Publications by authors named "Hyun Kim"

6,912 Publications

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Thoracoscopic anterior mediastinal mass removal using an articulating laparoscopic instrument.

Interact Cardiovasc Thorac Surg 2021 Apr 21. Epub 2021 Apr 21.

Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Republic of Korea.

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http://dx.doi.org/10.1093/icvts/ivab110DOI Listing
April 2021

Clinical profile of cutaneous adverse events of immune checkpoint inhibitors in a single tertiary center.

J Dermatol 2021 Apr 20. Epub 2021 Apr 20.

Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have demonstrated their efficacy in the treatment of various malignancies. Despite their benefits, their immunomodulatory activities can cause unpredictable cutaneous adverse events (CAE). This study aimed to identify characteristics of CAE in patients treated with PD-1/PD-L1 inhibitors through the medical records, photographs, and pathology reports. Fifty CAE occurred in 47 (2.75%) of 1711 patients treated with PD-1/PD-L1 inhibitors. Pruritic, psoriasiform, urticarial, and acneiform eruptions were the four most common types. Melanoma patients showed CAE more frequently than other malignancies. Acneiform eruption occurred more often at ages under 60 years. Urticarial eruption appeared earlier, while keratoacanthoma appeared later after immunotherapy. The overall survival times were not significantly different between the two groups with and without CAE by Kaplan-Meier analysis (p = 0.055). Studies on CAE may provide more information to understand these drugs and to help manage the patients.
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http://dx.doi.org/10.1111/1346-8138.15824DOI Listing
April 2021

Description of Nocardioides piscis sp. nov., Sphingomonas piscis sp. nov. and Sphingomonas sinipercae sp. nov., isolated from the intestine of fish species Odontobutis interrupta (Korean spotted sleeper) and Siniperca scherzeri (leopard mandarin fish).

J Microbiol 2021 Apr 20. Epub 2021 Apr 20.

Department of Biology and Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, 02447, Republic of Korea.

A polyphasic taxonomic approach was used to characterize three novel bacterial strains, designated as HDW12A, HDW-15B, and HDW15C, isolated from the intestine of fish species Odontobutis interrupta or Siniperca scherzeri. All isolates were obligate aerobic, non-motile bacteria, and grew optimally at 30°C. Phylogenetic analysis based on 16S rRNA sequences revealed that strain HDW12A was a member of the genus Nocardioides, and closely related to Nocardioides allogilvus CFH 30205 (98.9% sequence identities). Furthermore, strains HDW15B and HDW15C were members of the genus Sphingomonas, and closely related to Sphingomonas lutea JS5 and Sphingomonas sediminicola Dae 20 (97.1% and 97.9% sequence identities), respectively. Strain HDW12A contained MK-8 (H), and strains HDW15B and HDW15C contained Q-10 as the respiratory quinone. Major polar lipid components of strain HDW12A were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylinositol, and those of strains HDW15B and HDW15C were sphingoglycolipid, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylcholine. The G + C content of strains HDW12A, HDW15B, and HDW15C were 69.7, 63.3, and 65.5%, respectively. The results of phylogenetic, phenotypic, chemotaxonomic, and genotypic analyses suggest that strain HDW12A represents a novel species within the genus Nocardioides, and strains HDW15B and HDW15C represent two novel species within the genus Sphingomonas. We propose the names Nocardioides piscis for strain HDW12A (= KACC 21336 = KCTC 49321 = JCM 33670), Sphingomonas piscis for strain HDW15B (= KACC 21341 = KCTC 72588 = JCM 33738), and Sphingomonas sinipercae for strain HDW15C (= KACC 21342 = KCTC 72589 = JCM 33739).
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http://dx.doi.org/10.1007/s12275-021-1036-5DOI Listing
April 2021

Smoking and Drinking Adjusted Association between Head and Neck Cancers and Oral Health Status Related to Periodontitis: a Meta-Analysis.

J Korean Med Sci 2021 Apr 19;36(15):e98. Epub 2021 Apr 19.

Department of Preventive and Social Dentistry, School of Dentistry, Seoul National University, Seoul, Korea.

Background: Not so many reports about the association between head and neck cancer (HNC) and oral health status related to periodontitis (OHS-P) has been published in different countries with different methods. So, there is a need for an extensive meta-analysis with the total articles published until 2020. Hence, this study aimed to estimate the association between HNC and OHS-P through a meta-analysis.

Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines, 22 studies were selected through PubMed and Cochrane Library databases. Meta-analysis using them was performed to evaluate the association. The risk of bias assessment using the Newcastle-Ottawa Scale (NOS) was applied to evaluate the quality of non-randomized studies. Publication bias was evaluated by funnel plot and Egger's regression test.

Results: Since heterogeneity was significant (I² = 88%, < 0.001), we adopted the random effect model for 22 studies. Those with bad OHS-P, compared to those with good OHS-P, were more likely to have the risk of HNC by 2.4 times (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.88-3.13) for random effect model. The association included publication bias (Egger's regression, value < 0.001). The association among five studies (I² = 39%, = 0.16) using alveolar bone loss (ABL) or clinical attachment level (CAL) for assessing periodontitis increased to OR of 3.85 (CI, 3.04-4.88) in the fixed effect model without publication bias (Egger's regression, = 0.66). Moreover, the association was higher in 10 fair or good NOS studies (OR, 3.08) and in 7 Asian studies (OR, 2.68), which were from the fixed model without publication bias.

Conclusion: Our meta-analysis showed that bad OHS-P was associated with the risk of HNC. The association was stronger in studies using ABL or CAL for assessing periodontitis.
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http://dx.doi.org/10.3346/jkms.2021.36.e98DOI Listing
April 2021

Investigation of antioxidant and anticancer activities of unsaturated oligo-galacturonic acids produced by pectinase of Streptomyces hydrogenans YAM1.

Sci Rep 2021 Apr 19;11(1):8491. Epub 2021 Apr 19.

Department of Chemical Engineering, Soongsil University, Seoul, 06978, Republic of Korea.

Pectin, a diverse carbohydrate polymer in plants consists of a core of α-1,4-linked D-galacturonic acid units, includes a vast portion of fruit and agricultural wastes. Using the wastes to produce beneficial compounds is a new approach to control the negative environmental impacts of the accumulated wastes. In the present study, we report a pectinase producing bacterium Streptomyces hydrogenans YAM1 and evaluate antioxidative and anticancer effects of the oligosaccharides obtained from pectin degradation. The production of oligosaccharides due to pectinase activity was detected by thin layer chromatography (TLC) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Our results revealed that S. hydrogenans YAM1 can degrade pectin to unsaturated pectic oligo-galacturonic acids (POS) with approximately 93% radical scavenging activity in 20 mg/mL which it is more than 50% of the same concentration of pectin. Flow cytometric analysis revealed that MCF-7 cells viability decreased more than 32 and 92% following treatment with 6 and 20 mg/mL POS after 24 h, respectively. It is suggested that pectin degradation by S. hydrogenans YAM1 is not only a new approach to produce highly active compounds from fruit wastes, but also is an effective method to remove fibrous pollutants from different environments.
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http://dx.doi.org/10.1038/s41598-021-87804-9DOI Listing
April 2021

Significance of albumin to globulin ratio as a predictor of febrile urinary tract infection after ureteroscopic lithotripsy.

Yeungnam Univ J Med 2021 Apr 20. Epub 2021 Apr 20.

Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea.

Background: We aimed to analyze the effectiveness of albumin to globulin ratio (AGR) in predicting postoperative febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URS) and retrograde intrarenal surgery (RIRS).

Methods: From January 2013 to May 2018, 332 patients underwent URS and RIRS. The rate of postoperative fUTI and risk factors for postoperative fUTI were analyzed using logistic regression. Patients were divided into postoperative fUTI and non-postoperative fUTI (non-fUTI) groups. AGR with other demographic and perioperative data were compared between the two groups to predict the development of fUTI after URS.

Results: Of the 332 patients, postoperative fUTI occurred in 41 (12.3%). Preoperative pyuria, microscopic hematuria, diabetes mellitus, hypoalbuminemia, and hyperglobulinemia were more prevalent in the fUTI group. Patients in the fUTI group had larger stone size, lower preoperative AGR, longer operation time, and longer preoperative antibiotic coverage period. In a multivariable logistic analysis, preoperative pyuria, AGR, and stone size were independently correlated with postoperative fUTI (p<0.001, p=0.008, and p=0.041, respectively). Receiver operating curve analysis showed that the cutoff value of AGR that could predict a high risk of fUTI after URS was 1.437 (sensitivity, 77.3%; specificity, 76.9%), while the cutoff value of stone size was 8.5 mm (sensitivity, 55.3%; specificity, 44.7%).

Conclusion: This study demonstrated that preoperative pyuria, AGR, and stone size can serve as prognostic factors for predicting fUTI after URS.
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http://dx.doi.org/10.12701/yujm.2021.00955DOI Listing
April 2021

Theranostic potential of biodegradable polymeric nanoparticles with paclitaxel and curcumin against breast carcinoma.

Biomater Sci 2021 Apr 19. Epub 2021 Apr 19.

Department of BIN Convergence Technology, Department of Polymer Nano Science & Technology, Jeonbuk National University, Jeonju, 54896, Republic of Korea.

In this study, integrin-mediated targeting and near-infrared fluorescence (NIRF) traceable polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-PLGA)-based polymeric nanoparticles (NPs) were prepared to investigate the effects of paclitaxel (PTX) and curcumin (CUR) combination therapy on breast cancer. Cyclic (arginine-glycine-aspartic acid-phenylalanine-lysine) (cRGDfK) was selected as a ligand for breast cancer and conjugated to the end of NPs (cRGDfK-NPs). For fluorescence imaging, sulfo-cyanine 5.5 (Cy5.5) was incorporated into NPs (Cy5.5-NPs). A series of hybrid NPs consisting of NPs, cRGDfK-NPs, and Cy5.5-NPs with drugs encapsulated inside the core (Cy5.5-cRGDfK-NPs/PTX + CUR) were prepared by self-assembly. The efficacy of PTX and CUR combination and the ability of the integrin-mediated targeting of NPs were systemically investigated using a 4T1 mouse breast cancer cell line and a nude mouse xenograft model. We suggested that Cy5.5-cRGDfK-NPs/PTX + CUR has superior theranostic potential against breast carcinoma.
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http://dx.doi.org/10.1039/d1bm00370dDOI Listing
April 2021

Improvement of testosterone deficiency by fermented extracts in aging male rats.

Food Sci Biotechnol 2021 Mar 6;30(3):443-454. Epub 2021 Feb 6.

Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Geosan-eup , Goesan-gun, Chungbuk 28024 South Korea.

This study evaluated the efficacy of (MC; bitter melon) extracts against andropause symptoms. We fermented MC with and verified the ability of the fermented MC extracts (FMEs) to control testosterone deficiency by using aging male rats as an animal model of andropause. FME administration considerably increased total and free testosterone levels, muscle mass, forced swimming time, and total and motile sperm counts in aging male rats. In contrast, sex hormone-binding globulin, retroperitoneal fat, serum cholesterol, and triglyceride levels were significantly reduced in the treated groups compared to the non-treated control aging male rats. Furthermore, we observed that FME enhanced the expression of testosterone biosynthesis-related genes but reduced the expression of testosterone degradation-related genes in a mouse Leydig cell line. These results suggest that FME has effective pharmacological activities that increase and restore free testosterone levels and that FME may be employed as a promising natural product for alleviating testosterone deficiency syndrome.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-020-00872-x.
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http://dx.doi.org/10.1007/s10068-020-00872-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017075PMC
March 2021

Identification and Characterization of Xanthomonas arboricola pv. juglandis Causing Bacterial Blight of Walnuts in Korea.

Plant Pathol J 2021 Apr 1;37(2):137-151. Epub 2021 Apr 1.

Department of Plant Medicals, Andong National University, Andong 36729, Korea.

The present study describes the bacterial blight of walnut, caused by Xanthomonas arboricola pv. juglandis (Xaj) in the northern Gyeongbuk province, Korea. Disease symptoms that appear very similar to anthracnose symptoms were observed in walnut trees in June 2016. Pathogens were isolated from disease infected leaves, fruits, shoots, bud, flower bud of walnut, and cultured onto yeast dextrose carbonate agar plates. Isolated bacteria with bacterial blight symptoms were characterized for their nutrient utilization profiles using Biolog GN2 and Vitek 2. In addition, isolates were subjected to physiological, biochemical, and morphological characterizations. Furthermore, isolates were identified using 16S rDNA sequence analysis, and multi-locus sequence analysis using atpD, dnaK, efp, and rpoD. To confirm pathogenicity, leaves, fruits, and stems of 3-year-old walnut plants were inoculated with bacterial pathogen suspensions as a foliar spray. One week after inoculation, the gray spots on leaves and yellow halos around the spots were developed. Fruits and stems showed browning symptoms. The pathogen Xaj was re-isolated from all symptomatic tissues to fulfill Koch's postulates, while symptoms were not appeared on control plants. On the other hand, the symptoms were very similar to the symptoms of anthracnose caused by Colletotrichum gloeosporioides. When walnut plants were inoculated with combined pathogens of Xaj and C. gloeosporioides, disease symptoms were greater in comparison with when inoculated alone. Xaj population size was more in the month of April than March due to their dormancy in March, and sensitive to antibiotics such as oxytetracycline and streptomycin, while resistant to copper sulfate.
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http://dx.doi.org/10.5423/PPJ.OA.12.2020.0217DOI Listing
April 2021

Morphology and histology of the olfactory organ of two African lungfishes, Protopterus amphibius and P. dolloi (Lepidosirenidae, Dipnoi).

Appl Microsc 2021 Apr 17;51(1). Epub 2021 Apr 17.

Department of Biological Science and Institute for Biodiversity Research, College of Natural Sciences, Jeonbuk National University, Jeonju, 54896, South Korea.

The olfactory organs of two African lungfishes, Protopterus amphibius and P. dolloi, were investigated using a stereo microscope and a compound light microscope and were described anatomically, histologically, and histochemically. Like other lungfishes, these species present the following general features: i) elongated olfactory chamber (OC), ii) anterior nostril at the ventral tip of the upper lip, iii) posterior nostril on the palate of the oral cavity, iv) lamellae with multiple cell types such as olfactory receptor neurons, supporting cells, basal cells, lymphatic cells, and mucous cells (MC), and vi) vomero-like epithelial crypt (VEC) made of glandular epithelium (GE) and crypt sensory epithelium. Some of these features exhibit differences between species: MCs are abundant in both the lamellar and inner walls of the OC in P. amphibius but occur only in lamellae in P. dolloi. On the other hand, some between feature differences are consistent across species: the GE of both P. amphibius and P. dolloi is strongly positive for Alcian blue (pH 2.5)-periodic acid Schiff (deep violet coloration), and positive with hematoxylin and eosin and with Masson's trichrome (reddish-brown staining), unlike the MCs of the two species which stain dark red with both Alcian blue (pH 2.5)-periodic acid Schiff and Masson's trichrome but respond faintly to hematoxylin and eosin. The differing abundance of MCs in the two lungfishes might reflect different degrees in aerial exposure of the olfactory organ, while the neutral and acid mucopolysaccharide-containing VEC, as indicated by staining properties of the MCs, is evolutionary evidence that P. amphibius and P. dolloi are the closest living relatives to tetrapods, at least in the order Dipnoi.
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http://dx.doi.org/10.1186/s42649-021-00054-xDOI Listing
April 2021

Selective colorimetric urine glucose detection by paper sensor functionalized with polyaniline nanoparticles and cell membrane.

Anal Chim Acta 2021 May 12;1158:338387. Epub 2021 Mar 12.

Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, South Korea; Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, South Korea. Electronic address:

For the diabetes diagnosis, noninvasive methods are preferred to invasive methods; urine glucose measurement is an example of a noninvasive method. However, conventional noninvasive methods for urine glucose measurement are not intuitive. Furthermore, such methods exhibit low selectivity because they can detect interfering molecules in addition to glucose. Herein, we fabricate a noninvasive, intuitive, and highly selective paper sensor consisting of polyaniline nanoparticles (PAni-NPs) and red blood cell membranes (RBCMs). The PAni-NPs (adsorbed on the paper) are highly sensitive to hydrogen ions and change color from emeraldine blue to emeraldine green within a few seconds. The RBCM (coated on the PAni-NP-adsorbed paper) having the glucose transporter-1 protein plays the role of a smart filter that transports glucose but rejects other interfering molecules. In particular, the selectivity of the RBCM-coated PAni-NP-based paper sensor was approximately improved ∼85%, compared to the uncoated paper sensors. The paper sensor could detect urine glucose over the range of 0-10 mg/mL (0-56 mM), with a limit of detection of 0.54 mM. The proposed paper sensor will facilitate the development of a highly selective and colorimetric urine glucose monitoring system.
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http://dx.doi.org/10.1016/j.aca.2021.338387DOI Listing
May 2021

From Chaos to Control: Programmable Crack Patterning with Molecular Order in Polymer Substrates.

Adv Mater 2021 Apr 15:e2008434. Epub 2021 Apr 15.

Department of Bioengineering, University of Texas at Dallas, Richardson, TX, 75080, USA.

Cracks are typically associated with the failure of materials. However, cracks can also be used to create periodic patterns on the surfaces of materials, as observed in the skin of crocodiles and elephants. In synthetic materials, surface patterns are critical to micro- and nanoscale fabrication processes. Here, a strategy is presented that enables freely programmable patterns of cracks on the surface of a polymer and then uses these cracks to pattern other materials. Cracks form during deposition of a thin film metal on a liquid crystal polymer network (LCN) and follow the spatially patterned molecular order of the polymer. These patterned sub-micrometer scale cracks have an order parameter of 0.98 ± 0.02 and form readily over centimeter-scale areas on the flexible substrates. The patterning of the LCN enables cracks that turn corners, spiral azimuthally, or radiate from a point. Conductive inks can be filled into these oriented cracks, resulting in flexible, anisotropic, and transparent conductors. This materials-based processing approach to patterning cracks enables unprecedented control of the orientation, length, width, and depth of the cracks without costly lithography methods. This approach promises new architectures of electronics, sensors, fluidics, optics, and other devices with micro- and nanoscale features.
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http://dx.doi.org/10.1002/adma.202008434DOI Listing
April 2021

constituent fargesin has an anti-allergic effect ORAI1 channel inhibition.

Korean J Physiol Pharmacol 2021 May;25(3):251-258

Department of Physiology, Dongguk University College of Medicine, Gyeongju 38066, Korea.

magnoliae (FM), the dry flower buds of or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4 T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC = 12.46 ± 1.300 µM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 µM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.
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http://dx.doi.org/10.4196/kjpp.2021.25.3.251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050608PMC
May 2021

Establishment of Local Diagnostic Reference Levels of Pediatric Abdominopelvic and Chest CT Examinations Based on the Body Weight and Size in Korea.

Korean J Radiol 2021 Apr 1. Epub 2021 Apr 1.

Department of Radiology, Ajou University Hospital, School of Medicine, Ajou University, Suwon, Korea.

Objective: The purposes of this study were to analyze the radiation doses for pediatric abdominopelvic and chest CT examinations from university hospitals in Korea and to establish the local diagnostic reference levels (DRLs) based on the body weight and size.

Materials And Methods: At seven university hospitals in Korea, 2494 CT examinations of patients aged 15 years or younger (1625 abdominopelvic and 869 chest CT examinations) between January and December 2017 were analyzed in this study. CT scans were transferred to commercial automated dose management software for the analysis after being de-identified. DRLs were calculated after grouping the patients according to the body weight and effective diameter. DRLs were set at the 75th percentile of the distribution of each institution's typical values.

Results: For body weights of 5, 15, 30, 50, and 80 kg, DRLs (volume CT dose index [CTDI]) were 1.4, 2.2, 2.7, 4.0, and 4.7 mGy, respectively, for abdominopelvic CT and 1.2, 1.5, 2.3, 3.7, and 5.8 mGy, respectively, for chest CT. For effective diameters of < 13 cm, 14-16 cm, 17-20 cm, 21-24 cm, and > 24 cm, DRLs (size-specific dose estimates [SSDE]) were 4.1, 5.0, 5.7, 7.1, and 7.2 mGy, respectively, for abdominopelvic CT and 2.8, 4.6, 4.3, 5.3, and 7.5 mGy, respectively, for chest CT. SSDE was greater than CTDI in all age groups. Overall, the local DRL was lower than DRLs in previously conducted dose surveys and other countries.

Conclusion: Our study set local DRLs in pediatric abdominopelvic and chest CT examinations for the body weight and size. Further research involving more facilities and CT examinations is required to develop national DRLs and update the current DRLs.
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http://dx.doi.org/10.3348/kjr.2020.0890DOI Listing
April 2021

Perforation on the superior side of duodenum is a risk factor of laparoscopic primary repair for duodenal ulcer perforation.

Ann Surg Treat Res 2021 Apr 30;100(4):228-234. Epub 2021 Mar 30.

Department of Surgery, Hanyang University Guri Hospital, Hanyang University School of Medicine, Guri, Korea.

Purpose: Primary repair is the standard surgical method for treating duodenal ulcer perforations, with very good results usually anticipated because of the simplicity of the associated surgical techniques. Therefore, this study aimed to analyze the risk factors that affect laparoscopic primary repair outcomes for duodenal ulcer perforation.

Methods: Between June 2010 and June 2020, 124 patients who underwent laparoscopic primary repair for duodenal ulcer perforations were reviewed. Early surgical outcomes were evaluated and risk factors for postoperative complications were assessed.

Results: All surgeries were performed laparoscopically without open conversion. Multivariate analysis showed that the elderly (over 70 years), and perforations that needed more than 2 stitches for closure were risk factors for overall postoperative complications. Perforations that needed more than 2 stitches and perforations on the superior side of the duodenum were major risk factors for severe postoperative complications. Severe postoperative complications occurred in 6 of the patients, and 1 of them died of multiorgan failure.

Conclusion: Based on our results, we suggest that laparoscopic primary repair can be safely performed in duodenal ulcer perforation. However, more careful surgery and postoperative care are needed to improve the surgical outcomes of patients who need more than 2 stitches to close their perforation or who have perforations on the superior side of the duodenum.
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http://dx.doi.org/10.4174/astr.2021.100.4.228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019982PMC
April 2021

Direct Growth of Highly Conductive Large-Area Stretchable Graphene.

Adv Sci (Weinh) 2021 Apr 1;8(7):2003697. Epub 2021 Feb 1.

Department of Materials Science and Engineering Chungnam National University Daeduk Science Town Daejeon 34134 Republic of Korea.

The direct synthesis of inherently defect-free, large-area graphene on flexible substrates is a key technology for soft electronic devices. In the present work, in situ plasma-assisted thermal chemical vapor deposition is implemented in order to synthesize 4 in. diameter high-quality graphene directly on 10 nm thick Ti-buffered substrates at 100 °C. The in situ synthesized monolayer graphene displays outstanding stretching properties coupled with low sheet resistance. Further improved mechanical and electronic performances are achieved by the in situ multi-stacking of graphene. The four-layered graphene multi-stack is shown to display an ultralow resistance of ≈6 Ω sq, which is consistently maintained during the harsh repeat stretching tests and is assisted by self--doping under ambient conditions. Graphene-field effect transistors fabricated on polydimethylsiloxane substrates reveal an unprecedented hole mobility of ≈21 000 cm V s at a gate voltage of -4 V, irrespective of the channel length, which is consistently maintained during the repeat stretching test of 5000 cycles at 140% parallel strain.
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http://dx.doi.org/10.1002/advs.202003697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025006PMC
April 2021

Delphi Consensus Recommendations on Management of Dosing, Adverse Events, and Comorbidities in the Treatment of Idiopathic Pulmonary Fibrosis with Nintedanib.

Clin Med Insights Circ Respir Pulm Med 2021 30;15:11795484211006050. Epub 2021 Mar 30.

Vanderbilt University School of Medicine, Nashville, TN, USA.

Purpose: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF), which slows disease progression. Management of patients with IPF receiving nintedanib can be complicated by tolerability issues, comorbidities, and concomitant medications. We developed consensus recommendations on the management of dosing, adverse events and comorbidities in patients with IPF treated with nintedanib.

Methods: A modified Delphi process using 3 questionnaires was used to survey 14 pulmonologists experienced in using nintedanib. Panelists rated their agreement with statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). Consensus was predefined as a mean score of ⩽-2.5 or ⩾+2.5 with a standard deviation not crossing zero.

Results: The panelists' recommendations were largely aligned with clinical trial data, real-world evidence, and the prescribing information, and provided additional guidance regarding minimizing gastrointestinal effects, periodic monitoring for liver dysfunction, caution with respect to concomitant administration of cytochrome P450 3A4 and P-glycoprotein 1 inhibitors and inducers and anticoagulants, and management of comorbidities. The panelists unanimously agreed that adverse event management should be individualized, based on careful consideration of the risks and benefits of each possible intervention and discussion with the patient.

Conclusions: These consensus recommendations provide additional guidance on the appropriate management of IPF with nintedanib, for use alongside evidence-based literature and the prescribing information.
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http://dx.doi.org/10.1177/11795484211006050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013629PMC
March 2021

The effects of direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute exacerbation of interstitial lung disease.

Acute Crit Care 2021 Apr 15. Epub 2021 Apr 15.

Division of Pulmonology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.

Background: Acute exacerbation of interstitial lung disease (AE-ILD) causes clinically significant deterioration and has an extremely poor prognosis with high mortality. There are currently no demonstrated effective treatments. Recently, several studies reported the effectiveness of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) in patients with AE-ILD as a potential therapy. This study describes the clinical effectiveness and safety of PMX-DHP in patients with AE-ILD.

Methods: We retrospectively reviewed the medical records of 10 patients (11 episodes) with AE-ILD treated with PMX-DHP from January 2018 to June 2019. We compared laboratory and physiologic data of the ratio of partial pressure arterial oxygen to fraction of inspired oxygen (P/F ratio) and inflammatory markers before and after implementation of PMX-DHP.

Results: Ten patients (11 episodes) were included according to the 2016 revised definition of acute exacerbation of idiopathic pulmonary fibrosis (IPF). Nine patients had IPF and one patient had fibrotic nonspecific interstitial pneumonia. Most patients (90.9%) were treated with a steroid pulse, and four patients (36.4%) were treated with an immunosuppressant. The median number of PMX-DHP cycles was 2, and the median duration of each cycle was 6 hours. After PMX-DHP, the mean P/F ratio improved (86 [range, 63-106] vs. 145 [86-260], P=0.030) and interleukin-6 and c-reactive protein decreased (79 [35-640] vs. 10 [5-25], P=0.018 and 14 [4-21] vs. 5 [2-6], P=0.019, respectively). The 30-day mortality rate was 27.3% and the 90-day mortality rate was 72.7%. There were no adverse events related to PMX-DHP treatment.

Conclusion: PMX-DHP treatment improved P/F ratio and reduced inflammatory markers in AE-ILD patients.
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http://dx.doi.org/10.4266/acc.2021.00073DOI Listing
April 2021

Formaldehyde exposure and leukemia risk: a comprehensive review and network-based toxicogenomic approach.

Genes Environ 2021 Apr 12;43(1):13. Epub 2021 Apr 12.

Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.

Formaldehyde is a widely used but highly reactive and toxic chemical. The International Agency for Research on Cancer classifies formaldehyde as a Group 1 carcinogen, based on nasopharyngeal cancer and leukemia studies. However, the correlation between formaldehyde exposure and leukemia incidence is a controversial issue. To understand the association between formaldehyde exposure and leukemia, we explored biological networks based on formaldehyde-related genes retrieved from public and commercial databases. Through the literature-based network approach, we summarized qualitative associations between formaldehyde exposure and leukemia. Our results indicate that oxidative stress-mediated genetic changes induced by formaldehyde could disturb the hematopoietic system, possibly leading to leukemia. Furthermore, we suggested major genes that are thought to be affected by formaldehyde exposure and associated with leukemia development. Our suggestions can be used to complement experimental data for understanding and identifying the leukemogenic mechanism of formaldehyde.
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http://dx.doi.org/10.1186/s41021-021-00183-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042688PMC
April 2021

Synthesis of Bidentate Nitrogen Ligands by Rh-Catalyzed C-H Annulation and Their Application to Pd-Catalyzed Aerobic C-H Alkenylation.

Org Lett 2021 Apr 12. Epub 2021 Apr 12.

Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea.

A new class of bidentate ligands was prepared by a modular approach involving Rh-catalyzed C-H annulation reactions. The resulting conformationally constrained ligands enabled the Pd-catalyzed C-H alkenylation at electron-rich and sterically less hindered positions of electron-rich arenes while promoting the facile oxidation of Pd(0) intermediates by oxygen. This newly introduced ligand class is complementary to the ligands developed for Pd-catalyzed oxidative reactions and may find broad application in transition-metal-catalyzed reactions.
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http://dx.doi.org/10.1021/acs.orglett.1c01040DOI Listing
April 2021

Nationwide "Pediatric Nutrition Day" survey on the nutritional status of hospitalized children in South Korea.

Nutr Res Pract 2021 Apr 22;15(2):213-224. Epub 2020 Sep 22.

Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Background/objectives: To evaluate the nutritional status and prevalence of malnutrition in hospitalized children at admission and during hospitalization in South Korea.

Subjects/methods: This first cross-sectional nationwide "Pediatric Nutrition Day (pNday)" survey was conducted among 872 hospitalized children (504 boys, 368 girls; 686 medical, 186 surgical) from 23 hospitals in South Korea. Malnutrition risk was screened using the Pediatric Yorkhill Malnutrition Score (PYMS) and the Screening Tool Risk on Nutritional status and Growth. Nutritional status was assessed by z-scores of weight-for-age for underweight, weight-for-height for wasting, and height-for-age for stunting as well as laboratory tests.

Results: At admission, of the 872 hospitalized children, 17.2% were underweight, and the prevalence of wasting and stunting was 20.2% and 17.3%, respectively. During hospitalization till pNday, 10.8% and 19.6% experienced weight loss and decreased oral intake, respectively. During the aforementioned period, fasting was more prevalent in surgical patients (7.5%) than in medical patients (1.6%) ( < 0.001). According to the PYMS, 34.3% and 30% of the children at admission and on pNday, respectively, had a high-risk of malnutrition, requiring consultation with the nutritional support team (NST). However, only 4% were actually referred to the NST during hospitalization.

Conclusions: Malnutrition was prevalent at admission and during hospitalization in pediatric patients, with many children experiencing weight loss and poor oral intake. To improve the nutritional status of hospitalized children, it is important to screen and identify all children at risk of malnutrition and refer malnourished patients to the multidisciplinary NST for proper nutritional interventions.
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http://dx.doi.org/10.4162/nrp.2021.15.2.213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007407PMC
April 2021

Effects of the fermented in the amyloid β-induced Alzheimer's disease mouse model.

Nutr Res Pract 2021 Apr 25;15(2):173-186. Epub 2020 Sep 25.

Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Backgroud/objectives: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Due to the increased incidence of dementia, there is a corresponding increase concerning the importance of AD. In this study, we investigated the protective effects conferred by (Zj) and fermented by yeast (Zj-Y), on cognitive impairment in an AD mouse model.

Materials/methods: AD was induced by injecting amyloid beta (Aβ) in ICR mice, and subsequently 200 mg/kg Zj or Zj-Y was administered daily for 14 days. The cognitive ability of AD mice was observed through behavioral experiments in T-maze, novel object recognition, and Morris water maze tests. We subsequently measured the levels of malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase, and alanine aminotransferase in either tissues or serum.

Results: In behavioral tests, deterioration was revealed in the short- and long-term learning and memory functions in the Aβ-injected control group compared to the normal group, indicating that Aβ injection impairs cognitive functions. However, administration of Zj and Zj-Y improved cognitive function in mice, as compared to the Aβ-injected control mice. In addition, the Aβ induced elevations of MDA and NO in the brain, kidney, and liver were suppressed after exposure to Zj and Zj-Y. Especially, Zj-Y showed stronger scavenging effect against MDA and NO, as compared to Zj.

Conclusions: Results of the present study indicate that Zj-Y exerts a protective effect on cognitive impairment and memory dysfunction, which is exerted by attenuating the oxidative stress induced by Aβ.
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http://dx.doi.org/10.4162/nrp.2021.15.2.173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007403PMC
April 2021

Risk Factors for Disease Behavior Evolution and Efficacy of Biologics in Reducing Progression in Pediatric Patients with Nonstricturing, Nonpenetrating Crohn's Disease at Diagnosis: A Single-Center Experience in Korea.

Gut Liver 2021 Apr 9. Epub 2021 Apr 9.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: : Recently, the treatment of Crohn's disease (CD) has changed to a treat-totarget strategy, in which disease progression is prevented with early intervention. We analyzed the long-term evolution of nonstricturing, nonpenetrating (B1) disease at diagnosis and factors related to disease evolution in pediatric CD.

Methods: We retrospectively analyzed 402 patients between 2000 and 2013 who were younger than 18 years and had B1 disease at CD diagnosis. The median follow-up was 6.1 years (range, 1 to 13 years). The cumulative probabilities of developing stricturing (B2) or penetrating (B3) disease and associations between risk factors and disease behavior evolution were evaluated.

Results: Among the 402 patients, 75 (18.7%) had B2 or B3 disease by the final follow-up. The cumulative probabilities of disease behavior evolution were 18.3%, 34.3%, and 50.9% at 5, 10, and 13 years, respectively. Patients whose disease progressed had an increased risk of intestinal resection (hazard ratio [HR], 3.61; 95% confidence interval [CI], 2.25 to 6.03; p<0.001). Firstdegree family history of inflammatory bowel disease (HR, 2.38; 95% CI, 1.07 to 5.28; p=0.032), isolated ileal involvement at diagnosis (HR, 7.55; 95% CI, 1.04 to 15.57; p=0.045), and positive anti-Saccharomyces cerevisiae antibody titers (HR, 2.10; 95% CI, 1.03 to 4.25; p=0.040) were associated with disease behavior evolution. Early treatment with biologics significantly reduced disease progression (HR, 0.46; 95% CI, 0.79 to 3.39; p=0.042).

Conclusions: Despite having B1 disease at diagnosis, patients with risk factors for disease behavior evolution should receive more aggressive treatment in the early phase to improve longterm outcomes.
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http://dx.doi.org/10.5009/gnl20279DOI Listing
April 2021

Discovery of novel potent migrastatic Thiazolo[5,4-b]pyridines targeting Lysyl-tRNA synthetase (KRS) for treatment of Cancer metastasis.

Eur J Med Chem 2021 Mar 30;218:113405. Epub 2021 Mar 30.

College of Pharmacy, CHA University, Gyeonggi-do, 11160, Republic of Korea; College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Recently, non-canonical roles of Lysyl-tRNA Synthetase (KRS), which is associated with cell migration and cancer metastasis, have been reported. Therefore, KRS has emerged as a promising target for the treatment of cell migration-related diseases, especially cancer metastasis, although the satisfying chemical inhibitors targeting KRS have not yet been identified. Here, we report the discovery of novel, mechanistically unique, and potent cell migration inhibitors targeting KRS, including the chemical and biological studies on the most effective N,N-dialkylthiazolo [5,4-b]pyridin-2-amine (SL-1910). SL-1910 exhibited highly potent migration inhibition (EC = 81 nM against the mutant KRS-overexpressed MDA-MB-231 cells) and was superior to the previously reported KRS inhibitor (migration inhibitory EC = 8.5 μM against H226 cells). The KRS protein binding study via fluorescence-based binding titration and KRS protein 2D-NMR mapping study, in vitro concentration-dependent cell migration inhibition, and in vivo anti-metastatic activity of SL-1910, which consists of a new scaffold, have been reported in this study. In addition, in vitro absorption, distribution, metabolism, and excretion studies and mouse pharmacokinetics experiments for SL-1910 were conducted.
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http://dx.doi.org/10.1016/j.ejmech.2021.113405DOI Listing
March 2021

Absent or impaired rectoanal inhibitory reflex as a diagnostic factor for high-grade (grade III-V) rectal prolapse: a retrospective study.

BMC Gastroenterol 2021 Apr 7;21(1):157. Epub 2021 Apr 7.

Department of Surgery, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea.

Background: Clinically diagnosing high-grade (III-V) rectal prolapse might be difficult, and the prolapse can often be overlooked. Even though defecography is the significant diagnostic tool for rectal prolapse, it is noticed that rectoanal inhibitory reflex (RAIR) can be associated with rectal prolapse. This study investigated whether RAIR can be used as a diagnostic factor for rectal prolapse.

Methods: In this retrospective study, we evaluated 107 patients who underwent both anorectal manometry and defecography between July 2012 and December 2019. Rectal prolapse was classified in accordance with the Oxford Rectal Prolapse Grading System. Patients in the high-grade (III-V) rectal prolapse (high-grade group, n = 30), and patients with no rectal prolapse or low-grade (I, II) rectal prolapse (low-grade group, n = 77) were analyzed. Clinical variables, including symptoms such as fecal incontinence, feeling of prolapse, and history were collected. Symptoms were assessed using yes/no surveys answered by the patients. The manometric results were also evaluated.

Results: Frequencies of fecal incontinence (p = 0.002) and feeling of prolapse (p < 0.001) were significantly higher in the high-grade group. The maximum resting (77.5 vs. 96 mmHg, p = 0.011) and squeezing (128.7 vs. 165 mmHg, p = 0.010) anal pressures were significantly lower in the high-grade group. The frequency of absent or impaired RAIR was significantly higher in the high-grade group (19 cases, 63% vs. 20 cases, 26%, p < 0.001). In a multivariate analysis, the feeling of prolapse (odds ratio [OR], 23.88; 95% confidence interval [CI], 4.43-128.78; p < 0.001) and absent or impaired RAIR (OR, 5.36; 95% CI, 1.91-15.04, p = 0.001) were independent factors of high-grade (III-V) rectal prolapse. In addition, the percentage of the absent or impaired RAIR significantly increased with grading increase of rectal prolapse (p < 0.001). The sensitivity of absent or impaired RAIR as a predictor of high-grade prolapse was 63.3% and specificity 74.0%.

Conclusions: Absent or impaired RAIR was a meaningful diagnostic factor of high-grade (III-V) rectal prolapse. Furthermore, the absent or impaired reflex had a positive linear trend according to the increase of rectal prolapse grading.
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http://dx.doi.org/10.1186/s12876-021-01729-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028073PMC
April 2021

Genetic and clinical spectrums in Korean Charcot-Marie-Tooth disease patients with myelin protein zero mutations.

Mol Genet Genomic Med 2021 Apr 6:e1678. Epub 2021 Apr 6.

Department of Biological Sciences, Kongju National University, Gongju, Korea.

Background: Charcot-Marie-Tooth disease (CMT) is the most common disorder of inherited peripheral neuropathies characterized by distal muscle weakness and sensory loss. CMT is usually classified into three types, demyelinating, axonal, and intermediate neuropathies. Mutations in myelin protein zero (MPZ) gene which encodes a transmembrane protein of the Schwann cells as a major component of peripheral myelin have been reported to cause various type of CMT.

Methods: This study screened MPZ mutations in Korean CMT patients (1,121 families) by whole exome sequencing and targeted sequencing.

Results: We identified 22 pathogenic or likely pathogenic MPZ mutations in 36 families as the underlying cause of the CMT1B, CMTDID, or CMT2I subtypes. Among them, five mutations were novel. The frequency of CMT patients with the MPZ mutations was similar or slightly lower compared to other ethnic groups.

Conclusions: We showed that the median onset ages and clinical phenotypes varied by subtypes: the most severe in the CMT1B group, and the mildest in the CMT2I group. This study also observed a clear correlation that earlier onsets cause more severe symptoms. We believe that this study will provide useful reference data for genetic and clinical information on CMT patients with MPZ mutations in Korea.
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http://dx.doi.org/10.1002/mgg3.1678DOI Listing
April 2021

Effect of combined pulmonary fibrosis and emphysema on patients with connective tissue diseases and systemic sclerosis: a systematic review and meta-analysis.

Arthritis Res Ther 2021 04 6;23(1):100. Epub 2021 Apr 6.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

Background: This study aimed to analyze the literature systematically to determine the clinical characteristics and prognosis of patients with connective tissue disease (CTD) with combined pulmonary fibrosis and emphysema (CPFE) compared to those of patients with CTD-interstitial lung disease (CTD-ILD) without emphysema.

Methods: We searched MEDLINE, EMBASE, Cochrane Library, and KoreaMed for relevant articles published before July 2019. Studies meeting all the following criteria were included: (1) original research studies evaluating the effect of CPFE on CTD, (2) studies that compared patients with CTD-CPFE to those with CTD-ILD without emphysema, and (3) studies providing data on physical capacity, pulmonary function, or death in patients with CTD. Clinical characteristics of patients with CTD-CPFE were compared with those of patients with CTD-ILD without emphysema, and the influence of CPFE on physical capacity, pulmonary function, and death was analyzed.

Results: Six studies between 2013 and 2019 were included. Two hundred ninety-nine (29.5%) and 715 (70.5%) patients had CTD-CPFE and CTD-ILD without emphysema, respectively. Regarding the type of CTD, 711 (68.3%) patients had systemic sclerosis, 263 (25.3%) rheumatoid arthritis, and 67 (6.4%) other CTDs. Patients with CTD-CPFE had a higher frequency of pulmonary hypertension and pulmonary fibrosis > 20% of the total lung volume, higher ratio of the forced vital capacity to the diffusion capacity of the lung for carbon monoxide (DLCO), lower arterial oxygen pressure at rest, and lower DLCO compared to those in patients with CTD-ILD without emphysema. In addition, more deaths occurred among those with CTD-CPFE (odds ratio, 2.95; 95% confidence interval, 1.75-4.96).

Conclusion: CTD-CPFE is associated with worse physical and pulmonary function and more deaths compared to those in CTD-ILD without emphysema. These findings indicate the need for increased awareness and close monitoring of patients with CTD-CPFE.
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http://dx.doi.org/10.1186/s13075-021-02494-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022385PMC
April 2021

Tissue-specific biomarkers in gingival crevicular fluid are correlated with external root resorption caused by constant mechanical load: an in vivo study.

Clin Oral Investig 2021 Apr 6. Epub 2021 Apr 6.

Department of Orthodontics, The Institute of Craniofacial Deformity, College of Dentistry, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.

Objectives: This study investigated the association of changes in cementum protein-1 (CEMP-1), dentine phosphoprotein (DPP), and c-terminal cross-linked telopeptide of type I collagen (CTX-I) levels in human gingival crevicular fluid (GCF) under constant load with external root resorption volume and amount of tooth movement.

Materials And Methods: In total, 11 healthy adult patients (mean age, 23.5 years [range, 18.3-37.7]; four men and seven women) were enrolled. GCF samples were obtained from premolars at T0, T1 (1 day), T2 (1 week), T3 (2 weeks), T4 (4 weeks), and T5 (8 weeks) under constant 100-gm buccal tipping force. Opposite premolars were used as controls. Teeth were extracted at T5, followed by quantification of external root resorption volume and histological analysis.

Results: In the test group, T5/T0 ratios of CEMP-1 and DPP levels, differential CEMP-1 levels between T5 and T0, and differential DPP levels between T2 and T0 correlated positively with root resorption volume (r = 0.734, 0.730, 0.627, and 0.612, respectively, all p < 0.05). CEMP-1 levels at T0 and T3 correlated negatively with root resorption volume (r = -0.603 and -0.706; all p < 0.05). CTX-I levels at T5 correlated positively with the amount of tooth movement (r = 0.848, p < 0.01).

Conclusions: Alterations in CEMP-1 and DPP levels in human GCF at specific timepoints during orthodontic treatment may be associated with different degrees of external root resorption.

Clinical Relevance: This study demonstrates that changes in the levels of tissue-specific biomarkers in GCF may facilitate early detection of external root resorption during orthodontic tooth movement.
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http://dx.doi.org/10.1007/s00784-021-03932-6DOI Listing
April 2021

2021 Korean Society of Myocardial Infarction Expert Consensus Document on Revascularization for Acute Myocardial Infarction.

Korean Circ J 2021 Apr;51(4):289-307

Department of Cardiovascular Medicine, Chonnam National University Hospital, Gwangju, Korea.

Acute myocardial infarction (AMI) is a fatal manifestation of ischemic heart disease and remains a major public health concern worldwide despite advances in its diagnosis and management. The characteristics of patients with AMI, as well as its disease patterns, have gradually changed over time in Korea, and the outcomes of revascularization have improved dramatically. Several characteristics associated with the revascularization of Korean patients differ from those of patients in other countries. The sophisticated state of AMI revascularization in Korea has led to the need for a Korean expert consensus. The Task Force on Expert Consensus Document of the Korean Society of Myocardial Infarction has comprehensively reviewed the outcomes of large clinical trials and current practical guidelines, as well as studies on Korean patients with AMI. Based on these comprehensive reviews, the members of the task force summarize the major guidelines and recent publications, and propose an expert consensus for revascularization in patients with AMI.
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http://dx.doi.org/10.4070/kcj.2021.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022023PMC
April 2021

High dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis.

Allergy 2021 Apr 5. Epub 2021 Apr 5.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Flow cytometry is a well-accepted approach for immune profiling, however its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOFoffers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL-21 may be involved in inflammatory skin diseases but its role in AD is not well established.

Methods: We studied T-cell polarization in the blood of 20 moderate-to-severe AD and 15 controls. Using CyTOF and an unsupervised analysis we measured the frequencies and mean metal intensities of activated polar CD4 /CD8 T-cell subsets. Immunohistochemistry, immunofluorescence and qRT-PCR were used to analyze skin samples.

Results: Examining24 surface, intracellular markers and transcription factors, we identified six CD4 and five CD8 T-cell metaclusters. A CD4 skin homing IL-13 monocytokineand a novel IL-13 IL-21 multicytokinemetaclusterswere increased in AD vs. controls (P<0.01). While IL-13 signature characterized both clusters, levels were significantly higher in the IL-21 group. Both clusters correlated with AD severity (r=0.49, P=0.029). Manual gating corroborated these results and identified additional multicytokinesubsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression,displayed significantly increasedIL-21 counts and colocalization with IL-13/IL-4R in AD skin.

Conclusion: Amulticytokine signature characterizesmoderate-to-severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL-21 signature in blood and skinhints for a potential pathogenic role of IL-21 in AD.
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http://dx.doi.org/10.1111/all.14845DOI Listing
April 2021