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The fourth KSTAR campaign in 2011 concentrated on active edge-localized mode (ELM) control by various methods such as non-axisymmetric magnetic perturbations, supersonic molecular beam injection (SMBI), vertical jogs of the plasma column and edge electron heating. The segmented in-vessel control coil (IVCC) system is capable of applying n2 perturbed field with different phasing among top, middle and bottom coils. Application of an n=1 perturbed field showed a desirable ELM suppression result. Fast vertical jogs of the plasma column achieved ELM pace-making and ELMs locked to 50Hz vertical jogs were observed with a high probability of phase locking. A newly installed SMBI system was used for ELM control and the state of mitigated ELMs was sustained by the optimized repetitive SMBI pulse for a few tens of ELM periods. A change in ELM behaviour was seen due to edge electron heating although the effect of ECH launch needs supplementary analyses. The ECEI images of suppressed/mitigated ELM states showed apparent differences when compared with natural ELMy states. Further analyses are ongoing to explain the observed ELM control results. © 2012 IAEA, Vienna.

We previously reported that a novel alkylphospholipid type antitumor agent edelfosine (ET-18-O-CH3 ; 1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine) induced apoptosis in human breast epithelial cells transfected with the H-ras oncogene (MCF10A-ras) which was causally linked to cyclooxygenase-2 (COX-2) up-regulation and production of 15-deoxy-Delta 12,14-prostaglandins J2 (15d-PGJ2). ET-18-O-CH3 treatment also enhanced the production of prostaglandin E2 (PGE2), a major COX-2 product. In this study, we found that ET-18-O-CH3 treatment resulted in elevated mRNA expression of the PGE2 receptor subunit, EP2 receptor. Exogenously added PGE2 inhibited the growth of MCF10A-ras cells and induced proteolytic cleavage of caspase 3. ET-18-O-CH3 also inhibited constitutive activation of ERK1/2, p38 MAPK, and Akt/protein kinase B, which was blunted by a selective COX-2 inhibitor SC58635. In addition, ET-18-O-CH3 inhibited DNA binding activity of NF-kappa B in MCF10A-ras cells, and this was again attenuated by SC58635. Based on these findings, it is likely that ET-18-O-CH3 inactivates ERK1/2, Akt, and NF-kappaB signaling via COX-2 induction in MCF10A-ras cells, thereby inducing apoptosis of these cells. [ABSTRACT FROM AUTHOR]

Background/aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them., Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness., Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4., Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Background/aims: Chicago classification version 4.0 enhances the diagnosis of esophageal motility disorders using position change and provocative tests such as multiple rapid swallows and a rapid drink challenge. This study investigates the diagnostic role of the rapid drink challenge based on Chicago classification 4.0 using a functional luminal imaging probe to estimate the cutoff value., Methods: This study included 570 patients who underwent esophageal manometry with a rapid drink challenge between January 2019 and October 2022. The diagnostic flow was analyzed according to Chicago classification 4.0., Results: Ninety-nine patients (38, achalasia; 11, esophagogastric junction outflow obstruction; 7, ineffective esophageal motility; 1, hypercontractile esophagus; and 42, normal esophageal function) failed the rapid drink challenge. Among the 453 participants, 50 and 86 were diagnosed with achalasia and esophagogastric junction outflow obstruction, respectively, using Chicago classification 4.0. In 249/453 (55.0%) patients initially diagnosed with esophagogastric junction outflow obstruction using Chicago classification 3.0, the diagnosis was changed to achalasia (n = 28), hypercontractile esophagus (n = 7), ineffective esophageal motility (n = 7), or normal esophageal function (n = 121) using Chicago classification 4.0. Rapid drink challenge-integrated relaxation pressure's diagnostic cutoff value was 19 mmHg. Nine patients had diagnoses changed after the rapid drink challenge, including 3 with panesophageal pressurization., Conclusions: Chicago classification 4.0 increased the diagnostic yield of the rapid drink challenge by 2.0% (9/453 patients). However, the rapid drink challenge had a failure rate of 17.9% (99/552 patients). Given the relatively low diagnostic yield and high failure rate of the rapid drink challenge, we recommend adopting an individualized approach to manometry.

Background/aims: The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE. Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established. This study aims to establish these thresholds for the first time among Asian patients with EoE., Methods: Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 and November 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index., Results: Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively ( P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology were available for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold (sensitivity, 0.95; specificity, 0.88; Youden index, 0.83)., Conclusions: The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3, respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. Cyclooxygenase-2 (COX-2) is a key enzyme involved in inflammatory signaling. While being transiently upregulated upon inflammatory stimuli, COX-2 has been found to be consistently overexpressed in human colorectal cancer and several other malignancies. The association between chronic inflammation and cancer has been revisited: cancer can arise when inflammation fails to resolve. Besides its proinflammatory functions, COX-2 also catalyzes the production of pro-resolving as well as anti-inflammatory metabolites from polyunsaturated fatty acids. This may account for the side effects caused by long term use of some COX-2 inhibitory drugs during the cancer chemopreventive trials. This review summarizes the latest findings highlighting the dual functions of COX-2 in the context of its implications in the development, maintenance, and progression of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: The co-occurrence of amyloid-β pathology in Parkinson's disease (PD) is common; however, the role of amyloid-β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD., Methods: Ninety-six patients with PD who underwent 18 F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan., Results: The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa-induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group., Conclusions: These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Military-civilian partnerships (MCP) provide a bidirectional exchange of information and trauma best practices. In 2021, Penn Presbyterian Medical Center and the U.S. Navy signed a 3-year memorandum of understanding to embed active duty trauma providers into the Trauma Division to facilitate the training and sustainment of combat casualty care (CCC) skills. To date, there is little evidence to demonstrate the efficacy of military-civilian partnerships in maintaining combat casualty readiness in non-physician trauma providers., Methods: We evaluated the impact of combat casualty readiness for non-physician providers by mapping clinical experiences in an urban Level I trauma center against the Defense Health Agency's Joint Trauma Systems (JTS) Clinical Practice Guidelines (CPG). The JTS CPGs provide best practices for CCCand highlight the critical skills providers need to know before deploying to an austere environment. Patient acuity data and specific JTS CPG skills performed by a non-physician providers were collected in their respective specialties for each patient seen between January 2023 to January 2024. Analyses were performed using descriptive statistics via Redcap., Results: A sample of 6 Navy personnel in different specialties: 1 Physician Assistant, 3 Registered Nurses (emergency medicine, perioperative, critical care), and 2 corpsmen (scrub tech and search & rescue/prehospital medic) completed 1299 records on patients treated. In all, 685 (52.7%) were trauma patients and 614 (47.3%) were non-trauma patients. Categories of injuries seen, listed from the most frequent to the least, were as follows: Other (764), Falls (250), Motor Vehicle Crashes (164), Gunshot Wound (126), Stab-related injuries (41). Category 1 skills, defined as "essential to know," were performed in 921 (36.1%) of the patients treated. In Category 2, skills described as "important to know" were performed in 889 (34.8%) of the patients treated. Category 3 skills, identified as "less urgent" as they are rare among trauma patients, were performed in 486 (19.0%) of the patients treated, and 252 (9.8%) required none of the JTS CPG skills. These categories were further broken down based on the frequency of the skills performed. Analysis revealed strengths and identified opportunities to direct clinical experience for underperforming skills., Conclusion: Military-civilian partnerships support CCC readiness. The data presented and the continuation of mapping personnel's clinical experience to military CPGs can gauge readiness in non-physician trauma providers. Notably, several skills in each category were identified as opportunities to modify the clinical exposure of the military provider. These findings indicate that modifications in clinical assignments could enhance active duty combat casualty readiness in these critical skills., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The objectives of this study were to investigate the variable factors associated with cognitive function and cortical atrophy and estimated variable importance of those factors in affecting cognitive function and cortical atrophy in patients with EOAD and LOAD. Patients with EOAD (n = 40), LOAD (n = 34), and healthy volunteers with normal cognition were included (n = 65). All of them performed 3T MRI, [ 18 F]THK5351 PET (THK), [ 18 F]flutemetamol PET (FLUTE), and detailed neuropsychological tests. To investigate factors associated with neuropsychological test results and cortical thickness in each group, we conducted multivariable linear regression models, including amyloid, tau, cerebral small vessel disease markers on MRI, and vascular risk factors. Then, we estimated variable importance in associating cognitive functions and cortical thickness, using relative importance analysis. In patients with EOAD, global THK retention was the most important contributor to the model variances for most neuropsychological tests, except for memory. However, in patients with LOAD, multiple contributors beyond tau were important in explaining variance of neuropsychological tests. In analyses with mean cortical thickness, global THK retention was the main contributor in patients with EOAD, while in LOAD patients, multiple factors contributed equally to mean cortical thickness. Therefore, EOAD and LOAD may have different pathomechanistic courses., (© 2024. The Author(s).)

Background: With the increasing resistance to antimicrobial agents, susceptibility-guided tailored therapy has been emerging as an ideal strategy for Helicobacter pylori treatment. However, susceptibility-guided tailored therapy requires additional cost, time consumption, and invasive procedure (endoscopy) and its superiority over empirical quadruple therapy as the first-line H. pylori treatment remains unclear., Aims: To compare the efficacy of culture-based susceptibility-guided tailored versus empirical concomitant therapy as the first-line Helicobacter pylori treatment., Methods: This open-label, randomized trial was performed in four Korean institutions. A total of 312 Patients with H. pylori-positive culture test and naïve to treatment were randomly assigned in a 3:1 ratio to either culture-based susceptibility-guided tailored therapy (clarithromycin-based or metronidazole-based triple therapy for susceptible strains or bismuth quadruple therapy for dual-resistant strains, n = 234) or empirical concomitant therapy (n = 78) for 10 days. Eradication success was evaluated by 13 C-urea breath test at least 4 weeks after treatment., Results: Prevalence of dual resistance to both clarithromycin and metronidazole was 8%. H. pylori eradication rates for tailored and concomitant groups were 84.2% and 83.3% by intention-to-treat analysis (p = 0.859), respectively, and 92.9% and 91.5% by per-protocol analysis, respectively (p = 0.702), which were comparable between the two groups. However, eradication rates for dual-resistant strains were significantly higher in the tailored group than in the concomitant group. All adverse events were grade 1 or 2 based on the Common Terminology Criteria for Adverse Events and the incidence was significantly lower in the tailored group. The proportion of patients discontinuing treatment for adverse events was comparable between the two groups (2.1% vs. 2.6%)., Conclusions: The culture-based susceptibility-guided tailored therapy failed to show superiority over the empirical concomitant therapy in terms of eradication rate. Based on these findings, the treatment choice in clinical practice would depend on the background rate of antimicrobial resistance, availability of resources and costs associated with culture and susceptibility testing., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to -25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Olfactory dysfunction or dysautonomia is one of the earliest prodromal nonmotor symptoms of Parkinson's disease (PD). We aimed to investigate whether PD patients with dysautonomia and hyposmia at the de novo stage present different prognoses regarding PD dementia (PDD) conversion, motor complication development, and change in levodopa-equivalent doses (LED)., Methods: In this retrograde cohort study, we included 105 patients with newly diagnosed PD patients who underwent cross-cultural smell identification test (CC-SIT), autonomic function tests (AFT), and dopamine transporter (DAT) scan at the de novo stage. PD patients were divided into Hyposmia + /Dysautonomia + (H + /D +) and Hyposmia - /Dysautonomia - (H - /D -) groups depending on the result of AFT and CC-SIT. Baseline clinical, cognitive, imaging characteristics, longitudinal risks of PDD development and motor complication occurrence, and longitudinal LED changes were compared between the two groups., Results: When compared with the H - /D - group, the H + /D + group showed lower standardized uptake value ratios in all subregions, lower asymmetry index, and steeper ventral - dorsal gradient in the DAT scan. The H + /D + group exhibited poorer performance in frontal/executive function and a higher risk of PDD development. The risk of motor complications including levodopa-induced dyskinesia, wearing off, and freezing of gait, was comparable between the two groups. The analysis of longitudinal changes in LED using a linear mixed model showed that the increase of LED in the H + /D + group was more rapid., Conclusions: Our results suggest that PD patients with dysautonomia and hyposmia at the de novo stage show a higher risk of PD dementia conversion and rapid progression of motor symptoms., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Alzheimer's disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research., Materials and Methods: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [ 18 F]THK5351 and [ 18 F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests., Results: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD., Conclusion: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown., Methods: In this retrospective cohort study, we enrolled 113 patients who underwent 18 F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive 18 F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region., Results: More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia., Discussion: Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection. Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence., Methods: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. Of these patients, 112 without any information about Helicobacter pylori infection status, 164 who underwent APC for salvage therapy, 5 with high-grade dysplasia, and 12 with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed., Results: A total of 618 patients with LGD (median age, 64 years) were followed up for a median of 30 months, and local recurrence has happened in 21 (3.4%) patients. Multivariate analysis showed that lesion size (hazard ratio, 1.06; 95% confidential interval, 1.01-1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 (2.6%) cases, and local recurrence was found in 7 (9.5%) cases of 109 tumors larger than 10 mm (P < .004)., Conclusions: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of endoscopic resection. However, when a lesion is larger, APC should be selected carefully with close monitoring., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024. Published by Elsevier Inc.)

This study investigates the applicability of six transition metal dichalcogenides to efficient therapeutic drug monitoring of ten antiepileptic drugs using laser desorption/ionization-mass spectrometry. We found that molybdenum ditelluride and tungsten ditelluride are suitable for the sensitive quantification of therapeutic drugs. The contribution of tellurium to the enhanced efficiency of laser desorption ionization was validated through theoretical calculations utilizing an integrated model that incorporates transition-metal dichalcogenides and antiepileptic drugs. The results of our theoretical calculations suggest that the relatively low surface electron density for the tellurium-containing transition metal dichalcogenides induces stronger Coulombic interactions, which results in enhanced laser desorption and ionization efficiency. To demonstrate applicability, up to 120 patient samples were analyzed to determine drug concentrations, and the results were compared with those of immunoassay and liquid chromatography-tandem mass spectrometry. Agreements among these methods were statistically evaluated using the Passing-Bablok regression and Bland-Altman analysis. Furthermore, our method has been shown to be applicable to the simultaneous detection and multiplexed quantification of antiepileptic drugs.

Background: Postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) is commonly observed after performing endoscopic submucosal dissection (ESD) for esophageal neoplasia. However, data on the incidence and risk factors for PEECS in the esophagus are lacking due to an unclear definition of PEECS and varied clinical settings. Therefore, we aimed to determine the risk factors for PEECS in patients undergoing ESD for esophageal neoplasia., Methods: We retrospectively reviewed data of relevant clinical and endoscopy-specific parameters from 202 consecutive patients with esophageal neoplasias (139 carcinomas and 63 dysplasias) who underwent ESD under general anesthesia. Esophageal PEECS was defined by satisfying at least two of the following criteria: fever ≥ 37.8 °C, leukocytosis ≥ 10,800/mm 3 , and localized chest pain ≥ 5/10 points as assessed on a numeric rating scale within 24 h after ESD. Significant factors associated with PEECS were determined by regression analysis., Results: PEECS was recorded in 98 of 202 (48.5%) patients. Patients with PEECS exhibited a larger tumor size (25.0 vs. 17.0 mm, P = 0.002), longer procedure (40.0 vs. 29.5 min, P = 0.021) and hemostasis times (5.0 vs. 3.5 min, P = 0.004), required greater submucosal injection volume (60.0 mL vs. 50.0 mL, P = 0.030), and had a lower rate of local steroid injection (4.1% vs. 12.5%, P = 0.029) than those without PEECS. Multivariate regression analysis revealed tumor size ≥ 17 mm (P = 0.047), procedure time ≥ 33 min (P = 0.027), and hemostasis time ≥ 5 min (P = 0.007) as risk factors for PEECS. In addition, local steroid injection was a significant negatively associated factor (P = 0.001)., Conclusions: Patients with a large tumor, prolonged procedure and hemostasis times are at a high risk of PEECS occurrence. Further, local steroid injection is a negatively associated factor., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: There is limited knowledge regarding the management of duodenal subepithelial lesions (SELs) owing to a lack of understanding of their natural course. This study aimed to assess the natural course of asymptomatic duodenal SELs and provide management recommendations., Methods: Patients diagnosed with duodenal SELs and followed up for a minimum of 6 months were retrospectively investigated., Results: Among the 443,533 patients who underwent esophagogastroduodenoscopy between 2008 and 2020, duodenal SELs were identified in 0.39% (1,713 patients). Among them, 396 duodenal SELs were monitored for a median period of 72.5 months (interquartile range, 37.7-111.3 mo). Of them, 16 SELs (4.0%) showed substantial changes in size or morphology at a median follow-up of 35.1 months (interquartile range, 21.7-51.4 mo). Of these SELs with substantial changes, tissues of two SELs were acquired using endoscopic ultrasound-guided fine needle aspiration biopsy: one was a lipoma and the other was non-diagnostic. Three SELs were surgically or endoscopically removed; two were diagnosed as gastrointestinal stromal tumors, and one was a lipoma. An initial size of 20 mm or larger was associated with substantial changes during follow-up (p = 0.016)., Conclusion: While the majority of duodenal SELs may not exhibit substantial interval changes, regular follow-up with endoscopy may be necessary for cases with an initial size of 20 mm or larger, considering a possibility of malignancy.

Background and Objectives: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population., Methods: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS)., Results: A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS ( p for trend <0.001) and BG-EPVS ( p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS., Discussion: BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.

Objective: This study aimed to investigate the efficacy and safety of repeated photodynamic therapy (PDT) with a chlorin e6 (Ce6)-embedded intragastric satiety-inducing device (ISD) to maintain therapeutic effects of obesity in a juvenile pig., Methods: The Ce6-embedded ISD was fabricated with a dipping method. Twelve pigs were divided into four groups of three and were administered control, single, biweekly, or weekly PDT, respectively. The therapeutic effects were assessed by comparing the results of phototoxicity, endoscopy, fluoroscopy, hormone and weight changes, and histological examination., Results: The percentage of total body weight gain was significantly suppressed in PDT-treated pigs compared with control pigs (all p < 0.001). This suppression persisted in the repeated PDT groups, but percentage of total body weight gain gradually increased when PDT was stopped. Ghrelin levels in the PDT-treated groups were significantly lower and leptin levels were significantly higher than those in the control group (all p < 0.05). Inflammatory cell infiltration, collagen, TUNEL, and anti-ghrelin-positive deposition in the weekly group were significantly higher than those in the control, single, and biweekly groups (all p < 0.01)., Conclusions: Repeated and periodic PDT was technically feasible and safe and successfully maintained the therapeutic effects against obesity while eliminating the indwelling time and reducing ISD-related complications in pigs., (© 2024 The Obesity Society.)

Background/aims: To overcome the technical limitations of classic endoscopic resection for gastric gastrointestinal stromal tumors (GISTs), various methods have been developed. In this study, we examined the role and feasibility of clip-and-cut procedures (clip-and-cut endoscopic full-thickness resection [cc-EFTR]) for gastric GISTs., Methods: Medical records of 83 patients diagnosed with GISTs after endoscopic resection between 2005 and 2021 were retrospectively reviewed. Moreover, clinical characteristics and outcomes were analyzed., Results: Endoscopic submucosal dissection (ESD) and cc-EFTR were performed in 51 and 32 patients, respectively. The GISTs were detected in the upper third of the stomach for ESD (52.9%) and cc-EFTR (90.6%). Within the cc-EFTR group, a majority of GISTs were located in the deep muscularis propria or serosal layer, accounting for 96.9%, as opposed to those in the ESD group (45.1%). The R0 resection rates were 51.0% and 84.4% in the ESD and cc-EFTR groups, respectively. Seven (8.4%) patients required surgical treatment (six patients underwent ESD and one underwent cc-EFTR,) due to residual tumor (n=5) and post-procedure adverse events (n=2). Patients undergoing R0 or R1 resection did not experience recurrence during a median 14-month follow-up period, except for one patient in the ESD group., Conclusions: cc-EFTR displayed a high R0 resection rate; therefore, it is a safe and effective therapeutic option for small gastric GISTs.

Background: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas., Methods: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the follow-up period, and the secondary outcome was the histopathologic results in cases that underwent resection., Results: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2-4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2-91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma., Conclusions: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection., Methods: A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set., Results: The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed., Conclusion: Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.

Background: Previous studies have demonstrated that 50% of patients with normal high-resolution manometry (HRM) findings or ineffective esophageal motility (IEM) may have abnormal functional luminal imaging probe (FLIP) results. However, the specific HRM findings associated with abnormal FLIP results are unknown. Herein, we investigated the relationship between nonspecific manometry findings and abnormal FLIP results., Methods: We retrospectively analyzed 684 patients who underwent HRM at a tertiary care center in Seoul, Korea, based on the Chicago Classification version 4.0 protocol., Key Results: Among the 684 patients, 398 had normal HRM findings or IEM. Of these 398 patients, eight showed esophageal wall thickening on endoscopic ultrasonography or computed tomography; however, no abnormalities were seen during esophagogastroduodenoscopy. Among these eight patients, seven showed repetitive simultaneous contractions (RSCs) in at least one of the two positions: 61% (±29%) in 10 swallows in the supine position and 51% (±30%) in five swallows in the upright position. Four patients who underwent FLIP had a significantly decreased esophagogastric junction distensibility index (1.0 ± 0.5 m m 2 mmHg - 1 at 60 mL). Two of these patients underwent per-oral endoscopic myotomy (POEM) due to a lack of response to medication. Esophageal muscle biopsy revealed hypertrophic muscle with marginal eosinophil infiltration., Conclusions & Inferences: A subset of patients (2%) with normal HRM findings or IEM and RSCs experienced dysphagia associated with poor distensibility of the thickened esophageal wall. FLIP assessment or combined HRM and impedance protocols may help better define these patients who may respond well to POEM., (© 2024 John Wiley & Sons Ltd.)

Objective: The Montreal Cognitive Assessment (MoCA) is recommended for general cognitive evaluation in Parkinson's disease (PD) patients. However, age- and education-adjusted cutoffs specifically for PD have not been developed or systematically validated across PD cohorts with diverse education levels., Methods: In this retrospective analysis, we utilized data from 1,293 Korean patients with PD whose cognitive diagnoses were determined through comprehensive neuropsychological assessments. Age- and education-adjusted cutoffs were formulated based on 1,202 patients with PD. To identify the optimal machine learning model, clinical parameters and MoCA domain scores from 416 patients with PD were used. Comparative analyses between machine learning., Methods: and different cutoff criteria were conducted on an additional 91 consecutive patients with PD., Results: The cutoffs for cognitive impairment decrease with increasing age within the same education level. Similarly, lower education levels within the same age group correspond to lower cutoffs. For individuals aged 60-80 years, cutoffs were set as follows: 25 or 24 years for those with more than 12 years of education, 23 or 22 years for 10-12 years, and 21 or 20 years for 7-9 years. Comparisons between age- and education-adjusted cutoffs and the machine learning method showed comparable accuracies. The cutoff method resulted in a higher sensitivity (0.8627), whereas machine learning yielded higher specificity (0.8250)., Conclusion: Both the age- and education-adjusted cutoff., Methods: and machine learning., Methods: demonstrated high effectiveness in detecting cognitive impairment in PD patients. This study highlights the necessity of tailored cutoffs and suggests the potential of machine learning to improve cognitive assessment in PD patients.

ViSiON (visualization materials composed of silicon-based optical nanodisks) is presented, which offers a unique optical combination of near-infrared (NIR) optical properties and biodegradability. Initially, numerical simulations are conducted to calculate the total extinction and scattering effects of ViSiON by the diameter-to-thickness ratio, predicting precise control over its scattering properties in the NIR region. A top-down patterning technique is employed to synthesize ViSiON with accurate diameter and thickness control. ViSiON with a 50 nm thickness exhibits scattering properties over 400 times higher than that of 30 nm, rendering it suitable as a contrast agent for optical coherence tomography (OCT), especially in ophthalmic applications. Furthermore, ViSiON possesses inherent biodegradability in media, with ≈95% degradation occurring after 48 h, and the degradation rate can be finely tuned based on the quantity of protein coating applied to the surface. Subsequently, the OCT imaging capability is validated even within vessels smaller than 300 µm, simulating retinal vasculature using a retinal phantom. Then, using an ex ovo chick embryo model, it is demonstrated that ViSiON enhances the strength of protein membranes by 6.17 times, thereby presenting the potential for ViSiON as an OCT imaging probe capable of diagnosing retinal diseases., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

The need exists for biosensing technologies capable of sensitively and accurately detecting various biomarkers. In response, the development of nanozymes is actively underway; they have advantages in stability, cost, performance, and functionalization over natural enzymes commonly used for signal amplification in sensing technologies. However, the performance of nanozymes is interdependent with factors such as shape, size, and surface functional moiety, making it challenging to perform quantitative performance comparisons based on the nanozyme material. In this study, we propose a physical synthetic approach to fabricate double-layered bimetallic nanozymes with identical shapes, sizes, and surfaces but different material compositions. These Janus nanozymes consist of a nanozymatic layer responsible for catalytic activity and a gold layer responsible for quantification and efficient surface modification. Based on their identical physicochemical properties, the synthesized double-layered bimetallic nanozymes allow, for the first time, a quantitative comparison of nanozymatic activities in terms of various kinetic parameters. We compared several candidates and found that the Ir-Au nanozyme exhibited the best performance. Subsequently, we applied this nanozyme to detect neutralizing antibodies against SARS-CoV-2 based on a surrogate virus neutralization test. The results demonstrated a limit of detection as low as 2 pg/mL and selectivity specifically toward MERS-CoV. The performance of this assay was further validated using vaccinated samples, demonstrating the potential of our approach as a cost-effective, rapid, and sensitive diagnostic tool for neutralizing antibody detection against viruses such as SARS-CoV-2.

Background/aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008., Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed., Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004)., Conclusions: In this nationwide study, achalasia was associated with increased risk of mortality. Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.

Background and Purpose: This study aimed to determine the neuropsychological differences between patients with early-stage Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) with a Clinical Dementia Rating (CDR) score of ≤1., Methods: We examined 168 patients with AD (126 with CDR score=0.5, 42 with CDR score=1) and 169 patients with DLB (104 with CDR score=0.5, 65 with CDR score=1) whose diagnoses were supported by 18 F-flobetaben positron-emission tomography (PET) and 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane PET. Neuropsychological test scores were compared after controlling for age, sex, and education duration. Using a cutoff motor score on the Unified Parkinson's Disease Rating Scale of 20, patients with AD were further divided into AD with parkinsonism (AD P+ , n =86) and AD without parkinsonism (AD P- , n =82)., Results: At CDR scores of both 0.5 and 1, the DLB group had lower scores on the attention (digit-span forward at CDR score=0.5 and backward at CDR score=1), visuospatial, and executive (color reading Stroop test at CDR score=0.5 and phonemic fluency test, Stroop tests, and digit symbol coding at CDR score=1) tests than the AD group, but higher scores on the memory tests. The AD P- and AD P+ subgroups had comparable scores on most neuropsychological tests, but the AD P+ subgroup had lower scores on the color reading Stroop test., Conclusions: Patients with DLB had worse attention, visuospatial, and executive functions but better memory function than patients with AD. Parkinsonism was not uncommon in the patients with AD and could be related to attention and executive dysfunction., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

Diverse strategies have been developed to visualize latent fingerprints (LFPs) that are undetectable by the naked eye. Among them, fluorescence-based approaches have emerged as an attractive method for enabling high-resolution LFP imaging. However, the use of fluorescent probes for LFP detection remains challenging due to cumbersome processing, low selectivity, and high background interference. Here, we demonstrate highly efficient, sensitive, and background-free LFP detection with dual-color emission arising from manganese (Mn)-doped lead halide perovskite (CsPb(Cl 1-y Br y ) 3 ) nanocrystals (NCs). The resulting bright, fluorescent, solid-state nanopowder (NP) permits the visualization of LFP ridge structures and the resolution of level 1-3 LFP features. The dual-color emission of the Mn-doped perovskite NP provides a simple, robust, and effective route to overcome background interference, thereby increasing the resolution and sensitivity of the LFP detection. The combination of the high quantum efficiency and dual emission of Mn-doped perovskite NP offers great potential for forensic science.

To ensure the operational stability of transistor-based biosensors in aqueous electrolytes during multiple measurements, effective electrode passivation is crucially important for reliable and reproducible device performances. This paper presents a highly effective and efficient electrode passivation method using a facile solution-processed self-assembled multilayer (SAML) with excellent insulation property to achieve operational stability and reproducibility of electrolyte-gated transistor (EGT) biosensors. The SAML is created by the consecutive self-assembly of three different molecular layers of 1,10-decanedithiol, vinyl-polyhedral oligomeric silsesquioxane, and 1-octadecanethiol. This passivation enables EGT to operate stably in phosphate-buffered saline (PBS) during repeated measurements over multiple cycles without short-circuiting. The SAML-passivated EGT biosensor is fabricated with a solution-processed In 2 O 3 thin film as an amorphous oxide semiconductor working both as a semiconducting channel in the transistor and as a functionalizable biological interface for a bioreceptor. The SAML-passivated EGT including In 2 O 3 thin film is demonstrated for the detection of Tau protein as a biomarker of Alzheimer's disease while employing a Tau-specific DNA aptamer as a bioreceptor and a PBS solution with a low ionic strength to diminish the charge-screening (Debye length) effect. The SAML-passivated EGT biosensor functionalized with the Tau-specific DNA aptamer exhibits ultrasensitive, quantitative, and reliable detection of Tau protein from 1 × 10 -15 to 1 × 10 -10 M, covering a much larger range than clinical needs, via changes in different transistor parameters. Therefore, the SAML-based passivation method can be effectively and efficiently utilized for operationally stable and reproducible transistor-based biosensors. Furthermore, this presented strategy can be extensively adapted for advanced biomedical devices and bioelectronics in aqueous or physiological environments.

Background: The likelihood of recurrence of gastric hyperplastic polyps (GHPs) following endoscopic resection and the need for long-term follow-up remain unknown. We, therefore, aimed to investigate the factors associated with the recurrence and cumulative incidence of GHPs over a 10-year period., Methods: Between May 1995 and December 2020, 1,018 GHPs > 1 cm were endoscopically resected from 869 patients. Medical records of these patients were retrospectively reviewed and their clinical features and outcomes were assessed. Groups of GHPs with recurrence and those without recurrence group were compared, and univariate and multivariable analyses were performed to identify the potential risk factors for GHP recurrence., Results: A total of 104 (12.0%) patients who underwent endoscopic removal of GHPs experienced recurrence. Compared to patients without recurrent GHPs, those with recurrent GHPs showed considerably larger median polyp size (28 mm vs. 14 mm, P < 0.001), a higher proportion of multiple polyps (41.3% vs. 29.3%, P = 0.020), polyps with lobulation (63.5% vs. 40.3%, P = 0.001), and exudate (63.5% vs. 46.8%, P = 0.001). Compared to the local recurrence (n = 52) group, the metachronous recurrence (n = 52) group had larger median polyp size (20 mm vs. 16 mm, P = 0.006) as well as higher rates of polyp lobulation (86.5% vs. 40.4%, P < 0.001) and exudate (82.7% vs. 44.4%, P = 0.001). After primary GHP excision, the cumulative incidence of recurrence was 7.2%, 12.7%, and 19.6% at 2 years, 5 years, and 10 years, respectively., Conclusion: The incidence of GHP recurrence following endoscopic excision increased as the follow-up period increased, especially in patients whose GHPs were large-sized, multiple, or characterized by surface exudates/lobulations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Neuropsychiatric symptoms (NPS) are closely associated with cognitive decline in patients with Parkinson disease (PD). We investigated which profiles of NPS are associated with the risk of dementia in PD with mild cognitive impairment (PD-MCI)., Methods: We retrospectively assessed 338 patients with PD-MCI from a single tertiary hospital, who underwent neuropsychological tests and a neuropsychiatric inventory (NPI) questionnaire. We conducted a factor analysis of the dichotomized presence of 12 NPI symptoms, yielding 3 NPI factors: factor 1, mood symptoms; factor 2, hyperactivity-related symptoms; and factor 3, psychotic symptoms. Factor analysis of the severity of NPI symptoms also identified similar NPI factors. The neuropsychiatric correlates of NPI factors were evaluated using general linear models for cognitive tests. Subsequently, we evaluated the hazard ratio (HR) of NPI factors on conversion to dementia., Results: A higher prevalence factor 1 score was associated with lower scores in the verbal memory (β = -0.15; 95% CI -0.24 to -0.06; p = 0.001) and executive domains (β = -0.16; 95% CI -0.28 to -0.04; p = 0.007), whereas higher severity factor 2 scores were associated with lower scores in the naming (β = -0.16; 95% CI -0.28 to -0.03; p = 0.012), visuospatial (β = -0.24; 95% CI -0.41 to -0.07; p = 0.005), and verbal memory domains (β = -0.15; 95% CI -0.24 to -0.05; p = 0.005). A higher severity factor 3 score was associated with lower scores in the visuospatial domain (β = -0.25; 95% CI -0.46 to -0.07; p = 0.007). Cox regression models demonstrated that the risk of dementia was increased in those with higher prevalence factor 1 (HR = 1.48, 95% CI 1.17-1.88, p = 0.001) and factor 2 scores (HR = 1.27, 95% CI 1.07-1.51, p = 0.007) and severity factor 3 score (HR = 1.52, 95% CI 1.29-1.80, p < 0.001) after adjusting for age, sex, education, disease duration, scores for cognition and parkinsonism, and levodopa equivalent dose., Discussion: This study demonstrated that a higher burden of NPS is associated with dementia conversion in patients with PD-MCI., (© 2023 American Academy of Neurology.)

Background: Exosomes are extracellular vesicles secreted by eukaryotic cells and have been extensively studied for their surface markers and internal cargo with unique functions. A deeper understanding of exosomes has allowed their application in various research areas, particularly in diagnostics and therapy., Main Body: Exosomes have great potential as biomarkers and delivery vehicles for encapsulating therapeutic cargo. However, the limitations of bare exosomes, such as rapid phagocytic clearance and non-specific biodistribution after injection, pose significant challenges to their application as drug delivery systems. This review focuses on exosome-based drug delivery for treating rheumatoid arthritis, emphasizing pre/post-engineering approaches to overcome these challenges., Conclusion: This review will serve as an essential resource for future studies to develop novel exosome-based therapeutic approaches for rheumatoid arthritis. Overall, the review highlights the potential of exosomes as a promising therapeutic approach for rheumatoid arthritis treatment., (© 2023. The Korean Society for Biomaterials.)

An intragastric satiety-inducing device (ISD) located in the stomach induce satiety and fullness in the absence of food by continuously pressing on the distal esophagus and cardia of the stomach. To improve the therapeutic function of ISD, Chlorin e6 (Ce6) was embedded in a disk portion of ISD, generating reactive oxygen species and stimulating endocrine cells under the laser irradiation. Since Ce6 has remarkable light efficiency but poor solubility in various solvents, it is essential to use a polymeric photosensitizer and optimize a suitable coating solution composition. Methoxy polyethylene glycol-Ce6 was uniformly coated and the spontaneous release amount of the Ce6 from the device could be reduced, which induced photo-responsive cell death and reduced ghrelin levels in vitro. In mini pigs operated single therapy (PDT or ISD) or combination therapy (Photoreactive ISD), there were differences in body weight (control: 28% vs. Photoreactive ISD: 4%, P < 0.001), ghrelin (control: 4% vs. Photoreactive ISD: 35%, P < 0.001), and leptin levels (control: 8% vs. Photoreactive PDT: 35%, P < 0.001) at 4 weeks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background/aims: We aim to investigate the diagnostic accuracy and differences between Chicago classification version 3.0 (CC v3.0) and 4.0 (CC v4.0)., Methods: Patients who underwent high-resolution esophageal manometry (HRM) for suspected esophageal motility disorders were prospectively recruited between May 2020 and February 2021. The protocol of HRM studies included additional positional change and provocative testing designed by CC v4.0., Results: Two hundred forty-four patients were included. The median age was 59 (interquartile range, 45-66) years, and 46.7% were males. Of these, 53.3% (n = 130) and 61.9% (n = 151) were categorized as normalcy by CC v3.0 and CC v4.0, respectively. The 15 patients diagnosed of esophagogastric junction outflow obstruction (EGJOO) by CC v3.0 was changed to normalcy by position (n = 2) and symptom (n = 13) by CC v4.0. In seven patients, the ineffective esophageal motility (IEM) diagnosis by CC v3.0 was changed to normalcy by CC v4.0. The diagnostic rate of achalasia increased from 11.1% (n = 27) to 13.9% (n = 34) by CC v4.0. Of patients diagnosed IEM by CC v3.0, 4 was changed to achalasia based on the functional lumen imaging probe (FLIP) results by CC v4.0. Three patients (2 with absent contractility and 1 with IEM in CC v3.0) were newly diagnosed with achalasia using a provocative test and barium esophagography by CC v4.0., Conclusions: CC v4.0 is more rigorous than CC v3.0 for the diagnosis of EGJOO and IEM and diagnoses achalasia more accurately by using provocative tests and FLIP. Further studies on the treatment outcomes following diagnosis with CC v4.0 are needed.

Background: Endoscopic submucosal dissection (ESD) is sometimes performed for early gastric cancer (EGC) which is not indicated for endoscopic resection (ER) in elderly patients considering old age and comorbidities. We aimed to compare outcomes between ESD and surgery in elderly patients with EGC that is not indicated for ER., Methods: Elderly patients aged ≥ 75 years who underwent either ESD or surgery for EGC which was not indicated for ER between 2005 and 2015 were retrospectively investigated., Results: Among a total of 294 patients, 59 (20.1%) and 235 (79.9%) patients underwent ESD and surgery as the initial treatment, respectively. The ESD group had smaller size of tumors (25 vs. 30 mm, p = .001) and higher rate of differentiated-type cancer than the surgery group had (88.1% vs. 60.9%, p = 0.001). With a median observation period of 91.8 months (range 11.6-198.1 months), 141 (48.0%) patients died: 25 (42.4%) and 116 (49.4%) patients in the ESD group and the surgery group, respectively. Overall survival and disease-free survival between the two groups had no significant differences (p = 0.982. p = 0.155, respectively)., Conclusions: ESD may be an alternative option for EGC which is not indicated for ER in elderly patients aged ≥ 75 years, considering old age and comorbidity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Although Dieulafoy's lesion (DL) is an important cause of nonvariceal upper gastrointestinal (GI) bleeding, few studies have investigated the clinico-epidemiological outcomes due to its rarity. Here, we investigated clinical features of upper GI bleeding caused by peptic ulcer (PU) or DL and compared endoscopic treatment outcomes., Methods: Patients with upper GI bleeding resulting from PU or DL who visited emergency room between January 2013 and December 2017 were eligible. Clinical features and treatment outcomes were retrospectively investigated., Results: Overall, 728 patients with upper GI bleeding due to PU (n = 669) and DL (n = 59) were enrolled. The median age was 64 years (interquartile range [IQR], 56-75 years), and 74.3% were male. Endoscopic intervention was performed in 53.7% (n = 359) and 98.3% (n = 58) of the PU and DL groups, respectively (P < 0.0001). Patients were matched by sex, age, body mass index, comorbidity, and past medical history, and 190 PU and 52 DL were finally selected. The rebleeding rates within 7 (7.37% vs 17.31%, P = 0.037) and 30 (7.37% vs 26.92%, P < 0.001) days after initial endoscopy were significantly lower in the PU than in the DL group after propensity score matching. During the median follow-up period of 52 months (IQR, 34-70 months), there was no difference in overall survival rate (67.9% vs 82.7%, P = 0.518)., Conclusions: Although DL is a rare cause of upper GI bleeding, it requires endoscopic hemostasis more frequently and has a higher rate of rebleeding than PU even after therapeutic endoscopy. Endoscopists should pay attention and perform active endoscopic hemostasis for DL bleeding., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background/aims: Real-time polymerase chain reaction (RT-PCR) is a fast and simple method for the simultaneous detection of clarithromycin (CLR) resistance and Helicobacter pylori . We evaluated the effectiveness of RT-PCR compared to that of the rapid urease test (RUT) and assessed its value in verifying CLR resistance., Methods: A total of 70 specimens with confirmed H. pylori infection in culture were enrolled and analyzed in this prospective study. All specimens were subjected to RT-PCR assay using fluorescence melting peak signals to detect H. pylori infection and CLR resistances caused by either A2142G or A2143G mutations in the 23S ribosomal RNA gene (23S rRNA). The results were compared to those of RUT and antimicrobial susceptibility culturing tests to investigate the efficacy of RT-PCR., Results: Among the 70 specimens analyzed, the positivity rate was 97.1% (68/70) with RT-PCR and 82.9% (58/70) with RUT. CLR resistance (minimum inhibitory concentration >1.0 μg/mL) was confirmed in 18.6% (13/70), and fluorescence melting curve analysis showed that 84.6% (11/13) had point mutations in 23S rRNA. Ten specimens had only A2143G mutation, and one specimen contained both A2142G and A2143G mutations., Conclusions: RT-PCR assay was found to be more efficient than RUT in detecting H. pylori infection and could effectively verify CLR resistance compared to the antimicrobial susceptibility culturing test. Considering the high sensitivity and accessibility of RT-PCR method, it could be used to easily detect CLR-resistant H. pylori , thus helping clinicians select suitable treatment regimen and improve the eradication rate.

Objective: Although growing evidence suggests that perivascular space (PVS) serves as a clearance route for amyloid and tau, the association between enlarged PVS (EPVS) and Alzheimer disease is highly inconsistent across studies. As the conventional visual rating systems for EPVS were insufficient to predict amyloid/tau/neurodegeneration (A/T/N) status, we developed a new rating scale for EPVS located in the temporal lobe (T-EPVS)., Methods: EPVS located in the basal ganglia (BG-EPVS), centrum semiovale (CS-EPVS), and T-EPVS was visually rated in 272 individuals (healthy controls, n = 96; mild cognitive impairment, n = 106; dementia, n = 70) who underwent structural magnetic resonance imaging (MRI) and dual positron emission tomography scans ( 18 F-flortaucipir and 18 F-florbetaben). T-EPVS and BG-EPVS were defined as high degree when the counts in any hemisphere were >10, and the CS-EPVS cutoff was >20. Logistic regression models were constructed to investigate whether the regional EPVS burden was predictive of A/T/N status. The derived models were externally validated in a temporal validation cohort (n = 195) that underwent MRI studies using a different scanner., Results: Compared with those with low-degree T-EPVS (23/136, 16.9%), individuals with high-degree T-EPVS/CS-EPVS but low-degree BG-EPVS were more likely to exhibit amyloid positivity (46/56, 82.1%). High-degree T-EPVS burden (odds ratio [OR] = 7.251, 95% confidence interval [CI] = 3.296-15.952) and low-degree BG-EPVS (OR = 0.241, 95% CI = 0.109-0.530) were predictive of amyloid positivity. Although high-degree T-EPVS was associated with tau positivity, the association was no longer significant after adjusting for amyloid and neurodegeneration status., Interpretation: Investigating the burden and topographic distribution of EPVS including T-EPVS may be useful for predicting amyloid status, indicating that impaired perivascular drainage may contribute to cerebral amyloidosis. ANN NEUROL 2023;93:965-978., (© 2023 American Neurological Association.)

Background: Dihydropyridines (DHPs) may have neuroprotective effects against Parkinson's disease (PD)., Objective: This study investigated the effects of DHPs on nigrostriatal dopaminergic denervation and longitudinal motor and cognitive outcomes in PD., Methods: We classified 476 patients with drug-naive PD who had undergone dopamine transporter imaging into three groups. They were selected according to a prior diagnosis of hypertension and use of DHPs and were matched using propensity scores: patients without hypertension (HTN-; n = 50) and patients with hypertension treated without DHP (HTN+/DHP-; n = 50) or with DHP (HTN+/DHP+; n = 50). Multiple linear regression and linear mixed model analyses were performed to determine intergroup differences in baseline dopamine transporter availability and longitudinal changes in the levodopa-equivalent dose, respectively. Using Kaplan-Meier analyses, we compared the risks of levodopa-induced dyskinesia, wearing off, and dementia-free survival during the 5.06 years of the mean follow-up period. The Cox regression model determined the independent effects of DHPs on dementia conversion., Results: Dopamine transporter availability in all striatal subregions was comparable between the HTN-, HTN+/DHP-, and HTN+/DHP+ groups. The risks of levodopa-induced dyskinesia and wearing off, as well as longitudinal changes in the levodopa-equivalent dose, did not differ between the groups. The HTN+/DHP+ group had a lower risk of developing dementia than the HTN+/DHP- (Bonferroni-corrected P log-rank  = 0.036) group. The use of DHP was independently associated with a lower risk of dementia conversion after controlling for other antihypertensive drugs and confounding factors (hazard ratio, 0.242; 95% confidence interval, 0.087-0.668; P = 0.006)., Conclusions: DHPs may be associated with better long-term cognitive outcomes in hypertensive patients with PD. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Background and Aims: As the incidence of duodenal neuroendocrine tumors (DNET) is steadily increasing, the role of endoscopic treatment for appropriate lesions is becoming more significant. We aimed to compare the outcomes according to lesion size and endoscopic mucosal resection (EMR) techniques for DNET treatment., Patients and Methods: Patients who underwent endoscopic treatment for DNET between June 2000 and December 2019 were included. The clinicopathologic features and treatment outcomes were investigated by reviewing medical records., Results: Overall, 104 cases underwent endoscopic resection for nonampullary DNET, including conventional EMR (n = 57), cap-assisted EMR (EMR-C, n = 19), and precut EMR (EMR-P, n = 28). The en bloc resection rates (100% vs. 94.7% vs. 96.4%) and histologic complete resection rates (45.6% vs. 52.6% vs. 57.1%) were not significantly different between the EMR, EMR-C, and EMR-P groups. The histologic complete resection rates were significantly higher in lesions < 10 mm than in lesions ≥ 10 mm (69.8% vs. 38.9%, P = 0.013). In lesions < 10 mm, perforation occurred more frequently in the modified EMR group than in the conventional EMR group (13.2% vs. 0.0%, P = 0.007). During the median follow-up period of 88.0 months, the recurrence-free survival (92.2% vs. 94.4% vs. 92.1%) and overall survival (98.0% vs. 88.1% vs. 100.0%) rates did not show significant differences between the EMR, EMR-C, and EMR-P groups., Conclusion: Conventional EMR and modified EMR are feasible and effective for the treatment of nonampullary DNET sized < 10 mm and limited to mucosal and submucosal layer. Additionally, endoscopists should be aware of the high risk of perforation in modified EMR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Marginal ulcer bleeding (MUB) is a complication that can occur following several types of surgery. However, few studies exist on it. Therefore, this study aimed to compare the clinical outcomes of MUB with those of peptic ulcer bleeding (PUB)., Methods: Between January 2013 and December 2017, 5,076 patients underwent emergent esophagogastroduodenoscopy for suspected upper gastrointestinal bleeding. We retrospectively reviewed and analyzed the medical records of MUB and PUB patients and developed a propensity score matching (PSM) method to adjust for between-group differences in baseline characteristics with 1:2 ratios. Sex, age, body mass index (BMI), underlying diseases, and drugs were included as matching factors., Results: A total of 64 and 678 patients were diagnosed with MUB and PUB, respectively, on emergent esophagogastroduodenoscopy, and 62 and 124 patients with MUB and PUB, respectively, were selected after PSM. Rebleeding was significantly higher in patients with MUB than in those with PUB (57.8% vs 9.1%, p < 0.001). Mortality caused by bleeding was higher in patients with MUB than in those with PUB (4.7% vs. 0.4%, p < 0.001). Multivariate analysis revealed that proton pump inhibitor (PPI) administration (odds ratio [OR], 0.14; 95% confidence interval [CI], 0.03-0.56; p = 0.011) after first bleeding was inversely correlated with MUB rebleeding. Large ulcer size (> 1 cm) (OR, 6.69; 95% CI, 1.95-27.94; p = 0.005) and surgery covering pancreas (OR, 3.97; 95% CI, 1.19-15.04) were independent risk factors for MUB rebleeding., Conclusions: MUB showed a severe clinical course than PUB. Therefore, MUB should be managed more cautiously, especially for large ulcers and pancreatic surgery. Prophylactic PPI administration may be helpful in reducing rebleeding in MUB., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Left gastric artery (LGA) pseudoaneurysm presenting with upper gastrointestinal (UGI) bleeding is rare but fatal, unless treated., Aims: We aimed to describe the clinical and endoscopic features of patients with UGI bleeding due to LGA pseudoaneurysms., Methods: We performed a computerized search of our hospital's de-identified clinical data warehouse to identify patients with UGI bleeding due to an LGA pseudoaneurysm between 2000 and 2020. Patients' electronic medical records and data on esophagogastroduodenoscopy and digital subtraction angiography were reviewed retrospectively., Results: Of 26 patients with an LGA pseudoaneurysm, six patients had UGI bleeding related to an LGA pseudoaneurysm. No patients had previous vascular diseases or pancreatitis. One patient had liver cirrhosis and a history of radiofrequency ablation for hepatocellular carcinoma, one had colon cancer, two had undergone abdominal surgeries, one had received chemoradiotherapy for renal cell carcinoma, and one had no intraabdominal diseases. Symptoms were hematemesis in two, hematochezia in the other two, and melena in the remaining two patients. Esophagogastroduodenoscopy showed a pulsating bulge in the ulcer in two and a large Dieulafoy's lesion-like structure in four patients. All patients achieved hemostasis by angioembolization., Conclusion: LGA pseudoaneurysm should be suspected in UGI bleeding if a large Dieulafoy's lesion-like structure or a pulsating bulge in the ulcer is found at the lesser curvature of the gastric body on endoscopy and if the patient has any intra-abdominal inflammatory disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)