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S100 calcium-binding protein P (S100P) is a secretory protein that is expressed in various healthy tissues and tumors. Megakaryocyte-secreted S100P promotes osteoclast differentiation and function; however, its receptor and cellular signaling in osteoclasts remain unclear. Receptor for advanced glycation end products (RAGE), which is the receptor for S100P on cancer cells, was expressed in osteoclast precursors, and S100P-RAGE binding was confirmed through co-immunoprecipitation. Additionally, the phosphorylation of ERK and NF-κB was increased in S100P-stimulated osteoclast precursors but was inhibited by addition of the RAGE antagonistic peptide (RAP). S100P-induced osteoclast differentiation and excessive bone resorption activity were also reduced by the addition of RAP. This study demonstrates that S100P, upon binding with RAGE, activates the ERK and NF-κB signaling pathways in osteoclasts, leading to increased cell differentiation and bone resorption activity., 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.)

Prognostic markers for long-term outcomes are lacking in patients with deferred (nonculprit) coronary artery lesions. This study aimed to identify the morphological criteria for predicting adverse outcomes and validate their clinical impact. Using deep learning models, we extracted geometrical parameters and maximal attenuation (or calcium) burden index (ABI-max or CBI-max) from the intravascular ultrasound (IVUS) images of nonculprit vessels in 1115 patients. The endpoints included cardiac death, myocardial infarction, and target vessel revascularization of nonculprit vessel. Cardiac death occurred in 27 (2.4 %) patients at 3 years and 39 (3.5 %) patients at 5 years. At 5 years, the cardiac death-free survival rate was significantly lower with ABP-max ≥11.37 % vs. < 11.37 % (90.0 % vs. 98.7 %), CBI-max ≥13.40 % vs. < 13.40 % (92.8 % vs. 98.4 %), and percent atheroma volume ≥ 51.35 % vs. < 51.35 % (94.0 % vs. 97.7) (all log-rank p < 0.001). The independent predictors of 5-year cardiovascular mortality were age (hazard ratio [HR] 1.21), female sex (HR 0.33), history of heart failure (HR 6.06), chronic kidney disease (HR 18.28), ABI-max (HR 1.04), and CBI-max (HR 1.05). The independent determinants of 5-year target vessel revascularization of nonculprit vessel were fractional flow reserve (HR 0.95 per 0.01 increase), minimal lumen area (HR 0.63), and plaque burden (HR 1.15). In patients with nonculprit coronary artery lesions, a large burden of attenuated or calcified plaques predicted cardiac mortality, while IVUS geometry was associated with repeat revascularization. Thus, deep learning-based IVUS analysis of the whole target vessel may help clinicians identify high-risk lesions., Competing Interests: Declaration of competing interest The sponsors played no role in this study. There was no industry involvement in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: The aim of this study was to investigate the non-inferiority of alveolar ridge preservation (ARP) with membrane stabilization compared with non-stabilization, focusing on changes of soft-tissue contour in periodontally compromised extraction sockets. Secondary outcomes included changes in hard-tissue contour, patient-reported outcomes and new bone formation., Materials and Methods: Twenty-four patients with periodontally compromised teeth were randomly assigned to ARP with (test group) or without (control group) membrane stabilization. To assess profilometric and hard-tissue dimensional changes, dental impressions and cone beam computed tomography scans were performed at baseline (T0), immediately after ARP (T1) and 4 months post surgery (T2). Soft-tissue healing in open healing sites was evaluated at T2, and wound closure was assessed 10 days post surgery. Patient-reported outcomes were documented, and core biopsies were obtained for histomorphometric analysis., Results: The absolute profilometric horizontal width change at 3 mm below the crest in the test group was not inferior to that in the control group. For the relative values, horizontal width reduction (3 and 5 mm below the crest) and volumetric shrinkage (3-5 mm below the crest) were lower in the test group. No significant differences were observed in bone dimensional changes, wound healing, pain and swelling or histomorphometric outcomes., Conclusion: ARP with membrane stabilization in periodontally compromised extraction sockets is non-inferior in terms of soft-tissue contour changes to those without membrane fixation., Trial Registration: Clinical Research Information Service (CRIS), KCT0005280. Registered 4 August 2020, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=19165&search&#95;page=L., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.)

Anti-CD19 chimeric antigen receptor (CAR)-engineered T and NK cell therapies have revolutionized the treatment of B cell malignancies, but challenges including CD19 antigen loss greatly hinder their full therapeutic potential. Here we demonstrated that co-treatment with anti-CD19 monoclonal antibody enhances antitumor activity of anti-CD19 CAR-T and -NK cells. Even though the treated antibody interferes with CD19 antigen binding of CAR, it significantly induces rapid detachment of anti-CD19 CAR effector cells from target cells, facilitating improved serial killing. This reduced interaction between CAR effector cells and target cells also leads to the alleviation of CAR-mediated trogocytosis. Interestingly, co-treatment with anti-CD19 antibody reveals time-dependent effects on the antitumor activity of anti-CD19 CAR-T cells, characterized by a reduction in early T cell activation followed by sustained high activity during prolonged exposure to target cells. This temporal modulation ultimately results in enhanced antitumor potency in vivo. These findings underscore the improved therapeutic efficacy achieved by combining anti-CD19 antibody with anti-CD19 CAR-T or -NK cells against B cell malignancies., (Copyright © 2024 American Society of Hematology.)

Electron-transporting transparent conducting oxides (TCOs) are a commercial reality, however, hole-transporting counterparts are far more challenging because of limited material design. Here, we propose a strategy for enhancing the hole conductivity without deteriorating the band gap ( E g ) and workfunction ( Φ ) by Cu incorporation in a strongly correlated NiWO 4 insulator. The optimal Cu-doped NiWO 4 (Cu 0.185 Ni 0.815 WO 4 ) exhibits a resistivity reduction of ∼10 9 times versus NiWO 4 as well as band-like charge transport with the hole mobility approaching 7 cm 2 V -1 s -1 at 200 K, a deep Φ of 5.77 eV, and E g of 2.8 eV. Experimental and theoretical data reveal that the strength of the electron correlation in NiWO 4 is unaffected by Cu incorporation, while the promoted polarizability weakens electron-phonon coupling, promoting the formation of large polarons. Quantum dot light-emitting and oxide p/n junction devices incorporating Cu 0.185 Ni 0.815 WO 4 exhibit remarkable performances, demonstrating that our approach can be deployed to discover new p-type TCOs.

Extracellular vesicles (EVs) possess the characteristics of their parent cells, based on which various studies have actively investigated treatments for diseases using mesenchymal stem cell-derived EVs due to their regenerative activity. Furthermore, in recent years, there have been significant efforts to engineer EVs to improve their native activities and integrate additional functions. Although both endogenous and exogenous methods are used for engineering EVs, endogenous methods may pose the problem of administering substances to cells undergoing metabolic changes, which can cause potential side effects. In addition, exogenous methods may have the limitation of losing beneficial factors inside EVs due to membrane disruption during engineering processes. Surface modification of EVs may also impair efficiency due to the presence of proteins on the EV surface. Therefore, in this study, a stable and efficient engineering method was achieved through the ethanol-mediated hybridization of EVs and functionalized lipid nanoparticles (LNPs) with a fusogenic lipid component. During hybridization, the internal bioactive factors and targeting moiety were maintained to possess the characteristics of both LNPs and EVs. The Ab-Hybrid, which was successfully synthesized through hybridization with nicotinamide-encapsulated and Col2A1 antibody-modified liposome and Transforming growth factor-β1 (TGF-β1) - overexpressed EVs, was administered to osteoarthritis (OA)-induced rats undergoing the destabilization of the medial meniscus surgery. Ultimately, the Ab-Hybrid demonstrated excellent chondroprotective and anti-inflammatory effects with targeting and long-lasting properties in OA lesions. We anticipate that this approach for manufacturing hybrid particles will serve as a valuable EV engineering method and a versatile platform technology applicable to various diseases.

Lithium-sulfur batteries (LSBs) have emerged as a promising next-generation energy storage application owing to their high specific capacity and energy density. However, inherent insulating property of sulfur, along with its significant volume expansion during cycling, and shuttling behavior of lithium-polysulfides (LiPSs), hinder their practical application. To overcome these issues, a crosslinked cationic waterborne polyurethane (CCWPU) is rationally designed as a binder for LSBs. The mechanical robustness of CCWPU enables it to withstand the high stress derived from volume expansion of sulfur, facilitating charge-transferring through conserved charge-transfer pathway and promoting interconversion of LiPSs. Additionally, polar urethane groups offer favorable interaction sites with LiPSs, mitigating shuttling behavior of LiPSs via polar-polar interaction. Density functional theory investigations further elucidate that the incorporation of cationic moieties enhances LiPSs immobilization by confining S n x- (x = 1 or 2) in LiPSs, thereby improving sulfur utilization. Benefiting from these, the cell with CCWPU demonstrates reduced polarization, superior LiPSs conversion rates, and stable cycling performance. Moreover, water-processable nature of CCWPU aligns with environmental consciousness. These diverse functionalities of CCWPU provide valuable insights for the development of advanced binder for LSBs, ultimately improving the electrochemical performances of LSBs., (© 2024 Wiley‐VCH GmbH.)

During in vitro maturation (IVM), median antral follicles (MAFs) were mechanically aspirated from the porcine ovarian cortex, and this process causes an early disconnection of follicular somatic cells from oocytes within antral follicles before the formation of graafian follicles. Thus, nuclear maturation is accelerated ahead of the completion of cytoplasmic maturation. Dibutyryl-cAMP (dbcAMP), a well-known cAMP modulator, is used to inhibit the resumption of meiosis in immature oocytes. However, there is no information on the optimal timeframe for sustaining meiotic arrest to enhance oocyte maturity during IVM. To determine the optimal duration of meiotic arrest, immature cumulus-oocyte complexes (COCs) from MAFs were cultured with 1 mM dbcAMP for 0, 4, 8, 12, 16, or 22 h, followed by further IVM without dbcAMP for 44, 40, 36, 32, 28, or 22 h. Subsequently, nuclear maturation, cumulus cell expansion score, perivitelline space size, glutathione (GSH) and reactive oxygen species (ROS) levels, and preimplantation development of parthenogenetic and in vitro-fertilized embryos were assessed in oocytes from each group. The results showed that a 16-h treatment with 1 mM dbcAMP within the 44-h IVM process yielded the highest oocyte maturity. Accordingly, we established an advanced IVM protocol for producing oocytes with superior maturity from porcine MAFs by achieving nuclear maturation 36 h after initiating IVM, using a 16-h treatment with 1 mM dbcAMP within the 44-h IVM process., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eun Song Lee reports financial support was provided by National Research Foundation of Korea funded by the Ministry of Science. If there are other authors, they 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. Published by Elsevier B.V.)

Competing Interests: The authors report no conflicts of interest.

Background: The prevailing exposure to Adverse Childhood Experiences (ACEs) among youth is associated with adolescents' mental health. However, few studies have examined whether receiving help from mental health services affects mental health outcomes among adolescents with ACEs. Therefore, this study examines the moderated effects of mental health services use on the relationship between exposures to ACEs and mental health outcomes among US adolescents., Methods: The sample was restricted to adolescents aged 11-17 using data from the National Health Interview Survey (NHIS) from 2019, 2021, and 2022. Multivariate logistic regressions and descriptive analyses were performed to estimate the moderation effect of mental health services use., Results: Using mental health services buffered the associations between ACEs and severe anxiety and depressive symptoms. Receiving counseling/therapy moderated the impact of ever living with an individual who had severe anxiety (Adjusted Odds Ratio, AOR: 0.58, p < .05) and depressive symptoms (AOR: 0.38, p < .01) among adolescents. Furthermore, counseling/therapy moderated the effect of ever living with an individual with a history of alcohol or drug abuse on severe depressive symptoms (AOR: 0.49, p < .05) and the effect of being a victim or witness of violence on severe anxiety symptoms (AOR: 0.45, p < .01). In addition, taking prescription medication moderated the effect of the experience of incarcerated family members on severe anxiety symptoms (AOR: 0.41, p < .05)., Conclusion: Our findings suggest that policy and practice need to encourage access to mental health care for vulnerable adolescents with ACEs to reduce the detrimental effect of their experiences on their mental health problems., (© 2024 Association for Child and Adolescent Mental Health.)

4-tert-Octylphenol (OP), an endocrine disrupting chemical is widely used in the production of industrial products. Prenatal exposure to endocrine-disrupting chemicals negatively affects the brain. However, the influence of OP exposure during neurodevelopment in adult offspring remains unclear. Thus, in the present study, we investigated the effects of maternal OP exposure on brain development in adult offspring by analyzing primary glial cell cultures and mice. Our findings revealed that OP exposure led to a specific increase in the mRNA expression of the ionized calcium-binding adapter molecule 1 (Iba-1) and the proportion of amoeboid microglia in the primary glial cell culture and adult offspring mice. Exposure to OP increased the transcriptional activation of Iba-1 and estrogen response element, which were counteracted by estrogen receptor antagonists ICI 182,780. Moreover, OP exposure increased the nuclear localization of the estrogen receptor. Remarkably, OP exposure decreased the mRNA expression levels of proinflammatory cytokines and genes associated with immune response in the brains of the offspring. OP exposure upregulated actin filament-related genes and altered cytoskeletal gene expression, as demonstrated by microarray analysis. The morphological changes in microglia did not result in an inflammatory response following lipopolysaccharide treatment. Taken together, the effects of OP exposure during neurodevelopment persist into adulthood, resulting in microglial dysfunction mediated by estrogen receptor signaling pathways in the brains of adult offspring mice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eui-Man Jung reports financial support was provided by the National Research Foundation of Korea (NRF) funded by the Korean Government (MSIT) (grant number: 2021R1C1C100328611) and Global - Learning & Academic research institution for Master’s·PhD students, and Postdocs (LAMP) Program of the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (No. RS-2023-00301938)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Particulate matter (PM) exposure during pregnancy increases the risk of developing asthma in children. However, the placental mechanisms have yet to be elucidated. This study aims to evaluate the mechanisms associated with PM exposure during pregnancy and asthma susceptibility via placental epigenetic dysregulation. We analyzed data from two independent Korean birth cohorts (COCOA, 684 children; PSKC, 818 children). Physician-diagnosed current asthma and bronchial hyperresponsiveness (BHR) via methacholine challenge tests were evaluated at age seven. We estimated PM exposure with a diameter < 10 μm (PM 10 ) during pregnancy using land-use regression models. We performed genome-wide methylation profiling in the placenta of 40 samples in the COCOA study and analyzed the gene expression levels. High PM 10 exposure during pregnancy increased the risk of developing current asthma and BHR in the COCOA study (aOR 2.36, 95% CI 1.06-5.22; aOR 2.14, 95% CI 1.40-3.27, respectively) and current asthma in the PSKC (aOR 2.62, 95% CI 1.35-5.09). The genes involved in neuronal differentiation and proliferation and Notch signaling pathways were significantly hypermethylated in children with high PM 10 -exposed asthma. The methylation and expression levels of eight genes (PAX6, REST, OLIG2, GLI1, ZBTB7A, NOTCH4, NOTCH1, and NOTCH3) in these pathways correlated with clinical parameters. This may effectively predict PM-related asthma through a prediction model using degrees of gene-based or CpG-based methylation (AUC = 0.96 and 0.93, respectively). PM 10 exposure during pregnancy impacts asthma development in offspring via placental DNA hypermethylation via neuronal differentiation and proliferation and Notch signaling pathways., 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. Published by Elsevier Ltd.)

Introduction and Objectives: Recent randomized controlled trials support the use of intravascular imaging-guided percutaneous coronary intervention (PCI) to improve patient prognosis. However, the subsequent risk of clinical events in patients with coronary artery disease is not determined solely by lesion characteristics or how these lesions are treated. The current study investigated whether the effects of intravascular imaging in complex PCI vary according to atherothrombotic risks., Methods: This study was a post hoc analysis of the RENOVATE-COMPLEX-PCI trial, which compared intravascular imaging-guided PCI with angiography-guided PCI in patients with complex coronary artery lesions. The study population was stratified by atherothrombotic risk, assessed using the Thrombolysis in Myocardial Infarction risk score for secondary prevention (TRS-2P). TRS-2P is calculated based on the presence of the following factors: age ≥ 75 years, diabetes mellitus, hypertension, smoking, peripheral arterial disease, stroke, coronary artery bypass grafting, heart failure, and renal dysfunction. Patients were categorized into low-risk (TRS-2P < 3) or high-risk (TRS-2P ≥ 3) groups. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization., Results: Among the total study population, 1247 patients were categorized as low-risk, and 392 as high-risk. The risk of target vessel failure was significantly higher in the high-risk group than in the low-risk group (15.5% vs 7.2%; hazard ratio [HR], 2.13; 95% confidence interval [95%CI], 1.51-3.00; P < .001). The benefits of intravascular imaging-guided PCI over angiography-guided PCI did not differ between the low-risk group (5.6% vs 10.4%; HR, 0.56; 95%CI, 0.36-0.86) and the high-risk group (14.1% vs 18.5%; HR, 0.71; 95%CI, 0.41-1.24), with no significant interaction (interaction P = .496)., Conclusions:  In this hypothesis-generating post hoc analysis of the RENOVATE-COMPLEX-PCI trial, patients with high atherothrombotic risk had significantly worse clinical outcomes than those with low atherothrombotic risk. Nevertheless, the prognostic impact of intravascular imaging-guided PCI compared with angiography-guided PCI was similarly observed in both low- and high-risk groups. RENOVATE-COMPLEX-PCI clinical trial register number: NCT03381872., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: This study determined the prevalence of cauda equina clumping among patients with Schizas grade C or higher central stenosis after decompression and compared the radiographic and clinical outcomes between patients with and without clumping., Methods: We conducted a single-center retrospective cohort study involving 98 patients who underwent biportal endoscopic spine surgery between January 2019 and June 2022. Based on postoperative magnetic resonance imaging findings, the patients were divided into the clumping (n = 40) and non-clumping (n = 58) groups. Clinical outcomes were assessed using the visual analog scale for back and leg pain, Oswestry Disability Index (ODI), and EuroQol 5-Dimension (EQ-5D-5 L) questionnaire at 1, 3, 6, and 12 months postoperatively. Radiographic evaluations included measuring the cross-sectional area of the dural sac preoperatively and 1 month postoperatively using the PACS software., Results: Postoperative cauda equina clumping was observed in 40.8% of the patients. Despite an average dural sac expansion of approximately 270%, the clumping group exhibited significantly higher radiating pain at 3 and 6 months (p < 0.05) than the non-clumping group. The ODI and EQ-5D scores were worse in the clumping group at 3 months (p < 0.05). At 12 months postoperatively, differences in clinical outcomes between the two groups were not significant. Patients in the clumping group required longer duration of postoperative medication than those in the non-clumping group (p = 0.024)., Conclusion: Post-decompression cauda equina clumping is commonly observed in patients with severe lumbar stenosis and impacts intermediate-term clinical recovery. Although long-term outcomes at 1 year are similar, tailored postoperative care is essential for patients exhibiting clumping to effectively manage prolonged symptoms., Competing Interests: Declarations. Ethics approval and consent: This retrospective cohort study was approved by the institutional review board (IRB) of Korea University Anam Hospital (IRB No. 2024AN0321) and adhered to the ethical guidelines of the World Medical Association Declaration of Helsinki. The IRB waived the documentation of patients’ informed consent due to the retrospective nature of the study. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lipid nanoparticles (LNPs) are widely recognized as crucial carriers of mRNA in therapeutic and vaccine development. The typical lipid composition of mRNA-LNP systems includes an ionizable lipid, a helper lipid, a polyethylene glycol (PEG)-lipid, and cholesterol. Concerns arise regarding cholesterol's susceptibility to oxidation, potentially leading to undesired immunological responses and toxicity. In this study, we formulated novel LNPs by replacing cholesterol with phytochemical-derived compounds, specifically ginsenoside Rg2 and its derivative phytosterol protopanaxadiol (PPD), and validated their efficacy as mRNA delivery systems. The mRNA-LNP complexes were manually prepared through a simple mixing process. The biocompatibility of these Rg2-based LNPs (Rg2-LNP) and PPD-based LNPs (PPD-LNP) was assessed through cell viability assays, while the protective function of LNPs for mRNA was demonstrated by RNase treatment. Enhanced green fluorescent protein (EGFP) mRNA delivery and expression in A549 and HeLa cells were analyzed using optical microscopy and flow cytometry. The expression efficiency of Rg2-LNP and PPD-LNP was compared with that of commercially available LNPs, with both novel formulations demonstrating superior transfection and EGFP expression. Furthermore, in vivo tests following intramuscular (I.M.) injection in hairless mice demonstrated efficient luciferase ( Luc ) mRNA delivery and effective Luc expression using Rg2-LNP and PPD-LNP compared to commercial LNPs. Results indicated that the efficiency of EGFP and Luc expression in Rg2-LNP and PPD-LNP surpassed that of the cholesterol-based LNP formulation. These findings suggest that Rg2-LNP and PPD-LNP are promising candidates for future drug and gene delivery systems.

Background: Various treatment modalities are used to treat keloids. However, a comprehensive assessment comparing the effectiveness of these modalities in terms of patient-reported outcomes is warranted., Objective: To assess and compare the effectiveness of various treatment modalities for keloids., Methods: We assessed treatment outcomes in a cohort of 250 patients diagnosed with keloids. The patients were categorized into four treatment groups: triamcinolone acetonide (TA), TA + cryotherapy, TA + pulsed dye laser (PDL), and TA + cryotherapy + PDL. The Vancouver Scar Scale was used to evaluate the keloid severity before and after treatment., Results: Significant differences were noted in the Vancouver Scale scores among the treatment groups ( p =0.023). Notably, the TA + cryotherapy + PDL group exhibited the most substantial improvement in the Vancouver Scale scores, whereas the TA + PDL group showed the least difference. Pliability was the most significantly improved in the TA + cryotherapy + PDL group ( p =0.039). Male patients experienced a greater reduction in pigmentation scores than female patients ( p =0.037)., Conclusion: Our findings highlight the effectiveness of combined therapies, particularly TA + cryotherapy + PDL, in improving keloid-related parameters. These results offer valuable insights for clinicians in tailoring keloid treatment strategies and support the implementation of combination therapies for enhanced outcomes. This study underscores the importance of comprehensively assessing treatment modalities for keloid management. Combination therapies such as TA + cryotherapy + PDL irradiation have demonstrated significant promise in improving keloid characteristics., Competing Interests: The authors have nothing to disclose., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: We aimed to assess the incidence of infective endocarditis (IE) and evaluate the impact of hypertension (HTN) with underweight on the risk of IE among patients with diabetic mellitus (DM) using a nationwide population-based cohort in Korea., Methods: We identified 2,603,012 participants (57.4 ± 12.3 years) in the national health insurance database. Of these, 374,586 were normotensive, 750,006 were at pre-HTN status, and the remainder had HTN. The risk of IE was compared between the groups, and the impact of being underweight (body mass index < 18.5) was also evaluated., Results: During follow-up (7.14 years; interquartile range 6.01-8.08 years), 1,703 cases of IE occurred; 168 (0.0647 person per 1000 person-years [PY]), 303 (0.05836 per 1000 PY), and 1,232 (0.12235 per 1000 PY) in normotensive, pre-HTN and HTN group, respectively. Hypertensive participants presented a higher risk of IE (subdistribution hazard ratio, 1.360; 95% confidence interval, 1.152-1.607) than normotensive participants. Being underweight increased the risk of IE by 90% among subjects with HTN. In subgroup analysis, age, duration of DM, insulin use, and habitual factors were not associated with the incidence of IE., Conclusions: Diabetic patients may require rigorous blood pressure control and simultaneous avoidance of excessive weight loss to prevent IE., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the institutional review board of Soongsil University (Approval no. SSU-202003-HR-201-01). The requirement for written informed consent was waived in the present study because data in the K-NHIS database are anonymized in adherence to strict confidentiality guidelines. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Competing Interests: The authors have nothing to disclose.

Background: The choice of an appropriate type of orthosis depends on the patient's specific condition and needs. Different types of orthoses can affect plantar pressure distribution during certain gait patterns. Toe and heel gaits are common patterns of gait assigned for optimal recovery in patients with foot or ankle injuries. This study aimed to evaluate differences in plantar pressure between postoperative shoes and walker boots during toe and heel gaits in healthy individuals., Methods: A total of 30 healthy individuals with a mean age of 21.7 ± 1.2 years were included in this study. Two types of gaits, toe and heel, were performed while wearing each orthosis on the right side of the foot. A standardized running shoe was worn on the left side of the foot. Plantar pressure variables including contact area, peak pressure, and maximum force were collected using the Pedar-X in-shoe pressure measuring system., Results: During toe gait, while both orthoses demonstrated similar offloading in the hindfoot areas, walker boots were superior in reducing the peak pressure (first toe, p = 0.003; second to fifth toes, p < 0.001) and contact area (first toe, p = 0.003; second to fifth toes, p = 0.003) in the forefoot areas. During heel gait, both orthoses demonstrated similar offloading in the toe areas; however, the walker boots were superior in reducing the peak pressure in the lateral hindfoot ( p < 0.001)., Conclusions: The results of our study can serve as a guideline for orthopedic physicians in prescribing an appropriate type of orthosis during specific types of gait for patients following foot and ankle injury and postoperative recovery., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Purpose: Smoking is causally related to alcohol use disorder. Although polycyclic aromatic hydrocarbons (PAHs) are major neurotoxic pollutants in tobacco smoke, evidence is lacking on the role of PAHs in the relationship between smoking and alcohol use disorder. This study investigated the types of PAHs associated with smoking and whether exposure to those PAHs mediated the effect of smoking on alcohol use disorder., Materials and Methods: A total of 968 male firefighters were analyzed. Smoking history and cumulative pack-years were obtained using self-reported questionnaires. Alcohol use disorder was defined using the Alcohol Use Disorder Identification Test. PAH exposure was assessed by urinary metabolites. Regression analyses were performed between exposure (smoking), outcome (alcohol use disorder), and mediator (PAH metabolites) variables. A mediation analysis was performed to test the indirect effect of PAH metabolites on the association between smoking and alcohol use disorder. All analyses were repeated for 770 participants who were followed up after 2 years, while alcohol use disorder was redefined from follow-up data ensuring the temporal sequence of the variables., Results: Both 2-naphthol [β=0.78, 95% confidence interval (CI): 0.59-0.98] and 2-hydroxyfluorene (β=0.69, 95% CI: 0.56-0.82) were associated with smoking history. Furthermore, 2-naphthol and 2-hydroxyfluorene mediated the associations of smoking history (proportion mediated: 14.2%, 23.6% respectively) or cumulative pack-years (proportion mediated: 14.4%, 25.4% respectively) with alcohol use disorder. The results were consistent in longitudinal settings., Conclusion: Exposure to PAHs mediated the association between tobacco smoking and alcohol use disorder. PAH exposure from tobacco may increase the risk of addictive disorders., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

African swine fever (ASF), a contagious and lethal haemorrhagic disease of domestic pigs and wild boars, poses a significant threat to the global pig industry. Although experimental vaccine candidates derived from naturally attenuated, genetically engineered, or cell culture-adapted ASF virus have been tested, no commercial vaccine is accepted globally. We developed a safe and effective cell-adapted live attenuated vaccine candidate (ASFV-MEC-01) by serial passage of a field isolate in CA-CAS-01-A cells. ASFV-MEC-01, isolated via repeated plaque purification using next-generation sequencing analysis, was obtained at passage 18 and showed significant attenuation in 4- and 6-week-old pigs. ASFV-MEC-01 conferred 100% protection against challenge with lethal parental ASFV, which correlated with high ASFV-specific humoral and cellular immune responses. Additionally, ASFV-MEC-01 was not detected in blood until 28 days post-inoculation. Global transcriptome analysis showed that ASFV-MEC-01 lacking 12 genes triggered stronger innate antiviral responses than the parental virus, as exemplified by high levels of mRNA encoding interferon regulatory and inflammatory genes in PAM cells. Ectopic expression of most deleted genes increased replication of DNA viruses by suppressing production of interferons and pro-inflammatory cytokines. Among the genes deleted from ASFV-MEC-01, MGF100-1R interacted specifically with the scaffold dimerization domain of TBK1, thereby preventing TBK1 dimerization and impairing TBK1-mediated type I IFN and NF-κB signalling. These results suggest that attenuation of ASFV-MEC-01 may be mediated by induction of stronger type I IFN and NF-κB signalling within the host innate immune system. Thus, ASFV-MEC-01 could be a safe and effective live attenuated ASFV vaccine candidate with commercial potential.

The objective of this study is to develop and validate dementia risk prediction models for mid- and late-life individuals that are based on accessible variables within a primary care setting. Using the Korean National Health Insurance Service database (2010-2019), we analyzed 6,696,073 individuals aged 40 and older who participated in a national health screening program over a mean follow-up of 8.95 years. Potential predictors were selected based on a literature review and the available data. Dementia cases were identified using claim-based codes and validated by corresponding prescription information. 5-year dementia risk prediction models for mid-life (40-59 years), and late-life (60+ years) stages were developed using the Cox proportional hazards model. Model performance was assessed through discrimination and calibration. Both models included age, sex, body mass index, smoking, alcohol consumption, physical activity, diabetes, hypertension, dyslipidemia, and chronic kidney disease. The models' AUROCs were 0.764 for mid-life and 0.743 for late-life. The impact of predictors on dementia risk was consistently stronger in mid-life than in late-life stages. Our models showed good calibration with low-risk estimates in mid-life and overall in late-life. These findings underscore the crucial role of managing modifiable risk factors, particularly during mid-life to reduce dementia risk., Competing Interests: Declaration of competing interest The authors have no relevant conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Autotaxin (ATX) has emerged as a promising therapeutic target for liver diseases. In this study, we identified potential drug candidates through in silico high-throughput screening. Subsequently, we synthesized a series of small molecules, specifically KR-40795 (2c), a pyrrolidine-2,5-dione-based analogue that binds to the allosteric tunnel and hydrophobic pocket of ATX. This compound was designed to inhibit the enzymatic activity of ATX for the treatment of liver diseases. The inhibitory potency of KR-40795 was evaluated using a biochemical assay that measured the hydrolysis of a specific substrate (FS-3). Notably, KR-40795 demonstrated significant inhibition of both collagen formation and lipid accumulation in liver cells, suggesting its potential as a therapeutic agent for liver diseases, particularly fibrosis and steatosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kwang-seok Oh acknowledges financial support from the National Research Foundation of Korea and the Korea Research Institute of Chemical Technology. Any additional authors declare that they have no competing financial interests or personal relationships that could have influenced the work presented in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Complement Factor H-Related protein 5 (CFHR5) belongs to the factor H/CFHR family and regulates the complement system by modulating factor H's inhibitory activity against C3b. Despite its known role, the impact of CFHR5 on autoimmune arthritis and its relationship to pathophysiological changes in arthritis and bone loss remain unclear. This study aimed to assess the effect of CFHR5 on aggressive osteoclast activity and arthritis using a murine model of collagen antibody-induced arthritis (CAIA)., Methods: The effect of recombinant CFHR5 protein (rCFHR5) on arthritis were evaluated in CAIA. The mice were divided into three group and intraperitoneally treated with rCFHR5, methotrexate (MTX) as positive control or PBS as negative control. In the CAIA mouse model, the rCFHR5-treated group significantly reduced the incidence and clinical arthritis equivalent to the MTX group. Clinical arthritis scores, incidence and body weight were measured, and histological analysis of ankle joints was performed by Hematoxylin and Eosin (H&E) and Safranin O - Fast green (SOFG), Tartrate-resistant acid phosphatase (TRAP) staining and Immunohistochemistry. Moreover, to investigate the rCFHR5 role, we isolated murine osteoclast precursor cells (OCPs) from each group, induced osteoclasts with M-CSF and RANKL, and performed TRAP and F-actin staining. To verify the mechanism, mRNA and protein analyses were performed in OCPs., Results: Histological examination of ankle joints revealed substantial reductions in synovial hyperplasia, bone marrow inflammation, bone erosion, cartilage destruction and TRAP-positive cells in the rCFHR5 group compared to the vehicle group. The ankle joints of the rCFHR5 group showed markedly decreased expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6). Mechanically, treatment with rCFHR5 inhibited RANKL-mediated osteoclast differentiation from OCPs and disrupted the RANK-JNK signaling. These findings demonstrate that treatment with rCFHR5 attenuates joint inflammation and reduces osteoclast differentiation, indicating its potential anti-inflammatory effect in autoimmune arthritis models., 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 Ltd. All rights reserved.)

Aim: Studies on immune checkpoint inhibitor (ICI)-related potential neurological adverse events (pNAEs) in Korean lung cancer (LC) patients are scarce. We aimed to examine ICI prescription trends from 2018 to 2022, patient characteristics and factors associated with ICI prescription or concurrent pNAEs in LC. Research design & methods: This observational, cross-sectional study of Korean LC patients investigated four ICIs (pembrolizumab, nivolumab, atezolizumab and durvalumab). The annual ICI prescription rate was calculated by dividing the number of LC patients prescribed ICIs with the total annual number of LC patients. Factors associated with ICI prescriptions or concurrent pNAEs were assessed. Results: The annual ICI prescription rate increased from 3.29% to 9.74% (average: 6.20%). Higher Charlson Comorbidity Index (CCI) scores were associated with more ICI prescriptions (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.07-1.08). Targeted therapy was associated with fewer prescriptions (OR: 0.45; 95% CI: 0.41-0.49). The anti-programmed cell death protein 1 (anti-PD-1) prescription rate was higher in patients with concurrent pNAEs than those without pNAEs (53.09% vs. 50.84%), and this was associated with higher pNAEs prevalence (OR: 1.10; 95% CI: 1.03-1.18). Conclusion: ICI prescription for LC has increased in Korea, CCI and anti-PD-1 increased pNAEs prevalence.

Introduction: Elevated low-density lipoprotein cholesterol (LDL-C) is a major residual risk factor among patients with acute coronary syndrome (ACS). In the absence of sufficient real-world evidence, this observational (noninterventional) study investigated the effectiveness and safety of evolocumab in patients with hyperlipidemia treated with evolocumab for ACS in a real-world clinical setting in Korea., Methods: Between January 2022 and February 2023, patients from 10 hospitals in Korea who initiated evolocumab within 24 weeks of an ACS event were enrolled. Data collected at visit 1 (evolocumab initiation) included patients' characteristics, comorbidities, and lipid-lowering therapies. LDL-C reduction from visit 1 (week 0) to visit 2 (week 8) was assessed. The primary outcome was the proportion of patients who achieved LDL-C < 1.4 mmol/L (55 mg/dL) at follow-up; the secondary outcome was the proportion who achieved LDL-C < 1.8 mmol/L (70 mg/dL) at follow-up., Results: In this study, 89 out of 142 enrolled patients were included in the effectiveness analysis. The mean (SD) age of the included patients was 59.3 (12.3) years, with the majority being male (87.6%). Sixty-one patients received statin-ezetimibe combination therapy (68.5%). The median [Q1, Q3] LDL-C level at the start of the study was 2.5 [2.0, 3.0] mmol/L (98 [77, 115] mg/dL), which decreased to 1.3 [0.7, 1.7] mmol/L (49 [29, 67] mg/dL) after 8 weeks of evolocumab treatment, resulting in an mean (SD) 50.9 (28.6) % reduction and 1.4 (1.0) mmol/L (55.1 (37.9) mg/dL) absolute reduction. At follow-up, 55.1% and 78.7% of patients achieved LDL-C goals of < 1.4 mmol/L (55 mg/dL) and < 1.8 mmol/L (70 mg/dL), respectively. No adverse or serious adverse drug reactions were reported., Conclusion: Evolocumab treatment was associated with significant LDL-C lowering and favorable safety and guideline-recommended LDL-C goal achievement rates among patients with ACS in the real-world clinical practice setting in South Korea., Competing Interests: Declarations. Conflict of Interest: JinSeon Jeong is an employee of Amgen. Hojoon Lee is an employee of Amgen and owns equity in the company. Min Chul Kim, Seung Hun Lee, Joon Ho Ahn, Yongwhan Lim, Kyung-il Park, Choongki Kim, Jong-Hwa Ahn, and Woong Chol Kang have no competing interests. Ethical Approval: The study was conducted in accordance with recommendations of the 18th World Health Congress (Helsinki 1964) and all applicable amendments, and the International Conference on Harmonization guidelines for Good Clinical Practice (GCP). The protocol was approved by relevant independent ethics committees at each hospital (The complete list is available in online Supplementary Material). All participants had to sign an informed consent form to be included in the study., (© 2024. The Author(s).)

This study aimed to evaluate the influence of combination treatment with a natural colorant (Gardenia red) and additives (sodium caseinate and maltodextrin) on the physicochemical properties of emulsified pork sausages at 0 and 4 weeks. The experimental design included a control (sodium nitrite 0.01%) and 5 treatments: T1 (Gardenia red 0.04%); T2 (Gardenia red 0.04% + sodium caseinate 0.2%); T3 (Gardenia red 0.04% + maltodextrin 0.03%); T4 (Gardenia red 0.04% + sodium caseinate 0.2% + maltodextrin 0.06%), and T5 (Gardenia red 0.04% + sodium caseinate 0.4% + maltodextrin 0.03%). The T1-T5 emulsion treatments exhibited increased redness; in addition, the redness further increased in emulsified pork sausages during storage ( p  < 0.05). Among the emulsion treatments, T4 displayed the highest water and fat loss (%). Sodium caseinate and maltodextrin decreased the hardness of emulsified pork sausages. However, the additives had no apparent effects on texture properties. Therefore, Gardenia red may replace as a natural colorant and play a role in developing the meat industry. The findings suggest that maltodextrin and sodium caseinate should be considered adequate reformulation with the appropriate additives to improve the texture properties of emulsified pork sausages., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© Association of Food Scientists & Technologists (India) 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Accurate microbiological identification is crucial when managing chronic osteomyelitis (COM) and post-traumatic osteomyelitis (PTO). Although bone single photon emission computed tomography/computed tomography (SPECT/CT) has helped in localizing osteomyelitis lesions, its effectiveness in guiding microbiological sampling remains unclear. This study aimed to determine whether bone SPECT/CT can improve microbiological identification rates in COM or PTO of the extremities., Patients and Methods: From February 2020 to August 2024, 53 patients with suspected COM or PTO in the extremities were retrospectively analyzed. All patients underwent bone SPECT/CT, followed by microbiological sampling during surgery. Tissue samples were taken from the areas of high SPECT/CT uptake or based on intraoperative findings where no uptake was observed. Microorganism identification rates were analyzed, including a sub-group analysis based on antibiotic discontinuation., Results: Of the 53 patients, 42 had positive bone SPECT/CT scan findings, with pathogen identification in 30 patients (71.4 %). In contrast, pathogen identification occurred in one out of twelve patients (9.1 %) with negative findings (odds ratio 25, p< 0.001). Bone SPECT/CT demonstrated a sensitivity of 96.8 % and an overall accuracy of 75.5 %. When antibiotics had been discontinued for ≥2 weeks, the pathogen identification rate increased to 90 %, compared with 50 % for <2 weeks of discontinuation (odds ratio 10.0, p= 0.006). In a sub-group of 30 patients with adequate antibiotic discontinuation duration, a positive bone SPECT/CT scan yielded a pathogen identification rate of 90.1 % (odds ratio 60.0, p= 0.001)., Conclusion: Bone SPECT/CT effectively identifies optimal sites for microbiological sampling in COM and PTO of the extremities, particularly when antibiotics have been discontinued for ≥2 weeks, enhancing pathogen detection rates., Competing Interests: Declaration of competing interest The authors have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Thought-action fusion (TAF) is the metacognitive belief that the power of thoughts can have real-life consequences, often inducing unpleasant inner experiences and recruiting coping strategies such as rumination. Therefore, this study aimed to investigate the neural correlates of TAF and their associations with rumination in depression. A total of 37 patients with major depressive disorder (MDD) and 37 healthy controls (HCs) underwent functional magnetic resonance imaging with a TAF induction task and psychological assessments. In the TAF induction task, participants were asked to read the name of a close person (CP) or neutral person (NP) in association with negative (Neg) TAF and neutral (Neu) control statements. In this study, our TAF induction task activated brain regions, including the salient and default-mode networks, in the MDD and HC groups. However, along with higher likelihood TAF and rumination, behavioral data showed less negative feelings and longer reaction times under the NegCP condition in the MDD group compared with the HC group. Furthermore, in the MDD group, significantly higher activation in the bilateral caudate nuclei, left inferior frontal gyrus/anterior insula, putamen, and inferior parietal lobule under the NegCP condition was positively correlated with TAF and reflection. These findings suggest that during the TAF task, patients with MDD may activate different brain areas associated with the maintenance of high stimulus saliency and habit formation, which are important neural correlates linking TAF and rumination in depression., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Shortened multiday reaction experiments were conducted using the KIST chamber for atmospheric processes simulation (K-CAPS) to characterize the effects of ammonia (NH 3 ) and relative humidity (RH) on the formation of secondary organic aerosols (SOA) due to photooxidation of a mixture of toluene and inorganic gases such as NO x , SO 2 , and NH 3 . UV lamps were repeatedly turned on for 3 h (daytime) and off for 6 h (nighttime), and precursors were injected to a reaction bag once (Multiday Initial injection, MI) or repeatedly (Multiday Cyclic injection, MC) to simulate high particulate matter episode due to foreign inflow episode and domestic stagnation episodes, respectively. As a result, the amount of SOA formed in the humid (RH 80 %) MI experiments with ammonia was approximately 1.1 times more than in the traditional single day experiment and approximately 1.6 times more than in the MC experiment, implying that aging processes including nighttime effects without additional emission of precursors during transport can produce more SOA as reactions progressed further under the experimental conditions of this study. The higher the initial RH, the more SOA was formed, with a slope increasing approximately 1.2 μg/m 3 per unit RH, and the shorter run time required for SOA to increase to 30 μg/m 3 (twice the WHO PM 10 standard), with a slope decreasing approximately 0.3 h per unit RH, implying that more humid condition caused during long-range transport across the oceans is one of the possible reasons of high secondary aerosol formation. The SOA formation was reduced by approximately 60 % in the absence of ammonia, suggesting that ammonia reduction is needed to decrease not only secondary inorganic aerosols but also SOA. These results are useful to understand the major reason of high pollution of particulate matters by episode cases in urban areas., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Seung-Bok Lee reports financial support was provided by Korea Ministry of Science and ICT. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This study investigated bone mineral density (BMD) around the knee joint to clarify the mechanism by which tibia deformation exceeds that of the femur in patients with end-stage knee osteoarthritis (KOA)., Methods: We retrospectively analyzed 193 patients who underwent total knee arthroplasty for end-stage KOA with varus alignment. Preoperative T-score of the femur neck and femur total using dual-energy X-ray absorptiometry (DXA) and hounsfield units (HU) of the distal femur and proximal tibia using computed tomography (CT) were measured to asess the BMD. HU was measured by dividing the femur and tibia into medial, lateral, and total parts, respectively. Patients with medial proximal tibial angle (MPTA) ≥ 85° were considered 'group 1', and MPTA < 85° were 'group 2'. The HU between femur and tibia were compared in group 1. T-score, HU, and HU difference between group 1 and group 2 were compared., Results: The HU of the proximal tibia was lower than that of the distal femur (femur lateral > femur medial > tibia medial > tibia lateral). T-score (femur neck, femur total) and HU (femur lateral, femur total, tibia lateral) were lower in group 2 than in group 1. There was no difference in femur-tibia HU difference between groups., Conclusion: The medial tibia collapse more than the medial femur in varus endstage KOA was associated with the lower BMD of the proximal tibia than that of the distal femur, and the MPTA collapse was affected by the absolute value of BMD rather than by the femur-tibia BMD difference., 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 B.V. All rights reserved.)

Background: Early-stage lung cancers detected by low-dose computed tomography (CT) often require confirmation through invasive procedures due to the absence of endobronchial lesions. This study assesses the diagnostic utility of bronchial washing fluid (BW) sequencing, a less invasive alternative, aiming to identify patient characteristics most suited for this approach., Methods: From June 2017 to March 2018, we conducted a prospective cohort study by enrolling patients with incidental lung lesions suspected of early-stage lung cancer at two independent hospitals, and 114 were diagnosed with lung cancer while 50 were diagnosed with benign lesions. BW sequencing was performed using a targeted gene panel, and the clinical characteristics of patients detected with cancer through sequencing were identified., Results: Malignant cells were detected in 33 patients (28.9 %) through BW cytology. By applying specificity-focused mutation criteria, BW sequencing classified 42 patients (36.8 %) as having cancer. Among the cancer patients who were BW sequencing positive and BW cytology negative, 15 patients (75.0 %) showed necrosis on CT. The sensitivity of BW sequencing was particularly enhanced in patients with necrotic tumors, reaching 75 %., Conclusions: BW sequencing presents a viable, non-invasive diagnostic option for early-stage lung cancer, especially valuable in patients with necrotic lesions. By potentially reducing the reliance on more invasive diagnostic procedures, this method could streamline clinical workflows, decrease patient burden, and improve overall diagnostic efficiency., 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. Published by Elsevier Inc.)

Objectives: To assess the prognostic significance of extra-pancreatic organ invasion in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreas tail., Materials & Methods: This retrospective study included patients with resectable PDAC in the pancreas tail who received upfront surgery between 2014 and 2020 at a tertiary institution. Preoperative pancreas protocol computed tomography (CT) scans evaluated tumor size, peripancreatic tumor infiltration, suspicious metastatic lymph nodes, and extra-pancreatic organ invasion. The influence of extra-pancreatic organ invasion, detected by CT or postoperative pathology, on pathologic resection margin status was evaluated using logistic regression. The impact on recurrence-free survival (RFS) was analyzed using multivariable Cox proportional hazard models (clinical-CT and clinical-pathologic)., Results: The study included 158 patients (mean age, 65 years ± 8.8 standard deviation; 93 men). Extra-pancreatic organ invasion identified by either CT (p = 0.92) or pathology (p = 0.99) was not associated with a positive resection margin. Neither CT (p = 0.42) nor pathological (p = 0.64) extra-pancreatic organ invasion independently correlated with RFS. Independent predictors for RFS included suspicious metastatic lymph node (hazard ratio [HR], 2.05; 95 % confidence interval [CI], 1.08-3.9; p = 0.03) on CT in the clinical-CT model, pathological T stage (HR, 2.97; 95 % confidence interval [CI], 1.39-6.35; p = 0.005 for T2 and HR, 3.78; 95 % CI, 1.64-8.76; p = 0.002 for T3) and adjuvant therapy (HR, 0.62; 95 % confidence interval [CI], 0.42-0.92; p = 0.02) in the clinical-pathologic model., Conclusion: Extra-pancreatic organ invasion does not independently influence pathologic resection margin status and RFS in patients with resectable PDAC in the pancreas tail after curative-intent resection; therefore, it should not be considered a high-risk factor., 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 B.V. All rights reserved.)

Multicollinearity, characterized by significant co-expression patterns among genes, often occurs in high-throughput expression data, potentially impacting the predictive model's reliability. This study examined multicollinearity among closely related genes, particularly in RNA-Seq data obtained from embryoid bodies (EB) exposed to 5-fluorouracil perturbation to identify genes associated with embryotoxicity. Six genes-Dppa5a, Gdf3, Zfp42, Meis1, Hoxa2, and Hoxb1-emerged as candidates based on domain knowledge and were validated using qPCR in EBs perturbed by 39 test substances. We conducted correlation studies and utilized the variance inflation factor (VIF) to examine the existence of multicollinearity among the genes. Recursive feature elimination with cross-validation (RFECV) ranked Zfp42 and Hoxb1 as the top two among the seven features considered, identifying them as potential early embryotoxicity assessment biomarkers. As a result, a t test assessing the statistical significance of this two-feature prediction model yielded a p value of 0.0044, confirming the successful reduction of redundancies and multicollinearity through RFECV. Our study presents a systematic methodology for using machine learning techniques in transcriptomics data analysis, enhancing the discovery of potential reporter gene candidates for embryotoxicity screening research, and improving the predictive model's predictive accuracy and feasibility while reducing financial and time constraints., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Hearing loss causes numerous functional deficits. However, few studies have been conducted to assess the association between hearing loss and physical inactivity. This study aimed to evaluate the physical activity and sedentary behavior of hearing loss patients and their relation with the use of hearing aids., Materials and Methods: We extracted participants over 60 years of age with information on hearing status and physical activities from the eighth Korea National Health and Nutritional Examination Survey conducted from 2019 to 2020. We classified them into four groups: a normal hearing group (≤25 dB), a mild hearing loss group (>25 dB and ≤40 dB), a moderate hearing loss group (>40 dB and ≤50 dB), and a non-serviceable hearing group (>50 dB). Additionally, we extracted hearing aid users with hearing levels exceeding 50 dB., Results: After adjusting other factors, the non-serviceable hearing group walked less frequently than the moderate (p = 0.004) and mild hearing loss group (p < 0.001) and walked less and sat more than the normal hearing group (walking frequency: p < 0.001; walking time: p = 0.020; and sitting time: p = 0.034). Also, the hearing aid users walked more frequently (p = 0.003) and for longer (p = 0.045) than the non-serviceable hearing group., Conclusion: Hearing loss is associated with reduced walking and a sedentary lifestyle. The use of hearing aids is associated with improved physical activity. Appropriate interventions, including hearing aids, should be provided to hearing loss patients., Level of Evidence: 3 (individual cross-sectional study) Laryngoscope, 134:5109-5115, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict a return to alcohol use after a liver transplant (LT) for alcohol-associated liver disease. A retrospective analysis of deceased donor LT from October 2018 to April 2022 was performed. All patients underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. After LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol testing. Patients with alcohol-associated liver disease were stratified by < or > 6 months of sobriety before listing. Those with <6 months were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was the utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict a return to alcohol use (+phosphatidylethanol) within 1 year after LT. Of the 365 LT, 86 had > 6 months of sobriety, and 85 had <6 months of sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, the return to drinking was similar in the AH (24%) compared to <6-month non-AH (15%) and >6-month alcohol-associated liver disease (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict a return to alcohol was low (accuracy 61%-63%) with poor sensitivity (46% and 37%), specificity (67%-68%), positive predictive value (22%-26%) with moderate negative predictive value (81%-83%), respectively with higher negative predictive values (95%) in predicting a return to heavy drinking. Both SALT and HRAR scores had good negative predictive value in identifying patients at low risk for recidivism., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495)., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Summary: Deep inferior epigastric perforator (DIEP) flap surgery is a common technique for breast reconstruction. However, the long and noticeable abdominal scar is one of its greatest disadvantages. Here, the authors suggest a minimal scarring DIEP flap harvest with a novel abdominal design. The key to this method is to preserve more skin tissue with a circular design centered around the navel. Three circular incisions are made: (1) the smallest circle represents an incision around the umbilicus; (2) the middle circle with a radius of less than 3.5 cm indicates another skin incision because the donut-like skin paddle between the small and middle circles is included in the flap; and (3) the largest circle with a radius of greater than 10 cm represents the extent of flap dissection that was performed diagonally from the skin toward the Scarpa fascia. Pedicle dissection proceeds with the conventional method. For closure, a purse-string suture is performed with the umbilicus at its center, leaving only a single small circular scar around the umbilicus as the final scar. Closure of the donor-site is possible with the patient in a supine or slightly flexed position because of less skin excision., (Copyright © 2023 by the American Society of Plastic Surgeons.)

In the present study, we investigated the potential immunomodulatory effects of heat-killed (hLR) and live Limosilactobacillus reuteri PSC102 (LR; formerly Lactobacillus reuteri PSC102) in RAW264.7 macrophage cells and Sprague-Dawley rats. RAW264.7 murine macrophage cells were stimulated with hLR and LR for 24 h. Cyclophosphamide (CTX)-induced immunosuppressed Sprague-Dawley rats were orally administered with three doses of hLR (L-Low, M-Medium, and H-High) and LR for 3 weeks. The phagocytic capacity, production of nitric oxide (NO), and expression of cytokines in RAW264.7 cells were measured, and the different parameters of immunity in rats were determined. hLR and LR treatments promoted phagocytic activity and induced the production of NO and the expression of iNOS, TNF-α, IL-1β, IL-6, and Cox-2 in macrophage cells. In the in vivo experiment, hLR and LR treatments significantly increased the immune organ indices, alleviated the spleen injury, and ameliorated the number of white blood cells, granulocytes, lymphocytes, and mid-range absolute counts in immunosuppressive rats. hLR and LR increased neutrophil migration and phagocytosis, splenocyte proliferation, and T lymphocyte subsets (CD4 + , CD8 + , CD45RA + , and CD28 + ). The levels of immune factors (IL-2, IL-4, IL-6, IL-10, IL-12A, TNF-α, and IFN-γ) in the hLR and LR groups were upregulated compared with those in the CTX-treatment group. hLR and LR treatments could also modulate the gut microbiota composition, thereby increasing the relative abundance of Bacteroidetes and Firmicutes but decreasing the level of Proteobacteria. hLR and LR protected against CTX-induced adverse reactions by modulating the immune response and gut microbiota composition. Therefore, they could be used as potential immunomodulatory agents.

Aim: The study's aim was to examine how workplace incivility and workload influence nurses' work attitudes (turnover intention, job satisfaction, and organizational commitment) using the stress-strain-outcome framework., Background: There is a lack of comprehensive research on the combined effects of workplace incivility and workload on nurses' work attitudes., Introduction: Two workplace stressors, incivility and workload, were hypothesized to lead to burnout, which in turn influences nurses' work attitudes., Methods: A cross-sectional, descriptive correlational study was conducted. Survey data were collected from 1,255 direct care nurses with a minimum of 6 months' nursing experiences in 34 general hospitals across Korea. Structural equation modeling was used to test the hypothesized model. This study is reported using the STROBE checklist., Results: As hypothesized, both workplace incivility and workload increased burnout. Heightened burnout correlated with increased turnover intention, lowered job satisfaction, and reduced organizational commitment. While workplace incivility impacted these outcomes both directly and indirectly via its effect on burnout, workload influenced the outcomes solely through burnout., Conclusion: The study's findings are based on one, nonrandomized sample of nurses working at South Korean hospitals. Despite such study limitations, the study findings support the adverse impact of two workplace stressors on burnout and nurses' work attitudes., Implications for Nursing: Evidence-informed interventions for both workplace stressors include training programs, clear policy guidelines, open communication channels, and supportive work environments., Implications for Nursing and Health Policy: Zero tolerance and equity, diversity and inclusivity policies to promote workplace civility must be enforced. Workload needs to be patient-centered, ensuring a "fit" between patient needs and nurse staffing., (© 2024 The Authors. International Nursing Review published by John Wiley & Sons Ltd on behalf of International Council of Nurses.)

Introduction and Objectives: There are no clinical data on the efficacy of intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI in patients with acute myocardial infarction (AMI) and cardiogenic shock. The current study sought to evaluate the impact of intravascular imaging-guided PCI in patients with AMI and cardiogenic shock., Methods: Among a total of 28 732 patients from the nationwide pooled registry of KAMIR-NIH (November, 2011 to December, 2015) and KAMIR-V (January, 2016 to June, 2020), we selected a total of 1833 patients (6.4%) with AMI and cardiogenic shock who underwent PCI of the culprit vessel. The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, a composite of cardiac death, myocardial infarction, repeat revascularization, and definite or probable stent thrombosis., Results: Among the study population, 375 patients (20.5%) underwent intravascular imaging-guided PCI and 1458 patients (79.5%) underwent angiography-guided PCI. Intravascular imaging-guided PCI was associated with a significantly lower risk of 1-year MACE than angiography-guided PCI (19.5% vs 28.2%; HR, 0.59; 95%CI, 0.45-0.77; P<.001), mainly driven by a lower risk of cardiac death (13.7% vs 24.0%; adjusted HR, 0.53; 95%CI, 0.39-0.72; P<.001). These results were consistent in propensity score matching (HR, 0.68; 95%CI, 0.46-0.99), inverse probability weighting (HR, 0.61; 95%CI, 0.45-0.83), and Bayesian analysis (Odds ratio, 0.66, 95% credible interval, 0.49-0.88)., Conclusions: In AMI patients with cardiogenic shock, intravascular imaging-guided PCI was associated with a lower risk of MACE at 1-year than angiography-guided PCI, mainly driven by the lower risk of cardiac death., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Aggressive hydration using lactated Ringer's solution prevents postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Concerns of this strategy are large volume and lengthy hydration. Our study aimed to evaluate the efficacy of tailored aggressive hydration (TAH) for PEP prevention., Methods: In this prospective, multicenter, double-blinded, randomized trial conducted across 3 tertiary Korean hospitals, patients who underwent ERCP for the first time were randomly assigned (1:1) to the tailored standard hydration (TSH) and TAH groups. The TSH group received 1.5 mL/kg/hr lactated Ringer's solution during and after ERCP, whereas the TAH group was administered a 20 mL/kg bolus post-ERCP and 3 mL/kg/hr during and after the procedure. Both groups were assessed for elevated serum amylase levels and pain 4-6 hours after ERCP. If both were absent, hydration was discontinued. If either was present, hydration was continued at the original rate until 8 hours. The primary end point was PEP development and was analyzed on an intention-to-treat analysis., Results: A total of 344 patients were randomly assigned to treatment groups (171 to the TSH group and 172 to the TAH group). PEP was observed in 9.4% (16/171) in the TSH group and 3.5% (6/172) in the TAH group (relative risk 0.37, 95% confidence interval 0.15-0.93, P = 0.03). No difference was identified between the 2 groups in PEP severity ( P = 0.80) and complications related to volume overload ( P = 0.32)., Discussion: TAH according to the presence of abdominal pain or elevated serum amylase levels at 4-6 hours after ERCP is safe and prevents PEP development., (Copyright © 2024 by The American College of Gastroenterology.)

We examined the relative effectiveness of a college-level self-management (SM) course and a physical exercise (PE) course on improving self-control. In Study 1, Barratt Impulsiveness Scale (BIS-11) and general regulatory behavior questionnaire were administered before and after the courses to students from an SM course (experimental group 1; n  = 87), a PE course (experimental group 2; n  = 22), and a liberal arts course (control group; n  = 28). There was a significant decrease in impulsivity and improvement in daily self-control behaviors in the SM group only. In Study 2, the same tests were administered before, after, and 3 months after the courses to the SM ( n  = 47) and PE groups ( n  = 20). Impulsivity and daily self-control behaviors were improved only in the SM group and maintained after 3 months. Thus, self-control can be improved and stabilized by teaching and directing self-control behaviors among college students.

Bioaerosols pose significant risks to indoor environments and public health, driving interest in advanced antimicrobial air filtration technologies. Conventional antimicrobial filters often suffer from diminished efficacy over time and require additional binders to retain antimicrobial agents. This study introduces CV@PAN, a self-disinfecting nanofiber fabricated via electrospinning of crystal violet (CV) and polyacrylonitrile (PAN). The process effectively incorporated CV into the PAN framework, minimizing environmental release. We comprehensively analyzed the physical and chemical properties of CV@PAN nanofibers, including fiber morphology, size distribution, chemical composition, thermal stability, and transparency. The CV@PAN nanofibers exhibited an average diameter of 0.28 μm. The fabricated filter achieved a bioaerosol removal efficiency of >99.2% against Staphylococcus epidermidis, with a low-pressure drop of 401.6 Pa at a face velocity of 16 cm/s. The filter demonstrated an optical transparency exceeding 50%. Upon visible light exposure, the embedded CV generated reactive oxygen species, resulting in an antibacterial efficacy of >99.9%. These findings demonstrate the significant potential of CV@PAN nanofiber filters for air quality management and their promise as an advancement in antibacterial air filtration technology., 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.)