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Adolescence is a time when important changes occur in behavioral development, and previous studies have confirmed the relationship between excessive Internet use and decreased oral health behavior. Our purpose is to identify the indirect effects and behavioral factors of smartphone screen time on the caries symptom experience of adolescents. Using data from the 16-17th Korea youth risk behavior web based survey (2020-2021), we investigated the smartphone screen time of 109,796 students in middle school 1 st to high school 3 rd . Adolescents who used smartphones more than 6 h per week were 28% more likely to experience caries symptoms than those who used smartphones less than 2 h (odds ratio = 1.28; 95% confidence interval, 1.22-1.35). Those who consumed cariogenic drinks more than once a day were 25% more likely to experience caries symptoms, and those who brushed their teeth less than once a day were 26% more likely to experience caries symptoms (odds ratio = 1.25, 1.26; 95% confidence interval, 1.07-1.46, 1.06-1.51). Excessive smartphone screen time is associated with addictive eating habits and reduced physical activity that increase cariogenic dietary behaviors, and decrease oral health behaviors. It suggests that excessive smartphone use indirectly related to the experience of caries symptoms., (© 2024. The Author(s).)

Background/aim: Endoscopic submucosal dissection (ESD) effectively treats selected early gastric cancers (EGCs). However, the association of microsatellite instability (MSI), Epstein-Barr virus (EBV), p53, and β-catenin status with clinicopathologic parameters in EGCs treated with ESD have not been well studied., Patients and Methods: We retrospectively collected 312 consecutive EGC cases treated with ESD from January 2021 to December 2023 at Kyungpook National University Chilgok Hospital. MSI polymerase chain reaction, EBV encoded RNA in situ hybridization, and p53 and β-catenin immunostaining were performed for all cases., Results: Among 312 EGC cases, there were 42 MSI-High (MSI-H) cases (13.5%), 13 EBV-associated gastric cancer (EBVaGC) cases (4.2%), 249 intestinal type cases (79.8%), and eight poorly cohesive carcinoma cases (2.6%). MSI-H was significantly associated with lymphovascular invasion (p=0.02), local recurrence (p=0.03), and synchronous tumors (p<0.001). More than half of EBVaGC cases showed submucosal invasion (61.5%, 8/13) (p=0.016). Consequently, non-curative ESD was more frequently found in EBVaGC than in other subtypes (p<0.001). Mutant p53 patterns and nuclear translocation of β-catenin were almost exclusively found in the intestinal type (p<0.001), without association with clinicopathologic parameters. Margin involvement was frequent in poorly cohesive carcinoma (p=0.003)., Conclusion: We demonstrated that MSI-H and EBVaGC are strongly associated with clinicopathologic parameters and risk factors in EGCs treated with ESD. Molecular testing of gastric cancers should be considered before ESD for better patient management., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study investigates the changes in hippocampal proteomic profiles during demyelination and remyelination using the cuprizone model. Employing two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry for protein profiling, we observed significant alterations in the expression of ketimine reductase mu-crystallin (CRYM) and protein disulfide isomerase A3 precursor (PDIA3) following exposure to and subsequent withdrawal from cuprizone. Immunohistochemical staining validated these protein expression patterns in the hippocampus, revealing that both PDIA3 and CRYM were downregulated in the hippocampal CA1 region during demyelination and upregulated during remyelination. Additionally, we explored the potential protective effects of CRYM and PDIA3 against cuprizone-induced demyelination by synthesizing cell-permeable Tat peptide-fusion proteins (Tat-CRYM and Tat-PDIA3) to facilitate their crossing through the blood-brain barrier. Our results indicated that administering Tat-CRYM and Tat-PDIA3 mitigated the reduction in proliferating cell and differentiated neuroblast counts compared to the group receiving cuprizone alone. Notably, Tat-PDIA3 demonstrated significant effects in enhancing myelin basic protein expression alongside phosphorylation of CREB in the hippocampus, suggesting its potential therapeutic role in the prevention or treatment of demyelination, and by extension, in conditions such as multiple sclerosis., (© 2024. The Author(s).)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain, resulting in severe motor impairments. Inorganic pyrophosphatase 1 (PPA1) plays a key role in various biological processes, and this study introduces a cell-penetrating PPA1 fusion protein (TAT-PPA1) to explore its transduction into cells and brain tissues. TAT-PPA1 effectively penetrates SH-SY5Y cells and the SN region of PD animal models without toxicity, exhibiting protective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-)-induced cell death. TAT-PPA1 revealed an inhibitory influence on the MAPK signaling pathway and MPTP-induced reactive oxygen species (ROS) production. TAT-PPA1 suppresses JNK, AKT, p53, ERK, and p38 phosphorylation, showcasing its multifaceted role in cell survival pathways. In the MPTP-induced PD animal model, TAT-PPA1 prevents dopaminergic cell death and enhances motor function. This study shows that TAT-PPA1 protects against oxidative stress and cell death in neurodegenerative diseases, suggesting potential as a PD treatment., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationship., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) plays an essential role in glycolysis and in the antioxidant pathway associated with glutathione. Therefore, we investigated the effects of PFKFB3 on oxidative and ischemic damage. We synthesized a fusion protein of transactivator of transcription (Tat)-PFKFB3 to facilitate its passage into the intracellular space and examine its effects against oxidative stress induced by hydrogen peroxide (H 2 O 2 ) treatment and ischemic damage caused by occlusion of the common carotid arteries for 5 min in gerbils. The Tat-PFKFB3 protein was efficiently delivered into HT22 cells in a concentration- and time-dependent manner, with higher levels observed 18 h after treatment. Furthermore, treatment with 6 µM Tat-PFKFB3 demonstrated intracellular delivery into HT22 cells, as analyzed through immunocytochemical staining. Moreover, it significantly ameliorated the reduction of cell viability induced by 200 µM H 2 O 2 treatment. Tat-PFKFB3 treatment also alleviated H 2 O 2 -induced DNA fragmentation and reactive oxygen species formation in HT22 cells. In gerbils, the intraperitoneal administration of 2 mg/kg Tat-PFKFB3 efficiently delivered the substance to all hippocampal areas, including the hippocampal CA1 region. This administration significantly mitigated ischemia-induced hyperlocomotion, long-term memory deficits, and ischemic neuronal death in the hippocampal CA1 region after ischemia. Additionally, treatment with 2 mg/kg Tat-PFKFB3 significantly ameliorated the translocation of Cdk5 from the cytosol to the nucleus in the hippocampal CA1 region 24 h after ischemia, but not in other regions. The treatment also significantly reduced reactive oxygen species formation in the CA1 region. These findings suggest that Tat-PFKFB3 reduces neuronal damage in the hippocampal CA1 region after ischemia through the reduction of Cdk5 signaling and reactive oxygen species formation. Therefore, Tat-PFKFB3 may have potential applications in reducing ischemic damage., (© 2024. The Author(s).)

This study was conducted to allow us to understand the subjective experiences of medical students participating in rowing exercise classes at a medical school in South Korea and to derive implications for medical education. Accordingly, we analyzed their reflective journals, focusing on leadership and teamwork development. The study involved 40 second-year premedical students, and Colaizzi's analysis was employed to understand and structure their experiences. The comprehensive analysis revealed 149 meaningful statements expressing students' thoughts and experiences regarding the rowing exercise. From these statements, 13 meanings were synthesized, resulting in nine themes and four overarching categories, which provided a multilayered understanding of students' experiences. The factors that enhanced teamwork included communication, trust, respect among team members, and a sense of responsibility. By contrast, the hindering factors were competitiveness, impatience, and avoidance of responsibility. Before the class, a mix of anticipation, excitement, and dissatisfaction regarding the rowing exercise course was observed. However, after the class, students realized that the role of the entire team, rather than individual ability, is crucial, and collaboration with peers is key-the concept of shared leadership. This study is significant in that it demonstrates rowing's potential as a team sport to serve as an effective program for fostering collaboration and leadership within the medical school curriculum.

Background : The peptidyl-prolyl isomerase (PIN1) plays a vital role in cellular processes, including intracellular signaling and apoptosis. While oxidative stress is considered one of the primary mechanisms of pathogenesis in brain ischemic injury, the precise function of PIN1 in this disease remains to be elucidated. Objective : We constructed a cell-permeable PEP-1-PIN1 fusion protein and investigated PIN1's function in HT-22 hippocampal cells as well as in a brain ischemic injury gerbil model. Methods : Transduction of PEP-1-PIN1 into HT-22 cells and signaling pathways were determined by Western blot analysis. Intracellular reactive oxygen species (ROS) production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. Protective effects of PEP-1-PIN1 against ischemic injury were examined using immunohistochemistry. Results : PEP-1-PIN1, when transduced into HT-22 hippocampal cells, inhibited cell death in H 2 O 2 -treated cells and markedly reduced DNA fragmentation and ROS production. This fusion protein also reduced phosphorylation of mitogen-activated protein kinase (MAPK) and modulated expression levels of apoptosis-signaling proteins in HT-22 cells. Furthermore, PEP-1-PIN1 was distributed in gerbil hippocampus neuronal cells after passing through the blood-brain barrier (BBB) and significantly protected against neuronal cell death and also decreased activation of microglia and astrocytes in an ischemic injury gerbil model. Conclusions : These results indicate that PEP-1-PIN1 can inhibit ischemic brain injury by reducing cellular ROS levels and regulating MAPK and apoptosis-signaling pathways, suggesting that PIN1 plays a protective role in H 2 O 2 -treated HT-22 cells and ischemic injury gerbil model.

Natural and artificial endolysins exhibit bactericidal effects by destroying peptidoglycans in the cell wall of gram-positive bacteria and are usually composed of an N-terminal catalytic domain (CTD) and a C-terminal cell wall-binding domain (CBD). The structures and receptors of CBDs are variable, but bacterial Src homology 3 (SH3b) CBDs are prevalent among the natural endolysins of Staphylococcus aureus. Moreover, although recombinant endolysins with a C-terminal 6-histidine tag (His-tag) are often produced and convenient to purify, the deleterious effects of His-tags on antibacterial activity have not been evaluated thoroughly. Recently, we reported that the antibacterial activity of a commercial lysostaphin without a His-tag differed from that of cell-free lysostaphin with a C-terminal His-tag, and lysostaphin also contains a C-terminal SH3b CBD. In this study, we directly compared the effects of His-tags on the antibacterial activities of lysostaphin and several chimeric lysins possessing different SH3b CBDs. We confirmed that antibacterial activity decreased 16.0-32.0-fold after a His-tag was added to the SH3b CBD.

Liver cancer is the second leading cause of cancer-related deaths worldwide, motivating major scientific efforts to understand and treat this cancer type. Over 30% of patients with liver cancer progress to metastasis, which reduces the survival rate. Extensive studies on primary tumors have been conducted to improve the prognosis. However, there is a lack of appropriate and accessible models for studying the progression and metastasis of liver cancer. Moreover, conventional metastasis models do not reproduce metastasis as it occurs in patients. To address this lack of an appropriate model for the monitoring of cancer progression and evaluation of anticancer drugs, we established a spontaneous metastatic xenograft model using NSG mice subcutaneously transplanted with SK-Hep-1 cells. Compared to the conventional experimental metastasis model (intravenous transplantation), in which only lung metastasis was observed, the established spontaneous metastatic xenograft model was superior, as it showed both a primary tumor and metastatic patterns similar to those observed in human patients. Additionally, this model was successfully used to assess the antimetastatic efficacy of sorafenib. In conclusion, our results demonstrate that the established spontaneous metastatic xenograft model better reflects liver cancer metastasis and can be utilized to assess the efficacy of anticancer drugs for liver cancer., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is a form of hepatic steatosis in which more than 5% of the liver's weight is fat, primarily due to the overconsumption of soft drinks and a Western diet. In this study, we investigate the potential of plant-derived exosome-like nanovesicles (PENs) to prevent liver fibrosis and leaky gut resulting from NAFLD. Specifically, we examine whether hemp sprout-derived exosome-like nanovesicles (HSNVs) grown on smart farms could exert protective effects against NAFLD by inhibiting liver fibrosis. HSNVs ranging from 100-200 nm were measured using nanoparticle tracking analysis (NTA). HSNVs (1 mg kg -1 ) were orally administered for 5 weeks to mice with NAFLD induced by feeding them a Western diet (WD; a fat- and cholesterol-rich diet) and fat-, fructose-, and cholesterol-rich (FFC) diet for 8 weeks. Importantly, the administration of HSNVs markedly reduced oxidative stress and fibrosis marker proteins in NAFLD mouse models and LX2 cells. Furthermore, treatment with HSNVs prevented a significant decrease in the quantity of gut barrier proteins and endotoxin levels in NAFLD mouse models. For the first time, these results demonstrate that HSNVs can exhibit a hepatoprotective effect against gut leakiness and WD/FFC-induced liver fibrosis by inhibiting oxidative stress and reducing fibrosis marker proteins.

Background/Objectives: Alu element insertion in the exon 4 of the RP1 gene was newly identified through whole genome sequencing (WGS). This was not detected in previous next-generation sequencing (NGS) analysis. We report three cases of Korean retinitis pigmentosa (RP) patients with compound heterozygous variants including Alu element insertion in the RP1 gene, indicating that Alu element insertion could be a cause of RP; Methods: Among patients diagnosed with RP having variants in the RP1 gene in the Asan Medical Center, WGS was additionally performed for genetically unsolved cases in previous NGS analysis to detect any presence of Alu element insertion. For cases detected to have Alu element insertion in the exon 4 of the RP1 gene, genetic and clinical characteristics were analyzed; Results : Among 16 patients with RP, 3 patients were detected to have Alu element insertion in the RP1 gene. Alu element insertion in the RP1 gene was also detected using WGS. It was revealed to be a pathogenic variant. Therefore, RP1 gene mutation was the confirmed genetic cause of RP for these three cases and genetic counseling was enabled for them; Conclusions : Alu element insertion in the RP1 gene could be a genetic cause of autosomal recessive RP patients with compound heterozygous variants. Through WGS, the identification of this pathogenic variant was possible. Confirmation is needed to check the presence of Alu element insertion in patients with compound heterozygous variants in the RP1 gene.

Purpose: Clear cell renal cell carcinoma (ccRCC) often harbors Polybromo 1 (PBRM1) alterations. These alterations are associated with immune checkpoint blockade response in ccRCC, particularly antiprogrammed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1)-targeted therapy. However, the association between PBRM1 alterations and PD-L1 expression in ccRCC remains unclear., Materials and Methods: We analyzed alterations in PBRM1 and PD-L1 expression using immunohistochemistry (IHC) targeting PBRM1 and PD-L1 (22C3) in tissues collected from patients with localized ccRCC (Cohort 1) and advanced ccRCC (Cohort 2). Additionally, next-generation sequencing (NGS) was conducted on Cohort 2 patients to analyze PBRM1 alterations., Results: Cohort 1 comprised 526 patients, of whom 139 (26.4%) exhibited PD-L1 positivity and 205 (38.9%) exhibited loss of PBRM1 expression in IHC. PD-L1 expression was positively associated with the loss of PBRM1 expression (P < 0.001) in localized ccRCC. Kaplan-Meier analysis indicated that PBRM1 expression loss and PD-L1 expression positively correlated with tumor recurrence (P < 0.001 and P = 0.003, respectively). Cohort 2 comprised 59 patients with advanced ccRCC, of whom 33 (56.9%) exhibited PBRM1 genetic alterations. PBRM1 IHC exhibited a sensitivity of 84.48% and specificity of 87.5% compared to NGS results. We did not find a significant association between PBRM1 mutation and PD-L1 expression, in contrast to the findings in Cohort 1. However, we frequently observed that PBRM1 mutation and PD-L1 expression occur concurrently, with 60% of PBRM1-altered ccRCC cases being PD-L1 positive., Conclusion: Although our study did not establish a correlation between PBRM1 mutations and PD-L1 expression, it demonstrated that the occurrence of PBRM1-altered ccRCC with PD-L1 expression is not uncommon. Therefore, the presence of PBRM1 alterations may challenge the use of PD-L1 IHC as a predictive marker for PD-L1 blockade in ccRCC., 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.)

We have previously identified Ertredin (3-(2-amino-5-bromophenyl) quinoxalin-2(1H)-one) as a compound that suppresses 3D spheroid formation and tumorigenesis in NIH3T3 cells induced by Epidermal Growth Factor Receptor variant III ( EGFRvIII ) transduction. One of its targets has been shown to be NDUFA12 (NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex Subunit 12), a component protein of oxidative phosphorylation complex I. In this report, we compared the growth inhibitory activity of Ertredin with its methylated analogue 7MeERT (3-(2-amino-5-bromophenyl)-7-methylquinoxalin-2(1H)-one) on human cancer cells. 7MeERT induced the inhibition of the proliferation of various cancer cells similarly to Ertredin and showed higher activity in glioblastoma cells, A431 cells overexpressing EGFR (wild type), and multiple myeloma cells. Molecular docking analysis and a Cellular Thermal Shift Assay (CETSA) suggested that 7MeERT binds to NDUFA12 similarly to Ertredin. The binding of 7MeERT and Ertredin to NDUFA12 in glioblastoma was further supported by the inhibition of the oxygen consumption rate. These results suggest that 7MeERT also binds to NDUFA12, inhibits oxidative phosphorylation, and has a higher anti-cancer cell growth inhibitory activity than Ertredin.

It has been our observation that unicoronal synostosis and deformational plagiocephaly (DP) are not mutually exclusive. The incidence and phenotypical manifestations of a patient presenting with both conditions have not been studied previously. The authors performed a retrospective review of patients presenting with unicoronal synostosis, examining their 3DCT scans for the presence of DP and assessing their endocranial and orbital morphology. The authors found that 38.4% of patients with unicoronal synostosis also have DP. Ipsilateral DP is less common than contralateral DP, but these patients tend to have a delayed presentation due to a reduction in forehead asymmetry corresponding to the parallelogram deformity. Regardless, DP has no impact on the endocranial nor orbital morphology in unicoronal synostosis., Competing Interests: The authors report noconflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD., (© 2024. The Author(s).)

Actionable mutations of RET kinase have been identified as oncogenic drivers of solid tumors, including thyroid cancer, metastatic colorectal cancer, and nonsmall cell lung cancer. Although multikinase inhibitors and RET selective inhibitors are used to treat patients with RET alterations, there is insufficient research addressing certain issues: which actionable mutations arise from these therapies, how to improve the clinical response rate to RET inhibitors, and how to design new inhibitors to overcome drug resistance. Therefore, the development of sophisticated tool compounds is required to investigate the molecular mechanisms of actionable mutations and to develop breakthrough therapeutics for different RET alterations. Herein, we present our investigation into the side chains of imidazopyridazine hinge binders that are capable of inducing protein-ligand interaction patterns from the gatekeeper to the waterfront regions. Extending the substituents at the second and sixth positions enhanced the IC 50 up to < 0.5 nM for diverse RET alterations., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Purpose: We evaluated the feasibility, safety, and learning curve of extraperitoneal single-port robot-assisted radical prostatectomy (SP-RARP) and introduced innovative surgical techniques to maintain the instrument positions during the procedures., Materials and Methods: A cohort of 100 patients underwent extraperitoneal SP-RARP at our institution from December 2021 to April 2023. The procedures were performed by an experienced urology surgeon utilizing two surgical techniques for dissecting the posterior aspect of the prostate-"changing instrument roles" and "using camera inversion"-to prevent positional shifts between the camera and instruments., Results: The mean operation time for SP-RARP was 93.58 minutes, and the mean console time was 65.16 minutes. The mean estimated blood loss during the procedures was 109.30 mL. No cases necessitated conversion to multi-port robot, laparoscopy, or open surgery, and there were no major complications during the hospital stay or in the short-term follow-up. Early outcomes of post-radical prostatectomy indicated a biochemical recurrence rate of 4.0% over a mean follow-up duration of 6.40 months, with continence and potency recovery rates of 92.3% and 55.8%, respectively. Analysis of the learning curve showed no significant differences in operation time, console time, and positive surgical margin rates between the initial and latter 50 cases., Conclusions: Extraperitoneal SP-RARP is a feasible and safe option for the treatment of localized prostate cancer in skilled hands. Continued accrual of cases is essential for future comparisons of SP-RARP with multiport approaches., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

While mechanical thrombectomy is known to be effective for distal medium vessel occlusion (DMVO) as well as large vessel occlusion, tortuous DMVO are predisposed to vessel injury during stent retriever thrombectomy. Furthermore, getting access to the thrombus may be difficult during suction thrombectomy using a dedicated suction catheter. Most studies describe DMVO treatment using stent retrievers and dedicated suction catheters, but there are limited studies reporting DMVO treated with suction thrombectomy using a microcatheter. Herein, we describe three cases of DMVO treated with suction thrombectomy that was performed using a microcatheter and subsequently showed good results. Therefore, suction thrombectomy using a microcatheter is a viable alternative treatment for tortuous DMVO.

Background: Contrast-enhanced T1-weighted magnetic resonance cholangiography (CE-T1-MRC) after gadoxetate disodium administration can be used for preoperative evaluation of the bile ducts in live liver donors. This study aimed to determine whether CE-T1-MRC with 3-hour delayed imaging improves bile duct visualization both qualitatively and quantitatively compared with 20-minute delayed imaging in potential living liver donors., Methods: We retrospectively identified 33 potential living liver donors (mean age, 30.1 years; 18 men and 15 women) who underwent preoperative CE-T1-MRC with both 20-minute delayed and 3-hour delayed imaging in a single session. The radiologist scored biliary visualization for right and left hepatic ducts (RHD and LHD), their secondary confluences and segmental bile ducts, common hepatic duct (CHD), and cystic duct (CD), and measured relative contrast ratio (rC) and relative signal intensity (rS) for RHD, LHD, and CHD. The data were analyzed using Wilcoxon's signed-rank test and paired t-test., Results: In qualitative analysis, duct visualization scores for RHD and LHD, their secondary confluences and segmental bile ducts, CHD, and CD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P ≤ .046). In quantitative analysis, both rC and rS of RHD, LHD, and CHD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P < .001)., Conclusions: CE-T1-MRC with 3-hour delay imaging improves bile duct visualization both qualitatively and quantitatively in potential living liver donors., Competing Interests: Declaration of competing interest Sunyoung Lee reports honoraria from Bracco and Bayer. The remaining authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Bisphenol A (BPA), a widespread environmental contaminant, poses concerns due to its disruptive effects on physiological functions of the uterine endometrium. In contrast, melatonin (MT) and Resveratrol (RSV) are under scrutiny for their potential protective roles against BPA-induced damage. For the efficacy and ethical concerns in the animal test, endometrial organoids, three-dimensional models mimicking endometrium, serve as crucial tools for unraveling the impact of environmental factors on reproductive health. This study aimed to comprehensively characterize the morphological, molecular and metabolic responses of porcine endometrial organoids to BPA and assess the potential protective effects of MT and RSV. Porcine uteri were prepared, digested with collagenase, mixed with Matrigel, and incubated at 38°C with 5 % CO 2 . Passaging involved dissociation through trypsin-EDTA treatment and subculturing. The culture medium was refreshed every 2-3 days. To investigate the environmental impact on reproductive health, endometrial organoids were treated with BPA (0.5 µM), MT (with/without BPA at 0.1 µM), and/or RSV (10 µM). Various molecular screening using gene expression, western blotting, immunofluorescence staining, and metabolites profiling were assessed the effects of BPA, MT, and RSV in terms of cell viability, morphology, reproductivity, and metabolism alteration in the endometrial organoids. As expected, BPA induced structural and molecular disruptions in organoids, affecting cytoskeletal proteins, Wnt/β-catenin signaling, and epithelial/mesenchymal markers. It triggered oxidative stress and apoptotic pathways, altered miRNA expression, and disrupted the endocannabinoid system. The level of glucose, galactose, and essential amino acids were increased or decreased by approximately 1.5-3 times in BPA-treated groups compared to the control groups (p-value < 0.05), indicating metabolic changes. Moreover, MT and RSV treated groups exhibited protective effects, mitigating BPA-induced disruptions across multiple pathways. For the first time, our study models endometrial organoids, advancing understanding of environmental impacts on reproductive health., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aim: Silibinin, has been investigated for its potential benefits and mechanisms in addressing vanadium pentoxide (V2O5)-induced pulmonary inflammation. This study explored the anti-inflammatory activity of silibinin and elucidate the mechanisms by which it operates in a mouse model of vanadium-induced lung injury., Materials and Methods: Eight-week-old male BALB/c mice were exposed to V2O5 to induce lung injury. Mice were pretreated with silibinin at doses of 50 mg/kg and 100 mg/kg. Histological analyses were performed to assess cell viability and infiltration of inflammatory cells. The expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and activation of the MAPK and NF-[Formula: see text]B signaling pathways, as well as the NLRP3 inflammasome, were evaluated using real-time PCR, western blot analysis, and immunohistochemistry. Whole blood analysis was conducted to measure white blood cell counts., Results: Silibinin treatment significantly improved cell viability, reduced inflammatory cell infiltration, and decreased the expression of pro-inflammatory cytokines in V2O5-induced lung injury. It also notably suppressed the activation of the MAPK and NF-[Formula: see text]B signaling pathways, along with a marked reduction in NLRP3 inflammasome expression levels in lung tissues. Additionally, silibinin-treated groups exhibited a significant decrease in white blood cell counts, including neutrophils, lymphocytes, and eosinophils., Conclusion: These findings underscore the potent anti-inflammatory effects of silibinin in mice with V2O5-induced lung inflammation, highlighting its therapeutic potential. The study not only confirms the efficacy of silibinin in mitigating inflammatory responses but also provides a foundational understanding of its role in modulating key inflammatory pathways, paving the way for future therapeutic strategies against pulmonary inflammation induced by environmental pollutants., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic is a serious global threat with surging new variants of concern. Although global vaccinations have slowed the pandemic, their longevity is still unknown. Therefore, new orally administrable antiviral agents are highly demanded. Among various repurposed drugs, niclosamide (NIC) is the most potential one for various viral diseases such as COVID-19, SARS (severe acute respiratory syndrome), MERS (middle east respiratory syndrome), influenza, RSV (respiratory syncytial virus), etc. Since NIC cannot be effectively absorbed, a required plasma concentration for antiviral potency is hard to maintain, thereby restricting its entry into the infected cells. Such a 60-year-old bioavailability challenging issue has been overcome by engineering with MgO and hydroxypropyl methylcellulose (HPMC), forming hydrophilic NIC-MgO-HPMC, with improved intestinal permeability without altering NIC metabolism as confirmed by parallel artificial membrane permeability assay. The inhibitory effect on SARS-CoV-2  replication is confirmed in the Syrian hamster model to reduce lung injury. Clinical studies reveal that the bioavailability of NIC hybrid drug can go 4 times higher than the intact NIC. The phase II clinical trial shows a dose-dependent bioavailability of NIC from hybrid drug  suggesting its potential applicability as a game changer in achieving the much-anticipated endemic phase., (© 2023 Wiley‐VCH GmbH.)

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

This study investigated the potential of phosphodiesterase type 5 (PDE-5) inhibitors, specifically tadalafil, in preventing the delayed cerebral ischemia (DCI) post-rupture of cerebral aneurysms. A total of 19 rabbits were used in this study, divided into different treatment groups, including nimodipine alone, tadalafil alone, and a combination of nimodipine and tadalafil. Both nimodipine and tadalafil showed some impact on reducing endothelial apoptosis in the basilar arteries, although the effects were not statistically significant. Notably, the nimodipine group exhibited significantly lower levels of Bax in the small arterioles compared to the SAH group. These findings suggest that while tadalafil may not directly prevent endothelial cell death like nimodipine, its neuroprotective properties hint at its potential utility in DCI treatment. Further research involving a broader range of apoptosis-related proteins is recommended to enhance our understanding in this area.

The primary purpose of high-intensity focused ultrasound (HIFU), a non-invasive medical therapy, is to precisely target and ablate tumors by focusing high-frequency ultrasound from an external power source. A series of ablations must be performed in order to treat a big volume of tumors, as a single ablation can only remove a small amount of tissue. To maximize therapeutic efficacy while minimizing adverse side effects such as skin burns, preoperative treatment planning is essential in determining the focal site and sonication duration for each ablation. Here, we introduce a machine learning-based approach for designing HIFU treatment plans, which makes use of a map of the material characteristics unique to a patient alongside an accurate thermal simulation. A numerical model was employed to solve the governing equations of HIFU process and to simulate the HIFU absorption mechanism, including ensuing heat transfer process and the temperature rise during the sonication period. To validate the accuracy of this numerical model, a series of tests was conducted using ex vivo bovine liver. The findings indicate that the developed models properly represent the considerable variances observed in tumor geometrical shapes and proficiently generate well-defined closed treated regions based on imaging data. The proposed strategy facilitated the formulation of high-quality treatment plans, with an average tissue over- or under-treatment rate of less than 0.06%. The efficacy of the numerical model in accurately predicting the heating process of HIFU, when combined with machine learning techniques, was validated through quantitative comparison with experimental data. The proposed approach in cooperation with HIFU simulation holds the potential to enhance presurgical HIFU plan., (© 2024. The Author(s).)

Soft sensors based on deep learning regression models are promising approaches to predict real-time fermentation process quality measurements. However, experimental datasets are generally sparse and may contain outliers or corrupted data. This leads to insufficient model prediction performance. Therefore, datasets with a fully distributed solution space are required that enable effective exploration during model training. In this study, the robustness and predictive capability of the underlying model of a soft sensor was improved by generating synthetic datasets for training. The monitoring of intensified ethanol fermentation is used as a case study. Variational autoencoders were employed to create synthetic datasets, which were then combined with original datasets (experimental) to train neural network regression models. These models were tested on original versus augmented datasets to assess prediction improvements. Using the augmented datasets, the soft sensor predictive capability improved by 34%, and variability was reduced by 82%, based on R 2 scores. The proposed method offers significant time and cost savings for dataset generation for the deep learning modeling of ethanol fermentation and can be easily adapted to other fermentation processes. This work contributes to the advancement of soft sensor technology, providing practical solutions for enhancing reliability and robustness in large-scale production.

Purpose: To report a case of bilateral retinal vasculitis in a patient with non-small cell lung cancer undergoing treatment with osimertinib., Case Report: A 58-year-old woman with lung adenocarcinoma (T4N3M1a stage IV) presented with blurry vision in both eyes (OU). Eighteen months before symptom onset, the treatment was changed from afatinib (20 mg/day) to osimertinib (80 mg/day) because of tumor progression. The visual acuity was 20/30 and 20/25 in the right and left eyes, respectively. Clinical examination revealed few anterior chamber cells, 2+ vitreous cells, haze, and multiple retinal hemorrhages in the peripheral retinas (OU). Fluorescein angiography revealed retinal vasculitis with a severely non-perfused area in the periphery. These findings indicated hemorrhagic occlusive retinal vasculitis (HORV). Osimertinib was reduced to 40 mg/day, and oral prednisolone was started at 30 mg/day. This improved retinal vasculitis; however, the ischemic area did not improve. Pan-retinal photocoagulation was performed while tapering the oral prednisolone to 10 mg/day. Although macular edema (ME) occasionally occurred (OU), systemic and local treatment with steroid-stabilized HORV and ME helped increase the dose of osimertinib to 80 mg/day without cancer progression for 18 months. Her visual acuity remained 10/20 (OU)., Conclusion: Osimertinib, a third-generation tyrosine kinase inhibitor, can be used to treat advanced non-small cell lung cancer with epidermal growth factor receptor mutation-induced bilateral HORV. This adverse effect can be managed with systemic and local steroid treatment and continued osimertinib administration.

Background: Cancer is a leading cause of death worldwide, posing a significant threat to human health and life expectancy. Numerous existing studies explored the correlation between coal-fired power plants and cancer development. Currently, Chungcheongnam-do Province hosts 29 coal-fired power plants, constituting half of the total 58 plants across South Korea., Methods: This study assessed the cancer incidence by proximity to coal-fired power plants in Chungcheongnam-do Province, Korea. In this study, the exposed group comprised individuals residing within a 2-km radius of the coal-fired power plants, whereas the control group comprised individuals who had no prior residency within the 2-km radius of such plants or elsewhere in the province. Standardized incidence ratios were calculated using the cancer incidence cases retrieved from the National Health Insurance System data from 2007 to 2017., Results: The study found that exposed men had a 1.11 (95% confidence interval [CI], 1.09-1.21) times higher risk of developing all cancer types and a 1.15 (95% CI, 1.09-1.22) times higher risk of developing cancers excluding thyroid cancer compared with control men. Exposed women had a 1.05 (95% CI, 1.00-1.14) times higher risk of developing all cancer types and a 1.06 (95% CI, 0.98-1.13) times higher risk of developing cancers excluding thyroid cancer than did control women. The colorectal, liver, prostate, and bladder cancer incidence rates were significantly higher in exposed men than that in all control groups. The incidence of esophageal, stomach, liver, and lung cancers were significantly higher in exposed women compared with all control groups., Conclusion: The residents near coal-fired power plants had a higher risk of developing cancer than did those living in other areas. In the future, long-term follow-up investigations in residents living in the vicinity of power plants are warranted., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: In rabbits, renal abscesses (pus-filled sores) are rare and diagnosis remains challenging. Therefore, in this study, we aimed to determine the clinical manifestation and diagnostic tests associated with renal abscess identification in rabbits., Case Description: A four-and-a-half-year-old castrated male Lionhead rabbit with a history of poor appetite and abdominal distension was admitted to the animal hospital. Blood analysis, radiography, ultrasonography, and computed tomography scans revealed a kidney abscess found within the renal parenchyma, with severe loss of the cortex and medulla, extending toward the capsule. Consequently, the rabbit underwent nephrectomy. The enlarged right kidney was surgically removed. Histopathological examination of the affected kidney showed severe necrosis and ischemic zones, atrophy of the renal tubules, and prominent heterophils with mixed inflammatory cell infiltrates. Immunohistochemistry and polymerase chain reaction confirmed Encephalitozoon cuniculi and Escherichia coli infections, respectively., Conclusion: This report provides novel insights into the diagnosis of renal abscesses in Lionhead rabbits., Competing Interests: All authors declare no potential conflicts of interest.

The development of cost-effective and high-performance oxygen evolution reaction (OER) catalysts is a significant challenge. This study presents the synthesis of binder-free NiFe@NiFe layered double hydroxide (NNF) via one-pot electrodeposition on carbon paper and Ni foam at high current densities. The presence of Ni sulfate residues on the prepared NNF is also investigated. The findings indicate that Ni sulfate significantly improves OER performance and durability. The sulfate content can be controlled by varying the method and duration of washing. NNF prepared through dipping (NNF-D) exhibits outstanding OER activity with a low overpotential of 241 mV, which is 25 mV lower than that of NNF washed for 60 s (NNF-W-60 s) at 10 mA cm -2 in 1 m KOH. Furthermore, density functional theory analyses indicate that the Ni sulfate residue helps modify the electronic structure, thereby optimizing the binding strength of *OOH. This synthetic strategy is expected to inspire the development of next-generation catalysts utilizing various adsorbates., (© 2024 Wiley‐VCH GmbH.)

Recent studies have shown that novel antibody-drug conjugates (ADCs) can improve clinical outcomes in patients with HER2-low breast cancers. This study aimed to investigate alteration of HER2 status during breast cancer progression with an emphasis on HER2-low status. Using 386 paired samples of primary and recurrent breast cancers, HER2 discordance rate between primary and matched recurrent samples, the relationships between HER2 discordance and clinicopathological characteristics and clinical outcomes of the patients were analyzed. HER2 discordance rate between primary breast cancer and first recurrence was 25.9% (κ = 0.586) with mostly zero-to-low (10.6%) or low-to-zero (9.3%) conversion. There was no significant difference in the discordant rates according to type or location of the recurrence. Of 70 cases with a second recurrence, HER2 discordance rate between the primary tumor and the second recurrence was 27.1% (κ = 0.554). HER2 discordance was associated with lower HER2 level, lymphovascular invasion, and progesterone receptor positivity of the primary tumor. In further analyses, HER2-zero-to-low conversion was associated with lymph node metastasis and hormone receptor (HR) positivity, whereas HER2-low-to-zero conversion was associated with HR negativity and triple-negative subtype. In survival analyses, HER2 discordance was associated with decreased overall survival of patients in the HR-positive group but not in the HR-negative group. Furthermore, patients with HER2-low-to-zero converted tumors showed worse overall survival compared with those with HER2-low concordant tumors. In conclusion, HER2 status changes during breast cancer progression in significant proportions, mostly between zero and low status. As HER2 instability increases during progression and affects clinical outcome, HER2 status needs to be reevaluated in recurrent settings., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1-deficient mice are resistant to metastasis and further protected by combined immune-checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF-β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK-target cell responses, which is dysregulated and hijacked by tumors during metastatic progression., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To evaluate the feasibility and durability of coil embolization for MCAB aneurysms by analyzing clinical and radiological results., Methods: From January of 2008 to June of 2018, we treated a total of 1785 aneurysms using coil embolization. The aneurysms were treated by both coiling and stent-assisted coiling. Among these cases, 223 MCAB aneurysms were analyzed retrospectively. Clinical and radiological assessments were conducted at admission, after treatment, at discharge, and at last clinical follow-up., Results: Coil embolization was performed on 223 MCAB aneurysms in 217 patients. Peri-procedural ischemic, hemorrhagic, and other complications within 30 days after coil embolization occurred at rates of 8.0 %, 8.0 %, and 2.0 %, respectively, in the ruptured group and at 2.9 %, 1.2 %, and 0 %, respectively, in the unruptured group. The overall morbidity and mortality rates associated with complications were 2.3 % and 2.0 %. The cumulative major recurrence rates were 5.1 % at 12 months, 7.1 % at 18 months, and 11.9 % at three years after coil embolization. The mean follow-up period was 33.27 ± 25.48 months. Independent risk factors for major recurrence after coil embolization for MCAB aneurysms were a ruptured aneurysm, initial incomplete occlusion, the aneurysm size, and the neck size., Conclusion: Coil embolization is a good alternative treatment option for MCAB aneurysms compared to surgical clipping. Considering the risk factors for major recurrence, the follow-up angiography should continue up to three years after coil embolization., 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.)

Dried Blood Spots (DBS) revolutionize therapeutic drug monitoring using LC-MS for the precise quantification of cardiovascular drugs (CDs), enabling personalized treatment adapted to patient-specific pharmacokinetics with minimal invasiveness. This study aims to achieve simultaneous quantification of eight CDs in DBS, overcoming physicochemical challenges. A two-step protein precipitation method was used for simple and precise sample preparation. The drugs were analyzed using LC-MS/MS in ESI positive-ion mode, showing high sensitivity and linearity, with a correlation coefficient (r 2 ) exceeding 0.999, after being separated on a reversed-phase chromatography by gradient elution of DW-acetonitrile containing 0.1 % formic acid + 2 mM ammonium formate. The validation results indicate good selectivity, with no observed matrix effect and carry-over. The intra- and inter-day accuracy and precision were within 6 % for most drugs, except for digoxin and deslanoside at low therapeutic levels where the variation was within 20 %. Stability tests confirmed suitable DBS handling and storage conditions, indicating drug stability for at least 30 days at room temperature. The analysis of whole spot has demonstrated remarkable precision and reliability in all target drugs. The analysis of 3 mm internal diameter discs, punched in and out of DBS, presumed to contain 3 µL of blood, showed acceptable accuracy for most drugs, with less polar drugs like digoxin and deslanoside showing lower accuracy, indicating a need for further correction due to non-uniform drug distribution. Consequently, the developed LC-MS/MS method enables the quantification of multiple CDs in a single DBS analysis, while suggesting the potential for accuracy-based analysis., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Plants of the Asteraceae family have been cultivated worldwide for economic, medicinal, and ornamental purposes, including genera such as Aster , Helianthus , and Cosmos . Numerous studies examined their secondary metabolites; however, those of Aster × chusanensis , which is a natural hybrid species in South Korea, are unclear, and optimized propagation methods should be identified. We analyzed phenolic acid concentrations in each part of Aster × chusanensis through HPLC. Further, we investigated the growth characteristics and secondary metabolite concentrations under various growth temperatures using division propagation, followed by growing at 20, 25, and 30 °C in a growth chamber. Chlorogenic acid was the primary compound, which was particularly high in the leaves. The growth characteristics did not differ significantly between temperatures, and 30 °C was most efficient for phenolic acid biosynthesis. Our results provide valuable information on optimized propagation and secondary metabolite concentrations under different temperatures of Aster × chusanensis .

Bacterial vaginosis (BV) is defined as dysbiosis of the vaginal microbiome associated with the depletion of Lactobacilli and excessive growth of commensal or pathogenic bacteria. This study investigated the effects of lactic acid bacteria (LAB) mixture (LM; InoRexyne™) on the vaginal bacterial community of Gardnerella vaginalis ( G. vaginalis )-infected BV mice. Single LAB and LM exhibited antibacterial and anti-inflammatory effects by inhibiting G. vaginalis growth and pro-inflammatory markers in RAW 264.7 cells. Administering LM did not significantly alter the vaginal architecture or fecal short-chain fatty acids but did significantly inhibit the vaginal interleukin-6 levels in the high LM group compared to the GV group. LM administration decreased the relative abundances of Enterobacter, Escherichia coli , and Bacteroides vulgatus in vaginal flushing fluids compared to the GV group. LM partially alleviated BV by inhibiting G. vaginalis growth and modulating the vaginal bacterial community, providing new insights into its modulatory effects on the vaginal microbiome in BV., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01641-w., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Korean Society of Food Science and Technology 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: While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy., Methods: Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders., Results: Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort., Discussion: Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Szadai, Bartha, Parada, Lakatos, Pál, Lengyel, de Almeida, Jánosi, Nogueira, Szeitz, Doma, Woldmar, Guedes, Ujfaludi, Pahi, Pankotai, Kim, Győrffy, Baldetorp, Welinder, Szasz, Betancourt, Gil, Appelqvist, Kwon, Kárpáti, Kuras, Murillo, Németh, Malm, Fenyö, Pawłowski, Horvatovich, Wieslander, Kemény, Domont, Marko-Varga and Sanchez.)

To assess the diagnostic utility of bone turnover markers (BTMs) and demographic variables for identifying individuals with osteoporosis. A cross-sectional study involving 280 participants was conducted. Serum BTM values were obtained from 88 patients with osteoporosis and 192 controls without osteoporosis. Six machine learning models, including extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), CatBoost, random forest, support vector machine, and k-nearest neighbors, were employed to evaluate osteoporosis diagnosis. The performance measures included the area under the receiver operating characteristic curve (AUROC), F1-score, and accuracy. After AUROC optimization, LGBM exhibited the highest AUROC of 0.706. Post F1-score optimization, LGBM's F1-score was improved from 0.50 to 0.65. Combining the top three optimized models (LGBM, XGBoost, and CatBoost) resulted in an AUROC of 0.706, an F1-score of 0.65, and an accuracy of 0.73. BTMs, along with age and sex, were found to contribute significantly to osteoporosis diagnosis. This study demonstrates the potential of machine learning models utilizing BTMs and demographic variables for diagnosing preexisting osteoporosis. The findings highlight the clinical relevance of accessible clinical data in osteoporosis assessment, providing a promising tool for early diagnosis and management., 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.

Ferroelectric field-effect transistors (FeFETs) are increasingly important for in-memory computing and monolithic 3D (M3D) integration in system-on-chip (SoC) applications. However, the high-temperature processing required by most ferroelectric memories can lead to thermal damage to the underlying device layers, which poses significant physical limitations for 3D integration processes. To solve this problem, the study proposes using a nanosecond pulsed laser for selective annealing of hafnia-based FeFETs, enabling precise control of heat penetration depth within thin films. Sufficient thermal energy is delivered to the IGZO oxide channel and HZO ferroelectric gate oxide without causing thermal damage to the bottom layer, which has a low transition temperature (<250 °C). Using optimized laser conditions, a fast response time (<1 µs) and excellent stability (cycle > 10 6 , retention > 10 6 s) are achieved in the ferroelectric HZO film. The resulting FeFET exhibited a wide memory window (>1.7 V) with a high on/off ratio (>10 5 ). In addition, moderate ferroelectric properties (2·P r of 14.7 µC cm -2 ) and pattern recognition rate-based linearity (potentiation: 1.13, depression: 1.6) are obtained. These results demonstrate compatibility in HZO FeFETs by specific laser annealing control and thin-film layer design for various structures (3D integrated, flexible) with neuromorphic applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIP Cre ) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIP Cre mice, despite being TXNIP deficient, TXNIP Cre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M pro ) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro , there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC 50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

Background: Cervical epidural block (CEB) is an effective intervention for managing cervical radicular pain. This study aimed to investigate the current status of performing CEB in South Korea., Methods: Pain physicians affiliated with the Korean Pain Society were asked to complete anonymous questionnaires regarding CEB between September and October 2022. The questionnaire consisted of 24 questions assessing the current status and methods of CEB in detail., Results: Of the 198 surveys collected, 171 physicians (86.4%) reported performing CEB. Among those, the majority (94.7%) used fluoroscopy during the procedure. The paramedian interlaminar (IL) approach was the most preferred method (50.3%). Respondents performing fluoroscopic-guided IL CEB were categorized into two groups based on clinical experience: those with ≤10 years of experience (≤10-year group, n = 91) and those with >10 years of experience (>10-year group, n = 71). The proportion of physicians obtaining informed consent in the ≤10-year group and >10-year group was 50.5% and 56.3%, respectively. When entering the epidural space during IL CEB, the contralateral oblique view was the second most frequently used in both groups (≤10-year group, 42.9%; >10-year group, 29.6%). In targeting the upper cervical lesions (C3-4), the proportion of respondents who used an IL space higher than C6-7 was 17.6% in the ≤10-year group and 29.5% in the >10-year experience group., Conclusions: This study demonstrated variability in the CEB technique used by pain physicians in South Korea. The findings highlight the need for education on informed consent and techniques to enhance safety.

In this study, scalp tissues from Korean adults between 20 and 80 without skin disease were used. Scalp tissues were processed, and hair follicles were isolated and cultured with different treatments (including Bioscalp, Ultra Exo Booster, and Ultra S Line Plus) from Ultra V company. Over 12 days, observations and measurements of hair follicle characteristics were recorded at intervals (Days 0, 3, 6, 9, and 12). The study assessed the impact of these substances on hair follicle growth and morphology. Bioscalp, combined with Ultra Exo Booster and Ultra S Line Plus, showed significant hair elongation in ex vivo. Preservation of hair bulb diameter was observed, indicating potential for sustained hair growth by exosome-based products. The hair growth cycle analysis suggested a lower transition to the catagen stage in test products from Ultra V compared to non-treated groups. The research findings indicated that the tested formulations, especially the combination of Bioscalp, Ultra Exo Booster, and Ultra S Line Plus, demonstrated significant effectiveness in promoting hair growth, maintaining the integrity of the hair bulb, and reducing the transition to the catagen stage. The study suggests promising alternative treatments for hair loss, illustrating results that were as good as those of the conventional testing product groups., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Morning glory disc anomaly is a rare congenital anomaly affecting the optic disc and is frequently associated with retinal detachment. This report presents a unique case of a 10-year-old boy with morning glory disc anomaly and serous retinal detachment, treated with oral acetazolamide. Remarkably, half of the retina exhibiting bullous detachment was reattached leading to full recovery of vision within a few days after starting acetazol-amide treatment. There was no recurrence after discontinuation of medication. Oral acetazolamide can be considered an alternative treatment option for retinal detachment associated with morning glory disc anomaly of non-rhegmatogenous origin. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:415-417.] .

Background: The aim of this study is to investigate the perioperative composite textbook outcomes of pancreatic surgery after minimally invasive pancreatoduodenectomy (MIPD)., Materials and Methods: The cohort study was conducted across 10 institutions and included 1552 patients who underwent MIPD registered with the Korean Study Group on Minimally Invasive Pancreatic Surgery between May 2007 and April 2020. We analyzed perioperative textbook outcomes of pancreatic surgery after MIPD. Subgroup analyses were performed to assess outcomes based on the hospital volume of MIPD., Results: Among all patients, 21.8% underwent robotic pancreatoduodenectomy. High-volume centers (performing >20 MIPD/year) performed 88.1% of the procedures. The incidence of clinically relevant postoperative pancreatic fistula was 11.5%. Severe complications (Clavien-Dindo grade ≥IIIa) occurred in 15.1% of the cases. The 90-day mortality rate was 0.8%. The mean hospital stay was 13.7 days. Textbook outcomes of pancreatic surgery success were achieved in 60.4% of patients, with higher rates observed in high-volume centers than in low-volume centers (62.2% vs. 44.7%, P <0.001). High-volume centers exhibited significantly lower conversion rates (5.4% vs. 12.5%, P =0.001), lower 90-day mortality (0.5% vs. 2.7%, P =0.001), and lower 90-day readmission rates (4.5% vs. 9.6%, P =0.006) than those low-volume centers., Conclusion: MIPD could be performed safely with permissible perioperative outcomes, including textbook outcomes of pancreatic surgery, particularly in experienced centers. The findings of this study provided valuable insights for guiding surgical treatment decisions in periampullary disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Human epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody-drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status., Methods: This retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed., Results: The overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion., Conclusions: Incorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity., (© 2024. The Author(s).)

High- k polymeric layers were prepared by combining various functional groups and were applied as gate dielectrics for practical organic field-effect transistors (OFETs). Crosslinking of the polymeric layers through UV-assisted organic azide fluorine-based crosslinkers induced dramatic improvements in the electrical performance of the OFET, such as field-effect mobility and bias-stress stability. Our synthesis and manufacturing method can be a useful technique for ensuring device operation stability and electrical property enhancement. With this analysis, we further applied our polymer-dielectric OFETs to flexible-platform-based electronic components, including unit OFETs and simple logic devices (NOT, NAND, and NOR gates). The outcomes of this research and development suggest a suitable method for the low-cost mass production of large-area flexible and printable devices, using a printing-based approach to replace current processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)