Keimyung University

Background Elective switching from intravenous (IV) to subcutaneous (SC) infliximab (IFX) has shown efficacy in patients with inflammatory bowel disease (IBD). However, long-term outcomes for patients not in remission remain unclear. Objectives We evaluated the effectiveness of SC IFX switching in both remission and non-remission patients. Design This study was a retrospective multicentre study conducted across five tertiary hospitals in Korea. Methods Patients with IBD who switched to SC IFX between January 2021 and January 2023 were included. Clinical remission was defined as a Crohn’s Disease Activity Index of <150 or a partial Mayo score of <2. Biochemical remission was defined as faecal calprotectin of <250 µg/g and C-reactive protein of <0.5 mg/dL. We investigated the treatment persistence rate of SC IFX and trends in pharmacokinetics, clinical indices and biomarkers over 1 year of follow-up, analysing the data based on the baseline remission state. Results Among 127 patients included, 90 (70.9%) were in clinical remission, and 37 (29.1%) were not at the time of switching. The one-year treatment persistence rate was 92.1%, with no significant difference between the clinical remission and non-remission groups (p = 0.139). Persistence was also unaffected by baseline biochemical remission status. IFX pharmacokinetics and biomarkers improved significantly in both clinical groups over 12 months (p < 0.005). Disease activity indices remained stable in the remission group and decreased in the non-remission group after switching. Previous biologics exposure was the only significant predictor of treatment persistence (hazard ratio, 5.634; 95% confidence interval, 1.357–23.384; p = 0.017). Adverse events related to SC IFX occurred in 15.7% of patients. The optimal SC IFX cutoff levels associated with clinical and biochemical remission were 11 and 17 μg/mL, respectively. Conclusion Switching from IV to SC IFX during maintenance therapy demonstrated high treatment persistence and safety, irrespective of clinical and biochemical remission status.

Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by dopaminergic neuronal loss and α-synuclein accumulation, which leads to progressive motor and non-motor impairments. Conventional treatments are symptomatic and lack disease-modifying potential; however, gene therapy (GT) technologies are emerging as promising approaches for treating PD. Effective drug delivery systems are central to the success of GT in overcoming challenges, such as the blood-brain barrier, immunogenicity, and targeting specificity. This review highlights advancements in GT delivery systems for PD, focusing on viral and non-viral vector delivery systems. Key therapeutic strategies are discussed, such as dopamine enhancement, neuroprotection using neurotrophic factors, ribonucleic acid (RNA) interference, and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR/Cas9) genome editing. Clinical progress in targeting PD-related genes, including SNCA and LRRK2, underscores the potential of GT delivery systems for slowing disease progression. Challenges such as immune responses, limited transgene capacity, and targeting specificity have been addressed alongside innovations in non-viral vectors to overcome these limitations. Advances in GT delivery systems are driving a paradigm shift in PD treatment by enabling targeted delivery of therapeutic genes to the brain, potentially modifying disease pathology. While challenges remain, emerging tools, such as CRISPR interference and hybrid delivery approaches, provide promising solutions. However, further translational research must address challenges such as long-term stability, consistent transgene expression, and large-scale production. Optimized delivery systems hold the key to unlocking the full potential of GT in the treatment of PD and related neurodegenerative diseases.

In this paper, we provide necessary and sufficient conditions on a triple of weights (u, v, w) so that the t-Haar multipliers $T^t_{w,\sigma }$, $t\in \mathbb {R}$, are uniformly (on the choice of signs $\sigma$) bounded from $L^2(u)$ into $L^2(v)$. These dyadic operators have symbols $s(x,I)=\sigma _I\,(w(x)/\langle w\rangle _I)^t$ which are functions of the space variable $x\in \mathbb {R}$ and the frequency variable $I\in \mathcal {D}$, making them dyadic analogues of pseudo-differential operators. Here $\mathcal {D}$ denotes the dyadic intervals, $\sigma _I=\pm 1$, and $\langle w\rangle _I$ denotes the integral average of w on I. When $w\equiv 1$ we have the martingale transform and our conditions recover the known two-weight necessary and sufficient conditions of Nazarov, Treil and Volberg. We also show how these conditions are simplified when u=v. In particular, the martingale one-weight and the t-Haar multiplier unsigned and unweighted (corresponding to $\sigma _I\equiv 1$ and $u=v\equiv 1$) known results are recovered or improved. We also obtain necessary and sufficient testing conditions of Sawyer type for the two-weight boundedness of a single variable Haar multiplier similar to those known for the martingale transform.

Introduction Subthreshold depression and major depressive symptoms are prevalent mental health conditions that significantly impact quality of life and contribute to South Korea’s high suicide rate. Despite their importance, few studies have examined temporal changes in the occurrence of these disorders in the Korean population. Objective This study aimed to estimate the prevalence of subthreshold depression and MDD using a large, representative sample of the South Korean population and analyze trends over time. Methods Data were obtained from 10,848 participants aged 19 and above in the Korean National Health and Nutrition Examination Survey (KNHNES) in 2014 and 2018. Depression severity was categorized using cutoff scores of 5-14 for subthreshold symptoms and ≥ 15 for severe symptoms. Results The prevalence of subthreshold depression increased from 12.90% in 2014 to 15.20% in 2018, while MDD rose from 4.7% to 7.0% (p < 0.001). Logistic regression analysis revealed that MDD (OR = 8.1, 95% CI = 2.34-11.23), college education (OR = 7.9, 95% CI = 4.23-10.00), and age above 65 years (OR = 8.1, 95% CI = 2.58-12.58) exhibited similar risks for suicide attempts. Conclusion Since 2014, there has been a sharp and sustained increase in both subthreshold and severe depressive symptoms among the Korean population. This alarming trend underscores the critical need for targeted prevention and intervention strategies.

Purpose Variation in fat mass and obesity-associated gene (FTO) is a critical risk factor in the etiology of obesity. FTO is associated with preference and sensory perception of nutrients and dietary intake. However, the effect of genetic variation on overall dietary quality has not yet been fully elucidated. This study examined whether FTO rs9939609 (T > A) was associated with dietary quality in Koreans. Methods Data of 46,928 individuals from the Korean Genome and Epidemiology Study were analyzed according to FTO rs9939609 genotype, general characteristics, and diet quality based on the Korean Healthy Eating Index (KHEI), employing sex- and age-stratified approaches. Results The FTO genotype did not significantly influence overall diet quality; however, female carriers of the obesity risk allele A (TA + AA) showed significantly higher KHEI scores for balance of energy nutrient consumption, especially for carbohydrate ratio (2.00 ± 1.99 versus 1.90 ± 1.98, Padjusted <0.001) and fat ratio (2.87 ± 2.15 versus 2.76 ± 2.17, Padjusted <0.001) than A-allele non-carriers (TT). Furthermore, when the females were grouped based on their median age (51 years), such an association between the FTO genotype and energy nutrient ratio was only evident in the younger group. However, such an effect of the genetic variant on diet quality and energy nutrient consumption was not evident in males, and the interactive effect of FTO and sex and age was not statistically significant. Conclusion The FTO rs9939609 (T > A) polymorphism is associated with dietary quality, particularly influencing the balance of energy nutrient intake in Korean females.

Increased exposure to particulate matter (PM) from air pollution causes lung inflammation and increases morbidity and mortality due to respiratory diseases. Pirfenidone is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis. Background/Objectives: In this experiment, we studied the therapeutic effects of pirfenidone on PM-induced pulmonary fibrosis. Methods: Pulmonary fibrosis was induced by the intratracheal application of 100 μg/kg PM10 mixed with 200 μL saline. After 42 days of PM10 infusion, 0.2 mL of distilled water with pirfenidone was orally administered to the pirfenidone-treated groups (200 and 400 mg/kg) every other day for a total of 15 times over 30 days. Results: The intratracheal administration of PM resulted in lung injury and a significant decrease in the number of bronchoalveolar lavage fluid cells. PM administration increased the lung injury score, level of lung fibrosis, and production of pro-inflammatory cytokines. Pirfenidone treatment effectively suppressed transforming growth factor-β-activated kinase 1 in PM-induced pulmonary fibrosis. The present changes inhibited the expressions of mitogen-activated protein kinase kinase 3 and p38, which suppressed transforming growth factor-β, ultimately alleviating lung fibrosis. PM exposure upregulated the expressions of fibronectin and type 1 collagen. PM exposure enhanced connective tissue growth factor and hydroxyproline levels in the lung tissue. The levels of these fibrosis-related factors were inhibited by pirfenidone treatment. Conclusions: These results suggest that pirfenidone is therapeutically effective against PM-induced pulmonary fibrosis.

Background Video-assisted thoracoscopic surgery (VATS) is a minimally invasive and safe procedure. However, lung deflation during the operation causes anatomic landmark distortion, complicating small nodules detection. Computed tomography (CT)-guided hookwire localization promotes the success rates of VATS, but faces issues with hookwire dislodgement, potentially losing intraoperative tumor reference. This study was conducted to identify the relative importance ranking of potential factors influencing dislodgement in CT-guided hookwire localization. Methods This retrospective study reviewed 123 cases of CT-guided hookwire localization followed by VATS resection. Variables analyzed included sex, age, nodule size, emphysema, chest wall/muscle/total depth, distance from the nodule (DNP) or wire tip to the pleura (DWP), procedure time, nodule subtypes, multiple localization, post-procedural hemorrhage, pneumothorax, nodule penetration, and time intervals between completion of procedure to initiation of surgery (PS interval). Variables were compared using chi-square tests or Mann-Whitney tests. A random forest model, enhanced with the Synthetic Minority Over-sampling Technique (SMOTE) for oversampling, was employed to determine the relative importance of each variable. The relative importance of variables was presented using the mean decrease Gini and mean decrease accuracy metrics. For sensitivity analysis, relative variable importance was analyzed using extreme gradient boosting (XGBoost) model, and the relative importance of variables was presented using the gain metric. Results Among the 123 cases, dislodgement occurred in 15. In univariable analysis, only the PS interval was statistically significant (134.1 ± 73.1 vs. 104.1 ± 46.1 minutes in dislodgement or non-dislodgement, p = 0.031). The random forest and XGBoost model identified the top five important variables as the PS interval, DWP, DNP, total depth, and age. The top five factors demonstrated a distinct difference when compared to the other factors. Conclusions The study identified the PS interval as the most critical factor in hookwire dislodgement, along with DNP, DWP, total depth, and age. These results identified the presence of modifiable factors within the hospital and can assist practitioners and surgeons in recognizing the dislodgement risk of procedures based on various patient factors.

Background Rapid and accurate identification of large vessel occlusion (LVO) is crucial for determining eligibility for endovascular treatment. We aimed to validate whether computed tomography combined with clinical information (CT&CI) or diffusion-weighted imaging (DWI) offers better predictive accuracy for anterior circulation LVO. Methods Computed tomography combined with clinical information and DWI data from patients diagnosed with acute ischemic stroke were collected. Three deep-learning models, convolutional neural network, EfficientNet-B2, and DenseNet121, were used to compare CT&CI and DWI for detecting anterior circulation LVO. Results A total of 456 patients, 228 patients with LVO [68.91 ± 12.84 years, 63.60% male; initial National Institutes of Health Stroke Scale (NIHSS) score: median 11 (7–14)] and without LVO [67.06 ± 12.29 years, 64.04% male; initial NIHSS score: median 2 (1–4)] were enrolled. Diffusion-weighted imaging achieved better results than CT&CI did in each performance metric. In DenseNet121, the area under the curves (AUCs) were found to be 0.833 and 0.756, respectively, while in EfficientNet-B2, the AUCs were 0.815 and 0.647, respectively. Conclusions In detecting the presence of anterior circulation LVO, DWI showed better results in each performance metric than CT&CI did, and the best-performing deep-learning model was DenseNet121.

Backgrounds and Objectives The purpose of this study was to examine the influence of self-perceptions of aging on positive and negative affect and to examine whether this association is mediated by sense of hopelessness. It was hypothesized that increases in positive self-perceptions of aging would be associated with decreases in hopelessness over time, which in turn would be associated with higher future levels of affective well-being. Methods The study used longitudinal data from the Health and Retirement Study collected in 2008, 2012, 2016, and 2020 (N ≈ 11,500, average age ≈ 62). The random-intercept cross-lagged panel model was used for analyzing the data. The mediation was tested at the temporal within-person level. Results The mediation hypothesis was supported for negative affect but not for positive affect. The results showed that higher-than-typical levels of positive perceptions of aging were associated with lower-than-typical levels of hopelessness, which in turn was related to lower-than-typical future levels of negative affect. Conclusion Hopelessness mediates the longitudinal relationship between self-perceptions of aging and negative affect. The findings emphasize the significance of considering hope in interventions designed to address negative affect and subjective beliefs about aging.

Background: Ocular infections can cause severe complications, including blindness, and distinguishing bacterial from fungal keratitis based on clinical features alone is difficult. This study compared broad-range conventional PCR and real-time PCR methods targeting the 16S rRNA gene with traditional culture for diagnosing bacterial ocular infections. Methods: We analyzed 160 ocular specimens from 111 patients, categorizing them as septic or aseptic. The results of both conventional PCR and real-time PCR methods targeting the 16S rRNA gene were compared with traditional culture outcomes. Results: Real-time PCR demonstrated higher sensitivity than conventional PCR, and receiver operating characteristic analysis determined optimal ΔCT cutoff values of −2.13 and −4.09 for septic and aseptic specimens, respectively. Delays in specimen processing significantly affected real-time PCR accuracy. The 16S rRNA meta-taxonomic analysis using nanopore sequencing only validated the PCR results when the DNA concentration was sufficient. Conclusions: Broad-range real-time PCR proved to be a valuable diagnostic tool, particularly in aseptic specimens, with greater sensitivity and specificity than conventional PCR. The established ΔCT cutoff values improved diagnostic accuracy and showed that standardized specimen collection and processing are crucial for maximizing PCR efficacy.

This study empirically tested the reciprocal associations between work-life conflict and subjective wellbeing (life satisfaction, domain satisfaction, positive affect, and negative affect) using 21 waves of the Household, Income, and Labour Dynamics in Australia (HILDA) survey. Responses collected from working adults who responded to the work-family questions at least once were selected for the analysis (N ≈ 11,007). The study results demonstrate temporal within-person associations between work-life conflict and subjective wellbeing suggesting a feedback loop: an increased level of work-life conflict is associated with reduced subjective well-being in the following year while the reduced subjective well-being is linked to increased work-life conflict in the year to come. In addition to temporal effects, the results suggest contemporaneous within-person associations: in years when a person experiences higher-than-usual work-life conflict, they simultaneously report lower-than-usual well-being, and vice versa. Furthermore, the results also suggest moderate between-person associations between work-life conflict and subjective well-being. Overall, these findings highlight the immediate and long-term associations between work-life conflict and subjective wellbeing. Policy implications are discussed along with study limitations and suggestions for future research.

CKD-495 is a newly developed drug extracted from Cinnamomum cassia Presl. This phase II study assessed the clinical benefits of CKD-495 in the treatment of acute and chronic gastritis. This study randomly assigned 250 patients with endoscopically-proven gastric mucosal erosion to five groups. The groups received either 75 mg or 150 mg of CKD-495, 100 mg of rebamipide, 60 mg of Artemisiae argyi folium 95% ethanol ext. (20 ⟶ 1) (Stillen; Dong-A ST Co., Ltd., Seoul, Korea), or placebo for 2 weeks, respectively. The primary endpoint was the erosion improvement rate, and the secondary endpoints were erosion cure rates, improvement rates of gastrointestinal symptoms, edema, redness, and hemorrhage. Drug-related adverse events were evaluated. The endoscopic erosion improvement rate was significantly higher in the 75 mg CKD-495 group than in the other groups in both the full analysis set (73% vs. 41%, 45%, 52%, 48% for the 75 mg CKD-495, 150 mg CKD-495, placebo, 60 mg Stillen, and 100 mg rebamipide groups, respectively) and the per-protocol set (PPS) (75% vs. 37%, 45%, 51%, 50%). The cure rate of gastric erosion was significantly higher in the 75 mg CKD-495 group than in the other groups. The improvement rates of hemorrhage erosion were significantly higher in the 150-mg CKD-495 group. No significant differences were observed in the safety profiles. No serious adverse events or drug reactions were observed. These results demonstrate that 75 mg of CKD-495 has excellent efficacy for the treatment of endoscopic and symptomatic improvements for acute and chronic gastritis. Trial Registration: ClinicalTrials.gov identifier: NCT03437785

Background Chronic kidney disease (CKD) is associated with poor psychological well-being. Whether early-stage CKD is a risk factor for suicide warrants further research. Methods This nationwide, retrospective, cohort study aimed to evaluate the risk of suicide in patients with early-stage CKD and identify the associated risk factors. A total of 3.945,198 individuals aged ≥ 19 years who underwent the 2009 national health screening in South Korea were studied. Among them, 202,291 patients had early-stage CKD (estimated glomerular filtration rate (eGFR) ≥ 30 and < 60 mL/min per 1.73 m ² and/or dipstick albuminuria ≥ 1 +). The study outcome was suicide as confirmed by the nationwide death register based on death certificates. Results The study population had a mean age of 59 ± 15 years, and 47% were male. We identified 930 suicides (incidence rate, 0.45 per 1000 person-years) in the CKD group and 11,332 suicides (incidence rate, 0.27 per 1000 person-years) in the non-CKD group. Early-stage CKD was significantly associated with an increased risk of suicide in multivariable analysis adjusted for demographic characteristics; lifestyle habits; comorbidities, including diabetes and hypertension; economic status; and depression, bipolar disorder, schizophrenia (hazard ratio, 1.18; 95% confidence interval 1.10‒1.26). Suicide incidence was higher in individuals with proteinuria but preserved kidney function (eGFR > 60 mL/min per 1.73 m ² and dipstick albuminuria > 1 +) than in those without CKD. Conclusion Healthcare providers may need to examine the mental health of patients with early-stage CKD to prevent suicide. Graphical abstract

Aqueous metal-air batteries have received great attention as possible candidates for environmentally sustainable energy storage systems (ESS) based on their high energy density, high safety and low cost. Particularly, a variety of aqueous metal-air batteries have been studied for practical application. However, there are limitations arising from the intrinsic properties of their components and battery designs. To address these drawbacks, a wide range of materials have been developed as promising components for next-generation aqueous metal-air batteries. This review focuses on recent progress in materials design and engineering of aqueous metal-air batteries including Zn–, Al–, Mg– and Fe–air batteries, which highlights the development of novel materials and fabrication of innovative battery systems based on the metal anode, air cathode, aqueous electrolyte and electrocatalysts. Furthermore, flexible and flow batteries are intensively introduced as advanced aqueous metal-air batteries for future electronic devices. On the basis of these viewpoints, this review provides a future direction for the commercialization of aqueous metal-air batteries.

Visual question answering (VQA) is a dynamic field of research that aims to generate textual answers from given visual and question information. It is a multimodal field that has garnered significant interest from the computer vision and natural language processing communities. Furthermore, recent advances in these fields have yielded numerous achievements in VQA research. In VQA research, achieving balanced learning that avoids bias towards either visual or question information is crucial. The primary challenge in VQA lies in eliminating noise, while utilizing valuable and accurate information from different modalities. Various research methodologies have been developed to address these issues. In this study, we classify these research methods into three categories: Joint Embedding, Attention Mechanism, and Model-agnostic methods. We analyze the advantages, disadvantages, and limitations of each approach. In addition, we trace the evolution of datasets in VQA research, categorizing them into three types: Real Image, Synthetic Image, and Unbiased datasets. This study also provides an overview of evaluation metrics based on future research directions. Finally, we discuss future research and application directions for VQA research. We anticipate that this survey will offer useful perspectives and essential information to researchers and practitioners seeking to address visual questions effectively.