Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry.

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan-Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p < 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p < 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Genotypic and phenotypic analysis of Korean patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder caused by mutations in the TSC1 or TSC2 gene. The aim of this study was to analyze the genotypes and phenotypes of Korean patients diagnosed with TSC and expand our understanding of this disorder. This retrospective observational study included 331 patients clinically diagnosed with TSC between November 1990 and April 2023 at Severance Children's Hospital, Seoul, South Korea. The demographic and clinical characteristics of the patients were investigated. Thirty novel variants were identified. Of the 331 patients, 188 underwent genetic testing, and genotype-phenotype variation was analyzed according to the type of gene mutation and functional domain. Fourty-nine patients (49/188, 26%) were had TSC1 mutations, 103 (55%) had TSC2 mutations, and 36 (19%) had no mutation identified (NMI). Hotspots were identified in exons 8 of TSC1 and exons 35 and 41 of TSC2. Patients with TSC2 mutations exhibited a significantly younger age at the time of seizure onset and had refractory epilepsy. Infantile epileptic spasms syndrome (IESS) was more common in the middle mutation domain of TSC2 than in the hamartin domain. Additionally, retinal hamartoma, cardiac rhabdomyoma, and renal abnormalities were significantly associated with TSC2 compared with other gene types. This study contributes to our understanding of TSC by expanding the genotypic spectrum with novel variants and providing insights into the clinical spectrum of patients with TSC in Korea.

Efficacy of enteral feeding by gastrostomy tube placement in patients with Lennox-Gastaut syndrome on body weight and days of hospitalization: A retrospective case series.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe form of drug-resistant epilepsy that begins during childhood and frequently leads to significant neurological impairments. Patients with LGS are likely to receive improper oral nutrition because of issues such as dysphagia and aspiration risk, potentially resulting in long-term tube feeding and eventual gastrostomy tube placement. Therefore, we investigated the effects of gastrostomy tube placement on nutrition outcomes and frequency of hospitalization in LGS. METHODS: We retrospectively examined 67 patients diagnosed with LGS who had undergone gastrostomy tube placement between January 2005 and August 2022. Comprehensive clinical data and complications arising from the procedure were collected. Patients' nutrition condition and frequency of hospitalizations were analyzed before and after gastrostomy tube placement. RESULTS: Gastrostomy tube placement was performed for the following reasons: high risk of aspiration (50 out of 67, 74.6%), dysphagia (13 out of 67, 25.4%), persistent nasogastric tube feeding (2 out of 67, 3.0%), and severe malnutrition (2 out of 67, 3.0%). After the procedure, z scores for weight-for-age improved significantly, shifting from -3.35 ± 3.57 to -2.54 ± 2.70 over a 2-year interval (P < 0.001). Additionally, the total days of hospitalization and days of hospitalization due to respiratory symptoms reduced significantly from 41.94 ± 51.76 to 15.27 ± 26.68 (P < 0.001) and from 23.75 ± 36.92 to 10.52 ± 22.98 (P = 0.009), respectively. Among the patients, 50 (74.6%) experienced complications resulting from gastrostomy, with a relatively small proportion of major complications (11 out of 67, 16.4%) and no mortality. CONCLUSION: Gastrostomy tube placement is a relatively safe procedure with favorable effects on nutrition status and hospitalization rates in patients with LGS.

Lithiophilic Multichannel Layer to Simultaneously Control the Li-Ion Flux and Li Nucleation for Stable Lithium Metal Batteries.

Although the Li metal has been gaining attention as a promising anode material for the next-generation high-energy-density rechargeable batteries owing to its high theoretical specific capacity (3860 mAh g-1), its practical use remains challenging owing to inherent issues related to Li nucleation and growth. This paper reports the fabrication of a lithiophilic multichannel layer (LML) that enables the simultaneous control of Li nucleation and growth in Li-metal batteries. The LML, composed of lithiophilic ceramic composite nanoparticles (Ag-plated Al2O3 particles), is fabricated using the electroless plating method. This LML provides numerous channels for a uniform Li-ion diffusion on a nonwoven separator. Furthermore, the lithiophilic Ag on the Li metal anode surface facing the LML induces a low overpotential during Li nucleation, resulting in a dense Li deposition. The LML enables the LiNi0.8Co0.1Mn0.1O2|| Li cells to maintain a capacity higher than 75% after 100 cycles, even at high charge/discharge rates of 5.0 C at a cutoff voltage of 4.4 V, and achieve an ultrahigh energy density of 1164 Wh kg-1. These results demonstrate that the LML is a promising solution enabling the application of Li metal as an anode material in the next-generation Li-ion batteries.

Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy.

BACKGROUND AND PURPOSE: There is extensive literature on monogenic epilepsies caused by mutations in familiar channelopathy genes such as SCN1A. However, information on other less-common channelopathy genes is scarce. This study aimed to explore the genetic and clinical characteristics of patients diagnosed with unusual voltage-gated sodium and potassium channelopathies related to epilepsy. METHODS: This observational, retrospective study analyzed pediatric patients with epilepsy who carried pathogenic variants of unusual voltage-gated sodium and potassium channelopathy genes responsible for seizure-associated phenotypes. Targeted next-generation sequencing (NGS) panel tests were performed between November 2016 and June 2022 at Severance Children's Hospital, Seoul, South Korea. Clinical characteristics and the treatment responses to different types of antiseizure medications were further analyzed according to different types of gene mutation. RESULTS: This study included 15 patients with the following unusual voltage-gated sodium and potassium channelopathy genes: SCN3A (n=1), SCN4A (n=1), KCNA1 (n=1), KCNA2 (n=4), KCNB1 (n=6), KCNC1 (n=1), and KCNMA1 (n=1). NGS-based genetic testing identified 13 missense mutations (87%), 1 splice-site variant (7%), and 1 copy-number variant (7%). Developmental and epileptic encephalopathy was diagnosed in nine (60%) patients. Seizure freedom was eventually achieved in eight (53%) patients, whereas seizures persisted in seven (47%) patients. CONCLUSIONS: Our findings broaden the genotypic and phenotypic spectra of less-common voltage-gated sodium and potassium channelopathies associated with epilepsy.

High-Efficiency In Vitro Root Induction in Pear Microshoots (Pyrus spp.).

Extensive research has been conducted on the in vitro mass propagation of pear (Pyrus spp.) trees through vegetative propagation, demonstrating high efficiency in shoot multiplication across various pear species. However, the low in vitro rooting rates remain a significant barrier to the practical application and commercialization of mass propagation. This study aims to determine the favorable conditions for inducing root formation in the in vitro microshoots of Pyrus genotypes. The base of the microshoots was exposed to a high concentration (2 mg L-1) of auxins (a combination of IBA and NAA) for initial root induction at the moment when callus formation begins. The microshoots were then transferred to an R1 medium (1/2 MS with 30 g L-1 sucrose without PGRs) to promote root development. This method successfully induced rooting in three European pear varieties, one Asian pear variety, and a European-Asian hybrid, resulting in rooting rates of 66.7%, 87.2%, and 100% for the European pear (P. communis), 60% for the Asian pear (P. pyrifolia), and 83.3% for the hybrid pear (P. pyrifolia × P. communis) with an average of 25 days. In contrast, the control group (MS medium) exhibited rooting rates of 0-13.3% after 60 days of culture. These findings will enhance in vitro root induction for various pear varieties and support the mass propagation and acclimatization of pear. The in vitro root induction method developed in this study has the potential for global commercial application in pear cultivation.

Identification of etiologies according to baseline clinical features of pediatric new-onset refractory status epilepticus in single center retrospective study.

PURPOSE: New-onset refractory status epilepticus (NORSE) is defined as a state of prolonged seizure activity that does not improve despite the appropriate administration of medications, with underlying causes unknown after the initial diagnosis of status epilepticus. Because episodes of NORSE are accompanied by severe complications and a high risk of mortality, the prompt identification of the underlying cause is crucial for effective treatment and outcome prediction. This study assessed the relationship of NORSE etiologies with baseline clinical features in pediatric population. METHODS: Seventy-one pediatric patients, under 18 years of age at the initial diagnosis (4.50 ± 4.04, mean ± standard deviation), who experienced at least one episode of NORSE and underwent a comprehensive diagnostic evaluation between January 2005 and June 2020 at our center, were retrospectively selected. We reviewed clinical features at disease onset and long-term follow-up data. Uniform manifold approximation and projection (UMAP) was used to distinguish etiological clusters according to baseline clinical characteristics, and further analysis was performed based on underlying etiologies. RESULTS: Two distinct etiological groups-genetic and non-genetic-were identified based on the UMAP of clinical characteristics. Dravet syndrome (12/15, 80%) was more predominant in patients with a genetic diagnosis, whereas cryptogenic NORSE and encephalitis were prevalent in patients without a genetic diagnosis. The analysis of etiological categories revealed that age at the onset of status epilepticus (P=0.021) and progression to super refractory status epilepticus (SRSE) (P=0.038) were independently associated with differences in etiologies. CONCLUSION: Several clinical features in patients with NORSE, including the age of onset and the development of SRSE, can help identify underlying causes, which necessitate prompt and adequate treatment.

A computational clinical decision-supporting system to suggest effective anti-epileptic drugs for pediatric epilepsy patients based on deep learning models using patient's medical history.

BACKGROUND: Epilepsy, a chronic brain disorder characterized by abnormal brain activity that causes seizures and other symptoms, is typically treated using anti-epileptic drugs (AEDs) as the first-line therapy. However, due to the variations in their modes of action, identification of effective AEDs often relies on ad hoc trials, which is particularly challenging for pediatric patients. Thus, there is significant value in computational methods capable of assisting in the selection of AEDs, aiming to minimize unnecessary medication and improve treatment efficacy. RESULTS: In this study, we collected 7,507 medical records from 1,000 pediatric epilepsy patients and developed a computational clinical decision-supporting system for AED selection. This system leverages three multi-channel convolutional neural network (CNN) models tailored to three specific AEDs (vigabatrin, prednisolone, and clobazam). Each CNN model predicts whether a respective AED is effective on a given patient or not. The CNN models showed AUROCs of 0.90, 0.80, and 0.92 in 10-fold cross-validation, respectively. Evaluation on a hold-out test dataset further revealed positive predictive values (PPVs) of 0.92, 0.97, and 0.91 for the three respective CNN models, representing that suggested AEDs by our models would be effective in controlling epilepsy with a high accuracy and thereby reducing unnecessary medications for pediatric patients. CONCLUSION: Our CNN models in the system demonstrated high PPVs for the three AEDs, which signifies the potential of our approach to support the clinical decision-making by assisting doctors in recommending effective AEDs within the three AEDs for patients based on their medical history. This would result in a reduction in the number of unnecessary ad hoc attempts to find an effective AED for pediatric epilepsy patients.

Costotransverse joint ankylosis and their association with syndesmophyte progression in patients with radiographic axial spondyloarthritis.

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

Injectable and Self-Curing Single-Component Hydrogel for Stem Cell Encapsulation and In Vivo Bone Regeneration.

An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single-component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA-PBA-SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear-thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post-injection "self-curing," which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs-containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA-based hydrogel enabled efficient gelation with shear-thinning and self-curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration.

Aetiology and Prognosis of Encephalitis in Korean Children: A Retrospective Single-Centre Study, 2005-2020.

PURPOSE: Encephalitis is a heterogeneous syndrome that occurs in childhood and is not rare. However, epidemiological studies of encephalitis based on the International Encephalitis Consortium (ICS) and expert recommendations are lacking. We investigated the aetiology and prognosis of encephalitis in Korean children. MATERIALS AND METHODS: This retrospective study included children aged <19 years hospitalised for encephalitis at Severance Children's Hospital between 2005 and 2020. The 2013 ICS criteria were used to diagnose encephalitis, and causality was classified according to the site from which the specimen was obtained. Neurological sequelae were categorised using the modified Rankin Scale (mRS) score. RESULTS: In total, 551 children were included, with 7% classified as possible, 77% as probable, and 15% as proven cases. A cause was identified in 42% of the cases (n=222), with viruses being the most common (42%), followed by bacteria (38%) and autoimmune encephalitis (12%). In cases of proven/probable encephalitis (n=65), bacteria accounted for 52%, followed by viruses (25%) and autoimmune encephalitis (22%). In cases with a single pathogen, the anti-N-methyl-D-aspartate receptor autoantibody (n=14) was the most common, followed by Group B streptococcus (n=13), herpes simplex virus (n=11), enterovirus (n=4), and others. Approximately 37% of patients had severe sequelae (mRS score ≥3) at discharge, which decreased to 31% 6 months after discharge. CONCLUSION: This large-scale study showed that autoimmune and infectious causes accounted for a significant proportion of encephalitis in Korean children. Further studies are needed to determine whether early targeted treatment following early diagnosis leads to a favourable prognosis in these populations.

Changes in Competitors, Stress Tolerators, and Ruderals (CSR) Ecological Strategies after the Introduction of Shrubs and Trees in Disturbed Semiarid Steppe Grasslands in Hulunbuir, Inner Mongolia.

To reveal the changes in the life history characteristics of grassland plants due to vegetation restoration, plant species and communities were analyzed for their competitor, stress tolerator, and ruderal (CSR) ecological strategies after the introduction of woody plants in the damaged steppe grassland and were compared with those in reference sites in Hulunbuir, Inner Mongolia. As a result, it was found that the introduction of the woody plants (Corethrodeneron fruticosum, Caragana microphylla, Populus canadensis, and Pinus sylvestris var. mongolica) into the damaged land greatly increased the plant species diversity and CSR eco-functional diversity as the succession progressed. The plant strategies of the temperate typical steppe (TTS) and woodland steppe (WS) in this Asian steppe are CSR and S/SR, respectively, which means that the plants are adapted to disturbances or stress. As the restoration time elapsed in the damaged lands exhibiting (R/CR) (Corispermum hyssopifolium), the ecological strategies were predicted to change in two ways: (1) →R/CSR (Cynanchum thesioides, Astragalus laxmannii, etc.) → CSR in places (TSS) (Galium verum var. asiaticum, Saussurea japonica, etc.) where only shrubs were introduced, and (2) → S/SR (Allium mongolicum, Ulmus pumila, etc.) → S/SR in sites (WS) (Ulmus pumila, Thalictrum squarrosum, etc.) where trees and shrubs were planted simultaneously. The results mean that the driving force that causes succession in the restoration of temperate grasslands is determined by the life-form (trees/shrubs) of the introduced woody plants. This means that for the restoration of these grasslands to be successful, it is necessary to introduce woody tree species at an early stage.

Exploring influential factors on patient safety culture in delirium nursing care within long-term care facilities: a cross-sectional survey.

BACKGROUND: Elderly residents with physical and cognitive impairments in long-term care facilities are vulnerable to safety risks. PURPOSE: This study investigated factors that influence patient safety cultures in delirium nursing care in long-term care facilities. METHODS: A cross-sectional survey was conducted among 214 nurses working in 12 long-term care facilities using a structured questionnaire from February 15, 2022, to March 14, 2022. Data analysis was performed using Pearson's correlation coefficients and hierarchical analysis with SPSS/WIN 25.0 software. RESULTS: Significant factors associated with patient safety culture were identified. Organizational factors included the availability of delirium care manuals, nursing education and experience in delirium care, and the perceived necessity of delirium education. Individual factors included nurse-to-patient ratios, and nurses marital status. CONCLUSION: To foster a strong patient safety culture, attention should be given to the availability of delirium care resources, the promotion of specialized and ongoing education and experience, and adequate staffing levels.

Corrigendum: Computed tomography-based assessment of radiographic progression in spine and sacroiliac joints after pregnancy in women with radiographic axial spondyloarthritis.

[This corrects the article DOI: 10.3389/fmed.2022.970546.].