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Yujin Choi,1,* Na-Yeon Ha,2,* Ae-Ran Kim,3 Haein Jeong,2 Ojin Kwon,1 Ki-Sun Park,1 Jieun Kim,1 Jinsung Kim,2 Hyungjun Kim1 1KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 2Division of Digestive Diseases, Department of Korean Internal Medicine, Kyung Hee University College of Korean Medicine, Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea; 3R&D Strategy Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea*These authors contributed equally to this workCorrespondence: Jinsung Kim, Department of Digestive Diseases, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea, Tel +82 2 958 8895, Email oridoc@khu.ac.kr Hyungjun Kim, Division of KM Science Research, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea, Tel +82 42 869 2796, Email heyjoon73@kiom.re.krIntroduction: Irritable bowel syndrome (IBS) is a chronic condition characterized by recurrent abdominal pain associated with bowel movements. Modified Gwakjeongtang (MGT), an herbal prescription rooted in traditional East Asian medicine, consists of thirteen botanical drugs known for their potential to enhance intestinal barrier function, regulate gastrointestinal motility, and exhibit anti-inflammatory and antioxidant properties. Despite a few previous clinical trials highlighting MGT’s potential for IBS symptom management, limited evidence exists with placebo control.Methods and Analysis: In this pilot randomized clinical trial protocol, we aim to exploratively evaluate the efficacy and safety of MGT in patients with diarrhea-predominant IBS (IBS-D) by comparing it with a placebo. A total of 60 IBS-D patients will be enrolled, and eligible participants will be randomly allocated to either the MGT or placebo groups. Over a 4-week period, they will receive MGT or placebo granules three times a day. The primary end

Polysomnography (PSG) is an indispensable diagnostic tool in sleep medicine, essential for identifying various sleep disorders. By capturing physiological signals, including EEG, EOG, EMG, and cardiorespiratory metrics, PSG presents a patient's sleep architecture. However, its dependency on complex equipment and expertise confines its use to specialized clinical settings. Addressing these limitations, our study aims to perform PSG by developing a system that requires only a single EEG measurement. We propose a novel system capable of reconstructing multi-signal PSG from a single-channel EEG based on a masked autoencoder. The masked autoencoder was trained and evaluated using the Sleep-EDF-20 dataset, with mean squared error as the metric for assessing the similarity between original and reconstructed signals. The model demonstrated proficiency in reconstructing multi-signal data. Our results present promise for the development of more accessible and long-term sleep monitoring systems. This suggests the expansion of PSG's applicability, enabling its use beyond the confines of clinics., Comment: Proc. 12th IEEE International Winter Conference on Brain-Computer Interface

Brain modulation is a modification process of brain activity through external stimulations. However, which condition can induce the activation is still unclear. Therefore, we aimed to identify brain activation conditions using 40 Hz monaural beat (MB). Under this stimulation, auditory sense status which is determined by frequency and power range is the condition to consider. Hence, we designed five sessions to compare; no stimulation, audible (AB), inaudible in frequency, inaudible in power, and inaudible in frequency and power. Ten healthy participants underwent each stimulation session for ten minutes with electroencephalogram (EEG) recording. For analysis, we calculated the power spectral density (PSD) of EEG for each session and compared them in frequency, time, and five brain regions. As a result, we observed the prominent power peak at 40 Hz in only AB. The induced EEG amplitude increase started at one minute and increased until the end of the session. These results of AB had significant differences in frontal, central, temporal, parietal, and occipital regions compared to other stimulations. From the statistical analysis, the PSD of the right temporal region was significantly higher than the left. We figure out the role that the auditory sense is important to lead brain activation. These findings help to understand the neurophysiological principle and effects of auditory stimulation., Comment: Accepted to EMBC 2023

Electroencephalography (EEG) has been widely used to study the relationship between naps and working memory, yet the effects of naps on distinct working memory tasks remain unclear. Here, participants performed word-pair and visuospatial working memory tasks pre- and post-nap sessions. We found marked differences in accuracy and reaction time between tasks performed pre- and post-nap. In order to identify the impact of naps on performance in each working memory task, we employed clustering to classify participants as high- or low-performers. Analysis of sleep architecture revealed significant variations in sleep onset latency and rapid eye movement (REM) proportion. In addition, the two groups exhibited prominent differences, especially in the delta power of the Non-REM 3 stage linked to memory. Our results emphasize the interplay between nap-related neural activity and working memory, underlining specific EEG markers associated with cognitive performance., Comment: Submitted to 2024 12th IEEE International Winter Conference on Brain-Computer Interface

The monaural beat is known that it can modulate brain and personal states. However, which changes in brain waves are related to changes in state is still unclear. Therefore, we aimed to investigate the effects of monaural beats and find the relationship between them. Ten participants took part in five separate random sessions, which included a baseline session and four sessions with monaural beats stimulation: one audible session and three inaudible sessions. Electroencephalogram (EEG) were recorded and participants completed pre- and post-stimulation questionnaires assessing mood and sleepiness. As a result, audible session led to increased arousal and positive mood compared to other conditions. From the neurophysiological analysis, statistical differences in frontal-central, central-central, and central-parietal connectivity were observed only in the audible session. Furthermore, a significant correlation was identified between sleepiness and EEG power in the temporal and occipital regions. These results suggested a more detailed correlation for stimulation to change its personal state. These findings have implications for applications in areas such as cognitive enhancement, mood regulation, and sleep management.

Chronic wounds, such as those exhibited by diabetic ulcers are a global health issue affecting approximately 3.75 million people worldwide. Chronic wounds are slower to heal, or fail to heal, due to decreased vascularisation among other factors. Growth factors are key signalling molecules which promote wound healing, however, they experience rapid degradation by proteolytic enzymes present in the chronic wound environment. Proteoglycans (PGs) are the natural binding, protective and signalling partners for many growth factors. However, the yield of PGs from natural sources is limited due to their low abundance in tissues and cell cultures. Recombinant DNA technology and metabolic engineering offer alternative PG production methods to increase the yield of PGs and to alter the structure of their glycosaminoglycan (GAG) chains. Serglycin is an intracellular PG, which has eight GAG attachment sites. Unlike other PGs, serglycin can be decorated with heparin, heparan sulphate (HS), chondroitin sulphate (CS) and/or dermatan sulphate (DS). Through these various GAG chains, serglycin present in intracellular granules can bind and release cytokines, chemokines and growth factors, which are ideal properties for growth factor delivery and signalling applications. Thus, this thesis examined the influence of various culture microenvironments on the yield and GAG structure of recombinant serglycin produced by both adherent and suspension mammalian cells. In addition, this thesis explored the ability of recombinant serglycin to support angiogenic growth factor binding and signalling. Adherent human embryonic kidney cells expressing recombinant serglycin (HEK-SGN) cultured in shaker flasks and continuously stirred tank reactors (CSTR) produced more protein decorated with GAGs compared to culture flasks. The cells cultured in CSTR produced more HS/heparin and CS/DS chains compared to the other culture flasks. HEK-SGN cells maintained in medium containing 25 mM glucose achieved the hi

Ji Hae Hwang,1,2,&ast; Kyeongmin Lee,1,&ast; Eunji Choi,1,3 Ha Na Cho,1 Boyoung Park,4 Yumie Rhee,5 Kui Son Choi1 1Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea; 2Center for Emergency Operations, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea; 3Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, CA, USA; 4Department of Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea; 5Department of Internal Medicine, Endocrine Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Kui Son ChoiGraduate School of Cancer Science and Policy, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Republic of KoreaTel +82-31-920-2912Fax +82-31-920-2189Email kschoi@ncc.re.krPurpose: Poor sleep quality is a common problem among middle-aged women. Few studies, however, have assessed differences in sleep quality among premenopausal, perimenopausal, and postmenopausal women and related risk factors in Korea women. The aim of this study was to assess sleep quality and factors associated therewith according to menopausal status in Korean women.Patients and Methods: This study was based on the 2016 Korean Study of Women’s Health Related Issues (K-Stori), a cross-sectional survey employing nationally representative random sampling. In total, 3000 Korean women aged 45 to 64 years completed the Pittsburgh Sleep Quality Index (PSQI). Comparison of demographic characteristics and sleep quality among pre-, peri-, and postmenopausal women was conducted.Results: Among the participants, 26% suffered from poor sleep quality based on the PSQI. The prevalence of poor sleep quality increased with later menopausal stage (from 18.8% in the premenopausal stage to 29.5% in the postmenopausal stage P < 0.001). M

Tae-Eun Kim,1 Na Ha,2 Yunjeong Kim,2 Hyunsook Kim,1 Jae Wook Lee,3 Ji-Young Jeon,2 Min-Gul Kim2,4 1Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, 2Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk, 3Nephrology Clinic, National Cancer Center, Goyang, Gyeonggi-do, 4Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea Abstract: Previous in vitro studies have demonstrated the inhibitory effect of green tea on drug transporters. Because rosuvastatin, a lipid-lowering drug widely used for the prevention of cardiovascular events, is a substrate for many drug transporters, there is a possibility that there is interaction between green tea and rosuvastatin. The aim of this study was to investigate the effect of green tea on the pharmacokinetics of rosuvastatin in healthy volunteers. An open-label, three-treatment, fixed-sequence study was conducted. On Day 1, 20 mg of rosuvastatin was given to all subjects. After a 3-day washout period, the subjects received 20 mg of rosuvastatin plus 300 mg of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea (Day 4). After a 10-day pretreatment of EGCG up to Day 14, they received rosuvastatin (20 mg) plus EGCG (300 mg) once again (Day 15). Blood samples for the pharmacokinetic assessments were collected up to 8 hours after each dose of rosuvastatin. A total of 13 healthy volunteers were enrolled. Compared with the administration of rosuvastatin alone, the concomitant use at Day 4 significantly reduced the area under the concentration–time curve from time 0 to the last measurable time (AUClast) by 19% (geometric mean ratio 0.81, 90% confidence interval [CI] 0.67–0.97) and the peak plasma concentration (Cmax) by 15% (geometric mean ratio 0.85, 90% CI 0.70–1.04). AUClast or Cmax of rosuvastat

ObjectiveTo compare the stability and clinical applicability of a novel orthodontic mini-implant design (N2) with the most widely used commercially available (CA) design.Materials and methodsTwo groups of mini-implants were tested: a CA design (1.5-mm diameter, 6-mm length) and N2 (3-mm diameter, 2-mm length, tapered shape). Implants were inserted in bone blocks of cortical bone simulation with varying densities (20 pounds per cubic foot [pcf], 30 pcf, and 40 pcf). A torque test was used to measure maximum insertion torque (MIT) and maximum removal torque (MRT). Compression and tension force vectors were applied at angles of 10°, 20°, 30°, and 40° using customized load pins to determine primary stability.ResultsMean MIT and MRT were higher in the N2 than the CA design at all three cortical bone densities except MRT in 20 pcf bone (not statistically significant). The mean compression force required to displace the N2 at all distances and angulations was greater for the N2 than the CA design. At all displacement distances, the highest mean tension force required for N2 displacement was at 10° angulation, whereas at 30° and 40°, the mean tension force required to displace the CA design was greater.ConclusionsThe primary stability of the N2 is superior to that of the CA design and is promising for both orthodontic and orthopedic clinical applicability, especially under compression force. The short length of the N2 reduces risk of damage to anatomic structures and root proximity during placement and orthodontic treatment. The stability of the N2 may be compromised in areas of high bone density and highly angulated tension force.

Objective: The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. Design: In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. Results: Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. Conclusions: Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.

Objective: The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. Design: In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. Results: Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. Conclusions: Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.

We have assembled absorption systems by visually identifying $C~IV\lambda\lambda1548,1551$ absorption doublets in the quasar spectra of the Baryon Oscillation Spectroscopic Survey (BOSS) one by one. This paper is the first of the series work. In this paper, we concern quasars with relatively low redshifts and high signal-to-noise ratios for their spectra, and hence we limit our analysis on quasars with $z_{em}\le2.4$ and on the doublets with $W_r\lambda1548\ge0.2$ \AA. Out of the more than 87,000 quasars in the Data Release 9, we limit our search to 10,121 quasars that have the appropriate redshifts and spectra with high enough signal-to-noise ratios to identify narrow C IV absorption lines. Among them, 5,442 quasars are detected to have at least one $C~IV\lambda\lambda1548,1551$ absorption doublet. We obtain a catalog containing 8,368 $C~IV\lambda\lambda1548,1551$ absorption systems, whose redshifts are within $z_{abs}=1.4544$ - $2.2805$. In this catalog, about $33.7\%$ absorbers have $0.2$ \AA$\le W_r\lambda1548<0.5$ \AA, about $45.9\%$ absorbers have $0.5$ \AA$\le W_r\lambda1548<1.0$ \AA, about $19.2\%$ absorbers have $1.0$ \AA$\le W_r\lambda1548<2.0$ \AA, and about $1.2\%$ absorbers have $W_r\lambda1548\ge2.0$ \AA.

We have assembled absorption systems by visually identifying $C~IV\lambda\lambda1548,1551$ absorption doublets in the quasar spectra of the Baryon Oscillation Spectroscopic Survey (BOSS) one by one. This paper is the first of the series work. In this paper, we concern quasars with relatively low redshifts and high signal-to-noise ratios for their spectra, and hence we limit our analysis on quasars with $z_{em}\le2.4$ and on the doublets with $W_r\lambda1548\ge0.2$ \AA. Out of the more than 87,000 quasars in the Data Release 9, we limit our search to 10,121 quasars that have the appropriate redshifts and spectra with high enough signal-to-noise ratios to identify narrow C IV absorption lines. Among them, 5,442 quasars are detected to have at least one $C~IV\lambda\lambda1548,1551$ absorption doublet. We obtain a catalog containing 8,368 $C~IV\lambda\lambda1548,1551$ absorption systems, whose redshifts are within $z_{abs}=1.4544$ - $2.2805$. In this catalog, about $33.7\%$ absorbers have $0.2$ \AA$\le W_r\lambda1548<0.5$ \AA, about $45.9\%$ absorbers have $0.5$ \AA$\le W_r\lambda1548<1.0$ \AA, about $19.2\%$ absorbers have $1.0$ \AA$\le W_r\lambda1548<2.0$ \AA, and about $1.2\%$ absorbers have $W_r\lambda1548\ge2.0$ \AA.

Ha Na Woo1*, Hye Kyung Chung2*, Eun Jin Ju1, Joohee Jung1,3, Hye-Won Kang4, Sa-Won Lee4, Min-Hyo Seo4, Jin Seong Lee5, Jung Shin Lee1,6, Heon Joo Park7, Si Yeol Song1,8, Seong-Yun Jeong1, Eun Kyung Choi1,2,81Institute for Innovative Cancer Research, 2Center for Development and Commercialization of Anti-cancer Therapeutics, Asan Medical Center, Seoul, 3College of Pharmacy, Duksung Women's University, Seoul, 4Department of Parenteral Delivery Program, Samyang Pharmaceuticals R&D, Daejeon, 5Department of Radiology and Research Institute of Radiology, 6Department of Internal Medicine, Asan Medical Center, Seoul, 7Department of Microbiology, College of Medicine, Inha University, Inchon, 8Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea*These authors contributed equally to this studyAbstract: Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)–sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP–sirolimus has prolonged circulation in the blood. In addition, PNP–sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP–sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP–sirolimus is a promising strategy for human cancer treatment.Keywords

Ha Na Woo1*, Hye Kyung Chung2*, Eun Jin Ju1, Joohee Jung1,3, Hye-Won Kang4, Sa-Won Lee4, Min-Hyo Seo4, Jin Seong Lee5, Jung Shin Lee1,6, Heon Joo Park7, Si Yeol Song1,8, Seong-Yun Jeong1, Eun Kyung Choi1,2,81Institute for Innovative Cancer Research, 2Center for Development and Commercialization of Anti-cancer Therapeutics, Asan Medical Center, Seoul, 3College of Pharmacy, Duksung Women's University, Seoul, 4Department of Parenteral Delivery Program, Samyang Pharmaceuticals R&D, Daejeon, 5Department of Radiology and Research Institute of Radiology, 6Department of Internal Medicine, Asan Medical Center, Seoul, 7Department of Microbiology, College of Medicine, Inha University, Inchon, 8Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea*These authors contributed equally to this studyAbstract: Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)–sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP–sirolimus has prolonged circulation in the blood. In addition, PNP–sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP–sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP–sirolimus is a promising strategy for human cancer treatment.Keywords

Ha Na Oh,1 Joo Eun Lee,2 Hyun Woong Kim,1 Jae Wook Yang,1 Il Han Yun11Department of Ophthalmology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea; 2Department of Ophthalmology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, KoreaPurpose: To report on a case that developed an atypical form of occult choroidal neovascularization (CNV) after successful macular hole surgery.Methods: Visual acuity change, color fundus photographs, fluorescein and indocyanine green angiograms, and optical coherence tomography results were compared throughout the follow-up duration.Patients: A 64-year-old woman with a macular hole in the right eye and drusen in both eyes underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. One month after the operation she developed occult CNV, in which pigment epithelial detachment and fine retinal pigment epithelial (RPE) layer wrinkles were observed under the completely sealed macular hole. After 3-monthly intravitreal injections of ranibizumab, the lesion did not change significantly.Conclusion: CNV can develop after otherwise successful macular hole surgery, especially in patients with pre-existing aging changes in the macula, such as drusen. Care should be taken in such patients, to prevent the development of CNV after macular hole surgery.Keywords: drusen, macular hole surgery, occult choroidal neovascularization, ranimizumab injection