Background: Hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) is used for the differential diagnosis of thyrotoxicosis, but its dependence on CT and complex analysis remains debated. This study evaluated whether CT-free thyroid SPECT using artificial intelligence (AI) could substitute for conventional SPECT/CT.Methods: This prospective multicenter noninferiority clinical trial (KCT0008387) included 152 patients with thyrotoxicosis from three tertiary referral hospitals. A pretrained AI model generated technetium thyroid uptake (TcTU) values using SPECT images without CT. These values were compared with TcTU derived from conventional SPECT/CT. The primary endpoint was diagnostic accuracy for Graves' disease. Noninferiority was defined as a lower confidence interval (CI) limit greater than -10%. Secondary endpoints included diagnostic accuracy for destructive thyroiditis and prediction of antithyroid drug (ATD) prescription within one month.Results: Among 152 patients, 84 had Graves' disease, 45 had indeterminate disease, and 23 had thyroiditis. For Graves' disease, CT-free SPECT demonstrated 86.2% accuracy compared with 85.5% for conventional SPECT/CT. The lower bound of the CI of the accuracy difference was -3.0%, meeting the prespecified noninferiority margin. For thyroiditis and ATD prescription, the lower bounds were -7.4% and -3.2%, respectively. Omission of CT resulted in a 33.5% reduction of radiation exposure from 3.34 mSv to 2.22 mSv, and CT-free SPECT automatically generated TcTU values more quickly than SPECT/CT (40 minutes vs. 4 minutes).Conclusions: CT-free SPECT using AI demonstrated noninferior diagnostic performance for thyrotoxicosis compared with conventional hybrid imaging while reducing radiation exposure and analysis time.Trial Registration: https://cris.nih.go.kr (KCT0008387).

STUDY OBJECTIVES:The long-term trajectory of cognitive changes in isolated REM sleep behavior disorder (iRBD) remains unclear. Increasing evidence suggests potential heterogeneity in disease progression. METHODS:People who maintained an iRBD diagnosis without phenoconversion for at least 5 years were included in this study. Cognitive changes over time were assessed using linear mixed models. Subgroup analyses were conducted for men and women separately, and for people with longstanding iRBD. RESULTS:A total of 318 neuropsychological assessments from 162 people with iRBD (28% women) were analyzed. The mean age at diagnosis was 65.6 years, with an average follow-up duration of 7.7 years. Significant linear declines were observed across attention/working memory and memory domains, with notable decreases in Digit Symbol ($\beta$= -0.084, 95% confidence intervals [CI] -0.102 to -0.066), the Stroop color-naming test ($\beta$= -0.054, 95% CI -0.074 to -0.054), and Word List Recall ($\beta$= -0.054, 95% CI -0.078 to -0.030) as representative examples. In the longstanding-iRBD subgroup (n = 33) and among men, cognitive decline patterns largely mirrored those observed in the full cohort, with significant declines in attention/working memory and memory. In contrast, women exhibited a more restricted decline, limited to digit span forward ($\beta$= -0.055, 95% CI -0.102 to -0.008) and digit symbol ($\beta$= -0.082, 95% CI -0.121 to -0.043). CONCLUSIONS:Gradual cognitive decline in attention/working memory and memory may represent a natural course of neurodegeneration in men with iRBD, without necessarily indicating imminent phenoconversion. Women with iRBD appeared to show greater resilience to cognitive decline compared to men. Statement of Significance Cognitive impairment is common in isolated REM sleep behavior disorder (iRBD) and is considered a potential marker of phenoconversion to overt neurodegenerative disorders, such as Parkinson's disease or dementia with Lewy bodies. This study, overcoming prior limitations of short follow-up and small samples, provides long-term data demonstrating a gradual decline in attention/working memory and memory domains among people with iRBD. It also reveals sex-specific vulnerability, with men showing more pronounced decline than women, and confirms that even people with longstanding iRBD experience cognitive deterioration over time. These findings highlight the need for sex-specific approaches when monitoring cognitive progression in iRBD, and future studies should map distinct cognitive-decline trajectories to subsequent phenoconversion risk and clarify the mechanisms underlying the observed sex differences.

Introduction:Helicobacter pylori (H. pylori) is a major cause of gastric cancer (GC); however, GC also develops in H. pylori-negative patients, and the characteristics of non-H. pylori microbial communities remain unclear. Methods:We characterized gastric microbiota in patients with GC according to H. pylori status, sex, GC subtype, and longitudinal changes following H. pylori eradication therapy. Gastric corpus mucosal samples were collected from 35 patients with GC who underwent endoscopic therapy and longitudinal follow-up. Some patients were followed for more than 10 years, and gastric microbiota were analyzed using 16S rRNA gene sequencing. Results:H. pylori-negative samples exhibited significantly higher microbial diversity and distinct community structures compared with H. pylori-positive samples, which was consistent across sex and GC subtypes. Multiple non-H. pylori taxa were enriched in H. pylori-negative samples, including organisms with reported urease and nitrate-reducing activities. Longitudinal analyses demonstrated that successful eradication induced significant but non-uniform microbial shifts, whereas persistent infection maintained stable H. pylori-dominated profiles. Notably, species-level analyses revealed selective and H. pylori eradication-specific microbial changes, with Actinomyces naeslundii consistently enriched only in the H. pylori eradicated group across longitudinal modeling and differential abundance analyses. Functional prediction analyses revealed a reduced representation of host-pathogen interaction-related pathways in H. pylori-negative samples. Discussion:These findings suggest that H. pylori-negative gastric microbiota harbor functionally distinct microbial communities that may contribute to gastric carcinogenesis through alternative microbial and ecological pathways. In addition, H. pylori eradication revealed a longitudinal remodeling of gastric microbiota.

Objective.:Oropharyngeal squamous cell carcinoma (OPSCC) has undergone a major epidemiologic transition, with high-risk human papillomavirus (HPV) emerging as the dominant etiologic factor. Although HPV-16 accounts for most HPV-positive OPSCC worldwide, a substantial minority of tumors harbor non-HPV- 16 genotypes, the clinical and prognostic significance of which remains uncertain, particularly in Asian populations. This study aimed to investigate HPV genotype distribution and survival outcomes in a singleinstitution cohort of HPV DNA-positive OPSCC regardless of p16 and to assess the prognostic significance of HPV genotype. Methods.:We retrospectively reviewed patients treated with curative intent for HPV-positive OPSCC at Seoul National University Bundang Hospital between 2003 and 2023. HPV status was determined using p16 immunohistochemistry and HPV DNA genotyping. Patients were classified as having HPV-16 or non-HPV-16 genotype. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier method and compared using the log-rank test. Results.:Of 254 eligible patients, 174 with HPV DNA-positive tumors and available HPV genotyping results were included in the final analysis. HPV-16 accounted for 74.7% of tumors, while non-HPV-16 genotypes comprised 25.3%, most commonly HPV-33, HPV-35, HPV-58, and HPV-18. A marked male predominance was observed across all genotypes. The clinical stage distribution did not differ significantly between the HPV-16 and non-HPV-16 groups overall; however, HPV-33-positive tumors showed higher nodal stage compared with HPV-16. OS and DFS were similar between the HPV-16 and pooled non-HPV-16 groups. In genotype-specific analyses, DFS did not differ significantly across groups, whereas HPV-35 was associated with poorer OS compared with HPV-16. Conclusion.:In this cohort, non-HPV-16 genotypes accounted for approximately one-quarter of HPV-positive OPSCC cases and demonstrated clinicopathologic heterogeneity with selected genotype-specific prognostic differences. Given the substantial proportion of non-HPV-16 genotypes and the marked male predominance observed in our cohort, our findings may have implications for future HPV prevention strategies.

We aimed to predict axillary pathologic complete response (pCR) in patients with clinical N2-3 breast cancer who underwent neoadjuvant chemotherapy (NAC) followed by breast and axillary surgeries. These patients were retrospectively analyzed between 2016 and 2020. Imaging metrics (lesion size and reduction ratios measured using magnetic resonance imaging (MRI) and ultrasonography (US)) and clinical and pathological factors were analyzed. Axillary pCR was achieved in 49.3% (n = 136/276) of the patients. Post-NAC significant predictors included breast lesion and lymph node (LN) sizes on MRI and LN cortical thickness on US. Pre-NAC tumor-specific factors were also associated with axillary pCR. In multivariable logistic regression analyses using three models, Model 3 (imaging variables, tumor characteristics, and molecular subtypes) demonstrated the best predictive performance (AUC: 0.9). Integrating molecular subtype-specific imaging and tumor characteristics enabled precise prediction of axillary pCR in patients with cN2-3 breast cancer, supporting tailored surgical approaches based on individual responses.

This pilot study evaluates an artificial intelligence (AI)-assisted electrocardiography (ECG) analysis system, QCG, to enhance urgent coronary angiography (CAG) decision-making for acute chest pain in the emergency department (ED). We retrospectively analyzed 300 ED cases, categorized as non-coronary chest pain (Group 1), acute coronary syndrome (ACS) without occlusive coronary artery disease (CAD) (Group 2), and ACS with occlusive CAD (Group 3). Six clinicians made urgent CAG decision using a conventional approach (clinical data and ECG) and a QCG-assisted approach (including QCG scores). The QCG-assisted approach improved correct CAG decisions in Group 2 (36.0% vs. 45.3%, P = 0.003) and Group 3 (85.3% vs. 90.0%, P = 0.017), with minimal impact in Group 1 (92.7% vs. 95.0%, P = 0.125). Diagnostic accuracy for ACS improved from 77% to 81% with QCG assistance and reached 82% with QCG alone, supporting AI's potential to enhance urgent CAG decision-making for ED chest pain cases.

In this study, we present an all-fiber sensor based on porous cholesteric liquid crystal film (CLCF) coated on the cross-section of an optical fiber ferrule for real-time monitoring of flammable vapors in industrial environments. Reflection band shifts according to the concentration of gases were measured using a broadband wavelength-swept laser, and the sensitivity were 3.19 pm/ppm, 4.88 pm/ppm, and 6.61 pm/ppm were obtained for acetone, toluene, and benzene vapors, respectively, with benzene vapor showing the highest sensitivity. Compared to nonporous CLCFs, the porous CLCF showed six times higher sensitivity. This sensor, which operates passively without a battery, is immune to electromagnetic interference, suggesting its potential as a reliable sensor.

[This corrects the article DOI: 10.1017/ash.2024.75.].

The disease course of inflammatory bowel disease (IBD) is highly variable; early and precise identification of patients with poor outcomes is crucial. We aimed to classify the long-term disease course of IBD using biochemical markers and evaluate the clinical factors associated with different disease courses. A latent class mixed model was employed to identify distinct trajectories of C-reactive protein (CRP) and fecal calprotectin (FCP) levels in 256 and 635 patients with Crohn’s disease (CD) and ulcerative colitis (UC), respectively, from a tertiary hospital cohort. Multinomial logistic regression was used to evaluate the relationships between various trajectories and clinical variables. Three trajectories were identified for CD and UC: class 1, early and sustained biochemical remission; class 2, delayed remission; and class 3, prolonged difficulty in achieving remission for > 5 years. For patients with CD, early immunomodulator initiation was associated with a high likelihood of belonging to class 1 in the CRP trajectory analysis, whereas early advanced therapy increased the probability of belonging to class 1 in the FCP trajectory analysis. CRP trajectory analysis showed no significant associations in patients with UC. Younger age at diagnosis and early immunomodulator initiation were associated with higher odds of being in class 2 or 3, whereas current smoking was associated with a high likelihood of being in class 1 in the FCP trajectory analysis. Early aggressive medical treatment for CD may lead to long-term biochemical remission, whereas no similar association was observed in UC.

Background/Aims : The relationship between Helicobacter pylori (HP) eradication and osteoporosis development remains inadequately elucidated. This study aimed to ascertain whether HP eradication therapy confers protective effects against osteoporosis progression. Methods : Subjects without osteoporosis who underwent esophagogastroduodenoscopy with concurrent HP testing were prospectively recruited between May 2003 and February 2023 at Seoul National University Bundang Hospital. Participants were stratified into two cohorts: those with successful HP eradication and those without. Osteoporosis was diagnosed using dual-energy X-ray absorptiometry, and the risk of osteoporosis was assessed using Cox proportional hazards regression analysis. Results : The successfully eradicated cohort comprised 730 individuals (mean age, 56.4 years; 67.5% female), compared with 116 individuals (mean age, 56.2 years; 74.1% female) in the non-eradicated cohort. Osteoporosis occurred in 179 subjects (24.5%) in the eradicated group and in 40 subjects (34.5%) in the non-eradicated group. Significant risk factors for osteoporosis included female sex (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.93 to 5.05; p<0.001), advanced age (HR, 1.08; 95% CI, 1.06 to 1.10 per year; p<0.001), and persistent HP infection (HR, 1.60; 95% CI, 1.13 to 2.28; p=0.009). In subgroup analyses according to sex and age, HP eradication demonstrated a significant reduction in osteoporosis risk in females (p=0.005) than in males, especially among females aged ≥50 years (p=0.003). However, this change was not pronounced in males. Conclusions : HP eradication may serve as a preventive intervention against osteoporosis development, particularly among female subjects (ClinicalTrials.gov: NCT06818591).

OBJECTIVE:To estimate the learning curve of laparoscopic articulated instrument (LAI) surgery by analyzing data from a multi-institutional gynecologic surgery cohort using surgical time as the primary metric for evaluation. METHODS:A total of 400 patients scheduled to undergo gynecologic surgery (adnexal surgery, myomectomy, hysterectomy, and cancer surgery) using LAI were prospectively enrolled at 14 institutes in the Republic of Korea between November 2021 and April 2022 (KGOG 4002). After excluding patients who did not undergo surgery with LAI (n=43), those in whom LAI was rarely used (n=11), and those operated on by surgeons with prior LAI experience (n=147), 199 patients were included in the analysis. Changes in surgical time according to the surgery index were evaluated using linear regression analysis. RESULTS:Fifty-four adnexal surgeries, 40 myomectomies, 68 hysterectomies, and 37 cancer surgeries were performed by 24 surgeons. Each surgeon performed between one and 24 surgeries. Surgical time did not decrease as the surgery index increased for any type of surgery. Among surgeons who performed ≥10 surgeries, surgical time similarly showed no decrease with increasing surgery index. CONCLUSION:In gynecologic surgery using LAI, surgical time did not decrease despite accumulating surgical experience.

The scanning speed stability of a wavelength-swept laser (WSL) with a polygon-scanner-based wavelength filter (PSWF) is affected by the speed of the brushless direct current (BLDC) motor driving a polygonal scanner mirror (PSM). In particular, the PSM running at low speeds experiences fluctuations in rotational speed, causing the output of the WSL to fluctuate in the temporal domain. The speed variation of the WSL causes critical measurement errors in the fiber Bragg grating (FBG) interrogator sensors. In this study, we successfully corrected the output error of the FBG array sensor caused by the PSM rotational speed fluctuations in a WSL running at a low scanning rate. The FBG array used five FBGs, and the time intervals of the FBGs were corrected according to the PSM rotation speed variation based on the periodic interval of the array signal. A WSL with a scanning rate of 1.0 kHz suggested a 97% improvement after compensating for rotational speed variations of the PSM.

PURPOSE:Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea. MATERIALS AND METHODS:We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed. RESULTS:Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-Barr virus (EBV) infection (odds ratio [OR], 7.46; p < 0.001), antral location of GC (OR, 1.84; p=0.027), and macrosatellite instability-high (MSI-H) (OR, 5.04; p=0.027). Diffuse-type histology was inversely associated (OR, 0.22; p=0.041). In males, EBV (OR, 36.27) and antral location (OR, 2.38) were significant. In females, only MSI-H was significant (OR, 11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (hazard ratio, 0.70; p=0.080), with a borderline-significant interaction by sex (p=0.073). CONCLUSION:PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlight the importance of sex-based immunobiology in tailoring GC treatment strategies.

Background Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5–16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. Methods A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV–ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. Results A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males ( P < 0.001), a predominant presence in the proximal stomach ( P < 0.001), a higher proportion of undifferentiated cancer ( P < 0.001), and a lower cancer stage ( P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall ( P = 0.021) and GC-specific survival ( P = 0.007) on the Kaplan–Meier survival curve. However, this effect was evident only in males. Conclusions EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Background/Aims: A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. Methods: This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. Results: Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). Conclusion : s: This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

ABSTRACTIn 2015, Staphylococcus argenteus and Staphylococcus schweitzeri were proposed as new species, distinct from Staphylococcus aureus and collectively referred to as the S. aureus complex. However, no clinical reports of these new species exist in Korea. Upon the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for all bloodstream isolates since September 2022, S. argenteus was identified in one patient. Therefore, we aimed to search for new species among the archives of the S. aureus bacteremia cohort and describe their clinical and microbiological characteristics. Among the 691 archived S. aureus isolates between 2012 and 2018, one was identified as S. argenteus via MALDI-TOF MS. Both S. argenteus isolates (one in 2022) were obtained from patients with extensive pneumonia accompanied by bacteremia and both cases had fatal outcomes. They harbored multiple virulence genes (clfA, clfB, fnbpA, sdrC, sdrD, sdrE, bbp, cna, see, seg, sei, blaZ, fnbpB, and map) but did not harbor mecA and pvl. No matched sequence type (ST) was found in either isolate, and both S. argenteus isolates were closely related to ST1594, ST1593, ST1793, and ST1303, which belonged to S. argenteus. S. argenteus accounted for <1% of the S. aureus complex but had clinical characteristics similar to S. aureus. Therefore, clinicians should be aware of these factors to avoid misidentifying these strains as coagulase-negative staphylococci, and appropriate reporting is required to minimize confusion.IMPORTANCEStaphylococcus argenteus, a member of Staphylococcus aureus complex, has been reported as an important pathogen that causes clinically invasive infections in humans similar to S. aureus. Clinical isolates of S. argenteus have been reported across the world, showing a large geographical difference in prevalence and genomic profile. However, there have been no clinical reports regarding this new species in Korea. This is the first report to investigate the clinical and genetic characteristics of S. argenteus identified in patients with bacteremia, and the proportion of S. argenteus bacteremia among S. aureus bacteremia cohort in Korea.

Liquid-liquid phase separation of biomolecules is increasingly recognized as being relevant to various cellular functions, and complex coacervation of biomacromolecules, particularly proteins, is emerging as a key mechanism for this phenomenon. Complex coacervation is also being explored as a potential protein purification method due to its potential scalability, aqueous operation, and ability to produce a highly concentrated product. However, to date, most studies of complex coacervation have evaluated the phase behavior of a binary mixture of two oppositely charged macromolecules. Therefore, a comprehensive understanding of the phase behavior of complex biological mixtures is yet to be established. To address this, a panel of engineered proteins was designed to allow for quantitative analysis of the complex coacervation of individual proteins within a multicomponent mixture. The behavior of individual proteins was evaluated using a defined mixture of proteins that mimics the charge profile of the Escherichia coli proteome. To allow for the direct quantification of proteins in each phase, spectrally separated fluorescent proteins were used to construct the protein mixture. From this quantitative analysis, we observed that protein coacervation was synchronized in the mixture, which was distinctive from the behavior when each protein was evaluated in a single-protein system. Subtle differences in biophysical properties between the proteins, such as the ionization of individual charged residues and overall charge density, became noticeable in the mixture, which allowed us to elucidate parameters for protein complex coacervation. With this understanding, we successfully designed methods to enrich a range of proteins of interest from a mixture of proteins.