Amyloid precursor protein combinatorial phosphorylation code regulates AMPA receptor removal during distinct forms of synaptic plasticity.

Synaptic plasticity is essential for memory encoding and stabilization of neural network activity. Plasticity is impaired in neurodegenerative conditions including Alzheimer disease (AD). A central factor in AD is amyloid precursor protein (APP). Previous studies have suggested APP involvement in synaptic plasticity, but physiological roles of APP are not well understood. Here, we identified combinatorial phosphorylation sites within APP that regulate AMPA receptor trafficking during different forms of synaptic plasticity. Dual phosphorylation sites at threonine-668/serine-675 of APP promoted endocytosis of the GluA2 subunit of AMPA receptors during homeostatic synaptic plasticity. APP was also required for GluA2 internalization during NMDA receptor-dependent long-term depression, albeit via a distinct pair of phosphoresidues at serine-655/threonine-686. These data implicate APP as a central gate for AMPA receptor internalization during distinct forms of plasticity, unlocked by specific combinations of phosphoresidues, and suggest that APP may serve broad functions in learning and memory.

Deep learning-based long-term risk evaluation of incident type 2 diabetes using electrocardiogram in a non-diabetic population: a retrospective, multicentre study.

Background: Diabetes is a major public health concern. We aimed to evaluate the long-term risk of incident type 2 diabetes in a non-diabetic population using a deep learning model (DLM) detecting prevalent type 2 diabetes using electrocardiogram (ECG). Methods: In this retrospective study, participants who underwent health checkups at two tertiary hospitals in Seoul, South Korea, between Jan 1, 2001 and Dec 31, 2022 were included. Type 2 diabetes was defined as glucose ≥126 mg/dL or glycated haemoglobin (HbA1c) ≥ 6.5%. For survival analysis on incident type 2 diabetes, we introduced an additional variable, diabetic ECG, which is determined by the DLM trained on ECG and corresponding prevalent diabetes. It was assumed that non-diabetic individuals with diabetic ECG had a higher risk of incident type 2 diabetes than those with non-diabetic ECG. The one-dimensional ResNet-based model was adopted for the DLM, and the Guided Grad-CAM was used to localise important regions of ECG. We divided the non-diabetic group into the diabetic ECG group (false positive) and the non-diabetic ECG (true negative) group according to the DLM decision, and performed a Cox proportional hazard model, considering the occurrence of type 2 diabetes more than six months after the visit. Findings: 190,581 individuals were included in the study with a median follow-up period of 11.84 years. The areas under the receiver operating characteristic curve for prevalent type 2 diabetes detection were 0.816 (0.807-0.825) and 0.762 (0.754-0.770) for the internal and external validations, respectively. The model primarily focused on the QRS duration and, occasionally, P or T waves. The diabetic ECG group exhibited an increased risk of incident type 2 diabetes compared with the non-diabetic ECG group, with hazard ratios of 2.15 (1.82-2.53) and 1.92 (1.74-2.11) for internal and external validation, respectively. Interpretation: In the non-diabetic group, those whose ECG was classified as diabetes by the DLM were at a higher risk of incident type 2 diabetes than those whose ECG was not. Additional clinical research on the relationship between the phenotype of ECG and diabetes to support the results and further investigation with tracked data and various ECG recording systems are suggested for future works. Funding: National Research Foundation of Korea.

α-Tocopherol-loaded multi-layer nanoemulsion using chitosan, and dextran sulfate: Cellular uptake, antioxidant activity, and in vitro bioaccessibility.

The potential of multi-layer nanoemulsions (NEs) for improving the cellular uptake, antioxidant activity, and in vitro bioaccessibility of α-tocopherol (ToC) was examined. ToC-loaded multi-layer NEs were prepared using lecithin (primary-NEs, P-NEs), chitosan (secondary-NEs, S-NEs), and dextran sulfate (tertiary-NEs, T-NEs) as wall materials. The bioadhesion, cellular permeability, and uptake of the multi-layer NEs were significantly higher than that of the free coumarin 6 (C6). As a result of cellular uptake, the mean fluorescence intensity of T-NEs was the highest among the three types of multi-layer NEs and was 9.8-fold higher than that of free C6. The cellular antioxidant abilities of P-NEs, S-NEs, and T-NEs were 40, 45, and 50 %, respectively. Multi-layer nanoencapsulation sustains free fatty acid release after digestion. Moreover, the bioavailability of T-NEs exhibited a two-fold increase compared with that of the free ToC. These findings indicate that by multi-layer NEs using a layer-by-layer method, the cellular uptake, in vitro bioaccessibility, and antioxidant activity of ToC can be improved. Furthermore, T-NEs using chitosan and dextran sulfate can potentially enhance the cellular uptake, in vitro bioaccessibility, and antioxidant activity of ToC. These findings would facilitate the application of multi-layer NEs for lipophilic bioactive compounds using biopolymers.

Identification of Risk Groups for and Factors Affecting Metabolic Syndrome in South Korean Single-Person Households Using Latent Class Analysis and Machine Learning Techniques: Secondary Analysis Study.

BACKGROUND: The rapid increase of single-person households in South Korea is leading to an increase in the incidence of metabolic syndrome, which causes cardiovascular and cerebrovascular diseases, due to lifestyle changes. It is necessary to analyze the complex effects of metabolic syndrome risk factors in South Korean single-person households, which differ from one household to another, considering the diversity of single-person households. OBJECTIVE: This study aimed to identify the factors affecting metabolic syndrome in single-person households using machine learning techniques and categorically characterize the risk factors through latent class analysis (LCA). METHODS: This cross-sectional study included 10-year secondary data obtained from the National Health and Nutrition Examination Survey (2009-2018). We selected 1371 participants belonging to single-person households. Data were analyzed using SPSS (version 25.0; IBM Corp), Mplus (version 8.0; Muthen & Muthen), and Python (version 3.0; Plone & Python). We applied 4 machine learning algorithms (logistic regression, decision tree, random forest, and extreme gradient boost) to identify important factors and then applied LCA to categorize the risk groups of metabolic syndromes in single-person households. RESULTS: Through LCA, participants were classified into 4 groups (group 1: intense physical activity in early adulthood, group 2: hypertension among middle-aged female respondents, group 3: smoking and drinking among middle-aged male respondents, and group 4: obesity and abdominal obesity among middle-aged respondents). In addition, age, BMI, obesity, subjective body shape recognition, alcohol consumption, smoking, binge drinking frequency, and job type were investigated as common factors that affect metabolic syndrome in single-person households through machine learning techniques. Group 4 was the most susceptible and at-risk group for metabolic syndrome (odds ratio 17.67, 95% CI 14.5-25.3; P<.001), and obesity and abdominal obesity were the most influential risk factors for metabolic syndrome. CONCLUSIONS: This study identified risk groups and factors affecting metabolic syndrome in single-person households through machine learning techniques and LCA. Through these findings, customized interventions for each generational risk factor for metabolic syndrome can be implemented, leading to the prevention of metabolic syndrome, which causes cardiovascular and cerebrovascular diseases. In conclusion, this study contributes to the prevention of metabolic syndrome in single-person households by providing new insights and priority groups for the development of customized interventions using classification.

Deep learning based on dynamic susceptibility contrast MR imaging for prediction of local progression in adult-type diffuse glioma (grade 4).

Adult-type diffuse glioma (grade 4) has infiltrating nature, and therefore local progression is likely to occur within surrounding non-enhancing T2 hyperintense areas even after gross total resection of contrast-enhancing lesions. Cerebral blood volume (CBV) obtained from dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) is a parameter that is well-known to be a surrogate marker of both histologic and angiographic vascularity in tumors. We built two nnU-Net deep learning models for prediction of early local progression in adult-type diffuse glioma (grade 4), one using conventional MRI alone and one using multiparametric MRI, including conventional MRI and DSC-PWI. Local progression areas were annotated in a non-enhancing T2 hyperintense lesion on preoperative T2 FLAIR images, using the follow-up contrast-enhanced (CE) T1-weighted (T1W) images as the reference standard. The sensitivity was doubled with the addition of nCBV (80% vs. 40%, P = 0.02) while the specificity was decreased nonsignificantly (29% vs. 48%, P = 0.39), suggesting that fewer cases of early local progression would be missed with the addition of nCBV. While the diagnostic performance of CBV model is still poor and needs improving, the multiparametric deep learning model, which presumably learned from the subtle difference in vascularity between early local progression and non-progression voxels within perilesional T2 hyperintensity, may facilitate risk-adapted radiotherapy planning in adult-type diffuse glioma (grade 4) patients.

Taste masking and stability improvement of Korean red ginseng (Panax ginseng) by nanoencapsulation using chitosan and gelatin.

In this study, red ginseng extract (RGE)-loaded nanoparticles (NPs) were prepared by ionic gelation between chitosan (CS) and gelatin (Gel), and the physical characteristics of the RGE-loaded CS-Gel NPs (RGE-CS/Gel NPs), including particle size and polydispersity index (PDI), using different ratios of CS and Gel were examined. The particle size and PDI were 398.1 ± 41.3 nm and 0.433 ± 0.033, respectively for the optimal ratio of CS (0.075 mg/mL) and Gel (0.05 mg/mL). In vitro taste masking test and in vivo sensory evaluation using 10 panelists demonstrated that the CS/Gel NPs significantly reduced the bitter taste of RGE. Additionally, the CS/Gel NPs improved the thermal and acid stabilities, which were almost 6 and 8 times higher than those in the free RGE (p < 0.05), respectively. Likewise, our findings revealed that the RGE-CS/Gel NPs effectively maintain their inhibitory function against platelet aggregation (76.30 %) in an acidic environment. Therefore, the CS/Gel NPs can be used as a potential delivery system to mask the bitterness and improve the stability of RGE, which may enhance its application as a more palatable functional food ingredient with high anti-platelet activity.

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

BACKGROUND/AIMS: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. METHODS: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). RESULTS: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. CONCLUSION: Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Reconstruction of Fibrocartilage with Fibrous Alignment of Type I Collagen in Scaffold-Free Manner.

For functional reconstruction of fibrocartilage, it is necessary to reproduce the essential mechanical property exhibited by natural fibrocartilage. The distinctive mechanical property of fibrocartilage is originated from the specific histological features of fibrocartilage composed of highly aligned type I collagen (Col I) and an abundant cartilaginous matrix. While the application of tensile stimulation induces highly aligned Col I, our study reveals that it also exerts an antichondrogenic effect on scaffold-free tissues constructed with meniscal chondrocytes (MCs) and induces downregulation of Sox-9 expression and attenuated glycosaminoglycan production. Modulation of mechanotransduction by blocking nuclear translocation of Yes-associated protein (YAP) ameliorated the antichondrogenic effect in the presence of tensile stimulation. Since MCs subjected to mechanical doses either by surface stiffness or tensile stimulation showed reversibility of YAP status even after a long-term exposure to mechanotransduction, fibrocartilage tissue was constructed by sequentially inducing tissue alignment by tensile stimulation followed by inducing cartilaginous matrix production in a tension-released state. The minimal tensile dose to constitute durable tissue alignment was screened by investigating the alignment of cytoskeleton and Col I after culturing the scaffold-free tissue constructs with various tensile doses (10% static tension for 1, 3, 7, and 10 days) followed by maintaining in a released state for 5 days. Fluorescence-conjugated phalloidin binding and immunofluorescence of Col I indicated that the duration of static tension for more than 7 days resulted in durable tissue alignment for at least 5 days in the tension-released state. The tissues subjected to tensile stimulation for 7 days followed by 14 days in a released state in chondrogenic media resulted in abundant cartilaginous matrix as well as uniaxial anisotropic alignment. Our results show that the optimized tensile dose can facilitate the successful reconstruction of fibrocartilage by modulating the characteristics of matrix production by MCs.

Site-specific fabrication of a melanin-like pigment through spatially confined progressive assembly on an initiator-loaded template.

Melanin-like nanomaterials have emerged in surface biofunctionalization in a material-independent manner due to their versatile adhesion arising from their catechol-rich structures. However, the unique adhesive properties of these materials ironically raise difficulties in their site-specific fabrication. Here, we report a method for site-specific fabrication and patterning of melanin-like pigments, using progressive assembly on an initiator-loaded template (PAINT), different from conventional lithographical methods. In this method, the local progressive assembly could be naturally induced on the given surface pretreated with initiators mediating oxidation of the catecholic precursor, as the intermediates generated from the precursors during the progressive assembly possess sufficient intrinsic underwater adhesion for localization without diffusion into solution. The pigment fabricated by PAINT showed efficient NIR-to-heat conversion properties, which can be useful in biomedical applications such as the disinfection of medical devices and cancer therapies.

Developing a Classification Algorithm for Prediabetes Risk Detection From Home Care Nursing Notes: Using Natural Language Processing.

This study developed and validated a rule-based classification algorithm for prediabetes risk detection using natural language processing from home care nursing notes. First, we developed prediabetes-related symptomatic terms in English and Korean. Second, we used natural language processing to preprocess the notes. Third, we created a rule-based classification algorithm with 31 484 notes, excluding 315 instances of missing data. The final algorithm was validated by measuring accuracy, precision, recall, and the F1 score against a gold standard testing set (400 notes). The developed terms comprised 11 categories and 1639 words in Korean and 1181 words in English. Using the rule-based classification algorithm, 42.2% of the notes comprised one or more prediabetic symptoms. The algorithm achieved high performance when applied to the gold standard testing set. We proposed a rule-based natural language processing algorithm to optimize the classification of the prediabetes risk group, depending on whether the home care nursing notes contain prediabetes-related symptomatic terms. Tokenization based on white space and the rule-based algorithm were brought into effect to detect the prediabetes symptomatic terms. Applying this algorithm to electronic health records systems will increase the possibility of preventing diabetes onset through early detection of risk groups and provision of tailored intervention.

Major depression-related factor NEGR1 controls salivary secretion in mouse submandibular glands.

Salivary gland cells, which secrete water in response to neuronal stimulation, are closely connected to other neurons. Transcriptomic studies show that salivary glands also express some proteins responsible for neuronal function. However, the physiological functions of these common neuro-exocrine factors in salivary glands are largely unknown. Here, we studied the function of Neuronal growth regulator 1 (NEGR1) in the salivary gland cells. NEGR1 was also expressed in mouse and human salivary glands. The structure of salivary glands of Negr1 knockout (KO) mice was normal. Negr1 KO mice showed tempered carbachol- or thapsigargin-induced intracellular Ca2+ increases and store-operated Ca2+ entry. Of interest, the activity of the large-conductance Ca2+-activated K+ channel (BK channel) was increased, whereas Ca2+-activated Cl- channel ANO1 channel activity was not altered in Negr1 KO mice. Pilocarpine- and carbachol-induced salivation was decreased in Negr1 KO mice. These results suggest that NEGR1 influence salivary secretion though the muscarinic Ca2+ signaling.

Anatomic consideration of the radial nerve in relation to humeral length for unilateral external fixation: a retrospective study using magnetic resonance imaging findings in korean.

BACKGROUND: This study aimed to present a safe zone for distal pin insertion for external fixation using magnetic resonance imaging (MRI) images. METHODS: All patients who took at least one upper arm MRI from June 2003 to July 2021 were searched via a clinical data warehouse. For measuring the humerus length, proximal and distal landmarks were set as the highest protruding point of the humeral head and lowermost margin of ossified bone of the lateral condyle, respectively. For children or adolescents with incomplete ossification, the uppermost and lowermost ossified margin of the ossification centers were set as proximal and distal landmarks respectively. The anterior exit point (AEP) was defined as the location of the radial nerve exiting the lateral intermuscular septum to the anterior humerus and distance between the distal margin of the humerus and AEP was measured. The proportions between the AEP and full humeral length were calculated. RESULTS: A total of 132 patients were enrolled for final analysis. The mean humerus length was 29.4 cm (range 12.9-34.6 cm). The mean distance between the ossified lateral condyle and AEP was 6.6 cm (range 3.0-10.6 cm). The mean ratio of the anterior exit point and humeral length was 22.5% (range 15.1-30.8%). The minimum ratio was 15.1%. CONCLUSION: A percutaneous distal pin insertion for humeral lengthening with an external fixator may be safely done within 15% length of the distal humerus. If pin insertion is required more proximal than distal 15% of the humeral shaft, an open procedure or preoperative radiographic assessment is advised to prevent iatrogenic radial nerve injury.

Association between polycystic ovarian morphology and insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE: The aim of the present study was to determine whether polycystic ovarian morphology (PCOM) is related to insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: A total of 147 Korean women aged 18 to 35 years and diagnosed with PCOS were included in this study. Fasting blood tests and standard 2-hour 75-g oral glucose tolerance tests were performed for all participants. PCOM-related parameters including total antral follicle count (TFC) and total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasonography. Correlation analysis was conducted to assess the relationships of TFC and TOV with insulin resistance-related clinical and biochemical parameters using Spearman rank correlation coefficients and linear regression analysis, with partial correlations used to control for the effects of confounding covariates. RESULTS: Fasting insulin levels, low-density lipoprotein levels, and insulin sensitivity assessment indices (ISAIs) were significantly correlated with TFC, but neither postprandial blood glucose levels nor insulin levels were significantly associated with TFC. No insulin resistance-related parameter was significantly correlated with TOV. These results did not change after adjustments for other anthropometric covariates. Fasting insulin and some ISAIs differed significantly between groups categorized by the median TFC value (TFC ≤54 and TFC >54). CONCLUSION: TFC, but not TOV, was found to be related to fasting insulin resistance-related parameters in women with PCOS.

Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness. METHODS: EMPA-VISION (Assessment of Cardiac Energy Metabolism, Function and Physiology in Patients With Heart Failure Taking Empagliflozin) is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction ≤40%; New York Heart Association class ≥II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≥125 pg/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction ≥50%; New York Heart Association class ≥II; NT-proBNP ≥125 pg/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr/ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated. RESULTS: Empagliflozin treatment did not change cardiac energetics (ie, PCr/ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin - placebo], -0.25 [95% CI, -0.58 to 0.09]; P=0.14) or HFpEF (adjusted mean treatment difference, -0.16 [95% CI, -0.60 to 0.29]; P=0.47]. Likewise, there were no changes in PCr/ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, -0.13 [95% CI, -0.35 to 0.09]; P=0.23) or HFpEF (adjusted mean treatment difference, -0.22 [95% CI, -0.66 to 0.23]; P=0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed. CONCLUSIONS: In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03332212.

Nanoencapsulation of Grapefruit Seed Extract and Cinnamon Oil for Oral Health: Preparation, In Vitro, and Clinical Antimicrobial Activities.

This study aimed to formulate mucoadhesive antimicrobial nanoparticles using natural antimicrobials and biopolymers for oral health and verify their antimicrobial activity in clinical studies. A combination of grapefruit seed extract and cinnamon oil (GCN) and chitosan/carrageenan (CS/CR) were selected as synergistic antimicrobial combinations and mucoadhesive wall materials for nanoparticles, respectively. GCN nanoparticles (NPs; size = 357 nm and polydispersity index = 0.188) prepared by ionic gelation between CS and CR exhibited synergistic antimicrobial activity between grapefruit seed extract and cinnamon oil and significantly higher antimicrobial activity against Streptococcus mutans and sobrinus than free GCN in a time-kill assay. The clinical antibacterial activity of GCN was significantly increased and sustained by nanoencapsulation in the mouth-rinse test and GCN NP-treated drinking yogurt. These results suggest that GCN-loaded CS/CR nanoencapsulation is a promising technique that can inhibit oral bacteria with or without the presence of other food ingredients.

Comparative validation of AI and non-AI methods in MRI volumetry to diagnose Parkinsonian syndromes.

Automated segmentation and volumetry of brain magnetic resonance imaging (MRI) scans are essential for the diagnosis of Parkinson's disease (PD) and Parkinson's plus syndromes (P-plus). To enhance the diagnostic performance, we adopt deep learning (DL) models in brain MRI segmentation and compared their performance with the gold-standard non-DL method. We collected brain MRI scans of healthy controls ([Formula: see text]) and patients with PD ([Formula: see text]), multiple systemic atrophy ([Formula: see text]), and progressive supranuclear palsy ([Formula: see text]) at Samsung Medical Center from January 2017 to December 2020. Using the gold-standard non-DL model, FreeSurfer (FS), we segmented six brain structures: midbrain, pons, caudate, putamen, pallidum, and third ventricle, and considered them as annotated data for DL models, the representative convolutional neural network (CNN) and vision transformer (ViT)-based models. Dice scores and the area under the curve (AUC) for differentiating normal, PD, and P-plus cases were calculated to determine the measure to which FS performance can be reproduced as-is while increasing speed by the DL approaches. The segmentation times of CNN and ViT for the six brain structures per patient were 51.26 ± 2.50 and 1101.82 ± 22.31 s, respectively, being 14 to 300 times faster than FS (15,735 ± 1.07 s). Dice scores of both DL models were sufficiently high (> 0.85) so their AUCs for disease classification were not inferior to that of FS. For classification of normal vs. P-plus and PD vs. P-plus (except multiple systemic atrophy - Parkinsonian type) based on all brain parts, the DL models and FS showed AUCs above 0.8, demonstrating the clinical value of DL models in addition to FS. DL significantly reduces the analysis time without compromising the performance of brain segmentation and differential diagnosis. Our findings may contribute to the adoption of DL brain MRI segmentation in clinical settings and advance brain research.

Serum Urate-Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial.

OBJECTIVE: To evaluate the safety and efficacy of the nonpurine xanthine oxidase inhibitor tigulixostat for lowering serum urate level in gout patients with hyperuricemia. METHODS: We conducted a multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding trial. After screening, gout patients with hyperuricemia were randomly assigned, after appropriate washout, to receive daily oral administration of 50 mg, 100 mg, or 200 mg of tigulixostat, or placebo for 12 weeks. Colchicine gout flare prophylaxis was administered to all patients. The primary end point was the proportion of patients with a serum urate level <5.0 mg/dl at week 12. RESULTS: A total of 143 patients were randomized to receive tigulixostat 50 mg (n = 34), 100 mg (n = 38), or 200 mg (n = 37), or placebo (n = 34). A significantly greater proportion of patients in the tigulixostat groups achieved the target serum urate level <5.0 mg/dl at week 12 (47.1% in the 50 mg group, 44.7% in the 100 mg group, and 62.2% in the 200 mg group) compared to the placebo group (2.9%) (P < 0.0001). The mean percentage change in serum urate level from baseline was also significantly greater in the tigulixostat groups (-38.8% to -61.8%) than in the placebo group at all time points (P < 0.0001). The rate of gout flares requiring rescue treatment ranged from 9.4% to 13.2% in the tigulixostat and placebo groups. The incidence of adverse events was 50.0% to 56.8% across all groups, and their severity was mild or moderate. CONCLUSION: Tigulixostat significantly lowered serum urate compared to placebo at all doses studied with an acceptable safety profile.

Incidence and prevalence of seropositive rheumatoid arthritis among Korean women of childbearing age: a nationwide population-based study.

BACKGROUND/AIMS: Women with rheumatoid arthritis (RA) are often diagnosed with the disease during their reproductive years; however, its incidence and prevalence among women of childbearing age have not been studied. The objective of this study was to estimate the incidence and prevalence of seropositive rheumatoid arthritis (SPRA) among Korean women of childbearing age. METHODS: Women aged 20 to 44 years with SPRA were identified from National Health Insurance Service-National Health Information Database (2009 to 2016). SPRA was defined by International Classification of Diseases, 10th revision code, M05. Incidence and prevalence were calculated per 100,000 person-years and stratified by year and age. RESULTS: The average incidence and prevalence of SPRA from 2011 to 2016 among women of childbearing age was 24.1/100,000 person-years (95% confidence interval [CI], 23.7 to 24.5) and 105.2/100,000 person-years (95% CI, 100.9 to 109.5), respectively. The incidence increased annually from 21.0/100,000 person-years (95% CI, 20.1 to 21.9) in 2009 to 28.4 person-years (95% CI, 27.3 to 29.5) in 2016. Similarly, the prevalence increased annually from 95.7/100,000 person-years (95% CI, 93.7 to 97.6) in 2009 to 111.0 person-years (95% CI, 108.9 to 113.2) in 2015, with a slight decrease in 2016 (110.4 person-years; 95% CI, 108.2 to 112.6). The incidence and prevalence of SPRA increased with advancing age. The peak age for both incidence and prevalence of SPRA among women of childbearing age was 40 to 44 years. CONCLUSION: The risk of SPRA is high in women during their childbearing years; this population bears a significant disease burden. This calls for special attention to this particular population group to reduce the risk and burden of this disease.