Search

Abstract Background Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please™ stent is a newly developed drug eluting stent using the Coroflex™ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please™ stent were within the range of those of Taxus, the 1st generation paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please™ stent with the Taxus Liberte™ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please™ stent compared with Taxus Liberte™ stent in a head-to-head manner. Methods In the comparison of Efficacy between COroflex PLEASe™ ANd Taxus™ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please™ stent and Taxus Liberte™ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints. Discussion The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please™ versus Taxus Liberte™ stent. On the basis of this trial, we will be able to find out whether the Coroflex Please™ stent is non-inferior to Taxus Liberte™ stent or not. Trial registration ClinicalTrials.gov number, NCT00699543.

Background/aims: The prevalence of gallstone disease in patients with ulcerative colitis (UC) is higher than in the general population. However, risk factors of gallstone disease in these patients remain unclear. Thus, we investigated the prevalence and risk factors of gallstone disease in Korean patients with UC., Methods: Patients diagnosed with UC who underwent abdominal imaging studies between 1997 and 2020 were investigated using a well-established referral center-based large volume inflammatory bowel disease cohort. The prevalence and clinical characteristics of patients with gallstone disease were evaluated and compared with those without gallstone disease., Results: Overall, 2,811 patients with UC were enrolled. During the follow-up period (mean, 5.7 years), 198 patients (7.0%) were diagnosed with gallstone disease and compared with those without gallstone disease (n = 2,613). The proportion of extensive colitis at maximum extent, primary sclerosing cholangitis (PSC), history of cytomegalovirus, corticosteroid use, immunomodulatory use, colectomy, and appendectomy were significantly higher in the gallstone group (all P< 0.05). In multivariate analyses, age ≥ 60 years at gallstone evaluation (odds ratio [OR], 1.027; 95% confidence interval [CI], 1.002-1.052; P= 0.033), PSC (OR, 6.304; 95% CI, 3.162-12.565; P< 0.001), and history of colectomy (OR, 2.494; 95% CI, 1.222-5.087; P= 0.012) were significant risk factors for gallstone disease in patients with UC., Conclusions: The prevalence of gallstone disease in Korean patients with UC was 7.0%, and age ≥ 60 years at gallstone evaluation, PSC, and history of colectomy were significant risk factors for UC patients with gallstone disease.

Objectives: To develop and evaluate an automated method for combining a digital photograph with a lateral cephalogram., Materials and Methods: A total of 985 digital photographs were collected and soft tissue landmarks were manually detected. Then 2500 lateral cephalograms were collected, and corresponding soft tissue landmarks were manually detected. Using the images and landmark identification information, two different artificial intelligence (AI) models-one for detecting soft tissue on photographs and the other for identifying soft tissue on cephalograms-were developed using different deep-learning algorithms. The digital photographs were rotated, scaled, and shifted to minimize the squared sum of distances between the soft tissue landmarks identified by the two different AI models. As a validation process, eight soft tissue landmarks were selected on digital photographs and lateral cephalometric radiographs from 100 additionally collected validation subjects. Paired t-tests were used to compare the accuracy of measures obtained between the automated and manual image integration methods., Results: The validation results showed statistically significant differences between the automated and manual methods on the upper lip and soft tissue B point. Otherwise, no statistically significant difference was found., Conclusions: Automated photograph-cephalogram image integration using AI models seemed to be as reliable as manual superimposition procedures., (© 2024 by The EH Angle Education and Research Foundation, Inc.)

Background: The Wnt/β-catenin signaling pathway is crucial for the development, initiation, and growth of hair follicles (HFs). The Dickkopf-related protein (DKK) gene family encodes secreted proteins modulating the Wnt/β-catenin signaling pathway. Studies have reported that DKK1 promotes the regression of HFs and serves as a pathogenic mediator in male pattern baldness. However, the role of DKK2 on human hair growth has not yet been explored., Objective: This study investigates direct effect of DKK2 on hair growth using human dermal papilla cell (DPC) cultures and ex vivo human HF organ cultures., Methods: To elucidate the effect of DKK2 on hair growth, we examined the effect of recombinant human DKK2 (rhDKK2) treatment on cell viability, expression of mRNA and protein related to the Wnt/β-catenin signaling pathway, and cell growth in cultured human DPCs. We also performed ex vivo organ culture of HFs with rhDKK2 and measured changes in hair shaft length for 8 days., Results: Treatment with rhDKK2 led to a dose-dependent rise in the proliferation of human DPCs ( p <0.05), reaching levels comparable to those induced by 1 μM minoxidil. Moreover, rhDKK2 increased the expression of Wnt/β-catenin target genes, phosphorylated extracellular signal-regulated kinase, and cyclin-D1; it also increased the BAX-to-Bcl-2 ratio and downregulated the bone morphogenetic protein 2 gene. In human HF organ cultures, relative to the control treatment, rhDKK2 treatment significantly increased hair shaft elongation ( p <0.01)., Conclusion: Our results indicate that rhDKK2 could promote hair growth by facilitating the proliferation of human DPCs through activation of the Wnt/β-catenin signaling pathway., Competing Interests: The authors have nothing to disclose., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background : Distal bile duct cancer is an aggressive malignancy. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment are crucial for predicting prognosis in various cancers. In this study, we analyzed TIICs based on CD11b, CD163, and CD8 expression, and evaluated their association with clinicopathologic factors and prognosis in distal bile duct cancer. Methods: A total of 90 patients who underwent curative resection for distal bile duct cancer were enrolled. We analyzed CD11b+ tumor-infiltrating myeloid cells (TIMs), CD163+ tumor-infiltrating macrophages (TAMs), and CD8+ tumor-infiltrating lymphocytes (TILs) using immunohistochemistry and tissue microarrays. The correlation between TIICs and clinicopathologic characteristics was assessed. Results: Low levels of CD11b+ TIMs ( p < 0.001) and high levels of CD8+ TILs ( p = 0.003) were significantly associated with improved overall survival (OS). A combined low level of CD11b+ TIMs and high level of CD8+ TILs was identified as an independent favorable prognostic factor (hazard ratio, 0.159; confidence interval, 0.061-0.410; p < 0.001). Conclusions: CD11b+ TIMs play a crucial role in the tumor microenvironment and the prognosis of distal bile duct cancer. The combined analysis of CD11b+ TIMs and CD8+ TILs can predict survival in patients with distal bile duct cancer., Competing Interests: The authors declare no conflicts of interest.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. While many treatments exist, our understanding of its genomic progression, especially from the epidermis to the deep dermis, remains limited. This study aims to identify genetic mutations associated with the progression of cSCC into the deep dermis, providing insights into its aggressive behavior and high-risk features. We performed high-depth whole-exome sequencing on 12 cSCC tissues, along with paired normal tissues from six patients, using microdissection techniques. The mutational analysis focused on identifying alterations enriched during cSCC progression. Gene Ontology enrichment analysis, immunohistochemical assays, and external single-cell RNA data were utilized for validation. A total of 8863 non-synonymous somatic mutations were identified in 4092 genes across the superficial and deep portions of cSCCs. Analysis of deep portion mutations revealed a significant correlation with gene ontology biological processes, particularly cell junction organization, and cell-cell adhesion. Clonal mutations in these processes were more prevalent in the deep portions, indicating their impact on the cSCC mutation landscape. Genetic evolution analysis identified 29 causal genes associated with dermal invasion in cSCC. We highlight somatic mutations in cSCC, revealing heterogeneity between superficial and deep regions. Altered genes in cell junction organization and cell-cell adhesion emerged as pivotal in dermal invasion. We identified 29 causal genes primarily in deep tumor regions. Our findings emphasize analyzing multiple tumor regions to capture varied mutational landscapes. These insights advance our understanding of cSCC progression, emphasizing genetic and cellular changes during tumor evolution., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Colloidal PbS quantum dot solar cells (QDSCs) have been primarily demonstrated in n-i-p structures by incorporating a solution-processed ZnO electron transporting layer (ETL). Nevertheless, the inherent energy barrier for the electron extraction at the ZnO/PbS junction along with the defective nature significantly diminishes the performance of the PbS QDSCs. In this study, by employing Sn-doped ZnO (ZTO) ETL, we have tuned the conduction band offset at the junction from spike-type to cliff-type so that the electron extraction barrier can be eliminated and the overall photovoltaic parameters can be enhanced (open-circuit voltage of 0.7 V, fill factor over 70%, and efficiency of 11.3%) as compared with the counterpart with the undoped ZnO ETL. The X-ray photoelectron spectroscopy (XPS) analysis revealed a mitigation of oxygen vacancies in the ZTO ETL of our PbS QDSCs. Our work signifies the importance of Sn doping into the conventional ZnO ETL for the superior electron extraction in PbS QDSCs.

Background: Alopecia, a benign dermatologic condition affecting both genders, particularly harms female patients due to psychosocial effects. Female pattern hair loss (FPHL), the primary cause of hair loss in women, lacks sufficient Korean epidemiological studies examining its psychosocial aspects., Objective: This study aimed to explore FPHL's psychosocial impacts, including quality of life (QoL), depression, anxiety, medical consumption, and hair loss factors in Korean women., Methods: A total of 202 patients with FPHL were interviewed using a validated questionnaire to assess the QoL, psychological impact, and pattern of medical consumption. The severity of hair loss was evaluated using the "basic and specific (BASP) classification" by dermatologists. The Hair-Specific Skindex-29 (HSS29) was used to assess the QoL and Beck depression inventory (BDI), Beck anxiety inventory (BAI) to evaluate psychological aspects, and medical expenses and the number of clinic visits to determine medical consumption., Results: The global HSS29 score of FPHL was 40.97±18.92, indicating a notable impact on QoL. The mean BDI and BAI scores were 14.47 and 10.06, respectively. In multivariable regression analysis, HSS29, BDI, and BAI scores were most affected by the severity of hair loss ( p <0.001)., Conclusion: FPHL damages the psychosocial aspects of patients, such as QoL, depression, and medical consumption, according to the severity of hair loss., Competing Interests: The authors have nothing to disclose., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Objectives: Clinical studies have suggested an association between migraine and the occurrence of Parkinson's disease (PD). However, it is unknown whether migraine affects PD risk. We aimed to investigate the incidence of PD in patients with migraine and to determine the risk factors affecting the association between migraine and PD incidence., Methods: Using the Korean National Health Insurance System database (2002-2019), we enrolled all Koreans aged ≥40 years who participated in the national health screening program in 2009. International Classification of Diseases (10th revision) diagnostic codes and Rare Incurable Diseases System diagnostic codes were used to define patients with migraine (within 12 months of enrollment) and newly diagnosed PD., Results: We included 214,193 patients with migraine and 5,879,711 individuals without migraine. During 9.1 years of follow-up (55,435,626 person-years), 1,973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were newly diagnosed with PD. Following covariate adjustment, patients with migraine showed a 1.35-fold higher PD risk than individuals without migraine. The incidence of PD was not significantly different between patients with migraine with aura and those without aura. In males with migraine, underlying dyslipidemia increased the risk of PD (p=0.012). In contrast, among females with migraine, younger age (<65 years) increased the risk of PD (p=0.038)., Conclusions: Patients with migraine were more likely to develop PD than individuals without migraine. Preventive management of underlying comorbidities and chronic migraine may affect the incidence of PD in these patients. Future prospective randomized clinical trials are warranted to clarify this association.

Competing Interests: The authors have nothing to disclose.

The adoption of dynamic mechanomodulation to regulate cellular behavior is an alternative to the use of chemical drugs, allowing spatiotemporal control. However, cell-selective targeting of mechanical stimuli is challenging due to the lack of strategies with which to convert macroscopic mechanical movements to different cellular responses. Here, we designed a nanoscale vibrating surface that controls cell behavior via selective repetitive cell deformation based on a poroelastic cell model. The vibrating indentations induce repetitive water redistribution in the cells with water redistribution rates faster than the vibrating rate; however, in the opposite case, cells perceive the vibrations as a one-time stimulus. The selective regulation of cell-cell adhesion through adjusting the frequency of nanovibration was demonstrated by suppression of cadherin expression in smooth muscle cells (fast water redistribution rate) with no change in vascular endothelial cells (slow water redistribution rate). This technique may provide a new strategy for cell-type-specific mechanical stimulation.

Alternative polyadenylation (APA) generates mRNA isoforms and diversifies gene expression. Here we report the discovery that the mTORC1 signaling pathway balances the expression of two Trim9/TRIM9 isoforms through APA regulation in human and mouse. We showed that CFIm components, CPSF6 and NUDT21, promote the short Trim9/TRIM9 isoform ( Trim9-S/TRIM9-S ) expression. In addition, we identified an evolutionarily conserved twin UGUA motif, UGUAYUGUA, in TRIM9-S polyadenylation site (PAS) that is critical for its regulation by CPSF6. We found additional CPSF6-regulated PASs with similar twin UGUA motifs in human and experimentally validated the twin UGUA motif functionality in BMPR1B , MOB4 , and BRD4-L . Importantly, we showed that inserting a twin UGUA motif into a heterologous PAS was sufficient to confer regulation by CPSF6 and mTORC1. Our study reveals an evolutionarily conserved mechanism to regulate gene isoform expression by mTORC1 and implicates possible gene isoform imbalance in cancer and neurological disorders with mTORC1 pathway dysregulation., Competing Interests: RH, AK, JM, VA, MM, HH No competing interests declared, (© 2023, Herron et al.)

Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, to address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed dedicated regression-based methods to analyse ribosome profiling and alternative polyadenylation data, and identified heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a translational controller of a specific mRNA regulon. We found that HNRNPC is downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3' untranslated region lengthening and, subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. In addition, the reduced expression of HNRNPC and its regulon is associated with the worse prognosis in breast cancer patient cohorts., (© 2023. The Author(s).)

Rationale: Near-infrared spectroscopy (NIRS) is a noninvasive bedside tool for monitoring regional cerebral oxygen saturation (rSO2). The sinus conversion of atrial fibrillation (AF) was shown to be responsible for increasing rSO2. However, the reason for this improvement has not yet been clearly explained., Patient Concerns: We report the case of a 73-year-old woman who underwent cardioversion during an off-pump coronary artery bypass under NIRS and live hemodynamic monitoring., Interventions: Unlike previous studies that failed to control and compare all conditions during procedures, this case showed real-time fluctuating hemodynamic and hematological values, such as hemoglobin (Hgb), central venous pressure (CVP), mean arterial pressure (MAP), cardiac index (CI), left ventricular end-diastolic pressure (LVEDP), and SVO2., Outcomes: The rSO2 increased immediately after cardioversion and decreased during the obtuse marginal (OM) graft and after AF was obtained. However, no other hemodynamic data showed the same or opposite directional changes in the rSO2., Lessons: Significant instantaneous changes were observed in rSO2 using NIRS after sinus conversion, without obvious hemodynamic alterations in the systemic circulation or other monitoring values., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

PELVIS syndrome describes the constellation of perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag. A 2-month-old girl presented with infantile hemangioma on her perineum and genitalia with imperforate anus, rectovaginal fistula and perineal skin tag at birth. Under the impression of PELVIS syndrome, consequential spinal sonography was conducted and revealed an intrasacral meningocele without clinical neurologic deficit. The anorectal malformation was surgically corrected, she was taking oral propranolol for the cutaneous lesion, and she showed improvement and no complications., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Bioactive peptides (BPs) are protein fragments that benefit human health. To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

A narrowed sacroiliac joint (SIJ) space has been considered to be a major morphologic parameter of ankylosing spondylitis (AS). Previous studies revealed that the sacroiliac joint thickness (SIJT) correlated with AS in patients. However, irregular narrowing is different from thickness. Thus, we devised a method using the sacroiliac joint cross-sectional area (SIJA) as a new morphological parameter for use in evaluating AS. We hypothesized that the SIJA is a key morphologic parameter in diagnosing AS. SIJ samples were collected from 107 patients with AS, and from 85 control subjects who underwent SIJ-view X-rays that revealed no evidence of AS. We measured the SIJT and SIJA at the SIJ margin on X-rays using our picture archiving and communications system. The SIJT was measured at the narrowest point between the sacrum and the ilium. The SIJA was measured as the entire cross-sectional joint space area of the SIJ in the X-ray images. The average SIJT was 3.09 ± 0.61 mm in the control group, and 1.59 ± 0.52 mm in the AS group. The average SIJA was 166.74 ± 39.98 mm2 in the control group, and 68.65 ± 24.11 mm2 in the AS group. AS patients had significantly lower SIJT (P < .001) and SIJA (P < .001) than the control subjects. Receiver operating characteristics curve analysis showed that the best cutoff point for the SIJT was 2.33 mm, with 92.5% sensitivity, 94.1% specificity, and an area under the curve of 0.97 (95% confidence interval: 0.95-0.99). The optimal cutoff point for the SIJA was 106.19 mm2, with 93.5% sensitivity, 95.3% specificity, and an area under the curve of 0.98 (95% confidence interval: 0.97-1.00). Although the SIJT and SIJA were both significantly associated with AS, the SIJA parameter was a more sensitive measurement. We concluded that the SIJA is an easy-to-use, fast, cheap, and useful new morphological parameter for predicting AS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To develop a facial growth prediction model incorporating individual skeletal and soft tissue characteristics., Materials and Methods: Serial longitudinal lateral cephalograms were collected from 303 children (166 girls and 137 boys), who had never undergone orthodontic treatment. A growth prediction model was devised by applying the multivariate partial least squares (PLS) algorithm, with 161 predictor variables. Response variables comprised 78 lateral cephalogram landmarks. Multiple linear regression analysis was performed to investigate factors influencing growth prediction errors., Results: Using the leave-one-out cross-validation method, a PLS model with 30 components was developed. Younger age at prediction resulted in greater prediction error (0.03 mm/y). Further, prediction error increased in proportion to the growth prediction interval (0.24 mm/y). Girls, subjects with Class II malocclusion, growth in the vertical direction, skeletal landmarks, and landmarks on the maxilla were associated with more accurate prediction results than boys, subjects with Class I or III malocclusion, growth in the anteroposterior direction, soft tissue landmarks, and landmarks on the mandible, respectively., Conclusions: The prediction error of the prediction model was proportional to the remaining growth potential. PLS growth prediction seems to be a versatile approach that can incorporate large numbers of predictor variables to predict numerous landmarks for an individual subject., (© 2022 by The EH Angle Education and Research Foundation, Inc.)

Nitric oxide (NO) has been shown to promote revascularization and nerve regeneration after peripheral nerve injury. However, in vivo application of NO remains challenging due to the lack of stable carrier materials capable of storing large amounts of NO molecules and releasing them on a clinically meaningful time scale. Recently, a silica nanoparticle system capable of reversible NO storage and release at a controlled and sustained rate was introduced. In this study, NO-releasing silica nanoparticles (NO-SNs) were delivered to the peripheral nerves in rats after acute crush injury, mixed with natural hydrogel, to ensure the effective application of NO to the lesion. Microangiography using a polymer dye and immunohistochemical staining for the detection of CD34 (a marker for revascularization) results showed that NO-releasing silica nanoparticles increased revascularization at the crush site of the sciatic nerve. The sciatic functional index revealed that there was a significant improvement in sciatic nerve function in NO-treated animals. Histological and anatomical analyses showed that the number of myelinated axons in the crushed sciatic nerve and wet muscle weight excised from NO-treated rats were increased. Moreover, muscle function recovery was improved in rats treated with NO-SNs. Taken together, our results suggest that NO delivered to the injured sciatic nerve triggers enhanced revascularization at the lesion in the early phase after crushing injury, thereby promoting axonal regeneration and improving functional recovery., Competing Interests: None

Food-derived bioactive peptides (BPs) have received considerable attention as postbiotics for human gut health. Here we used a genomics-based semirational approach to expand the postbiotic potential of collagen peptides (CPs) produced from probiotic fermentation. In silico digestion revealed distinct BPs embedded in fish collagen in a protease-dependent manner. Anaerobic digestion of collagen by representative Lactobacillaceae species revealed differential substrate utilization and collagen degradation patterns. Nanoliquid chromatography-mass spectrometry analysis of CPs showed that each species exhibited different cleavage patterns and unique peptide profiles. Remarkably, the 1-10 kDa CPs produced by Lacticaseibacillus paracasei showed agonistic activities toward G protein-coupled receptor 35 (GPR35). These CPs could repair intestinal epithelium through the GPR35-mediated extracellular signal-regulated protein kinase (ERK) 1/2 signaling pathway, suggesting that probiotic-aided collagen hydrolysates can serve as postbiotics for host-microbe interactions. Therefore, this study provides an effective strategy for the rapid screening of CPs for gut health in the gastrointestinal tract.

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 μm thick) were deposited onto poly- l -lactic acid (PLLA) substrates by DC magnetron sputtering, and a long-term immersion test using biodegradable hybrid materials was performed in phosphate-buffered solution (PBS) for 2 weeks. The concentrations of superoxide anions and hydrogen peroxide generated by the corrosion of biodegradable metallic films were monitored every 1 or 2 days. Both superoxide anions and hydrogen peroxide were seamlessly generated even after the complete consumption of the anodic Mg layer. It was confirmed that the superoxide anions and hydrogen peroxide were formed not only by the galvanic corrosion between the anode and cathode layers but also by the corrosion of a single Mg or Zn layer. The corrosion products of the Mg and Zn films in PBS were phosphate, oxide, or chloride of the biodegradable metals. Thus, it is concluded that ROS generation by the corrosion of PLLA-based hybrid materials can be sustained until the exhaustion of the cathode metal layer.

This study aimed to investigate the association between Bacille Calmette-Guérin (BCG) vaccination and nontuberculous mycobacterial pulmonary disease (NTM-PD). Patients in the prospective NTM-PD cohort were matched to healthy controls to measure the association between BCG and NTM-PD development. The clinical course of NTM-PD patients was also evaluated to investigate the association between BCG and NTM-PD progression. BCG scars were not associated with NTM-PD development (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 0.96-4.34) or progression (adjusted OR, 1.61; 95% CI, 0.92-2.81). In conclusion, BCG vaccination was not associated with the development or progression of NTM-PD., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Dexmedetomidine has sedative, sympatholytic, analgesic, and anti-inflammatory effects. We investigated the effects of intraoperative dexmedetomidine infusion without a loading dose in the prevention of pain and inflammation after laparoscopic hysterectomy. In this study, 100 patients undergoing laparoscopic hysterectomy under desflurane anesthesia were randomized to receive either 0.9% saline or dexmedetomidine (0.4 μg/kg/h) after induction to trocar removal. The primary endpoints were postoperative pain and inflammatory response presented by the level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-10, and C-reactive protein (CRP). The secondary endpoints were hemodynamics during the anesthesia and surgery and postoperative nausea and vomiting. Postoperative pain was decreased in the dexmedetomidine group for every time point, and post-anesthesia care unit (PACU) rescue fentanyl doses were decreased in the dexmedetomidine group. The inflammatory response representing TNF-α, IL-6, IL-10, and CRP were similar across the two groups. Postoperative nausea and vomiting from PACU discharge to 24 h post-surgery were reduced in the dexmedetomidine group. During anesthesia and surgery, the patient's heart rate was maintained lower in the dexmedetomidine-receiving group. Dexmedetomidine of 0.4 μg/kg/h given as an intraoperative infusion significantly reduced postoperative pain but did not reduce the inflammatory responses in patients undergoing laparoscopic hysterectomy.

Background/aims: The worldwide coronavirus disease 2019 pandemic has led endoscopists to use personal protective equipment (PPE) for infection prevention. This study aimed to investigate whether wearing a face shield as PPE affects the quality of colonoscopy., Methods: We reviewed the medical records and colonoscopy findings of patients who underwent colonoscopies at Asan Medical Center, Korea from March 10 to May 31, 2020. The colonoscopies in this study were performed by five gastroenterology fellows and four expert endoscopists. We compared colonoscopy quality indicators, such as withdrawal time, adenoma detection rate (ADR), mean number of adenomas per colonoscopy (APC), polypectomy time, and polypectomy adverse events, both before and after face shields were added as PPE on April 13, 2020., Results: Of the 1,344 colonoscopies analyzed, 715 and 629 were performed before and after the introduction of face shields, respectively. The median withdrawal time was similar between the face shield and no-face shield groups (8.72 minutes vs 8.68 minutes, p=0.816), as was the ADR (41.5% vs 39.8%, p=0.605) and APC (0.72 vs 0.77, p=0.510). Polypectomy-associated quality indicators, such as polypectomy time and polypectomy adverse events were also not different between the groups. Quality indicators were not different between the face shield and no-face shield groups of gastroenterology fellows, or of expert endoscopists., Conclusions: Colonoscopy performance was not unfavorably affected by the use of a face shield. PPE, including face shields, can be recommended without a concern about colonoscopy quality deterioration.

The American Society of Clinical Oncology and College of American Pathologists guidelines for HER2 testing in breast cancer (BC) have been updated with more stringent criteria regarding immunohistochemistry (IHC) 2 + interpretation. The aim of our study was to determine HER2 status in IHC 2 + cases based on 2013 and 2018 guidelines and to investigate specific histologic characteristics that might predict HER2 status in tumors with equivocal IHC staining. Two hundred eighty BC cases reported as IHC 2 + and 24 cases reported as non-IHC 2 + were reviewed with 12 histologic characteristics. Of the IHC 2 + cases based on 2013 guideline, 21% were reclassified to IHC 1 + when applying the 2018 guidelines. Consequently, it led to an 8% increase of HER2 amplification rate in 2018 IHC 2 + group. Seven characteristics were significantly associated with prediction of HER2 amplification in IHC 2 + BCs, including high tumor-infiltrating lymphocytes (TILs), distinct cellular membrane, no apical snout, large nuclear size, nuclear size variation, high nuclear grade, and tubule formation < 10%. Using these criteria, the presence of four or more characteristics significantly indicates HER2 amplification. Moreover, four characteristics among them, including high TILs, distinct cellular membrane, nuclear size variation, and high nuclear grade, were also associated with HER2 amplification in non-IHC 2 + cases, demonstrating their predictive value as complements to IHC. In conclusion, we provide specific morphologic features that will improve pathologist performance in identifying more HER2-positive BCs. We further suggest an algorithm for trastuzumab therapy decisions using a combination of histomorphologic evaluation and the updated 2018 guidelines., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To determine if an automated superimposition method using six landmarks (Sella, Nasion, Porion, Orbitale, Basion, and Pterygoid) would be more suitable than the traditional Sella-Nasion (SN) method to evaluate growth changes., Materials and Methods: Serial lateral cephalograms at an average interval of 2.7 years were taken on 268 growing children who had not undergone orthodontic treatment. The T1 and T2 lateral images were manually traced. Three different superimposition methods: Björk's structural method, conventional SN, and the multiple landmark (ML) superimposition methods were applied. Bjork's structural method was used as the gold standard. Comparisons among the superimposition methods were carried out by measuring the linear distances between Anterior Nasal Spine, point A, point B, and Pogonion using each superimposition method. Multiple linear regression analysis was performed to identify factors that could affect the accuracy of the superimpositions., Results: The ML superimposition method demonstrated smaller differences from Björk's method than the conventional SN method did. Greater differences among the cephalometric landmarks tested resulted when: the designated point was farther from the cranial base, the T1 age was older, and the more time elapsed between T1 and T2., Conclusions: From the results of this study in growing patients, the ML superimposition method seems to be more similar to Björk's structural method than the SN superimposition method. A major advantage of the ML method is likely to be that it can be applied automatically and may be just as reliable as manual superimposition methods., (© 2022 by The EH Angle Education and Research Foundation, Inc.)

Fibroma of the tendon sheath is a benign slow-growing fibrous tumor. Although rare, cases occurring in the upper extremities usually involve the fingers. It appears as a well-defined, roundor oval-shaped mass originating from the flexor tendon. Abundant fibrous stroma makes fibromas appear as a low intensity mass in all MRI sequences. Most of the fibromas manifest as painless soft tissue masses. Herein, we report a case of fibroma of the tendon sheath with an unusual clinical presentation, triggering carpal tunnel syndrome during wrist movement., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2021 The Korean Society of Radiology.)

Background: Chronic viral hepatitis is associated with a wide range of extrahepatic diseases; however, evidence on a link between chronic viral hepatitis and colorectal neoplasia is still lacking., Aims: To analyze the association between chronic viral hepatitis and prevalence of colorectal neoplasia., Methods: A systematic review of articles published in the MEDLINE, EMBASE, and Cochrane Library between 2000 and 2020 was performed. Subgroup analyses based on the types of colorectal neoplasia and the etiology of chronic viral hepatitis were conducted., Results: Twelve eligible studies with 48,428 hepatitis B virus (HBV) patients and 46,561 hepatitis C virus (HCV) patients were included. Chronic viral hepatitis was significantly associated with an increased risk of both colorectal adenoma (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.16-2.02; I 2  = 83%) and colorectal cancer (CRC) (OR, 1.32; 95% CI, 1.08-1.61; I 2  = 94%). The etiology of chronic viral hepatitis was an independent factor related to heterogeneity for CRC subgroup analysis revealed an increased risk of CRC in both HBV (OR, 1.18; 95% CI, 1.09-1.27; I 2  = 37%) and HCV (OR, 1.88; 95% CI, 1.78-1.97; I 2  = 0%). HCV was associated with an increased risk of colorectal adenoma (OR, 1.48; 95% CI, 1.22-1.79; I 2  = 0%); however, HBV was not associated with an increased risk of colorectal adenoma and had considerable heterogeneity (OR, 1.65; 95% CI, 0.88-3.09; I 2  = 90%)., Conclusion: Our meta-analysis showed that chronic viral hepatitis is associated with an increased risk of colorectal neoplasia. The strategy of stricter screening colonoscopy may benefit from patients with chronic viral hepatitis., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

DNA damage reshapes the cellular transcriptome by modulating RNA transcription and processing. In cancer cells, these changes can alter the expression of genes in the immune surveillance and cell death pathways. Here, we investigate how DNA damage impacts alternative polyadenylation (APA) using the PAPERCLIP technique. We find that APA shifts are a coordinated response for hundreds of genes to DNA damage, and we identify PCF11 as an important contributor of DNA damage-induced APA shifts. One of these APA shifts results in upregulation of the full-length MSL1 mRNA isoform, which protects cells from DNA damage-induced apoptosis and promotes cell survival from DNA-damaging agents. Importantly, blocking MSL1 upregulation enhances cytotoxicity of chemotherapeutic agents even in the absence of p53 and overcomes chemoresistance. Our study demonstrates that characterizing adaptive APA shifts to DNA damage has therapeutic implications and reveals a link between PCF11, the MSL complex, and DNA damage-induced apoptosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Acute severe lower gastrointestinal bleeding (LGIB) in patients with Crohn's disease (CD) is uncommon; however, it is a potentially life-threatening complication, and its recurrence is common. We thus aimed to identify the predictors for rebleeding in CD patients with acute severe LGIB and particularly focused on whether anti-tumor necrosis factor (TNF) therapy lowers the risk of rebleeding compared with conventional medical therapy (CMT) or surgery., Methods: The risk of rebleeding was analyzed in 131 CD patients with acute severe LGIB. Patients were classified into the CMT group (n = 99), anti-TNF therapy group (n = 22), and surgery group (n = 10). No patients in the surgery group received anti-TNF therapy., Results: During the median follow-up of 98 months after the first episode of acute severe LGIB, rebleeding occurred in 50.5%, 18.2%, and 30.0% of the CMT group, anti-TNF therapy group, and surgery group, respectively (P = 0.015). The cumulative risks of rebleeding at 1 and 10 years were 20.0% and 64.7% in the CMT group, 13.6% and 18.4% in the anti-TNF therapy group, and 0% and 40.7% in the surgery group, respectively (P = 0.020). Multivariable Cox regression analysis showed that anti-TNF therapy was associated with a lower risk of rebleeding compared with CMT (hazard ratio, 0.303; 95% confidence interval, 0.108-0.849; P = 0.023)., Conclusions: In CD patients with acute severe LGIB, anti-TNF therapy may reduce the risk of rebleeding compared with CMT. Although surgery is considered effective in preventing early rebleeding, concomitant anti-TNF therapy may be helpful in further lowering the long-term risk of rebleeding., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Acute severe lower gastrointestinal bleeding (LGIB) is an uncommon but challenging complication of Crohn's disease (CD)., Aim: To identify the predictors of acute severe LGIB and to evaluate the impact of acute severe LGIB on the subsequent clinical course in CD patients., Methods: A retrospective inception cohort study was conducted in 75 CD patients with acute severe LGIB and 1359 CD patients without acute severe LGIB who were diagnosed between February 1991 and November 2019 at Asan Medical Center, a tertiary university hospital in Korea. Multivariable analysis with Cox proportional hazard regression was performed to identify the risk factors for acute severe LGIB. A matched analysis using 72 patients with bleeding and 267 matched patients without within the cohort was also conducted to investigate whether acute severe LGIB is a predictor of clinical outcomes of CD., Results: Multivariable Cox regression analysis revealed that early use of thiopurines [hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.12-0.48; P < 0.001] and female sex (HR: 0.51, 95%CI: 0.27-0.94; P = 0.031) were significantly associated with a lower risk of acute severe LGIB. The cumulative risks of behavioral progression and intestinal resection were not significantly different between the two matched groups ( P = 0.139 and P = 0.769, respectively). The hospitalization rate was higher in the bleeding group than in the matched non-bleeding group (22.1/100 vs 13.2/100 patient-years; P = 0.012). However, if hospitalizations due to bleeding episodes were excluded from the analysis, the hospitalization rate was not significantly different between the bleeding group and the matched non-bleeding group (14.5/100 vs 13.2/100 patient-years; P = 0.631)., Conclusion: Early use of thiopurines may reduce the risk of acute severe LGIB. History of acute severe LGIB may not have a significant prognostic value in patients with CD., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interest related to the study., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear., Methods: A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed., Results: RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P <  0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P <  0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35-0.97, P <  0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81-2.26, P = 0.251)., Conclusions: Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.

Objectives: To compare an automated cephalometric analysis based on the latest deep learning method of automatically identifying cephalometric landmarks (AI) with previously published AI according to the test style of the worldwide AI challenges at the International Symposium on Biomedical Imaging conferences held by the Institute of Electrical and Electronics Engineers (IEEE ISBI)., Materials and Methods: This latest AI was developed by using a total of 1983 cephalograms as training data. In the training procedures, a modification of a contemporary deep learning method, YOLO version 3 algorithm, was applied. Test data consisted of 200 cephalograms. To follow the same test style of the AI challenges at IEEE ISBI, a human examiner manually identified the IEEE ISBI-designated 19 cephalometric landmarks, both in training and test data sets, which were used as references for comparison. Then, the latest AI and another human examiner independently detected the same landmarks in the test data set. The test results were compared by the measures that appeared at IEEE ISBI: the success detection rate (SDR) and the success classification rates (SCR)., Results: SDR of the latest AI in the 2-mm range was 75.5% and SCR was 81.5%. These were greater than any other previous AIs. Compared to the human examiners, AI showed a superior success classification rate in some cephalometric analysis measures., Conclusions: This latest AI seems to have superior performance compared to previous AI methods. It also seems to demonstrate cephalometric analysis comparable to human examiners., (© 2021 by the EH Angle Education and Research Foundation, Inc.)

We aimed to investigate the endoscopic features and clinical course of CMV gastroenterocolitis in immunocompetent patients. We reviewed the medical records and endoscopic images of 86 immunocompetent patients with CMV gastroenterocolitis. Immunocompetent patients were defined as those without congenital or acquired immunodeficiency syndrome, use of anti-cancer chemotherapeutic and immunosuppressive agents, and inflammatory bowel diseases. The mean age was 65.5 ± 11.8 years and 53 (61.6%) were male. Sixty-eight (79.1%) patients had comorbidities. Upper gastrointestinal-dominant, small bowel-dominant, and colon-dominant types were observed in 19, 7, and 60 patients, respectively. Endoscopic features could be classified into discrete ulcerative type with/without exudate and diffuse erythematous type with/without exudate. Antiviral treatment with ganciclovir was initiated in 51 patients (59.3%), 40 of whom improved and 1 improved after changing ganciclovir to foscarnet. Thirty-three patients (38.4%) improved without antiviral treatment. Surgery was necessary in two patients because of colon perforation before antiviral treatment. Another two patients underwent surgery because of sigmoid stricture and cecal perforation during antiviral treatment. Endoscopic type was not associated with clinical outcomes, such as surgery and death. CMV gastroenterocolitis in immunocompetent patients mostly occur in older patients with comorbidities, and the endoscopic features vary with no association with clinical outcomes.

Biodegradable electronics are disposable green devices whose constituents decompose into harmless byproducts, leaving no residual waste and minimally invasive medical implants requiring no removal surgery. Stretchable and flexible form factors are essential in biointegrated electronic applications for conformal integration with soft and expandable skins, tissues, and organs. Here a fully biodegradable MgZnCa metallic glass (MG) film is proposed for intrinsically stretchable electrodes with a high yield limit exploiting the advantages of amorphous phases with no crystalline defects. The irregular dissolution behavior of this amorphous alloy regarding electrical conductivity and morphology is investigated in aqueous solutions with different ion species. The MgZnCa MG nanofilm shows high elastic strain (≈2.6% in the nano-tensile test) and offers enhanced stretchability (≈115% when combined with serpentine geometry). The fatigue resistance in repeatable stretching also improves owing to the wide range of the elastic strain limit. Electronic components including the capacitor, inductor, diode, and transistor using the MgZnCa MG electrode support its integrability to transient electronic devices. The biodegradable triboelectric nanogenerator of MgZnCa MG operates stably over 50 000 cycles and its fatigue resistant applications in mechanical energy harvesting are verified. In vitro cell toxicity and in vivo inflammation tests demonstrate the biocompatibility in biointegrated use., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Aims: To investigate the added value of endoscopic ultrasound (EUS) with computed tomography (CT) in distinguishing heterotopic pancreas (HP) from other pathologies, when gastroduodenal subepithelial tumors (SETs) are suspected on an upper endoscopic examination., Material and Methods: We retrospectively included 54 consecutive patients with gastroduodenal SETs who had undergone both abdominal CT and EUS within a 3-month interval. All EUS, endoscopy, and CT images were reviewed and evaluated in a blinded manner by an endoscopist and a radiologist, respectively. Univariate and multivariate analyses were performed to identify EUS/CT findings related to HP. Diagnostic performance of CT only and CT combined with EUS was compared for distinguishing HP from other SETs., Results: We included patients with HP (n=17; pathologically confirmed, n=6), gastrointestinal stromal tumor (GIST, n=24), and other pathologies (n=13). Multivariate logistic regression analyses revealed that irregular margin, origin from submucosal layer, internal microcystic-tubular structure, and oval shape were independent factors in diagnosing HP by EUS, whereas a micro-lobulating contour was the only significantly independent factor in CT. In assessments of diagnostic performance, CT combined with EUS showed significantly superior diagnostic performance in comparison with CT only (area under the curve, 0.961 vs. 0.833, p=0.028) in the consensus interpretation of an endoscopist and a radiologist., Conclusions: CT combined with EUS with a comprehensive and complementary interpretation showed significant added value compared to CT only in diagnosing gastroduodenal HP.

Background and Purpose: The predictors of progressive motor deficits in acute subcortical infarctions are still controversial. It is not known whether glycemic control influences on stroke progression., Methods: A total of 268 consecutive patients with diabetes or prediabetes who had acute (< 24 h) subcortical infarction were enrolled. (1) All patients were divided into 4 groups by quartile of glycated hemoglobin (HbA1c). (2) Only the patients with diabetes were divided by effective glycemic control. Progressive motor deficits were prospectively captured and defined as an increase of motor score ≥ 1 on the upper or lower limb items of the National Institute of Health Stroke Scale within 72 h from stroke onset., Results: Progressive motor deficits occur in 8/78 (10.3%) for ≤ 5.9, 15/61 (24.6%) for 6.0-6.4, 16/62 (25.8%) for 6.5-7.4, and 30/67 (44.8%) for ≥ 7.5. In diabetic patients alone, those occur in 5/37 (13.5%) for ≤ 6.5, 10/42 (23.8%) for 6.6-7.0, 12/42 (28.6%) for 7.1-8.0, and 24/50 (48.0%) for ≥ 8.1. An adjusted OR of progressive motor deficits was 2.61 (95% confidence interval [CI] 0.98-7.00, P = .056) for 6.0-6.4, 3.42 (95% CI 1.27-9.18, P = .015) for 6.5-7.4, and 6.65 (95% CI 2.38-18.62, P < .001) for ≥ 7.5. In diabetic patients alone, those were 3.15 (95% CI 0.89-11.15, P = .075) for 6.6-7.0, 2.90 (95% CI 0.79-10.61, P = .107) for 7.1-8.0, and 4.17 (95% CI 1.07-16.25, P = .038) for ≥ 8.1. The optimal cutoff value of HbA1c was 6.65% in discriminating progressive motor deficits., Conclusion: Increased HbA1c was associated with higher incidence of progressive motor deficits in acute subcortical infarction with diabetes and prediabetes.

The ability to generate cell-type specific mRNA polyadenylation (pA) maps from complex tissues is crucial for understanding how alternative polyadenylation (APA) is regulated in individual cell types in their physiological environment under different conditions. In this chapter, we discuss cTag-PAPERCLIP, a recently developed method combining the well-established CLIP (crosslinking immunoprecipitation) technique and the Cre-lox system to achieve customized cell-type specific APA profiling from mouse tissue without cell purification or enrichment. In cTag-PAPERCLIP, selective expression of GFP-tagged poly(A) binding protein (PABP-GFP) in the desired cell type is achieved through Cre-mediated activation of a latent knock-in allele of PABP-GFP. Immunoprecipitation of PABP-GFP then allows mRNA 3' end fragments in the desired cell type to be specifically retrieved from ultraviolet (UV)-irradiated whole tissue lysate. The mRNA fragments are subsequently turned into a cDNA library to provide a comprehensive APA map and an mRNA expression profile of the chosen cell type through deep sequencing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sex-determining region Y-box 2 (SOX2) is a transcriptional factor that drives embryonic stem cells to neuroendocrine cells in lung development and is highly expressed in small-cell lung cancer (SCLC). However, the prognostic role of SOX2 and its relationship with tumor-infiltrating lymphocytes (TILs) has not been determined in SCLC. Herein, we assessed the expression of SOX2 and CD8+ TILs to obtain insights into the prognostic role of SOX2 and CD8+ TILs in limited-stage (LS)-SCLC., Methods: A total of 75 patients with LS-SCLC was enrolled. The SOX2 expression and CD8+ TILs were evaluated by immunohistochemistry., Results: High SOX2 and CD8+ TIL levels were identified in 52 (69.3%) and 40 (53.3%) patients, respectively. High SOX2 expression was correlated with increased density of CD8+ TILs (p = 0.041). Unlike SOX2, high CD8+ TIL numbers were associated with significantly longer progression-free survival (PFS; 13.9 vs. 8.0 months, p = 0.014). Patients with both high SOX2 expression and CD8+ TIL numbers (n = 29, 38.7%) had significantly longer PFS and overall survival (OS) compared to those from the other groups (median PFS 19.3 vs. 8.4 months; p = 0.002 and median OS 35.7 vs. 17.4 months; p = 0.004, respectively). Multivariate Cox regression analysis showed that the combination of high SOX2 expression and CD8+ TIL levels was an independent good prognostic factor for OS (HR = 0.471, 95% CI, 0.250-0.887, p = 0.02) and PFS (HR = 0.447, 95% CI, 0.250-0.801, p = 0.007) in SCLC., Conclusions: Evaluation of the combination of SOX2 and CD8+ TIL levels may be of a prognostic value in LS-SCLC., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objectives: To determine the optimal quantity of learning data needed to develop artificial intelligence (AI) that can automatically identify cephalometric landmarks., Materials and Methods: A total of 2400 cephalograms were collected, and 80 landmarks were manually identified by a human examiner. Of these, 2200 images were chosen as the learning data to train AI. The remaining 200 images were used as the test data. A total of 24 combinations of the quantity of learning data (50, 100, 200, 400, 800, 1600, and 2000) were selected by the random sampling method without replacement, and the number of detecting targets per image (19, 40, and 80) were used in the AI training procedures. The training procedures were repeated four times. A total of 96 different AIs were produced. The accuracy of each AI was evaluated in terms of radial error., Results: The accuracy of AI increased linearly with the increasing number of learning data sets on a logarithmic scale. It decreased with increasing numbers of detection targets. To estimate the optimal quantity of learning data, a prediction model was built. At least 2300 sets of learning data appeared to be necessary to develop AI as accurate as human examiners., Conclusions: A considerably large quantity of learning data was necessary to develop accurate AI. The present study might provide a basis to determine how much learning data would be necessary in developing AI., (© 2020 by The EH Angle Education and Research Foundation, Inc.)

Aims: Histology-based tumour microenvironment (TME) scores are useful in predicting the prognosis of gastrointestinal cancer. However, their prognostic roles in distal bile duct cancer (DBDC) have not been previously studied. This study aimed to evaluate the prognostic significance of the TME scores using the Klintrup-Mäkinen (KM) grade, tumour stroma percentage (TSP) and the Glasgow microenvironment score (GMS) in resected DBDC., Methods and Results: Eighty-one patients with DBDC who underwent curative resection were enrolled. DBDC was graded according to KM grade, TSP and GMS. A high KM grade was found in 19 patients (24%) and a high TSP was found in 47 patients (58%). A high TSP was significantly correlated with a low KM grade (P < 0.001). The distribution of the GMS, which was developed by combining the KM grade and TSP, was as follows: 0 (n = 19, 24%), 1 (n = 19, 24%) and 2 (n = 43, 52%). A low KM grade, high TSP and high GMS were significantly associated with short overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P < 0.001). Furthermore, multivariate analysis showed that a low KM grade [hazard ratio (HR) = 3.826; confidence interval (CI) = 1.650-8.869; P = 0.014], high TSP (HR = 2.193; CI = 1.173-4.100, P = 0.002) and high GMS (HR = 7.148; CI = 2.811-18.173) were independent prognostic factors for short RFS; a low KM grade (HR = 4.324; CI = 1.594-11.733) and high GMS (HR = 6.332; CI = 2.743-14.594) were independent prognostic factors for short OS., Conclusion: Histology-based TME scores, including the KM grade, TSP and GMS, are useful for predicting the survival of patients with resected DBDC., (© 2020 John Wiley & Sons Ltd.)

Rationale: IgG4-related disease (IgG4-RD) is a systemic disease that can involve various organs and is characterized by the infiltrations of IgG4-positive plasma cells and lymphocytes, fibrosis, and elevated serum IgG4 levels. IgG4-related sclerosing cholangitis (IgG4-RSC) is a subtype of IgG4-RD. No certain relationship between IgG4-RSC and cholangiocarcinoma has been established as yet, and there have been few reports of the simultaneous diagnosis of IgG4-RSC and cholangiocarcinoma., Patient Concerns: A 76-year-old male visited our gastroenterology department due to the recent occurrence of pruritus and jaundice., Diagnosis: Computed tomography (CT) scan showed ductal wall swelling and enhancement from both intrahepatic duct confluence to the common bile duct, upper biliary dilatation, and accompanying autoimmune pancreatitis (a sub type of IgG4-RD). Biopsy of the distal common bile duct by endoscopic retrograde cholangiopancreatography (ERCP) resulted in a diagnosis of IgG4-RSC. Subsequently, adenocarcinoma was identified by repeated cytology of bile juice. Finally, Klatskin tumor type IIIA and IgG4-RSC were concurrently diagnosed., Interventions: IgG4-RSC was treated with steroid and Klatskin tumors by gemcitabine + cisplatin chemotherapy., Outcomes: The jaundice had improved and CT showed substantial improvement of the intrahepatic duct dilatation., Lessons: IgG4-RSC and cholangiocarcinoma are easily confused, but their treatments are quite different, and thus, care must be taken during diagnosis. Furthermore, these 2 diseases may co-exist. Therefore, even if IgG4-RSC is diagnosed first, the possibility of accompanying cholangiocarcinoma should be thoroughly investigated.

CD8+ tumor-infiltrating lymphocytes (TILs) play a major role in antitumor immunity. High endothelial venules (HEVs) are related to diverse immune cells in solid tumors. We analyzed CD8+ and Foxp3+ TILs in combination with HEVs to determine their prognostic role in advanced gastric cancer (AGC). We enrolled 157 patients with AGC in this study. The densities of CD8+ TILs and Foxp3+ TILs were calculated using immunohistochemical staining. HEVs were evaluated by MECA-79 expression. HEVs were identified in 60 (38.2%) cases and was significantly associated with an increased number of CD8+ TILs ( p = 0.027) but not of Foxp3+ TILs ( p = 0.455) and CD20+ TILs ( p = 0.163). A high CD8+/HEV+ level was significantly associated with nodal metastasis ( p = 0.048). In survival analysis, patients with high CD8+/HEV+ levels demonstrated the longest overall survival (OS) ( p = 0.015). Furthermore, a high CD8+/HEV+ level was an independent prognostic factor in AGC ( p = 0.011; hazard ratio (HR) = 0.435; 95% confidence interval (CI) = 0.245-0.837). HEVs were found to play an important role in antitumor immunity associated with CD8+ TILs in AGC. This analysis of HEVs and CD8+ TILs helps stratify patients with AGC and sheds light on tumor immunity.

Small dense low-density lipoprotein (sdLDL) is a distinct low-density lipoprotein (LDL) cholesterol subclass that has been reported to be associated with metabolic disease. On the other hand, the relationship between the sdLDL level and the nonalcoholic fatty liver disease (NAFLD) severity is unclear. In this study, the sdLDL level was measured in patients with NAFLD to assess its potential as a biomarker for evaluating NAFLD. One hundred and twenty-six patients diagnosed with NAFLD at a single referral hospital from January 2018 to August 2019 were enrolled. The lipoprotein profile was analyzed from a blood test of NAFLD patients, and transient elastography (TE, Fibroscan) was performed to evaluate the degree of NAFLD. Among the 126 patients, 83 patients that could confirm the lipoprotein profile and TE results were finally enrolled in the study. The controlled attenuation parameter (CAP) value obtained from TE did not show any correlation with the total cholesterol, LDL. But, the sdLDL level showed a significant positive correlation with the CAP value (r = 0.237, P = .031), and the sdLDL/LDL ratio also showed a significant positive correlation with the CAP value (r = 0.235, P = .032). The liver stiffness (LS) measured by TE and the sdLDL level were positively correlated in patients with NAFLD (rho = 0.217, P = .049). The sdLDL/LDL ratio also showed a significant positive correlation with the LS value (rho = 0.228, P = .038). In addition, the fatty liver index also showed a significant positive correlation with the sdLDL/LDL ratio (r = 0.448, P = .000). In this study, the sdLDL level measured by a blood test of NAFLD patients showed a positive correlation with the CAP value and LS, which indicate the degree of hepatic steatosis and fibrosis. These results suggest the possibility of the sdLDL level as a new biomarker of NAFLD, but further studies will be needed to support these results.

Objectives: To evaluate a new superimposition method compatible with computer-aided cephalometrics and to compare superimposition error to that of the conventional Sella-Nasion (SN) superimposition method., Materials and Methods: A total of 283 lateral cephalometric radiographs were collected and cephalometric landmark identification was performed twice by the same examiner at a 3-month interval. The second tracing was superimposed on the first tracing by both the SN superimposition method and the new, proposed method. The proposed method not only relied on SN landmarks but also minimized the differences between four additional landmarks: Porion, Orbitale, Basion, and Pterygoid. The errors between the landmarks of the duplicate tracings oriented by the two superimposition methods were calculated at Anterior Nasal Spine, Point A, Point B, Pogonion, and Gonion. The paired t-test was used to find any statistical difference in the superimposition errors by the two superimposition methods and to investigate whether there existed clinically significant differences between the two methods., Results: The proposed method demonstrated smaller superimposition errors than did the conventional SN superimposition method. When comparisons between the two superimposition methods were made with a 1-mm error range, there were clinically significant differences between them., Conclusions: The proposed method that was compatible with computer-aided cephalometrics might be a reliable superimposition method for superimposing serial cephalometric images., (© 2020 by The EH Angle Education and Research Foundation, Inc.)

After endoscopic resection (ER) of gastric dysplasia, metachronous gastric neoplasm (MGN) appears to have an incidence rate similar to that detected after ER of early gastric cancer (EGC). We investigated whether the risk of MGN after ER for gastric dysplasia is different between patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Between March 2011 and December 2016, 198 patients with LGD (LGD group) and 46 patients with HGD (HGD group) who underwent ER were included in the study. During a median follow-up of 2.5 years, MGNs developed in 21 patients (10.6%) in the LGD group and in 6 patients (13.0%) in the HGD group. Hazard ratios (HRs) for MGNs (HR, 1.45; P = 0.425) and for metachronous HGD or gastric cancer (HR, 2.41; P = 0.214) in the HGD group were not different than those of the LGD group. However, considering patients without Helicobacter pylori infection, those in the HGD group had a significantly increased risk of metachronous HGD or gastric cancer compared to those in the LGD group (HR in HGD-group, 5.23; P = 0.044). These results indicate that meticulous surveillance endoscopy is needed to detect MGNs after ER of gastric dysplasia, especially in patients with HGD, including those without H. pylori infection.

Objectives: To compare detection patterns of 80 cephalometric landmarks identified by an automated identification system (AI) based on a recently proposed deep-learning method, the You-Only-Look-Once version 3 (YOLOv3), with those identified by human examiners., Materials and Methods: The YOLOv3 algorithm was implemented with custom modifications and trained on 1028 cephalograms. A total of 80 landmarks comprising two vertical reference points and 46 hard tissue and 32 soft tissue landmarks were identified. On the 283 test images, the same 80 landmarks were identified by AI and human examiners twice. Statistical analyses were conducted to detect whether any significant differences between AI and human examiners existed. Influence of image factors on those differences was also investigated., Results: Upon repeated trials, AI always detected identical positions on each landmark, while the human intraexaminer variability of repeated manual detections demonstrated a detection error of 0.97 ± 1.03 mm. The mean detection error between AI and human was 1.46 ± 2.97 mm. The mean difference between human examiners was 1.50 ± 1.48 mm. In general, comparisons in the detection errors between AI and human examiners were less than 0.9 mm, which did not seem to be clinically significant., Conclusions: AI showed as accurate an identification of cephalometric landmarks as did human examiners. AI might be a viable option for repeatedly identifying multiple cephalometric landmarks.