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This study determined the concentrations of toxic metals including As, Cd, Hg and Pb in commonly consumed crustaceans collected from South Korea. The samples were prepared by wet digestion using HN...

This study aimed to investigate whether the influenza annual outbreak in Korea is related to hospitalisation-related flares in systemic lupus erythematosus (SLE) patients.The weekly frequency of hospitalisation-related SLE flares (2012-2015) was collected from the Korean National Health Insurance claim database. The weekly laboratory-confirmed detection rate of influenza infection was obtained from the Korea Centers for Disease Control and Prevention database. A generalised linear model was used to examine the relative risks (RRs) of hospitalisation-related SLE flares associated with influenza infection, after adjusting for time trends and meteorological data.A total of 2,223 hospitalisation-related SLE flares were analysed. An interquartile range (24.5%) increase in influenza infection was associated with a 14.0% increase in hospitalisation-related SLE flares (RR, 1.14; 95% confidence interval [CI]: 1.04-1.25; p=0.006). In addition, influenza infections at lag 0-1 (over 2 weeks including concurrent and 1 previous week) and lag 0-2 (over 3 weeks including concurrent and 2 previous weeks) were associated with increase in hospitalisation-related SLE flares (RR, 1.14; 95% confidence interval [CI]: 1.03-1.26; p=0.014 and RR, 1.13; 95% CI: 1.02-1.26; p=0.023). Significant associations were especially observed in women (RR, 1.15; 95% CI: 1.15-1.16; p=0.006) and immunosuppressant (RR, 1.26; 95% CI: 1.26-1.27; p0.001) or glucocorticoid recipients (RR, 1.17, 95% CI: 1.16-1.17; p=0.004).This study shows a significant association between seasonal influenza infection and flares in SLE patients, which suggests influenza can be a novel environmental risk factor for SLE flares.

Understanding the mechanistic features and molecular taxonomy of diseases holds promise for the development of more effective treatments, especially for complex heterogeneous diseases. Here, we analyzed transcriptomic datasets of salivary gland tissues from patients with Sjögren's syndrome (SjS) to identify shared and divergent cellular and molecular signatures. Three molecular subtypes of SjS salivary gland tissue were identified: oxidative phosphorylation (OxPhos)-dominant (C1), weak inflammatory with type I interferon signatures (C2), and B cell receptor (BCR) signaling pathway-dominant (C3). C3 had the highest focus score. Type I helper T cells and B cells were the dominant cell types in C1 and C3 tissues, respectively. Metformin and drugs targeting PI3K, BTK, and JAKs were predicted to be effective treatments for C1 and C3 subtypes, respectively. Three subtypes of SjS salivary gland with distinct molecular signatures were identified. The results could contribute to optimal stratification of patients for more effective treatment approaches.

Exposure to heavy metals, including arsenic (As), lead (Pb), cadmium (Cd), and mercury (Hg), is a major health hazard. The toxic effects of these heavy metals can exist in a latent state. These met...

Prediction and determination of drug efficacy for radiographic progression is limited by the heterogeneity inherent in axial spondyloarthritis (axSpA). We investigated whether unbiased clustering analysis of phenotypic data can lead to coherent subgroups of axSpA patients with a distinct risk of radiographic progression.A group of 412 patients with axSpA was clustered in an unbiased way using a agglomerative hierarchical clustering method, based on their phenotype mapping. We used a generalised linear model, naïve Bayes, Decision Trees, K-Nearest-Neighbors, and Support Vector Machines to construct a consensus classification method. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).axSpA patients were classified into three distinct subgroups with distinct clinical characteristics. Sex, smoking, HLA-B27, baseline mSASSS, uveitis, and peripheral arthritis were the key features that were found to stratifying the phenogroups. The three phenogroups showed distinct differences in radiographic progression rate (p0.05) and the proportion of progressors (p0.001). Phenogroup 2, consisting of male smokers, had the worst radiographic progression, while phenogroup 3, exclusively suffering from uveitis, showed the least radiographic progression. The axSpA phenogroup classification, including its ability to stratify risk, was successfully replicated in an independent validation group.Phenotype mapping results in a clinically relevant classification of axSpA that is applicable for risk stratification. Novel coupling between phenotypic features and radiographic progression can provide a glimpse into the mechanisms underlying divergent and shared features of axSpA.

Objective. Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disorder that impairs patients’ overall health-related quality of life (HRQOL). In this study, we evaluated the effect of adalimumab in Korean patients with active RA on HRQOL. Methods. Patients included in the study had moderate to severe active RA that did not respond to conventional drugs with a Disease Activity Score of 28 joints ＞3.2 and were biologics-naive. All patients received adalimumab 40 mg subcutaneously every other week and were followed for 24 weeks. The primary endpoint was the change in baseline Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 24. Secondary endpoints were changes in the EuroQol 5-dimension 3-Level (EQ-5D-3L) baseline score and Short Form 36-Item Health Survey (SF-36) domain scores at weeks 12 and 24 and change in baseline HAQ-DI score at week 12. Results. In total, 91 Korean patients were included. Ninety-three percent of patients were in high disease activity with a baseline mean DAS28 value of 6.1 within all patients. The mean change from baseline in HAQ-DI scores were -0.46 at week 12 and∼0.67 at week 24 (p＜0.0001). Additionally, EQ-5D-3L score at weeks 12 and 24 had significantly improved (p＜0.0001) compared to baseline. SF-36 at weeks 12 and 24 had significantly improved (p＜0.0001, p=0.0001) compared to baseline. Conclusion. Treatment with adalimumab resulted in significant improvement in HAQ-DI, EQ-5D-3L, and SF-36 scores at 12 and 24 weeks in Korean RA patient. (J Rheum Dis 2021;28:68-75)

Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) involves mixing oxaliplatin with 5% dextrose solution (5DW) to prevent the structural degradation of oxaliplatin in chloride-containing fluids. This study evaluated oxaliplatin degradation in carrier fluids containing different chloride ion concentrations to determine a carrier fluid that is optimal for use in oxaliplatin-based HIPEC.Five types of carrier fluids (normal saline, half saline, 5DW, Dianeal PD-2 peritoneal dialysis solution, and non-chloride Dianeal solution) were compared. An in vitro study was performed that monitored an oxaliplatin concentration of 1 ml (2 mg/ml) oxaliplatin mixed in 24 ml of each carrier fluid during 3 days to evaluate the rate of oxaliplatin degradation in each carrier fluid. An in vivo study, which subjected Sprague-Dawley rats to HIPEC for 60 min, also was performed. The efficacy of each carrier fluid for preserving oxaliplatin was evaluated using area under the curve (AUC) ratios between peritoneal fluid and plasma.The degradation rate of oxaliplatin in non-chloride fluids was significantly lower than in chloride-containing fluids. However, the rate was less than 10 to 15% at 30 min. The in vivo study indicated that oxaliplatin concentrations in peritoneal fluids did not differ significantly, whereas those in plasma did differ. The AUC ratios of both normal saline and Dianeal were higher than those of 5DW and non-ClChloride-containing fluids, such as normal saline or Dianeal, which display high absorption rates of oxaliplatin and acceptable degradation rates, may be more beneficial for use in oxaliplatin-based HIPEC than 5DW.

Cervical spine (C-spine) instability is a unique and significant characteristic of rheumatoid arthritis (RA) because its occurrence is not rare and it can cause compressive cervical myelopathy, which may lead to serious neurologic sequelae. This study evaluated the prevalence and risk factors of C-spine instabilities in RA patients with a focus on anti-citrullinated protein antibody (ACPA) and biologic disease-modifying antirheumatic drug (DMARD) therapies.The presence of C-spine instabilities in 1114 patients with RA was evaluated using C-spine radiographies according to the defined metrics. Multivariable logistic regression analyses were performed to identify independent predictors of C-spine instability. The initiation of biologic DMARDs was assessed via a Kaplan-Meier analysis and compared using log-rank tests.In total, 306 (27.5%) patients presented with C-spine instabilities. The most common type was atlantoaxial subluxation (AAS; n = 199 [17.9%]). Male sex, positivity for rheumatoid factor and ACPA, erosive change in the peripheral joints, and presence of osteoporosis were independently associated with C-spine instabilities (all P 0.05). In particular, positivity for ACPA was the most powerful risk factor (odds ratio: 2.33 [95% confidence interval: 1.37, 3.96], P = 0.002), and it was closely associated with AAS. Patients with AAS were at a higher risk for early initiation of biologic DMARDs.Positivity for ACPA was a significant risk factor for C-spine instability, and AAS was remarkably correlated to the early initiation of biologic DMARDs, a surrogate index of poor long-term outcomes. Key Points • The presence of antibodies against citrullinated proteins was a strong risk factor for C-spine instability in patients with rheumatoid arthritis. • Atlantoaxial subluxation was significantly associated with early initiation of biologic DMARDs, a surrogate index of poor long-term outcome.

This study determined the concentrations of toxic metals including As, Cd, Hg and Pb in commonly consumed crustaceans collected from South Korea. The samples were prepared by wet digestion using HNO3 and H2O2 by microwave assisted combustion. For As, Cd, and Pb, inductively coupled plasma���mass spectrometry (ICP-MS) was used. Hg content was determined using gold amalgation direct mercury analysis (DMA). The analytical techniques were validated by determining the correlation coefficients, limits of detection and quantification, coefficients of variance, spiking, and accuracy by analysis of an oyster tissue certified reference material (NIST CRM-1566b). The distribution of toxic metals was determined in whole, muscles, and digestive tracts of crustaceans. Furthermore, to provide information on consumer safety, risk assessment in terms of estimated dietary daily/weekly intake, target hazard quotient, and hazard index values was performed. The concentration (mg/kg) was in decreasing order of As (2.17���6.05) > Cd (0.154���4.57) > Pb (0.033���0.128) > Hg (0.011���0.086). The estimated dietary daily/weekly intake, target hazard quotient, and hazard indices were compared with the standards established by United States Environmental Protection Agency, and Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives and were below the threshold values. The analyzed crustaceans are not expected cause threats to consumers upon normal consumption.

Background Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a high clinical burden. The molecular signatures of IPF were analyzed to distinguish molecular subgroups and identify key driver genes and therapeutic targets. Methods Thirteen datasets of lung tissue transcriptomics including 585 IPF patients and 362 normal controls were obtained from the databases and subjected to filtration of differentially expressed genes (DEGs). A functional enrichment analysis, agglomerative hierarchical clustering, network-based key driver analysis, and diffusion scoring were performed, and the association of enriched pathways and clinical parameters was evaluated. Results A total of 2,967 upregulated DEGs was filtered during the comparison of gene expression profiles of lung tissues between IPF patients and healthy controls. The core molecular network of IPF featured p53 signaling pathway and cellular senescence. IPF patients were classified into two molecular subgroups (C1, C2) via unsupervised clustering. C1 was more enriched in the p53 signaling pathway and ciliated cells and presented a worse prognostic score, while C2 was more enriched for cellular senescence, profibrosing pathways, and alveolar epithelial cells. The p53 signaling pathway was closely correlated with a decline in forced vital capacity and carbon monoxide diffusion capacity and with the activation of cellular senescence. CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators as evidence by high diffusion scores in the disease module. Currently available and investigational drugs showed differential diffusion scores in terms of their target molecules. Conclusions An integrative molecular analysis of IPF lungs identified two molecular subgroups with distinct pathobiological characteristics and clinical prognostic scores. Inhibition against CDKs or HDACs showed great promise for controlling lung fibrosis. This approach provided molecular insights to support the prediction of clinical outcomes and the selection of therapeutic targets in IPF patients.

Arsenic is a human carcinogen. Data on urinary arsenic species analyses of Koreans is limited. This study evaluated the arsenic exposure level, contributing factors, and health effects in Korean adults. Dietary intake information and urine samples were obtained from 2,044 participants. Arsenic exposure was assessed based on urinary concentrations of arsenic species, such as inorganic arsenic, As(III) and As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), using high-performance liquid chromatography with inductively coupled plasma mass spectrometry, followed by determination of biomarkers, malondialdehyde and c-peptide. The geometric mean concentrations were 30.9 ㎍/L for the sum of inorganic arsenic and their metabolites, and 84.7 ㎍/L for the total sum of arsenic measured. Urinary concentrations of arsenic species were influenced by age, inhabitant area (inland or coastal), and seafood intake, which was positively correlated with inorganic arsenic, DMA, and AsB. Rice intake was positively correlated with inorganic arsenic and its metabolites but not with AsB. Additionally, malondialdehyde and c-peptide levels were significantly associated with urinary concentrations of various arsenic species. Seafood and rice are major sources of organic/inorganic arsenic exposure in Korean adults; however, it is necessary to evaluate whether their overconsumption could have a potentially detrimental effect on human health.

Machine learning is applied to characterize the risk and predict outcomes in multi-dimensional data. The prediction of radiographic progression in axial spondyloarthritis (axSpA) remains limited. Hence, we tested the feasibility of supervised machine learning algorithms to predict radiographic progression in axSpA.This is a retrospective and hospital-based study. Clinical and laboratory data obtained from two independent axSpA groups were used as training and testing datasets. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and mSASSS worsening by ≥ two units was defined as progression. Seven machine learning models with different algorithms were fitted, and their performance for the testing dataset was assessed using receiver-operating characteristic (ROC) and precision-recall (PR) curve.The training and testing groups had equivalent characteristics, and radiographic progression was identified in 25.3% and 23.7%, respectively. The generalized linear model (GLM) and support vector machine (SVM) were the top two best-performing models with an average area-under-curve (AUC) of ROC of over 0.78. SVM had the higher AUC of PR compared with GLM (0.56 versus 0.51). Balanced accuracy was over 65% in all models. mSASSS was the most informative variable, followed by the presence of syndesmophyte(s) at the baseline and sacroiliac joint grades.Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA. Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients.Key Points• Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA.• Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients.

Purpose – We examine the disclosures on foreign divestment from China by 77 Korean firms between 2007 and 2016 to identify the effects (and their determinants) on parent firm value. Design/methodology – We analyze how divestment affects firm value by examining the disclosure of divestment from China by Korean firms. Then, we examine the determinants of these disclosure effects using cross-sectional regression analyses. Findings – We find negative effects on parent firm value in the short and medium term, and both the KOSPI and KOSDAQ stock markets show negative correlations between foreign divestment and firm value. The parent firm’s financial condition and profitability and the reason for divesting are statistically significant determinants. Practical implications – Most Korean firms in China belong to the manufacturing industry. As a result, divestment signifies a loss of important manufacturing bases and assets. Originality/value – We analyze foreign direct divestment, which has not been studied in detail previously owing to a lack of data. In addition, this research is the first to compare the disclosure effects in the KOSPI market with those in the KOSDAQ market for the same period.

ObjectivesTreatment of patients with systemic sclerosis (SSc) can be challenging because of clinical heterogeneity. Integration of genome-scale transcriptomic profiling for patients with SSc can provide insights on patient categorisation and novel drug targets.MethodsA normalised compendium was created from 344 skin samples of 173 patients with SSc, covering an intersection of 17 424 genes from eight data sets. Differentially expressed genes (DEGs) identified by three independent methods were subjected to functional network analysis, where samples were grouped using non-negative matrix factorisation. Finally, we investigated the pathways and biomarkers associated with skin fibrosis using gene-set enrichment analysis.ResultsWe identified 1089 upregulated DEGs, including 14 known genetic risk factors and five potential drug targets. Pathway-based subgrouping revealed four distinct clusters of patients with SSc with distinct activity signatures for SSc-relevant pathways. The inflammatory subtype was related to significant improvement in skin fibrosis at follow-up. The phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) signalling pathway showed both the closest correlation and temporal pattern to skin fibrosis score. COMP, THBS1, THBS4, FN1, and TNC were leading-edge genes of the PI3K-Akt pathway in skin fibrogenesis.ConclusionsConstruction and analysis of normalised skin transcriptomic compendia can provide useful insights on pathway involvement by SSc subsets and discovering viable biomarkers for a skin fibrosis index. Particularly, the PI3K-Akt pathway and its leading players are promising therapeutic targets.

ObjectivesInterstitial lung disease is a significant comorbidity and the leading cause of mortality in patients with systemic sclerosis. Transcriptomic data of systemic sclerosis-associated interstitial lung disease (SSc-ILD) were analysed to evaluate the salient molecular and cellular signatures in comparison with those in related pulmonary diseases and to identify the key driver genes and target molecules in the disease module.MethodsA transcriptomic dataset of lung tissues from patients with SSc-ILD (n=52), idiopathic pulmonary fibrosis (IPF) (n=549), non-specific interstitial pneumonia (n=49) and pulmonary arterial hypertension (n=81) and from normal healthy controls (n=331) was subjected to filtration of differentially expressed genes, functional enrichment analysis, network-based key driver analysis and kernel-based diffusion scoring. The association of enriched pathways with clinical parameters was evaluated in patients with SSc-ILD.ResultsSSc-ILD shared key pathogenic pathways with other fibrosing pulmonary diseases but was distinguishable in some pathological processes. SSc-ILD showed general similarity with IPF in molecular and cellular signatures but stronger signals for myofibroblasts, which in SSc-ILD were in a senescent and apoptosis-resistant state. The p53 signalling pathway was the most enriched signature in lung tissues and lung fibroblasts of SSc-ILD, and was significantly correlated with carbon monoxide diffusing capacity of lung, cellular senescence and apoptosis. EEF2, EFF2K, PHKG2, VCAM1, PRKACB, ITGA4, CDK1, CDK2, FN1 and HDAC1 were key regulators with high diffusion scores in the disease module.ConclusionsIntegrative transcriptomic analysis of lung tissues revealed key signatures of fibrosis in SSc-ILD. A network-based Bayesian approach provides deep insights into key regulatory genes and molecular targets applicable to treating SSc-ILD.

In patients with systemic lupus erythematosus (SLE), there are concerns that infections may increase the risk of flares. We evaluated the association between influenza infection and SLE flares resulting in hospitalization. SLE flares resulting in hospitalization and influenza cases were ascertained from the Korean national healthcare insurance database (2014–2018). We used a self-controlled case series design. We defined the risk interval as the first 7 days after the influenza index date and the control interval was defined as all other times during the observation period of each year. We estimated the incidence rates of SLE flares resulting in hospitalization during the risk interval and control interval and compared them using a Poisson regression model. We identified 1624 influenza infections among the 1455 patients with SLE. Among those, there were 98 flares in 79 patients with SLE. The incidence ratio (IR) for flares during the risk interval as compared with the control interval was 25.75 (95% confidence interval 17.63–37.59). This significantly increased the IRs for flares during the risk interval in both women (IR 27.65) and men (IR 15.30), all age groups (IR 17.00–37.84), with and without immunosuppressive agent (IR 24.29 and 28.45, respectively), and with and without prior respiratory diseases (IR 21.86 and 26.82, respectively). We found significant association between influenza infection and SLE flares resulting in hospitalization. Influenza infection has to be considered as a risk factor for flares in all SLE patients regardless of age, sex, medications, and comorbidities.

Rheumatoid arthritis (RA) patients may benefit from exercise for several reasons. However, whole-limb strengthening exercises for such patients remain poorly studied. We hypothesized that systemic strength training that includes the upper and lower extremities would improve strength per se and enhance the quality of life. Here, we investigated the effects of 12 weeks of upper- and lower-limb strengthening exercise on the strength and quality of life of RA patients using the International Classification of Functioning, Disability, and Health model. This was a prospective, interventional controlled trial. Forty female RA patients were recruited and assigned to two groups not based on willingness to exercise, with 20 patients in the exercise group and 20 in the control group. All patients in the exercise group received once-weekly training sessions of 60 min over 12 weeks. All participants were assessed before and after the 12-week intervention period. We measured the hand grip strength and isometric quadriceps contraction, the cross-sectional area of the rectus femoris (CSA-RF) (via ultrasonography), and performed the 30 s sit-to-stand test and the 6 min walk test (6MWT). We derived the Borg scale score after the 6MWT and assessed the extent of social participation and quality of life using a Korean version of the 36-Item Short Form Health Survey (SF-36). A total of 35 subjects completed the experiment (18 in the exercise group, 17 in the control group). After the 12-week intervention period, the lower-limb strength and the CSA-RF were significantly increased in the exercise group. The activity level did not change significantly in either group. The exercise group exhibited significant improvements in the SF-36 mental health domain scores. Thus, strengthening exercise is useful for patients with RA.

The network-based proximity between drug targets and disease genes can provide novel insights regarding the repercussions, interplay, and repositioning of drugs in the context of disease. Current understanding and treatment for reversing of the fibrotic process is limited in systemic sclerosis (SSc). We have developed a network-based analysis for drug effects that takes into account the human interactome network, proximity measures between drug targets and disease-associated genes, genome-wide gene expression and disease modules that emerge through pertinent analysis. Currently used and potential drugs showed a wide variation in proximity to SSc-associated genes and distinctive proximity to the SSc-relevant pathways, depending on their class and targets. Tyrosine kinase inhibitors (TyKIs) approach disease gene through multiple pathways, including both inflammatory and fibrosing processes. The SSc disease module includes the emerging molecular targets and is in better accord with the current knowledge of the pathophysiology of the disease. In the disease-module network, the greatest perturbing activity was shown by nintedanib, followed by imatinib, dasatinib, and acetylcysteine. Suppression of the SSc-relevant pathways and alleviation of the skin fibrosis was remarkable in the inflammatory subsets of the SSc patients receiving TyKI therapy. Our results show that network-based drug-disease proximity offers a novel perspective into a drug’s therapeutic effect in the SSc disease module. This could be applied to drug combinations or drug repositioning, and be helpful guiding clinical trial design and subgroup analysis.

The clinical manifestations and treatment outcome in patients with rheumatoid arthritis (RA) are heterogeneous. We classified RA patients into subgroups with distinct phenotypes through unsupervised clustering and evaluated the utility of this subclassification for evaluation of clinical outcome.A total of 1,103 patients with RA were clustered in an unbiased manner using a k-means clustering method, based on their clinical and phenotypic profiles. Initiation of biological disease-modifying anti-rheumatic drugs (bDMARDs) was evaluated in the segregated clusters to investigate the differential clinical course of each cluster.Patients with RA were classified into four clusters, each with distinct phenotypes. The key features for subclassification were sex, smoking, hypertension, and dyslipidaemia. Cluster 1 consisted of male smokers, who were most likely to initiate bDMARDs by 30 months (p=0.04). Multivariate analysis revealed that overweight, smoking, erythrocyte sedimentation rate, autoantibodies of high titre, and disease activity were the independent predictors of bDMARD initiation at 30 months. Cluster 1 was the highest or the second highest for these independent predictors, suggesting that cluster 1 contained a high-risk group for early initiation of bDMARDs.The unsupervised clustering of RA patients demonstrated the feasibility of the novel subclassification with respect to predicting clinical outcome. Identifying high-risk patients by a combination of clinical parameters may be useful for the management of RA.

The pregnancy rate in systemic lupus erythematosus (SLE) is not fully understood and comparisons of adverse pregnancy outcomes (APOs) with SLE versus the general population are limited. This study aimed to estimate the pregnancy rate and APOs in Korean SLE compared to those without SLE.Pregnant women were identified using the ICD-10 codes for delivery and abortion in the Korean national health claims database (2013-2015). APOs were classified as fetal loss, intrauterine growth retardation (IUGR), pre-eclampsia/eclampsia, and gestational diabetes. Annual incidence rates (IRs) of pregnancy and APOs were calculated in women with SLE and the general population without SLE and the two groups were compared using age-adjusted incidence rate ratios (IRRs). Age-stratified IRRs were further analyzed.The annual IRs of pregnancy in SLE were 29.54-30.70 per 1000 persons. The IRRs were lower in women with SLE than in the general population: 0.68 (0.61-0.76), 0.66 (0.60-0.74), and 0.74 (0.66-0.82) in each respective year. The IRRs of fetal loss, IUGR, and pre-eclampsia/eclampsia were 1.30 (1.14-1.49), 4.65 (3.55-6.09), and 3.43 (2.70-4.36), respectively. However, the IRR of gestational diabetes in SLE did not significantly differ from that of women without SLE. Among the APOs, fetal loss, IUGR, and pre-eclampsia/eclampsia showed decreasing tendencies as age increased.Pregnancy rates in SLE were approximately 30% lower than those in the general population. Except for gestational diabetes, fetal loss, IUGR, and pre-eclampsia/eclampsia were higher in SLE and showed a decreasing tendency with age. Key Points • This population-based cohort study showed that pregnancy rates in SLE were approximately 30% lower than those in the general population. • SLE had a 1.3-fold higher rate of fetal loss, more than 4-fold higher IUGR rate, and more than 3-fold pre-eclampsia or eclampsia rate compared with the general population. • Adverse pregnancy outcomes in SLE showed a decreasing tendency with age.

BackgroundTreatment of patients with Sjögren’s syndrome (SjS) is a clinical challenge with high unmet needs. Gene expression profiling and integrative network-based approaches to complex disease can offer an insight on molecular characteristics in the context of clinical setting.MethodsAn integrated dataset was created from salivary gland samples of 30 SjS patients. Pathway-driven enrichment profiles made by gene set enrichment analysis were categorized using hierarchical clustering. Differentially expressed genes (DEGs) were subjected to functional network analysis, where the elements of the core subnetwork were used for key driver analysis.ResultsWe identified 310 upregulated DEGs, including nine known genetic risk factors and two potential biomarkers. The core subnetwork was enriched with the processes associated with B cell hyperactivity. Pathway-based subgrouping revealed two clusters with distinct molecular signatures for the relevant pathways and cell subsets. Cluster 2, with low-grade inflammation, showed a better response to rituximab therapy than cluster 1, with high-grade inflammation. Fourteen key driver genes appeared to be essential signaling mediators downstream of the B cell receptor (BCR) signaling pathway and to have a positive relationship with histopathology scores.ConclusionIntegrative network-based approaches provide deep insights into the modules and pathways causally related to SjS and allow identification of key targets for disease. Intervention adjusted to the molecular traits of the disease would allow the achievement of better outcomes, and the BCR signaling pathway and its leading players are promising therapeutic targets.

A study of the lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) contents in popular cereals was conducted using inductively coupled plasma – mass spectrometry (ICP-MS), direct mercury analys...

Background Carrier solutions play an important role in the distribution, plasma absorption, chemical stability, and solubility of anticancer agents during hyperthermic intraperitoneal chemotherapy (HIPEC). In the current study, lipophilic properties of carrier solutions were evaluated to determine whether they improved anticancer drug absorption rates using mitomycin-C (MMC) or oxaliplatin HIPEC as compared to hydrophilic carrier solutions. Methods Sprague-Dawley rats were divided into two groups: MMC and oxaliplatin treatment groups. Each group was then further subdivided by carrier solution: Dianeal® PD-2 peritoneal dialysis solution, 5% dextrose solution and 20% lipid solution (Lipision®). HIPEC was performed over 60 min at 41–42 °C using the anticancer drugs MMC (35 mg/m2) or oxaliplatin (460 mg/m2). The plasma area under the curve (AUC; AUCplasma), peritoneal AUC (AUCperitoneum), and peritoneal/plasma AUC ratios were compared among HIPEC carrier solutions. Results Plasma drug concentrations were significantly different among carrier solutions, varying by time. In contrast, peritoneal drug concentrations did not change with carrier solution. In the MMC group, the peritoneal/plasma AUC ratio of a lipid solution was three times higher than Dianeal® (p