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Abstract The misuse and overtreatment of antibiotics in hospitalized patients with community-acquired pneumonia (CAP) can cause multi-drug resistance and worsen clinical outcomes. We aimed to analyze the trends and appropriateness of antibiotic changes in hospitalized patients with CAP and their impact on clinical outcomes. This retrospective study enrolled patients with CAP, aged > 18 years, admitted from January 2017 to December 2021 at Seoul National University Bundang Hospital, South Korea. We examined the pathogens identified, antibiotics prescribed, and the appropriateness of antibiotic changes as reviewed by infectious disease specialists. Antibiotic appropriateness was assessed based on adherence to the 2019 ATS/IDSA guidelines and the 2018 Korean national guidelines for CAP, targeting appropriate pathogens, proper route, dosage, and duration of therapy. Outcomes measured included time to clinical stability (TCS), length of hospital stay, duration of antibiotic treatment, and in-hospital mortality. The study included 436 patients with a mean age of 72.11 years, of whom 35.1% were male. The average duration of antibiotic treatment was 13.5 days. More than 55% of patients experienced at least one antibiotic change, and 21.7% had consecutive changes. Throughout their hospital stay, 273 patients (62.6%) received appropriate antibiotic treatment, while 163 patients (37.4%) received at least one inappropriate antibiotic prescription. Those who received at least one inappropriate prescription experienced longer antibiotic treatment durations and extended hospital stays, despite having similar TCS. In conclusion, inappropriate antibiotic prescribing in hospitalized patients with CAP is associated with prolonged antibiotic treatment and increased length of stay. Emphasizing the appropriate initial antibiotic selection may help mitigate these negative effects.

Abstract Objectives To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). Methods Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth’s penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. Results A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16–3.10), baseline diffusing capacity for carbon monoxide (DLCO)

Background/Aims This cross-sectional study aimed to investigate biologics treatment disparities in rheumatoid arthritis (RA) patients based on socioeconomic status (SES). Methods Data from the KOrean Observational Study Network for Arthritis (KORONA) database were analyzed to assess various factors associated with SES, health behaviors, and biologics use. Logistic regression and structured equation modeling (SEM) were utilized for data analysis. Results Among 5,077 RA patients included, 393 (7.7%) patients were identified as biologics users. Within the entire cohort, 31.8% of the participants were in the low-income and low-education groups, and 39.3% of the participants were in the high-income and high-education groups. Despite the patients with low income or low education experienced higher disease activity at diagnosis, had more comorbidities, exhibited higher medication compliance, underwent more check-ups, and had more hospital admissions than their counterparts, the odds of patients with low-income receiving biologics were 34% lower (adjusted odds ratio = 0.76, 95% confidence interval: 0.60–0.96, p = 0.021) after adjustment for demographics and comorbidities. SEM and pathway analyses confirmed the negative impact of low SES on biologics use. Conclusions The findings suggest that SES plays a significant role in biologics use among RA patients, indicating potential healthcare inefficiencies for low SES patients. Moreover, adverse healthcare habits negatively affect biologics use in RA patients. The study highlights the importance of considering socioeconomic factors while discussing biologics use and promoting equitable access to biologics for optimal RA management.

Background To evaluate the effectiveness of Korean Red Ginseng (KRG) in managing fatigue in Korean patients with rheumatic diseases Methods Patients were randomly assigned to KRG (2 g/day, n = 60) or placebo (n = 60) groups for 12 weeks of blind phase and then open-label KRG from weeks 12 to 24 (placebo-KRG, continuous-KRG). The primary outcome was the improvement rate in fatigue, defined by an increase in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores at 12 weeks. Secondary outcomes included changes in FACIT-Fatigue and fatigue visual analog scale (VAS) between 0 and 12 weeks and those changes in both indices at 24 weeks. Results The study enrolled 120 patients (Sjogren syndrome [n = 53], rheumatoid arthritis [n = 43], or both diseases [n = 24]). The mean age was 50.9 ± 11.6 years, with 97.5% being female. Baseline characteristics were similar between the two groups. The improvement rate in FACIT-Fatigue after 12 weeks was higher in the KRG group than in the placebo group, but the difference was statistically insignificant (38.3% vs. 26.7%, p = 0.242). Improvement in fatigue was observed in both groups by increases in FACIT-F (4.6 vs. 4.0) and reductions in fatigue VAS (-16.0 vs. -12.2) scores at 12 weeks. The most frequently reported adverse events during KRG use were pruritus and urticarial, with no significant difference between the two groups. Conclusions Both KRG and placebo groups showed significant reductions in fatigue. KRG treatment for 24 weeks did not reduce fatigue symptoms more than the placebo in patients with rheumatic diseases.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Abstract Background The hospitalist system has been introduced to improve the quality and safety of inpatient care. As its effectiveness has been confirmed in previous studies, the hospitalist system is spreading in various fields. However, few studies have investigated the feasibility and value of hospitalist-led care of patients with cancer in terms of quality and safety measures. This study aimed to evaluate the efficacy of the Hospitalist-Oncologist co-ManagemEnt (HOME) system. Methods Between January 1, 2019, and January 31, 2021, we analyzed 591 admissions before and 1068 admissions after the introduction of HOME system on January 1, 2020. We compared the length of stay and the types and frequencies of safety events between the conventional system and the HOME system, retrospectively. We also investigate rapid response system activation, cardiopulmonary resuscitation, unplanned intensive care unit transfer, all-cause in-hospital mortality, and 30-day re-admission or emergency department visits. Results The average length of stay (15.9 days vs. 12.9 days, P

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

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

BackgroundMeasurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)–based imaging was performed to determine sodium intake in these patients. ObjectiveThe applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. MethodsBased on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. We used a hybrid model that first leveraged the capabilities of the You Only Look Once, version 4 (YOLOv4) architecture for the detection of food and dish areas in images. Following this initial detection, 2 distinct approaches were adopted for further classification: a custom ResNet-101 model and a hyperspectral imaging-based technique. These methodologies focused on accurate classification and estimation of the food quantity and sodium amount, respectively. The 24-hour urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. ResultsResults were analyzed using complete data from 25 participants out of the total 54 enrolled individuals. The median sodium intake calculated by the AI algorithm (AI-Na) was determined to be 2022.7 mg per day/person (adjusted by administered fluids). A significant correlation was observed between AI-Na and 24-hour UNa, while there was a notable disparity between them. A regression analysis, considering patient characteristics (eg, gender, age, renal function, the use of diuretics, and administered fluids) yielded a formula accounting for the interaction between AI-Na and 24-hour UNa. Consequently, it was concluded that AI-Na holds clinical significance in estimating salt intake for hospitalized patients using images without the need for 24-hour UNa measurements. The degree of correlation between AI-Na and 24-hour UNa was found to vary depending on the use of diuretics. ConclusionsThis study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.

Abstract We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05–22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low.

Background/Aims Although a management fee for hospitalist service was established in Korea, the number of hospitalists required for the system to run remains outmatched. Methods In January 2020 and February 2022, before and after the establishment of the hospitalist fee system respectively, cross-sectional online surveys were conducted among internal medicine board-certified hospitalists. Results There were 59 and 64 respondents in the 2020 and 2022 surveys, respectively. The percentage of respondents who cited financial benefits as a motive for becoming a hospitalist was higher in the 2022 survey than in the 2020 survey (34.4% vs. 10.2%; p = 0.001). The annual salary of respondents was also higher in the 2022 survey than in the 2020 survey (mean, 182.9 vs. 163.0 million in South Korean Won; p = 0.006). A total of 81.3% of the respondents were willing to continue a hospitalist career in the 2022 survey. In multivariate regression analysis, the possibility of being appointed as a professor was found to be an independent predictive factor of continuing a hospitalist career (odds ratio, 4.00; 95% confidence interval, 1.09–14.75; p = 0.037). Conclusions Since the establishment of the hospitalist fee system, monetary compensation has improved for hospitalists. The possibility of being appointed as a professor could predict long-term work as hospitalists.

Abstract Background To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD. Methods Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients. Results Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P

IntroductionAlicyclobacillus has been isolated from extreme environments such as hot springs, volcanoes, as well as pasteurized acidic beverages, because it can tolerate extreme temperatures and acidity. In our previous study, Alicyclobacillus was isolated during the enrichment of methane oxidizing bacteria from Yellowstone Hot Spring samples.MethodsPhysiological characterization and genomic exploration of two new Alicyclobacillus isolates, AL01A and AL05G, are the main focus of this study to identify their potential relationships with a thermoacidophilic methanotroph (Methylacidiphilum) isolated from the same hot spring sediments.Results and discussionIn the present study, both Alicyclobacillus isolates showed optimal growth at pH 3.5 and 55°C, and contain ω-alicyclic fatty acids as a major lipid (ca. 60%) in the bacterial membrane. Genomic analysis of these strains revealed specific genes and pathways that the methanotroph genome does not have in the intermediary carbon metabolism pathway such as serC (phosphoserine aminotransferase), comA (phosphosulfolactate synthase), and DAK (glycerone kinase). Both Alicyclobacillus strains were also found to contain transporter systems for extracellular sulfate (ABC transporter), suggesting that they could play an important role in sulfur metabolism in this extreme environment. Genomic analysis of vitamin metabolism revealed Alicyclobacillus and Methylacidiphilum are able to complement each other’s nutritional deficiencies, resulting in a mutually beneficial relationship, especially in vitamin B1(thiamin), B3 (niacin), and B7 (biotin) metabolism. These findings provide insights into the role of Alicyclobacillus isolates in geothermal environments and their unique metabolic adaptations to these environments.

Understanding the effects of dosing non-toxigenic Clostridia to cows is rare and has received little attention so far. In the present study, a total of eight lactating dairy cows were divided in two groups: control (n = 4) or Clostridia challenged (oral supplementation of five diverse strains of Paraclostridium bifermentans, n = 4). Bacterial communities were analyzed by qPCR and next-generation sequencing (NGS) in the buccal mucosa as well as digesta and mucosal samples of the gastrointestinal (GI) tract from rumen to rectum (10 compartments), as well as fecal samples. Transcriptomic analysis of barrier and immune-related gene expression was performed on rumen, jejunum, and liver samples. We observed increased microbial populations with the Clostridial challenge in the buccal tissues and the proximal GI tract (forestomach), correlating with Clostridial loads in the feed. Otherwise, there were no significant differences in microbial populations (p > 0.05) throughout the distal part of the GI tract. The NGS approach, however, revealed that the Clostridial challenge changed the relative abundance of gut and fecal microbiota. In particular, in the challenge group, no Bifidobacterium was observed in the mucosa-associated microbiota and abundance of Pseudomonadota increased in the feces. These results indicated potential adverse effects of Clostridia to cow health. In general, immune responses to the Clostridial challenge were weak. However, transcriptional analysis revealed the down-regulation of junction adhesion molecule encoding gene (−1.44 of log2 fold-change), which might impact intestinal permeability.

Background No consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia. Methods Patients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108). Results The rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups. Conclusion Early co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

Background Although bicarbonate has traditionally been used to treat patients with rhabdomyolysis at high risk of acute kidney injury (AKI), it is unclear whether this is beneficial. This study compared bicarbonate therapy to non-bicarbonate therapy for the prevention of AKI and mortality in rhabdomyolysis patients. Methods In a propensity score-matched cohort study, patients with a creatine kinase (CK) level of >1,000 U/L during hospitalization were divided into bicarbonate and non-bicarbonate groups. Patients were subgrouped based on low-volume (

Abstract Extracellular PKM2 (exPKM2) levels have been reported to be increased in several cancers and inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to investigate the association of circulating exPKM2 levels with radiographic progression in RA patients and the effect of exPKM2 on osteoclastogenesis. Plasma and synovial fluid exPKM2 levels were significantly elevated in RA patients. Plasma exPKM2 levels were correlated with RA disease activity and were an independent predictor for radiographic progression in RA patients with a disease duration of ≤ 12 months. CD14+ monocytes but not RA fibroblast-like synoviocytes secreted PKM2 upon stimulation with inflammatory mediators. Recombinant PKM2 (rPKM2) increased the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and resorption pit in osteoclast precursors, dose-dependently, even in the absence of receptor activator of nuclear factor-kappa B ligand (RANKL). rPKM2 treatment upregulated the expression of dendrocyte-expressed seven transmembrane protein (DC-STAMP) and MMP-9 via the ERK pathway. Although rPKM2 did not directly bind to RAW264.7 cells, extracellular application of pyruvate, the end-product of PKM2, showed effects similar to those seen in rPKM2-induced osteoclastogenesis. These results suggest that exPKM2 is a potential regulator of RA-related joint damage and a novel biomarker for subsequent radiographic progression in patients with early-stage RA.

Abstract Accumulation of lipids and their metabolites induces lipotoxicity in diabetic cardiomyopathy. Lowering ceramide concentration could reduce the impact of metabolic damage to target organs. Adiponectin improves lipotoxicity through its receptors (AdiopRs), which have sequence homology with ceramidase enzymes. Therefore, cardioprotective role of AdipoR agonism by AdipoRon was investigated. Sixteen-week-old male db/m and db/db mice were fed a diet containing AdipoRon for four weeks. Phenotypic and metabolic profiles with associated cellular signaling pathways involved in lipid metabolism were investigated in the mice heart and human cardiomyocytes to establish treatment effect of AdipoRon. AdipoRon ameliorated insulin resistance, fibrosis, M1-dominant inflammation, and apoptosis in association with reduced accumulations of free fatty acid, triglycerides, and TLR4-related ceramide in the heart. This resulted in overall reduction in the level of oxidative stress which ameliorated cardiac hypertrophy and its function. AdipoRon increased the expression of AdipoR1 and AdipoR2 via pAMPK/FoxO1-induced Akt phosphorylation resulting from a decrease in PP2A level. It also increased acid ceramidase activity which reduced ceramide and increased sphingosine-1 phosphate levels in the heart of db/db mice and cultured human cardiomyocytes. Consistent upregulation of AdipoRs and their downstream regulatory pathways involving pAMPK/PPARα/PGC-1α levels led to lipid metabolism enhancement, thereby improving lipotoxicity-induced peroxisome biogenesis and oxidative stress. AdipoRon might control oxidative stress, inflammation, and apoptosis in the heart through increased AdipoR expression, acid ceramidase activity, and activation of AMPK-PPARα/PGC-1α and related downstream pathways, collectively improving cardiac lipid metabolism, hypertrophy, and functional parameters.

ObjectiveDeciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice.MethodsWe selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis.Results145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01-1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95-1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01-0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01-0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51-2.38) and previous tacrolimus use (OR 2.05, CI 1.20-3.51) were factors suggesting selection of JAKis than TNF inhibitors.ConclusionAge, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea.

Abstract Conventional deep learning (DL) algorithm requires full supervision of annotating the region of interest (ROI) that is laborious and often biased. We aimed to develop a weakly-supervised DL algorithm that diagnosis breast cancer at ultrasound without image annotation. Weakly-supervised DL algorithms were implemented with three networks (VGG16, ResNet34, and GoogLeNet) and trained using 1000 unannotated US images (500 benign and 500 malignant masses). Two sets of 200 images (100 benign and 100 malignant masses) were used for internal and external validation sets. For comparison with fully-supervised algorithms, ROI annotation was performed manually and automatically. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map, we determined how accurately the weakly-supervised DL algorithms localized the breast masses. For internal validation sets, the weakly-supervised DL algorithms achieved excellent diagnostic performances, with AUC values of 0.92–0.96, which were not statistically different (all Ps > 0.05) from those of fully-supervised DL algorithms with either manual or automated ROI annotation (AUC, 0.92–0.96). For external validation sets, the weakly-supervised DL algorithms achieved AUC values of 0.86–0.90, which were not statistically different (Ps > 0.05) or higher (P = 0.04, VGG16 with automated ROI annotation) from those of fully-supervised DL algorithms (AUC, 0.84–0.92). In internal and external validation sets, weakly-supervised algorithms could localize 100% of malignant masses, except for ResNet34 (98%). The weakly-supervised DL algorithms developed in the present study were feasible for US diagnosis of breast cancer with well-performing localization and differential diagnosis.

Bacterial co-culture studies using synthetic gut microbiomes have reported novel research designs to understand the underlying role of bacterial interaction in the metabolism of dietary resources and community assembly of complex microflora. Since lab-on-a-chip mimicking the gut (hereafter “gut-on-a-chip”) is one of the most advanced platforms for the simulative research regarding the correlation between host health and microbiota, the co-culture of the synthetic bacterial community in gut-on-a-chip is expected to reveal the diet–microbiota relationship. This critical review analyzed recent research on bacterial co-culture with perspectives on the ecological niche of commensals, probiotics, and pathogens to categorize the experimental approaches for diet-mediated management of gut health as the compositional and/or metabolic modulation of the microbiota and the control of pathogens. Meanwhile, the aim of previous research on bacterial culture in gut-on-a-chip has been mainly limited to the maintenance of the viability of host cells. Thus, the integration of study designs established for the co-culture of synthetic gut consortia with various nutritional resources into gut-on-a-chip is expected to reveal bacterial interspecies interactions related to specific dietary patterns. This critical review suggests novel research topics for co-culturing bacterial communities in gut-on-a-chip to realize an ideal experimental platform mimicking a complex intestinal environment.

Peach (Prunus persica) is one of the representative climacteric fruits susceptible to environmental stresses, including microbial contamination. This article analyzed major findings from the literature on pre- and post-harvest technologies for maintaining the quality of peach fruit to figure out the strengths and limitations of each treatment strategy. The key implication from studies of pre-harvest agents directly applied to the fruit surface or supplemented as fertilizer was the application of a mixture regarding substances with diverse working mechanisms to prevent excessive use of the agent. The common objectives of previous research on pre-harvest treatments were not only the improvement in the quality of harvested fruit but also the storability during long-term refrigeration due to the short lifespan of peaches. In the case of post-harvest treatments, the efficacy was considerably affected by various determinant factors (e.g., a cultivar of fruit, the sort of technologies, and storage environments), and thus operating conditions optimized for peach fruit were described in this article. Whereas, although the combined treatment of technologies categorized into principles (physical, chemical, and biological approaches) has been adopted to achieve the synergistic effect, undesirable antagonistic effects (i.e., the inhibition of efficacies expectable from singular treatments) were also reported to highlight the importance for exploring adequate treatment conditions.

Verrucomicrobiotal methanotrophs are thermoacidophilic methane oxidizers that have been isolated from volcanic and geothermal regions of the world. We used a metagenomic approach that entailed obtaining the whole genome sequence of a verrucomicrobiotal methanotroph from a microbial consortium enriched from samples obtained from Nymph Lake (89.9 °C, pH 2.73) in Yellowstone National Park in the USA. To identify and reconstruct the verrucomicrobiotal genome from Illumina NovaSeq 6000 sequencing data, we constructed a bioinformatic pipeline with various combinations of de novo assembly, alignment, and binning algorithms. Based on the marker gene (pmoA), we identified and assembled the Candidatus Methylacidiphilum sp. YNP IV genome (2.47 Mbp, 2392 ORF, and 41.26% GC content). In a comparison of average nucleotide identity between Ca. Methylacidiphilum sp. YNP IV and Ca. Methylacidiphilum fumariolicum SolV, its closest 16S rRNA gene sequence relative, is lower than 95%, suggesting that Ca. Methylacidiphilum sp. YNP IV can be regarded as a different species. The Ca. Methylacidiphilum sp. YNP IV genome assembly showed most of the key genes for methane metabolism, the CBB pathway for CO2 fixation, nitrogen fixation and assimilation, hydrogenases, and rare earth elements transporter, as well as defense mechanisms. The assembly and reconstruction of a thermoacidophilic methanotroph belonging to the Verrucomicrobiota phylum from a geothermal environment adds further evidence and knowledge concerning the diversity of biological methane oxidation and on the adaptation of this geochemically relevant reaction in extreme environments.

As a foodborne and environmental pathogen, Shiga toxin-producing Escherichia coli O157:H7 could pose a health threat to immunocompromised astronauts during a space mission. In this study, novel approaches, including real-time testing and direct evaluation of resistance mechanisms, were used to evaluate antibiotic efficacy against E. coli O157:H7 under low-shear modeled microgravity (LSMMG) produced using a rotary cell culture system. When compared with normal gravity (NG), bacterial growth was increased under LSMMG in the presence of sub-inhibitory nalidixic acid concentrations and there was an accompanying up-regulation of stress-related genes. LSMMG also induced transcriptional changes of the virulence genes stx1 and stx2, highlighting the potential risk of inappropriate antibiotic use during a spaceflight. The degree of bacterial cell damage induced by the antibiotics was reduced under LSMMG, suggesting low induction of reactive oxygen species. Efflux pumps were also shown to play an important role in these responses. Increased cell filamentation was observed under LSMMG upon ampicillin treatment, possibly reflecting a protective mechanism against exposure to antibiotics. These observations indicate that, in the presence of antibiotics, the survival of E. coli O157:H7 is greater under LSMMG than under NG, indicating that antibiotic therapies may need to be adjusted during space missions.

Abstract Septic arthritis is the infection of a joint by an infectious agent, leading to arthritis. It is therefore important to identify and treat the correct bacteria in septic arthritis. However, accurate identification of bacteria by conventional methods is difficult because of the distinct biochemical characteristics of individual bacteria. This case report aims at assessing septic arthritis caused by Streptococcus dysgalactiaesubsp. equisimilis(SDSE) using nucleotide sequences and discusses the associated treatment. Here, Streptococcus agalactiaewas determined to be the causative bacteria for septic arthritis in a 77 year-old woman using the conventional method of hemolysis pattern interpretation and morphology. However, nucleotide sequence analysis of 16S ribosomal RNA revealed that SDSE was the causative strain. 16S rRNA gene sequencing can correctly identify bacteria strains that are difficult to be identified by traditional method, and this correct identification can provide patients with the opportunity for adequate treatment using the proper antibiotics.

Food-handling behaviors and risk perceptions among primary food handlers were investigated by consumer surveys from different subjects in 2010 (N = 609; 1st survey will be called here “Year 2010”) and 2019 (N = 605; 2nd survey will be called here “Year 2019”). Year 2010 was characterized by consumers’ risk perception-behavior gap (i.e., consumers knew safe methods for food-handling, but responses regarding the behaviors did not support their confidence in food safety): they (1) did not wash/trim foods before storage, (2) thawed frozen foods at room temperature, and (3) exposed leftovers to danger zone temperatures. These trends were not improved and the gaps in Year 2010 remained in Year 2019. Year 2010 was also characterized by other common high-risk behaviors improved during 8 years for the following aspects: (1) 70.0% of consumers divided a large portion of food into smaller pieces for storage, but few consumers (12.5%) labeled divided foods with relevant information, and (2) they excessively reused kitchen utensils. Whereas in Year 2019, more consumers (25.7%) labeled food and usage periods for kitchen utensils were shortened. Consumers usually conformed to food safety rules in both Year 2010 and 2019: (1) separate storage of foods, (2) storage of foods in the proper places/periods, (3) washing fruits/vegetables before eating, (4) washing hands after handling potentially hazardous foods, and (5) cooking foods and reheating leftovers to eat. Our findings provided resources for understanding consumers’ high-risk behaviors/perceptions at home, highlighting the importance of behavioral control.

Although antibacterial spectrum of essential oils (EOs) has been analyzed along with consumers’ needs on natural biocides, singular treatments generally require high concentration of EOs and long-term exposures to eliminate target bacteria. To overcome these limitations, antibacterial complex has been developed and this review analyzed previous reports regarding the combined antibacterial effects of EOs. Since unexpectable combined effects (synergism or antagonism) can be derived from the treatment of antibacterial complex, synergistic and antagonistic combinations have been identified to improve the treatment efficiency and to avoid the overestimation of bactericidal efficacy, respectively. Although antibacterial mechanism of EOs is not yet clearly revealed, mode of action regarding synergistic effects especially for the elimination of pathogens by using low quantity of EOs with short-term exposure was reported. Whereas comprehensive analysis on previous literatures for EO-based disinfectant products implies that the composition of constituents in antibacterial complexes is variable and thus analyzing the impact of constituting substances (e.g., surfactant, emulsifier) on antibacterial effects is further needed. This review provides practical information regarding advances in the EO-based combined treatment technologies and highlights the importance of following researches on the interaction of constituents in antibacterial complex to clarify the mechanisms of antibacterial synergism and/or antagonism.

Curcumin and catechin are nutraceuticals and natural health products that have shown several health benefits. However, due to their unstable nature, these compounds cannot be included in food products as such. The prime objective of the current study was to examine the formulation factors that determine the stability of these nutraceuticals and their carrier systems as well as to fabricate water-in-oil-in-water emulsions (W/O/W) to prevent the degradation of both curcumin and catechin in beverage systems. The fabricated emulsion had a volume-weighted mean diameter (d43) of ~4 µm, with an encapsulation efficiency of >90%. Encapsulating the catechin within the inner aqueous phase of the double emulsion increased the stability of catechin by >20% at 23 ± 2 °C and by >40% at 4 °C after 15 days of incubation, as compared to free catechin. In the case of curcumin, >80% was detected after incubation in the beverage system in the form of emulsions, whereas it was reduced to ~40% in the case of free curcumin.

Herein we report a rare case of an intracortical chondroma with the histologic appearance of an enchondroma but located within the cortical bone.

Styrene can be formed by the microbial metabolism of bacteria and fungi. In our previous study, styrene was determined as a spoilage marker of Fuji apples decayed by Penicillium expansum, which is responsible for postharvest diseases. In the present study, P. expansum was cultivated in potato dextrose broth added with phenylalanine—which is a precursor of styrene—using different initial pH values and cultivation times. Volatile compounds were extracted and analyzed using gas chromatography-mass spectrometry (GC-MS) combined with stir-bar sorptive extraction. The 76 detected volatile compounds included 3-methylbutan-1-ol, 3-methyl butanal, oct-1-en-3-ol, geosmin, nonanal, hexanal, and γ-decalactone. In particular, the formation of 10 volatile compounds derived from phenylalanine (including styrene and 2-phenylethanol) showed different patterns according to pH and the cultivation time. Partial least square-discriminant analysis (PLS-DA) plots indicated that the volatile compounds were affected more by pH than by the cultivation time. These results indicated that an acidic pH enhances the formation of styrene and that pH could be a critical factor in the production of styrene by P. expansum. This is the first study to analyze volatile compounds produced by P. expansum according to pH and cultivation time and to determine their effects on the formation of styrene.

Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors.Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually.Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8-66.7] months).Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in AS patients could be safe under effective coverage of tuberculosis.

The aim of this study was to investigate augmented pain processing in the cortical somatosensory system in patients with fibromyalgia (FM). Cortical evoked responses were recorded in FM (n = 19) and healthy subjects (n = 21) using magnetoencephalography after noxious intra-epidermal electrical stimulation (IES) of the hand dorsum (pain rating 6 on a numeric rating scale, perceptually-equivalent). In addition, healthy subjects were stimulated using the amplitude corresponding to the average stimulus intensity rated 6 in patients with FM (intensity-equivalent). Quantitative sensory testing was performed on the hand dorsum or thenar muscle (neutral site) and over the trapezius muscle (tender point), using IES (thresholds, ratings, temporal summation of pain, stimulus-response curve) and mechanical stimuli (threshold, ratings). Increased amplitude of cortical responses was found in patients with FM as compared to healthy subjects. These included the contralateral primary (S1) and bilateral secondary somatosensory cortices (S2) in response to intensity-equivalent stimuli and the contralateral S1 and S2 in response to perceptually-equivalent stimuli. The amplitude of the contralateral S2 response in patients with FM was positively correlated with average pain intensity over the last week. Quantitative sensory testing results showed that patients with FM were more sensitive to painful IES as well as to mechanical stimulation, regardless of whether the stimulation site was the hand or the trapezius muscle. Interestingly, the slope of the stimulus-response relationship as well as temporal summation of pain in response to IES was not different between groups. Together, these results suggest that the observed pain augmentation in response to IES in patients with FM could be due to sensitization or disinhibition of the cortical somatosensory system. Since the S2 has been shown to play a role in higher-order functions, further studies are needed to clarify the role of augmented S2 response in clinical characteristics of FM.

The manipulation of vascular endothelial growth factor (VEGF)-receptors (VEGFRs) in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity. Such notion instigated us to investigate on whether selective VEGFR1 inhibition with GNQWFI hexamer aggravates the progression of diabetic nephropathy in db/db mice. While diabetes suppressed VEGFR1, it did increase VEGFR2 expressions in the glomerulus. Db/db mice with VEGFR1 inhibition showed more prominent features with respect to, albuminuria, mesangial matrix expansion, inflammatory cell infiltration and greater numbers of apoptotic cells in the glomerulus, and oxidative stress than that of control db/db mice. All these changes were related to the suppression of diabetes-induced increases in PI3K activity and Akt phosphorylation as well as the aggravation of endothelial dysfunction associated with the inactivation of FoxO3a and eNOS-NOx. In cultured human glomerular endothelial cells (HGECs), high-glucose media with VEGFR1 inhibition induced more apoptotic cells and oxidative stress than did high-glucose media alone, which were associated with the suppression of PI3K-Akt phosphorylation, independently of the activation of AMP-activated protein kinase, and inactivation of FoxO3a and eNOS-NOx pathway. In addition, transfection with VEGFR1 siRNA in HGECs also suppressed PI3K-Akt-eNOS signaling. In conclusion, the specific blockade of VEGFR1 with GNQWFI caused severe renal injury related to profound suppression of the PI3K-Akt, FoxO3a and eNOS-NOx pathway, giving rise to the oxidative stress-induced apoptosis of glomerular cells in type 2 diabetic nephropathy.

PURPOSE: Osteoporosis poses a great threat to the aging society. Hypochlorhydric or achlorhydric conditions are risk factors for osteoporosis. Atrophic gastritis also decreases gastric acid production; however, the role of atrophic gastritis as a related factor for osteoporosis is unclear. We investigated the relationship between atrophic gastritis and osteoporosis in postmenopausal women over 60 years of age. SUBJECTS AND METHODS: A total of 401 postmenopausal women were included in this cross-sectional study, which was conducted during their medical check-ups. Bone mineral densitometry was measured using a dual energy X-ray absorptiometry. Atrophic gastritis was defined endoscopically if gastric mucosa in the antrum and the body were found to be atrophied and thinned and submucosal vessels could be well visualized. RESULTS: The proportion of people with atrophic gastritis was higher in the osteoporotic group than in the group without osteoporosis. A linear relationship was observed in the proportion of atrophic gastritis according to the categories of normal, osteopenia, and osteoporosis at the lumbar spine (p for trend = 0.039) and femur (p for trend = 0.001). A multiple logistic regression analysis revealed that the presence of atrophic gastritis was associated with an increased odds of osteoporosis after adjusting for age, body mass index, triglyceride, high-density lipoprotein cholesterol, alcohol consumption, and smoking status (odds ratio 1.89, 95% confidence interval 1.15-3.11). CONCLUSIONS: Atrophic gastritis is associated with an increased likelihood of osteoporosis in Korean elderly women.

Peroxisome proliferator-activated receptor (PPAR)-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks. In db/db mice, fenofibrate ameliorated albuminuria, mesangial area expansion and inflammatory cell infiltration. Fenofibrate inhibited accumulation of intra-renal free fatty acids and triglycerides related to increases in PPARα expression, phosphorylation of AMP-activated protein kinase (AMPK), and activation of Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)-estrogen-related receptor (ERR)-1α-phosphorylated acetyl-CoA carboxylase (pACC), and suppression of sterol regulatory element-binding protein (SREBP)-1 and carbohydrate regulatory element-binding protein (ChREBP)-1, key downstream effectors of lipid metabolism. Fenofibrate decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and FoxO3a phosphorylation in kidneys, increasing the B cell leukaemia/lymphoma 2 (BCL-2)/BCL-2-associated X protein (BAX) ratio and superoxide dismutase (SOD) 1 levels. Consequently, fenofibrate recovered from renal apoptosis and oxidative stress, as reflected by 24 hr urinary 8-isoprostane. In cultured mesangial cells, fenofibrate prevented high glucose-induced apoptosis and oxidative stress through phosphorylation of AMPK, activation of PGC-1α-ERR-1α, and suppression of SREBP-1 and ChREBP-1. Our results suggest that fenofibrate improves lipotoxicity via activation of AMPK-PGC-1α-ERR-1α-FoxO3a signaling, showing its potential as a therapeutic modality for diabetic nephropathy.

Neural vascular insufficiency plays an important role in diabetic peripheral neuropathy (DPN). Peroxisome proliferative-activated receptor (PPAR)α has an endothelial protective effect related to activation of PPARγ coactivator (PGC)-1α and vascular endothelial growth factor (VEGF), but its role in DPN is unknown. We investigated whether fenofibrate would improve DPN associated with endothelial survival through AMPK-PGC-1α-eNOS pathway. Fenofibrate was given to db/db mice in combination with anti-flt-1 hexamer and anti-flk-1 heptamer (VEGFR inhibition) for 12 weeks. The db/db mice displayed sensory-motor impairment, nerve fibrosis and inflammation, increased apoptotic cells, disorganized myelin with axonal shrinkage and degeneration, fewer unmyelinated fibers, and endoneural vascular rarefaction in the sciatic nerve compared to db/m mice. These findings were exacerbated with VEGFR inhibition in db/db mice. Increased apoptotic cell death and endothelial dysfunction via inactivation of the PPARα-AMPK-PGC-1α pathway and their downstream PI3K-Akt-eNOS-NO pathway were noted in db/db mice, human umbilical vein endothelial cells (HUVECs) and human Schwann cells (HSCs) in high-glucose media. The effects were more prominent in response to VEGFR inhibition. In contrast, fenofibrate treatment ameliorated neural and endothelial damage by activating the PPARα-AMPK-PGC-1α-eNOS pathway in db/db mice, HUVECs and HSCs. Fenofibrate could be a promising therapy to prevent DPN by protecting endothelial cells through VEGF-independent activation of the PPARα-AMPK-PGC-1α-eNOS-NO pathway.

Purpose To evaluate an educational effect of the mammography boot camp (MBC) for radiology residents and analyze affecting factors. Materials and Methods Between December 2014 and February 2015, radiology residents in 16 institutions performed the MBC program. We compared the educational effect (score difference between pre- and post-camp test) using 25 case series and analyzed the affecting factors including institution, grades of residents, training periods, presence of sub-specialized breast staff, breast density, and types of cases. Results The mean scores of 92 residents were 52.80 ± 18.10 and 72.50 ± 12.91 in the pre- and post-camp test, respectively (p = 0.001). There was no significant difference of educational effect according to institution (19.70 ± 16.31), grade, or training period. Although the educational effect of non-trainees was superior to that of trainees (28.10 ± 17.55 vs. 15.90 ± 14.22; p = 0.001), the scores of trainees were higher than those of non-trainees. The diagnostic accuracy showed more improvement in a fatty breast and cases with microcalcifications than compared with others. Conclusion The MBC showed an effective educational result for radiology residents when interpretating a mammography. It was helpful even for non-trainees. The institution, grades training period, and presence of sub-specialized breast staff did not affect the educational effect.