Comparative efficacy and safety of subcutaneous infliximab and vedolizumab in patients with Crohn's disease and ulcerative colitis included in randomised controlled trials.

BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.

Uncovering the health implications of abandoned mines through protein profiling of local residents.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

CT and MRI findings beyond the subchondral bone in osteonecrosis of the femoral head to distinguish between ARCO stages 2 and 3A.

OBJECTIVES: To determine the diagnostic values of deep changes beyond the subchondral bone in osteonecrosis of the femoral head (ONFH) to distinguish between Association Research Circulation Osseous (ARCO) stages 2 and 3A. METHODS: This retrospective study included 124 hips with ONFH of stages 2 (n = 49; 23 females; mean age, 50.7 years) and 3A (n = 75; 20 females; mean age, 53.2 years) from May 2017 to August 2022, who underwent CT (n = 124) and MRI (n = 85). Deep changes beyond subchondral bone were analyzed on CT (bone resorption area and cystic change) and on MRI (bone marrow edema [BME] and joint effusion). Diagnostic performance and multivariate analysis were evaluated for detecting stage 3A. RESULTS: Stage 3A showed more frequent bone resorption area (72.0% vs. 4.1%), cystic change (52.0% vs. 0.0%), BME (93.5% vs. 43.6%), and joint effusion (76.0% vs. 24.5%) than stage 2 (p < 0.001, all). Bone resorption area and cystic change showed low sensitivities (52.0~72.0%) but high specificities (96.0~100.0%), while BME and joint effusion showed high sensitivities (76.0~93.0%) but low specificities (56.0~76.0%) for stage 3A. Predictors were in the order of bone resorption area, cystic change, and joint effusion (odds ratio: 32.952, 26.281, 9.603, respectively), and combined bone resorption area and cystic change had the best predictive value (AUC, 0.900) for stage 3A. CONCLUSIONS: Among deep changes, bone resorption area and cystic changes were highly specific and BME and joint effusion were highly sensitive for stage 3A. Combined bone resorption area and cystic change had the best predictive value for predicting ARCO stage 3A. KEY POINTS: • The exact classification between ARCO stage 2 and 3A is essential but it is sometimes difficult to distinguish between ARCO stage 2 and 3A only by subchondral fracture, especially early post-collapse stage with preservation of femoral head contour. • The predictors of stage 3A were in the order of bone resorption area, cystic change, and joint effusion and combined bone resorption area and cystic change had the best predictive value for predicting stage 3A. • Analysis of deep changes beyond the subchondral bone may make it easier to distinguish between ARCO stage 2 and 3A.

A regional brain volume-based age prediction model for neonates and the derived brain maturation index.

OBJECTIVE: To develop a postmenstrual age (PMA) prediction model based on segmentation volume and to evaluate the brain maturation index using the proposed model. METHODS: Neonatal brain MRIs without clinical illness or structural abnormalities were collected from four datasets from the Developing Human Connectome Project, the Catholic University of Korea, Hammersmith Hospital (HS), and Dankook University Hospital (DU). T1- and T2-weighted images were used to train a brain segmentation model. Another model to predict the PMA of neonates based on segmentation data was developed. Accuracy was assessed using mean absolute error (MAE), root mean square error (RMSE), and mean error (ME). The brain maturation index was calculated as the difference between the PMA predicted by the model and the true PMA, and its correlation with postnatal age was analyzed. RESULTS: A total of 247 neonates (mean gestation age 37 ± 4 weeks; range 24-42 weeks) were included. Thirty-one features were extracted from each neonate and the three most contributing features for PMA prediction were the right lateral ventricle, left caudate, and corpus callosum. The predicted and true PMA were positively correlated (coefficient = 0.88, p < .001). MAE, RMSE, and ME of the external dataset of HS and DU were 1.57 and 1.33, 1.79 and 1.37, and 0.37 and 0.06 weeks, respectively. The brain maturation index negatively correlated with postnatal age (coefficient = - 0.24, p < .001). CONCLUSION: A model that calculates the regional brain volume can predict the PMA of neonates, which can then be utilized to show the brain maturation degree. CLINICAL RELEVANCE STATEMENT: A brain maturity index based on regional volume of neonate's brain can be used to measure brain maturation degree, which can help identify the status of early brain development. KEY POINTS: • Neonatal brain MRI segmentation model could be used to assess neonatal brain maturation status. • A postmenstrual age (PMA) prediction model was developed based on a neonatal brain MRI segmentation model. • The brain maturation index, derived from the PMA prediction model, enabled the estimation of the neonatal brain maturation status.

Autodisplay of streptococcal protein G for construction of an orientation-controlled immunoaffinity layer.

An immunoaffinity layer with orientation-controlled antibodies was constructed to express streptococcal protein G in Escherichia coli cells using autodisplay technology. The sequence of protein G, a specific IgG-binding protein, was inserted into the autodisplay vector using recombinant technology and the constructed plasmid vector was transformed into E. coli cells. Protein G was confirmed to be autodisplayed with a high density of 2 × 105 copies per cell by SDS-PAGE analysis, and its IgG-binding affinity was confirmed by fluorescence microscopy. Autodisplayed protein G showed higher affinity than the IgG-binding Z-domain for goat IgG. Immunoassays based on E. coli cells were established to detect horseradish peroxidase (HRP) and C-reactive protein (CRP). Protein G autodisplaying E. coli cells were utilized as a solid support and immunoassays showed improved sensitivity by orientation control of autodisplayed protein G. The outer membrane (OM) of protein G autodisplaying E. coli was isolated and layered to construct an immunoaffinity layer. The OM was coated on a microplate to perform the immunoassays, which showed limits of detection of 5 and 0.2 ng mL-1 for HRP and CRP, respectively. An OM layer with autodisplayed protein G was applied as the immunoaffinity layer of a surface plasmon resonance (SPR) biosensor. After CRP detection, the SPR responses showed good linearity, with an R2 value of 0.99. The immunoaffinity layer with orientation control by autodisplayed protein G was confirmed to be applicable in immunoassays and immunosensors to improve sensitivity.

What Is New in Stage 3 of the 2019 Revised Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head: A Relationship to Bone Resorption.

PURPOSE: The aim of the study is to evaluate the stage 3 findings of the 2019 revision of the Association Research Circulation Osseous (ARCO) staging system for osteonecrosis of the femoral head between 3A and 3B and the relationship with bone resorption area. MATERIALS AND METHODS: We retrospectively enrolled 87 patients with ARCO stage 3 osteonecrosis of the femoral head, divided into stage 3A (n = 73) and 3B (n = 14). The revised stage 3 findings included subchondral fracture, fracture in necrotic portion, and flattening of the femoral head and were compared between stage 3A and 3B. The association between these findings and the causative features of bone resorption area was also evaluated. RESULTS: All stage 3 cases had subchondral fractures. In stage 3A, these fractures were generated by crescent sign (41.1%) and by fibrovascular reparative zone in 58.9%; however, in stage 3B, fibrovascular reparative zone generated 92.9% of these fractures and crescent sign only 7.1% with statistical significance ( P = 0.034). Necrotic portion fracture was noted in 36.7% and femoral head flattening was observed in 14.9% of all stage 3. Necrotic portion fracture (92.9% vs 26.0%) and femoral head flattening (71.4% vs 4.1%) were observed more frequently in stage 3B than 3A ( P < 0.001). Almost all subchondral fractures by fibrovascular reparative zone (96.4%) and necrotic portion fracture (96.9%), and all femoral head flattening was presented with bone resorption area with expanding areas. CONCLUSIONS: The ARCO stage 3 descriptions reflect severity in this order: subchondral fracture, necrotic portion fracture, and femoral head flattening. More severe findings are usually associated with expanding bone resorption areas.

Tenosynovial giant cell tumors of digits: MRI differentiation between localized types and diffuse types with pathology correlation.

OBJECTIVE: To compare the MRI findings between the localized- and diffuse-type tenosynovial giant cell tumors (TSGCTs) of digits with pathology correlation. METHODS: Twenty-eight patients with newly diagnosed TSGCTs of digits (22 localized and 6 diffuse types) who underwent preoperative MRI and surgical excision were included from Jan. 2015 to September 2021. MRI findings regarding nodularity, margins, morphology of hypointensity with pathology correlation, and disease extent (bone erosion, articular involvement, muscle involvement, tendon destruction, and neurovascular encasement) were assessed. RESULTS: Diffuse type was significantly larger (P = 0.006), more multinodular on both MRI and pathology (P = 0.038, both) with significant agreement, and infiltrative on both MRI and pathology (P < 0.001, both) with substantial agreement, and showed central granular on MRI and strong hemosiderin deposition on pathology (P = 0.022 and P = 0.021) with moderate agreement than localized type. Localized type showed significantly more frequent peripheral capsules on both MRI and pathology (P < 0.001, both) with moderate agreement than diffuse type. However, the septum on both MRI and pathology showed no statistically significant difference between the two groups (P = 0.529 and P = 0.372) without significant agreement. The disease extent was more severe in the diffuse type than the localized type regarding articular involvement (P < 0.001), muscle involvement (P < 0.001), and tendon destruction (P = 0.010). No statistically significant differences were found between the two groups regarding bone erosion (P = 0.196) or neurovascular bundle encasement (P = 0.165). CONCLUSIONS: Diffuse-type TSGCTs of digits presented as locally aggressive lesions with larger, multinodular, infiltrative masses exhibiting stronger hemosiderin deposition and more severe disease extents of articular, muscle, and tendon involvement than the localized type.

Acute left iliofemoral vein thrombosis: Comparison between simple and bony May-Thurner syndrome in CT venography.

OBJECTIVES: To explore the etiology of May-Thurner syndrome (MTS) with acute iliofemoral deep vein thrombosis (DVT) regarding imaging findings and clinical features. METHODS: We retrospectively analyzed 57 patients with acute left iliofemoral DVT from 2015 to 2020. The diameter of left common iliac vein (LCIV) at the maximal compression site and its percent compression regarding the average diameter of the uncompressed iliac vein were recorded in central and distal portions of the LCIV according to the location in the quadrant of lumbar vertebral body. Compression was categorized into simple and bony MTS; Simple MTS as LCIV compressed by the right common iliac artery (RCIA) versus Bony MTS as LCIV by lower lumbar degenerative changes regardless of RCIA compression. Initial computed tomographic venography (CTV) regarding chronic change of LCIV such as fibrotic atrophy or cordlike obliteration, extent of thrombus, and lumbar degenerative changes were evaluated. Therapeutic effect after initial therapy was assessed in follow-up CTVs after 3-6 months. RESULTS: All patients showed LCIV compression with 19 simple MTS (mean age, 42.8 ± 14.1 years [23-67 years]; 12 females; symptom for 4.4 ± 5.5 days) and 38 bony MTS (mean age, 73.0 ± 10.2 years [49-85 years]; 26 females; symptom for 5.5 ± 4.8 days). There was significant difference in age (p < .001) and no significant difference in sex or symptom duration between two groups (p = .691 and 0.415, respectively). All simple MTS showed compression only in the central LCIV and half of bony MTS showed compression in both central and distal LCIV (p < .001). Among the lumbar degenerative changes, symmetric anterolateral osteophyte (p < .001) and asymmetric osteophyte (p < .001) were significantly associated with bony MTS, but not scoliosis (p = .799), compared to simple MTS. Although there was no significant difference in chronic change of LCIV, thrombosis extent, and therapeutic effect between two groups (p > .05), chronic change of LCIV showed significant difference between single and dual compression (23.7% vs. 57.9%, p = .024) and residual thrombus after initial therapy was occurred in 21.1% of single compression and 47.4% in dual compression with non-significant trend (p = .082). CONCLUSION: Bony MTS related to lumbar degenerative changes with acute iliofemoral DVT occurs in older patients, presenting more than one stenosis at LCIV, inducing more chronic change with possibly weaker therapeutic effect than simple MTS.

A Fully Automated Visual Grading System for White Matter Hyperintensities of T2-Fluid Attenuated Inversion Recovery Magnetic Resonance Imaging.

BACKGROUND: The Fazekas scale is one of the most commonly used visual grading systems for white matter hyperintensity (WMH) for brain disorders like dementia from T2-fluid attenuated inversion recovery magnetic resonance (MR) images (T2-FLAIRs). However, the visual grading of the Fazekas scale suffers from low-intra and inter-rater reliability and high labor-intensive work. Therefore, we developed a fully automated visual grading system using quantifiable measurements. METHODS: Our approach involves four stages: (1) the deep learning-based segmentation of ventricles and WMH lesions, (2) the categorization into periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH), (3) the WMH diameter measurement, and (4) automated scoring, following the quantifiable method modified for Fazekas grading. We compared the performances of our method and that of the modified Fazekas scale graded by three neuroradiologists for 404 subjects with T2-FLAIR utilized from a clinical site in Korea. RESULTS: The Krippendorff's alpha across our method and raters (A) versus those only between the radiologists (R) were comparable, showing substantial (0.694 vs. 0.732; 0.658 vs. 0.671) and moderate (0.579 vs. 0.586) level of agreements for the modified Fazekas, the DWMH, and the PWMH scales, respectively. Also, the average of areas under the receiver operating characteristic curve between the radiologists (0.80 ± 0.09) and the radiologists against our approach (0.80 ± 0.03) was comparable. CONCLUSIONS: Our fully automated visual grading system for WMH demonstrated comparable performance to the radiologists, which we believe has the potential to assist the radiologist in clinical findings with unbiased and consistent scoring.

CheSS: Chest X-Ray Pre-trained Model via Self-supervised Contrastive Learning.

Training deep learning models on medical images heavily depends on experts' expensive and laborious manual labels. In addition, these images, labels, and even models themselves are not widely publicly accessible and suffer from various kinds of bias and imbalances. In this paper, chest X-ray pre-trained model via self-supervised contrastive learning (CheSS) was proposed to learn models with various representations in chest radiographs (CXRs). Our contribution is a publicly accessible pretrained model trained with a 4.8-M CXR dataset using self-supervised learning with a contrastive learning and its validation with various kinds of downstream tasks including classification on the 6-class diseases in internal dataset, diseases classification in CheXpert, bone suppression, and nodule generation. When compared to a scratch model, on the 6-class classification test dataset, we achieved 28.5% increase in accuracy. On the CheXpert dataset, we achieved 1.3% increase in mean area under the receiver operating characteristic curve on the full dataset and 11.4% increase only using 1% data in stress test manner. On bone suppression with perceptual loss, we achieved improvement in peak signal to noise ratio from 34.99 to 37.77, structural similarity index measure from 0.976 to 0.977, and root-square-mean error from 4.410 to 3.301 when compared to ImageNet pretrained model. Finally, on nodule generation, we achieved improvement in Fréchet inception distance from 24.06 to 17.07. Our study showed the decent transferability of CheSS weights. CheSS weights can help researchers overcome data imbalance, data shortage, and inaccessibility of medical image datasets. CheSS weight is available at https://github.com/mi2rl/CheSS .

Iliac vein compression syndrome by lumbar degenerative changes is associated with deep vein thrombosis after total knee arthroplasty.

INTRODUCTION: This study aimed to identify whether iliac vein compression syndrome(IVCS) is associated with deep vein thrombosis(DVT) after total knee arthroplasty(TKA) and whether lower lumbar degenerative changes were risk factors for IVCS. MATERIALS AND METHODS: A total of 259 consecutive patients who underwent TKA from January 2019 to March 2022 was retrospectively reviewed. Preoperative plain radiographs of lumbar spines and CT venography (CTV) for DVT diagnosis at postoperative 7 days were performed in all patients. Imaging findings of lower lumbar degenerative changes were analyzed on plain radiograph including lateral osteophytes, scoliosis, lateralolisthesis, retrolisthesis, anterolisthesis, and lower lumbar lordosis angle (LLLA). Percent compression at the left common iliac vein (LCIV) and right common iliac vein (RCIV) as well as DVT were evaluated on CTV. Moreover, IVCS was defined as greater than 50% of compression of the iliac vein on CTV. RESULTS: DVT occurred in 79 patients (30.5%) after TKA. The overall occurrence of DVT was significantly higher in patients with IVCS of LCIV (52.8%) than those without (18.8%, P < 0.001). When DVT was further subdivided, compared to non-IVCS, IVCS of LCIV was significantly associated with bilateral DVT (P < 0.001, both), especially distal DVT (P < 0.001, both), and IVCS of RCIV was significantly associated with right-side DVT (P = 0.031), especially popliteal (P = 0.008) and distal DVT(P = 0.011). Female patients (OR: 3.945, P = 0.039), presence of left osteophyte (OR: 2.348, P = 0.006), and higher LLLA (OR: 1.082, P < 0.001) were significantly associated with IVCS of LCIV, and presence of right osteophyte (OR: 3.494, P = 0.017) was significantly associated with IVCS of RCIV. CONCLUSION: IVCS was significantly associated with DVT after TKA and lumbar degenerative changes with lateral osteophytes and hyperlordosis were significant risk factors for IVCS.

Highly accelerated 3D MPRAGE using deep neural network-based reconstruction for brain imaging in children and young adults.

OBJECTIVES: This study aimed to accelerate the 3D magnetization-prepared rapid gradient-echo (MPRAGE) sequence for brain imaging through the deep neural network (DNN). METHODS: This retrospective study used the k-space data of 240 scans (160 for the training set, mean ± standard deviation age, 93 ± 80 months, 94 males; 80 for the test set, 106 ± 83 months, 44 males) of conventional MPRAGE (C-MPRAGE) and 102 scans (77 ± 74 months, 52 males) of both C-MPRAGE and accelerated MPRAGE. All scans were acquired with 3T scanners. DNN was developed with simulated-acceleration data generated by under-sampling. Quantitative error metrics were compared between images reconstructed with DNN, GRAPPA, and E-SPIRIT using the paired t-test. Qualitative image quality was compared between C-MPRAGE and accelerated MPRAGE reconstructed with DNN (DNN-MPRAGE) by two readers. Lesions were segmented and the agreement between C-MPRAGE and DNN-MPRAGE was assessed using linear regression. RESULTS: Accelerated MPRAGE reduced scan times by 38% compared to C-MPRAGE (142 s vs. 320 s). For quantitative error metrics, DNN showed better performance than GRAPPA and E-SPIRIT (p < 0.001). For qualitative evaluation, overall image quality of DNN-MPRAGE was comparable (p > 0.999) or better (p = 0.025) than C-MPRAGE, depending on the reader. Pixelation was reduced in DNN-MPRAGE (p < 0.001). Other qualitative parameters were comparable (p > 0.05). Lesions in C-MPRAGE and DNN-MPRAGE showed good agreement for the dice similarity coefficient (= 0.68) and linear regression (R2 = 0.97; p < 0.001). CONCLUSIONS: DNN-MPRAGE reduced acquisition time by 38% and revealed comparable image quality to C-MPRAGE. KEY POINTS: • DNN-MPRAGE reduced acquisition times by 38%. • DNN-MPRAGE outperformed conventional reconstruction on accelerated scans (SSIM of DNN-MPRAGE = 0.96, GRAPPA = 0.43, E-SPIRIT = 0.88; p < 0.001). • Compared to C-MPRAGE scans, DNN-MPRAGE showed improved mean scores for overall image quality (2.46 vs. 2.52; p < 0.001) or comparable perceived SNR (2.56 vs. 2.58; p = 0.08).

Association between prenatal cadmium exposure and cord blood DNA methylation.

Prenatal cadmium exposure is known to affect infant growth and organ development. Nonetheless, the role of DNA methylation in cadmium-related health effects has yet to be determined. To this end, we investigated the relationship between prenatal cadmium exposure and cord blood DNA methylation in Korean infants through an epigenome-wide association study. Cadmium concentrations in maternal blood during early and late pregnancy and in cord blood collected from newborns were measured using atomic adsorption spectrometry and DNA methylation analysis was conducted using HumanMethylationEPIC BeadChip kits. After adjusting for infant sex, maternal pregnancy body mass index, smoking status, and estimated leukocyte composition, we analyzed the association between CpG methylation and cadmium concentration in 364 samples. Among 835,252 CpG sites, maternal blood cadmium concentration in early pregnancy was significantly associated with two differentially methylated CpG sites, cg05537752 and cg24904393, which were annotated ATP9A and no gene, respectively. The study findings indicate that prenatal cadmium exposure is significantly associated with methylation statuses of several CpG sites and regions in Korean infants, especially during early pregnancy.

Association between plasma sRAGE and emphysema according to the genotypes of AGER gene.

BACKGROUND: Higher soluble receptor for advanced glycation end product (sRAGE) levels are considered to be associated with severe emphysema. However, the relationship remains uncertain when the advanced glycation end-product specific receptor (AGER) gene is involved. We aimed to analyse the association between sRAGE levels and emphysema according to the genotypes of rs2070600 in the AGER gene. METHODS: We genotyped rs2070600 and measured the plasma concentration of sRAGE in each participant. Emphysema was quantified based on the chest computed tomography findings. We compared sRAGE levels based on the presence or absence and severity of emphysema in each genotype. Multiple logistic and linear regression models were used for the analyses. RESULTS: A total of 436 participants were included in the study. Among them, 64.2% had chronic obstructive pulmonary disease and 34.2% had emphysema. Among the CC-genotyped participants, the sRAGE level was significantly higher in participants without emphysema than in those with emphysema (P < 0.001). In addition, sRAGE levels were negatively correlated with emphysema severity in CC-genotyped patients (r = - 0.268 P < 0.001). Multiple regression analysis revealed that sRAGE was an independent protective factor for the presence of emphysema (adjusted odds ratio, 0.24; 95% confidence interval (CI) 0.11-0.51) and severity of emphysema (ß = - 3.28, 95% CI - 4.86 to - 1.70) in CC-genotyped participants. CONCLUSION: Plasma sRAGE might be a biomarker with a protective effect on emphysema among CC-genotyped patients of rs2070600 on the AGER gene. This is important in determining the target group for the future prediction and treatment of emphysema.

Prenatal lead exposure and cord blood DNA methylation in the Korean Exposome Study.

BACKGROUND: Prenatal lead exposure has been reported to affect infant growth and nervous system development, as well as to influence DNA methylation. We conducted an epigenome-wide association study to identify associations between prenatal lead exposure and cord blood DNA methylation in Korean infants. METHODS: Cord blood samples were assayed with the Illumina HumanMethylationEPIC BeadChip kits, and maternal blood lead levels during early and late pregnancy, as well as cord blood lead level, were measured. The association between CpG methylation and lead level was analyzed using the limma package, with adjusting for infant sex, maternal pre-pregnancy body mass index, and estimated leukocyte composition. RESULTS: Among 364 blood samples (182 males and 182 females), those for which maternal and cord blood lead concentrations during early and later pregnancy was known were used for analysis. Maternal lead concentration in blood during early pregnancy was significantly associated with the methylation status of specific positions. After data stratification by infant sex, we found that, in males, the level of maternal blood lead was associated with 18 CpG sites during early pregnancy, and with one CpG site near the NBAS gene, during late pregnancy. In female samples, there was no significant association between DNA methylation and lead concentrations. CONCLUSIONS: Prenatal lead exposure was associated with altered, gender-specific patterns of DNA methylation in Korean infants.

Word Embedding Reveals Cyfra 21-1 as a Biomarker for Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD. Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. METHODS: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. RESULTS: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219, P = 0.015). CONCLUSION: Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.

Advanced Kidney Volume Measurement Method Using Ultrasonography with Artificial Intelligence-Based Hybrid Learning in Children.

In this study, we aimed to develop a new automated method for kidney volume measurement in children using ultrasonography (US) with image pre-processing and hybrid learning and to formulate an equation to calculate the expected kidney volume. The volumes of 282 kidneys (141 subjects, <19 years old) with normal function and structure were measured using US. The volumes of 58 kidneys in 29 subjects who underwent US and computed tomography (CT) were determined by image segmentation and compared to those calculated by the conventional ellipsoidal method and CT using intraclass correlation coefficients (ICCs). An expected kidney volume equation was developed using multivariate regression analysis. Manual image segmentation was automated using hybrid learning to calculate the kidney volume. The ICCs for volume determined by image segmentation and ellipsoidal method were significantly different, while that for volume calculated by hybrid learning was significantly higher than that for ellipsoidal method. Volume determined by image segmentation was significantly correlated with weight, body surface area, and height. Expected kidney volume was calculated as (2.22 × weight (kg) + 0.252 × height (cm) + 5.138). This method will be valuable in establishing an age-matched normal kidney growth chart through the accumulation and analysis of large-scale data.

Repeated Irradiation with γ-Ray Induces Cancer Stemness through TGF-ß-DLX2 Signaling in the A549 Human Lung Cancer Cell Line.

Cancer stem cells (CSCs) play an important role in cancer recurrence and metastasis. It is suggested that the CSC properties in heterogeneous cancer cells can be induced by ionizing radiation (IR). This study investigated the role of DLX2 in the radioresistance and CSC properties induced by IR in NSCLC cancer cells. Here, A549 cells were exposed to fractionated irradiation at a cumulative dose of 52 Gy (4 Gy × 13 times) for a generation of radioresistant cells. After fractionated irradiation, surviving A549 cells exhibited resistance to IR and enhanced expression of various cancer stem cell markers. They also showed upregulation of mesenchymal molecular markers and downregulation of epithelial molecular markers, correlating with an increase in the migration and invasion. Fractionated irradiation triggered the secretion of TGF-ß1 and DLX2 expression. Interestingly, the increased DLX2 following fractionated irradiation seemed to induce the expression of the gene for the EGFR-ligand betacellulin via Smad2/3 signaling. To contrast, DLX2 knockdown dramatically decreased the expression of CSC markers, migration, and proliferation. Moreover, A549 cells expressing DLX2 shRNA formed tumors with a significantly smaller volume compared to those expressing control shDNA in a mouse xenograft assay. These results suggest that DLX2 overexpression in surviving NSCLC cancer cells after fractionated IR exposure is involved in the cancer stemness, radioresistance, EMT, tumor survival, and tumorigenic capability.

Intramuscular peripheral nerve sheath tumors: schwannoma, ancient schwannoma, and neurofibroma.

PURPOSE: To analyze the prevalence of classic magnetic resonance imaging (MRI) findings of intramuscular peripheral nerve sheath tumors (PNSTs), including schwannoma, ancient schwannoma, and neurofibroma. METHOD: Thirty pathologically confirmed benign intramuscular PNSTs (24 schwannomas, 3 ancient schwannomas, and 3 neurofibromas) were retrospectively reviewed. Classic MRI findings of PNSTs including split fat sign, fascicular sign, target sign, entering and exiting nerve, and thin hyperintense rim were assessed for each intramuscular PNST. Denervation change of the affected muscle was also assessed. In ancient schwannoma and neurofibroma, the signal intensity (SI) and enhancement pattern were analyzed. RESULTS: All intramuscular schwannomas revealed two more classic MRI findings. Eight of the 24 intramuscular schwannomas revealed affected muscle denervation change. All intramuscular ancient schwannomas showed only split fat sign. All intramuscular ancient schwannomas showed denervation change of the associated muscle. All intramuscular neurofibroma showed split fat sign and one case with target sign was detected. Ancient schwannomas were isointense SI on T1-weighted image (T1WI) and one case had hyperintense foci. They showed heterogeneously hyperintense SI on T2-weighted image (T2WI) with heterogeneous enhancement. Neurofibromas were isointense SI (2/3) and slight hyperintense SI (1/3) on T1WI and heterogeneously hyperintense SI on T2WI with heterogeneous enhancement. One ancient schwannoma showed conglomerated calcifications. CONCLUSIONS: Intramuscular schwannomas were easily diagnosed based on MRI. In the case of intramuscular ancient schwannoma and neurofibroma with only split fat sign among the classic MRI findings, they might be distinguished from other intramuscular soft tissue tumors based on muscle denervation change or typical crescent split fat sign.

Non-ionic detergents Nonidet P-40 and Triton X-100 increase enzymatic activity of plasmin.

Plasmin is a potent serin protease involved in a variety of biological functions, such as fibrinolysis and tissue remodeling. On performing an in vitro control assay to measure the activity of endogenous plasmin in cell lysates, a stimulatory effect of non-ionic detergent NP-40 on plasmin activity was discovered. Another non-ionic detergent, TX-100, also enhanced plasmin activity, while ionic detergents sodium deoxycholate and sodiem dodecyl sulfate abolished plasmin enzyme activity. Kinetic analysis of plasmin activity in the presence of NP-40 and TX-100 demonstrated an increase in Vmax; however, there was no change in Km values, suggesting that these detergents stimulate plasmin activity in a non-competitive manner. Fibrin plate assay indicates that NP-40 and TX-100 functionally stimulate plasmin activity by showing a dose-dependent increase in fibrinolysis.