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Abstract Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Background/Aims: We investigated how interactions between humans and computer-aided detection (CADe) systems are influenced by the user’s experience and polyp characteristics.Methods: We developed a CADe system using YOLOv4, trained on 16,996 polyp images from 1,914 patients and 1,800 synthesized sessile serrated lesion (SSL) images. The performance of polyp detection with CADe assistance was evaluated using a computerized test module. Eighteen participants were grouped by colonoscopy experience (nurses, fellows, and experts). The value added by CADe based on the histopathology and detection difficulty of polyps were analyzed.Results: The area under the curve for CADe was 0.87 (95% confidence interval [CI], 0.83 to 0.91). CADe assistance increased overall polyp detection accuracy from 69.7% to 77.7% (odds ratio [OR], 1.88; 95% CI, 1.69 to 2.09). However, accuracy decreased when CADe inaccurately detected a polyp (OR, 0.72; 95% CI, 0.58 to 0.87). The impact of CADe assistance was most and least prominent in the nurses (OR, 1.97; 95% CI, 1.71 to 2.27) and the experts (OR, 1.42; 95% CI, 1.15 to 1.74), respectively. Participants demonstrated better sensitivity with CADe assistance, achieving 81.7% for adenomas and 92.4% for easy-to-detect polyps, surpassing the standalone CADe performance of 79.7% and 89.8%, respectively. For SSLs and difficult-to-detect polyps, participants' sensitivities with CADe assistance (66.5% and 71.5%, respectively) were below those of standalone CADe (81.1% and 74.4%). Compared to the other two groups (56.1% and 61.7%), the expert group showed sensitivity closest to that of standalone CADe in detecting SSLs (79.7% vs 81.1%, respectively).Conclusions: CADe assistance boosts polyp detection significantly, but its effectiveness depends on the user’s experience, particularly for challenging lesions.

This study was carried out to screen the antifungal activity against Colletotrichum acutatum, Colletotrichum dematium, and Colletotrichum coccodes. Bacterial isolate GP-P8 from pepper soil was found to be effective against the tested pathogens with an average inhibition rate of 70.7% in in vitro dual culture assays. 16S rRNA gene sequencing analysis result showed that the effective bacterial isolate as Bacillus siamensis. Biochemical characterization of GP-P8 was also performed. According to the results, protease and cellulose, siderophore production, phosphate solubilization, starch hydrolysis, and indole-3-acetic acid production were shown by the GP-P8. Using specific primers, genes involved in the production of antibiotics, such as iturin, fengycin, difficidin, bacilysin, bacillibactin, surfactin, macrolactin, and bacillaene were also detected in B. siamensis GP-P8. Identification and analysis of volatile organic compounds through solid phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS) revealed that acetoin and 2,3-butanediol were produced by isolate GP-P8. In vivo tests showed that GP-P8 significantly reduced the anthracnose disease caused by C. acutatum, and enhanced the growth of pepper plant. Reverse transcription polymerase chain reaction analysis of pepper fruits revealed that GP-P8 treated pepper plants showed increased expression of immune genes such as CaPR1, CaPR4, CaNPR1, CaMAPK4, CaJA2, and CaERF53. These results strongly suggest that GP-P8 could be a promising biocontrol agent against pepper anthracnose disease and possibly a pepper plant growth-promoting agent.

BackgroundUteroglobin is a multifunctional protein with anti-inflammatory properties. Studies have revealed the importance of inflammation in type 2 diabetes mellitus (T2D) pathogenesis. Here, we investigated the relationship between uteroglobin and T2D.MethodsWe performed diagnostic tests for diabetes in subjects who had not been diagnosed with or treated for T2D. We established three groups, containing those with normal glucose tolerance (NGT), prediabetes and T2D, consisting of 80 people each, and compared their uteroglobin levels. In addition, 28 patients newly diagnosed with T2D were treated with metformin for 12 weeks, and 63 patients newly diagnosed with dyslipidaemia during the treatment for T2D were treated with statin for 12 weeks.ResultsThis study showed that uteroglobin levels were significantly lower in prediabetes and T2D groups than in the NGT group. Uteroglobin levels were not significantly correlated with other metabolic parameters, except BMI, HOMA-β and eGFR. In the group treated with metformin or statin, uteroglobin levels increased after treatment compared to before treatment.ConclusionsUteroglobin is a sensitive factor that was decreased even in prediabetes and increased upon treatment with drugs with anti-inflammatory effects. Uteroglobin is a potential early biomarker that reflects a chronic inflammatory condition in T2D.

BackgroundOral anticoagulants (OACs) are essential for the prevention and treatment of thromboembolic disorders, but bleeding, a major complication, can have a fatal impact on the patient’s treatment.ObjectivesWe aimed to estimate the nationwide, real-world incidence rate of bleeding in patients taking OACs and confirm the incidence by indications and risk factors.MethodsThis cross-sectional study identified OAC users from April 1 to December 31, in both 2019 and 2020, using the HIRA-NPS database. The primary outcome variables were the incidence rate of major bleeding events during OAC treatment and within 30 days of treatment discontinuation. We estimated the adjusted incidence rate ratio (aIRR) in subpopulations.ResultsAmong 18,822 OAC users, the incidence rate of major bleeding was 27.9 (95% CI: 24.6–31.5) per 1,000 person-years. The incidence rate of major bleeding was higher in patients with a bleeding history, with an aIRR of 11.51; those at high bleeding risk (HAS-BLED score ≥3), with an aIRR of 1.51; those with high CCI scores ≥3, with an aIRR of 1.88; and those with liver disease, with an aIRR of 1.41. For indications, compared to patients with nonvalvular atrial fibrillation (NVAF), the aIRR of major bleeding was significantly higher at an aIRR of 2.35 in patients undergoing VTE treatment. Patients with ischemic stroke showed a higher incidence of major bleeding with an aIRR of 2.13 than NVAF patients. The aIRR of major bleeding in the oral anticoagulant group, compared to the matched control group, was 2.25 (95% CI: 1.93–2.63).ConclusionThese findings may be useful for implementing strategies to improve the evaluation and management of anticoagulation-related bleeding.

Abstract Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image–based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model’s decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Abstract Background Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. Results We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5ʹ region and 3ʹ region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5ʹ region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5ʹ region was impaired and rather increased in the 3ʹ region. Conclusions This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2’s binding to the transcribed genes and Set1 redistributes the Swd2 to the 5ʹ region for accomplishments of H3K4me3 in the genome-wide level.

Abstract Background The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. Methods RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein–protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. Results Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein–protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. Conclusion The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.

Background: The rising global incidence of cancer has increased the demand for chemotherapy, which is a crucial treatment modality. Recent advancements in cancer treatment, including targeted agents and immunotherapy, have introduced complications owing to their specific mechanisms. However, comprehensive studies of the combined complications of these approaches are lacking. Objectives: This study aimed to comprehensively assess and analyze the overall incidence of anticancer drug-related complications in a nationwide patient cohort, utilizing a customized National Health Insurance Sharing Service database in Korea. Design: Retrospective cohort study. Methods: We included patients who were prescribed anticancer drugs (excluding endocrine agents) and diagnosed with cancer. For the type of cancer classification, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) was used and anticancer drugs were classified based on the Anatomical Therapeutic Chemical code. We classified cancer into 18 types based on the ICD-10 code and delineated cancer-related complications into 12 categories. Complications included hematological, gastrointestinal, infectious, cardiovascular, major bleeding, endocrine, neurotoxic, nephrotoxic, dermatological, pulmonary, musculoskeletal, and hepatotoxic effects. Result: We included 294,544 patients diagnosed with cancer and administered anticancer drugs between 2016 and 2018, with follow-up continuing until 2021. We identified 486,929 anticancer drug-related complications, with an incidence of 1843.6 per 1000 person-years (PY). Anemia was the most common complication, with a rate of 763.7 per 1000 PY, followed by febrile neutropenia (295.7) and nausea/vomiting (246.9). Several complications peaked during the first months following the initiation of anticancer drug therapy; however, herpes, skin infection, heart failure, and peripheral neuropathy peaked at 6–12 months. Among major cancers, breast cancer had the lowest overall incidence of complications. Targeted therapies revealed lower complication rates than cytotoxic chemotherapy; however, they also required careful monitoring of rash. Conclusion: This study highlights the importance of the proactive management of anticancer drug-related complications for patient care improvement.

Abstract Objectives The exclusive endoscopic transcanal transpromontorial approach (EETTA) has recently been developed for the removal of small‐sized acoustic neuromas in the labyrinth (intralabyrinthine schwannoma [ILS]) or internal auditory canal (IAC). Although small tumors that meet the indications for EETTA are also good candidates for cochlear implantation (CI), there are few reports on CI after schwannoma removal using EETTA. Here we present an outcome of patients who underwent simultaneous EETTA and CI. Methods Five patients (two with IAC fundus tumors and three with ILS) who underwent simultaneous EETTA and CI between 2020 and 2022 were retrospectively enrolled. Their medical charts and test results were reviewed. Results After at least 12 months of follow‐up, there were no severe surgical complications such as meningitis, infection, or skin necrosis. Four of the five patients responded to auditory stimulation. Three out of four auditory‐responsive patients scored >80% on sentence recognition. Conclusion Simultaneous EETTA and CI are feasible for the treatment of ILS and IAC fundus tumors. Preservation of the cochlear nerve and modiolus is important for favorable CI outcomes. Therefore, ILS and IAC fundus tumors in patients with nonserviceable hearing should be surgically removed as early as possible to enable proper hearing rehabilitation with CI. Level of Evidence Level 4.

Abstract Background Sigmoid sinus diverticulum/dehiscence (SSD) is one of the treatable causes of venous pulsatile tinnitus. It can be diagnosed using temporal bone computed tomography (CT) or magnetic resonance angiography/venography (MRA). In cases where patients find their symptoms intolerable, surgical treatment is typically preferred. Here, we have presented a novel surgical technique involving sigmoid sinus re‐roofing and have analyzed its feasibility. Methods Between January 2020 and July 2023, approximately 150 patients with pulsatile tinnitus were evaluated at two different tertiary hospitals. Of these, 12 patients were diagnosed with SSD, and seven underwent surgical treatment. Five patients were treated with tailored reroofing (TRR) of the sigmoid sinus and two with transmastoid resurfacing (MRS) of the sigmoid sinus. We compared the Korean tinnitus handicap inventory (K‐THI) score, pure tone audiogram (PTA) threshold, and CT findings before and a month after surgeries for these two techniques. The operation time was also analyzed. Results In TRR cases, the K‐THI score reduced from 55.0 ± 31.4 preoperatively to 4.0 ± 3.0 postoperatively, and the SSD was well‐repositioned and covered by a bone chip postoperatively. In MRS cases, the K‐THI score reduced from 41.0 ± 9.9 preoperatively to 15.0 ± 21.2 postoperatively, and the SSD was well‐covered with bone cement postoperatively. The average surgical time of five TRR and two MRS cases were 77.5 ± 32.5 and 174.0 ± 75.0 min, respectively. No complications were noted. Conclusions Despite the insufficient number of cases, we noted that TRR requires a reasonable amount of time, involves a smaller incision, and may provide favorable outcomes compared to conventional MRS in cases of pulsatile tinnitus associated with SSD. Level of evidence IV.

Poly(3-hydroxybutyrate) (PHB), a biodegradable polymer, has been studied as a substitute for petroleum-based polymers used for barrier coating to improve the barrier and mechanical properties of paper. In this study, ethyl cellulose (EC), a cellulose derivative, was used to prepare a polymer blend for enhancing the barrier properties of PHB. The prepared PHB/EC blend was then applied as a paper coating material. Additionally, the barrier and mechanical properties of the PHB/EC blend-coated paper based on the PHB/EC mixing ratio and coating weight were analyzed. The results showed that the EC could act as a binder for the PHB/EC blend-coated paper. Consequently, the PHB/EC blend-coated paper exhibited significant improvements in mechanical and barrier properties, including a substantial increase of over 100% in internal bond strength, more than 20% in tensile strength, exceeding 60% enhancement in water resistance, and a remarkable increase of over 90% in air permeability.

Background Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. Methods A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. Results The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. Conclusion Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Abstract Adequate bowel preparation is an important factor in high-quality colonoscopy. It is generally accepted that a Boston Bowel Preparation Scale (BBPS) score ≥ 6 is adequate, but some reports suggest ≥ 7. Subjects who underwent colonoscopy at least twice within 3 years from August 2015 to December 2019 were included. Polyp detection rates (PDRs), adenoma detection rates (ADRs), and number of polyps including adenomas were compared stratified by baseline colonoscopy (C1) BBPS score. Among 2352 subjects, 529 had BBPS 6 (group 1) and 1823 had BBPS 7–9 (group 2) at C1. There was no significant difference in PDR or ADR at C1 and follow-up colonoscopy (C2) between the two groups. However, the numbers of polyps (1.84 vs. 1.56, P = 0.001) and adenomas (1.02 vs. 0.88, P = 0.034) at C2 were significantly higher in group 1 than group 2, respectively. Segmental BBPS score 2 in group 1 compared to group 2, especially, showed higher PDR (P = 0.001) and ADR (P = 0.007) at C2. BBPS 6 is associated with a higher number of polyps and adenomas in short-term follow-up colonoscopy than BBPS 7–9. To reduce the risk of missed polyps, a thorough examination is necessary for BBPS 6.

This study leverages explainable artificial intelligence (XAI) techniques to analyze public sentiment towards Environmental, Social, and Governance (ESG) factors, climate change, and green finance. It does so by developing a novel multi-task learning framework combining aspect-based sentiment analysis, co-reference resolution, and contrastive learning to extract nuanced insights from a large corpus of social media data. Our approach integrates state-of-the-art models, including the SenticNet API, for sentiment analysis and implements multiple XAI methods such as LIME, SHAP, and Permutation Importance to enhance interpretability. Results reveal predominantly positive sentiment towards environmental topics, with notable variations across ESG categories. The contrastive learning visualization demonstrates clear sentiment clustering while highlighting areas of uncertainty. This research contributes to the field by providing an interpretable, trustworthy AI system for ESG sentiment analysis, offering valuable insights for policymakers and business stakeholders navigating the complex landscape of sustainable finance and climate action. The methodology proposed in this paper advances the current state of AI in ESG and green finance in several ways. By combining aspect-based sentiment analysis, co-reference resolution, and contrastive learning, our approach provides a more comprehensive understanding of public sentiment towards ESG factors than traditional methods. The integration of multiple XAI techniques (LIME, SHAP, and Permutation Importance) offers a transparent view of the subtlety of the model’s decision-making process, which is crucial for building trust in AI-driven ESG assessments. Our approach enables a more accurate representation of public opinion, essential for informed decision-making in sustainable finance. This paper paves the way for more transparent and explainable AI applications in critical domains like ESG.

Objective Employing three cycles of Design Science Research (DSR) to develop a mobile app ‘ESSC (Excellent Self Supervised HIV Care)’ to improve self-management among people living with HIV (PLWH). Methods This study is based on the DSR framework comprising three iterative cycles. In the Relevance cycle, PLWH participated in a survey of mobile health (mHealth) experiences and needs. In the Rigor cycle, the information-motivation-behavioural skills (IMB) model was applied to foundations of the app, and HIV specialists verified the contents. Experts evaluated the heuristic system and the app quality with the Mobile Application Rating Scale (MARS). In the Design cycle, ESSC was built on the findings of the other two cycles, and end-users tested the usability using uMARS. Results The contents of the app were developed based on user requirements. The IMB model led ESSC to supplement motivational components for self-management, which built five functions: information contents; health life records including mental and sexual health; interactive counselling with healthcare providers; setting health goals after watching videos; and my page for self-reflection. To reduce social stigma and promote acceptance of the information-driven app, we created animated characters with neutral and bright features. The HIV specialists evaluated content validity as highly appropriate. The MARS score by the overall raters was between 3- acceptable and 4- good : functionality, 4.38; information, 4.12; aesthetics, 3.96; engagement, 3.37; and subjective quality, 3.25. Conclusions The DSR approach is effective for implementing usable and useful mHealth. The ESSC app would be feasible and contribute PLWH to retention in care.

ObjectivesChronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to β-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers.MethodsIn this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication.ResultsThe fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (−4.5 ± 14.1% and −1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339).ConclusionsWe observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.

Atopic dermatitis (AD) is a common allergic inflammatory skin condition marked by severe itching, skin lichenification, and chronic inflammation. AD results from a complex immune response, primarily driven by T lymphocytes and environmental triggers, leading to a disrupted epidermal barrier function. Traditional treatments, such as topical corticosteroids, have limitations due to long-term side effects, highlighting the need for safer alternatives. Here, we aimed to show that Agrimonia coreana extract (ACext) can be used in treating AD-related dermatologic symptoms. ACext could inhibit CRAC (Calcium Release-Activated Calcium) channel activity, reducing Orai1/CRAC currents and decreasing intracellular calcium signaling. This inhibition was further confirmed by the reduced IL-2 levels and T cell proliferation upon ACext treatment. In a mouse model of AD, ACext significantly ameliorates symptoms, improves histological parameters, and enhances skin barrier function, demonstrating its potential for treating AD.

Global public health is facing a major issue with emerging resistance to antimicrobial agents. Antimicrobial agents that are currently on the market are strong and efficient, but it has not been ruled out that these medications will eventually cause resistance to bacteria. Exploring novel bioactive compounds derived from natural sources is therefore, crucial to meet future demands. The present study evaluated the mode of action of the antimicrobial potential protease enzyme SH21. Protease SH21 exhibited antimicrobial activity, strong heat stability (up to 100 °C), and pH stability (pH 3.0 to 9.0). In terms of mode of action, we found that protease SH21 was able to disrupt the bacterial cell membrane as the results of the nucleotide leakage and cell membrane permeability assay. In addition, we also checked inner membrane permeability by PI uptake assay which suggested that protease SH21 has the ability to enter the bacterial cell membrane. Our results revealed that the antimicrobial protease SH21 might be a promising candidate for treating microbial infections.

Objectives: To evaluate radiation exposure, image quality, and diagnostic performance of coronary CT angiography (CCTA) using the invasive coronary angiography (ICA) as the reference standard in patients with irregular heart rhythm on a 0.25 s rotation time, 16 cm coverage, single-beat, CT scanner with AI-assisted motion correction. Methods: CCTA data-sheets of 427 patients using a CT scanner with an ECG monitoring system and motion correction algorithm were collected retrospectively. All the patients were divided into two groups: regular heart rhythm (357 patients) and irregular heart rhythm (70 patients). 22 patients in irregular heart rhythm underwent ICA. Image quality and effective dose in both groups were evaluated and compared. Image quality was evaluated on 5-point scales. The diagnostic performance of CCTA in irregular heart rhythm group was compared with the results of ICA. Results: The image quality in both groups was similar (4.34 ± 0.47 vs 4.37 ± 0.48, p > 0.05). No significant difference was observed in effective dose between two groups (2.7 ± 0.7 vs 2.9 ± 1.3, p > 0.05). The diagnostic accuracy was 90.91% in a patient-based analysis, 96.97% in a vessel-based analysis, and 98.61% in a segment-based analysis. In irregular heart rhythm group, gender was an important factor affecting the number of CCTA scans in a single examination and the radiation dose exposed to the patient. Conclusions: For patients with irregular heart rhythm, a CT scanner with an ECG monitoring system and motion correction algorithm can not only reduce the radiation dose to the same level as patients with normal heart rhythms, but also ensure that the images with high diagnostic accuracy.

Abstract The primary objective of this study was to investigate the factors contributing to hyperglycemic adverse events (AEs) associated with the administration of remdesivir in hospitalized patients diagnosed with coronavirus disease 2019 (COVID‐19). Furthermore, the study aimed to develop a risk score model employing various machine learning approaches. A total of 1262 patients were enrolled in this investigation. The relationship between covariates and hyperglycemic AEs was assessed through logistic regression analysis. Diverse machine learning algorithms were employed for the purpose of forecasting hyperglycemia‐related complications. After adjusting for covariates, individuals with a body mass index ≥23 kg/m2, those using proton pump inhibitors, cholinergic medications, or individuals with cardiovascular diseases exhibited approximately 2.41‐, 2.73‐, 2.65‐, and 1.97‐fold higher risks of experiencing hyperglycemic AEs (95% CI 1.271–4.577, 1.223–6.081, 1.168–5.989, and 1.119–3.472, respectively). Multivariate logistic regression, elastic net, and random forest models displayed area under the receiver operating characteristic curve values of 0.65, 0.66, and 0.60, respectively (95% CI 0.572–0.719, 0.640–0.671, and 0.583–0.611, respectively). This study comprehensively explored factors associated with hyperglycemic complications arising from remdesivir administration and, concurrently, leveraged a range of machine learning methodologies to construct a risk scoring model, thereby facilitating the tailoring of individualized remdesivir treatment regimens for patients with COVID‐19.

IntroductionLateral semicircular canal (LSCC) dysplasia is the most common inner ear malformation. The severity of dysplasia can appear in various spectrums, from a short and broad LSCC with normal or small-sized central bony island (CBI) to a single fluid-filled cavity confluent with the vestibule without CBI. However, reports on the association between LSCC dysplasia and the loss of vestibular function are still lacking. In this study, the results of vestibular function tests [caloric test and video-head impulse test (vHIT)] in patients with LSCC dysplasia were analyzed and compared between groups with and without CBI.MethodsThis study retrospectively enrolled 17 patients (23 ears) who had LSCC dysplasia following computed tomography or magnetic resonance imaging and underwent vestibular function tests.ResultsLSCC dysplasia was observed unilaterally in 11 patients and bilaterally in six patients. Nine of 23 ears had CBIs, and 14 ears had no CBI. Three of 17 patients experienced dizziness. Abnormal caloric tests were detected in 11 of the 16 patients who underwent the caloric tests (69%); in contrast, 11 of 12 patients who underwent the vHIT (92%) had normal LSCC vestibulo-ocular reflex (VOR) gain on vHIT. A significant correlation was found between the maximum slow-phase velocity of the caloric test and LSCC VOR gain of the vHIT (correlation coefficient 0.792, p = 0.004). The CBI-absent group showed significantly lower SPV and LSCC VOR gains than the CBI-present group (p = 0.001 and 0.004, respectively).DiscussionLSCC dysplasia impairs VOR function, especially in the absence of CBI.

The use of laboratory animals in biomedical research has significantly advanced scientific understanding, yet it raises ethical concerns about animal welfare and the mental health of researchers Recent research has highlighted the potential for stress and compassion fatigue among researchers working with distressed animals. Attending veterinarians (AVs) are crucial in mitigating the pain and stress experienced by animals and, by extension, researchers. However, the impact of AVs on researchers’ psychological well-being remains understudied. This study explores how AVs contribute to researchers’ research capability and psychological well-being in animal research institutions. AVs oversee animal housing, health, and welfare; their involvement is mandated or strongly recommended in developed countries. AVs enhance animal welfare by ensuring proper housing, nutrition, and social interaction. They monitor animal health, educate researchers on pain assessment, and promote compliance with post-surgical care. AVs also contribute to researchers’ well-being by addressing euthanasia procedures, which can be emotionally challenging. Programs for rehoming animals after experiments offer an alternative to euthanasia and positively impact researchers’ psychological well-being. Moreover, AVs promote workplace well-being by fostering positive workplace cultures, offering peer counseling, and providing social support. Programs considering animal welfare and researchers’ emotions are crucial for a healthy research environment. In conclusion, AVs are essential in balancing scientific progress with animal welfare and researchers’ psychological well-being. Therefore, their role should be recognized as vital in achieving social equity that considers the welfare of humans and laboratory animals.

Recent advancements in understanding the intricate molecular mechanisms underlying immunological responses have underscored the critical involvement of ion channels in regulating calcium influx, particularly in inflammation. Nootkatone, a natural sesquiterpenoid found in Alpinia oxyphylla and various citrus species, has gained attention for its diverse pharmacological properties, including anti-inflammatory effects. This study aimed to elucidate the potential of nootkatone in modulating ion channels associated with calcium signaling, particularly CRAC, KV1.3, and KCa3.1 channels, which play pivotal roles in immune cell activation and proliferation. Using electrophysiological techniques, we demonstrated the inhibitory effects of nootkatone on CRAC, KV1.3, and KCa3.1 channels in HEK293T cells overexpressing respective channel proteins. Nootkatone exhibited dose-dependent inhibition of channel currents, with IC50 values determined for each channel. Nootkatone treatment did not significantly affect cell viability, indicating its potential safety for therapeutic applications. Furthermore, we observed that nootkatone treatment attenuated calcium influx through activated CRAC channels and showed anti-proliferative effects, suggesting its role in regulating inflammatory T cell activation. These findings highlight the potential of nootkatone as a natural compound for modulating calcium signaling pathways by targeting related key ion channels and it holds promise as a novel therapeutic agent for inflammatory disorders.

Plant-derived extracellular vesicles (EVs) elicit diverse biological effects, including promoting skin health. EVs isolated from Ecklonia cava (EV-EC) carry heat shock protein 70 (HSP70), which inhibits key regulators such as TNF-α, MAPKs, and NF-κB, consequently downregulating matrix metalloproteinases (MMPs). Aging exacerbates oxidative stress, upregulating MAPK and NF-κB signaling and worsening extracellular matrix degradation in the skin. E. cava-derived phlorotannin (PT) mitigates MAPK and NF-κB signaling. We evaluated the impact of EV-EC and PT on skin rejuvenation using an in vitro keratinocyte senescence model and an in vivo aged-mouse model. Western blotting confirmed the presence of HSP70 in EV-EC. Treatment with EV-EC and PT in senescent keratinocytes increased HSP70 expression and decreased the expression of TNF-α, MAPK, NF-κB, activator protein-1 (AP-1), and MMPs. Oxidative stress was also reduced. Sequential treatment with PT and EV-EC (PT/EV-EC) yielded more significant results compared to individual treatments. The administration of PT/EV-EC to the back skin of aged mice mirrored the in vitro findings, resulting in increased collagen fiber accumulation and improved elasticity in the aged skin. Therefore, PT/EV-EC holds promise in promoting skin rejuvenation by increasing HSP70 expression, decreasing the expression of MMPs, and reducing oxidative stress in aged skin.