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Kiyon Rhew,1 Jisu Choi,1 Kyungim Kim,2,3 Kyung Hee Choi,4 So-Hee Lee,5 Heung-Woo Park6 1College of Pharmacy, Dongduk Women’s University, Seoul, Republic of Korea; 2Institute of Pharmaceutical Science, Korea University, Sejong, Republic of Korea; 3College of Pharmacy, Korea University, Sejong, Republic of Korea; 4College of Pharmacy, Gachon University, Incheon, Republic of Korea; 5Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea; 6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaCorrespondence: Kiyon Rhew; Heung-Woo Park, Tel +82 2 940 4519 ; +82 2 742 3291, Fax +82-2-940-4159 ; +82 2 2072 0699, Email kiyon@dongduk.ac.kr; guinea71@snu.ac.krPurpose: Asthma can cause a systemic inflammatory response, and anemia of chronic disease (ACD) is known to be caused by other disorders with a chronic inflammatory state. However, it is unclear whether the incidence of anemia is increased in patients with asthma. The objective of this study was to compare the incidence of anemia in patients with asthma and healthy adults.Patients and Methods: This retrospective cohort study included patients newly diagnosed with asthma at Seoul National University Hospital from 2010 to 2017. Patients with comorbidities before the first visit (index date) that may increase anemia risk were excluded. Cox regression models adjusting for patient age, sex, and obesity were used to compare anemia hazard ratios (HRs) between asthma patients (n=1354) and healthy adults (n=1731).Results: This study included 3085 patients. During 5-y follow-up, anemia occurred in 203 (15.0%) patients with asthma and 79 (4.6%) healthy adults. Compared with healthy adults, the HR for anemia after adjusting for age, sex, and obesity was 4.06 (95% CI: 2.70– 6.09) in patients with asthma. In patients aged 18– 64.9 y, the adjusted HR of anemia was 3.27 (95% CI: 2.12– 5.04) in patients with asthma, compared to healthy patients. In patients > 65 y, this adjusted HR was 5.56 (95% CI: 1.31– 23.67).Conclusion: The risk of anemia was increased in patients with asthma after adjusting for sex, age, and obesity and excluding comorbidities that can cause anemia. These results suggest the need for regular monitoring for anemia in patients with asthma.Keywords: anemia, asthma, inflammation, anemia of chronic disease

This paper examines international relations as perceived by the public in their social media conversations. It examines over 1.8 billion Facebook postings in English and 51 million Chinese posts on Weibo, to reveal the relations among nations as expressed in social media conversations. It argues that social media represent a transnational electronic public sphere, in which public discussions reveal characteristics of international relations as perceived by a foreign public. The findings show that the international relations in social media postings match the core-peripheral structure proposed in the World Systems Theory. Additionally, the relations are associated with the amount of news coverage and public attention a country receives. Overall, the study demonstrates the value of webometric data in revealing how international relations are perceived by average citizens.

This study describes the evolution of the international hyperlink network. The World Wide Web is a distributed hypertext system consisting of a virtual network of content and hyperlinks with billions of interlinked pages. Since the Web has no "engineered architecture," it can be understood as a self-organized system with a well-defined structure of linkage that implies an underlying social structure. This article examines the evolution of the Web’s emergent social structure and communication network at the level of nation-states. It reviews the literature on the international hyperlink network and then focuses on changes between 2009 and 2010 using data on the frequency of bilateral hyperlinks between nations. The article discusses special problems associated with the top-level domain .com as well as other generic top-level domains that do not refer to specific nations whose domain names refer to commercial or vanity applications.

Objectives: To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics.Methods: Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis.Results: TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV(1) and FVC (P < 0.05).Conclusions: Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT.Key Points: • In asthmatics, xenon ventilation decreases after methacholine and increases after salbutamol inhalation. • Inner airway area (IA) correlates well with xenon ventilation. • IA is the most reliable parameter reflecting airway changes in drug responses. [ABSTRACT FROM AUTHOR]

Background: Ankle valgus deformity secondary to proximal migration of the fibula following an Ilizarov tibial lengthening has not been discussed in detail in the literature. The purposes of this study were to determine the underlying mechanism of and to identify factors associated with proximal migration of the fibula that caused ankle valgus deformity after an Ilizarov tibial lengthening.Methods: We reviewed the outcome of seventy-four bilateral Ilizarov tibial lengthenings for short stature in thirty-seven patients. The mean age at the time of surgery was 21.7 years (range, thirteen to thirty-one years), and the mean duration of follow-up was forty-five months. Proximal migration of the fibula was assessed with changes in the malleolar tip distance. A valgus change of ≥ 5° in the tibiotalar angle was regarded as ankle valgus deformity following tibial lengthening.Results: The average length gain was 6.9 cm (range, 4.7 to 11.5 cm), and the average lengthening index was 1.5 mo/cm. Valgus deformity developed in six ankles (8%) and fibular nonunion developed in ten (14%). Proximal migration of the lateral malleolus of ≥ 5 mm was related to valgus talar tilting. Bifocal tibial lengthening, rapid distraction rate of the fibula (>1 mm per day), and development of a fibular nonunion were factors associated with proximal migration of the distal end of the fibula of ≥ 5 mm, which suggests that regenerated bone of poor quality in the distraction gap may cause proximal migration of the distal end of the fibula following tibial lengthening.Conclusions: Proximal migration of the distal end of the fibula following tibial lengthening may occur even with the use of an Ilizarov ring fixator. This migration seems to be caused by collapse of regenerated bone of poor quality or fibular nonunion. Proximal migration of ≥ 5 mm is associated with the risk of valgus talar tilting. Surgeons should consider earlier intervention with bone-grafting if there are conditions that compromise regenerated bone formation in the fibular distraction gap, such as can occur with extensive tibial lengthening by bifocal corticotomy. [ABSTRACT FROM AUTHOR]

Unlabelled: Premature closure of the proximal epiphysis in patients with Legg-Calvé-Perthes disease can cause overgrowth of the greater trochanter. We asked whether distal transfer of the greater trochanter relieved pain and improved limp and whether the operation changed frontal plane kinematic and kinetic parameters of the hip and pelvis in the gait analysis. We reviewed 15 patients (15 hips) with an average age of 16.9 years (range, 13-26 years) who had the operation and were followed for a minimum of 28 months (average, 42 months; range, 28-54 months). The Iowa hip score increased from 85.0 (range, 75.5-87.0) before surgery to 89.1 (range, 83.0-97.0) at the final followup. Only three patients had no pain and Trendelenburg sign postoperatively. Pelvic obliquity angle of affected and contralateral normal hips in ipsilateral stance and contralateral swing phases remained unchanged after surgery. Hip adduction angle and abductor moment during single stance phase of affected and contralateral normal hips were not changed. We concluded trochanteric advancement does little to relieve pain and improve limp in patients with relative overgrowth of the greater trochanter and Legg-Calvé-Perthes disease.Level Of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

On March 25th 2019, the Belle II detector recorded the first collisions delivered by the SuperKEKB accelerator. This marked the beginning of the physics run with vertex detector. The vertex detector was aligned initially with cosmic ray tracks without magnetic field simultaneously with the drift chamber. The alignment method is based on Millepede II and the General Broken Lines track model and includes also the muon system or primary vertex position alignment. To control weak modes, we employ sensitive validation tools and various track samples can be used as alignment input, from straight cosmic tracks to mass-constrained decays. With increasing luminosity and experience, the alignment is approaching the target performance, crucial for the first physics analyses in the era of Super-BFactories. We will present the software framework for the detector calibration and alignment, the results from the first physics run and the prospects in view of the experience with the first data.

The Belle II experiment features a substantial upgrade of the Belle detector and will operate at the SuperKEKB energy-asymmetric e+e− collider at KEK in Tsukuba, Japan. The accelerator completed its first phase of commissioning in 2016, and the Belle II detector saw its first electron-positron collisions in April 2018. Belle II features a newly designed silicon vertex detector based on double-sided strip layers and DEPFET pixel layers. A subset of the vertex detector was operated in 2018 to determine background conditions (Phase 2 operation). The collaboration completed full detector installation in January 2019, and the experiment started full data taking. This paper will report on the final arrangement of the silicon vertex detector part of Belle II with a focus on online monitoring of detector conditions and data quality, on the design and use of diagnostic and reference plots, and on integration with the software framework of Belle II. Data quality monitoring plots will be discussed with a focus on simulation and acquired cosmic and collision data.

Abstract Solvation free energy is a fundamental thermodynamic quantity that should be determined to estimate various physicochemical properties of a molecule and the desolvation cost for its binding to macromolecular receptors. Here, we propose a new solvation free energy function through the improvement of the solvent-contact model, and test its applicability in estimating the solvation free energies of organic molecules with varying sizes and shapes. This new solvation free energy function is constructed by combining the existing solute-solvent interaction term with the self-solvation term that reflects the effects of intramolecular interactions on solvation. Four kinds of atomic parameters should be determined in this solvation model: atomic fragmental volume, maximum atomic occupancy, atomic solvation, and atomic self-solvation parameters. All of these parameters for total 37 atom types are optimized by the operation of a standard genetic algorithm in such a way to minimize the difference between the experimental solvation free energies and those calculated by the solvation free energy function for 362 organic molecules. The solvation free energies estimated from the new solvation model compare well with the experimental results with the associated squared correlation coefficients of 0.88 and 0.85 for training and test sets, respectively. The present solvation model is thus expected to be useful for estimating the solvation free energies of organic molecules.

STUDY DESIGN.: Behavior, mRNA and immunohistochemical assessment of the expression of fractalkine (CX3CL1) and its receptor (CX3CR1) in a rat model of disc herniation by autologous nucleus pulposus (NP) implantation. OBJECTIVE.: To evaluate the changes in expression of fractalkine and its receptor in the spinal cord and their association with pain behavior in a rat model of disc herniation. SUMMARY OF BACKGROUND DATA.: Chemokines have recently been implicated in the pathophysiology of neuropathic pain. They mediate astrocytic migration and microglial proliferation, which are involved in the regulation of nociceptive transmission. Fractalkine is a chemokine, which participates in the mechanisms of neuropathic pain as a mediator of neuron-glia interactions. METHODS.: Sixty-six rats (NP-treated = 47, sham = 19) were implanted with autologous NP (approximately 3 mg) on the left L5 nerve root, just proximal to the dorsal root ganglion and tested for thermal hyperalgesia and mechanical allodynia before surgery and on days 1, 5, 10, 20, and 30 after surgery. The changes of expression of fractalkine and its receptor in the spinal cord were studied using real time PCR and immunohistochemistry. RESULTS.: Rats developed ipsilateral mechanical allodynia at day 1 and bilateral thermal hyperalgesia at day 5 after surgery, and these changes in sensitivity persisted throughout the observation period. The expression of mRNA for fractalkine in the spinal cord was increased by day 5 and remained upregulated for the duration of the experiment. The immunostaining for fractalkine increased in neurons and astrocytes and that for the fractalkine receptor increased in microglia in the dorsal horn ipsilateral to the disc herniation. CONCLUSION.: Our results indicate that autologous implantation of NP induces thermal hyperalgesia and mechanical allodynia, and leads to an upregulation of fractalkine and its receptor in spinal neurons and glia, implicating fractalkine in association with radicular pain. [ABSTRACT FROM AUTHOR]

Study Design: Prospective study of 31 patients who underwent anterior cervical fusion. Objective: To investigate the efficacy of polyetheretherketone (PEEK) cages and demineralized bone matrix (DBM) for anterior cervical discectomy and fusion (ACDF). Summary Of Background Data: Although high fusion rates can be achieved with autogenous bone grafts, donor-site morbidity affects the patient's satisfaction with the surgical outcome. Methods: Thirty-one consecutive patients treated with ACDF using the PEEK cage with DBM (Grafton, Osteotech, Inc., Shrewsbury, NJ) at 42 levels were prospectively evaluated with a minimum of 12-month follow-up (mean: 16 months). Twenty-one patients underwent a single-level ACDF, 9 patients underwent a 2-level ACDF, and 1 patient had a 3-level ACDF. The affected level was C3-C4 in 7 patients; C4-C5 in 9, C5-C6 in 16, and C6-C7 in 10. The neurologic outcomes were evaluated using the VAS score for neck and arm pain and the Japanese Orthopedic Association scoring system for myelopathy at 3, 6, and 12 months. The cervical lordosis and fusion status were assessed on radiographs including flexion/extension radiographs. Results: At 12 months, the radiographs demonstrated grades I, II, and III new bone formation at 1, 13, and 28 levels, respectively. There was a significant improvement in both the neck and arm pain and a significant improvement in the Japanese Orthopedic Association scores at the last follow-up. There was no case with implant-related complications such as cage failure or migration, and no complications associated with the use of Grafton. Conclusion: ACDF using the Solis cage packed with Grafton demonstrated good clinical and radiologic outcomes. The fusion rate was comparable with the published results of the traditional ACDF using tricortical iliac crest grafts. Therefore, the results of this study suggest that the ongoing use of the PEEK cage packed with DBM and autologous bone chips in ACDF is a safe and effective alternative to the gold standard of autologous iliac bone grafts. [ABSTRACT FROM AUTHOR]

Background: Although the presence of both obesity and reduced muscle mass presents a dual metabolic burden and additively has a negative effect on a variety of cardiometabolic parameters, data regarding the associations between their combined effects and left ventricular diastolic function are limited. This study investigated the association between the ratio of skeletal muscle mass to visceral fat area (SVR) and left ventricular diastolic dysfunction (LVDD) in patients with preserved ejection fraction using random forest machine learning., Methods: In total, 1,070 participants with preserved left ventricular ejection fraction who underwent comprehensive health examinations, including transthoracic echocardiography and bioimpedance body composition analysis, were enrolled. SVR was calculated as an index of sarcopenic obesity by dividing the appendicular skeletal muscle mass by the visceral fat area., Results: In the random forest model, age and SVR were the most powerful predictors of LVDD. Multivariate logistic regression analysis demonstrated that older age (adjusted odds ratio [OR], 1.11; 95% confidence interval [CI], 1.07 to 1.15) and lower SVR (adjusted OR, 0.08; 95% CI, 0.01 to 0.57) were independent risk factors for LVDD. SVR showed a significant improvement in predictive performance and fair predictability for LVDD, with the highest area under the curve noted in both men and women, with statistical significance. In non-obese and metabolically healthy individuals, the lowest SVR tertile was associated with a greater risk of LVDD compared to the highest SVR tertile., Conclusion: Decreased muscle mass and increased visceral fat were significantly associated with LVDD compared to obesity, body fat composition, and body muscle composition indices.

Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway. Depletion of TAZ in tumor-associated macrophages promoted tumor growth by suppressing the recruitment of tumor-infiltrating lymphocytes. Moreover, in a diet-induced metabolic dysfunction-associated steatohepatitis model, macrophage-specific deletion of TAZ ameliorated liver inflammation and hepatic fibrosis. Thus, targeted therapies being developed against YAP/TAZ-TEAD are ineffective in macrophages. Together, our results introduce Golgi-associated TAZ as a potential molecular target for therapeutic intervention to treat tumor progression and chronic inflammatory diseases.

Background: Intravascular ultrasound (IVUS) guidance has been shown to yield favorable outcomes for endovascular treatment of femoropopliteal artery (FPA) disease with drug-coated balloon (DCB) angioplasty. However, the specific benefits of IVUS for treatment of complex FPA lesions remain uncertain., Objectives: In this study, the authors compared the clinical impact of IVUS-guided vs angiography-guided DCB angioplasty in patients with complex or noncomplex FPA lesions., Methods: This study was a prespecified, primary subgroup analysis of the randomized IVUS-DCB trial. Patients with FPA undergoing DCB angioplasty were randomized to receive the procedure under IVUS or angiography guidance. The primary endpoint was 12-month primary patency; secondary endpoints included clinically driven target lesion revascularization (CD-TLR), sustained clinical improvement, and hemodynamic improvement., Results: Among the 237 patients enrolled, 158 had complex FPA (Trans-Atlantic Inter-Society Consensus II [TASC II] type C/D), and 79 had noncomplex FPA (TASC II type A/B). In complex FPA, IVUS guidance was associated with significantly higher rates of primary patency (82.1% vs 60.3%; HR for loss of primary patency: 0.34; 95% CI: 0.16-0.70; P = 0.002), freedom from CD-TLR (90.0% vs 76.9%; HR: 0.31; 95% CI: 0.13-0.75; P = 0.01), and sustained clinical and hemodynamic improvement relative to angiography guidance. There was no significant difference in primary patency (87.5% vs 88.2%; HR: 1.84; 95% CI: 0.39-8.60; P = 0.44) or occurrence secondary endpoints between the IVUS-guidance and angiography-guidance groups for patients with noncomplex FPA., Conclusions: In endovascular treatment of FPA using DCB, IVUS guidance was significantly associated with improved 12-month clinical outcomes, particularly in patients with complex FPA lesions.(Intravascular Ultrasound-Guided Drug-Coated Balloon Angioplasty for Femoropopliteal Artery Disease [IVUS-DCB] trial; NCT03517904)., Competing Interests: Funding Support and Author Disclosures This study was funded by Medtronic Inc. and Korea United Pharmaceutical, and supported by the Cardiovascular Research Center, Seoul, Korea. Dr Ko has received research grants from Medtronic, Korea United Pharm, Cook Medical, Boston Scientific, Otsuka Korea, Dong-A ST, Samjin Pharm, and Cordis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Particulate matter (PM) exposure has been proposed as one of the causes of steroid resistance. However, studies investigating this using patient samples or animals are still lacking. Therefore, in this study, we aimed to investigate the changes in cytokines and mTOR (mammalian target of rapamycin) activation in patients with steroid resistant asthma and the role of mTOR in a mouse model of steroid resistant asthma induced by PM. In mouse experiment, on administering PM10 and allergen (Dp) through the intranasal route for 3 weeks, airway hyperresponsiveness (AHR), eosinophils, and airway inflammation were increased. However, administering rapamycin (mTOR inhibitor) together with PM and Dp led to significant decrease in all of the abovementioned features; additionally, the population of IL-13 + or IL-17 + cells in CD62 low CD44 high subset of CD4 + T cells, which serves as an effector/memory cell marker, showed a significant decrease when compared to the group that received PM and Dp. When Dp was administered once after a rest period, the mice exposed to PM and Dp exhibited resurgence in asthma features and elevated effector/memory IL-13 + or IL-17 + cell populations. Rapamycin administration inhibited this effect. In human PBMC, in the steroid Non-Responder (NR) group, cytokines with p-mTOR double-positive population of effector/memory CD4 T cells (CCR7-CD45RA-CD4 + in CD62-CD27-CD45RO+) was significantly higher than that of the Normal or steroid Responder (R) groups. These data demonstrates that rapamycin can inhibit asthmatic features in mouse model of PM induced steroid-resistant asthma. And we suggest that rapamycin could act on effector/memory CD4 + T cells through in vitro and patient sample experiments., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study was approved by the Institutional Review Board of the Seoul National University Hospital. And the mouse experimental protocol was approved by the Institutional Animal Care and Use Committee of the Institute of Laboratory Animal Resources at Seoul National University Hospital., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The ionic mechanism underlying Brugada syndrome (BrS) arises from an imbalance in transient outward current flow between the epicardium and endocardium. Previous studies report that artemisinin, originally derived from a Chinese herb for antimalarial use, inhibits the Ito current in canines. In a prior study, we showed the antiarrhythmic effects of artemisinin in BrS wedge preparation models. However, quinidine remains a well-established antiarrhythmic agent for treating BrS. Therefore, this study aims to investigate the efficacy of combining artemisinin with low-dose quinidine in suppressing ventricular tachyarrhythmia (VTA) in experimental canine BrS models., Methods: Transmural pseudo-electrocardiogram and epicardial/endocardial action potential (AP) were recorded from coronary-perfused canine right ventricular wedge preparation. To mimic the BrS model, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and Ito agonist NS5806 (6-10 μM) were administered until VTA was induced. Subsequently, low-dose quinidine (1-2 μM) combined with artemisinin (100 μM) was perfused to mitigate VTA. Key parameters, including AP duration, J wave area, notch index, and T wave dispersion, were measured., Results: After administering the provocation agents, all sample models exhibited prominent J waves and VTA. Artemisinin alone (100-150 μM) suppressed VTA and restored the AP dome in all three preparations. Its infusion resulted in reductions in the J wave area and epicardial notch index. Consequently, low-dose quinidine (1-2 μM) did not fully restore the AP dome in all six sample models. However, when combined with additional artemisinin (100 μM), low-dose quinidine effectively suppressed VTA in all six models and restored the AP dome while also decreasing the J wave area and epicardial notch index., Conclusion: Low-dose quinidine alone fails to fully alleviate VTA in the BrS wedge model. However, its combination with artemisinin effectively suppresses VTA. Artemisinin may reduce the therapeutic dose of quinidine, potentially minimizing its associated adverse effects., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2025 The Korean Academy of Medical Sciences.)

Objectives: MicroRNAs (miRNAs) are pivotal in post-transcriptionally modulating gene expression in both animals and plants. This study investigates the relationship between microRNA polymorphisms and the occurrence of primary ovarian insufficiency in Korean women. Our hypothesis posits that polymorphisms in microRNAs-specifically miR-10aA > T, miR-30cA > G, miR-181aT > C, and miR-499bA > G-may be linked to primary ovarian insufficiency, influencing the risk of developing the condition., Methods: We conducted a case-control study of 141 Korean women with primary ovarian insufficiency and 281 control individuals with at least one live birth and no history of pregnancy loss., Results: Our findings indicate that various combinations of these four microRNA polymorphic sites are associated with an increased risk of primary ovarian insufficiency. The combination analysis indicated a significant decrease in the frequency of the miR-181a/miR-499b TC/AA allele combination in individuals with primary ovarian insufficiency (P < 0.05). Additionally, one-way analysis of variance of data from patients with primary ovarian insufficiency revealed that, in comparison with miR-181aTT, the miR-181aCC genotype was associated with significantly lower levels of both follicle-stimulating hormone and luteinizing hormone, suggesting potential protective effects., Conclusions: Our data suggest that dysregulation of the miR-10aA > T, miR-30cA > G, miR-181aT > C, and miR-499bA > G polymorphisms in these microRNAs contributes to the regulation of target genes related to primary ovarian insufficiency., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024. Published by Elsevier B.V.)

The present study investigated the anti‑melanogenesis effects of Giant Centella asiatica (GCA), a new cultivator of Centella asiatica (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.

X-ray fluorescence (XRF) is widely used to analyze elemental distributions in samples. Micro-XRF (µ-XRF), the most basic conventional XRF technique, offers good spatial resolution through precise 2D scanning with a micrometre-sized X-ray source. Recently, synchrotron based XRF analysis platforms have achieved nano-XRF with highly focused X-rays using polycapillary optics or mirrors, leveraging the excellent coherence of synchrotron radiation. However, XRF techniques are hindered by long data acquisition times (exceeding several hours) due to their point-by-point scanning approach, impeding large-area elemental mapping. Full-field XRF (FF-XRF), developed in the 2010s and based on the high brilliance of synchrotron X-rays, enables significantly shorter (less than a few minutes) data acquisition times via single-exposure imaging using a 2D X-ray detector. Nevertheless, it is constrained by relatively low spatial resolution and sensitivity. Hence, a new XRF platform is required to accommodate resolution demands to cover diverse experimental purposes. In this study, we developed a preliminary model of a novel XRF system that combines micro- and full-field XRF setups to address these limitations. This system allows easy mode switching while maintaining the region of interest of the imaging system within a single apparatus, simply by rotating the sample to face either detector depending on research purposes. We anticipate that this new XRF system will be widely utilized in various research fields as the initial XRF setup at Pohang Light Source-II., (open access.)

Endometrial cancer, a common gynecological malignancy, poses significant clinical challenges, particularly in advanced or recurrent cases. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, plays crucial roles in inflammation and immunity by activating nuclear factor (NF)-κB and interferon regulatory factor 3. However, its specific roles in endometrial cancer remain unknown. In this study, we aimed to investigate the anti-cancer effects and underlying mechanisms of amlexanox, a TBK1 inhibitor, against endometrial cancer. The main genetic mutations in TBK1 were found to be mRNA downregulation and missense mutations. Kaplan-Meier plotter analysis revealed that low TBK1 expression was associated with a good prognosis in patients with uterine corpus endometrial carcinoma (UCEC). In vitro experiments demonstrated that TBK1 knockdown or amlexanox significantly inhibited the proliferation, cell cycle progression, and migration of endometrial cancer cells. Furthermore, the inhibitory effects of targeting TBK1 on cancer cell proliferation and migration were mediated by the protein kinase B (AKT)/NF-κB signaling pathway. Xenograft experiments revealed that both amlexanox treatment and TBK1 knockdown effectively suppressed the tumor growth. Overall, this study highlights the potent anti-cancer effects of amlexanox against endometrial cancer by modulating AKT/NF-κB signaling, thus providing a new avenue for the development of novel TBK1-targeting therapeutic strategies for UCEC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Small-cell lung cancer (SCLC) is highly lethal because the tumors grow and metastasize rapidly. Effective treatments for SCLC are lacking currently. A recent study demonstrated that the E1A binding protein P300 (EP300) KIX domain has pro-tumorigenic activity and is selectively involved in the development and growth of SCLC. These findings suggest the possibility of developing small-molecule inhibitors of EP300 KIX as new targeted therapies for SCLC. In this study, we reported the crystal structure of the human EP300 KIX domain at 2.9 Å resolution except for a flexible loop and C-terminal end. The overall structure was almost identical to that of the cAMP response element-binding protein (CBP) KIX. Nine EP300 KIX residues were different from those of CBP KIX. Among these non-strictly conserved residues, Ala627, which corresponds to Asp647 in CBP KIX, reduces the negative surface potential. Asn581 and Arg613 contributed to the formation of additional hydrogen bonds in the EP300 KIX structure. Further structural analysis revealed that the hydrophobic residues that form the allosteric network in CBP KIX were well conserved in the EP300 KIX structure. This study lays the groundwork for structure-based drug design for SCLC., 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: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited., Objectives: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation., Methods: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery., Results: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027)., Conclusions: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548)., Competing Interests: Funding Support and Author Disclosures This research was supported by the CardioVascular Research Foundation (Seoul, Korea) (grant number: AMCCV2016-10), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HC19C0022), and Medtronic. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The traditional gamma evaluation method combines dose difference (DD) and distance-to-agreement (DTA) to assess the agreement between two dose distributions. However, while gamma evaluation can identify the location of errors, it does not provide information about the type of errors., Purpose: The purpose of this study is to optimize and apply the structural similarity (SSIM) index algorithm as a supplementary metric for the quality evaluation of radiation therapy plans alongside gamma evaluation. By addressing the limitations of gamma evaluation, this study aims to establish clinically meaningful SSIM criteria to enhance the accuracy of patient-specific quality assurance (PSQA)., Methods: We analyzed the relationship between the gamma passing rate (GPR) and the SSIM index with respect to distance and dose errors. For SSIM analysis corresponding to gamma evaluation criteria of 3%/2 mm, we introduce the concept of SSIM passing rate (SPR). We determined a valid SSIM index that met the gamma evaluation criteria and applied it. Evaluations performed for 40 fields measured with an electronic portal imaging device (EPID) were analyzed using the GPR and the applied SPR., Results: The study results showed that distance errors significantly affected both the GPR and the SSIM index, whereas dose errors had some influence on the GPR but little impact on the SSIM index. The SPR was 100% for distance error of 2 mm but began to decrease for distance errors of 3 mm or more. An optimal SSIM index threshold of 0.65 was established, indicating that SPR fell below 100% when distance errors exceeded 2 mm., Conclusions: This study demonstrates that the SSIM algorithm can be effectively applied for the quality evaluation of radiation therapy plans. The SPR can serve as a supplementary metric to gamma evaluation, offering a more precise identification of distance errors. Future research should further validate the efficacy of SSIM algorithm across a broader range of clinical cases., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: Scalp hair plays a crucial role in social communication by expressing personal appearance and self-identity. Consequently, hair loss often leads to a perception of unattractiveness, negatively impacting an individual's life and mental health. Currently, the use of Food and Drug Administration (FDA)-approved drugs for hair loss is associated with several side effects, highlighting the need for identifying new drug candidates, such as plant-derived phytochemicals, to overcome these issues., Objective: This study investigated the hair growth-promoting effects of araliadiol, a polyacetylene compound found in plants such as Centella asiatica ., Methods: We employed an in vitro model comprising human hair follicle stem cells (HHFSCs) and human dermal papilla cells (HDPCs) to evaluate the hair growth-promoting effects of araliadiol. The proliferation-stimulating effects of araliadiol were assessed using water-soluble tetrazolium salt assay, adenosine triphosphate content assay, and crystal violet staining assay. In addition, we performed luciferase reporter assay, polymerase chain reaction analysis, cell fractionation, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) to elucidate the mechanism underlying the hair growth-inductive effects of araliadiol., Results: Araliadiol exhibited both proliferation- and hair growth-promoting effects in HHFSCs and HDPCs. Specifically, it increased the protein expression of cyclin B1 and Ki67. In HHFSCs, it elevated the expression of hair growth-promoting factors, including CD34, vascular endothelial growth factor (VEGF), and angiopoietin-like 4. Similarly, araliadiol increased the expression of hair growth-inductive proteins such as fibroblast growth factor 7, VEGF, noggin, and insulin-like growth factor 1 in HDPCs. Subsequent Western blot analysis and ELISA using inhibitors such as GW9662 and SB202190 confirmed that these hair growth-promoting effects were dependent on the p38/PPAR-γ signaling in both HHFSCs and HDPCs., Conclusion: Araliadiol promotes hair growth through the p38/PPAR-γ signaling pathway in human hair follicle cells. Therefore, araliadiol can be considered a novel drug candidate for the treatment of alopecia., Competing Interests: Authors HP, DS, and DY were employed by ASK Company Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Park, Park, Seo, Yoo and Bae.)