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Purpose Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin–stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients.Materials and Methods A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study.Results The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis.Conclusion In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

With the developments in computer-aided engineering, more complex and difficult simulations have become possible, and the demand for fluid/structure interaction (FSI) analysis has been increasing. Various approximation methods have been developed for pressure/load data mapping for FSI analysis. However, for most existing mapping algorithms, the sum of force/moment, which is one of the most important physical properties to be conserved, is not generally conserved. In this paper, we propose a new pressure mapping technique that is intuitive and easy to implement while algorithmically preserving force/moment for interfaces with complex and simple shapes. This technique distributes the pressure of the computational fluid dynamics (CFD) boundary mesh as concentrated loads to the nodes of the nearest structural element. The load distribution from each CFD cell is assumed to satisfy a plane equation, and the mapping loads are obtained by solving the equations to determine the coefficients of the plane equation. Furthermore, an algorithm to search for neighboring structural nodes for load mapping has been developed for various situations. To verify the proposed method, a simple plate model, pipe model with internal flow, and full-scale aircraft model were used. The results of the validation examples showed reliable load distributions and structural deformations with force/moment conservation.

The brain is a common target organ for breast cancer metastasis, and the risk of brain metastasis is usually high for patients with HER2-positive breast cancer. While T-DXd showed positive results in HER2-positive breast cancer brain metastasis (BCBM), its activity and blood-brain barrier (BBB) permeability in active BCBM need to be further validated (TUXEDO-1 included 15 patients with active brain metastasis). Tucatinib plus Trastuzumab and Capecitabine triplet showed efficacy in patients with brain metastasis, but Tucatinib alone has poor BBB penetration. There is still an unmet medical need for active HER2-positive BCBM. VRN101099 is a highly selective kinase inhibitor of HER2 (Eurofins scanMAX Kinase Profiling, S-score (35) of 0.01). VRN101099 has single- to double-digit nanomolar (IC50) cellular potency in HER2-dependent cancer cells, and Ba/F3 cells expressing HER2 wild type or mutations with selectivity over wildtype EGFR. VRN101099 inhibited proliferation of BT474 with 3.6 nM IC50 but HaCaT with 829.2 nM IC50. VRN101099 binds HER2 kinase by forming a covalent bond to the Cys805 and its irreversible inhibition resulted in a longer target resident time than Tucatinib, confirmed by in vitro washout experiments. Robust in vivo activity of VRN101099 was observed in HER2-positive BT474 xenograft models. Moreover, once daily oral administration of VRN101099 significantly regressed intracranial BT474 tumor, demonstrating greater efficacy than twice daily oral administration of Tucatinib. These results were well explained by the superior brain to plasma exposure of VRN101099 to Tucatinib. Also, VRN101099 showed high exposure in the target organ, the fat pad, which potentiated better clinical translation. These anti-tumor efficacies are correlated with pharmacodynamic responses, as confirmed by decreased HER2, AKT, and ERK phosphorylation. In summary, VRN101099 is a brain penetrant, orally bioavailable, irreversible, and highly selective inhibitor of HER2 with therapeutic potential in HER2-positive BCBM. These data support the clinical development of VRN101099 in HER2-driven cancers. Citation Format: Yikyung Ko, Jihye yoo, Hong-ryul Jung, Hyerim Lim, YeongDeok Lee, Se Hyuk Kim, Dong Guk Shin, Serin Cho, Myung hoe Heo, Haelee Kim, Ha Yeon Cho, Ah Reum Han, Eunhwa Ko, Hwan Geun Choi, Deakwon Kim, Sunghwan Kim. VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-03.

Background: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD’s effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content. Methods: The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography. Results: Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not. Conclusions: The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization.

Background. Kami Guibi-tang (KGT), a traditional Korean herbal medicine is mainly used to treat insomnia and nervousness. Acetylcholinesterase inhibitors (AChEIs) are the main treatments for mild Alzheimer’s disease (AD), a degenerative brain disease. However, currently no drug can fundamentally treat AD or reverse the advanced cognitive decline. This clinical study explored the efficacy and safety of adding KGT to AChEI for cognitive function in mild AD. Methods. This was a pilot study for a larger randomized, double-blind, placebo-controlled trial. Participants between 55–90 years diagnosed with mild AD were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea. They were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary outcome was treatment efficacy, as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D). Changes in SNSB subscores were assessed as secondary outcomes. Safety parameters, including adverse events and abnormalities in blood tests, electrocardiograms, and brain magnetic resonance imaging were also monitored. Results. Between March 2018 and November 2020, seven participants each in the KGT group and the placebo group completed the 24-week trial. There were no significant changes in SNSB-D total or subindex scores for either group ( p = 0.69 and 0.63, respectively), and no significant differences were observed between them ( p = 0.71 ). No adverse events related to KGT were reported. We also compared and analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment (aMCI) using protocol of this study. The aMCI group showed a significant improvement in the total SNSB-D score, especially in the memory domain, compared to the mild AD group ( p = 0.04 and 0.02, respectively). The Korean Mini-Mental State Exam and Korean Instrumental Activities of Daily Living scores also significantly improved in the aMCI group ( p = 0.01 and 0.02, respectively). Conclusions. Compared to placebo, adding KGT to AChEI did not significantly improve cognitive function in SNSB in patients with mild AD. We suggest that KGT would have a positive effect on patients with early stages of cognitive impairment such as aMCI. The findings could assist design larger, longer-term clinical trials of KGT use in elderly patients with mild AD. This study was registered in the Korean Clinical Trial Registry on December 26, 2017, with the CRIS approval number KCT0002904.

Taste receptor cells are taste bud epithelial cells that are dependent upon the innervating nerve for continuous renewal and are maintained by resident tissue stem/progenitor cells. Transection of the innervating nerve causes degeneration of taste buds and taste receptor cells. However, a subset of the taste receptor cells is maintained without nerve contact after glossopharyngeal nerve transection in the circumvallate papilla in adult mice. Here, we revealed that injury caused by glossopharyngeal nerve transection triggers the remaining differentiated K8-positive taste receptor cells to dedifferentiate and acquire transient progenitor cell-like states during regeneration. Dedifferentiated taste receptor cells proliferate, express progenitor cell markers (K14, Sox2, PCNA) and form organoids in vitro. These data indicate that differentiated taste receptor cells can enter the cell cycle, acquire stemness, and participate in taste bud regeneration. We propose that dedifferentiated taste receptor cells in combination with stem/progenitor cells enhance the regeneration of taste buds following nerve injury.

In this study, a smoothing method was applied to improve the accuracy of peak wave period estimation using the water surface elevation observed from the Oceanographic and Meteorological Observation Tower located on the west coast of the Korean Peninsula. Validation of the application of the smoothing method was performed using variance of the surface elevation and total amount wave energy, and then the effect on the application of smoothing was analyzed. As a result of the analysis, the correlation coefficient between variance of the surface elevation and total amount wave energy was 0.9994, confirming that there was no problem in applying the method. Thereafter, as a result of reviewing the effect of smoothing, it was found to be reduced by about 4 times compared to the confidence interval of the existing estimated spectrum, confirming that the accuracy of the estimated peak wave period was improved. It was found that there was a statistically significant difference in probability density between 4 and 6 seconds due to the smoothing application. In addition, for optimal smoothing, the appropriate number of smoothings according to the significant wave height range was calculated using a statistical technique, and the number of smoothings was found to increase due to the unstable spectral shape as the significant wave height decreased.

The persistence analysis of marine physical environment factors is a basic analysis that must precede the use of sea areas as an analysis required in the coastal engineering such as downtime and design. In this study, the persistence analysis was implemented for wind speed and significant wave height data from four observation points of Deokjeokdo, Oeyeondo, Geomundo, and Geojedo among the marine meteorological observation buoys of the Korea Meteorological Administration. The persistence time means the consecutive time of observation data beyond specific level. The threshold wind speed and significant wave height were set in the range of 1~15 m/s and the range of 0.25~3.0 m, respectively. Then, the persistence time was extracted. As a result of the analysis, the persistence time of wind speed and significant wave height decreased rapidly as the reference value increased. The median persistence times under the maximum reference thresholds were assessed as a maximum of 5 hours for wind speed and a maximum of 8 hours for significant wave height. When the reference wind speed and significant wave height were 15 m/s and 3 m, respectively, the persistence time that could occur with a 1% probability were 52 and 56 hours. This study can be expanded to all coastal areas in Korea, and it is expected that various engineering applications by performing a persistence analysis of the metocean data.

Objectives: Parkinson’s disease (PD) patients experience various non-motor symptoms, among which constipation is the second most common after anosmia. However, there are no clear guidelines or effective treatment for constipation in PD.Methods: To investigate the efficacy of Majainhwan (MH) on constipation in patients with PD, we conducted a retrospective chart review study of PD or Parkinsonism patients with constipation who received outpatient or inpatient treatment and whose previous laxatives were replaced by MH from August 2016 to July 2019.Results: In this study, a total of 68 patients’ medical records were reviewed. Among the 44 outpatients with MH treatment, “effective” results were observed in 86.4% patients. Similarly, among the 24 inpatients, “effective” results were noted in 95.8% patients. The adverse effect was "diarrhea" reported in five cases.Conclusion: Based on these findings, we could suggest that MH is relatively safe and may be effective in the treatment of constipation in patients with PD.

This paper presents a scalable software architecture based on robot operating system 2 (ROS2) for service robots. ROS2 supports the data distribution service (DDS) protocol that provides benefits such as real-time operation and security and performance enhancements. However, ROS2 still lacks task management capabilities, essential for practical robotic applications consisting of multiple threads and processes. Moreover, integrating new devices into ROS2 requires additional development effort to create specific drivers for specific devices. The proposed software architecture addresses these drawbacks and provides a simple and user-friendly programming interface for easier integrating of various devices and existing ROS2 applications. Moreover, it is designed using python with multi-processing to avoid issues related to the python global interrupt lock (GIL). To verify the developed software architecture, an application for a custom-made service robot called the SeoulTech service robot (SSR) is implemented on a Jetson Xavier NX board with various features, such as ROS2 navigation and SLAM, text-to-speech (TTS), speech recognition, and face recognition.

The most common definition of postherpetic neuralgia is the presence of pain more than a month after the onset of the eruption of zoster. This case report suggests the effect of Korean medicine on postherpetic neuralgia. An 85-year-old male patient with postherpetic neuralgia was treated with a combination of Korean medical remedies. Kyung Hee Gongjin-dan and Hyangbujapalmul-tang-gagam were applied for 23 days. The Numerical Rating Scale was used to measure pain intensity. The Barthel Index and Beck Depression Inventory were used for the functional assessment and depression evaluation, respectively. After treatment, the patient’s pain intensity decreased. Additionally, the patient’s independence increased during activity, and the severity of their depression decreased. Thus, this case suggests that a combination of Korean medicine treatments might be effective for postherpetic neuralgia. In particular, it shows that Kyung Hee Gongjin-dan and Hyangbujapalmul-tang-gagam can be therapeutic options in the treatment of postherpetic neuralgia.

This case report determines the effects of Korean medicine treatment on a pontine hemorrhage with a cavernous malformation. In this study, Korean medicine treatments, such as herbal medicine, acupuncture, electro-acupuncture, and moxibustion, were administered for 30 days. During the hospitalization period, evaluations were performed using the Scott and Kraft Scale, eye movement, 9-gaze photography, the House-Brackmann grading system, and Yanagihara’s unweighted grading system on days 1, 12, and 30. The Scott and Kraft Scale increased from -4 to -2, while eye movement increased from 43.1% to 72.3%. The House-Brackmann grading system improved from 4 to 2, and Yanagihara’s unweighted grading system increased from 13 to 31. We also discovered that the movement of the left eye was improved by 9-gaze photography. Our findings suggest that Korean medicine treatment has potential effects on esotropia and facial palsy caused by a pontine hemorrhage with a cavernous malformation.

The pathogenic Listeria monocytogenes bacterium produces the flagellum as a locomotive organelle at or below 30°C outside the host, but it halts flagellar expression at 37°C inside the human host to evade the flagellum-induced immune response. Listeria monocytogenes GmaR is a thermosensor protein that coordinates flagellar expression by binding the master transcriptional repressor of flagellar genes (MogR) in a temperature-responsive manner. To understand the regulatory mechanism whereby GmaR exerts the antirepression activity on flagellar expression, we performed structural and mutational analyses of the GmaR–MogR system. At or below 30°C, GmaR exists as a functional monomer and forms a circularly enclosed multidomain structure via an interdomain interaction. GmaR in this conformation recognizes MogR using the C-terminal antirepressor domain in a unique dual binding mode and mediates the antirepressor function through direct competition and spatial restraint mechanisms. Surprisingly, at 37°C, GmaR rapidly forms autologous aggregates that are deficient in MogR neutralization capabilities.

Characterized by impaired mucociliary clearance with subsequent compromised microbial elimination, chronic rhinosinusitis (CRS) is known as a multifactorial disease process in which bacterial infection or colonization could play a role in the initiation or propagation of the inflammatory response. Various non-systemic, topical therapies have recently emerged as an alternative to conventional oral regimens in managing CRS. A topical sinonasal drug delivery system using a bioabsorbable stent represents one of the most attractive methods among multiple topical delivery options. This review discusses the commercially available topical drug delivery platform (sinus stents) for CRS and its shortcomings. Based on the current drawbacks of sinus stents, this article has also highlighted the future developmental perspectives to create the next generation of a sinus stent, thereby harnessing the full potential of the sinus stent as efficient topical drug delivery for recalcitrant CRS.

Objectives: To investigate the effects of acupuncture at GV20 and EX-HN1 on cerebral blood flow (CBF) velocity and cerebrovascular reactivity (CVR) in the middle cerebral arteries (MCA) and anterior cerebral arteries (ACA) and to compare the effects to acupuncture at GV20.Methods: The study was a randomized, crossover trial that included 10 healthy men aged 20 to 29 years who underwent acupuncture treatment four times with a washout period of one week. The CBF velocity and CVR were measured by transcranial Doppler sonography (TCD) on both MCAs at the first and second visits, and both ACAs at the third and fourth visits. Participants were randomly assigned to one of two groups (A and B) before the first and third visits. Group A received two phases of acupuncture intervention at a single GV20 point and a combination of GV20 and EX-HN1 acupoints. Group B received the same interventions, but in the reverse order.Results: The increase in CO2 reactivity was significantly higher for the combination acupoints of GV20 and EX-HN1 than for the GV20 single acupoint in both MCAs (Right: 136 to 178, p=0.017; Left: 127 to 191, p=0.017) and ACAs (Right: 133 to 158, p=0.013; Left: 122 to 168, p=0.025). No significant change was noted in the corrected velocity at PETCO2 40 mmHg, blood pressure, or heart rate.Conclusions: The findings suggest that improvement of the CBF in the MCA and ACA after GV20 acupuncture increases when acupuncture is also performed at EX-HN1. These results clinically support the combined use of EX-HN1 and GV20 to treat disorders of MCA and ACA circulation.

Objectives: This study was designed to investigate the clinical effectiveness of Ikgibohyeol-tang(Yìqìbǔxuè-tāng) granules and Deer antler granules on fatigue symptoms.Methods: This is a 39-patient case series from a retrospective chart review of outpatients who were treated with Ikgibohyeol-tang granules and Deer antler granules at a Kyung Hee University Korean Medicine Hospital (Seoul) between 1st, January 2015 to 1st, August 2021. We reviewed the patients who complained of fatigue and analyzed changes in the degree of discomfort with fatigue and accompanying symptoms and HRV (Heart Rate Variability) score before and after treatment.Results: After taking Ikgibohyeol-tang granules and Deer antler granules, the degree of discomfort with fatigue and accompanying symptoms decreased significantly compared to before taking them. After treatment, Autonomic nervous system activity, Stress resistance, Heart Stability increased, and Stress index, Degree of fatigue decreased significantly.Conclusions: This study showed subjective symptoms and objective indicator (HRV score) were improved by taking Ikgibohyeol-tang granules and Deer antler granules.

Objectives: This study investigates the effect of parenting stress on mothers of infants and the participation of fathers in raising the infants as perceived by the mothers, and a mother’s satisfaction of her role as a paerent. The infant stage is a period change, and the mothers go through a lot of stress during the stage. We will explore the ways to improve the role satisfaction in parents considering that it is a major change in their lives.Methods: Participants comprised 159 mothers of infants who agreed to participate in the study. They answered questionnaires on parenting stress, fathers’ parenting participation, and satisfaction in parents’ role. Multiple regression analysis was conducted to understand the influence.Results: The results revealed that the parent’s role satisfaction as perceived by a mother was significantly related to her parenting stress and the father’s participation in parenting. The lower the parenting stress and the higher the father’s participation in parenting, the higher was the parent’s role satisfaction. In particular, it was found that the negative interaction between parents and children, and the life factors of fathers, had a direct effect.Conclusion: This study explores how the parenting stress in mothers of infants and the participation of fathers as perceived by mothers affect the mother’s satisfaction with her role as a parent. It is necessary to find ways to reduce the stress of the mothers raising infants in order to increase their role satisfaction, and fathers need to take an active part in nurturing the infant.

Tintinnids are a major group of planktonic ciliates. To determine a desirable sampling interval for analyzing the temporal dynamics of tintinnids, intensive monitoring was conducted on the southern coast of Korea. The mean sampling interval was 1.5 days. The abundance of tintinnids were analyzed by microscopy. The high- frequency temporal pattern showed detailed changes in concentrations and a distinct seasonality in the abundance of tintinnids. An optimal monitoring interval for tintinnid abundance estimations was determined by polynomial interpolation and statistical analysis, involving three steps, namely, interpolation by increasing the number of sampling intervals, graphical analysis with interpolated data and determination of the changepoint depending on the interpolated results. The value of changepoint was 7 days, indicating the optimal monitoring interval. Therefore, data collection at weekly intervals is sufficient and desirable for tracing the temporal signals of tintinnid ecology and its long-term trends.

Objectives: Bee venom (BV) is a widely used therapy in Traditional East Asian Medicine (TEAM). We previously reported that BV was clinically effective for treating Parkinson’s disease, that phospholipase A2 (PLA2) was the main component of BV, and that it induced regulatory T cells (Tregs) by binding CD206 on dendritic cells (DCs). Therefore, we aimed to reconfirm our findings in human blood samples and investigate the relationship between CD206+ DCs and clinical syndrome differentiation in TEAM.Methods: We surveyed 100 subjects with questionnaires on cold-heat patternization and obtained their blood samples. The obtained human peripheral blood monocytes (hPBMCs) were washed with phosphate-buffered saline (PBS). After resuspension with ex vivo media, numbers of cells were counted. Tregs were counted after culturing the samples in a 37℃ CO2 incubator for 72 h.Results: We divided the subjects into a relatively high CD206+ group or a relatively low CD206+ group. The heat factor scores of high CD206+ group were significantly higher than that of low CD206+ group (high vs low: 239.2 ± 54.1 vs 208.4 ± 55.1, p=0.023). After culturing with PLA2, Tregs increased in the high CD206+ group but decreased in the low CD206+ group.Conclusion: In this study, we reconfirm that CD206+ DCs induced Treg differentiation by incubating human blood samples with PLA2 and that they showed an association with syndrome differentiation, especially with heat patterns, in TEAM. A heat pattern in TEAM might be one indication for PLA2 therapy because its score was elevated in the high CD206+ group.

Objectives: This study examined the effectiveness of Korean medical treatment for two patients complaining of discomfort after receiving Pfizer COVID-19 vaccine.Methods: The patients were hospitalized for 50 days and 12 days, respectively. They were treated with herbal medicine, acupuncture, electroacupuncture, and moxibustion. We used the Numerical Rating Scale (NRS) on numbness in extremities and headache, Manual Muscle Testing Grading System (MMT), Criteria for Sweating Categorization, and 36-Item Short Form Health Survey (SF-36) to evaluate the clinical effects of the treatment.Results: In Case 1, headache improved from peak NRS 9 and average NRS 7 on admission day to both NRS 3 on discharge. The SF-36 score was also increased, suggesting that the quality of life was improved. In Case 2, numbness in the extremities improved from NRS 8 on the day before admission to NRS 2 on discharge, and general condition also improved.Conclusions: This study suggests that Korean medicine can be an effective treatment for patients who experience long-lasting discomfort after being vaccinated with COVID-19, but with no abnormal findings in the examination.