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Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

Background/Aims: Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. Methods : A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. Results : The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p

Background/Aims: Programmed death-ligand 1 (PD-L1) expression in tumor cells is associated with a poor biliary tract cancer (BTC) prognosis; tumor-infiltrating immune cells in the tumor microenvironment are associated with a better prognosis. The effect of PD-L1 expression on immune cells on survival is unclear. We investigated the relationship between PD-L1 expression in immune cells and BTC prognosis. Methods: PD-L1 expression was evaluated using an anti-PD-L1 22C3 mouse monoclonal primary antibody, and its relationships with clinical characteristics and prognosis were analyzed using the Cox proportional hazard model to investigate the prognostic performance of PD-L1 in BTC. Results: Among 144 analyzed cases, patients with positive PD-L1 expression in tumor cells and negative PD-L1 expression in immune cells showed poorer overall survival rates than those exhibiting other expressions (tumor cells: hazard ratio [HR]=1.023, p

Background/Aims: There are few reports regarding mixed carcinoma, defined as a mixture of glandular and poorly cohesive components, in patients with gastric cancer (GC). The aim of this study was to evaluate the proportion and characteristics of mixed carcinoma in GC patients. Methods: A total of 7,215 patients diagnosed with GC at Seoul National University Bundang Hospital were enrolled from March 2011 to February 2020. GC was divided into four groups (well-moderately differentiated GC, poorly differentiated GC, poorly cohesive carcinoma, and mixed carcinoma). The proportion of each GC type and the clinicopathological features were analyzed and divided into early GC and advanced GC. Results: The proportion of mixed carcinoma was 10.9% (n=787). In early GC, submucosal invasion was the most common in poorly differentiated (53.7%), and mixed carcinoma ranked second (41.1%). Mixed carcinoma showed the highest proportion of lymph node metastasis in early GC (23.0%) and advanced GC (78.3%). In advanced GC, the rate of distant metastasis was 3.6% and 3.9% in well-moderately differentiated GC and mixed carcinoma, respectively, lower than that in poorly differentiated GC (6.4%) and poorly cohesive carcinoma (5.7%), without statistical significance. Conclusions: Mixed carcinoma was associated with lymph node metastasis compared to other histological GC subtypes. And it showed relatively common submucosal invasion in early GC, but the rates of venous invasion and distant metastasis were lower in advanced GC. Further research is needed to uncover the mechanism underlying these characteristics of mixed carcinoma (Trial registration number: NCT04973631).

The significant growth of the global protein drug market, including fusion proteins, emphasizes the crucial role of optimizing amino acid sequences to enhance the productivity and bioefficacy. Among these fusion proteins, RBP-IIIA-IB, comprising retinol-binding protein in conjunction with the albumin domains, IIIA and IB, has displayed efficacy in alleviating liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs). This study aimed to address the issue of the low productivity in RBP-IIIA-IB. To induce structural changes, the linking sequence, EVDD, between domain IIIA and IB in RBP-IIIA-IB was modified to DGPG, AAAA, and GGPA. Among these, RBP-IIIA-AAAA-IB demonstrated an increase in yield (>4-fold) and a heightened inhibition of HSC activation. Furthermore, we identified amino acid residues that could form disulfide bonds when substituted with cysteine. Through the mutation of N453S-V480S in RBP-IIIA-AAAA-IB, the productivity further increased by over 9-fold, accompanied by an increase in anti-fibrotic activity. Overall, there was a more than 30-fold increase in the fusion protein’s yield. These findings demonstrate the effectiveness of modifying linker sequences and introducing extra disulfide bonds to improve both the production yield and biological efficacy of fusion proteins.

Background/Aims: The incidence and prognosis of gastric cancer (GC) shows sex difference. This study aimed to evaluate the effect of body mass index (BMI) on GC survival depending on sex. Methods: The sex, age, location, histology, TNM stages, BMI, and survival were analyzed in GC patients from May 2003 to February 2020 at the Seoul National University Bundang Hospital. Results: Among 14,688 patients, there were twice as many males (66.6%) as females (33.4%). However, under age 40 years, females (8.6%) were more prevalent than males (3.1%). Cardia GC in males showed a U-shaped distribution for underweight (9.6%), normal (6.4%), overweight (6.1%), obesity (5.6%), and severe obesity (9.3%) but not in females (p=0.003). Females showed decreased proportion of diffuse-type GC regarding BMI (underweight [59.9%], normal [56.8%], overweight [49.5%], obesity [44.8%], and severe obesity [41.7%]), but males did not (p

ABSTRACT: Innate immunity, as an organism's first line of defense, plays a crucial role in rapidly responding to and protecting the body against invading pathogens. As a cytosolic RNA sensor for viral infections, including infections caused by influenza virus, the innate immune system in chickens has 2 major pathogen-recognition receptors (PRRs): Toll-like receptor 3 (TLR3) and melanoma differentiation-associated protein 5 (MDA5). The signaling pathways activated by PRRs are complex, systemic processes that underlie the response to foreign molecules. In this study, we investigated the interactions among MDA5, mitochondrial antiviral signaling protein (MAVS), and stimulator of interferon genes (STING) signaling in chicken cells. To exclude the effects of TLR3, we transfected the clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR-Cas9) expression vector and TLR3-targeted gRNA plasmid into chicken DF-1 cells. We selected TLR3-knockout (KO) cell line and sequentially, we established 2 double-KO cell lines: TLR3-MAVS KO and TLR3-STING KO. After treatment with polyinosinic:polycytidylic acid (poly(I:C)), type I interferon (IFN), IFN-stimulated gene, and antiviral gene (IFN regulatory factor 7, IFNβ, Mx1, and protein kinase R1) expression was not completely activated in TLR3-MAVS KO cells, whereas it was consistently upregulated in wild-type and TLR3-STING KO DF-1 cells. These results suggest that STING is not an intermediator between MDA5 and MAVS; moreover, it does not directly interact with MDA5 during innate immune activation in chicken DF-1 cells.

Abstract The Observation-Constrained Atmospheric BOX model (OCABOX) was used to analyze the formation of secondary inorganic PM species in the Seoul Metropolitan Area (SMA), South Korea. The measurement data of the ionic components of PM2.5 and their gaseous precursors made at the Olympic Park ground site (37.53°N, 127.12°E) during the Korea-United States Air Quality field campaign were used to run OCABOX in observation-based mode and compare the simulation results. The use of the HNO3 concentrations measured at a marine background site as the boundary conditions appeared to increase the accuracy of the model prediction of HNO3 and particulate NO3− concentrations. For the primary precursors emitted considerably throughout the SMA, such as NOx and NH3, using the data measured inside the SMA as the boundary conditions could lead to more accurate predictions. OCABOX was shown to be a reliable tool to analyze the formation of secondary inorganic aerosol in the SMA if used with appropriate regional background concentrations and observation-based constraints

Background : : This study aimed to identify chronicity predictors of pediatric primary immune thrombocytopenia (ITP). Methods : : This study retrospectively reviewed the medical records of patients with primary pediatric ITP admitted to a tertiary medical center between 2010 and 2021. Forty-five patients with a platelet count

As essential 21st century skills, creativity and critical thinking have garnered the attention of educators and researchers. The aim of this research was to investigate the nature of the relationship between these two essential skills through a content analysis of past empirical studies. Twenty-seven peer-reviewed journal articles were selected for a systematic review. The selection criteria include the utilization of psychometrically valid and reliable creativity and critical thinking measure and the report of either a correlation between measures of creativity and critical thinking or a report of effect size of intervention program on the development of creativity and critical thinking. The results of the study revealed that the correlation between the two ranged from non-significant to large, depending on the nature of the study. Two factors influenced the degree of correlation: the type of measurements used and the demographic of the participants (e.g., age and country of origin of the participants). Results also revealed that fostering creativity and critical thinking simultaneously is possible but the development of each skill can vary. Implications are discussed.

The proposed approach is a deep learning-based compact weighted binary classification (DL-CWBC) method to discriminate between targets and clutter in synthetic aperture radar (SAR) images. A new modified cross-entropy error function is proposed to improve the probability of detection by controlling the rate of false alarms (FAs). The unique feature of a CWBC algorithm is reducing the FA rate and maximizing the probability of target detection without missing any target. For pre-processing, targets and clutter are detected through a constant false alarm rate (CFAR) as a conventional detection algorithm. These are then manually divided into two classes. The classified targets and clutter were trained through a ResNet-101 network. There is a trade-off between the minimization of the FA rate and the maximization of the detection probability for targets of interest (TOIs). The weighted coefficient of the modified cross-entropy error function tries to maximize the performance of this trade-off. In addition, the proposed approach enables us not to miss any targets by an extreme distinction decision. Above all, the DL-CWBC algorithm performs very well despite its simplicity.

We compared the performance of computed tomography (CT) and magnetic resonance imaging (MRI) for preoperative clinical staging of mass‐forming intrahepatic cholangiocarcinoma (iCCA), using the eighth American Joint Committee on Cancer (AJCC) system. This retrospective, multicenter, cohort study consecutively identified patients who underwent partial hepatectomy for mass‐forming iCCA and had preoperative CT and MRI performed from January 2009 to December 2015. CT and MRI characteristics were used to determine clinical stage based on the eighth AJCC system. Performances of CT and MRI for clinical T and N staging were compared using generalized estimating equations. In 334 patients (median age, 63 years; 221 men), MRI sensitivities were significantly higher than CT sensitivities for detecting T1b or higher stages (91.0% vs. 80.5%, respectively, P 5 cm (i.e., T1b for single tumor) and extrahepatic organ invasion (i.e., T4). Sensitivities of CT and MRI were not different for N stage (65.0% vs. 64.0%, respectively, P = 0.808), but the specificity of CT was significantly higher than that of MRI (80.7% vs. 72.9%, respectively, P = 0.001) when using a composite reference standard. Conclusion: MRI showed superior sensitivity to CT for diagnosing T2 and T3 stages, particularly multiple tumors. CT and MRI had comparable sensitivity for N staging, but CT provided higher specificity than MRI.

Background Robot-assisted laparoscopic radical prostatectomy is an advanced and popular surgical technique. However, increased intracranial pressure which is caused by CO2 pneumoperitoneum and Trendelenburg position is the main cerebrovascular effect. Measurement of optic nerve sheath diameter using ocular ultrasound is a noninvasive and reliable method for the assessment of intracranial pressure. The primary endpoint of this study was to identify whether low blood pressure regulation has any benefit in attenuating an increase of optic nerve sheath diameter during robot-assisted laparoscopic radical prostatectomy. Methods Optic nerve sheath diameter and cerebral oxygen saturation were measured at baseline (supine position), one and two hours after pneumoperitoneum and Trendelenburg position respectively, and after return to supine position in normal (n = 27) and low blood pressure groups (n = 24). Results Mean optic nerve sheath diameter values measured at one and two hours after pneumoperitoneum and Trendelenburg position were significantly increased compared to the baseline value (P < 0.001 in normal blood pressure group; P = 0.003 in low blood pressure group). However, the mean optic nerve sheath diameter and cerebral oxygen saturation measured at any of the time points as well as degrees of change between the two groups did not show any significant changes. The peak values of optic nerve sheath diameter in normal and low blood pressure groups demonstrated 14.9% and 9.2% increases, respectively. Conclusions Low blood pressure group demonstrated an effect in maintaining an increase of optic nerve sheath diameter less than 10% during CO2 pneumoperitoneum and Trendelenburg position.

Abstract Activation of quiescent hepatic stellate cells (HSCs) to myofibroblasts plays a key role in liver fibrosis. We had previously shown that albumin and its derivative, R-III (a retinol-binding protein—albumin domain III fusion protein), inhibited HSC activation by sequestering retinoic acid (RA) and that R-III administration reduced carbon tetrachloride (CCl4)-induced liver fibrosis. In this study, we aimed to elucidate the mechanism of action of albumin downstream of RA sequestration. Nuclear factor-κB p65 was evenly distributed in the cytoplasm in activated mouse HSCs, whereas albumin expression or R-III treatment (albumin/R-III) caused the nuclear translocation of p65, probably via RA sequestration, resulting in a dramatic increase in interleukin-1beta (IL-1β) expression. Albumin/R-III in turn induced the phosphorylation of Smad3 at the linker region, inhibiting its nuclear import in an IL-1β-dependent manner. Consistent with the in vitro results, the level of IL-1β mRNA expression was higher in CCl4/R-III-treated livers than in CCl4-treated livers. These findings reveal that albumin/R-III inhibits the transforming growth factor-β-Smad3 signaling as well as the retinoic acid receptor-mediated pathway, which probably contributes to the inhibition of HSC activation, and suggest that R-III may be an anti-fibrotic drug candidate.

Enhancing creativity and critical thinking have garnered the attention of educators and researchers for decades. They have been highlighted as essential skills for the 21st century. A total of 103 United States students (53 female, 24 male, two non-binary, and 24 non-reporting) and 166 Chinese students (128 female, 30 male, one non-binary, and seven non-reporting) completed an online survey. The survey includes the STEAM-related creative problem solving, Sternberg scientific reasoning tasks, psychological critical thinking (PCT) exam, California critical thinking (CCT) skills test, and college experience survey, as well as a demographic questionnaire. A confirmatory factor analysis (CFA) yields a two-factor model for all creativity and critical thinking measurements. Yet, the two latent factors are strongly associated with each other (r=0.84). Moreover, Chinese students outperform American students in measures of critical thinking, whereas Americans outperform Chinese students in measures of creativity. Lastly, the results also demonstrate that having some college research experience (such as taking research method courses) could positively influence both United States and Chinese students’ creativity and critical thinking skills. Implications are discussed.

A vast disparity exists between science and practice for CT radiation dose. Despite high-level evidence supporting the use of low-dose CT (LDCT) in diagnosing appendicitis, a recent survey showed that many care providers were still concerned that the low image quality of LDCT may lead to incorrect diagnoses. For successful implementation of LDCT practice, it is important to inform and educate the care providers not only of the scientific discoveries but also of concrete guidelines on how to overcome more practical matters. Here, we discuss CT imaging techniques and other practical issues for implementing LDCT practice.

Crepidiastrum sonchifolium, a flowering plant in the daisy family (Asteraceae), is native to East Asia. In Korea, this plant is a locally cultivated vegetable, and its market size is gradually growing. Since the plants with downy mildew infection were initially found at a private farm of Chuncheon city, the occurrences have continued in commercial farms of other regions, highlighting that this disease is spreading throughout Korea. The pathogen was attributed to a member of the genus Bremia that contains many specialized species, each of which displays a narrow host spectrum on Asteraceae. Based on morphological and molecular phylogenetic analyses, along with the high host specificity recently proven for Bremia species, the identity of the causal agent was confirmed as a so far undescribed species of Bremia. Here, we introduce Bremia itoana sp. nov., specific to C. sonchifolium.

We report the sonographic features of confirmed malignant appendiceal tumors in seven cases. The histologic diagnoses of these tumors were mucinous cystadenocarcinoma (n = 2), colonic type adenocarcinoma (n = 4), and signet-ring cell carcinoma (n = 1). The 2 mucinous cystadenocarcinomas showed mucocele type, which had markedly enlarged inner luminal diameters (mean, 23 mm; range, 15–31 mm) and thick, irregular walls (mean wall thickness, 5.5 mm; range, 5–6 mm). In contrast, the 5 nonmucinous carcinomas (4 adenocarcinomas and 1 signet-ring cell carcinoma) showed nonmucocele type, which had relatively small inner luminal diameters (mean ± standard deviation [SD], 6.6 ± 4.5 mm; range, 2–15 mm) and prominent wall thickening (mean wall thickness ± SD, 6.2 ± 2.3 mm; range, 3–10 mm). Of the 5 nonmucinous tumors, only one had a discernible mass, three had thick irregular walls, two had loss of the wall layer pattern, and four had submucosal hypoechogenicity. Regardless of the histologic type, five of the seven malignant appendiceal tumors showed a severe periappendiceal fat infiltration or periappendiceal abscess, suggestive of perforation.Although the sonographic findings of the malignant appendiceal tumors were nonspecific, some of the sonographic features seen in these seven cases may help radiologists consider the possibility of underlying malignant appendiceal tumors.

This study was conducted for analyzing the contribution factors on ozone concentrations and its long term trends in each major city and province in Korea through several statistical methods such as simple linear regression, generalized linear model, KZ-filer, correlation matrix, Kringing method, and cluster analysis. The overall ozone levels in South Korea have been consistently increasing over the past 10 years. The ozone concentrations in Seoul, the biggest city in Korea, are the lowest in all areas with the highest increasing ratio for 95th% ozone. It is thought that the active photochemical reaction could affect the higher ozone concentration increase. On the other hand, the ozone concentrations in Jeju are the highest in Korea with the highest increasing ratio for 5th%, 33th%, and 50th% ozone. It is also thought that the weak NOx titration could be the reason of higher ozone concentrations in Jeju. In case of Jeju, transport related factors is the major factor affecting the ozone trend. Thus, it is assumed that the variation of ozone trend of Asian region affecting the ozone trend in Jeju, where domestic ozone photochemical reaction is less active than urban area. It is thought that the photochemical reaction plays the role of increasing of ozone concentrations in the urban area, even though the LRT affected on the increase of ozone concentrations in non-urban area.

Abstract This is the first report on the development of a covalently bone morphogenetic protein-2 (BMP2)-immobilized hydrogel that is suitable for osteogenic differentiation of human periodontal ligament stem cells (hPLSCs). O-propargyl-tyrosine (OpgY) was site-specifically incorporated into BMP2 to prepare BMP2-OpgY with an alkyne group. The engineered BMP2-OpgY exhibited osteogenic characteristics after in vitro osteogenic differentiation of hPLSCs, indicating the osteogenic ability of BMP2-OpgY. A methoxy polyethylene glycol-(polycaprolactone-(N3)) block copolymer (MC-N3) was prepared as an injectable in situ-forming hydrogel. BMP2 covalently immobilized on an MC hydrogel (MC-BMP2) was prepared quantitatively by a simple biorthogonal reaction between alkyne groups on BMP2-OpgY and azide groups on MC-N3 via a Cu(I)-catalyzed click reaction. The hPLSCs-loaded MC-BMP2 formed a hydrogel almost immediately upon injection into animals. In vivo osteogenic differentiation of hPLSCs in the MC-BMP2 formulation was confirmed by histological staining and gene expression analyses. Histological staining of hPLSC-loaded MC-BMP2 implants showed evidence of mineralized calcium deposits, whereas hPLSC-loaded MC-Cl or BMP2-OpgY mixed with MC-Cl, implants showed no mineral deposits. Additionally, MC-BMP2 induced higher levels of osteogenic gene expression in hPLSCs than in other groups. In conclusion, BMP2-OpgY covalently immobilized on MC-BMP2 induced osteogenic differentiation of hPLSCs as a noninvasive method for bone tissue engineering.

Abstract Most cancer cells have telomerase activity because they can express the human telomerase reverse transcriptase (hTERT) gene. Therefore, the inhibition of the hTERT expression can play an important role in controlling cancer cell proliferation. Our current study aims to inhibit hTERT expression. For this, we synthesized graphene oxide (GO) and a functionalized multiwall carbon nanotube (f-MWCNT), latter treated them with cold atmospheric pressure plasma for further analysis of the hTERT expression. The inhibition of hTERT expression by GO, f-MWCNT, plasma activated GO solution (PGOS), and plasma activated f-MWCNT solution (PCNTS), was studied using two lung cancer cell lines, A549 and H460. The hTERT experimental results revealed that GO and PGOS sufficiently decreased the hTERT concentration, while f-MWCNT and PCNTS were unable to inhibit the hTERT concentration. Therefore, to understand the inhibition mechanism of hTERT, we studied the binding properties of GO and PGOS with telomere binding protein (AtTRB2). The interaction studies were carried out using circular dichroism, fluorescence, 1H-15N NMR spectroscopy, and size-exclusion chromatography (SEC) binding assay. We also used docking simulation to have an better understanding of the interactions between GO nanosheets and AtTRB2 protein. Our results may provide new insights that can benefit in biomedical treatments.

Abstract The variation in the biological function of proteins plays an important role in plasma medicine and sterilization. Several non-thermal plasma sources with different feeding gases are used worldwide for plasma treatment, including dielectric barrier discharge (DBD) and atmospheric-pressure plasma jet (APPJ) as the most commonly used sources. Therefore, in the present work, we used both DBD and APPJ plasma sources with N2 and air as feeding gases to evaluate the effects on the structural, thermodynamic, and activity changes of enzymes. In the current work, we used lysozyme as a model enzyme and verified the structural changes using circular dichroism (CD), fluorescence, and X-ray crystallography. In addition, we investigated the lysozyme thermodynamics using CD thermal analysis and changes in the B-factor from X-ray crystallography. The results showed that lysozyme activity decreased after the plasma treatment. From these analyses, we concluded that N2-feeding gas plasma disturbs the structure and activity of lysozyme more than Air feeding gas plasma in our experimental studies. This study provides novel fundamental information on the changes to enzymes upon plasma treatment, which has been absent from the literature until now.

Abstract Background Ultrasonography (US) is widely used as a standard surveillance tool for patients who are at a high risk of having hepatocellular carcinoma (HCC); however, conventional B-mode US appears to be insufficient in order to ensure the early detection of HCC. Perfluorobutane allows very stable Kupffer phase imaging for at least 60 min, which is tolerable for examinations of the entire liver. The purpose of our study is to evaluate the added value of contrast-enhanced US using perfluorobutane to that of conventional B-mode US as an HCC surveillance tool for patients with liver cirrhosis. Methods/Design SCAN (Sonazoid-US for surveillance of hepatoCellulArcarciNoma) is a prospective, multi-institutional, diagnostic trial using an intra-individual comparison design in a single arm of patients. This study was approved by our five institutional review board and informed consent was obtained from all participating. We obtained consent for publication of these data (contrast enhanced US images, CT or MRI images, laboratory findings, age, sex) from all participating patients. All patients will undergo conventional B-mode US immediately followed by contrast-enhanced US. The standardized case report forms will be completed by operating radiologists after B-mode US and contrast-enhanced US, respectively. If any lesion(s) is detected, the likelihood of HCC will be recorded. The primary endpoints are a detection rate of early-stage HCC and a false referral rate of HCC. Intra-individual comparison using Mcnemar’s test will be performed between B-mode US and contrast-enhanced US. The study will include 523 patients under HCC surveillance in five medical institutions in Korea. Discussion SCAN is the first study to investigate the efficacy of contrast-enhanced US in surveillance using two reciprocal endpoints specialized for the evaluation of a surveillance test. SCAN will provide evidence regarding whether patients can truly benefit from contrast-enhanced US in terms of the detection of early stage HCC while avoiding additional unnecessary examinations. In addition to the study protocol, we elaborate on potentially debatable components of SCAN, including the design of an intra-individual comparison study, study endpoints, composite reference standards, and indefinite imaging criteria regarding the likelihood of HCC. Trial registration The date of trial registration (ClincalTrials.gov: NCT02188901 ) in this study is July 3, 2014. The last patient enrolled in August 30, 2016 and follow up to see the primary end point is still ongoing. All authors have no other relationships/conditions/circumstances that present a potential conflict of interest of relationships. Our study protocol has undergone peer-review by the funding body (GE Healthcare). No other relationships/conditions/circumstances that present a potential conflict of interest. Also, we clearly stated in the 'competing interests' section of my manuscript.

ObjectiveTo investigate the correlation between dyspeptic symptoms and gastric motility parameters measured by magnetic resonance imaging (MRI) using volumetry and motility indices in patients with Parkinson's disease (PD).Materials and methodsIn this IRB-approved study, MRI datasets obtained from August 2014 to May 2016 in 38 PD patients were retrospectively analyzed. Patients underwent a 120-minute-long MRI study using a liquid test meal and 8 sets of scans. Gastric content volume (GCV) and total volume (TGV), gastric half emptying time (T1/2), motility index (GMI), accommodation (GA), and emptying (GE) values were acquired. These measurements were compared between patients according to the presence of gastric symptoms: early satiety (n = 25), epigastric pain (n = 13), and dyspepsia (n = 28).ResultsPatients with early satiety showed significantly decreased GE of GCV and TGV (p < 0.001 and p = 0.017). Dyspeptic patients had significantly decreased GE of GCV and GMI (p = 0.001 and p = 0.029). GE of GCV at 90 and 120 minutes were significantly lower in patients with early satiety (p = 0.001 and p = 0.002). GE of GCV and GMI at 90 minutes were significantly decreased in patients with dyspepsia (p = 0.004 and p = 0.002). T1/2 of GCV was prolonged in patients with early satiety, epigastric pain, and dyspepsia (p = 0.004, p = 0.041, and p = 0.023). T1/2 of TGV also delayed in patients with early satiety (p = 0.023). GMI at 90 minutes was significantly correlated with dyspepsia on multivariable analysis (p = 0.028).ConclusionsGastric motility can be quantitatively assessed by MRI, showing decreased GMI, delayed GE, and prolonged T1/2 in PD patients with early satiety or dyspepsia.

Background & aimsElastography point quantification is a convenient method for measuring liver stiffness. It can be performed simultaneously with conventional ultrasonography. This study aimed to evaluate its diagnostic performance for assessing hepatic fibrosis in patients with autoimmune liver disease (AILD), including autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC).MethodsThe diagnostic performance of elastography point quantification (ElastPQ) was evaluated and compared with that of serum fibrosis markers, including the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4), using the receiver operating characteristics analysis with histologic evaluation as the reference standard.ResultsIn 49 AIH patients, sensitivity and specificity of ElastPQ were 93.6% and 44.4%, respectively, for significant fibrosis (≥ F2, cutoff 4.47 kPa), and 63.6% and 86.8% for cirrhosis (F4, cutoff 9.28 kPa). In 41 PBC patients, they were 81.8% and 73.3%, respectively, for significant fibrosis (≥ F2, cutoff 5.56 kPa), and 100% and 81.6%, respectively, for advanced fibrosis (≥ F3, cutoff 6.04 kPa). The areas under the receiver operating characteristic curves of ElastPQ for significant fibrosis (0.77, 95% CI 0.67-0.86) and cirrhosis (0.81, 95% CI 0.65-0.96) were higher than those of APRI and FIB-4 in AILD patients. According to the multivariable analysis, histological activity, steatosis, and body max index (BMI) were not significant factors that influenced the result of ElastPQ.ConclusionsElastPQ exhibited better diagnostic performance-without the influence of confounding factors-for assessing hepatic fibrosis in AILD patients than serum fibrosis markers.

Although ethanol dry reforming is an attractive carbon utilization technology, problems of severe coke formation and low catalytic activity should be solved for realization of the technology. We demonstrate the effects of alkali metal additives (lithium, sodium, and potassium) on nickel catalyzed ethanol dry reforming. Potassium doped nickel catalyst (Ni/K2O-Al2O3) showed enhanced catalytic activity and durability in ethanol dry reforming. Thermogravimetric analysis (TGA) showed that Ni/K2O-Al2O3 had a high resistance to coke formation. The amounts of coke formed on Ni/K2O-Al2O3 were 1/3 lower than the amounts of coke formed on Ni/Al2O3. The total coke quantities were closely correlated to the number of basic sites of the nickel catalysts. Raman spectroscopy and transmission electron microscopy analyses revealed that the alkali metals control the coke formation on the catalysts.

Background/AimsAnti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy.MethodsTen cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB.ResultsThe incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients.ConclusionsActive TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.

Inferior mesenteric arteriovenous fistula (AVF) is a rare vascular abnormality that may be either congenital or acquired. It usually presents with abdominal pain, gastrointestinal bleeding, and a palpable mass with thrill or portal hypertension; it may also elicit more serious complications such as colonic ischemia. We report a case of idiopathic inferior mesenteric AVF in a 75-year-old man who presented with recurrent ischemic colitis. To our knowledge, this is the first reported case in Korea of an idiopathic inferior mesenteric AVF without any surgical or traumatic history.

In this study, we developed injectable intratympanic hyaluronic acid (HA) depots for the treatment of hearing loss. We prepared an injectable click-crosslinking formulation by modifying HA with tetrazine (HA-TET) and trans-cyclooctene (HA-TCO), which crosslinked to form an HA depot (Cx-HA). Preparation of the click-crosslinking HA formulation was facile, and Cx-HA depot formation was reproducible. Additionally, the Cx-HA hydrogel was significantly stiffer than HA hydrogel. To monitor the degradation pattern of hydrogels, we mixed a zwitterionic near-infrared (NIR) fluorophore (e.g., ZW800-1C) in the click-crosslinking HA formulation. Then, HA-TET and HA-TCO solutions containing ZW800-1C were loaded separately into the compartments of a dual-barrel syringe for intratympanic injection. The Cx-HA depots formed quickly, and an extended residence time in the tympanic cavity was confirmed by performing NIR fluorescence imaging. We have successfully prepared an injectable click-crosslinking HA formulation that has promise as an intratympanic drug depot.

In biomedical applications, there is a need for tissue engineering scaffolds to promote and control cellular behaviors, including adhesion, proliferation and differentiation. In particular, the initial adhesion of cells has a great influence on those cellular behaviors. In this study, we concentrate on developing cell-adhesive substrates applicable for tissue engineering scaffolds. The hybrid nanofiber sheets were prepared by electrospinning poly(lactic-co-glycolic acid) (PLGA) and M13 phage, which was genetically modified to enhance cell adhesion thru expressing RGD peptides on their surface. The RGD peptide is a specific motif of extracellular matrix (ECM) for integrin receptors of cells. RGD peptide-decorated PLGA (RGD-PLGA) nanofiber sheets were characterized by scanning electron microscopy, immunofluorescence staining, contact angle measurement and differential scanning calorimetry. In addition, the initial adhesion and proliferation of four different types of mammalian cells were determined in order to evaluate the potential of RGD-PLGA nanofiber sheets as cell-adhesive substrates. Our results showed that the hybrid nanofiber sheets have a three-dimensional porous structure comparable to the native ECM. Furthermore, the initial adhesion and proliferation of cells were significantly enhanced on RGD-PLGA sheets. These results suggest that biomimetic RGD-PLGA nanofiber sheets can be promising cell-adhesive substrates for application as tissue engineering scaffolds.

To evaluate the association of computed tomography (CT) texture features of locally advanced rectal cancer with neoadjuvant chemoradiotherapy (CRT) response and disease-free survival (DFS).The institutional review board approved this retrospective study. 95 patients who received neoadjuvant CRT, followed by surgery, for locally advanced rectal cancer were included. Texture features (entropy, uniformity, kurtosis, skewness, and standard deviation) were assessed in pretreatment CT images and obtained without filtration and with Laplacian of Gaussian spatial filter of various filter values (1.0, 1.5, 2.0, and 2.5). Dworak pathologic grading was used for treatment response assessment. Independent t-test was used to compare each texture feature between the treatment responder and non-responder groups. DFS was assessed with Kaplan-Meier method, and differences were compared with log-rank test. Cox proportional hazards models were constructed to predict prognosis based on stage, age, and each texture feature. Treatment responders (n = 32) showed significantly lower entropy, higher uniformity, and lower standard deviation in no filtration, fine (1.0), and medium (1.5) filter values. Entropy, uniformity, and standard deviation without filtration showed significant difference in DFS in Kaplan-Meier analysis (P = 0.015, 0.025, and 0.038). Homogeneous texture features (≤ 6.7 for entropy, > 0.0118 for uniformity, and ≤ 28.06 for standard deviation) were associated with higher DFS. Entropy, uniformity, and standard deviation were independent texture features in predicting DFS (P = 0.017, 0.03, and 0.036).Homogeneous texture features are associated with better neoadjuvant CRT response and higher DFS in patients with locally advanced rectal cancer.

Background/AimsHyperglycemia is associated with decreased 2-18[F]fluoro-2-deoxy-D-glucose (FDG) uptake by tumors assessed by positron emission tomography (PET). In this retrospective study we investigated a comparison of standardized uptake values (SUVs) in patients with primary colorectal cancers who either had diabetes mellitus (DM) or were otherwise healthy.MethodsThe medical records of 397 patients who were diagnosed with colorectal cancer and underwent PET-CT between January 2006 and December 2012 were analyzed. Eighty patients with DM and 317 patients without DM were included. Clinical characteristics were reviewed and maximal standardized uptake values (SUVmax) were calculated in the primary colorectal lesions.ResultsThere was no significant difference between tumor SUVmax in DM patients (10.60±5.78) and those without DM (10.92±5.44). In addition, no significant difference was detected between tumor SUVmax in DM patients with glycated hemoglobin (HbA1c) levels

Although recent findings showed that the bioactive lipid metabolites can regulate the ES cell functions, the physiological relevance of interaction between sphingosine-1-phosphate (S1P) and Flk-1 and its related signaling molecules are not yet clear in ES cell proliferation. In the present study, S1P1–5 receptors were expressed in mouse ES cells and S1P increased S1P1–3 receptor expression level. S1P treatment stimulated the cellular proliferation in S1P1/3-dependent manner, located in lipid rafts. In response to S1P, β-arrestin was recruited to S1P1/3 receptor and c-Src was activated. S1P also increased the binding of S1P1/3 receptor with Flk-1. Similar to responses for VEGF, S1P increased Flk-1 phosphorylation, which was blocked by β-arrestin siRNA, and PP2, but not by VEGF-A164 antibody or VEGF siRNA. In addition, S1P induced VEGF expression and VEGFR2 kinase inhibitor (SU1498) blocked the S1P-induced cellular proliferation. However, VEGF-A164 antibody or VEGF siRNA partially blocked S1P-induced cellular proliferation, suggesting that both VEGF-dependent Flk-1 activation and VEGF-independent Flk-1 activation are involved in S1P-induced ES cell proliferation. S1P and VEGF-induced phosphorylation of ERK and JNK were blocked by pretreatment with SU1498. Moreover, inhibition of ERK and JNK blocked S1P-induced cellular proliferation. In conclusion, S1P-elicited transactivation of Flk-1 mediated by S1P1/3-dependent β-arrestin/c-Src pathways stimulated mouse ES cell proliferation.

Acute suppurative thyroiditis (AST) is a rare condition, as the thyroid gland is relatively resistant to infection. Thyroid function tests are usually normal in AST. A few cases of AST associated with thyrotoxicosis have been reported in adults. We report a case of AST that was associated with thyrotoxicosis in a 70-year-old woman. We diagnosed AST with thyroid ultrasonography and fine needle aspiration of pus. The patient improved after surgical intervention and had no anatomical abnormality. Fine needle aspiration is the best method for the difficult task of differentiating malignancy and subacute thyroiditis from AST with thyrotoxicosis. Earlier diagnosis and proper treatment for AST might improve the outcome.

Recently, several thermogelling materials have been developed for biomedical applications. In this study, we prepared methoxy polyethylene glycol (MPEG)-b-(poly(ε-caprolactone)-ran-poly(2-chloride-ε-caprolactone) (PCL-ran-PfCL)) (MP-Cl) diblock copolymers at room temperature via the ring-opening polymerization of caprolactone (CL) and 2-chloride-ε-caprolactone (fCL) monomers, using the terminal alcohol of MPEG as the initiator in the presence of HCl. MPEG-b-(poly(ε-caprolactone)-ran-poly(2-azide-ε-caprolactone) (PCL-ran-PCL-N3)) (MP-N3) was prepared by the reaction of MP-Cl with sodium azide. MPEG-b-(poly(ε-caprolactone)-ran-poly(2-amine-ε-caprolactone) (PCL-ran-PCL-NH2)) (MP-NH2) was subsequently prepared by Staudinger reaction. MP-Cl and MP-N3 showed negative zeta potentials, but MP-NH2 had a positive zeta potential. MP-Cl, MP-N3, and MP-NH2 solutions formed opaque emulsions at room temperature. The solutions exhibited a solution-to-hydrogel phase transition as a function of the temperature and were affected by variation of the chloride, azide, and the amine pendant group, as well as the amount of pendant groups present in their structure. Additionally, the phase transition of MP-Cl, MP-N3, and MP-NH2 copolymers was altered by pendant groups. The solution-to-hydrogel phase transition was adjusted by tailoring the crystallinity and hydrophobicity of the copolymers in aqueous solutions. Collectively, MP-Cl, MP-N3, and MP-NH2 with various pendant-group contents in the PCL segment showed a solution-to-hydrogel phase transition that depended on both the type of pendant groups and their content.

MicroRNAs (miRNAs) are small noncoding RNAs that mediate post-transcriptional gene silencing by binding to complementary target mRNAs and recruiting the miRNA-containing ribonucleoprotein complexes to the mRNAs. However, the molecular basis of this silencing is unclear. Here, we show that human Ago2 associates with the cap-binding protein complex and this association is mediated by human eIF4GI, a scaffold protein required for the translation initiation. Using a cap photo-crosslinking method, we show that Ago2 closely associates with the cap structure. Taken together, these data suggest that eIF4GI participates in the miRNA-mediated post-transcriptional gene silencing by promoting the association of Ago2 with the cap-binding complex.

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets.

Recently, electrospinning technology has been widely used as a processing method to make nanofiber sheets (NS) for biomedical applications because of its unique features, such as ease of fabrication and high surface area. To develop a sustained dexamethasone (Dex) delivery system, in this work, poly(ε-caprolactone-co-l-lactide) (PCLA) copolymer with controllable biodegradability was synthesized and further utilized to prepare electrospun Dex-loaded NS using water-insoluble Dex (Dex(b)) or water-soluble Dex (Dex(s)). The Dex-NS obtained by electrospinning exhibited randomly oriented and interconnected fibrillar structures. The in vitro and in vivo degradation of Dex-NS was confirmed over a period of a few weeks by gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR). The evaluation of in vitro and in vivo Dex(b) and Dex(s) release from Dex-NS showed an initial burst of Dex(b) at day 1 and, thereafter, almost the same amount of release as Dex(b) for up to 28 days. In contrast, Dex(s)-NS exhibited a small initial burst of Dex(s) and a first-order releasing profile from Dex-NS. In conclusion, Dex-NS exhibited sustained in vitro and in vivo Dex(s) release for a prolonged period, as well as controlled biodegradation of the NS over a defined treatment period.

DJ-1 is a Parkinson's disease-associated gene whose protein product has a protective role in cellular homeostasis by removing cytosolic reactive oxygen species and maintaining mitochondrial function. However, it is not clear how DJ-1 regulates mitochondrial function and why mitochondrial dysfunction is induced by DJ-1 deficiency. In a previous study we showed that DJ-1 null dopaminergic neuronal cells exhibit defective mitochondrial respiratory chain complex I activity. In the present article we investigated the role of DJ-1 in complex I formation by using blue native-polyacrylamide gel electrophoresis and 2-dimensional gel analysis to assess native complex status. On the basis of these experiments, we concluded that DJ-1 null cells have a defect in the assembly of complex I. Concomitant with abnormal complex I formation, DJ-1 null cells show defective supercomplex formation. It is known that aberrant formation of the supercomplex impairs the flow of electrons through the channels between respiratory chain complexes, resulting in mitochondrial dysfunction. We took two approaches to study these mitochondrial defects. The first approach assessed the structural defect by using both confocal microscopy with MitoTracker staining and electron microscopy. The second approach assessed the functional defect by measuring ATP production, O(2) consumption, and mitochondrial membrane potential. Finally, we showed that the assembly defect as well as the structural and functional abnormalities in DJ-1 null cells could be reversed by adenovirus-mediated overexpression of DJ-1, demonstrating the specificity of DJ-1 on these mitochondrial properties. These mitochondrial defects induced by DJ-1mutation may be a pathological mechanism for the degeneration of dopaminergic neurons in Parkinson's disease.

Solid oxide electrolysis cells (SOECs) have garnered interest as efficient systems for hydrogen production through water electrolysis. One critical limitation hindering the widespread adoption of this technology is the long-term degradation of electrodes. In addition, ensuring the durability of the electrolyte remains a significant challenge. This study delves into the degradation mechanism of yttria-stabilized zirconia (YSZ) with varying Y2O3 compositions under an applied electric potential. In a comprehensive investigation of the degradation behavior of YSZ electrolytes with Y2O3 doping ranging between 8 and 10 mol%, the 8YSZ composition exhibited a pronounced reduction in ionic conductivity compared to 9.5YSZ and 10YSZ. Although 8YSZ exhibits the highest ionic conductivity, it has been determined that, under SOEC operating conditions, a Y2O3 doping concentration exceeding 8 mol% is required for stability owing to the precipitation around the electrode induced by the electric field. Electrical analysis, X-ray diffraction, Raman spectroscopy, and transmission electron microscopy were utilized to assess the degradation behavior of the electrolyte. K-means clustering was applied to highlight the disorder in defects observed through energy-dispersive spectroscopy. This study elucidates the underlying mechanisms governing electrolyte degradation in SOECs and recommends optimal YSZ compositions for prolonged operation, considering thermal stability and durability under SOEC operating conditions. [ABSTRACT FROM AUTHOR]