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Mincheol Chae,1,* Jae-Ho Lee,2,* Jong Ho Park,2 Dong Yoon Keum,1 Hanna Jung,3 Youngok Lee,3 Deok Heon Lee3 1Department of Thoracic and Cardiovascular Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea; 2Department of Anatomy, Keimyung University School of Medicine, Daegu, Korea; 3Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Jung-gu, 41944, Korea*These authors contributed equally to this workCorrespondence: Deok Heon Lee, Tel +82-53-200-5665, Fax +82-53-426-4765, Email ldhms@knu.ac.krBackground: TRF1, TRF2, and TERT (Telomerase reverse transcriptase) are telomere-associated factors that regulate telomere length. Genetic changes in these genes may be associated with cancer pathogenesis; however, this relationship has not yet been comprehensively elucidated in lung cancer.Aim: : Exploring the clinicopathologic and prognostic values of TRF1, TRF2, and TERT mRNA expression in non-small cell lung cancers (NSCLC).Methods: : The clinical significance of TRF1, TRF2, and TERT expression in 141 patients with NSCLC was investigated. Additionally, these findings were supported by the open big data from The Cancer Genome Atlas (TCGA).Results: : TRF1 and TRF2 expression levels tended to be associated with smoking, and TERT expression was positively correlated with age. The survival analysis showed that TRF1 expression predicted a better prognosis for squamous cell carcinoma (SCC), whereas TRF2 expression was associated with a shorter survival in adenocarcinoma. TCGA data also showed a better prognosis for SCC with TRF1 expression. However, the TRF2 results were not in agreement with our data.Conclusions: : We present the clinical and prognostic values of TRF1, TRF2, and TERT expression in NSCLC tissues and TCGA. Our findings suggest that TRF1 expression is a possible prognostic marker for NSCLC, particularly SCC.Keywords: TRF1, TRF2, TERT, telomere, lung cancer

Je-Young Park,1,* Ji Su Lee,2,* Soo Ran Lee,2 Dong Hun Lee2– 4 1Apkoo-Jung Oracle Dermatology Center, Seoul, Republic of Korea; 2Department of Dermatology, Seoul National University Hospital, Seoul, Republic of Korea; 3Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; 4Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Dong Hun Lee, Department of Dermatology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Tel +82-2-2072-4916, Fax +82-2-742-7344, Email ivymed27@snu.ac.krBackground: Despite the increasing need for the improvement of enlarged facial pores, the treatment remains challenging. A few previous studies have reported the effects of micro-focused ultrasound with visualization (MFU-V) or intradermal incobotulinumtoxin-A (INCO) on enlarged facial pores.Objective: To evaluate the efficacy and safety of combined treatment with superficial MFU-V and intradermal INCO for enlarged facial pores.Methods: This single-center retrospective study included 20 patients treated with MFU-V and intradermal INCO to improve enlarged facial pores. Outcomes were evaluated 1, 4, 12, and 24 weeks after a single session of the combined procedure. Pore count and density were objectively quantitated using a three-dimensional scanner, and improvement was assessed using the physician and patient Global Aesthetic Improvement Scale (GAIS).Results: The mean pore count and density decreased after one week and decreased by up to 62% until 24 weeks. After one week, almost all patients (100% in physician GAIS and 95% in patient GAIS) showed improvement with a grade 3 (much improved) or higher. All adverse events were transient.Conclusion: Combined treatment with MFU-V and intradermal INCO could be effective and safe for reducing enlarged facial pores; the improvements can be sustained for up to 24 weeks.Keywords: pores, enlarged facial pores, incobotulinumtoxin-A, micro-focused ultrasound with visualization

Dong-Han Lee, Jung Eun Shin, Taesik Jung, Chang-Hee Kim Department of Otorhinolaryngology-Head and Neck Surgery, Konkuk University Medical Center, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of KoreaCorrespondence: Chang-Hee Kim, Department of Otorhinolaryngology-Head and Neck Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdong-ro (Hwayang-dong), Gwangjin-gu, Seoul, 05030, Republic of Korea, Tel +82-2-2030-7666, Fax +82-2-2030-5299, Email changhee.kim@kuh.ac.krPurpose: The present study investigated the impact of coronavirus disease 2019 (COVID-19) pandemic on benign paroxysmal positional vertigo (BPPV).Patients and Methods: The medical records of BPPV patients who were evaluated in the outpatient department (OPD) and emergency room (ER) during (435 patients) and before (517 patients) the COVID-19 pandemic were retrospectively reviewed. Dix-Hallpike and supine head-roll tests were used to classify the subtype of BPPV as posterior semicircular canal (PSCC), geotropic lateral semicircular canal (geotropic LSCC), or apogeotropic lateral semicircular canal (apogeotropic LSCC) BPPV.Results: More patients with PSCC BPPV were diagnosed at the OPD compared with those who were diagnosed at the ER both before and during the COVID-19 pandemic; however, more patients with LSCC BPPV were diagnosed at the ER compared with those who were diagnosed at the OPD during the same periods. The mean time interval between vertigo onset and initial evaluation was remarkably longer during the pandemic in patients with PSCC BPPV.Conclusion: This study demonstrated that the incidences of BPPV subtypes according to hospital visit type were not significantly different before and during the COVID-19 pandemic. Because hospital visits were delayed in patients with PSCC BPPV during the COVID-19 pandemic, telemedicine or e-health could be suitable alternatives to face-to-face medical care for these patients.Keywords: benign paroxysmal positional vertigo, COVID-19, emergency room, outpatient department, healthcare use behavior, hospital visit type

Moon Jung Choi,1 Kang Chan Choi,1 Do Hyun Lee,1 Hwa Yeon Jeong,1 Seong Jae Kang,1 Min Woo Kim,1 In Ho Jeong,1 Young Myoung You,1 Jin Suk Lee,2 Yeon Kyung Lee,1 Chan Su Im,1 Yong Serk Park1 1Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea; 2Department of Anatomy, Yonsei University Wonju College of Medicine, Wonju, Republic of KoreaCorrespondence: Chan Su Im; Yong Serk Park, Department of Biomedical Laboratory Science, Yonsei University, Wonju, Gangwon, 220-710, Republic of Korea, Email chanzzhu@nate.com; parkys@yonsei.ac.krIntroduction: Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.Methods: The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.Results: The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.Discussion: These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.Graphical Abstract: Keywords: cell-derived nanoparticles, immune surveillance, CD47, doxorubicin, tumor targeting, cancer therapy

Quang Luu Quoc,1 Ji-Young Moon,1 Dong-Hyun Lee,1 Ga-Young Ban,2 Seung-Hyun Kim,3 Hae-Sim Park1 1Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea; 2Department of Pulmonary, Allergy, and Critical Care Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine Institute for Life Sciences, Chuncheon, South Korea; 3Translational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon, South KoreaCorrespondence: Seung-Hyun KimTranslational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon, South Korea, Tel +82 31-219-4264, Fax +82 31-219-4265, Email kimsh@ajou.ac.krHae-Sim ParkDepartment of Allergy and Clinical Immunology, Ajou University School of Medicine, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, South Korea, Tel +82 31-219-5000, Fax +82 31-219-6380, Email hspark@ajou.ac.krBackground: Asthma is a chronic inflammatory airway disease characterized by the predominant infiltration of inflammatory cells in the airways. Thymus and activation-regulated chemokine/C–C motif chemokine 17 (TARC/CCL17) is a chemokine responsible for trafficking T helper 2 cells into sites of allergic inflammation.Objective: To validate the role of TARC in association with clinical and inflammatory parameters in adult asthmatics.Methods: We enrolled 128 asthmatic patients and 70 healthy controls (HCs). Asthma-related clinical and laboratory parameters, including lung function and eosinophil counts, were measured. Serum levels of TARC, free immunoglobulin E (IgE), and eosinophil-derived neurotoxin (EDN) were determined by using enzyme-linked immunosorbent assay; serum total IgE level was measured using ImmunoCAP. The levels of inflammatory lipid mediators, such as leukotriene E4 (LTE4), 15-hydroxyeicosatetraenoic acid (15-HETE), thromboxane B2 (TXB2), and prostaglandin F2α (PGF2α), were measured by liquid chromatography-tandem mass spectrometry.Results: Serum TARC levels are significantly higher in asthmatics than in HCs and in allergic asthmatics than in HCs (P < 0.010 for all), with significantly negative correlations between serum TARC levels and FEV1%/MMEF% values (r = − 0.314, r = − 0.268, P < 0.050 for both). The patients with higher serum TARC levels had higher levels of serum total and free IgE levels (P < 0.050 for both) with positive correlations to serum levels of EDN, TXB2, and 15-HETE (r = 0.233, r = 0.264, and r = 0.223, respectively, P < 0.050 for all).Conclusion: We suggest the role of TARC in allergic asthma via contributing to mast cell and eosinophilic inflammation.Keywords: asthma, allergic asthma, thymus and activation-regulated chemokine, IgE, T cells, mast cells, eosinophils

Min Jun Shin,1,2,&ast; Jun Young Park,1,2,&ast; Dae Ho Lee,3,4 Dongwoo Khang1,2,5 1Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, South Korea; 2Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, South Korea; 3Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, 21999, South Korea; 4Department of Internal Medicine, Gachon University College of Medicine, Incheon, 21999, South Korea; 5Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, South Korea&ast;These authors contributed equally to this workCorrespondence: Dongwoo KhangDepartment of Physiology, School of Medicine, Gachon University, Incheon, 21999, South KoreaTel +82 32 899 1525Email dkhang@gachon.ac.krDae Ho LeeDepartment of Internal Medicine, Gachon University College of Medicine, Incheon, 21565, South KoreaTel +82 32 458 2733Email drhormone@gachon.ac.krAbstract: Mesenchymal stem cells (MSCs) are considered a promising regenerative therapy due to their ability to migrate toward damaged tissues. The homing ability of MSCs is unique compared with that of non-migrating cells and MSCs are considered promising therapeutic vectors for targeting major cells in many pathophysiological sites. MSCs have many advantages in the treatment of malignant diseases, particularly rheumatoid arthritis (RA). RA is a representative autoimmune disease that primarily affects joints, and secreted chemokines in the joints are well recognized by MSCs following their migration to the joints. Furthermore, MSCs can regulate the inflammatory process and repair damaged cells in the joints. However, the functionality and migration ability of MSCs injected in vivo still show insufficient. The targeting ability and migration efficiency of MSCs can be enhanced by genetic engineering or modification, eg, overexpressing chemokine receptors or migration-related genes, thus maximizing their therapeutic effect. However, there are concerns about genetic changes due to the increased probability of oncogenesis resulting from genome integration of the viral vector, and thus, clinical application is limited. Furthermore, it is suspected that administering MSCs can promote tumor growth and metastasis in xenograft and orthotopic models. For this reason, MSC mimicking nanoencapsulations are an alternative strategy that does not involve using MSCs or bioengineered MSCs. MSC mimicking nanoencapsulations consist of MSC membrane-coated nanoparticles, MSC-derived exosomes and artificial ectosomes, and MSC membrane-fused liposomes with natural or genetically engineered MSC membranes. MSC mimicking nanoencapsulations not only retain the targeting ability of MSCs but also have many advantages in terms of targeted drug delivery. Specifically, MSC mimicking nanoencapsulations are capable of encapsulating drugs with various components, including chemotherapeutic agents, nucleic acids, and proteins. Furthermore, there are fewer concerns over safety issues on MSC mimicking nanoencapsulations associated with mutagenesis even when using genetically engineered MSCs, because MSC mimicking nanoencapsulations use only the membrane fraction of MSCs. Genetic engineering is a promising route in clinical settings, where nano-encapsulated technology strategies are combined. In this review, the mechanism underlying MSC homing and the advantages of MSC mimicking nanoencapsulations are discussed. In addition, genetic engineering of MSCs and MSC mimicking nanoencapsulation is described as a promising strategy for the treatment of immune-related diseases.Keywords: stem cell migration, stem cell mimicking nanoencapsulations, autoimmune disease targeting strategy, exosomes, ectosomes, liposomes

Dong Hyeon Lee,1 Jae Yong Jeong,2 Wan Song3 1Department of Urology, Ewha Womans University Medical Center, Ewha Womans University School of Medicine, Seoul, Korea; 2Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaCorrespondence: Wan SongDepartment of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 135-710, KoreaTel +82-2-3410-3558Fax +82-2-3410-3027Email wan.song@samsung.comPurpose: To investigate the prognostic value of programmed death ligand-1 (PD-L1) expression in tumor-infiltrating immune cells (ICs) in men treated with adjuvant chemotherapy (AC) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).Materials and Methods: We retrospectively reviewed 219 “high-risk” (≥pT3a and/or pN+) patients who underwent RC and received cisplatin-based AC for MIBC between March 2015 and September 2019. PD-L1 expression was measured using the VENTANA (SP-142) immunohistochemistry assay and categorized into the three groups according to the percentage of the tumor area covered by PD-L1 expression on ICs: IC0 (< 1%), IC1 (≥ 1% and < 5%), and IC2/3 (≥ 5%). Positive PD-L1 expression was defined as IC2/3 (≥ 5%). Kaplan–Meier survival analysis was used to assess recurrence-free survival (RFS), and Cox proportional hazard models were applied to identify factors predicting tumor recurrence.Results: In the entire cohort, the overall prevalence of PD-L1 IC0, IC1, and IC2/3 was 13.2%, 27.4%, and 59.4%, respectively. During the mean follow-up of 32.5 months, tumor recurrence was detected in 115 (52.5%) patients. On multivariable analysis, tumor stage (≥pT3; P=0.032), positive lymph nodes (P=0.001), and positive PD-L1 on ICs (P=0.005) were independent predictors of tumor recurrence. The 3 year RFS was 54.7% in patients with negative PD-L1 and 31.7% in patients with positive PD-L1.Conclusion: PD-L1 is widely expressed in ICs. Positive PD-L1 on ICs was significantly associated with shorter RFS in patients treated with cisplatin-based AC following RC. The present results support the use of adjuvant immunotherapy in “high-risk” patients with PD-L1-expressing ICs.Keywords: adjuvant chemotherapy, bladder cancer, programmed death ligand-1, recurrence, tumor-infiltrating immune cell

Sang Won Nam,1 Jinwoo Choi,1 Hyun Jeong Jeon,2 Tae Keun Oh,2 Dong-Hwa Lee1 1Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea; 2Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South KoreaCorrespondence: Dong-Hwa LeeDepartment of Internal Medicine, Chungbuk National University Hospital, 776, 1sunhwan-Ro, Seowon-Gu, Cheongju-si, Chungcheongbuk-do, 28644, South KoreaTel +82-43-269-7504Fax +82-43-273-3252Email roroko@hanmail.netBackground: Vitamin D receptor (VDR) polymorphisms are associated with osteoporosis, diabetes, immunological diseases, and cancers. However, the association of obesity with VDR polymorphisms has shown inconsistent results, and perhaps it depends upon the characteristics of a population. Therefore, we evaluated the association between BsmI (rs1544410) and ApaI (rs7975232) polymorphisms of VDR and obesity in Korean patients with type 2 diabetes mellitus (T2DM).Methods: A total of 506 patients with T2DM participated in the study. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze BsmI and ApaI polymorphisms; the genotypes were presented as BB, Bb, or bb for BsmI and AA, Aa, or aa for ApaI. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2.Results: The prevalence of obesity was higher in patients with the bb genotype than in those with BB or Bb genotypes (48.4% vs 33.9%, P = 0.031). The mean BMI was 25.2 ± 3.5 kg/m2 in patients with bb genotype and 24.1 ± 3.1 kg/m2 in patients with BB or Bb genotypes. Patients with Aa or aa genotypes showed a higher prevalence of obesity than patients with AA genotype (47.6% vs 26.1%, P = 0.043). Glycemic control parameters and lipid profiles did not show significant differences with either polymorphism.Conclusion: To our knowledge, this is the first study to assess the association between VDR polymorphisms and obesity in Korean patients with T2DM. Further studies in larger populations and multiethnic cohorts are needed to validate our findings.Keywords: type 2 diabetes mellitus, obesity, vitamin D, vitamin D receptor gene, polymorphism

Dong Hyeon Lee,1 Wan Song2 1Department of Urology, Ewha Womans University Medical Center, Ewha Womans University School of Medicine, Seoul, Korea; 2Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaCorrespondence: Wan SongDepartment of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 135-710, KoreaTel +82-2-3410-3558Fax +82-2-3410-3027Email wan.song@samsung.comPurpose: To present surgical methods and outcomes in women with bladder cancer (BCa) requiring correction of neobladder-vaginal fistula (NVF) after radical cystectomy (RC) with ileal orthotopic neobladder (IONB).Materials and Methods: The medical records of 163 women who underwent RC with IONB for BCa between January 2010 and December 2018 were retrospectively reviewed. The presence of NVF was confirmed by cystoscopy and/or voiding cystography. NVF repair was performed using a transvaginal approach, which included circumferential incision of the fistula tract, creation of a plane between the neobladder serosa and the vaginal epithelium, and multi-layered transvaginal closure.Results: During a median follow-up of 47.9 months, NVF was identified in 12 (8.8%) of the 163 included women. Eight (66.7%) fistulas were located in the proximal anterior vaginal wall and four (33.3%) in the vaginal apex. Median time from RC to NVF repair was 3.4 months (range, 2.1– 5.6 months), median NVF size was 6.0 mm (range, 4.0– 22.0 mm), and median duration of urethral Foley catheter indwelling was 24.0 days (range, 15.0– 43.0 days). Initial repair of NVF was successful in ten (83.3%) patients. Two (16.7%) patients who relapsed retained IONB through the subsequent operation. Two (16.7%) patients developed severe urinary incontinence after NVF repair, requiring anti-incontinence surgery with a synthetic transobturator mid-urethral sling.Conclusion: The transvaginal approach for NVF repair is feasible, yielding successful surgical outcomes. However, women should be counseled about the risks of relapse and urinary incontinence.Keywords: neobladder-vaginal fistula, orthotopic urinary diversion, radical cystectomy, surgical outcomes, vaginal approach

Dong Hyeon Lee,1 Wan Song2 1Department of Urology, Ewha Womans University Medical Center, Ewha Womans University School of Medicine, Seoul, Korea; 2Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaCorrespondence: Wan SongDepartment of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, KoreaTel +82-2-3410-3558Fax +82-2-3410-3027Email wan.song@samsung.comPurpose: To evaluate the risk factors affecting urethral recurrence (UR) in men after radical cystectomy (RC) with ileal orthotopic neobladder (IONB).Materials and Methods: We retrospectively reviewed 348 men who underwent RC with IONB for bladder cancer between January 2010 and December 2017. Clinicopathologic characteristics, including tumor location (trigone and/or bladder neck), prostatic urethral and/or stromal involvement, presence of carcinoma in situ (CIS), pathologic T and N stage, and urethral resection margin status, were identified. Kaplan–Meier survival analysis was used to illustrate urethral recurrence-free survival (URFS), and Cox proportional hazard models were applied to identify factors predicting UR.Results: Of the 348 patients, UR was identified in 7 (2.0%) patients during the mean follow-up of 33.3 months. The 2-, 3-, and 5-year URFS rates were 97.6%, 96.3%, and 93.8%, respectively. On multivariable analysis, prostatic urethral involvement (P = 0.033, hazard ratio: 6.25, 95% confidence interval: 1.06– 36.96) was an independent predictor of UR. When patients were divided according to prostatic urethral involvement (negative vs positive), the 2- and 3-year URFS rates were significantly different (93.8% and 96.8%, respectively, vs 92.0% and 92.0%, respectively; P = 0.020). All 7 patients with UR underwent transurethral surgery and maintained their IONB.Conclusion: In this series, UR occurred in approximately 2% of men after RC with IONB. Prostatic urethral involvement was the only significant prognostic factor for UR. Follow-up strategies considering UR risk should be adopted to facilitate early detection in those at high risk of UR.Keywords: bladder cancer, neobladder, radical cystectomy, risk factor, urethral recurrence

Hye Su Kim,1 Ha-Kyoung Kwon,2 Dong Hoon Lee,1 Thao Nguyen Le,1 Hye-Jin Park,2 Moon Il Kim1 1Department of BioNano Technology, Gachon University, Seongnam, Gyeonggi 13120, Republic of Korea; 2Department of Food Science and Biotechnology, Gachon University, Seongnam, Gyeonggi 13120, Republic of KoreaCorrespondence: Moon Il KimDepartment of BioNano Technology, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam, Gyeonggi 13120, Republic of KoreaTel +82 31 750 8563Fax +82 31 750 4748Email moonil@gachon.ac.krIntroduction: Hair growth-promoting herbal extract mixtures (4HGF) exhibits significant anti-inflammatory activities relevant to promoting hair growth; however, its efficacy in patients with hair loss has been limited majorly due to its low penetration ability into hair follicles. Herein, we prepared hydrogels via dropwise addition of poly(γ-glutamic acid) (PGA) solution containing 4HGF into chitosan (CS) solution, resulting in quick formation of ∼400 nm-sized hydrogel particles through electrostatic interaction-derived ionic gelation with over 50% encapsulation efficiency of 4HGF (PGA-4HGF).Methods: The size and morphology of PGA-4HGF were characterized by TEM, SEM, and dynamic light scattering analyses. Encapsulation efficiency and loading capacity of 4HGF within PGA-4HGF, as well as in vitro release profiles were determined by simply measuring the characteristic absorbance of 4HGF. Penetrating efficiency of PGA-4HGF was evaluated by tracking the respective fluorescence through model porcine skin with confocal laser microscope system. By treating PGA-4HGF on telogenic mice and dermal papilla cells (DPCs), we evaluated the size of hair bulbs in mice, as well as morphological changes in DPCs.Results: Negligible and sustained release of entrapped 4HGF from the hydrogel nanoparticles were observed under acidic and physiological pH conditions, respectively, which is quite advantageous to control their release and prolong their hair growth-promoting effect. The hydrogel nanoparticles were penetrable through the porcine skin after incubation with or without shaking. After treating telogenic mice and DPCs with PGA-4HGF, we detected enlargement of hair bulbs and remarkable shape changes, respectively, thereby showing its potential in induction of hair growth.Conclusion: These results suggest that the hydrogel nanoparticle formulation developed in this study can be employed as a potential approach for the preservation of hair growth-promoting compounds, their delivery of into hair follicles, and enhancing hair growth.Keywords: hair growth, poly(γ-glutamic acid), chitosan, hydrogel nanoparticle, cosmeceutical

Kiyoung Lee,1,2 Ie Byung Park,1,2 Seung Hee Yu,2 Soo-Kyung Kim,3 So Hun Kim,4 Da Hea Seo,4 Seongbin Hong,4 Ja Young Jeon,5 Dae Jung Kim,5 Soo Wan Kim,6 Cheol Soo Choi,1,2 Dae Ho Lee1,21Department of Internal Medicine, Gachon University College of Medicine, Incheon, Republic of Korea; 2Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 3Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea; 4Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea; 5Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea; 6Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaAim: We aimed to evaluate the clinical utility of blood ketone measurement and to test the performance of the diagnostic criteria for diabetic ketoacidosis (DKA) issued by the American Diabetes Association, the Joint British Diabetes Societies, and the American Association of Clinical Endocrinologists and the American College of Endocrinology.Methods: This retrospective analysis included 278 patients with suspected DKA who were hospitalized at 4 university hospitals and aged ≥16 years with a blood glucose level of >200 mg/dL and a blood ketone level of ≥1.0 mmol/L as well as other biochemical data. The patients were categorized into four subgroups (ketosis, typical DKA, atypical DKA, and DKA + lactic acidosis). Atypical DKA in each analysis was defined by our supplementary criteria if the biochemical data did not meet each set of diagnostic criteria from the aforementioned societies.Results: Blood ketone levels in patients with diabetic ketosis and those with DKA varied widely, 1.05–5.13 mmol/L and 1.02–15.9 mmol/L, respectively. Additionally, there were significant discrepancies between the guidelines in the diagnosis of DKA. Thus, the proportion of patients with atypical DKA ranged from 16.5% to 42.4%. Notably, the in-hospital mortality was comparable between patients with typical and atypical DKA, with a very high mortality in patients with DKA + lactic acidosis (blood lactate >5 mmol/L).Conclusions: Our results showed that considering variable presentations of DKA, blood ketone data need to be interpreted cautiously along with other biochemical data and suggested that a new system is required to better characterize DKA.Keywords: Diabetic ketoacidosis, ketone bodies, diagnosis, lactic acidosis, acid base imbalance

Dongseong Shin,1,2 Young Sil Eom, 3,4 Suk Chon,5 Byung-Joon Kim, 3,4 Kyung-Sang Yu,6,* Dae Ho Lee 3,4,*1Department of Pharmacology, Gachon University College of Medicine, Incheon, Korea; 2Clinical Trials Center, Gachon University Gil Medical Center, Incheon, Korea; 3Department of Internal Medicine, Gachon University College of Medicine, Incheon, Korea; 4Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea; 5Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea; 6Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea*These authors contributed equally to this workBackground and objective: The effects of age and related factors on insulin sensitivity have not been definitively evaluated in East Asian populations. We proposed a reference range for the glucose disposal rate (M-value) on hyperinsulinemic-euglycemic study and its association with other parameters.Methods: Healthy, non-diabetic young (n=10) and elderly (n=13) male subjects with normal body mass index were eligible for this study. Subjects who passed the oral glucose tolerance test (OGTT) underwent hyperinsulinemic-euglycemic clamp with high-dose (80 mU/m2·min) insulin infusion.Results: M-values were normalized to body weight (MBW) and fat-free mass (MFFM). Neither M-value was significantly different between age groups (P=0.458 and P=0.900, respectively). An inverse correlation was observed between MFFM and baseline insulin (r=−0.418; P=0.047), baseline C-peptide (r=−0.426; P=0.043) and OGTT 2-hour glucose (r=−0.452; P=0.030). Regarding correlations with other insulin sensitivity indices, M-values were positively associated with the Matsuda index but not with homeostasis model assessment of insulin resistance.Conclusion: Our results suggest that age is not a critical determinant of insulin sensitivity, while fasting insulin and C-peptide levels, OGTT 2-hour glucose level, and Matsuda index are predictable markers of insulin sensitivity in healthy Koreans.Keywords: insulin sensitivity, hyperinsulinemic-euglycemic clamp, glucose disposal rate, age, Matsuda index

Hong Jun Kim,1 Min Jee Jo,2 Bo Ram Kim,2 Jung Lim Kim,2 Yoon A Jeong,2 Yoo Jin Na,2 Seong Hye Park,2 Suk-young Lee,1 Dae-Hee Lee,1,2 Baek-hui Kim,3 Young Do Yoo,4 Sang Cheul Oh1,2 1Division of Oncology and Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea; 2Laboratory of Oncology, Graduate School of Medicine, Korea University, Seoul, Republic of Korea; 3Department of Pathology, College of Medicine, Korea University, Seoul, Republic of Korea; 4Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University, Seoul, Republic of Korea Introduction: Reactive oxygen species modulator-1 (Romo1) is a protein that modulates levels of reactive oxygen species (ROS) and has been reported to affect cancer cell invasion and proliferation via persistent inflammation. Several studies have demonstrated the clinical application of Romo1 as a prognostic marker in non-small cell lung cancer (NSCLC); however, there have been no studies investigating the mechanism by which Romo1 adversely affects the prognosis of these patients. Methods: We examined Romo1, ROS, and vascular endothelial growth factor (VEGF) in tumor tissues immunohistochemically. We conducted survival analyses of patients who had curative resection (n=30) in accordance with clinical parameters including levels of Romo1 expression. Results: Romo1 levels were associated with serologic inflammatory markers and high lymphatic metastatic tendencies. Significantly longer disease-free survival (68.7 vs 24.2 months, P=0.031) and overall survival (92.7 vs 51.6 months) were observed in the group with low Romo1 compared with high Romo1. Survival outcomes were also significantly associated with serologic inflammatory markers. Spearman’s correlation analyses demonstrated significant positive correlations of Romo1 expression with VEGF-C (P=0.008, R=0.478) and ROS (P=0.016, R=0.436) in tumor samples. Conclusion: The current study demonstrates that Romo1 induces lymphatic metastasis of NSCLC by modulating persistent inflammation and oxidative stress (ROS)/VEGF signaling. Lymphatic metastasis associated with elevated Romo1 was shown to be a key reason for unfavorable survival rates. Keywords: non–small cell lung carcinoma, inflammation, reactive oxygen species modulator-1, vascular endothelial growth factor A, reactive oxygen species

We present a theoretical framework for understanding the behavior of the normal and superconducting states of overdoped cuprate high temperature superconductors in the vicinity of the doping-tuned quantum superconductor-to-metal transition. The key ingredients on which we focus are d-wave pairing, a flat antinodal dispersion, and disorder. Even for homogeneous disorder, these lead to effectively granular superconducting correlations and a superconducting transition temperature determined in large part by the superfluid stiffness rather than the pairing scale.

Fluctuating superconductivity—vestigial Cooper pairing in the resistive state of a material—is usually associated with low dimensionality, strong disorder, or low carrier density. Here, we report single-particle spectroscopic, thermodynamic and magnetic evidence for persistent superconducting fluctuations in the heavily hole-doped cuprate superconductor () despite the high carrier density. With a sign-problem-free quantum Monte Carlo calculation, we show how a partially flat band at can help enhance superconducting phase fluctuations. Finally, we discuss the implications of an anisotropic band structure on the phase-coherence-limited superconductivity in overdoped cuprates and other superconductors.

The non-regularizability of free fermion field theories, which is the root of various quantum anomalies, plays a central role in particle physics and modern condensed matter physics. In this paper, we generalize the Nielsen-Ninomiya theorem to all minimal nodal free fermion field theories protected by the time reversal, charge conservation, and charge conjugation symmetries. We prove that these massless field theories cannot be regularized on a lattice.

Superconductivity emerges in proximity to a nematic phase in most iron-based superconductors. It is therefore important to understand the impact of nematicity on the electronic structure. Orbital assignment and tracking across the nematic phase transition prove to be challenging due to the multiband nature of iron-based superconductors and twinning effects. Here, we report a detailed study of the electronic structure of fully detwinned FeSe across the nematic phase transition using angle-resolved photoemission spectroscopy. We clearly observe a nematicity-driven band reconstruction involving dxz, dyz, and dxy orbitals. The nematic energy scale between dxz and dyz bands reaches a maximum of 50 meV at the Brillouin zone corner. We are also able to track the dxz electron pocket across the nematic transition and explain its absence in the nematic state. Our comprehensive data of the electronic structure provide an accurate basis for theoretical models of the superconducting pairing in FeSe.

We study strong electron-phonon interacting systems where the geometry of the crystalline lattice frustrates the formation of charge order. Our results show that under such condition, high-Tc superconductivity can occur in a wide range of electron-phonon coupling strengths. This result is obtained by studying the Holstein model on triangular lattice using sign-problem-free quantum Monte Carlo method.

In an earlier work [1] we developed a holographic theory for the phase transition between bosonic symmetry-protected topological (SPT) states. This paper is a continuation of it. Here we present the holographic theory for fermionic SPT phase transitions. We show that in any dimension d, the critical states of fermionic SPT phase transitions has an emergent Z2T symmetry and can be realized on the boundary of a d+1-dimensional bulk SPT with an extra Z2T symmetry.

The study of continuous phase transitions triggered by spontaneous symmetry breaking has brought revolutionary ideas to physics. Recently, through the discovery of symmetry protected topological phases, it is realized that continuous quantum phase transition can also occur between states with the same symmetry but different topology. Here we study a specific class of such phase transitions in 1+1 dimensions – the phase transition between bosonic topological phases protected by Zn×Zn. We find in all cases the critical point possesses two gap opening relevant operators: one leads to a Landau-forbidden symmetry breaking phase transition and the other to the topological phase transition. We also obtained a constraint on the central charge for general phase transitions between symmetry protected bosonic topological phases in 1+1D.

Inelastic neutron scattering measurements have been performed to investigate the spin waves of the quasi-one-dimensional antiferromagnetic ladder compound BaFe2S3, where a superconducting transition was observed under pressure [H. Takahashi, Nat. Mater. 14, 1008 (2015)1476-112210.1038/nmat4351; T. Yamauchi, Phys. Rev. Lett. 115, 246402 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.246402]. By fitting the spherically averaged experimental data collected on a powder sample to a Heisenberg Hamiltonian, we find that the one-dimensional antiferromagnetic ladder exhibits a strong nearest-neighbor ferromagnetic exchange interaction (SJR=-71±4 meV) along the rung direction, an antiferromagnetic SJL=49±3 meV along the leg direction, and a ferromagnetic SJ2=-15±2 meV along the diagonal direction. Our data demonstrate that the antiferromagnetic spin excitations are a common characteristic for the iron-based superconductors, while specific relative values for the exchange interactions do not appear to be unique for the parent states of the superconducting materials.

We report an inelastic neutron scattering study of the spin waves of the one-dimensional antiferromagnetic spin ladder compound RbFe2Se3. The results reveal that the products, SJ's, of the spin S and the magnetic exchange interaction J along the antiferromagnetic (leg) direction and the ferromagnetic (rung) direction are comparable with those for the stripe ordered phase of the parent compounds of the iron-based superconductors. The universality of the SJ's implies nearly universal spin wave dynamics and the irrelevance of the fermiology for the existence of the stripe antiferromagnetic order among various Fe-based materials.

We report a combined study of the spin resonances and superconducting gaps for underdoped (Tc=19 K), optimally doped (Tc=25 K), and overdoped (Tc=19 K) Ba(Fe1-xCox)2As2 single crystals with inelastic neutron scattering and angle resolved photoemission spectroscopy. We find a quasi-two-dimensional spin resonance whose energy scales with the superconducting gap in all three compounds. In addition, anisotropic low energy spin excitation enhancements in the superconducting state have been deduced and characterized for the under and optimally doped compounds. Our data suggest that the quasi-two-dimensional spin resonance is a spin exciton that corresponds to the spin singlet-triplet excitations of the itinerant electrons. However, the intensity enhancements of the anisotropic spin excitations are dominated by the out-of-plane spin excitations of the ordered moments due to the suppression of damping in the superconducting state. Hence we offer an interpretation of the double energy scales differing from previous interpretations based on anisotropic superconducting energy gaps and systematically explain the doping-dependent trend across the phase diagram.

We present the results of elastic and inelastic neutron scattering measurements on nonsuperconducting Ba(Fe0.957Cu0.043)2As2, a composition close to a quantum critical point between antiferromagnetic (AFM) ordered and paramagnetic phases. By comparing these results with the spin fluctuations in the low-Cu composition as well as the parent compound BaFe2As2 and superconducting Ba(Fe1-xNix)2As2 compounds, we demonstrate that paramagnon-like spin fluctuations are evident in the antiferromagnetically ordered state of Ba(Fe0.957Cu0.043)2As2, which is distinct from the AFM-like spin fluctuations in the superconducting compounds. Our observations suggest that Cu substitution decouples the interaction between quasiparticles and the spin fluctuations. We also show that the spin-spin correlation length ξ(T) increases rapidly as the temperature is lowered and find ω/T scaling behavior, the hallmark of quantum criticality, at an antiferromagnetic quantum critical point.

A combination of neutron diffraction and angle-resolved photoemission spectroscopy measurements on a pure antiferromagnetic stripe Rb1-δFe1.5-σS2 is reported. A neutron diffraction experiment on a powder sample shows that a 98% volume fraction of the sample is in the antiferromagnetic stripe phase with rhombic iron vacancy order and a refined composition of Rb0.66Fe1.36S2, and that only 2% of the sample is in the block antiferromagnetic phase with 5×5 iron vacancy order. Furthermore, a neutron diffraction experiment on a single crystal shows that there is only a single phase with the stripe antiferromagnetic order with the refined composition of Rb0.78Fe1.35S2, while the phase with block antiferromagnetic order is absent. Angle-resolved photoemission spectroscopy measurements on the same crystal with the pure stripe phase reveal that the electronic structure is gapped at the Fermi level with a gap larger than 0.325 eV. The data collectively demonstrate that the extra 10% iron vacancies in addition to the rhombic iron vacancy order effectively impede the formation of the block antiferromagnetic phase; the data also suggest that the stripe antiferromagnetic phase with rhombic iron vacancy order is a Mott insulator.

An inelastic neutron scattering study of the spin waves corresponding to the stripe antiferromagnetic order in insulating Rb0.8Fe1.5S2 throughout the Brillouin zone is reported. The spin wave spectra are well described by a Heisenberg Hamiltonian with anisotropic in-plane exchange interactions. Integrating the ordered moment and the spin fluctuations results in a total moment squared of 27.6±4.2μB2/Fe, consistent with S≈2. Unlike XFe2As2 (X=Ca, Sr, and Ba), where the itinerant electrons have a significant contribution, our data suggest that this stripe antiferromagnetically ordered phase in Rb0.8Fe1.5S2 is a Mott-like insulator with fully localized 3d electrons and a high-spin ground state configuration. Nevertheless, the anisotropic exchange couplings appear to be universal in the stripe phase of Fe pnictides and chalcogenides.

Li-substituted layered P2-Na0.80[Li0.12Ni 0.22Mn0.66]O2 is investigated as an advanced cathode material for Na-ion batteries. Both neutron diffraction and nuclear magnetic resonance (NMR) spectroscopy are used to elucidate the local structure, and they reveal that most of the Li ions are located in transition metal (TM) sites, preferably surrounded by Mn ions. To characterize structural changes occurring upon electrochemical cycling, in situ synchrotron X-ray diffraction is conducted. It is clearly demonstrated that no significant phase transformation is observed up to 4.4 V charge for this material, unlike Li-free P2-type Na cathodes. The presence of monovalent Li ions in the TM layers allows more Na ions to reside in the prismatic sites, stabilizing the overall charge balance of the compound. Consequently, more Na ions remain in the compound upon charge, the P2 structure is retained in the high voltage region, and the phase transformation is delayed. Ex situ NMR is conducted on samples at different states of charge/discharge to track Li-ion site occupation changes. Surprisingly, Li is found to be mobile, some Li ions migrate from the TM layer to the Na layer at high voltage, and yet this process is highly reversible. Novel design principles for Na cathode materials are proposed on the basis of an atomistic level understanding of the underlying electrochemical processes. These principles enable us to devise an optimized, high capacity, and structurally stable compound as a potential cathode material for high-energy Na-ion batteries. © 2014 American Chemical Society.

Although accurate intracranial pressure (ICP) monitoring is essential for the diagnosis and treatment of severe brain diseases, current methods are performed invasively. Therefore, a safe and less invasive ICP measurement is required. The purpose of our study was to develop a simplified cranial cavity model for a better understanding of the relationship between the ICP and the pressure measurement within the dural venous sinus (DVS) to support the validity of using sinus pressure as the surrogate of the ICP. The in-house cranial cavity model had three components: the brain part, the DVS part, and the subarachnoid space (SAS) part. Pressure in other parts was measured when the pressure in the SAS part and, separately, brain part was increased from 0 (baseline) to 50 mmHg at intervals of 10 mmHg. When the pressure in the SAS part was increased from 10 to 50 mmHg at 10 mmHg interval, pressures of both the brain and DVS parts increased without significant difference (all P > 0.05). However, pressures in both the SAS and DVS parts differed while the pressure in the brain part was increased. The pressures in both parts showed about 70% of the increase in the brain part. Nevertheless, the pressures in the SAS and DVS parts were not significantly different (P > 0.05). A simplified in-house cranial cavity model was developed consisting of three compartments to represent the actual intracranial spaces. The pressure measurement within the DVS was feasible to use as a surrogate for the ICP measurement. [ABSTRACT FROM AUTHOR]

We have performed resistivity and inelastic neutron scattering measurements on three samples of Fe0.98-zCuzTe0.5Se 0.5 with z=0, 0.02, and 0.1. It is found that with increasing Cu doping the sample's resistivity deviates progressively from that of a metal. However, in contrast to expectations that replacing Fe with Cu would suppress the magnetic correlations, the low-energy (≤12 meV) magnetic scattering is enhanced in strength, with greater spectral weight and longer dynamical spin-spin correlation lengths. Such enhancements can be a consequence of either enlarged local moments or a slowing down of the spin fluctuations. In either case, the localization of the conduction states induced by the Cu doping should play a critical role. Our results are not applicable to models that treat 3d transition metal dopants simply as effective electron donors. © 2013 American Physical Society.

We have developed a near-infrared spectrometer designed to measure the absolute intensity of the solar 854.2 nm Ca II Fraunhofer line, scattered by interplanetary dust, in the zodiacal light (ZL) spectrum. Based on the known equivalent line width in the solar spectrum, this measurement can derive the zodiacal brightness, testing models of the ZL based on morphology that are used to determine the extragalactic background light in absolute photometry measurements. The spectrometer is based on a simple high-resolution tipped filter placed in front of a compact camera with wide-field refractive optics to provide the large optical throughput and high sensitivity required for rocket-borne observations. We discuss the instrument requirements for an accurate measurement of the absolute ZL brightness, the measured laboratory characterization, and the instrument performance in flight. © 2013. The American Astronomical Society. All rights reserved.