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Abstract Chitinase-3-like 1 protein (CHI3L1) is a secreted glycoprotein, strongly correlated with fibrosis severity in chronic liver diseases including non-alcoholic steatohepatitis (NASH). However, the mechanisms by which CHI3L1 contributes to fibrogenesis remain undefined. Here, we showed that infiltrating monocyte-derived liver macrophages represent the main source of CHI3L1 in murine NASH. We developed a floxed CHI3L1 knock-out (KO) mouse to further study the cell-specific role of CHI3L1 ablation. Wildtype (WT) and myeloid cell-specific CHI3L1 KO mice (CreLyz) were challenged with a highly inflammatory and fibrotic dietary model of NASH by administering choline-deficient high-fat diet for 10 weeks. Macrophage accumulation and inflammatory cell recruitment were significantly ameliorated in the CreLyz group compared to WT (F4/80 IHC p p p p TGFB1 p CTGF p ACTA2 p COL1A1 p Key messages We showed that CHI3L1 expression is increased in murine CDAA-HFAT diet NASH model, and that infiltrating macrophages are a key source of CHI3L1 production. Myeloid cell-specific CreLyz CHI3L1 knock-out in mice fed with CDAA-HFAT diet improved the NASH phenotype, with significantly reduced accumulation of pro-inflammatory macrophages and neutrophils compared with WT group. DEG and qPCR analysis of genes in CreLyz CHI3L1 knock-out mouse liver showed the mechanistic role of CHI3L1 in cellular chemotaxis. HSC is directly activated by CHI3L1 via receptor IL13Rα2, leading to upregulation of collagen deposition and pro-fibrotic gene, TIMP-1 and TIMP-2 release in whole liver. Direct stimulation of macrophages with CHI3L1 leads to upregulated expression of HSC-activation factors, suggesting its role in modulating macrophage-HSC crosstalk.

Late spontaneous hematoma (> 6 months postoperatively) after breast reconstruction using implant is rare complication. We experienced a case of capsular contracture with a unique clinical form of intracapsular hematoma 13 years after implantation of smooth saline filled implants. This report presented the mechanism of complication examined through chart-review, histological morphological analysis, and literature review to help evaluation and treatment of various symptoms around the breast implant capsule. A 51-year-old woman underwent a unilateral breast reconstruction using tissue expander insertion in 2005, and underwent saline implant insertion after a year. A patient has been assessed through computed tomography (CT) and ultrasonography annually for cancer screening in General Surgery department, and in 14 years after implantation, she was referred to the Plastic Surgery department as a finding intracapsular multi-layering lesion around implant. She underwent implant removal and capsulectomy. The excised capsule was sent for histological evaluation. There were no trauma event, calcifications, or implant rupture. Symptoms of swelling and stiffness gradually developed. The etiology of late hematoma following implantation has been poorly characterized. There are opinions that delayed hematoma can be induced by capsule microfracture, which may be due to the rigidity of the contracted capsule, and that it may be caused by friction between the capsule and the implant when there is pathological contracture. It is thought to be an old hematoma capsule contracture that can be mistaken for tumor lesions, and it was concluded that our case corresponds.

Background/Aim: Alteration of F-box and leucine-rich repeat protein 5 (FBXL5), an iron-sensing ubiquitin ligase, might be related with carcinogenesis of hepatocellular carcinoma (HCC), by disturbing cellular iron homeostasis. However, the clinical implications of FBXL5 expression using patient samples need to be elucidated. Patients and Methods: We collected HCC tissue samples from two institutes: Samsung Medical Center (n=259) and Hallym University Sacred Heart Hospital (n=115) and evaluated FBXL5 expression using immunohistochemistry. Using cut-off values determined by X-tile software, association between FBXL5 expression and several clinicopathological parameters was investigated. For external validation, the Cancer Genome Atlas (TCGA) cohort was used. Results: The best cutoff value for FBXL5 IHC expression associated with recurrence-free survival (RFS) was 5%. Low FBXL5 expression was found in 18.7% of the total 374 HCCs and was associated with non-viral etiology (p=0.019). Low FBXL5 expression was related with inferior disease-specific survival (DSS, p=0.002) and RFS (p=0.001) and also was an independent prognostic factor for DSS and RFS. In addition, cases with low FBLX5 mRNA levels showed inferior DSS and RFS (p

China has expanded its economic footprint in Southeast Asian countries by providing a growing amount of development finance to the region. We examine the allocation of Chinese foreign aid toward Southeast Asian countries exploiting the exogenous variation of rotating leadership within Association of Southeast Asian Nation (ASEAN). As the ASEAN Chair possesses the agenda-setting power and represents the organization, China strategically allocates more development aid to the ASEAN Chair to augment its influence in the region. Our analysis of Chinese aid allocation between 2000 and 2017 finds that taking the leadership position at ASEAN appears to be significantly associated with an increase of official development aid flows from China, while other commercial flows are only weakly associated with the leadership position. Our findings underscore the importance of considering the regional context in examining foreign aid allocation and show that a donor can target a regional organization to exert its political influence in the region.

The treatment of chronic Achilles tendonitis (AT) often requires prolonged therapy and invasive therapeutic methods such as surgery or therapeutic endoscopy. To prevent the progression of chronic AT, excessive inflammation must be alleviated at an early stage. Corticosteroids or nonsteroidal anti-inflammatory drugs are generally prescribed to control inflammation; however, the high doses and long therapeutic periods required may lead to serious side effects. Herein, a local injectable poly(organophosphazene) (PPZ) - celecoxib (CXB) nanoparticle (PCNP) hydrogel system with long-term anti-inflammatory effects was developed for the treatment of tendonitis. The amphiphilic structure and thermosensitive mechanical properties of PPZ means that the hydrophobic CXB can be easily incorporated into the hydrophobic core to form PCNP at 4 °C. Following the injection of PCNP into the AT, PCNP hydrogel formed at body temperature and induced long-term local anti-inflammatory effects via sustained release of the PCNP. The therapeutic effects of the injectable PCNP system can alleviate excessive inflammation during the early stages of tissue damage and boost tissue regeneration. This study suggests that PCNP has significant potential as a long-term anti-inflammatory agent through sustained nonsteroidal anti-inflammatory drugs (NSAIDs) delivery and tissue regeneration boosting. STATEMENT OF SIGNIFICANCE: In the treatment of Achilles tendinitis, a long-term anti-inflammatory effect is needed to alleviate excessive inflammation and induce regeneration of the damaged Achilles tendon. Injectable poly(organophosphazene)(PPZ)-celecoxib(CXB) nanoparticles (PCNP) generated a long-term, localized-anti-inflammatory effect in the injected region, which successfully induced the expression of anti-inflammatory cytokines and suppressed pro-inflammatory cytokines, while the PCNPs degraded completely. Accordingly, regeneration of the damaged Achilles tendon was achieved through the long-term anti-inflammatory effect induced by a single PCNP injection. The PCNP system therefore has great potential in long-term NSAIDs delivery for various tissue engineering applications.

Purpose: To evaluate the changes in corneal astigmatism before and after epiblepharon correction surgery with a Scheimpflug camera.Methods: From April, 2019, to June, 2020, 48 eyes of 24 patients underwent epiblepharon correction surgery. The patients were divided into two subgroups by age and their best corrected visual acuity (BCVA) and corneal anterior and posterior astigmatism were compared before and after correction surgery.Results: There was no difference in BCVA after the correction surgery. To assess the changes in the keratometric value and astigmatism after epiblepharon surgery, a Scheimpflug camera was used. The anterior flat and mean keratometry changed from 42.10 ± 1.46 to 42.43 ± 1.10 D (p = 0.035) and from 42.97 ± 1.26 to 43.21 ± 1.15 D (p = 0.012), respectively, while the posterior corneal astigmatism changed from 0.44 ± 0.31 to 0.35 ± 0.17 D (p = 0.047). There were no significant changes in steep keratometry (p = 0.191) or anterior corneal astigmatism (p = 0.126).Conclusions: There were significant changes after epiblepharon correction surgery in anterior keratometry reading and posterior corneal astigmatism.

Purpose : This study aimed to provide basic data for developing strategies to improve the nursing performance of nurses working in the intensive care unit by identifying the degree of their communication ability, job satisfaction, organization commitment, and nursing performance, and the relation between each of these variables in the intensive care unit by examining the factors affecting nursing performance.Methods : The participants comprised of 150 nurses working in the intensive care unit in two advanced general hospitals. Data were collected using structured questionnaires and analyzed using a t-test, ANOVA, the Scheffé test, Pearson’s correlation coefficients, and multiple regression analysis using the SPSS/WIN 25.0 program.Results : Nursing performance of the participants was positively correlated with communication ability (r=.64, pppβ=.16, p=.032) and communication ability (β=.50, pp

A history of abdominal surgery is associated with difficulty in colonoscopy insertion. Few studies have reported effective colonoscopy insertion for patients who underwent abdominal surgery due to stomach cancer.We aimed to compare the impact of supine position (SP) and left lateral position (LLP) as the starting position of colonoscopy insertion in patients who underwent abdominal surgery due to stomach cancer.This was a prospective, randomized controlled trial. Patients undergoing colonoscopy for screening or post-polypectomy surveillance after gastrectomy due to stomach cancer were enrolled and randomized to the SP or LLP group as the starting position of colonoscopy insertion. All colonoscopic examinations were performed with a transparent cap. The primary outcome was to compare the cecal intubation time between the two groups.A total of 224 patients were enrolled. The mean cecal intubation time was not significantly different between the SP and LLP groups (364.5 s versus 306.9 s; p = 0.105). In patients with a lower body mass index ( 21 kg/mEither the SP or LLP could serve as a possible starting position of colonoscopy insertion for patients who underwent abdominal surgery due to stomach cancer.

The purpose of this study was to evaluate the impact of the different region-of-interest (ROI) methods of 2-D shear wave elastography (2-D SWE) on hepatic fibrosis diagnosis. In this retrospective study, 83 patients who underwent 2-D SWE with three ROI methods (a circle ROI, a box ROI and multiple ROIs in an elastogram) and transient elastography (TE) were included. Liver stiffness (LS) was measured five times with each ROI method. These LS values were compared, and their correlation with those obtained from TE was evaluated. The LS values obtained using the three different ROI methods differed statistically (p0.001). However, the LS values obtained using each ROI method of 2-D SWE were highly correlated with those obtained using TE (r0.7, p0.001). All three ROI methods of 2-D SWE had high areas under the receiver operating characteristic curve in diagnosing significant fibrosis and cirrhosis (0.841, 0.820 and 0.840, respectively; 0.962, 0.946 and 0.945, respectively). There were no significant differences in area under the receiver operating characteristic curve among the ROI methods of 2-D SWE. Regardless of the ROI method, 2-D SWE had high performance in diagnosing hepatic fibrosis.

This study aimed to evaluate the differences in hippocampal structural volumes and intra-hippocampal networks between patients with status epilepticus (SE) and healthy controls.We enrolled 45 patients with SE and 35 age- and sex-matched healthy controls. We excluded patients with active structural lesions, which could be a direct cause of SE, but included patients with co-existing lesions. Co-existing lesions were defined as any lesions possibly related to the occurrence of SE, including encephalomalacia, cavernous malformation, dural arteriovenous fistula, and normal pressure hydrocephalus, etc. We divided 45 patients into those with co-existing lesions (n = 21) and those without co-existing lesions (n = 24). We conducted a volumetric analysis using FreeSurfer (version 7), and the intra-hippocampal structural co-variance network was analyzed with a graph theoretical analysis based on the structural volumes of the hippocampal subfields.The structural volumes and intra-hippocampal structural co-variance networks were not different between patients with and without co-existing lesions. However, both structural volumes and intra-hippocampal structural co-variance networks were significantly different in patients with SE compared to healthy controls, and the ratio of the volume difference: [(volume of controls-volume of patients)/volume of controls] was highest in the left hippocampus (0.195), left amygdala (0.143), left thalamus (0.126), and right cortex (0.084). In addition, the global connectivity measurements including radius, diameter, eccentricity, and assortativity were significantly increased, and the small-worldness index was significantly decreased in patients with SE. Notably, structural volumes were negatively related to age but not to the duration of SE.Our study revealed significant alterations in structural volumes and intra-hippocampal structural co-variance networks in patients with SE compared to healthy controls, even though hippocampal atrophy was not evident on visual analysis; this is likely due to the direct effect of SE itself.

Background/Aims The appropriate number of band ligations during the first endoscopic session for acute variceal bleeding is debatable. We aimed to compare the technical aspects of endoscopic variceal ligation (EVL) in patients with variceal bleeding according to the number of bands placed per session. Methods We retrospectively reviewed multicenter data from patients who underwent EVL for acute variceal bleeding. Patients were classified into minimal EVL (targeting only the foci with active bleeding or stigmata of recent bleeding) and maximal EVL (targeting potential bleeding sources in addition to the aforementioned targets) groups. The primary endpoint was 5-day treatment failure. The secondary endpoints were 30-day rebleeding, 30-day mortality, and intraprocedural adverse events. Results Minimal EVL was associated with lower rates of hypoxia and shock during EVL than maximal EVL (hypoxia, 0.9% vs 2.9%; shock, 1.3% vs 3.4%). However, treatment failure was higher in the minimal EVL group than in the maximal EVL group (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.41). Age ≥60 years, Model for End-Stage Liver Disease score ≥15, Child-Turcotte-Pugh classification C, presence of hepatocellular carcinoma, and systolic blood pressure

Background Since 2017, automated assays have been used in most clinical laboratories for anti-Mullerian hormone (AMH) level measurement. We evaluated the analytical performance of the newly developed automated fluorescent immunoassay system (AFIAS) AMH assay (Boditech Med, Gangwon-do, Korea) in comparison with the Roche Elecsys and Beckman Coulter Access 2 AMH assays. Methods Analytical performance of the AFIAS AMH assay was assessed in terms of linearity, repeatability, and within-laboratory precision (CV%) using human recombinant AMH samples according to the Clinical and Laboratory Standards Institute (CLSI) guidelines EP05 and EP06. Using 293 serum samples collected from an infertility clinic, the AMH levels were compared across AFIAS, Elecsys, and Access 2 AMH assays according to the CLSI EP09 guidelines. Results The AFIAS AMH assay results were linear across the measurement range of 0.420-72.386 pmol/L AMH, with repeatability of 6.341%. CV% of the AFIAS AMH assay for three levels of control, 1.786, 7.143, and 56.857 pmol/L, were 5.801%, 5.714%, and 6.228%, respectively. The results of the three AMH assays showed strong correlation: AFIAS and Elecsys [slope, 1.055 (95% confidence interval (CI), 1.022-1.088) and Spearman's rho, 0.978 (95% CI, 0.973-0.983)], Elecsys and Access 2 [slope, 0.813 (95% CI, 0.791-0.834) and Spearman's rho, 0.986 (95% CI, 0.983-0.989)], and AFIAS and Access 2 [slope, 0.836 (95% CI, 0.821-0.853) and Spearman's rho, 0.984 (95% CI, 0.980-0.988)]. Conclusions The AFIAS AMH assay may be an alternative to the Roche Elecsys and Beckman Coulter Access 2 AMH assays.

Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC.Significance:OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.

Supplementary Table from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer

Supplementary Figure 2 from The Nuclear Receptor Coactivator Amplified in Breast Cancer-1 Is Required for Neu (ErbB2/HER2) Activation, Signaling, and Mammary Tumorigenesis in Mice

Supplementary Methods, Figure Legends 1-2 from The Nuclear Receptor Coactivator Amplified in Breast Cancer-1 Is Required for Neu (ErbB2/HER2) Activation, Signaling, and Mammary Tumorigenesis in Mice

Supplementary Figure 1 from The Nuclear Receptor Coactivator Amplified in Breast Cancer-1 Is Required for Neu (ErbB2/HER2) Activation, Signaling, and Mammary Tumorigenesis in Mice

PurposeThe aim of this study is to examine how brand trust moderates the effect of brand experience on brand loyalty mediated by brand love in the context of Korean smartphone users. The authors examine the relationships focused on Apple iPhone and Samsung Galaxy phone.Design/methodology/approachThe authors designed the conceptual model based on theoretical and empirical background. The authors collected data using a self-administered structured questionnaire through an online research company. The authors tested the hypotheses using a structural equation modeling in AMOS and PROCESS macro model number 8 based on 598 Korean smartphone users.FindingsThe authors found that brand experiences affect brand love, and brand love affects brand loyalty. The authors found that brand experiences affect brand loyalty directly, and brand love mediated the relationship between brand experiences and brand loyalty. The authors found that brand trust had a moderating effect between brand experiences and brand love but had no moderating effect between brand experiences and brand loyalty. Finally, the authors found that brand trust has a moderated mediation role between brand experiences, brand love and brand loyalty.Originality/valueThis is the first study to examine the moderated mediation role of brand trust in the relationship between brand experiences, brand love and brand loyalty focused on Apple iPhone and Samsung Galaxy phone users in the Korean context.

In response to the COVID-19 pandemic, governments around the world have imposed a wide variety of entry restrictions on international travel. Historical cases illustrate that public health concerns based on entrenched prejudices toward immigrant communities have led to restrictive measures against migration from foreign countries. Using our new dataset, COVID-19 Travel Restrictions and Categories, we examine whether Chinese migrant networks around the world have driven government decisions to bar the entry of Chinese nationals and travelers from China in the early months of the COVID-19 pandemic. Our survival analysis of China-specific travel restrictions from January to March 2020 shows that not all Chinese migrant networks were important determinants. We find that entry bans on travel from China emerged more quickly in countries where a large number of temporary Chinese migrants work in clustered sites of Chinese contracted projects.

Gamma-glutamyl transferase (GGT) has been predictive of chronic hepatitis C-related hepatocellular carcinoma (HCC) development. Its role in the risk of HCC in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs) is elusive.A total of 2172 CHB patients from East Asia were randomized into development and validation groups in a 1:2 ratio. Serum GGT levels before and 6 months (M6) after initiating NAs and the potential risk factors were measured. The primary endpoint was HCC development 12 months after NA initiation.The annual incidence of HCC was 1.4/100 person-years in a follow-up period of 11 370.7 person-years. The strongest factor associated with HCC development was high M6-GGT levels (25 U/L; hazard ratio [HR]/95% confidence interval [CI]: 3.31/2.02-5.42, P .001), followed by cirrhosis (HR/CI: 2.06/1.39-3.06, P .001), male sex (HR/CI: 2.01/1.29-3.13, P = .002) and age (HR/CI: 1.05/1.03-1.17, P .001). Among cirrhotic patients, the incidence of HCC did not differ between those with high or low M6-GGT levels (P = .09). In contrast, among non-cirrhotic patients, the incidence of HCC was significantly higher for those with M6-GGT level25 U/L than for their counterparts (P .001). Cox regression analysis revealed that the strongest factor associated with HCC development in non-cirrhotic patients was high M6-GGT levels (HR/CI: 5.05/2.52-10.16, P .001), followed by age (HR/CI: 1.07/1.04-1.09, P .001). Non-cirrhotic elderly patients with high M6-GGT levels had a similarly high HCC risk as cirrhotic patients did (P = .29).On-treatment serum GGT levels strongly predicted HCC development in CHB patients, particularly non-cirrhotic patients, treated with NAs.

We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). This is a retrospective study of 6189 adult treatment-naive CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR