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Young-Jee Jeon,1,&ast; Sangyoung Han,2,&ast; Gyung-Min Park,2 Tae Young Lee,3 Soon Eun Park,4 Hyunho Lee,4 Byung Ju Kang2 1Department of Family Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 2Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 3Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 4Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Byung Ju KangDepartment of Internal Medicine, Ulsan University Hospital, University of Ulsan, College of Medicine, 877, Bangeojinsunhwando-ro, Dong-gu, Ulsan, 44033, Republic of KoreaTel +82-52-250-8870Fax +82-52-250-8997Email pastnumber@naver.comPurpose: Low-attenuation muscle area (LAMA) and normal-attenuation muscle area (NAMA) indicate lipid-rich and lipid-poor skeletal muscle areas, respectively. Additionally, intermuscular adipose tissue (IMAT) indicates localized fat between muscle groups. In this study, we aimed to evaluate the intramuscular and intermuscular fat infiltration in individuals with chronic obstructive pulmonary disease (COPD) by performing quantitative assessment of the LAMA, NAMA, and IMAT observed on abdominopelvic computed tomography (APCT) images.Patients and Methods: We performed a cross-sectional study using data of subjects who underwent a general health examination with APCT at Ulsan University Hospital between March 2014 and June 2019. We classified the subjects into control and COPD groups based on age, smoking history, and pulmonary function results. We compared the attenuation and body mass index adjusted area of intra-abdominal components between the two groups using propensity score matching. We also evaluated these outcomes in COPD subgroups (mild and moderate stage subjects).Results: Overall, 6,965 subjects were initially enrolled, and 250 pairs of control and COPD subjects were selected after propensity score matching. The NAMA attenuation (unstandardized β=− 1.168, P< 0.001) was lower, and the IMAT (unstandardized β=0.042, P=0.006) and LAMA (unstandardized β=0.120, P< 0.001) indexes were greater in the COPD group than in the control group. In subgroup analysis, those with mild and moderate COPD also had high IMAT (unstandardized β=0.037, P=0.009 and unstandardized β=0.045, P< 0.001) and LAMA (unstandardized β=0.089, P=0.002 and unstandardized β=0.147, P< 0.001) indexes compared to the control subjects. However, the NAMA attenuation (unstandardized β=− 1.075, P< 0.001) and NAMA index (unstandardized β=− 0.133, P=0.015) were significantly lower in moderate COPD subjects only.Conclusion: Our study showed that intramuscular and intermuscular abdominal fat infiltration could be present in subjects with mild COPD, and it might be exacerbated in those with moderate COPD.Keywords: abdominal fat, abdominal muscles, chronic obstructive pulmonary disease, computed tomography

Yoo-Jeong Jeon,1 Seung Ku Lee,2,3 Chol Shin2– 5 1Department of Sports & Health Science, Hanbat National University, Daejeon, Korea; 2Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea; 3College of Medicine, Korea University, Seoul, Republic of Korea; 4Department of Pulmonary, Sleep and Critical Care Medicine, College of Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea; 5Transdisciplinary Major in Learning Health Systems, Department of Healthcare, Sciences, Graduate School, Korea University, Seoul, Republic of KoreaCorrespondence: Chol ShinDepartment of Pulmonary, Sleep and Critical Care Medicine, College of Medicine, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, Gyeonggi-do, Ansan-si, 15355, Republic of KoreaTel +82-31-412-5603Email chol-shin@hanmail.netPurpose: Muscle strength is associated with type 2 diabetes mellitus (T2DM). However, it is controversial whether muscle strength and normalized muscle strength is a risk factor for T2DM. Moreover, the relationship of back muscle strength (BMS) and incident T2DM has not been reported. In this study, we investigated the relationship between HGS, BMS, normalized HGS and BMS, and incident T2DM.Methods: A total of 2699 non-diabetes subjects aged 40– 69 years (1313 women and 1386 men) in the Korean Genome and Epidemiology Study (KoGES) Ansan cohort were followed for 16 years. At the baseline and biennial follow‐up visits, fasting glucose, postprandial 2-h glucose, clinical examinations, HGS, and BMS were measured by trained interviewers and examiners. HGS and BMS were measured at baseline. The relationships between incident T2DM, HGS, BMS, and normalized HGS and BMS were estimated using Cox proportional hazard regression models after adjusting for the confounding factors.Results: HGS and BMS were not associated with incident T2DM in multivariate analysis. However, the hazard ratio (HR) per one standard deviation (SD) increase in the body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR)-normalized HGS, and BMS was associated with a lower risk for incident T2DM in both women and men after adjusting for the confounding factors (HR = 0.842– 0.880-fold for women, p ≤ 0.015; HR = 0.887– 0.903-fold for men, p ≤ 0.024). In the sub-analysis of menopause status, the HR per one SD increase in BMI, weight2/3, WC, and WHR-normalized HGS was associated with a lower risk for incident T2DM in both pre- and post-menopausal women after adjusting for the confounding factors (HR = 0.860– 0.820-fold for premenopausal, P ≤ 0.006; HR = 0.900– 0.867-fold for postmenopausal, p ≤ 0.024). Additionally, we confirmed that the quartile group with higher muscle strength was associated with a lower risk for incident T2DM.Conclusion: The present study suggested that normalized HGS and BMS were associated with a lower risk for the future development of T2DM. Moreover, weak muscle strength in premenopausal women may be the cause of T2DM. Further research is needed to determine whether efforts to improve muscle strength, such as exercise can reduce the risk of T2DM.Keywords: incident type 2 diabetes mellitus, hand grip strength, back strength

We demonstrate that KIOM-79, combined extracts obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of RAW 264.7 cells with KIOM-79 inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohisto-chemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression. Immunostaining of p65, EMSA, and reporter gene assay showed that KIOM-79 inhibited NF-kappa/Rel nuclear translocation, DNA binding, and transcriptional activation, respectively. Western immunoblot analysis of p38 kinase showed KIOM-79 significantly inhibited the phosphoylation of p38 kinase which is important in the regulation of iNOS gene expression. Collectively, this series of experiments indicates that KIOM inhibits iNOS gene expression by blocking NF-kappa/Rel and p38 kinase signaling. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of KIOM-79 on iNOS suggest that KIOM-79 may represent a useful anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

Sarcopenia is a pertinent challenge in the super-aged societies causing reduced functional performance, poor quality of life and increased morbidity. In this study, the potential of perindopril erbumine-loaded ultradeformable liposomes (PE-UDLs) against sarcopenia was investigated. PE-UDLs were prepared by thin-film hydration and extrusion method using egg yolk L-α-phosphatidylcholine (EPC) as a lipid bilayer former and Tween 80 or sodium deoxycholate as an edge activator. Owing to the smallest particle size (75.0 nm) and the highest deformability (54.2) and entrapment efficiency (35.7 %), PE-UDLs with EPC to Tween 80 ratio of 8:2 was selected as the optimized formulation. The optimized PE-UDLs showed substantially higher cumulative amount of drug permeated and permeation rate across the rat skin compared to PE solution (485.7 vs. 50.1 µg and 13.4 vs. 2.3 µg/cm 2 /h, respectively). Topically applied PE-UDLs successfully ameliorated the effects of lipopolysaccharide (LPS)-induced sarcopenia in mice by improving body weight changes, grip strength and muscle weight. Furthermore, PE-UDLs reduced the shrinkage of muscle fibers as demonstrated by higher cross-sectional area than PE solution. PE-UDLs also increased the expression of myosin heavy chain (MHC) protein and reduced the expression of muscle atrophy F-box (Atrogin-1) and muscle ring-finger protein-1 (MuRF1), thereby improving muscles atrophy. In conclusion, these results demonstrate the therapeutic potential of PE-UDLs against sarcopenia., 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.)

Liver-expressed antimicrobial peptide-2 (LEAP-2) is a cysteine-rich peptide that plays a crucial role in the innate immune system of fish. To investigate the molecular function of LEAP-2 from olive flounder, Paralichthys olivaceus, we cloned the gene encoding LEAP-2 using PCR and expressed it in Escherichia coli. Analysis of LEAP-2 expression revealed predominant transcripts in the liver and lower levels in the intestine of olive flounder, whereas their expression levels in the liver and head kidney increased, during the initial stage of infection with the aquapathogenic bacterium Edwardsiella piscicida. Recombinant LEAP-2 (rOfLEAP-2) purified from E. coli exhibited antimicrobial activity, as demonstrated by the ultrasensitive radial diffusion assay, against both Gram-positive (Bacillus subtilis, Streptococcus parauberis, and Lactococcus garvieae) and Gram-negative (Vibrio harveyi and E. coli) bacteria, with minimum inhibitory concentrations ranging from 25 to 100 μg/mL depending on the species tested. The antibacterial activity of rOfLEAP-2 was attributed to its ability to disrupt bacterial membranes, validated by the N-phenylnaphthalen-1-amine uptake assays and scanning electron microscope analysis against E. coli, V. harveyi, B. subtilis, and L. garvieae treated with rOfLEAP-2. Furthermore, a synergistic enhancement of antibacterial activity was observed when rOfLEAP-2 was combined with ampicillin or synthetic LEAP-1 peptide, suggesting a distinct mechanism of action from those of other antimicrobial agents. These findings provide evidence for the antibacterial efficacy of LEAP-2 from olive flounder, highlighting its potential therapeutic application against pathogenic bacteria., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The upper mediastinum is the most common metastatic site of esophageal squamous cell carcinoma (ESCC), and complete dissection of this region is important for oncologic reasons. This study aimed to compare the oncologic outcomes and completeness of upper mediastinal dissection for ESCC patients undergoing the Ivor-Lewis (IL) or McKeown (MK) operations., Methods: Between 2013 and 2018, 680 patients (IL, 433; MK, 247) underwent upfront esophagectomy with two-field lymph node (LN) dissection for mid-to-lower ESCCs. Propensity score-matching (1:1 ratio) was performed to minimize the effects of confounding factors., Results: The mean age was 64.5 ± 8.8 years, and 635 (93.4%) of the patients were male. The median follow-up period was 71.66 months (interquartile range [IQR], 59.60-91.04 months). The IL group had a higher mean age, lower body mass index, higher proportion of advanced T and N, and higher adjuvant therapy rates, but these differences were well-balanced after propensity score-matching. The mean number of dissected LNs at the mediastinum and at the right recurrent laryngeal nerve (RLN) were similar between the two groups after matching, whereas the IL group exhibited a slightly greater number of dissected LNs at the left RLN. Among the matched patients, the IL and MK groups exhibited similar 5-year overall survival (OS: 75.1% vs 78.0%; p = 0.368). The multivariate model showed no differences in OS, disease-free survival, or recurrence-free survival for locoregional, upper mediastinum, or neck between the two groups., Conclusions: This study suggests that both the IL and MK operations are oncologically feasible for patients with mid-to-lower ESCC., (© 2024. Society of Surgical Oncology.)

Introduction: Preparing appropriate red blood cells (RBCs) before surgery is crucial for improving both the efficacy of perioperative workflow and patient safety. In particular, thoracic surgery (TS) is a procedure that requires massive transfusion with high variability for each patient. Hence, the precise prediction of RBC requirements for individual patients is becoming increasingly important. This study aimed to 1) develop and validate a machine learning algorithm for personalized RBC predictions for TS patients and 2) assess the usability of a clinical decision support system (CDSS) integrating this artificial intelligence model., Methods: Adult patients who underwent TS between January 2016 and October 2021 were included in this study. Multiple models were developed by employing both traditional statistical- and machine-learning approaches. The primary outcome evaluated the model's performance in predicting RBC requirements through root mean square error and adjusted R 2 . Surgeons and informaticians determined the precision MSBOS-Thoracic Surgery (pMSBOS-TS) algorithm through a consensus process. The usability of the pMSBOS-TS was assessed using the System Usability Scale (SUS) survey with 60 clinicians., Results: We identified 7,843 cases (6,200 for training and 1,643 for test sets) of TSs. Among the models with variable performance indices, the extreme gradient boosting model was selected as the pMSBOS-TS algorithm. The pMSBOS-TS model showed statistically significant lower root mean square error (mean: 3.203 and 95% confidence interval [CI]: 3.186-3.220) compared to the calculated Maximum Surgical Blood Ordering Schedule (MSBOS) and a higher adjusted R 2 (mean: 0.399 and 95% CI: 0.395-0.403) compared to the calculated MSBOS, while requiring approximately 200 fewer packs for RBC preparation compared to the calculated MSBOS. The SUS score of the pMSBOS-TS CDSS was 72.5 points, indicating good acceptability., Conclusions: We successfully developed the pMSBOS-TS capable of predicting personalized RBC transfusion requirements for perioperative patients undergoing TS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Financial support for this study was provided entirely by a grant from the Ministry of Health & Welfare, Republic of Korea. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: A sea cucumber ( Stichopus japonicus ) is an invertebrate rich in high-quality protein peptides that inhabits the coastal seas around East Asian countries. Such bioactive peptides can be utilized in targeted disease therapies and practical applications in the nutraceutical industry., Methods: Bioactive peptides were isolated from Stichopus japonicus through ultrafiltration and Sephadex G-10 size exclusion chromatography. The low-molecular-weight fraction (ACSH-III) showed the highest hydroxyl radical scavenging and angiotensin-converting enzyme (ACE) inhibitory activities. Subsequent purification of ACSH-III resulted in four fractions, of which ACSH-III-F3 and ACSH-III-F4 exhibited significant bioactivity., Results: Peptides identified in these fractions, including Phenylalanine-Proline-Threonine-Tyrosine (FPTY) and Tyrosine-Proline-Serine-Tyrosine-Proline-Serine (YPSYPS), were characterized using high-performance liquid chromatography (HPLC) and quadrupole time-of-flight mass spectrometry (QTOF-MS). FPTY demonstrated the most potent antioxidant and antihypertensive activities among these peptides, with IC 50 values of 0.11 ± 0.01 mg/mL for hydroxyl radicals and 0.03 ± 0.01 mg/mL for ACE inhibition. Docking simulations revealed strong binding affinities of these peptides to the active site of the ACE, with FPTY displaying interactions similar to those of the synthetic inhibitor lisinopril., Conclusions: These findings suggest that the identified peptides, particularly FPTY, have potential applications as natural antioxidants and functional foods., (© 2024 The Author(s). Published by IMR Press.)

Background: Previous research has shown that the use of renin-angiotensin system (RAS) blockers is linked to a lower prevalence of posttraumatic stress disorder (PTSD), but longitudinal studies are scarce. We aimed to estimate the association between the use of RAS blockers and the risk of PTSD among individuals taking antihypertensive medications., Methods: This longitudinal study included participants aged 40-69 from the UK Biobank. Exposure data were obtained from the initial assessment (2006-10), while outcome data were obtained from the online mental health questionnaire administered 6-11 years later (2016-17). We included participants who were under antihypertensive treatment and did not have a prior diagnosis of PTSD before the initial assessment. Use of RAS blockers was defined as self-reported regular use, at the initial assessment, of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Among participants who experienced adverse life experiences, cases of probable PTSD were defined with the six-item PTSD Checklist-Civilian version score ≥ 14. Logistic regression with inverse probability of treatment weighting was used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the association between RAS blocker use and the risk of probable PTSD., Results: Of the 15,954 participants (mean age = 59.9 years; 42.6% women) under antihypertensive treatment with no prior history of PTSD at the initial assessment, 64.5% were taking RAS blockers. After a mean follow-up of 7.5 years, 1,249 (7.8%) were newly identified with probable PTSD. RAS blocker users had a lower risk of probable PTSD than RAS blocker non-users (OR = 0.84 [95% CI: 0.75-0.94]), whereas the use of other antihypertensive medications showed no such association (users vs. non-users; calcium channel blockers, OR = 0.99 [95% CI: 0.88-1.11]; beta-blockers, 1.20 [1.08-1.34]; and thiazide-related diuretics, 1.15 [1.03-1.29]). The association between probable PTSD risk and the use of ACEi vs. ARB showed no significant difference (p = 0.96)., Conclusions: Among individuals under antihypertensive treatment, the use of RAS blockers was associated with a decreased risk of probable PTSD. This added benefit of RAS blockers should be considered in the selection of antihypertensive medications., (© 2024. The Author(s).)

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.)

Overexposure to ultraviolet (UV) radiation can lead to photoaging, which contributes to skin damage. The objective of this study was to evaluate the effects of an antioxidant peptide (SHP2) purified from seahorse ( Hippocampus abdominalis ) alcalase hydrolysate on UVB-irradiated skin damage in human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells and a zebrafish model. The data revealed that SHP2 significantly enhanced cell viability by attenuating apoptosis through the reduction of intracellular reactive oxygen species (ROS) levels in UVB-stimulated HaCaT cells. Moreover, SHP2 effectively inhibited ROS, improved collagen synthesis, and suppressed the secretion of matrix metalloproteinases (MMPs) in UVB-irradiated HDF cells. SHP2 restored the protein levels of HO-1, Nrf2, and SOD, while decreasing Keap1 expression in UVB-treated HDF, indicating stimulation of the Keap1/Nrf2/HO-1 signaling pathway. Furthermore, an in vivo study conducted in zebrafish confirmed that SHP2 inhibited photoaging by reducing cell death through the suppression of ROS generation and lipid peroxidation. Particularly, 200 µg/mL of SHP2 exerted a remarkable anti-photoaging effect on both in vitro and in vivo models. These results demonstrate that SHP2 possesses antioxidant properties and regulates skin photoaging activities, suggesting that SHP2 may have the potential for use in the development of cosmetic products.

Marine natural products comprise unique chemical structures and vast varieties of biological activities. This review aims to summarize halichondrin, a marine natural product, and its synthetic analogs along with its therapeutic properties and mechanisms. Halichondrin and its analogs, derived from marine sponges, exhibit potent antineoplastic properties, making them promising candidates for cancer therapeutics. These compounds, characterized by their complex molecular structures, have demonstrated significant efficacy in inhibiting microtubule dynamics, leading to cell cycle arrest and apoptosis in various cancer cell lines. Several types of halichondrins such as halichondrins B, C, norhalichondrin B, and homohalichondrin B have been discovered with similar anticancer and antitumor characteristics. Since naturally available halichondrins show hurdles in synthesis, recent advancements in synthetic methodologies have enabled the development of several halichondrin analogs, such as E7389 (eribulin), which have shown improved therapeutic indices. Eribulin has shown excellent immunomodulatory properties by several mechanisms such as reprogramming tumor microenvironments, facilitating the infiltration and activation of immune cells, and inhibiting microtubule dynamics. Despite promising results, challenges remain in the synthesis and clinical application of these compounds. This review explores the mechanisms underlying the immunomodulatory activity of halichondrin and its analogs in cancer therapy, along with their clinical applications and potential for future drug development.

The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney., 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.)

Extreme weather phenomena caused by climate change have exacerbated soil erosion and the subsequent dispersion of pollutants. Pseudomonas aeruginosa is known to contribute to the remediation of polluted water and reduce the geochemical mobility of heavy metals in contaminated soil. However, studies on the influence of biopolymers produced by soil microbes and P. aeruginosa on physical soil properties and soil erosion are limited. We aimed to investigate the influence of soil microbes on the mitigation of soil erosion and geochemical dispersion of heavy metals using a naturally occurring microbial substance, P. aeruginosa-based biopolymer (PBB). The PBB comprised carboxyl, hydroxyl, and amine surface functional groups; consequently, the biopolymer effectively sequestered Cd (maximum sorption capacity q m  = 45.7 mg/g), Cu (q m  = 26.7 mg/g), Pb (q m  = 64.9 mg/g), and Zn (q m  = 26.1 mg/g) in the solution. The PBB amendment of the soil improved the physical properties associated with soil erosion, increasing soil aggregation stability and shear strength by 41.6% and 36.8%, respectively. The extraction of heavy metals from soil via synthetic precipitate leaching decreased by 54.2% following the PBB amendment, and a negative correlation was observed between soil aggregate stability and heavy metal extraction, indicating that this microbial substance could immobilize pollutants by adsorbing cationic metal ions and inhibiting water-induced disaggregation. In the soil erosion experiments, soil loss and heavy metal extraction decreased by 70.9% and 43.8%, respectively, following the PBB amendment. These aggregation and sorption effects of the PBB underscore the potential of soil microbes to mitigate soil erosion and immobilize the geochemical dispersion of heavy metals, thereby contributing to the conservation of soil and water quality in areas surrounding contaminated slopes and heavy metal-contaminated areas, such as cut slopes, agricultural fields, mine dumps, and dams., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Myoung-Soo Ko reports financial support was provided by National Research Foundation of Korea. Myoung-Soo Ko reports financial support was provided by Korea Institute of Energy Technology Evaluation and Planning. 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 Elsevier B.V. All rights reserved.)

Rationale: Occult lymph node metastasis (OLNM) is frequently found in patients with resectable non-small cell lung cancer (NSCLC), despite using diagnostic methods recommended by guidelines., Objectives: To evaluate the risk of OLNM in NSCLC patients using the radiologic characteristics of the primary tumor on computed tomography (CT)., Methods: We retrospectively reviewed clinicopathologic features of 2042 clinical T1-4N0 NSCLC patients undergoing curative intent pulmonary resection. Unique radiological features (i.e., air-bronchogram throughout the whole tumor, heterogeneous ground-glass opacity (GGO), mainly cystic appearance, endobronchial location), percentage of solid portion, and shape of tumor margin were analyzed via a stepwise approach. We used multivariable logistic regression to assess the relationship between OLNM and tumor characteristics., Results: Compared with the other unique features, endobronchial tumors were associated with the highest risk of OLNM (OR = 3.9, 95% confidence interval (CI) = 2.29-6.62), and heterogeneous GGO and mainly cystic tumors were associated with a low risk of OLNM. For tumors without unique features, the percentage of the solid portion was measured, and solid tumors were associated with OLNM (OR = 2.49, 95% CI = 1.86-3.35). Among part-solid tumors with solid proportion > 50%, spiculated margin, and peri-tumoral GGO were associated with OLNM., Conclusions: The risk of OLNM could be assessed using radiologic characteristics on CT. This could allow us to adequately select optimal candidates for invasive nodal staging procedures (INSPs) and complete systematic lymph node dissection., Clinical Relevance Statement: These data may be helpful for clinicians to select appropriate candidates for INSPs and complete surgical systematic lymph node dissection in NSCLC patients., Key Points: Lymph node metastasis status plays a key role in both prognostication and treatment planning. Solid tumors, particularly endobronchial tumors, were associated with occult lymph node metastasis (OLNM). The risk of OLNM can be assessed using radiologic characteristics acquired from CT images., Competing Interests: Compliance with ethical standards Guarantor The scientific guarantor of this publication is Ho Yun Lee. Conflict of interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry No complex statistical methods were necessary for this paper. Informed consent Written informed consent was waived by the Institutional Review Board. Ethical approval Institutional Review Board approval was obtained. (IRB no. SMC 2019-04-123-003). Study subjects or cohorts overlap Not applicable. Methodology RetrospectiveObservationalPerformed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: Fear of cancer recurrence (FCR) is a multidimensional phenomenon among cancer survivors. This cross-sectional study aimed to identify the prevalence of FCR and its predictors among survivors of non-small cell lung cancer (NSCLC) in Korea., Methods: Participants who finished NSCLC treatment one or more months prior completed the Korean version of Fear of Cancer Recurrence Inventory-Short Form (K-FCRI-SF) and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) at single tertiary hospital in Korea. Multivariate-adjusted logistic regression and stepwise backward selection were used to determine the potential predictors of FCR., Results: Of the total 949 participants (mean age 63.4 ± 8.8 years, 44.3% women), 55.8% had high FCR. Female (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 1.06-1.95), pathologic stage III (aOR 1.97, 95% CI 1.18-3.30), poor overall quality of life (aOR 1.42, 95% CI 1.03-1.95), poor emotional functioning (aOR 3.91, 95% CI 2.64-5.81), poor social functioning (aOR 1.87, 95% CI 1.31-2.68), and severe dyspnea (aOR 2.91, 95% CI 1.03-8.21) were independent predictors of high FCR. Old age (≥ 70 years) was included in the final model (aOR 0.74, 95% CI 0.51-1.06) but did not show clinical significance., Conclusions: Our study demonstrated that high FCR was prevalent in NSCLC patients in Korea. To prevent this, we suggest screening and early detection of FCR based on sex, pathologic stage, quality of life, emotional and social functioning, and dyspnea., Implications for Cancer Survivors: Screening and early detection of FCR based on sex, pathologic stage, quality of life, emotional and social functioning, and dyspnea is suggested., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study evaluated the properties of 3D-printed Onyx-fiberglass composites. These composites were 3D-printed with zero, one, two, three, and four layers of fiberglass. Ten samples of each configuration were printed for the tensile and flexural tests. The average tensile strength of the Onyx specimens was calculated to be 44.79 MPa, which increased linearly by approximately 20-25 MPa with each additional fiberglass layer. The elastic moduli calculated from the micromechanics models were compared with the experimental values obtained from the tensile tests. The experimental elastic modulus increased more significantly than the model prediction when more fiberglass layers were added. The flexural modulus of Onyx was 17.6 GPa, which increased with each additional fiberglass layer. This quantitative analysis of composites fabricated using 3D printing highlights their potential for commercialization and industrial applications.

Cardiovascular diseases (CVDs) are responsible for significant mortality rates globally that have been raised due to the limitation of the available treatments and prevalence of CVDs. The innovative research and identification of potential preventives for CVDs are essential to alleviate global deaths and complications. The marine environment is a rich source of bioactive substances and provides a unique chemical arsenal against numerous ailments due to its unrivaled biodiversity. Marine polyphenolic compounds (MPCs) are unique because of their structural variety and biologically significant activity. Further, MPCs are well-reported for their valuable biological activities, such as anti-inflammatory, cardioprotective, and antioxidant, demonstrating encouraging results in preventing and treating CVDs. Therefore, investigation of the structure-activity relationship (SAR) between MPCs and CVDs provides insights that reveal how the structural components of these compounds affect their effectiveness. Further, comprehending this correlation is essential for advancing medications and nutraceuticals sourced from marine sources, which could transform the strategy for treating and preventing cardiovascular diseases. Therefore, this study provides a comprehensive analysis of existing research by emphasizing the role of MPCs in CVD treatments and evaluating the SAR between MPCs and CVDs with challenges and future directions.

Objectives: The supine sleep position and the rapid eye movement (REM) stage are widely recognized to exacerbate the severity of obstructive sleep apnea (OSA). Position-dependent OSA is generally characterized by an apnea-hypopnea index (AHI) that is at least twice as high in the supine position compared to other sleep positions. However, this condition can be misdiagnosed if a particular sleep stage-REM or non-REM (NREM)-predominates in a specific position. We explored the impact of the sleep stage on positional dependency in OSA., Methods: Polysomnographic data were retrospectively analyzed from 111 patients with OSA aged 18 years or older, all of whom had an AHI exceeding five events per hour and slept in both supine and non-supine positions for at least 5% of the total sleep time. The overall ratio of non-supine AHI to supine AHI (NS/S-AHI ratio) was compared between total, REM, and NREM sleep. Additionally, a weighted NS/S-AHI ratio, reflecting the proportion of time spent in each sleep stage, was calculated and compared to the original ratio., Results: The mean NS/S-AHI ratio was consistent between the entire sleep period and the specific sleep stages. However, the NS/S-AHI ratios for individual patients displayed poor agreement between total sleep and the specific stages. Additionally, the weighted NS/S-AHI ratio displayed poor agreement with the original NS/S-AHI ratio, primarily due to discrepancies in patients with mild to moderate OSA., Conclusion: The weighted NS/S-AHI ratio may help precisely assess positional dependency.

Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation., Competing Interests: Author Declarations 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 article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Dorsal preservation rhinoplasty (DPR) has shown promise in Western populations for nasal hump reduction, but its feasibility and long-term outcomes in Asian individuals remain unexplored. Objective: To measure the feasibility, as well as the functional and aesthetic outcomes, of DPR in Asian hump noses and to determine its effectiveness in adaptation to the unique characteristics of the Asian demographic. Methods: A retrospective review analyzed patients who underwent primary DPR between April 2019 and November 2022 with a follow-up period of over 12 months. The study included patients whose photographs met the criteria. Surgical techniques, aesthetic measurements using anthropometric factors, and subjective outcomes were evaluated. Results: Of the 17 patients (11/17, 64.7% female), the mean age was 22.53 years (standard deviation [SD] 5.22 years). The median follow-up period was 36.90 months (range 13-61 months). Measurements from pre- and postoperative photographs showed a significant reduction in both nasofacial angle (7.76°, SD 4.30°) and rhinion angle (0.85°, SD 0.69°) ( p < 0.0001). Patient-reported outcome scores with the Nasal Obstruction Symptom Evaluation scale decreased from 61.00 (SD 26.96) to 15.50 (SD 11.65), and Standardized Cosmesis and Health Nasal Outcomes Survey scores postoperatively were 10.90 (SD 7.71) overall, with the functional component at 3.50 (SD 2.64) and the aesthetic component at 7.40 (SD 6.24). No residual hump, recurrence of the hump, or complications were observed. Conclusion: In this study, the use of DPR techniques was effective and may support further development of the inclusion and exclusion criteria for its use in correcting the dorsal hump in Asian patients. Careful patient selection will be imperative to determine the ultimate indications for this technique.

Background: Linkage errors that occur according to linkage levels can adversely affect the accuracy and reliability of analysis results. This study aimed to identify the differences in results according to personally identifiable information linkage level, sample size, and analysis methods through empirical analysis., Methods: The difference between the results of linkage in directly identifiable information (DII) and indirectly identifiable information (III) linkage levels was set as III linkage based on name, date of birth, and sex and DII linkage based on resident registration number. The datasets linked at each level were named as database III (DB III ) and database DII (DB DII ), respectively. Considering the analysis results of the DII-linked dataset as the gold standard, descriptive statistics, group comparison, incidence estimation, treatment effect, and moderation effect analysis results were assessed., Results: The linkage rates for DB DII and DB III were 71.1% and 99.7%, respectively. Regarding descriptive statistics and group comparison analysis, the difference in effect in most cases was "none" to "very little." With respect to cervical cancer that had a relatively small sample size, analysis of DB III resulted in an underestimation of the incidence in the control group and an overestimation of the incidence in the treatment group (hazard ratio [HR] = 2.62 [95% confidence interval (CI): 1.63-4.23] in DB III vs. 1.80 [95% CI: 1.18-2.73] in DB DII ). Regarding prostate cancer, there was a conflicting tendency with the treatment effect being over or underestimated according to the surveillance, epidemiology, and end results summary staging (HR = 2.27 [95% CI: 1.91-2.70] in DB III vs. 1.92 [95% CI: 1.70-2.17] in DB DII for the localized stage; HR = 1.80 [95% CI: 1.37-2.36] in DB III vs. 2.05 [95% CI: 1.67-2.52] in DB DII for the regional stage)., Conclusions: To prevent distortion of the analyses results in health and medical research, it is important to check that the patient population and sample size by each factor of interest (FOI) are sufficient when different data are linked using DB DII . In cases involving a rare disease or with a small sample size for FOI, there is a high likelihood that a DII linkage is unavoidable., (© 2024. The Author(s).)

Background: Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA-N2 non-small cell lung cancer (NSCLC)., Methods: We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA-N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression., Results: A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p<0.01) were independent predictors of mortality in the multivariable analysis., Conclusion: In conclusion, the surgical outcomes following nCCRT are less favorable for individuals aged over 70 years or those undergoing pneumonectomy. Special attention is warranted for these patients due to their heightened risks of respiratory complications. In high-risk patients, such as elderly patients with decreased lung function, alternative treatment options like definitive CCRT should be considered instead of surgical resection.

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning., (© 2024. The Author(s).)

Objectives: Unlike the initial plan, some patients with oesophageal squamous cell carcinoma cannot or do not receive surgery after neoadjuvant chemoradiotherapy (nCRT). This study aimed to report the epidemiology of patients not receiving surgery after nCRT and to evaluate the potential risk of refusing surgery., Methods: We analysed patients with clinical stage T3-T4aN0M0 or T1-T4aN1-N3M0 oesophageal squamous cell carcinoma who underwent nCRT as an initial treatment intent between January 2005 and March 2020. Patients not receiving surgery were categorized using predefined criteria. To evaluate the risk of refusing surgery, a propensity-matched comparison with those who received surgery was performed. Recurrence-free (RFS) and overall survival (OS) was compared between groups, according to clinical response to nCRT., Results: Among the study population (n = 715), 105 patients (14.7%) eventually failed to reach surgery. There were three major patterns of not receiving surgery: disease progression before surgery (n = 25), functional deterioration at reassessment (n = 47), and patient's refusal without contraindications (n = 33). After propensity-score matching, the RFS curves of the surgery group and the refusal group were significantly different (P < 0.001), while OS curves were not significantly different (P = 0.069). In patients who achieved clinical complete response on re-evaluation, no significant difference in the RFS curves (P = 0.382) and in the OS curves (P = 0.290) was observed between the surgery group and the refusal group. However, among patients who showed partial response or stable disease on re-evaluation, the RFS and OS curves of the refusal group were overall significantly inferior compared to those of the surgery group (both P < 0.001). The 5-year RFS rates were 10.3% for the refusal group and 48.2% for the surgery group, and the 5-year OS rates were 8.2% for the refusal group and 46.1% for the surgery group., Conclusions: Patient's refusal remains one of the major obstacles in completing the trimodality therapy for oesophageal squamous cell carcinoma. Refusing surgery when offered may jeopardize oncological outcome, particularly in those with residual disease on re-evaluation after nCRT. These results provide significant implications for consulting patients who are reluctant to oesophagectomy after nCRT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2'-fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2'-fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARS-CoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

An 8-month-old, 3.4 kg, castrated male Toy Poodle was referred for progressive tetraparesis and respiratory disorder without a history of trauma. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) with different positions of the neck revealed concurrent atlanto-occipital dislocation (AOD) and atlantoaxial instability (AAI) with spinal cord compression. This case was unique due to its congenital nature and the absence of trauma. The surgical treatment involved precise removal of the C1 vertebra's ventral articular facet, which was compressing on the spinal cord, attributed to its fixed and malaligned position within the atlantooccipital joint. Following facetectomy, the stabilization of the occipital bone to the C2 vertebra was achieved by screws, wire, and polymethyl methacrylate. Two days after surgery, the dog recovered ambulation and showed gradual improvement in gait, despite mild residual ataxia. Postoperative CT and radiographs showed successful decompression of the spinal cord. The screw loosening was confirmed at 114 days, which was managed successfully by extracting the affected screws. Through the 21-month monitoring period, the dog showed a normal gait with a wide-based stance of the pelvic limbs when standing and experienced no pain. This case represents the first report of concurrent congenital AOD and AAI treated with a ventral surgical approach, contributing new insights to the understanding and management of such complex cranio-cervical junction disorders in veterinary neurosurgery.

Neuropathic pain (NP) results from lesions or diseases affecting the peripheral or central somatosensory system. However, there are currently no drugs that are particularly effective in treating this condition. SKI306X is a blend of purified extracts of three oriental herbs (Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris) commonly used to treat osteoarthritis for their chondroprotective effects. Chronic postischemic pain (CPIP) and spinal nerve ligation (SNL) models were created by binding the upper left ankle of mice with an O-ring for 3 h and ligating the L5 spinal nerve, respectively. Mice with allodynia were injected intraperitoneally with 0.9% normal saline (NS group) or different doses (25, 50, or 100 mg/kg) of SKI306X (SKI groups). We assessed allodynia using von Frey filaments before injection and 30, 60, 90, 120, 180, and 240 min and 24 h after injection to confirm the antiallodynic effect of SKI306X. We also measured glial fibrillary acidic protein (GFAP) levels in the spinal cord and dorsal root ganglia to confirm the change of SKI306X administration. Both models exhibited significant mechanical allodynia. The intraperitoneal injection of SKI306X significantly increased the paw withdrawal threshold in a dose-dependent manner, as the paw withdrawal threshold was significantly increased after SKI306X administration compared with at baseline or after NS administration. GFAP levels in the SKI group decreased significantly ( p < 0.05). Intraperitoneal administration of SKI306X dose-dependently attenuated mechanical allodynia and decreased GFAP levels, suggesting that GFAP is involved in the antiallodynic effect of SKI306X in mice with CPIP and SNL-induced NP.

A 2-year-old, intact female Pomeranian presented with bilateral forelimb lameness, characterized by the olecranon making contact with the ground. The patient experienced two separate incidents of falling, occurring four and three weeks before admission, respectively. Following each episode, non-weight-bearing lameness was initially observed in the left forelimb, followed by the development of crouch gait. Based on the physical examination, radiographic, and ultrasonographic findings, bilateral triceps brachii tendon disruption was diagnosed. Intraoperatively, excessive granulation tissue at the distal end of the tendon was excised. The footprint region of each triceps brachii tendon was decorticated with a high-speed burr until bleeding was observed. The triceps brachii tendon was reattached to completely cover its footprint on the olecranon using the Krackow suture technique. This method involves anchoring the suture through bone tunnels in the ulna. Trans-articular external skeletal fixation was applied to both forelimbs to immobile and stabilize the elbow joints for nine weeks. Subsequently, the dog gradually increased its walking activities while on a leash over a six-week period. At the three-year follow-up, the patient exhibited improved forelimb function and maintained a normal gait without signs of lameness. Suture-mediated anatomic footprint repair proved useful in this single case and may be an effective surgical alternative for the management of chronic triceps brachii tendon disruption in dogs.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors., (© 2024. The Author(s).)

Competing Interests: All authors declare no competing interests.

Aims: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for adjuvant immunotherapy and has been linked to poor differentiation in lung adenocarcinoma. However, its prevalence and prognostic role in the context of the novel histologic grade has not been evaluated., Methods: We analysed a cohort of 1233 patients with resected lung adenocarcinoma where PD-L1 immunohistochemistry (22C3 assay) was reflexively tested. Tumour PD-L1 expression was correlated with the new standardized International Association for the Study of Lung Cancer (IASLC) histologic grading system (G1, G2, and G3). Clinicopathologic features including patient outcome were analysed., Results: PD-L1 was positive (≥1%) in 7.0%, 23.5%, and 63.0% of G1, G2, and G3 tumours, respectively. PD-L1 positivity was significantly associated with male sex, smoking, and less sublobar resection among patients with G2 tumours, but this association was less pronounced in those with G3 tumours. PD-L1 was an independent risk factor for recurrence (adjusted hazard ratio [HR] = 3.25, 95% confidence intervals [CI] = 1.93-5.48, P < 0.001) and death (adjusted HR = 2.69, 95% CI = 1.13-6.40, P = 0.026) in the G2 group, but not in the G3 group (adjusted HR for recurrence = 0.94, 95% CI = 0.64-1.40, P = 0.778)., Conclusion: PD-L1 expression differs substantially across IASLC grades and identifies aggressive tumours within the G2 subgroup. This knowledge may be used for both prognostication and designing future studies on adjuvant immunotherapy., (© 2024 John Wiley & Sons Ltd.)

Background: This study investigated the survival outcomes for surgically treated esophageal squamous cell carcinoma (ESCC) patients based on clinically suspicious supraclavicular lymph node (SCN) metastasis (cSCN+) and pathologically confirmed SCN metastasis (pSCN+)., Methods: Using an institutional registry between 1994 and 2018, this study retrospectively analyzed 611 patients who received curative-intent esophagectomy with 3-field lymph node dissection for ESCC. The study used computed tomography and positron emission tomography to define cSCN+., Results: Among 611 patients, 24.4% had cSCN+ and 12.2% had pSCN+. The 5-year overall survival (OS) rates were 68.2% for cN0, 43.5% for cN+ without cSCN+, and 30.3% for cN+ with cSCN+ (p = 0.018). Although the univariable analysis showed that cSCN+ was associated with poorer survival than cN0 or cN+ with cSCN- (hazard ratio [HR], 1.818; p < 0.001), the multivariable analysis did not support this finding (HR, 1.281; p = 0.681). The 5-year OS rates were 64.2% for pN0, 41.5% for pN+ without pSCN+, and 25.6% for pN+ with pSCN+ (p = 0.054). Univariable analysis showed an association of pSCN+ with poor OS (HR, 1.830; p < 0.001), but the difference in the multivariable analysis was not significant (HR, 0.912; p = 0.587)., Conclusions: The presence of SCN metastasis did not have a significant impact on the OS of ESCC patients with 3-field lymph node dissection regardless of clinical suspicion or pathologic confirmation., (© 2023. Society of Surgical Oncology.)

Purpose: Fracture-related infections (FRIs) encompass a broad range of infections associated with bone fractures; they remain a significant clinical challenge. Here, we aimed to investigate the viability of focusing on soft-tissue management in patients suspected of chronic FRI, who exhibit no significant bony uptake on bone single photon emission computed tomography (SPECT)/computed tomography (CT) scans., Methods: Between January 2016 and January 2022, we managed 25 patients with chronic FRI or post-traumatic osteomyelitis using technetium 99m-methyl diphosphonate bone SPECT/CT to assess infection depth. Among them, 13 patients showing negligible bony uptake were included and categorized into two groups based on wound discharge reaching the bone/implant (Criteria 1, n = 6) or not (Criteria 2, n = 7)., Results: Patients in the Criteria 1 group were treated with antibiotics and soft tissue debridement without bony procedure. The average duration of antibiotic therapy was 6.7 weeks. Treatments were individualized, including implant changes, local flaps, skin grafts, and negative pressure wound therapy. No recurrence was reported in the mean follow-up of 21.3 months. Patients in the Criteria 2 group were treated with oral antibiotics (mean duration: 5.9 weeks) and daily wound dressings. No recurrence was reported in the mean follow-up of 26.0 months, and no surgical interventions were required., Conclusion: This study demonstrates the feasibility of focusing on soft-tissue management in patients with chronic FRI showing minimal bony uptake on bone SPECT/CT. Our treatment protocol avoided unnecessary surgical bone procedures, resulting in successful clinical outcomes with no recurrences., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: Esophageal squamous cell carcinoma (ESCC) shares common risk factors with liver cirrhosis (LC). The influence of LC in patients with ESCC has not been fully investigated. This study aimed to investigate the postoperative and long-term survival outcomes of esophagectomy for ESCC according to LC presence., Methods: Among patients who underwent curative-intent surgery for ESCC between 1994 and 2018, 121 patients with Child-Pugh class A LC and 2810 patients without LC were compared., Results: Among the LC patients, 73 (60.3%) were diagnosed with LC before surgery and 48 (39.7%) were diagnosed intraoperatively. There were no significant differences in baseline characteristics between patients with LC and those without LC. However, intraoperative blood loss was higher, and operation time, hospital stay, and ICU stay were longer in patients with LC than in those without LC. Moreover, the reoperation, 30-day morbidity (60.6 vs. 73.6%, P =0.006) and 90-day mortality (2.2 vs. 4.9%, P =0.049) were significantly higher in patients with LC. The 5-year overall survival (OS) rate was significantly higher in patients without LC than in those with LC. After adjusting the confounding variables, LC was an adverse risk factor of OS (hazard ratio 1.402, P =0.004). Among patients with LC, the Model of End-Stage Liver Disease score was related to the development of complications of grade more than III (odds ratio 1.459, P =0.013)., Conclusion: ESCC patients with Child-Pugh class A LC have high incidences of postoperative morbidity and mortality, and poor OS. Thus, careful patient selection, meticulous operation, and careful postoperative care are needed., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and - 140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This study explores olive flounder by-product Prozyme2000P (OFBP) hydrolysate as a potential treatment for age-related kidney decline. Ferroptosis, a form of cell death linked to iron overload and oxidative stress, is increasingly implicated in aging kidneys. We investigated whether OFBP could inhibit ferroptosis and improve kidney health. Using TCMK-1 cells, we found that OFBP treatment protected cells from ferroptosis induced by sodium iodate (SI). OFBP also preserved the mitochondria health and influenced molecules involved in ferroptosis regulation. In aging mice, oral administration of OFBP significantly improved kidney health markers. Microscopic examination revealed reduced thickening and scarring in the kidney's filtering units, a hallmark of aging. These findings suggest that OFBP hydrolysate may be a promising therapeutic candidate for age-related kidney decline. By inhibiting ferroptosis, OFBP treatment appears to improve both cellular and structural markers of kidney health. Further research is needed to understand how OFBP works fully and test its effectiveness in more complex models.