Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Background: and Purpose: To ensure data privacy, the development of defacing processes, which anonymize brain images by obscuring facial features, is crucial. However, the impact of these defacing methods on brain imaging analysis poses significant concern. This study aimed to evaluate the reliability of three different defacing methods in automated brain volumetry. Methods: Magnetic resonance imaging with three-dimensional T1 sequences was performed on ten patients diagnosed with subjective cognitive decline. Defacing was executed using mri_deface, BioImage Suite Web-based defacing, and Defacer. Brain volumes were measured employing the QBraVo program and FreeSurfer, assessing intraclass correlation coefficient (ICC) and the mean differences in brain volume measurements between the original and defaced images. Results: The mean age of the patients was 71.10±6.17 years, with 4 (40.0%) being male. The total intracranial volume, total brain volume, and ventricle volume exhibited high ICCs across the three defacing methods and 2 volumetry analyses. All regional brain volumes showed high ICCs with all three defacing methods. Despite variations among some brain regions, no significant mean differences in regional brain volume were observed between the original and defaced images across all regions. Conclusions The three defacing algorithms evaluated did not significantly affect the results of image analysis for the entire brain or specific cerebral regions. These findings suggest that these algorithms can serve as robust methods for defacing in neuroimaging analysis, thereby supporting data anonymization without compromising the integrity of brain volume measurements.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS. Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively. Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV. Conclusions The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Background and Objectives: We investigated whether extra-pulmonary vein (PV) ablation targeting a high maximal slope of the action potential duration restitution curve (Smax) improves the rhythm outcome of persistent atrial fibrillation (PeAF) ablation. Methods: In this open-label, multi-center, randomized, and controlled trial, 178 PeAF patients were randomized with 1:1 ratio to computational modeling-guided virtual Smax ablation (V-Smax) or empirical ablation (E-ABL) groups. Smax maps were generated by computational modeling based on atrial substrate maps acquired during clinical procedures in sinus rhythm. Smax maps were generated during the clinical PV isolation (PVI). The V-Smax group underwent an additional extra-PV ablation after PVI targeting the virtual high Smax sites. Results: After a mean follow-up period of 12.3±5.2 months, the clinical recurrence rates (25.6% vs. 23.9% in the V-Smax and the E-ABL group, p=0.880) or recurrence appearing as atrial tachycardia (11.1% vs. 5.7%, p=0.169) did not differ between the 2 groups. The postablation cardioversion rate was higher in the V-Smax group than E-ABL group (14.4% vs. 5.7%, p=0.027). Among antiarrhythmic drug-free patients (n=129), the AF freedom rate was 78.7% in the V-Smax group and 80.9% in the E-ABL group (p=0.776). The total procedure time was longer in the V-Smax group (p=0.008), but no significant difference was found in the major complication rates (p=0.497) between the groups. Conclusions Unlike a dominant frequency ablation, the computational modeling-guided V-Smax ablation did not improve the rhythm outcome of the PeAF ablation and had a longer procedure time.

Background/Aims: South Korean soldiers are exposed to similar environmental factors. In this study, we sought to evaluate the gut microbiome of healthy young male soldiers (HYMS) and to identify the primary factors influencing the microbiome composition. Methods: We prospectively collected stool from 100 HYMS and performed next-generation sequencing of the 16S rRNA genes of fecal bacteria. Clinical data, including data relating to the diet, smoking, drinking, and exercise, were collected. Results: The relative abundances of the bacterial phyla Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria were 72.3%, 14.5%, 8.9%, and 4.0%, respectively. Fifteen species, most of which belonged to Firmicutes (87%), were detected in all examined subjects. Using cluster analysis, we found that the subjects could be divided into the two enterotypes based on the gut microbiome bacterial composition. Compared with enterotype 2 subjects, subjects classified as enterotype 1 tended to be characterized by higher frequencies of potentially harmful lifestyle habits (current smoker: 55.6% vs 36.6%, p=0.222; heavy drinker: 16.7% vs 3.7%, p=0.120; insufficient physical activity: 27.8% vs 14.6%, p=0.318). We identified a significant difference in the microbiome compositions of current and noncurrent smokers (p=0.008); the former differed from the latter mainly in a relatively lower abundance of Bifidobacterium species and a higher abundance of Negativicutes. Conclusions A high abundance of Actinobacteria and low abundance of Bacteroidetes

Background: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

This study was performed to evaluate the effect of cyclic precalcification treatment on the improvement of bioactivity of Ti-6Al-4V mini-screws. The cutted plate-shaped specimens of 10 mm × 10 mm dimensions, and a mini-screw with a diameter of 1.6 mm × 6.0 mm in length were used. Anodic oxidation treatment was carried out in a glycerol electrolyte solution containing 20 wt% H2O and 1.5 wt% NH 4F. Voltage of 20 V with current density of 20 mA/cm2 was applied for 1 hour to form a nanotube TiO2 layer. Afterwards, to improve the bioactivity, specimens were immersed in 0.5 vol% silica aqueous solution at 37 ℃ for 5 minutes, and then cyclic precalcification treatment with 0.05 M NH 4H2PO4and 0.01 M Ca(OH)2 solution at 90 ℃ was repeated with 20 times. Based on surface treatment the experimental groups were divided into three groups, namely untreated group (UT), anodized and heat-treated group (AH), and anodized, silica-treated, cyclic precalcified and heat-treated group (ASPH). There were TiO2 nanotubes completely self-aligned and formed in a dense structure on the surface after anodic oxidation treatment. A fine granular cluster layer of hydroxyapatite and octacalcium phosphate were formed on the surface after the cyclic precalcification treatment. As a result of immersion test in the simulated body fluid (SBF), bioactivity was confirmed to be improved by the precipitation of protrusions appearing at the initial stage of formation of hydroxyapatite.

Purpose: To report a rare case of perinuclear anti-neutrophil cytoplasmic antibody-associated pachymeningitis presenting as bilateral orbital apex syndrome.Case summary: A 79-year-old female presented with a visual acuity decrease and ophthalmoplegia in both eyes from 1 week prior to her visit. Orbital magnetic resonance imaging showed diffuse hypertrophy and enhancement of the dura mater near the optic canal and superior orbital fissure causing orbital apex syndrome. The serum titer of perinuclear anti-neutrophil cytoplasmic antibody was elevated. Based on these findings, she was diagnosed with pachymeningitis related to perinuclear anti-neutrophil cytoplasmic antibody-associated vasculitis. The antibody titers decreased and ophthalmoplegia recovered after treatment with high dose intravenous steroid injection, cyclophosphamide, and long-term maintenance therapy with oral azathioprine and prednisolone. However, her visual acuity did not improve in either eye. Conclusions Perinuclear anti-neutrophil cytoplasmic antibody associated vasculitis can present as orbital apex syndrome and should be considered as a differential diagnosis.

Objective: The early prediction of multiple organ dysfunction syndrome (MODS) in trauma patients and provision ofprompt treatment may improve their outcomes. We investigated the efficacy of the mean platelet volume (MPV) for predictingMODS in cases of severe trauma. Methods: This retrospective, observational cohort study was performed with patients prospectively integrated in a criticalpathway of TRAUMA. We analyzed the severe trauma patients admitted to the emergency department (ED), based onthe Advanced Trauma Life Support guideline, between January 1, 2011 and May 31, 2017. The outcomes were developedfrom MODS at least 48 hours after ED admission. Results: A total of 348 patients were enrolled. An increase in the MPV at 12 hours (odds ratio [OR], 2.611; P<0.001) wasa strong independent predictor of MODS development. The increasing predictability of MODS was closely associatedwith an MPV at 12 hours>8.6 fL (OR, 4.831; P<0.001). The area under the receiver operating characteristic curve(AUROC) value of the MPV at 12 hours (0.751; 95% confidence interval [CI], 0.687-0.818; P<0.01) was not inferior thanthat of Acute Physiology and Chronic Health Evaluation II score, injury severity score, lactate, and total CO2 for predictingMODS. Conclusion MPV was an independent predictor of MODS development in severe trauma patients. Emergency physicianscan use the MPV as an ancillary biomarker for predicting MODS.