Summary Objective We investigated the roles of CXC chemokine ligand 12a (CXCL12a), also known as stromal cell-derived factor-1α (SDF-1α), in endochondral bone growth, which can give us important ...clues to understand the role of CXCL12a in osteoarthritis (OA). Methods Primary chondrocytes and tibial explants from embryonic 15.5 day-old mice were cultured with recombinant mouse CXCL12a. To assess the role of CXCL12a in chondrogenic differentiation, we conducted mesenchymal cell micromass culture. Results In tibia organ cultures, CXCL12a increased total bone length in a dose-dependent manner through proportional effects on cartilage and bone. In accordance with increased length, CXCL12a increased the protein level of proliferation markers, such as cyclin D1 and proliferating cell nuclear antigen (PCNA), in primary chondrocytes as well as in tibia organ culture. In addition, CXCL12a increased the expression of Runx2, Col10 and MMP13 in primary chondrocytes and tibia organ culture system, implying a role of CXCL12a in chondrocyte maturation. Micromass cultures of limb-bud mesenchymal progenitor cells (MPCs) revealed that CXCL12a has a limited effect on early chondrogenesis, but significantly promoted maturation of chondrocytes. CXCL12a induced the phosphorylation of p38 and Erk1/2 MAP kinases and IκB. The increased expression of cyclin D1 by CXCL12a was significantly attenuated by inhibitors of MEK1 and NF-κB. On the other hand, p38 and Erk1/2 MAP kinase and NF-κB signaling were associated with CXCL12a-induced expression of Runx2 and MMP13, the marker of chondrocyte maturation. Conclusion CXCL12a promoted the proliferation and maturation of chondrocytes, which strongly suggest that CXCL12a may have a negative effect on articular cartilage and contribute to OA progression.
Objective
Specific differences in cancer risk have been observed between systemic lupus erythematosus patients and the general population. Although meta-analyses have estimated cancer incidence in ...systemic lupus erythematosus patients, results have been inconclusive. Hence, we aimed to assess malignancy risk in systemic lupus erythematosus patients, compared to the risk in the general population.
Methods
Systemic lupus erythematosus patients (n = 21,016; mean age 41.67 ± 13.14 years; female 90.22%) were selected from the Korean National Health Insurance Service database between 2008 and 2014. Age- and sex-matched controls were randomly sampled in a 5:1 ratio (n = 105,080).
Results
During the 7 years of follow up, malignancy was detected in 763 (3.63%) systemic lupus erythematosus patients and 2667 (2.54%) controls. Systemic lupus erythematosus patients had a higher risk of malignancy than controls (odds ratio 1.44; 95% confidence interval 1.327–1.559), after multivariate adjustment. Systemic lupus erythematosus patients had a higher odds ratio for developing cervical, thyroid, ovarian, and oral cancer, as well as lymphoma, leukemia, and multiple myeloma than controls. Based on subgroup analysis, male systemic lupus erythematosus patients and patients younger than 40 years showed the highest lymphoma risk.
Conclusions
Systemic lupus erythematosus might be an independent risk factor for cancer. Therefore, the importance of cancer screening programs should be emphasized in systemic lupus erythematosus patients. Our study is the first large nationwide cohort study for evaluating the risk of cancer in systemic lupus erythematosus patients.
We analyze the multifractal spectra of daily foreign exchange rates for Japan, Hong-Kong, Korea, and Thailand with respect to the United States in the period from 1991 until 2005. We find that the ...return time series show multifractal spectrum features for all four cases. To observe the effect of the Asian currency crisis, we also estimate the multifractal spectra of limited series before and after the crisis. We find that the Korean and Thai foreign exchange markets experienced a significant increase in multifractality compared to Hong-Kong and Japan. We also show that the multifractality is stronger related to the presence of high values of returns in the series.
Peri-procedural myocardial infarction (MI) is a not infrequent complication of percutaneous coronary intervention (PCI), but conflicting information exists regarding incidence and prognostic impact ...of this event. We investigated frequency, causes, predictors, and clinical relevance of peri-procedural MI, using a large database.
We pooled individual patient-level data from 11 PCI studies in which peri-procedural creatine kinase-MB mass was routinely measured and mortality data were prospectively collected. Among 23 604 patients from 11 studies, 1677 {7.1% 95% confidence interval (CI) 6.8-7.5%} had peri-procedural MI. The most common mechanism of peri-procedural MI was side-branch occlusion. Independent predictors of peri-procedural MI were older age, female gender, diabetes, hypertension, renal dysfunction, multivessel disease, left anterior descending artery disease, left main disease, bifurcation lesion, long lesion, drug-eluting stents, and number of stents. Follow-up varied from 1 year to 5 years. In a crude analysis, patients with peri-procedural MI had significantly a higher risk of mortality than those without peri-procedural MI hazard ratio (HR) 1.47; 95% CI 1.24-1.74. After adjustment for baseline covariates, peri-procedural MI was associated with an increased risk of mortality (HR 1.20; 95% CI 1.04-1.39).
Among patients undergoing PCI, the occurrence of peri-procedural MI measured by CK-MB mass assay was ~7%, and more than half of cases were associated with side-branch occlusion. Several higher risk patients, lesions, and procedural characteristics were independent predictors of peri-procedural MI. Peri-procedural MI was associated with an increase in mortality.
There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC). MicroRNAs are stable in the circulation and may have utility as biomarkers of ...malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers.
To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28) and age-matched healthy donors (n = 28). Serum microRNA levels were assessed by quantitative RT-PCR following preamplification.
microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48) were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years) for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P < 0.05; 0.05; 0.0005 respectively) and in combination, miR-200b + miR-200c normalized to serum volume and miR-103 was the best predictive classifier of SEOC (ROC-AUC = 0.784). This predictive model (miR-200b + miR-200c) was further confirmed by leave one out cross validation (AUC = 0.784).
We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC.
Objectives
Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to ...determine the incidence and risk factors of IRIS in HIV‐infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS.
Methods
This retrospective analysis included adults living with HIV, seen at four university‐affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T‐cell count < 200 cells/μL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score‐matched case–control study between the non‐INSTI and INSTI groups was performed.
Results
The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB‐IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre‐ART CD4 T‐cell count (< 30 cells/μL), higher pre‐ART viral load (≥ 75 000 copies/mL), and TB‐OI.
Conclusions
The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.
In this study, we undertook a randomized phase III trial of 105 NSCLC patients with oligo (one to four) -brain metastases. Patients were randomly assigned (1:1) to receive either stereotactic ...radiosurgery (SRS) followed by chemotherapy or upfront chemotherapy alone. The results demonstrated that SRS followed by chemotherapy did not improve overall survival compared with upfront chemotherapy only.
It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases.
We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome.
The median age was 58 years (range, 29–85) with ECOG 0–1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months 95% confidence interval (CI), 9.2–20.0 in the SRS group and 15.3 months (95% CI, 7.2–23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy),P = 0.248. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance.
Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients.
NCT01301560.
The serious degradation of regional air quality is a critical social issue in East Asia despite continuous efforts to reduce the emission of pollutants and their precursors. To better understand ...high-pollution events in this region, the synoptic weather patterns associated with springtime non-dust high PM10 (High PM10) events and Asian Dust events in Seoul, South Korea, are examined for the 2001–2018 period. It is shown that the two high-pollution events accompany different atmospheric circulations. While High PM10 events are associated with weak surface cyclonic circulations over the Southeast China, Asian Dust events are characterized by strong cyclones over Northeast China. Composite weather maps show that mid-tropospheric circulation anomalies are exactly the opposite between the two events with anticyclonic anomalies over the Korean Peninsula for High PM10 events but cyclonic anomalies for Asian Dust events. The cluster analyses further reveal that High PM10 events are not determined by a single dominant weather pattern. They are associated with surface cyclonic circulations from southeastern China to the Sea of Okhotsk, anticyclonic circulations around the Korean Peninsula or their mixtures. This result is in contrast with the Asian Dust events which are primarily driven by vertically well-organized continental cyclones.
•Both High PM10 and Asian Dust events exhibit a distinct seasonality over the last 18 years.•Synoptic weather patterns of High PM10 and Asian Dust events, observed in Seoul, South Korea, are quite different.•High PM10 events are related to pollutant transport from external sources and accumulation of local pollutants.•All of Asian Dust events are characterized by well-developed synoptic-scale cyclones.
The differential cross sections of the Σ^{-}p→Λn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise ...angular information about the Σ^{-}p→Λn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 statistical error(stat.) ±0.65 systematic error(syst.) mb and 15.8±0.83(stat)±0.52(syst) mb for 470<p_{Σ}(MeV/c)<550 and 550<p_{Σ}(MeV/c)<650, respectively. These results show a drastic improvement compared with past measurements of the hyperon-proton scattering experiments. They will play essential roles in updating the theoretical models of the baryon-baryon interactions.
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