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Mi-Hong Min,1,2 Jin-Hyong Park,2 Jong-Hyun Hur,2 Ho-Chul Shin,2 YoungJoo Cho,2 Dae-Duk Kim11College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea; 2Central Research Institute, Whanin Pharmaceutical Company, Suwon 16229, Republic of KoreaPurpose: The aim of this study was to develop a tablet formulation of choline alfoscerate and to assess its bioequivalence by comparing its pharmacokinetic parameters with those of a commercially available soft gelatin capsule (Gliatilin®) in healthy Korean male volunteers.Materials and methods: Film-coated tablet formulation was optimized to control the hygroscopicity of choline alfoscerate. Bioequivalence study was performed under fasted condition with a randomized, single-dose, two-period crossover design. Subjects were orally treated with 1,200 mg of test or reference choline alfoscerate (400 mg × three doses) formulation. Blood samples were collected up to 12 hours the day before dosing to correct the baseline level of choline and 12 hours after dosing to obtain drug absorption profile. Pharmacokinetic parameters were determined after analyzing plasma concentration of choline by using LC–MS/MS.Results: Hygroscopicity of choline alfoscerate was successfully controlled by adding suitable amount of Neusilin® (magnesium aluminometasilicate) in the film-coated tablet. Stability of the tablet formulation was also confirmed under the accelerated condition for 3 months. Bioequivalence study showed that the mean area under the plasma concentration–time curve from time 0 to infinity of test tablet and reference soft capsule was 3.428±2.170 and 3.305±1.803 µg·h/mL, respectively; the mean Cmax was 0.365±0.158 and 0.380±0.108 µg/mL, respectively; and the mean Tmax was 3.51±2.57 and 3.85±3.19 hours, respectively. The 90% CIs for geometric mean ratios of test to reference formulation for AUC0–t and Cmax were 84.51%–111.98% and 83.31%–104.10%, respectively, and satisfied the EMA regulatory criteria for bioequivalence.Conclusion: Pharmacokinetic parameters including the Cmax and AUC0–t determined after oral administration of the two formulations in healthy Korean male volunteers showed that the differences between the formulations (tablet vs soft capsule) were not significant for bioequivalence. Both formulations were well tolerated, with no serious adverse events reported.Keywords: choline alfoscerate, bioequivalence study, tablet, healthy Korean male volunteers

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity

As the substance abuse service system shifts from primarily residential to primarily nonresidential settings, it becomes important to understand how substance abuse treatment processes and outcomes may vary across service setting. Research increasingly indicates that, along with specific treatment and service strategies, client-provider relationship is an important ingredient in effective substance abuse treatment. This study uses a moderator-mediator analysis of a comprehensive service model to examine how the relation between client-provider relationship and substance abuse treatment outcomes may differ in residential and nonresidential settings. The study used data collected for the National Treatment Improvement Evaluation Study, a prospective, cohort-based study of U.S. substance abuse treatment programs and their clients, with an analytic sample of 59 publicly funded service delivery units and 3,027 clients. Structural equation modeling is used to assess the structural relations and causal connections between treatment process and treatment outcome variables. Results indicate that for nonresidential settings, a better client-provider relationship is directly related to improved outcomes of treatment duration and reduced posttreatment substance use and is indirectly related to both outcomes through provision of services matched to client needs. In residential settings, the quality of the client-provider relationship is unrelated to process or outcome variables. The findings point to the importance of the client-provider relationship in all settings but particularly in outpatient settings where there are limited physical constraints on the treatment process. [ABSTRACT FROM AUTHOR]

Background: Improved life functioning along with substance use reduction is increasingly recognized as the definition of effective addiction treatment.Objectives: To assess whether targeted health and social services contribute to improved physical/mental health and employment.Methods: This study used data from the National Treatment Improvement Evaluation Study (N = 3027) and modeled the improvement in physical/mental health and employment at discharge or 12 months after discharge compared with intake measures as a function of receipts of matched services.Results: Receiving matched medical service improves physical health only at treatment discharge; receiving matched mental health services improves mental health at discharge and 12 months after discharge; receiving matched vocational services improves employment only 12 months after discharge.Conclusions: Need-service matching contributes to improved health and social outcomes when longitudinal assessments of treatment outcomes are used to evaluate treatment effectiveness.Scientific Significance: Study findings document the value of targeted services for achieving success in health and social functioning in comprehensive substance abuse treatment. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study of radiographic outcomes in patients undergoing single level cervical arthroplasty with the Bryan cervical disc (Medtronic Sofamor Danek, Memphis, TN). Objective: This study was designed to determine whether modification of disc insertion angle and insertion depth are effective in preventing segmental or whole cervical kyphosis after arthroplasty. Summary Of Background Data: Preservation of segmental motion and aggravation of kyphosis are known challenges after arthroplasty. However, there are currently no proven preventative factors for kyphosis. Change in disc insertion angle was only reported effective for avoiding endplate kyphosis. Additionally, it was difficult to predict the effect of insertion angle on overall sagittal alignment. There have been no studies regarding the correlation between insertion depth and sagittal alignment. Methods: A total of 41 patients with single-level arthroplasty were evaluated. Radiologic assessment using neutral cervical radiographs at the long-term was performed. Linear regression analysis between insertion angle, insertion depth, postoperative sagittal alignment, functional spinal unit angle, and shell angle were performed. Results: Disc insertion angle and insertion depth demonstrated significant negative correlation with the postoperative shell angle. Lordotic insertion angle and an anteriorly located disc led to lordosis in the shell angle. Overall sagittal alignment showed a tendency to correlate with insertion angle. By the result of effect of insertion angle ranging from 3.5 degrees to 7.5 degrees on the sagittal alignment and shell angle, we can hypothesize paradoxical biomechanical stress on the other segments. Conclusion: Arthroplasty using the Bryan disc provided a favorable clinical and radiologic outcome thus far; however, we should not underestimate emergent adverse outcomes. To prevent postoperative sagittal imbalance after cervical arthroplasty, intentional modification in disc insertion angle and depth would be helpful. Unexpected compensatory biomechanical loads should be elucidated in future studies. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Technical note. OBJECTIVE.: To describe the use of intraoperative indocyanine green (ICG) video-angiography for obliteration of a spinal dural arteriovenous fistula (DAVF) and to show a video clip. SUMMARY OF BACKGROUND DATA.: ICG video-angiography is an emerging tool for delineating intraoperative vascular anatomy, and it has a significant potential in the treatment of vascular diseases in the spine. METHODS.: The authors presented a case of a 73-year-old man with progressive and debilitating bilateral lower extremity weakness. The patient was diagnosed with a spinal DAVF of 10th thoracic spine based on the results of conventional spinal angiography. RESULTS.: The patient underwent T9-10 laminotomy for microsurgical clip occlusion. Intraoperative ICG video-angiography was used before clip placement to identify the arterialized veins of the fistula and after clip placement to confirm obliteration of the fistulous connection and restoration of normal blood flow. CONCLUSION.: Intraoperative ICG video-angiography serves an important role in the microsurgical treatment of DAVF. It is simple and provides real-time information about the precise location of spinal DAVF and result after obliteration of spinal DAVF. [ABSTRACT FROM AUTHOR]

Background: Kidney biopsy is the standard of care for the diagnosis of various kidney diseases. In particular, chronic histopathologic lesions, such as interstitial fibrosis and tubular atrophy, can provide prognostic information regarding chronic kidney disease progression. In this study, we aimed to evaluate historadiological correlations between CT-based radiomic features and chronic histologic changes in native kidney biopsies and to construct and validate a radiomics-based prediction model for chronicity grade., Methods: We included patients aged ≥ 18 years who underwent kidney biopsy and abdominal CT scan within a week before kidney biopsy. Left kidneys were three-dimensionally segmented using a deep learning model based on the 3D Swin UNEt Transformers architecture. We additionally defined isovolumic cortical regions of interest near the lower pole of the left kidneys. Shape, first-order, and high-order texture features were extracted after resampling and kernel normalization. Correlations and diagnostic metrics between extracted features and chronic histologic lesions were examined. A machine learning-based radiomic prediction model for moderate chronicity was developed and compared according to the segmented regions of interest (ROI)., Results: Overall, moderate correlations with statistical significance (P < 0.05) were found between chronic histopathologic grade and top-ranked radiomic features. Total parenchymal features were more strongly correlated than cortical ROI features, and texture features were more highly ranked. However, conventional imaging markers, including kidney length, were poorly correlated. Top-ranked individual radiomic features had areas under receiver operating characteristic curves (AUCs) of 0.65 to 0.74. Developed radiomics models for moderate-to-severe chronicity achieved AUCs of 0.89 (95% confidence interval [CI] 0.75-0.99) and 0.74 (95% CI 0.52-0.93) for total parenchymal and cortical ROI features, respectively., Conclusion: Significant historadiological correlations were identified between CT-based radiomic features and chronic histologic changes in native kidney biopsies. Our findings underscore the potential of CT-based radiomic features and their prediction model for the non-invasive assessment of kidney fibrosis., (© 2024. The Author(s).)

A useful theoretical lens that has emerged for understanding urban resilience is the four basic types of interdependencies in critical infrastructures: the physical, geographic, cyber, and logical types. This paper is motivated by a conceptual and methodological limitation-although logical interdependencies (where two infrastructures affect the state of each other via human decisions) are regarded as one of the basic types of interdependencies, the question of how to apply the notion and how to quantify logical relations remains under-explored. To overcome this limitation, this study focuses on institutions (rules), for example, rules and planned tasks guiding human interactions with one another and infrastructure. Such rule-mediated interactions, when linguistically expressed, have a syntactic form that can be translated into a network form. We provide a foundation to delineate these two forms to detect logical interdependence. Specifically, we propose an approach to quantify logical interdependence based on the idea that (1) there are certain network motifs indicating logical relations, (2) such network motifs can be discerned from the network form of rules, and that (3) the higher the frequency of these motifs between two infrastructures, the greater the extent of logical interdependency. We develop a set of such motifs and illustrate their usage using an example. We conclude by suggesting a revision to the original definition of logical interdependence. This rule-focused approach is relevant to understanding human error in risk analysis of socio-technical systems, as human error can be seen as deviations from constraints that lead to accidents., (© 2024 The Author(s). Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Veterinary drugs play a crucial role in the treatment of various animal diseases. However, their residues, stemming from issues, such as withdrawal period lapses, overuse, or abuse, can jeopardize food safety and human health. This study addresses recent regulations in Korea concerning specific veterinary drugs (anacolin, ephedrine, menichlopholan, piperonyl butoxide, and etisazole HCl) and their ongoing discussions. This study aimed to validate two pre-developed methods for quantifying residues in livestock and fishery products using QuEChERS and liquid chromatography-tandem mass spectrometry. Both methods exhibited excellent linearity, recoveries (70.3-119%), and coefficient of variations (1.3-28%), along with low limits of detection and quantification (0.3-4 ng/g and 1-12 ng/g). This study is significant for its contribution to the detection of veterinary drugs in livestock and fishery products, given the limited research available on the methods for analyzing these substances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Protein tyrosine phosphatase non-receptor type 21 (PTPN21) is a cytosolic protein tyrosine phosphatase that regulates cell growth and invasion. Due to its oncogenic properties, PTPN21 has recently emerged as a potential therapeutic target for cancer. In this study, the three-dimensional structure of the PTPN21 FERM domain was determined at 2.1 Å resolution by X-ray crystallography. The crystal structure showed that this domain harbors canonical FERM folding and consists of three subdomains that are tightly packed via highly conserved intramolecular hydrophobic interactions. Consistent with this, the PTPN21 FERM domain shares high structural homology with several other FERM domains. Moreover, structural superimposition demonstrated two putative protein-binding sites of the PTPN21 FERM domain, which are presumed to be associated with interaction with its binding partner, kinesin family member 1C. Thus, these data suggest that the FERM domain of PTPN21 serves as a module that mediates protein-protein interaction, like other FERM domains.

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).)

We report herein the potential of colony-stimulating factor-1 receptor (CSF1R) inhibitors as therapeutic agents in neuroinflammatory diseases, with a focus on Alzheimer's disease (AD). Employing a carefully modified scaffold, N -(4-heterocycloalkyl-2-cycloalkylphenyl)-5-methylisoxazole-3-carboxamide, we identify highly selective and potent CSF1R inhibitors─ 7dr i and 7ds i . Molecular docking studies shed light on the binding modes of these key compounds within the CSF1R binding site. Remarkably, kinome-wide selectivity assessment underscores the impressive specificity of 7dr i for CSF-1R. Notably, 7dr i emerges as a potent CSF-1R inhibitor with favorable cellular activity and minimal cytotoxicity among the synthesized compounds. Demonstrating efficacy in inhibiting CSF1R phosphorylation in microglial cells and successfully mitigating neuroinflammation in an in vivo LPS-induced model, 7dr i establishes itself as a promising antineuroinflammatory agent.

Background and objectives Laboratory tests conducted on survey respondents' biological specimens are a major component of the National Health and Nutrition Examination Survey. The National Center for Health Statistics' Division of Health and Nutrition Examination Surveys performs internal analytic method validation studies whenever laboratories undergo instrumental or methodological changes, or when contract laboratories change. These studies assess agreement between methods to evaluate how methodological changes could affect data inference or compromise consistency of measurements across survey cycles. When systematic differences between methods are observed, adjustment equations are released with the data documentation for analysts planning to combine survey cycles or conduct a trend analysis. Adjustment equations help ensure that observed differences from methodological changes are not misinterpreted as population changes. This report assesses the reliability of statistical methods used by the Division of Health and Nutrition Examination Surveys when conducting method validation studies to address concerns that adjustment equations are being overproduced (recommended too frequently). Methods Public-use 2017-2018 National Health and Nutrition Examination Survey laboratory data were used to simulate "new" measurements for 120 analytic method validation studies. Blinded studies were analyzed to determine the final adjustment recommendation for each study using difference plots, descriptive statistics, t-tests, and Deming regressions. Final recommendations were compared with simulated difference types to assess how often spurious results were observed. Concordance estimates (concordance, misclassification, sensitivity, specificity, and positive and negative predictive values) informed assessments. Results Adjustment equations were appropriately recommended for 75.0% of the studies, over-recommended for 5.8%, under-recommended for 15.8%, and recommended with an inappropriate technique for 3.3%. Across simulated difference types, sensitivity ranged from 65.9% to 84.4% and specificity from 74.7% to 97.5%. Conclusions Findings from this report suggest that the current methodology used by the Division of Health and Nutrition Examination Surveys performs moderately well. Based on these data and analyses, underadjustment was more prevalent than overadjustment, suggesting that the current methodology is conservative., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Purpose: Breast cancer is known to be influenced by genetic and environmental factors, and several susceptibility genes have been discovered. Still, the majority of genetic contributors remain unknown. We aimed to analyze the plasma proteome of breast cancer patients in comparison to healthy individuals to identify differences in protein expression profiles and discover novel biomarkers., Methods: This pilot study was conducted using bioresources from Seoul National University Bundang Hospital's Human Bioresource Center. Serum samples from 10 breast cancer patients and 10 healthy controls were obtained. Liquid chromatography-mass spectrometry analysis was performed to identify differentially expressed proteins., Results: We identified 891 proteins; 805 were expressed in the breast cancer group and 882 in the control group. Gene set enrichment and differential expression analysis identified 30 upregulated and 100 downregulated proteins in breast cancer. Among these, 10 proteins were selected as potential biomarkers. Three proteins were upregulated in breast cancer patients, including cluster of differentiation 44, eukaryotic translation initiation factor 2-α kinase 3, and fibronectin 1. Seven proteins downregulated in breast cancer patients were also selected: glyceraldehyde-3-phosphate dehydrogenase, α-enolase, heat shock protein member 8, integrin-linked kinase, tissue inhibitor of metalloproteinases-1, vasodilator-stimulated phosphoprotein, and 14-3-3 protein gamma. All proteins had been previously reported to be related to tumor development and progression., Conclusion: The findings suggest that plasma proteome profiling can reveal potential diagnostic biomarkers for breast cancer and may contribute to early detection and personalized treatment strategies. A further validation study with a larger sample cohort of breast cancer patients is planned., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

A carbonized interlayer effectively helps to improve the electrochemical performance of lithium-sulfur (Li-S) batteries. In this study, a simple and inexpensive carbon intermediate layer was fabricated using a traditional Korean paper called "hanji". This carbon interlayer has a fibrous porous structure, with a specific surface area of 91.82 m 2 g -1 and a BJH adsorption average pore diameter of 26.63 nm. The prepared carbon interlayer was utilized as an intermediary layer in Li-S batteries to decrease the charge-transfer resistance and capture dissolved lithium polysulfides. The porous fiber-shaped carbon interlayer suppressed the migration of polysulfides produced during the electrochemical process. The carbon interlayer facilitates the adsorption of soluble lithium polysulfides, allowing for their re-utilization in subsequent cycles. Additionally, the carbon interlayer significantly reduces the polarization of the cell. This simple strategy results in a significant improvement in cycle performance. Consequently, the discharge capacity at 0.5 C after 150 cycles was confirmed to have improved by more than twofold, reaching 230 mAh g -1 for cells without the interlayer and 583 mAh g -1 for cells with the interlayer. This study demonstrates a simple method for improving the capacity of Li-S batteries by integrating a functional carbon interlayer.

Native biodiversity and ecosystems of Antarctica safeguarded from biological invasion face recent threats from non-native species, accelerated by increasing human activities and climate changes. Over two decades ago, the winter crane fly, Trichocera maculipennis, was first detected on King George Island. It has now successfully colonized several research stations across King George Island. To understand the origin, genetic diversity, and population structure of this Holarctic species, we conducted mitochondrial DNA cytochrome c oxidase subunit I (COI) sequence analysis across both its native and invasive ranges. In parallel, we performed microsatellite loci analysis within the invasive ranges, utilizing 12 polymorphic microsatellite markers. Furthermore, we compared body sizes among adult males and females collected from three different locations of King George Island. Our COI sequence analysis exhibited two different lineages present on King George Island. Lineage I was linked to Arctic Svalbard and Polish cave populations and Lineage II was related to Canadian Terra Nova National Park populations, implying multiple origins. Microsatellite analysis further exhibited high levels of genetic diversity and significant levels of genetic differentiation among invasive populations. Body sizes of adult T. maculipennis were significantly different among invasive populations but were not attributed to genetics. This significant genetic diversity likely facilitated the rapid colonization and establishment of T. maculipennis on King George Island, contributing to their successful invasion. Molecular analysis results revealed a substantial amount of genetic variation within invasive populations, which can serve as management units for invasive species control. Furthermore, the genetic markers we developed in the study will be invaluable tools for tracking impending invasion events and the travel routes of new individuals. Taken together, these findings illustrate the highly invasive and adaptable characteristics of T. maculipennis. Therefore, immediate action is necessary to mitigate their ongoing invasion and facilitate their eradication., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies., Methods: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years., Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients., Trial Registration: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022., Competing Interests: Jiwon Koh reported receiving consultation fees from DCGen. Co., Ltd., outside the submitted work. Hee-Chul Shin, Wonshik Han, and Han-Byoel Lee reported being member of the board of directors of and holding stock and ownership interests at DCGen, Co, Ltd., outside the submitted work. Han-Byoel Lee reported receiving grants in the form of Mammotome® Elite needles from Devicor Medical Products, Inc. for this work. The grant source had no part in the design and preparation of the protocol. No other disclosures were reported., (© 2024 Korean Breast Cancer Society.)

Objective: Automated breast ultrasound (ABUS) is a relevant imaging technique for early breast cancer diagnosis and is increasingly being used as a supplementary tool for mammography. This study compared the performance of ABUS and handheld ultrasound (HHUS) in detecting and characterizing the axillary lymph nodes (LNs) in patients with breast cancer., Materials and Methods: We retrospectively reviewed the medical records of women with recently diagnosed early breast cancer (≤ T2) who underwent both ABUS and HHUS examinations for axilla (September 2017-May 2018). ABUS and HHUS findings were compared using pathological outcomes as reference standards. Diagnostic performance in predicting any axillary LN metastasis and heavy nodal-burden metastases (i.e., ≥ 3 LNs) was evaluated. The ABUS-HHUS agreement for visibility and US findings was calculated., Results: The study included 377 women (53.1 ± 11.1 years). Among 385 breast cancers in 377 patients, 101 had axillary LN metastases and 30 had heavy nodal burden metastases. ABUS identified benign-looking or suspicious axillary LNs (average, 1.4 ± 0.8) in 246 axillae (63.9%, 246/385). According to the per-breast analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of ABUS in predicting axillary LN metastases were 43.6% (44/101), 95.1% (270/284), 75.9% (44/58), 82.6% (270/327), and 81.6% (314/385), respectively. The corresponding results for HHUS were 41.6% (42/101), 95.1% (270/284), 75.0% (42/56), 82.1% (270/329), and 81.0% (312/385), respectively, which were not significantly different from those of ABUS ( P ≥ 0.53). The performance results for heavy nodal-burden metastases were 70.0% (21/30), 89.6% (318/355), 36.2% (21/58), 97.3% (318/327), and 88.1% (339/385), respectively, for ABUS and 66.7% (20/30), 89.9% (319/355), 35.7% (20/56), 97.0% (319/329), and 88.1% (339/385), respectively, for HHUS, also not showing significant difference ( P ≥ 0.57). The ABUS-HHUS agreement was 95.9% (236/246; Cohen's kappa = 0.883)., Conclusion: Although ABUS showed limited sensitivity in diagnosing axillary LN metastasis in early breast cancer, it was still useful as the performance was comparable to that of HHUS., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Background: Mammalian target of rapamycin (mTOR) is known to regulate self-renewal ability and potency of embryonic stem cells (ESCs) and adult stem cells in opposite manners. However, its effects vary even among adult stem cells and are not reported in fetal stem/progenitor cells. This study investigated the role of mTOR in the function of human fetal cartilage-derived progenitor cells (hFCPCs)., Methods: mTOR activity in hFCPCs was first examined via the level of phosphor-mTOR until passage 19, together with doubling time of cells and senescence-associated b-galactosidase (SA-bGal). Then, the effect of 100 nM rapamycin, the inhibitor of mTOR, was investigated on self-renewal ability, proliferation rate and osteogenic/adipogenic potential of hFCPCs in vitro. Expression of stemness genes (Oct-4, Sox2 and Nanog) and cell cycle regulators (CDK4 and Cyclin D1) was measured at mRNA or protein levels., Results: mTOR activity was maintained constantly at high levels in hFCPCs until passage 19, while their proliferation rate was decreasing from 48 h at passage 13 to 70 h at passage 9 and senescent cells were observed at passage 18 (8.3 ± 1.2%) and 19 (15.6 ± 1.9%). Inhibition of mTOR in hFCPCs impaired their colony forming frequency (CFU-F) by 4 folds, while showing no change in their doubling time and expression of CDK4 and Cyclin D1. Upon mTOR inhibition, Oct4 expression decreased by 2 folds and 4 folds at the mRNA and protein levels, respectively, while that of Sox2 and Nanog did not change significantly. Finally, mTOR inhibition reduced osteogenic and adipogenic differentiation of hFCPCs in vitro., Conclusion: This study has shown that mTOR plays an important role in the self-renewal ability of hFCPCS but not in their proliferation, The effect of mTOR appears to be associated with Oct-4 expression and important in the osteogenic and adipogenic differentiation ability of hFCPCs., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

The activation or inactivation of B-cell lymphoma-2 (Bcl-2) antagonist/killer (Bak) is critical for controlling mitochondrial outer membrane permeabilization-dependent apoptosis. Its pro-apoptotic activity is controlled by intermolecular interactions with the Bcl-2 homology 3 (BH3) domain, which is accommodated in the hydrophobic pocket of Bak. Bcl-2-interacting protein 5 (Bnip5) is a noncanonical BH3 domain-containing protein that interacts with Bak. Bnip5 is characterized by its controversial effects on the regulation of the pro-apoptotic activity of Bak. In the present study, we determined the crystal structure of Bak bound to Bnip5 BH3. The intermolecular association appeared to be typical at first glance, but we found that it is maintained by tight hydrophobic interactions together with hydrogen/ionic bonds, which accounts for their high binding affinity with a dissociation constant of 775 nM. Structural analysis of the complex showed that Bnip5 interacts with Bak in a manner similar to that of the Bak-activating pro-apoptotic factor peroxisomal testis-enriched protein 1, particularly in the destabilization of the intramolecular electrostatic network of Bak. Our structure is considered to reflect the initial point of drastic and consecutive conformational and stoichiometric changes in Bak induced by Bnip5 BH3, which helps in explaining the effects of Bnip5 in regulating Bak-mediated apoptosis., (© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

A low soybean self-sufficiency rate in South Korea has caused a high import dependence and considerable price variation between domestic and foreign soybeans, causing the false labeling of foreign soybeans as domestic. Conventional soybean origin discrimination methods prevent a single-grain analysis and rely on the presence or absence of several compounds or concentration differences. This limits the origin discrimination of mixed samples, demonstrating the need for a method that analyzes individual grains. Therefore, we developed a method for origin discrimination using genetic analysis. The whole-genome sequencing data of the Williams 82 reference cultivar and 15 soybean varieties cultivated in South Korea were analyzed to identify the dense variation blocks (dVBs) with a high single-nucleotide polymorphism density. The PCR primers were prepared and validated for the insertion-deletion (InDel) sequences of the dVBs to discriminate each soybean variety. Our method effectively discriminated domestic and foreign soybean varieties, eliminating their false labeling.

The N-end rule pathway is a proteolytic system involving the destabilization of N-terminal amino acids, known as N-degrons, which are recognized by N-recognins. Dysregulation of the N-end rule pathway results in the accumulation of undesired proteins, causing various diseases. The E3 ligases of the UBR subfamily recognize and degrade N-degrons through the ubiquitin-proteasome system. Herein, we investigated UBR4, which has a distinct mechanism for recognizing type-2 N-degrons. Structural analysis revealed that the UBR box of UBR4 differs from other UBR boxes in the N-degron binding sites. It recognizes type-2 N-terminal amino acids containing an aromatic ring and type-1 N-terminal arginine through two phenylalanines on its hydrophobic surface. We also characterized the binding mechanism for the second ligand residue. This is the report on the structural basis underlying the recognition of type-2 N-degrons by the UBR box with implications for understanding the N-end rule pathway., (© 2023. The Author(s).)

Background: The division of the Korean peninsula involved many neighbouring countries in the Korean War. The relations with those countries have since been reorganised due to active exchange. This study examined how the quantity and quality of contact with traditional alliance (US and Japan) and strategic partner (China and Russia) countries affected their national images., Methods: To this end, this study analyzed the relation with the national image by measuring the quantity and quality of contact of an individual with each country. The quantity of contact included an evaluation of the individual's subjective amount of contact, contact path, and contact status, and the quality of contact was measured as an evaluation for the pleasure, competitiveness, intimacy, spontaneity, and necessity when contacting each country's culture. A total of 387 participants were divided into two groups based on the presence of direct contact and the quantity and quality of their contact and national images were examined. The participants were followed by a completion of the self-questionnaires including the Culture Experience Questionnaire, National Image Questionnaire, and demographic information questionnaire., Results: The results of this study are as follow: first, regardless of the type of country, the national image was highly correlated with the degree of subjective contact evaluated by individuals, but there was a weak tendency with contact quality. Second, there was no significant interaction between the country type and contact status for national image, however, different national images for each country were detected. In other word, for contact quantity, contact groups showed more positive national images compared to non-contact groups in Russia, but not Japan, China, and the US. For contact quality, the positive contact experience group showed more positive national images compared to the negative contact experience group, but only in traditional alliance countries., Conclusion: This study highlights the importance of implementing different strategies for countries to maintain peaceful international relations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Wharton's jelly-derived mesenchymal stem cell (WJ-MSC)-derived exosomes contain a diverse cargo and exhibit remarkable biological activity, rendering them suitable for regenerative and immune-modulating functions. However, the quantity of secretion is insufficient. A large body of prior work has investigated the use of various growth factors to enhance MSC-derived exosome production. In this study, we evaluated the utilization of thermostable basic fibroblast growth factor (TS-bFGF) with MSC culture and exosome production. MSCs cultured with TS-bFGF displayed superior proliferation, as evidenced by cell cycle analysis, compared with wild-type bFGF (WT-bFGF). Stemness was assessed through mRNA expression level and colony-forming unit (CFU) assays. Furthermore, nanoparticle tracking analysis (NTA) measurements revealed that MSCs cultured with TS-bFGF produced a greater quantity of exosomes, particularly under three-dimensional culture conditions. These produced exosomes demonstrated substantial anti-inflammatory and wound-healing effects, as confirmed by nitric oxide (NO) assays and scratch assays. Taken together, we demonstrate that utilization of TS-bFGF for WJ-MSC-derived exosome production not only increases exosome yield but also enhances the potential for various applications in inflammation regulation and wound healing.

Protein glycosylation is a common post-translational modification on extracellular proteins. The conformational dynamics of several glycoproteins have been characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS). However, it is, in most cases, not possible to extract information about glycan conformation and dynamics due to the general difficulty of separating the deuterium content of the glycan from that of the peptide (in particular, for O-linked glycans). Here, we investigate whether the fragmentation of protonated glycopeptides by collision-induced dissociation (CID) can be used to determine the solution-specific deuterium content of the glycan. Central to this concept is that glycopeptides can undergo a facile loss of glycans upon CID, thereby allowing for the determination of their masses. However, an essential prerequisite is that hydrogen and deuterium (H/D) scrambling can be kept in check. Therefore, we have measured the degree of scrambling upon glycosidic bond cleavage in glycopeptides that differ in the conformational flexibility of their backbone and glycosylation pattern. Our results show that complete scrambling precedes the glycosidic bond cleavage in normal glycopeptides derived from a glycoprotein; i.e., all labile hydrogens have undergone positional randomization prior to loss of the glycan. In contrast, the glycosidic bond cleavage occurs without any scrambling in the glycopeptide antibiotic vancomycin, reflecting that the glycan cannot interact with the peptide moiety due to a conformationally restricted backbone as revealed by molecular dynamics simulations. Scrambling is also inhibited, albeit to a lesser degree, in the conformationally restricted glycopeptides ristocetin and its pseudoaglycone, demonstrating that scrambling depends on an intricate interplay between the flexibility and proximity of the glycan and the peptide backbone.

A sensitive and accurate analytical method was developed and validated to detect bambermycin, a commonly used antibiotic in animal feed and livestock. The presence of bambermycin residues in food products can pose health risks to consumers, emphasizing the need for a sensitive and accurate analytical method. A reversed-phase analytical column was utilized with a mobile phase comprising 0.005 mol/L ammonium acetate in 5% acetonitrile (A) and 0.005 mol/L ammonium acetate in 95% acetonitrile (B) to achieve effective chromatographic separation. Quantitative determination of bambermycin in various samples, including beef, pork, chicken, milk, eggs, flatfish, eel, and shrimp, was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry. Sample extraction involved a mixture of methanol and a 25% ammonium hydroxide solution, followed by low-temperature purification and phospholipid removal utilizing a Phree cartridge. The method exhibited a satisfactory recovery rate ranging from 69% to 100%. Validation results demonstrated the reliability, robustness, and accuracy of the method, exhibiting good linearity, precision, and recovery. This validated method can be applied for routine analysis of bambermycin residues, assisting in the development of effective monitoring and control measures to ensure the safety of livestock and aquatic products., (© 2023 Wiley-VCH GmbH.)

(1) Background: Breast core needle biopsy (CNB) is preferred over fine needle aspiration (FNA) as it has higher sensitivity and specificity and enables immunohistochemical evaluation. However, breast FNA remains widely used because of its low cost, minimally invasive nature, and quick results. Studies analyzing the effects of each test on the prognoses of patients with breast cancer are scarce and controversial, and the criteria for test selection remain unknown. (2) Methods: This study included adult female patients who underwent breast cancer surgery at 102 general hospitals. The trend of breast biopsies over time was analyzed, and the prognoses of patients with breast cancer who underwent CNB and FNA were compared. (3) Results: This study included 73,644 patients who underwent FNA ( n = 8027) and CNB ( n = 65,617). A multivariate Cox regression analysis showed that patients diagnosed using FNA had significantly worse overall survival (OS) and breast-cancer-specific survival (BCSS) than those diagnosed using CNB. In the subgroup analysis, patients with breast imaging reporting and data system (BI-RADS) 5 lesions, palpable tumors, or centrally located tumors had significantly worse OS and BCSS with FNA than with CNB. (4) Conclusions: CNB should be performed preferentially instead of FNA in patients with BI-RADS 5 lesions and nonpalpable or centrally located tumors.

Background: This study aimed to discuss several surgical approaches for advanced-stage breast cancer-related lymphedema and compared their treatment outcomes., Methods: The patients who underwent surgery with International Society of Lymphology stage III lymphedema were included in this study. The three surgical methods used here were (1) suction-assisted lipectomy with lymphovenous anastomosis, (2) autologous breast reconstruction with muscle-sparing transverse rectus abdominis muscle flap combined with inguinal lymph node transfer, and (3) vascularized lymph node transfer with free omental flap. Analysis of the postoperative outcomes in the patients was based on the difference in volume between patients pre- and postoperatively, LYMPH-Q questionnaire, and bioelectrical impedance analysis., Results: Eighty-seven patients with stage IIb or higher disease underwent surgery. 38 patients underwent suction-assisted lipectomy + lymphovenous anastomosis, 23 underwent autologous breast reconstruction with vascularized lymph node transfer + lymphovenous anastomosis, and 26 underwent right gastroepiploic omental vascularized lymph node transfer with lymphovenous anastomosis. The LYMPH-Q questionnaire, which evaluates patients' subjective satisfaction, showed that the autologous breast reconstruction group showed the greatest improvement, whereas in bioimpedance analysis, the omental flap group demonstrated the greatest postoperative improvement compared with preoperative values. However, suction-assisted lipectomy was considered the most effective surgical method for reducing limb volume in patients with high-stage lymphedema accompanied by fibrosis and volume increase., Conclusions: We observed slightly different clinical effects for each surgical method; however, all surgical methods demonstrated a reduction in the degree of edema and an increase in patient satisfaction., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)