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PDGFRA+ cells have been identified as adipocyte stem cells (ASCs) that differentiate into beige adipocytes in white adipose tissue (WAT) following thermogenic stimuli. To elucidate the molecular heterogeneity of ASCs, we conducted single-cell transcriptomic profiling of PDGFRA+ cells isolated from the inguinal WAT (iWAT) of mice treated with the beta3 adrenergic receptor agonist CL316243. Single-cell RNA-seq revealed nine major clusters, which were categorized into four groups: resting, proliferating, differentiating, and adipogenic factor-expressing cells (AFECs). Trajectory analysis revealed sequential activation of molecular pathways, including the Hedgehog and Notch signaling pathways, during beige adipogenesis. AFECs expressed Dpp4 and did not differentiate into adipocytes in culture or after transplantation. Furthermore, genetic lineage tracing studies indicated that DPP4+ cells did not differentiate into adipocytes in iWAT during CL316243-induced beige adipogenesis. However, high-fat diet feeding led to the recruitment of adipocytes from DPP4+ cells in iWAT. Overall, this study improved our understanding of the dynamic molecular basis of beige adipogenesis and the potential contribution of DPP4+ adipocyte lineages to the pathological expansion of WAT during diet-induced obesity., (© 2024. The Author(s).)

Metabolic syndrome increases the risks of cardiovascular diseases, type 2 diabetes, and certain cancers. The early detection of metabolic syndrome is clinically relevant, as it enables timely and targeted interventions. In the current study, we aimed to investigate the association between metabolic syndrome and heart rate measured using wearable devices in a real-world setting and compare this association with that for clinical resting heart rate. Data from 564 middle-aged adults who wore wearable devices for at least 7 days with a minimum daily wear time of 20 h were analyzed. The results showed significantly elevated all-day, sleeping, minimum, and inactive heart rates in men with pre-metabolic or metabolic syndrome compared with those in normal individuals, whereas sleeping heart rate and heart rate dips were significantly increased and decreased, respectively, in women with metabolic syndrome. After adjusting for confounders, every 10-beats-per-minute increment in all-day, sleeping, minimum, and inactive heart rates in men corresponded to odds ratios of 2.80 (95% confidence interval 1.53-5.44), 3.06 (1.57-6.40), 4.21 (1.87-10.47), and 3.09 (1.64-6.29), respectively, for the presence of pre-metabolic or metabolic syndrome. In women, the association was significant only for heart rate dips (odds ratio = 0.49 [95% confidence interval 0.25-0.96] for every 10% increment). Models incorporating inactive or minimum heart rate in men and heart rate dip in women demonstrated better fits, as indicated by lower Akaike information criterion values (170.3 in men and 364.9 in women), compared with models that included clinical resting heart rate (173.4 in men and 369.1 in women). These findings suggest that the heart rate indices obtained from wearable devices may facilitate early identification of metabolic syndrome., (© 2024. The Author(s).)

Acellular nerve grafts (ANGs) are a promising therapeutic for patients with nerve defects caused by injuries. Conventional decellularization methods utilize a variety of detergents and enzymes. However, these methods have disadvantages, such as long processing times and the presence of detergents that remain on the graft. In this study, we aimed to reduce process time and minimize the risks associated with residual detergents by replacing them with supercritical carbon dioxide (scCO 2 ) and compared the effectiveness to Hudson's decellularization method, which uses several detergents. The dsDNA and the expression of MHC1 and 2 were significantly reduced in both decellularized groups, which confirmed the effective removal of cellular debris. The extracellular matrix proteins and various factors were found to be better preserved in the scCO 2 ANGs compared to the detergent-ANGs. We conducted behavioral tests and histological analyses to assess the impact of scCO 2 ANGs on peripheral nerve regeneration in animal models. Compared with Hudson's method, the scCO 2 method effectively improved the efficacy of peripheral nerve regeneration. Therefore, the decellularization method using scCO 2 is not only beneficial for ANG synthesis, but it may also be helpful for therapeutics by enhancing the efficacy of peripheral nerve regeneration., (© 2024. The Author(s).)

Dyskalemia is a common electrolyte abnormality. Since dyskalemia can cause fatal arrhythmias and cardiac arrest in severe cases, it is crucial to monitor serum potassium (K + ) levels on time. We developed deep learning models to detect hyperkalemia (K +  ≥ 5.5 mEq/L) and hypokalemia (K +  < 3.5 mEq/L) from electrocardiograms (ECGs), which are noninvasive and can be quickly measured. The retrospective cohort study was conducted at two hospitals from 2006 to 2020. The training set, validation set, internal testing cohort, and external validation cohort comprised 310,449, 15,828, 23,849, and 130,415 ECG-K + samples, respectively. Deep learning models demonstrated high diagnostic performance in detecting hyperkalemia (AUROC 0.929, 0.912, 0.887 with sensitivity 0.926, 0.924, 0.907 and specificity 0.706, 0.676, 0.635 for 12-lead, limb-lead, lead I ECGs) and hypokalemia (AUROC 0.925, 0.896, 0.885 with sensitivity 0.912, 0.896, 0.904 and specificity 0.790, 0.734, 0.694) in the internal testing cohort. The group predicted to be positive by the hyperkalemia model showed a lower 30-day survival rate compared to the negative group (p < 0.001), supporting the clinical efficacy of the model. We also compared the importance of ECG segments (P, QRS, and T) on dyskalemia prediction of the model for interpretability. By applying these models in clinical practice, it will be possible to diagnose dyskalemia simply and quickly, thereby contributing to the improvement of patient outcomes., (© 2024. The Author(s).)

The E-Health Big Data Evidence Innovation Network (FeederNet) in Korea, based on the observational medical outcomes partnership (OMOP) common data model (CDM), had 72.3% participation from tertiary hospitals handling severe diseases as of October 2022. While this contributes to the activation of multi-institutional research, concerns about the comprehensiveness of device data persist due to the adoption of national health insurance corporation (NHIC) claim codes as device identifiers in the medical device field. This study critically evaluated the effectiveness and compatibility of NHIC claim codes and unique device identifier (UDI) within FeederNet to identify the optimal identifier for efficient Post-market surveillance (PMS). Specifically, this study addressed three main questions: (1) the number of UDIs classified as NHIC-covered items, (2) the number of UDIs included in each NHIC claim code, and (3) the number of NHIC claim codes each UDI covers. Among the 1,979,655 UDIs registered domestically, only 36.02% (712,983) were classified as covered by National Health Insurance. NHIC-covered medical devices were limited to categories (A) medical devices, (B) medical supplies, and (C) dental materials, excluding most software and in vitro diagnostics (IVD). Multiple UDIs could be registered under a single NHIC claim code, and a single UDI could be registered under multiple NHIC claim codes. Only 32.62% (13,756/42,171) of NHIC claim codes had registered UDIs, with an average of 53 UDIs per claim code. Of the UDIs listed as NHIC covered, 92.39% (659,046/713,341) had one claim code, while 7.25% (51,652) had multiple claim codes. Additionally, 2643 UDIs were listed as NHIC covered but had no registered claim codes. Due to this complex relationship, NHIC claim code-based PMS may pool safe and unsafe models or disperse problematic models across multiple claim codes, leading to a lower problem rate or insignificant differences between claim codes, thus reducing signal detection sensitivity compared to UDI-based PMS. In conclusion, NHIC claim code-based PMS has limitations in granularity and signal detection sensitivity, necessitating the adoption of UDI-based PMS to address these issues. The UDI system can enhance the accuracy of medical device identification and tracking, playing a crucial role in generating real-world evidence (RWE) by integrating data from various sources. Future research should explore specific strategies for integrating and utilizing UDI with NHIC claim codes, contributing to the implementation of a more reliable and comprehensive PMS in Korea's healthcare system., (© 2024. The Author(s).)

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management., (© 2024. The Author(s).)

This study aimed to evaluate the efficacy of Lactiplantibacillus argentoratensis AGMB00912 (LA) in reducing Salmonella Typhimurium infection in weaned piglets. The investigation focused on the influence of LA on the gut microbiota composition, growth performance, and Salmonella fecal shedding. The results indicated that LA supplementation significantly improved average daily gain and reduced the prevalence and severity of diarrhea. Fecal analysis revealed reduced Salmonella shedding in the LA-supplemented group. Furthermore, LA notably altered the composition of the gut microbiota, increasing the levels of beneficial Bacillus and decreasing those of harmful Proteobacteria and Spirochaetes. Histopathological examination showed less intestinal damage in LA-treated piglets than in the controls. The study also observed that LA affected metabolic functions related to carbohydrate, amino acid, and fatty acid metabolism, thereby enhancing gut health and resilience against infection. Short-chain fatty acid concentrations in the feces were higher in the LA group, suggesting improved gut microbial activity. LA supplementation enriched the population of beneficial bacteria, including Streptococcus, Clostridium, and Bifidobacterium, while reducing the number of harmful bacteria, such as Escherichia and Campylobacter. These findings indicate the potential of LA as a probiotic alternative for swine nutrition, offering protective effects to the gut microbiota against Salmonella infection., (© 2024. The Author(s).)

VISUMAX 800 was introduced to improve the patient experience and clinical outcomes of small incision lenticule extraction (SMILE). This was a retrospective, matched, and case-control study (1:2) controlled for preoperative central corneal thickness and refractive error that compared early refractive and visual outcomes after SMILE using VISUMAX 800 and VISUMAX 500 to treat myopia. We included 50 eyes that underwent the VISUMAX 800 SMILE and 100 eyes that underwent the VISUMAX 500 SMILE. SMILE using VISUMAX 800 was performed using the CentraLign aid for vertex centration. Cyclotorsion was controlled by an OcuLign assistant in the VISUMAX 800 group after corneal marking. Corneal higher-order aberrations (HOAs) were evaluated using a Pentacam 1 month after surgery. No differences were observed in the pre- and post-operative refractive and visual outcomes at 1 day, 1 month, and 6 months after surgery. VISUMAX 800 induced less total HOAs than VISUMAX 500 (P = 0.036). No statistically significant differences were observed in the amounts of induced spherical aberrations or vertical and horizontal comas. No differences were observed in the 1 month and 6 months refractive and visual outcomes between two SMILE procedures, except for VISUMAX 800, which resulted in lower postoperative total HOAs than VISUMAX 500., (© 2024. The Author(s).)

Severe intraventricular hemorrhage (IVH) in premature infants can lead to serious neurological complications. This retrospective cohort study used the Korean Neonatal Network (KNN) dataset to develop prediction models for severe IVH or early death in very-low-birth-weight infants (VLBWIs) using machine-learning algorithms. The study included VLBWIs registered in the KNN database. The outcome was the diagnosis of IVH Grades 3-4 or death within one week of birth. Predictors were categorized into three groups based on their observed stage during the perinatal period. The dataset was divided into derivation and validation sets at an 8:2 ratio. Models were built using Logistic Regression with Ridge Regulation (LR), Random Forest, and eXtreme Gradient Boosting (XGB). Stage 1 models, based on predictors observed before birth, exhibited similar performance. Stage 2 models, based on predictors observed up to one hour after birth, showed improved performance in all models compared to Stage 1 models. Stage 3 models, based on predictors observed up to one week after birth, showed the best performance, particularly in the XGB model. Its integration into treatment and management protocols can potentially reduce the incidence of permanent brain injury caused by IVH during the early stages of birth., (© 2024. The Author(s).)

Autophagy is a self-degradation system for recycling to maintain homeostasis. p62/sequestosome-1 (p62) is an autophagy receptor that accumulates in neuroglia in neurodegenerative diseases. The objective of this study was to determine the elevation of plasma p62 protein levels in patients with Charcot-Marie-Tooth disease 1A (CMT1A) for its clinical usefulness to assess disease severity. We collected blood samples from 69 CMT1A patients and 59 healthy controls. Plasma concentrations of p62 were analyzed by ELISA, and we compared them with Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2). A mouse CMT1A model (C22) was employed to determine the source and mechanism of plasma p62 elevation. Plasma p62 was detected in healthy controls with median value of 1978 pg/ml, and the levels were significantly higher in CMT1A (2465 pg/ml, p < 0.001). The elevated plasma p62 levels were correlated with CMTNSv2 (r = 0.621, p < 0.0001), motor nerve conduction velocity (r =  - 0.490, p < 0.0001) and disease duration (r = 0.364, p < 0.01). In C22 model, increased p62 expression was observed not only in pathologic Schwann cells but also in plasma. Our findings indicate that plasma p62 measurement could be a valuable tool for evaluating CMT1A severity and Schwann cell pathology., (© 2024. The Author(s).)

Many studies sought to demonstrate the association between smoking and fracture risk. However, the correlation between smoking and fractures remains controversial. This study aimed to examine the impact of smoking and smoking cessation on the occurrence of fractures using prospective nationwide cohort data. We enrolled those who underwent a National Health Insurance Service (NHIS) health checkup in 2009-2010 who had a previous health checkup 4-year prior (2005-2006). The study population of 4,028,559 subjects was classified into three groups (non-smoker, smoking cessation, current smoker). The study population was also analyzed according to fracture type (all fractures, vertebral fracture, hip fracture). Lastly, the smoking cessation group and current smoker group were divided into four subgroups based on a lifetime smoking amount cut-off of 20 pack-years (PY). Multivariate-adjusted hazard ratios (HRs) of fracture were examined through a Cox proportional hazards model. After multivariable adjustment, non-smokers showed the lowest risk of fracture (HR = 0.818, CI 0.807-0.828, p < 0.0001) and smoking cessation significantly lowered the risk of fracture (HR 0.938, 95% CI 0.917-0.959, p < 0.0001) compared to current smokers. Regardless of 20PY, all smoking cessation subgroups showed significantly less risk of fractures than current smokers with ≥ 20PYs. Smoking increases the risk of fracture, and smoking cessation lowers the risk of fracture., (© 2024. The Author(s).)

Little is known about the therapeutic outcomes of transforaminal epidural steroid injection (TFESI) in patients with lumbosacral radicular pain due to lumbar spinal stenosis (LSS). Using lumbar spine radiographs as input data, we trained a convolutional neural network (CNN) to predict therapeutic outcomes after lumbar TFESI in patients with lumbosacral radicular pain caused by LSS. We retrospectively recruited 193 patients for this study. The lumbar spine radiographs included anteroposterior, lateral, and bilateral (left and right) oblique views. We cut each lumbar spine radiograph image into a square shape that included the vertebra corresponding to the level at which the TFESI was performed and the vertebrae juxta below and above that level. Output data were divided into "favorable outcome" (≥ 50% reduction in the numeric rating scale [NRS] score at 2 months post-TFESI) and "poor outcome" (< 50% reduction in the NRS score at 2 months post-TFESI). Using these input and output data, we developed a CNN model for predicting TFESI outcomes. The area under the curve of our model was 0.920. Its accuracy was 87.2%. Our CNN model has an excellent capacity for predicting therapeutic outcomes after lumbar TFESI in patients with lumbosacral radicular pain induced by LSS., (© 2024. The Author(s).)

With the progress of robotic transaxillary thyroid surgery (RTTS), the indications for this procedure have gradually expanded. This study presents the insights gained from performing 10,000 RTTS cases at a single institution, along with the expansion of indications over time. RTTS was performed on 10,000 patients using the da Vinci robot system between October 2007 and April 2023 at the Yonsei University Health System, Seoul, Korea. Among 10,000 patients, 9461 (94.0%) were diagnosed with thyroid cancer, whereas 539 (5.4%) had either a benign thyroid nodule or Graves' disease. Surgical procedures were performed using four-arm-based robots (da Vinci S, Si, or Xi) for 8408 cases (84.1%), with the remaining 1592 cases (15.9%) being performed using the da Vinci SP surgical robotic system. Notably, for 53 patients with nodules ≥ 5 cm, which were not included in the eligibility criteria of the previous study, RTTS was performed safely without significant complications. The most common postoperative complication was transient hypoparathyroidism (37.91%), and recurrence occurred in 100 patients with thyroid cancer (1.1%). In conclusion, RTTS appears safe and feasible from both surgical and oncological perspectives, and the spectrum of indications suitable for RTTS surgery is progressively expanding., (© 2024. The Author(s).)

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient., (© 2024. The Author(s).)

Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system. Through single-cell RNA sequencing, we demonstrated that Baf knockdown induces prominent transcriptomic changes, particularly in type I neuroblasts. Among the differentially expressed genes, our genetic analyses identified teashirt (tsh), a transcription factor that interacts with beta-catenin, to be closely associated with Baf knockdown-induced phenotypes that were suppressed by the overexpression of tsh or beta-catenin. We also found that Baf and tsh colocalized in a region adjacent to heterochromatin in type I NBs. Notably, the subnuclear localization pattern remained unchanged when one of these two proteins was knocked down, indicating that both proteins contribute to the anchoring of heterochromatin to the inner nuclear membrane. Overall, this study reveals that the Baf-mediated transcriptional regulation of teashirt is a novel molecular mechanism that regulates the development of neural progenitor cell lineages., (© 2024. The Author(s).)

Galectin-3 levels have been studied as a potential biomarker for predicting cardiovascular (CV) risk and mortality in hemodialysis (HD) patients. Recently, a close relationship between galectin-3 and vascular calcification (VC) has been reported. Here, we investigated the role of VC as a mediating factor in the association between galectin-3 and mortality. Serum galectin-3 and baseline aortic arch calcification (AoAC) score were measured in 477 incident HD patients. Mortality data were obtained at a median follow-up of 40 months. Causal mediation analysis was performed to examine the effect of vascular risk factors on galectin-3-related mortality. The prevalence of AoAC in HD patients was 57% (n = 272), and elevated galectin-3 levels were associated with a significantly increased risk of AoAC. When the galectin-3 level was divided by the median level of 37 ng/mL, a higher galectin group increased the risk of all-cause mortality by 1.71-fold (95% CI 1.02-2.92, p = 0.048), even after adjustment for multiple CV risk factors. Mediation analysis showed that both the direct effect of the galectin-3 on mortality (β = 0.0368, bootstrapped 95% CI [0.0113-0.0622]) and the indirect effects were significant. AoAC score and high-sensitivity CRP levels significantly mediated the association between galectin-3 and mortality (total indirect effects: β = 0.0188, bootstrapped 95% CI [0.0066-0.0352]). This study suggests that the association between high galectin-3 and mortality may be partially mediated by higher VC and inflammatory state in HD patients., (© 2024. The Author(s).)

This study examined the link between fatty liver disease (FLD) and cataracts, as previous research has suggested that FLD may contribute to metabolic syndrome, systemic inflammation, and potentially cataracts. We studied a nationwide cross-sectional cohort of the Fifth Korean National Health and Nutrition Examination Survey 2010-2011. FLD was defined as nonalcoholic FLD (NAFLD) and metabolic dysfunction-associated FLD (MAFLD). Multinomial logistic regression was utilized to investigate the relationship between cataracts and FLD after adjustment for potential confounders. Participants with cataracts had higher liver fibrosis scores, including the NAFLD fibrosis score (NFS; P < 0.001), fibrosis-4 index (FIB4; P < 0.001), and fatty liver index (FLI; P = 0.001). NAFLD was not associated with a higher odds ratio (OR) for cataracts in the fully adjusted model (OR = 1.23, P = 0.058). MAFLD was significantly associated with a higher OR (OR = 1.34, P = 0.006). After adjusting for all factors, the severity of FLD was linked to an increased risk of cataracts, with significant linear trends (P values for linear trends of NFS, FIB4, and FLI < 0.05). After adjusting for well-known cataract risk factors, MAFLD was significantly associated with cataracts. Our analysis suggests that FLD may serve as an independent risk factor for cataracts., (© 2024. The Author(s).)

Spin nematic is a magnetic analogue of classical liquid crystals, a fourth state of matter exhibiting characteristics of both liquid and solid 1,2 . Particularly intriguing is a valence-bond spin nematic 3-5 , in which spins are quantum entangled to form a multipolar order without breaking time-reversal symmetry, but its unambiguous experimental realization remains elusive. Here we establish a spin nematic phase in the square-lattice iridate Sr 2 IrO 4 , which approximately realizes a pseudospin one-half Heisenberg antiferromagnet in the strong spin-orbit coupling limit 6-9 . Upon cooling, the transition into the spin nematic phase at T C  ≈ 263 K is marked by a divergence in the static spin quadrupole susceptibility extracted from our Raman spectra and concomitant emergence of a collective mode associated with the spontaneous breaking of rotational symmetries. The quadrupolar order persists in the antiferromagnetic phase below T N  ≈ 230 K and becomes directly observable through its interference with the antiferromagnetic order in resonant X-ray diffraction, which allows us to uniquely determine its spatial structure. Further, we find using resonant inelastic X-ray scattering a complete breakdown of coherent magnon excitations at short-wavelength scales, suggesting a many-body quantum entanglement in the antiferromagnetic state 10,11 . Taken together, our results reveal a quantum order underlying the Néel antiferromagnet that is widely believed to be intimately connected to the mechanism of high-temperature superconductivity 12,13 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Chub mackerels (Scomber japonicus) are a migratory marine fish widely distributed in the Indo-Pacific Ocean. They are globally consumed for their high Omega-3 content, but their population is declining due to global warming. Here, we generated the first chromosome-level genome assembly of chub mackerel (fScoJap1) using the Vertebrate Genomes Project assembly pipeline with PacBio HiFi genomic sequencing and Arima Hi-C chromosome contact data. The final assembly is 828.68 Mb with 24 chromosomes, nearly all containing telomeric repeats at their ends. We annotated 31,656 genes and discovered that approximately 2.19% of the genome contained DNA transposon elements repressed within duplicated genes. Analyzing 5-methylcytosine (5mC) modifications using HiFi reads, we observed open/close chromatin patterns at gene promoters, including the FADS2 gene involved in Omega-3 production. This chromosome-level reference genome provides unprecedented opportunities for advancing our knowledge of chub mackerels in biology, industry, and conservation., (© 2023. The Author(s).)

Warton's jelly-derived Mesenchymal stem cells (WJ-MSCs) play key roles in improving nerve regeneration in acellular nerve grafts (ANGs); however, the mechanism of WJ-MSCs-related nerve regeneration remains unclear. This study investigated how WJ-MSCs contribute to peripheral nerve regeneration by examining immunomodulatory and paracrine effects, and differentiation potential. To this end, WJ-MSCs were isolated from umbilical cords, and ANGs (control) or WJ-MSCs-loaded ANGs (WJ-MSCs group) were transplanted in injury animal model. Functional recovery was evaluated by ankle angle and tetanic force measurements up to 16 weeks post-surgery. Tissue biopsies at 3, 7, and 14 days post-transplantation were used to analyze macrophage markers and interleukin (IL) levels, paracrine effects, and MSC differentiation potential by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The WJ-MSCs group showed significantly higher ankle angle at 4 weeks and higher isometric tetanic force at 16 weeks, and increased expression of CD206 and IL10 at 7 or 14 days than the control group. Increased levels of neurotrophic and vascular growth factors were observed at 14 days. The WJ-MSCs group showed higher expression levels of S100β; however, the co-staining of human nuclei was faint. This study demonstrates that WJ-MSCs' immunomodulation and paracrine actions contribute to peripheral nerve regeneration more than their differentiation potential., (© 2023. The Author(s).)

Preterm birth prediction is essential for improving neonatal outcomes. While many machine learning techniques have been applied to predict preterm birth using health records, inflammatory markers, and vaginal microbiome data, the role of prenatal oral microbiome remains unclear. This study aimed to compare oral microbiome compositions between a preterm and a full-term birth group, identify oral microbiome associated with preterm birth, and develop a preterm birth prediction model using machine learning of oral microbiome compositions. Participants included singleton pregnant women admitted to Jeonbuk National University Hospital between 2019 and 2021. Subjects were divided into a preterm and a full-term birth group based on pregnancy outcomes. Oral microbiome samples were collected using mouthwash within 24 h before delivery and 16S ribosomal RNA sequencing was performed to analyze taxonomy. Differentially abundant taxa were identified using DESeq2. A random forest classifier was applied to predict preterm birth based on the oral microbiome. A total of 59 women participated in this study, with 30 in the preterm birth group and 29 in the full-term birth group. There was no significant difference in maternal clinical characteristics between the preterm and the full-birth group. Twenty-five differentially abundant taxa were identified, including 22 full-term birth-enriched taxa and 3 preterm birth-enriched taxa. The random forest classifier achieved high balanced accuracies (0.765 ± 0.071) using the 9 most important taxa. Our study identified 25 differentially abundant taxa that could differentiate preterm and full-term birth groups. A preterm birth prediction model was developed using machine learning of oral microbiome compositions in mouthwash samples. Findings of this study suggest the potential of using oral microbiome for predicting preterm birth. Further multi-center and larger studies are required to validate our results before clinical applications., (© 2023. The Author(s).)

Iron deficiency (ID) in very preterm infants born at 28-32 weeks of gestational age (GA) can lower mental and motor test scores. This study aimed to determine whether the rapid growth of very preterm infants might be associated with ID. Among 134 very preterm born between January 2014 and December 2020 at Jeonbuk National University Hospital and discharged home, 93 were included in this study. Rapid BMI increase (RBI) was defined as a z-score difference of > 1 standard deviation between birth and 8 months. ID occurred in 23 of 93 (24.7%) infants at 8 months of corrected age (CA). ID was more common in the RBI group (50%) than in the non-RBI group (18.7%). In the multivariate logistic regression corrected for GA, infants small for gestational age (SGA) (odds ratio [OR] 6.06, 95% confidence interval [CI] 1.34-30.21) and RBI by z-score (OR 4.26, 95% CI 1.28-14.65) were identified as independent risk factors for ID at 8 months of CA. Conclusively, both SGA and RBI in the early life of very preterm were risk factors for ID at 8 months of CA., (© 2023. Springer Nature Limited.)

Obesity-associated nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is the leading cause of liver failure and death. The function of AMP-activated protein kinase (AMPK), a master energy sensor, is aberrantly reduced in NAFLD, but the underlying mechanisms are not fully understood. Increasing evidence indicates that aberrantly expressed microRNAs (miRs) are associated with impaired AMPK function in obesity and NAFLD. In this review, we discuss the emerging evidence that miRs have a role in reducing AMPK activity in NAFLD and nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. We also discuss the underlying mechanisms of the aberrant expression of miRs that can negatively impact AMPK, as well as the therapeutic potential of targeting the miR-AMPK pathway for NAFLD/NASH., (© 2023. The Author(s).)

This study explores the potential of utilizing microwaves to sustain the expansion of transient laser ablation plasma of Zr target. By application of microwaves on the plasma, we observe a significant enhancement with a two to three order of magnitude increase in the plasma emission intensity, and 18 times increase in the plasma's spatial volume. We investigate the temperature change of the plasma and observe that it decreases from 10,000 K to approximately 3000 K. Electron temperature decreased with volume expansion owing to increased surrounding air interaction, while the plasma can be sustained in air using microwaves. The increase in electron temperature during temperature drop is indicative of non-equilibrium plasma. Our results emphasize the contribution of microwaves in promoting enhanced emission and plasma formation at controlled, low temperature, thereby demonstrating the potential of microwaves to enhance the accuracy and performance of laser-induced breakdown spectroscopy. Importantly, our study suggests that microwaves could also mitigate the generation of toxic fumes and dust during ablation, a critical benefit when handling hazardous materials. The system we've developed is highly valuable for a range of applications, notably including the potential to reduce the possible emergence of toxic fumes during the decommissioning of nuclear debris., (© 2023. Springer Nature Limited.)

Surveillance of influenza A viruses (IAVs) among migratory waterfowl is a first step in understanding the ecology, biology, and pathogenicity of IAVs. As part of the nationwide surveillance effort for IAVs in fowl in South Korea, we collected environmental fecal samples in different migratory bird stopover sites in South Korea during the winter seasons within November 2014 through January 2018. We collected a total of 6758 fecal samples, 75 of which were positive for IAV (1.11% positivity). Prevalence of IAVs varied per site and per year. Based on sequencing, the most prevalent hemagglutinin (HA) subtypes were H1, H6, and H5, and the most prevalent neuraminidase (NA) subtypes were N1, N3, and N2. Phylogenetic analyses showed that the genes we isolated clustered with reported isolates collected from other locations along the East Asian-Australasian Flyway. All the H5 and H7 isolates collected in this study were of low pathogenicity. None of the N1 and N2 genes carried amino acid markers of resistance against NA inhibitors. The winter 2016-2017 subset were primarily borne by migratory geese (Anser spp.). These results suggest that majority of the IAVs circulating among migratory wild fowl in South Korea in 2014-2018 were of low pathogenicity., (© 2023. The Author(s).)

The proliferation and migration of vascular smooth muscle cells (VSMCs) after vascular injury lead to neointimal hyperplasia, thus aggravating vascular diseases. However, the molecular mechanisms underlying neointima formation are not fully elucidated. Extracellular vesicles (EVs) are mediators of various intercellular communications. The potential of EVs as regulators in cardiovascular diseases has raised significant interest. In the current study we investigated the role of circulating small extracellular vesicles (csEVs), the most abundant EVs (10 10 EVs/mL serum) in VSMC functions. csEVs were prepared from bovine, porcine or rat serum. We showed that incubation with csEVs (0.5 × 10 10 -2 × 10 10 ) dose-dependently enhanced the proliferation and migration of VSMCs via the membrane phosphatidylserine (PS). In rats with ligation of right carotid artery, we demonstrated that application of csEVs in the ligated vessels aggravated neointima formation via interaction of membrane PS with injury. Furthermore, incubation with csEVs markedly enhanced the phosphorylation of AXL and MerTK in VSMCs. Pretreatment with BSM777607 (pan-TAM inhibitor), bemcentinib (AXL inhibitor) or UNC2250 (MerTK inhibitor) blocked csEV-induced proliferation and migration of VSMCs. We revealed that csEV-activated AXL and MerTK shared the downstream signaling pathways of Akt, extracellular signal-regulated kinase (ERK) and focal adhesion kinase (FAK) that mediated the effects of csEVs. We also found that csEVs increased the expression of AXL through activation of transcription factor YAP, which might constitute an AXL-positive feedback loop to amplify the signals. Finally, we demonstrated that dual inhibition of AXL/MerTK by ONO-7475 (0.1 µM) effectively hindered csEV-mediated proliferation and migration of VSMCs in ex vivo mouse aorta injury model. Based on these results, we propose an essential role for csEVs in proliferation and migration of VSMCs and highlight the feasibility of dual AXL/MerTK inhibitors in the treatment of vascular diseases., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

We developed a novel prediction model for recurrence and survival in patients with localized renal cell carcinoma (RCC) after surgery and a novel statistical method of machine learning (ML) to improve accuracy in predicting outcomes using a large Asian nationwide dataset, updated KOrean Renal Cell Carcinoma (KORCC) database that covered data for a total of 10,068 patients who had received surgery for RCC. After data pre-processing, feature selection was performed with an elastic net. Nine variables for recurrence and 13 variables for survival were extracted from 206 variables. Synthetic minority oversampling technique (SMOTE) was used for the training data set to solve the imbalance problem. We applied the most of existing ML algorithms introduced so far to evaluate the performance. We also performed subgroup analysis according to the histologic type. Diagnostic performances of all prediction models achieved high accuracy (range, 0.77-0.94) and F1-score (range, 0.77-0.97) in all tested metrics. In an external validation set, high accuracy and F1-score were well maintained in both recurrence and survival. In subgroup analysis of both clear and non-clear cell type RCC group, we also found a good prediction performance., (© 2023. The Author(s).)

We report on the analysis of pure gadolinium oxide (Gd 2 O 3 ) and its detection when mixed in surrogate nuclear debris using microwave-enhanced fiber-coupled micro-laser-induced breakdown spectroscopy (MWE-FC-MLIBS). The target application is remote analysis of nuclear debris containing uranium (U) inside the Fukushima Daiichi Nuclear Power Station. The surrogate nuclear debris used in this study contained gadolinium (Gd), cerium (Ce), zirconium (Zr), and iron (Fe). Ce is a surrogate for U, and Gd 2 O 3 is an excellent hazard index because it is incorporated into some fuel rods. Gd detection is essential for assessing debris prior to the retrieval process. Surrogate debris was ablated by an 849 ps 1064 nm micro-laser under atmospheric pressure conditions while a helical antenna propagated 2.45 GHz 1.0 kW microwaves for 1.0 ms into the laser ablation, which was then characterized by a high-speed camera and high-resolution spectrometers. The results showed that microwave-induced plasma expansion led to enhanced emission signals of Gd I, Zr I, Fe I, Ce I, and Ce II. No self-absorption of Gd emissions was evident from the detection limit calibration graphs. Moreover, microwave irradiation decreased the standard deviations of the Gd and Ce emissions and lowered the Gd detection limit by 60%., (© 2023. The Author(s).)

This study aimed to evaluate the alteration of PAP compliance after nasal surgery and to determine the optimal indications of nasal surgery in obstructive sleep apnea (OSA) subjects. Among OSA subjects using PAP devices, 29 subjects who underwent septoturbinoplasty due to nasal obstruction were included and their pre- and postoperative medical and PAP records were reviewed retrospectively. Postoperative autoPAP usage data was further assessed by grouping the compliance (the percentage of days with usage ≥ 4 h) data (group 1: the good compliance group; group 2: the poor compliance group). The data showed that 56% of subjects in group 1 complained of nasal obstruction as the only barrier to using a PAP device and about 89% reported experiencing the efficacy of PAP usage. Both the mean and peak average PAP pressures were significantly reduced in group 1 following nasal surgery. Group 2 had multiple subjective problems that interfered with wearing a PAP device and reported a lack of experiencing the efficacy of PAP usage. Preoperative nasal cavity volume values were smaller and absolute blood eosinophil counts were significantly lower in group 1. The current data demonstrate that nasal surgery might increase the compliance of PAP device wear in OSA subjects who complained of only nasal obstruction as a barrier to wearing PAP and who had small nasal cavity volumes combined with allergic inflammation., (© 2023. The Author(s).)

ST2 functions as a receptor for the cytokine IL-33. It has been implicated in carcinogenesis. In this study, we sought to mechanistically determine how ST2 and IL-33 function to support cancer stem cell (CSC) activity and drive gastric cancer (GC) pathogenesis. ST2+ subpopulation spontaneously arose during gastric tumorigenesis. A thorough evaluation of ST2 and IL-33 expression in gastric tumors revealed that they show an overlapping expression pattern, notably in poor differentiated GC and metastasis foci. Moreover, their expression levels are clinically correlated to cancer progression. Using a genetic model of CSC-driven gastric carcinogenesis, ST2+ subpopulation displays increased tumorigenicity, chemoresistance and metastatic potentials through increased survival fitness endowed by an elevated MAPK-regulated Bcl-xL. The IL-33/ST2 axis enhances the self-renewal and survival of GC stem cells and organoids. Importantly, we observed a synergistic cooperation between IL-33/ST2 and the canonical Wnt pathway in transactivating Wnt-dependent transcription and supporting CSC activity, a partnership that was abrogated by inhibiting Bcl-xL. Concordant with this, ST2+ subpopulation was targeted by MEK1/2 and Bcl-xL-specific inhibitors. These findings establish ST2 as a functional CSC marker that fortifies the Wnt signal while availing a novel therapeutic strategy to suppress GC progression by targeting the IL-33/ST2/Bcl-xL signaling axis., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The Arg/N-degron pathway, which is involved in the degradation of proteins bearing an N-terminal signal peptide, is connected to p62/SQSTM1-mediated autophagy. However, the impact of the molecular link between the N-degron and autophagy pathways is largely unknown in the context of systemic inflammation. Here, we show that chemical mimetics of the N-degron Nt-Arg pathway (p62 ligands) decreased mortality in sepsis and inhibited pathological inflammation by activating mitophagy and immunometabolic remodeling. The p62 ligands alleviated systemic inflammation in a mouse model of lipopolysaccharide (LPS)-induced septic shock and in the cecal ligation and puncture model of sepsis. In macrophages, the p62 ligand attenuated the production of proinflammatory cytokines and chemokines in response to various innate immune stimuli. Mechanistically, the p62 ligand augmented LPS-induced mitophagy and inhibited the production of mitochondrial reactive oxygen species in macrophages. The p62 ligand-mediated anti-inflammatory, antioxidative, and mitophagy-activating effects depended on p62. In parallel, the p62 ligand significantly downregulated the LPS-induced upregulation of aerobic glycolysis and lactate production. Together, our findings demonstrate that p62 ligands play a critical role in the regulation of inflammatory responses by orchestrating mitophagy and immunometabolic remodeling., (© 2023. The Author(s).)

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia., (© 2023. The Author(s).)

We attempted to assess the performance of an ethnic-specific polygenic risk score (PRS) designed from a Korean population to predict aggressive prostate cancer (PCa) and early-onset (age < 60). A PRS score comprised of 22 SNPs was computed in 3695 patients gathered from one of 4 tertiary centers in Korea. Males with biopsy or radical prostatectomy-proven PCa were included for analysis, collecting additional clinical parameters such as age, BMI, PSA, Gleason Group (GG), and staging. Patients were divided into 4 groups of PRS quartiles. Intergroup differences were assessed, as well as risk ratio and predictive performance based on GG using logistic regression analysis and AUC. No significant intergroup differences were observed for BMI, PSA, and rate of ≥ T3a tumors on pathology. Rate of GG ≥ 2, GG ≥ 3, and GG ≥ 4 showed a significant pattern of increase by PRS quartile (p < 0.001, < 0.001, and 0.039, respectively). With the lowest PRS quartile as reference, higher PRS groups showed sequentially escalating risk for GG ≥ 2 and GG ≥ 3 pathology, with a 4.6-fold rise in GG ≥ 2 (p < 0.001) and 2.0-fold rise in GG ≥ 3 (p < 0.001) for the highest PRS quartiles. Combining PRS with PSA improved prediction of early onset csPCa (AUC 0.759) compared to PRS (AUC 0.627) and PSA alone (AUC 0.736). To conclude, an ethnic-specific PRS was found to predict susceptibility of aggressive PCa in addition to improving detection of csPCa when combined with PSA in early onset populations. PRS may have a role as a risk-stratification model in actual practice. Large scale, multi-ethnic trials are required to validate our results., (© 2023. The Author(s).)

Appropriate storage of fecal samples is a critical step for unbiased analysis in human microbiome studies. The purpose of this study was to evaluate the stability of the fecal microbial community for up to 18 months. Ten healthy volunteers provided fecal samples at the Jeonbuk National University Hospital. Stool samples were stored under the following six conditions: four different storage temperatures (- 70 °C, - 20 °C, 4 °C, and room temperature [20-25 °C]) and two different collection tubes (OMNIgene-Gut and DNA/RNA shield-fecal collection tubes). The gut microbiome was analyzed with 16S rRNA sequencing. We compared the taxonomic composition, alpha diversity, beta diversity and inferred pathway abundance between the baseline and 18 months after storage. Samples collected in the DNA/RNA Shield-fecal collection tubes showed the best performance in preservation of the taxonomic composition at 18 months. Pairwise differences in alpha diversity metrics showed the least deviation from zero. The PERMANOVA test showed non-significant change of beta diversity metrics (Unweighted Unifrac: q-value 0.268; Weighted Unifrac: q-value 0.848). The functional stability was significantly well preserved in the DNA/RNA Shield-fecal collection tubes (adjusted p value < 0.05). Our results demonstrate the use of the DNA/RNA Shield-fecal collection tube as an alternative storage method for fecal samples to preserve the taxonomic and functional stability of the microbiome over a long term., (© 2023. The Author(s).)

The authors' institution utilizes multi-staged induced membrane technique protocol based on post-debridement culture in treating patients with critical-sized bone defect in lower extremity due to infected nonunion or post-traumatic osteomyelitis. This study aimed to evaluate the success rate of this limb reconstruction method and which risk factors are associated with recurrence of infection. 140 patients were treated with multi-staged induced membrane technique from 2013 to 2018 and followed up more than 24 months after bone grafting. The primary success rate of limb reconstruction was 75% with a mean follow-up of 45.3 months. The mean Lower Extremity Functional Scale in success group improved from 12.1 ± 8.5 to 56.6 ± 9.9 after the treatment. There were 35 cases of recurrence of infection at a mean of 18.5 months after bone grafting. Independent risk factors for recurrence of infection were infected free flap, surprise positive culture, deviation from our surgical protocol, and elevated ESR before final bone graft procedure. In conclusion, this study showed that multi-staged induced membrane technique protocol based on post-debridement culture resulted in 75% success rate and revealed a number of risk factors for recurrence of infection., (© 2022. The Author(s).)

The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69-7.63; P < 0.001; aHR 2.37; 95% CI 1.06-5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94-25.00; P < 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT., (© 2022. The Author(s).)

Congenital hyperinsulinism (CHI) is a rare genetic condition characterized by uncontrolled insulin secretion, resulting in hypoglycemia. Although glucagon has lately been regarded as a therapeutic option for CHI, its use is severely hampered by its poor solubility and stability at physiological pH, as well as its short duration of action. To address these constraints, we developed HM15136, a novel long-acting glucagon analog composed of a glucagon analog conjugated to the Fc fragment of human immunoglobulin G4 via a polyethylene glycol linker. In this study, we established that HM15136 was more soluble than natural glucagon (≥ 150 mg/mL vs 0.03 mg/mL). Next, we confirmed that HM15136 activated glucagon receptor in vitro and induced glycogenolysis and gluconeogenesis in rat primary hepatocytes. Pharmacokinetics (PK)/Pharmacodynamics (PD) analysis of HM15136 shows that HM15136 has a markedly longer half-life (36 h vs. < 5 min) and increased bioavailability (90%) compared to native glucagon in mice. Further, HM15136 could effectively reverse acute hypoglycemia induced by insulin challenge, and multiple doses of HM15136 could sustain increased blood glucose levels in CHI rats. In conclusion, our findings indicate that HM15136 promotes sustained elevation of blood glucose, demonstrating the potential for development as a once-weekly therapy for CHI., (© 2022. The Author(s).)

Background/objectives: This study aimed to evaluate a deep learning model for estimating uncorrected refractive error using posterior segment optical coherence tomography (OCT) images., Methods: In this retrospective study, we assigned healthy subjects to development (N = 688 eyes of 344 subjects) and test (N = 248 eyes of 124 subjects) datasets (prospective validation design). We developed and validated OCT-based deep learning models to estimate refractive error. A regression model based on a pretrained ResNet50 architecture was trained using horizontal OCT images to predict the spherical equivalent (SE). The performance of the deep learning model for detecting high myopia was also evaluated. A saliency map was generated using the Grad-CAM technique to visualize the characteristic features., Results: The developed model showed a low mean absolute error for SE prediction (2.66 D) and a significant Pearson correlation coefficient of 0.588 (P < 0.001) in the test dataset validation. To detect high myopia, the model yielded an area under the receiver operating characteristic curve of 0.813 (95% confidence interval [CI], 0.744-0.881) and an accuracy of 71.4% (95% CI, 65.3-76.9%). The inner retinal layers and relatively steepened curvatures were highlighted using a saliency map to detect high myopia., Conclusion: A deep learning algorithm showed that OCT could potentially be used as an imaging modality to estimate refractive error. This method will facilitate the evaluation of refractive error to prevent clinicians from overlooking the risks associated with refractive error during OCT assessment., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

This study was to analyze the clinical outcomes of immediate reapplication of small-incision lenticule extraction (SMILE) without adjusting the surgical parameters after suction loss and to compare the outcomes with contralateral eyes that underwent uneventful SMILE. A total of 74 patients who underwent uneventful SMILE in one eye (Uneventful group) and immediate reapplication of SMILE without adjusting the surgical parameters after suction loss in the contralateral eye (Suction loss group) were included. Suction loss occurred during the posterior lenticule surface cut in 39 eyes (53%) and the cap cut in 35 eyes (47%). Surgical outcomes, including visual acuity, manifest refraction, keratometry, and corneal wavefront aberrations, were evaluated at 6 months postoperatively. The mean uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalent were - 0.02 ± 0.07, - 0.04 ± 0.04, and - 0.10 ± 0.46 diopters (D), respectively, in the Suction loss group and - 0.02 ± 0.07, - 0.04 ± 0.05, and - 0.19 ± 0.53 D, respectively (P = 0.965, 0.519, and 0.265, respectively), in the Uneventful group. Changes between the preoperative and 6-month postoperative total corneal aberrations, spherical aberrations, and horizontal and vertical coma did not significantly differ between the Suction loss and Uneventful groups. Immediate reapplication of SMILE without adjusting the surgical parameters after suction loss resulted in good surgical outcomes that were comparable with those of uneventful SMILE., (© 2022. The Author(s).)

Sargassum horneri is a major bloom forming species in Korea and China. It is important to find a way to utilize the huge biomass of Sargassum horneri in the region. Seaweed-derived biostimulants are primarily derived from brown algae and are known to improve terrestrial crop growth and tolerance to abiotic stresses. Neopyropia yezoensis is the most important seaweed cultured species in Korea, and research is required to increase heat resistance as a solution against climate change. In this study, various extraction methods were used to obtain Sargassum horneri extract, and it was applied to Neopyropia yezoensis to evaluate the effect on physiological activity. Metabolites of Sargassum horneri were extracted by using four different methods: boiling (SBE), soaking (SSE), autoclaving (SAE) and ethanol (SEE). The SBE, SSE and SAE derived extracts showed increased tolerance to high-temperature stress that had inhibited the growth of Neopyropia yezoensis, and show improved growth compared to the control group. The SBE and SSE extraction methods improved the content of phycobiliprotein, but also the SBE increased superoxide dismutase (SOD) activity. Based on the results of this study, the boiling extraction method appears to be the most suitable method for the extraction of plants stimulants from Sargassum horneri., (© 2022. The Author(s).)

Locoregional recurrent thyroid cancer is commonly treated with re-do operation. This study aimed to investigate the feasibility of using robotic system for re-do operation in locoregional recurrent thyroid cancer. Sixty-five patients who underwent re-do robotic operation using trans-axillary approach for locoregional recurrent thyroid cancer from October 2007 to April 2021 at Yonsei University Hospital were analyzed. Completion total thyroidectomy (CTT) was performed in 26 cases, CTT and modified radical neck node dissection (mRND) in 16, and mRND in 23. Most of the re-do robotic operations were performed at site of previous incision. All patients were diagnosed with papillary thyroid carcinoma (PTC). CTT with central compartment neck dissection (CCND) took 117.6 ± 26.3 min, CTT with mRND 255.6 ± 38.6 min, and mRND, 211.7 ± 52.9 min. Transient hypocalcemia occurred in 17 (26.2%) patients and permanent hypocalcemia occurred in 3 (4.6%). There was one case of recurrent laryngeal nerve(RLN) injury. One patient was diagnosed with structural recurrence after re-do robotic operation. Median follow-up duration was 50.7 ± 37.1 months. Re-do robotic operation can be an alternative for patients who are diagnosed with locoregional recurrent thyroid cancer after thyroidectomy, with no increase in morbidity, similar oncologic outcomes, and superior cosmetic satisfaction., (© 2022. The Author(s).)

Gut dysbiosis is closely associated with the outbreak of inflammatory bowel disease (IBD) and psychiatric disorder. The Enterobacteriaceae population was higher in the feces of patients with inflammatory bowel disease (IBD-F) than in those of healthy control volunteers (HC-F). The Enterococcaceae and Lactobacillaceae populations were higher in the feces of IBD patients with depression (IBD/D + -F) vs. the feces of IBD patients without depression (IBD/D - -F). Therefore, we examined the effects of Klebsiella oxytoca, Escherichia coli, Cronobacter sakazakii, Enterococcus faecium, and Pediococcus acidolactici overpopulated in IBD/D + -F and their byproducts LPS and exopolysaccharide (EPS) on the occurrence of depression and colitis in mice. Oral gavages of Klebsiella oxytoca, Escherichia coli, and Cronobacter sakazakii belonging to Enterobacteriaceae, singly or together, caused dose-dependently colitis and depression-like behaviors in germ-free and specific-pathogen-free mice. Although Enterococcus faecium and Pediococcus acidolactici did not significantly cause colitis and depression-like behaviors, they significantly deteriorated Klebsiella oxytoca- or Escherichia coli-induced colitis, neuroinflammation, and anxiety/depression-like behaviors and increased blood LPS, corticosterone, and IL-6 levels. The EPSs from Enterococcus faecium and Pediococcus acidolactici also worsened Klebsiella oxytoca LPS-induced colitis, neuroinflammation, and depression-like behaviors in mice and increased the translocation of fluorescein isothiocyanate-conjugated LPS into the hippocampus. However, Bifidobacterium longum, which was lower in IBD/D + -F vs. IBD/D - -F, or its EPS suppressed them. In conclusion, Enterococcus faecium and Pediococcus acidolactici, known as a probiotic strain, and their EPSs may be a risk factor for the outbreak of depression and IBD., (© 2022. The Author(s).)

Anti-dementia medications are widely prescribed to patients with Alzheimer's dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format-the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009-2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-D-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea., (© 2022. The Author(s).)

In recent years, there has been an emerging interest in the use of claims and electronic health record (EHR) data for evaluation of medical device safety and effectiveness. In Korea, national insurance electronic data interchange (EDI) code has been used as a medical device data source for common data model (CDM). This study performed a preliminary feasibility assessment of CDM-based vigilance. A cross-sectional study of target medical device data in EHR and CDM was conducted. A total of 155 medical devices were finally enrolled, with 58.7% of them having EDI codes. Femoral head prosthesis was selected as a focus group. It was registered in our institute with 11 EDI codes. However, only three EDI codes were converted to systematized nomenclature of medicine clinical terms concept. EDI code was matched in one-to-many (up to 104) with unique device identifier (UDI), including devices classified as different global medical device nomenclature. The use of UDI rather than EDI code as a medical device data source is recommended. We hope that this study will share the current state of medical device data recorded in the EHR and contribute to the introduction of CDM-based medical device vigilance by selecting appropriate medical device data sources., (© 2021. The Author(s).)

Avian influenza viruses (AIVs) are carried by wild migratory waterfowl across migratory flyways. To determine the strains of circulating AIVs that may pose a risk to poultry and humans, regular surveillance studies must be performed. Here, we report the surveillance of circulating AIVs in South Korea during the winter seasons of 2009-2013. A total of 126 AIVs were isolated from 7942 fecal samples from wild migratory birds, with a total isolation rate of 1.59%. H1‒H7 and H9‒H11 hemagglutinin (HA) subtypes, and N1‒N3, N5, and N7‒N9 neuraminidase (NA) subtypes were successfully isolated, with H6 and N2 as the most predominant HA and NA subtypes, respectively. Sequence identity search showed that the HA and NA genes of the isolates were highly similar to those of low-pathogenicity influenza strains from the East Asian-Australasian flyway. No match was found for the HA genes of high-pathogenicity influenza strains. Thus, the AIV strains circulating in wild migratory birds from 2009 to 2013 in South Korea likely had low pathogenicity. Continuous surveillance studies such as this one must be performed to identify potential precursors of influenza viruses that may threaten animal and human health., (© 2021. The Author(s).)