was confirmed after culturing IL-17-treated RA FLS and Th17 cells with tocotrienol and monocytes. We analyzed the suppressive effect of tocotrienol on Th17 cells percentage or Th17-cytokine levels among peripheral blood mononuclear cells using flow cytometry. Results We found that IL-17 stimulated FLS to produce RANKL and tocotrienol decreased this IL-17-induced RANKL production. Tocotrienol decreased the IL-17-induced activation of mammalian target of rapamycin, extracellular signal-regulated kinase, and inhibitor of kappa B-alpha. When monocytes were incubated with IL-17, RANKL, IL-17-treated FLS or Th17 cells, osteoclasts were differentiated and tocotrienol decreased this osteoclast differentiation. Tocotrienol reduced Th17 cell differentiation and the production of IL-17 and sRANKL; however, tocotrienol did not affect Treg cell differentiation. Conclusions Tocotrienol inhibited IL-17- activated RANKL production in RA FLS and IL-17-activated osteoclast formation. In addition, tocotrienol reduced Th17 differentiation. Therefore, tocotrienol could be a new therapeutic choice to treat bone destructive processes in RA.

Purpose To investigate salivary gland ultrasonography (SGUS) findings in primary Sjögren’s syndrome (pSS) patients positive for the anti-centromere antibody (ACA) and compare these with those in ACA-negative pSS patients. Methods We analyzed demographic, clinical, laboratory, and SGUS data of pSS patients who fulfilled the 2002 American-European Consensus Group classification criteria for pSS. SGUS findings of four major salivary glands (bilateral parotid and submandibular glands) were scored in five categories and compared between ACA-positive and ACA-negative pSS patients. Linear regression analysis was performed to elucidate the factors associated with SGUS score. Results In total, 121 pSS patients were enrolled (19, ACA-positive). The ACA-positive patients were older (67.0 vs 58.0 years, P = 0.028), whereas anti-Ro/SSA and anti-La/SSB positivity was more prevalent in the ACA-negative group (89.2% vs 21.1%, P < 0.001, and 47.1% vs 10.5%, P = 0.007, respectively). The total SGUS and hypoechoic area scores were lower in ACA-positive patients (16.0 vs 23.0, P = 0.027, and 4.0 vs 7.0, P = 0.004, respectively). In univariate regression analysis, being positive for unstimulated salivary flow rate (USFR < 1.5 ml/15 min), anti-Ro/SSA, and rheumatoid factor were positively associated whereas ACA positivity was negatively associated with the SGUS score. In multivariate regression analysis, being positive for USFR, anti-Ro/SSA, and rheumatoid factor showed significant association with the SGUS score. Conclusions ACA-positive pSS patients showed a lower SGUS score than ACA-negative patients, which was especially prominent in the hypoechoic area component.

The feeding and spawning grounds for seahorses have been lost due to nationwide coastal developments in South Korea. However, little information on the feeding ecology of the Korean seahorse (Hippocampus haema) is currently available. The main objective in this study was to understand the feeding strategy of H. haema on the basis of DNA analysis of the contents of the guts. This is the first study on the feeding ecology of H. haema. Crustaceans were found to be major prey for H. haema in this study. Among the 12 identified species, arthropods were predominantly observed as potential prey of H. haema in this study. The Caprella sp. Was detected in all summer specimens followed by the Ianiropsis sp., whereas isopods were dominant, and amphipods accounted for a small proportion in winter specimens. According to the results in this study, there appears to be a seasonal shift in the major prey of H. haema. Moreover, a potential change in the habitats for adults was further discussed. Since this is a pilot study, further studies should be conducted for a better understanding of the feeding ecology of H. haema.

The Japanese sea lion (Z. japonicus) has been regarded as an extinct species since the last report on Dokdo in 1951. Not much ecological information on the Z. japonicus on Dokdo (hereafter Dokdo sea lion) is currently available. Using a discrete time stage-structured population model, we reconstructed the Dokdo sea lion population to explore the effect of human hunting pressure on them. This study provides the first estimate for the Dokdo sea lion population from 1900 to 1951. The reconstructed capture numbers of the Dokdo sea lion and the parameters estimated in this study were well matched with the recorded numbers and ecological parameters reported previously for the Californian sea lion. Based on the reconstructed population, their number rapidly declined after hunting started and it took less than 10 years for a 70% decline of the initial population, which would be considered to be an extinction risk. Since some caveats exist in this study, some caution about our results is necessary. However, this study demonstrates how rapidly human over-hunting can cause the extermination of a large local population. This study will be helpful to raise people’s awareness about endangered marine animals such as local finless porpoises in Korea.

The northern Bering and Chukchi seas are biologically productive regions but, recently, unprecedented environmental changes have been reported. For investigating the dominant phytoplankton communities and relative contribution of small phytoplankton (phaeocystis were dominant phytoplankton communities in 2016 whereas diatoms and Prasinophytes (Type 2) were dominant in 2017 and diatoms were found as major contributors for the small phytoplankton groups. For size-specific primary production, small phytoplankton contributed 38.0% (SD = ±19.9%) in 2016 whereas 25.0% (SD = ±12.8%) in 2017 to the total primary productivity. The small phytoplankton contribution observed in 2016 is comparable to those reported previously in the Chukchi Sea whereas the contribution in 2017 mainly in the northern Bering Sea is considerably lower than those in other arctic regions. Different biochemical compositions were distinct between small and large phytoplankton in this study, which is consistent with previous results. Significantly higher carbon (C) and nitrogen (N) contents per unit of chlorophyll-a, whereas lower C:N ratios were characteristics in small phytoplankton in comparison to large phytoplankton. Given these results, we could conclude that small phytoplankton synthesize nitrogen-rich particulate organic carbon which could be easily regenerated.

Objective To assess the efficacy of a 4-week swallowing rehabilitation program combined with pyriform sinus ballooning in patients with post-stroke dysphagia (PSD). Methods We evaluated a total of 30 patients (n=30) with PSD who were admitted to our medical institution between May of 2014 and October of 2016. These patients were randomly assigned to either the trial group (n=15; a 20-minute conventional rehabilitation followed by a 10-minute pyriform sinus ballooning) or the control group (n=15; a 30-minute conventional rehabilitation). In these patients, the efficacy outcome measures were pharyngeal remnant, the pharyngeal transit time, the Penetration Aspiration Scale (PAS) scores and the Videofluoroscopic Dysphagia Scale (VDS) scores. We compared the differences in efficacy outcome measures at 4 weeks from baseline between the two groups. Results There were significant changes in the pharyngeal remnant, the pharyngeal transit time, the PAS scores and the VDS scores at 4 weeks from baseline between the two groups (p

Dramatic environmental changes have been recently reported in the Yellow Sea (YS), the South Sea of Korea (SS), and the East/Japan Sea (EJS), but little information on the regional primary productions is currently available. Using the 13C-15N tracer method, we measured primary productions in the YS, the SS, and the EJS for the first time in 2018 to understand the current status of marine ecosystems in the three distinct seas. The mean daily primary productions during the observation period ranged from 25.8 to 607.5 mg C m−2 d−1 in the YS, 68.5 to 487.3 mg C m−2 d−1 in the SS, and 106.4 to 490.5 mg C m−2 d−1 in the EJS, respectively. In comparison with previous studies, significantly lower (t-test, p < 0.05) spring and summer productions and consequently lower annual primary productions were observed in this study. Based on PCA analysis, we found that small-sized (pico- and nano-) phytoplankton had strongly negative effects on the primary productions. Their ecological roles should be further investigated in the YS, the SS, and the EJS under warming ocean conditions within small phytoplankton-dominated ecosystems.

Phytoplankton community structure, which plays an important role in determining productivity and food web structure, can provide important information for understanding variations in marine ecosystems under projected climate change scenarios. Rising temperatures due to climate change will increase and intensify water stratification. To understand the community composition and distribution characteristics of phytoplankton under stratified conditions, phytoplankton pigments were analyzed in the Yellow Sea (YS) and East China Sea (ECS) during the late summer season. In addition, pigment production was measured to estimate the physiological characteristics of phytoplankton relating to light, which is an essential element of photosynthesis. During our observation period, no distinct differences were found in the community composition and pigment production of phytoplankton in the YS and the ECS, but differences in the vertical distribution were observed. Overall, the dominant phytoplankton classes at the surface depth were pico-sized cyanobacteria (46.1%), whereas micro- and nano-sized diatoms (42.9%) were the abundant most classes at a 1% light depth. The major factors controlling the vertical distributions of the phytoplankton community were temperature and nutrients (i.e., nitrate and ammonium). Cyanobacteria were positively correlated with water temperature and ammonium, whereas diatoms were negatively related to water temperature and positively correlated with nitrates. Based on the pigment production, it was found that cyanobacteria at the surface layer encountered excessive irradiance conditions during the study period. The productivity of the cyanobacterial community could be decreased under high-light and high-temperature conditions. This means that cyanobacteria could have a negative influence on the quantity and quality of food available to upper trophic organisms under warmer conditions.

The biochemical composition of particulate organic matter (POM) mainly originates from phytoplankton. Transparent exopolymer particles (TEPs) depend on environmental conditions and play a role in the food web and biogeochemical cycle in marine ecosystems. However, little information on their characteristics in the Southern Ocean is available, particularly in winter. To investigate the seasonal characteristics of POM and TEPSs, seawater samples were collected once every two weeks from November 2017 to October 2018 at Jang Bogo Station (JBS) located on the coast of Terra Nova Bay in the Ross Sea. The total chlorophyll-a (Chl-a) concentrations increased from spring (0.08 ± 0.06 μg L−1) to summer (0.97 ± 0.95 μg L−1) with a highest Chl-a value of 2.15 μg L−1. After sea ice formation, Chl-a rapidly decreased in autumn (0.12 ± 0.10 μg L−1) and winter (0.01 ± 0.01 μg L−1). The low phytoplankton Chl-a measured in this study was related to a short ice-free period in summer. Strong seasonal variations were detected in the concentrations of proteins and lipids (one-way ANOVA test, p < 0.05), whereas no significant difference in carbohydrate concentrations was observed among different seasons (one-way ANOVA test, p > 0.05). The phytoplankton community was mostly composed of diatoms (88.8% ± 11.6%) with a large accumulation of lipids. During the summer, the POM primarily consisted of proteins. The composition being high in lipids and proteins and the high caloric content in summer indicated that the phytoplankton would make a good food source. In winter, the concentrations of proteins decreased sharply. In contrast, relatively stable concentrations of carbohydrates and lipids have been utilized for respiration and long-term energy storage in the survival of phytoplankton. The TEPS values were significantly correlated with variations in the biomass and species of the phytoplankton. Our study site was characterized by dominant diatoms and low Chl-a concentrations, which could have resulted in relatively low TEP concentrations compared to other areas. The average contributions of TEP-C to the total POC were relatively high in autumn (26.9% ± 6.1%), followed by those in summer (21.9% ± 7.1%), winter (13.0% ± 4.2%), and spring (9.8% ± 3.1%).

Picocyanobacteria (Prochlorococcus and Synechococcus) play an important role in primary production and biogeochemical cycles in the subtropical and tropical Pacific Ocean, but little biological information on them is currently available in the North Pacific Ocean (NPO). The present study aimed to determine the picocyanobacterial contributions to the total primary production in the regions in the NPO using a combination of a dual stable isotope method and metabolic inhibitor. In terms of cell abundance, Prochlorococcus were mostly dominant (95.7 ± 1.4%) in the tropical Pacific region (hereafter, TP), whereas Synechococcus accounted for 50.8%–93.5% in the subtropical and temperate Pacific region (hereafter, SP). Regionally, the averages of primary production and picocyanobacterial contributions were 11.66 mg C m−2·h−1 and 45.2% (±4.8%) in the TP and 22.83 mg C m−2·h−1 and 70.2% in the SP, respectively. In comparison to the carbon, the average total nitrogen uptake rates and picocyanobacterial contributions were 10.11 mg N m−2·h−1 and 90.2% (±5.3%) in the TP and 4.12 mg N m−2·h−1 and 63.5%, respectively. These results indicate that picocyanobacteria is responsible for a large portion of the total primary production in the region, with higher contribution to nitrogen uptake rate than carbon. A long-term monitoring on the picocyanobacterial variability and contributions to primary production should be implemented under the global warming scenario with increasing ecological roles of picocyanobacteria.

We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE.