Publications by authors named "Yong-Jun Choi"

131 Publications

Hydrogen-rich gas production via steam gasification of food waste over basic oxides (MgO/CaO/SrO) promoted-Ni/AlO catalysts.

Chemosphere 2022 Jan 8;287(Pt 2):132224. Epub 2021 Sep 8.

School of Environmental Engineering, University of Seoul, 02504, Seoul, South Korea. Electronic address:

Food waste, a renewable resource, was converted to H-rich gas via a catalytic steam gasification process. The effects of basic oxides (MgO, CaO, and SrO) with 10 wt% Ni/AlO on the gasification properties of food waste were investigated using a U-shaped gasifier. All catalysts prepared by the precipitation method were analyzed by X-ray diffraction, H-temperature-programmed reduction, NH-temperature-programmed desorption, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The Ni/AlO catalyst was reduced incompletely, and low nickel concentrations were detected on the surface of the alumina. The basic oxides minimized the number of acid sites and suppressed the formation of nickel-aluminate (NiAlO) phase in catalyst. In addition, the basic oxides shifted nickel-aluminate reduction reaction to lower temperatures. It resulted in enhancing nickel concentration on the catalyst surface and increasing gas yield and hydrogen selectivity. The low gas yield of the Ni/AlO catalyst was attributed to the low nickel concentration on the surface. The maximum gas yield (66.0 wt%) and hydrogen selectivity (63.8 vol%) of the 10 wt% SrO- 10 wt% Ni/AlO catalyst correlated with the highly dispersed nickel on the surface and low acidity. Furthermore, coke deposition during steam gasification varied with the surface acidity of the catalysts and less coke was formed on 10 wt% SrO- 10 wt% Ni/AlO due to efficient tar cracking. This study showed that the steam gasification efficiency of the Ni/AlO catalyst could be improved significantly by the addition of SrO.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132224DOI Listing
January 2022

Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis.

Transl Oncol 2021 Nov 18;15(1):101277. Epub 2021 Nov 18.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

With the increasing interest in health screening with chest CT Ground-glass nodule (GGN) has become one of the common lung lesions encountered in daily medical practice. Because lung adenocarcinoma in the form of GGN is an ideal model for studying early lung carcinogenesis, 11 GGN and normal lung specimens from 6 never smoker patients were studied by single-cell RNA sequencing. Lung cancer cells showed enrichment of gene sets related to small vesicle processing and surfactant homeostasis compared to non-malignant lung epithelial cells, suggesting the dysregulation of surfactant pathway may be involved in early lung carcinogenesis. Along with cancer-associated fibroblasts showing enrichment of gene sets involved in negative regulation of protein kinase activity and negative regulation of endothelial cell proliferation, tumor microenvironment (TME) was dominated by infiltration of TNFRSF4+/TNFRSF18+/CTLA4+ regulatory T cells (Treg) and depletion of CD8+ cytotoxic T cells (TC) and γδTC. Majority of mucosa-associated lymphoid tissue B cells (BCs) and follicular BCs were detected within tumor tissue, which was associated with CXCL13 overexpressed in intratumoral Tregs and CD4+ memory TCs. Coordination of components of the TME towards immune evasion is governed by Tregs from the onset of lung cancer, requiring unremitting efforts to target and overcome them. This provision of information on changes in cancer cell-specific biomarkers and TME using early lung cancer from never smokers will provide new insight into early lung carcinogenesis and useful targets for treatment.
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http://dx.doi.org/10.1016/j.tranon.2021.101277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605359PMC
November 2021

Letter to the Editor: Enhancing COVID-19 vaccination coverage using financial incentives: arguments to help health providers counterbalance erroneous claims.

Authors:
Yong-Jun Choi

Epidemiol Health 2021 22;43:e2021087. Epub 2021 Oct 22.

Department of Social and Preventive Medicine, Hallym University College of Medicine, Chuncheon, Korea.

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http://dx.doi.org/10.4178/epih.e2021087DOI Listing
November 2021

Control of the Induced Handedness of Helical Nanofilaments Employing Cholesteric Liquid Crystal Fields.

Molecules 2021 Oct 6;26(19). Epub 2021 Oct 6.

Department of Advanced Materials Engineering for Information & Electronics, and Integrated Education Institute for Frontier Science & Technology (BK21 Four), Kyung Hee University, Yongin 17104, Gyeonggi-do, Korea.

In this paper, a simple and powerful method to control the induced handedness of helical nanofilaments (HNFs) is presented. The nanofilaments are formed by achiral bent-core liquid crystal molecules employing a cholesteric liquid crystal field obtained by doping a rod-like nematogen with a chiral dopant. Homochiral helical nanofilaments are formed in the nanophase-separated helical nanofilament/cholesteric phase from a mixture with a cholesteric phase. This cholesteric phase forms at a temperature higher than the temperature at which the helical nanofilament in a bent-core molecule appears. Under such conditions, the cholesteric liquid crystal field acts as a driving force in the nucleation of HNFs, realizing a perfectly homochiral domain consisting of identical helical nanofilament handedness.
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http://dx.doi.org/10.3390/molecules26196055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512387PMC
October 2021

Bone mineral density, cervical spine degeneration, head and neck posture, and neck pain in the post-menopausal females: A pilot study.

PLoS One 2021 20;16(9):e0257735. Epub 2021 Sep 20.

Clinic of Oral Medicine and Orofacial Pain, Institute of Oral Health Science, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea (ROK).

The purpose of the present study was to reveal the relationship between degenerative changes in the cervical spine, head and neck postures, neck pain, and bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine in post-menopausal females. In total, 116 females (mean age 60.4 ± 7.1 years; age range 50-80 years) were included. Participants were classified into three groups based on the T-score criteria of the total hip, femoral neck, and lumbar spine set by World Health Organization, respectively. The degree of neck pain was assessed using self-administered questionnaire, the Neck Disability Index. Cervical spine degeneration and head and neck postures were identified using the lateral cephalograms. Grading system for cervical degeneration included three categories of the radiographic alterations including disc height loss, osteophyte formation, and diffuse sclerosis. The areal BMD of the total hip, femoral neck, and lumbar spine were determined using dual-energy x-ray absorptiometry. Females with lower BMD exhibited lesser degree of neck pain and forward head posture (FHP) compared to those with normal BMD. Higher BMD seemed to be associated with more notable loss of the disc height at the level of C4-5. More prominent degenerative changes in the cervical spine were associated with higher areal BMD of the hip, femoral neck, and lumbar spine, altered head posture, and development of neck pain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257735PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452041PMC
November 2021

Complete Genome Sequence of Cupriavidus sp. Strain EM10, Isolated from Sewage Sludge.

Microbiol Resour Announc 2021 Sep 16;10(37):e0071421. Epub 2021 Sep 16.

School of Environmental Engineering, University of Seoul, Seoul, Republic of Korea.

Cupriavidus species have been known as versatile microorganisms in the field of industrial biotechnology. Cupriavidus sp. strain EM10 was isolated from sewage sludges. Here, we report the complete genome sequence of this bacterium, which contains 6,658,510 bp (GC content, 65.12%) and 6,248 genes.
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http://dx.doi.org/10.1128/MRA.00714-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444968PMC
September 2021

Large-scale generation and phenotypic characterization of zebrafish CRISPR mutants of DNA repair genes.

DNA Repair (Amst) 2021 11 8;107:103173. Epub 2021 Jul 8.

School of Life Sciences, Ulsan National Institute for Science and Technology (UNIST), Ulsan, 44919, Republic of Korea; Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan, 44919, Republic of Korea; Department of Biomedical Engineering, Ulsan National Institute for Science and Technology (UNIST), Ulsan, 44919, Republic of Korea. Electronic address:

A systematic knowledge of the roles of DNA repair genes at the level of the organism has been limited due to the lack of appropriate experimental approaches using animal model systems. Zebrafish has become a powerful vertebrate genetic model system with availability due to the ease of genome editing and large-scale phenotype screening. Here, we generated zebrafish mutants for 32 DNA repair and replication genes through multiplexed CRISPR/Cas9-mediated mutagenesis. Large-scale phenotypic characterization of our mutant collection revealed that three genes (atad5a, ddb1, pcna) are essential for proper embryonic development and hematopoiesis; seven genes (apex1, atrip, ino80, mre11a, shfm1, telo2, wrn) are required for growth and development during juvenile stage and six genes (blm, brca2, fanci, rad51, rad54l, rtel1) play critical roles in sex development. Furthermore, mutation in six genes (atad5a, brca2, polk, rad51, shfm1, xrcc1) displayed hypersensitivity to DNA damage agents. Our zebrafish mutant collection provides a unique resource for understanding of the roles of DNA repair genes at the organismal level.
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http://dx.doi.org/10.1016/j.dnarep.2021.103173DOI Listing
November 2021

Suppression of the hazardous substances in catalytically upgraded bio-heavy oil as a precautious measure for clean air pollution controls.

J Hazard Mater 2022 01 24;421:126732. Epub 2021 Jul 24.

School of Environmental Engineering, University of Seoul, 163 Seoulsiripdaero, Seoul 02504, Republic of Korea. Electronic address:

Bio-heavy oil (BHO) is a renewable fuel, but its efficient use is problematic because its combustion may emit hazardous air pollutants (e.g., polycyclic aromatic hydrocarbon (PAH) compounds, NO, and SO). Herein, catalytic fast pyrolysis over HZSM-5 zeolite was applied to upgrading BHO to drop-in fuel-range hydrocarbons with reduced contents of hazardous species such as PAH compounds and N- and S-containing species (NO and SO precursors). The effects of HZSM-5 desilication and linear low-density polyethylene (LLDPE) addition to the feedstock on hydrocarbon production were explored. The apparent activation energy for the thermal decomposition of BHO was up to 37.5% lowered by desilicated HZSM-5 (DeHZSM-5) compared with HZSM-5. Co-pyrolyzing LLDPE with BHO increased the content of drop-in fuel-range hydrocarbons and decreased the content of PAH compounds. The DeHZSM-5 was effective in producing drop-in fuel-range hydrocarbons from a mixture of BHO and LLDPE and suppressing the formation of N- and S-containing species and PAH compounds. The DeHZSM-5 enhanced the hydrocarbon production by up to 58.5% because of its enhanced porosity and high acid site density compared to its parent HZSM-5. This study experimentally validated that BHO can be upgraded to less hazardous fuel via catalytic fast co-pyrolysis with LLDPE over DeHZSM-5.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126732DOI Listing
January 2022

Bioremediation strategies with biochar for polychlorinated biphenyls (PCBs)-contaminated soils: A review.

Environ Res 2021 09 23;200:111757. Epub 2021 Jul 23.

School of Environmental Engineering, University of Seoul, Seoul, 02504, Republic of Korea. Electronic address:

Polychlorinated biphenyls (PCBs) are hazardous organic contaminants threatening human health and environmental safety due to their toxicity and carcinogenicity. Biochar (BC) is an eco-friendly carbonaceous material that can extensively be utilized for the remediation of PCBs-contaminated soils. In the last decade, many studies reported that BC is beneficial for soil quality enhancement and agricultural productivity based on its physicochemical characteristics. In this review, the potential of BC application in PCBs-contaminated soils is elaborated as biological strategies (e.g., bioremediation and phytoremediation) and specific mechanisms are also comprehensively demonstrated. Further, the synergy effects of BC application on PCBs-contaminated soils are discussed, in view of eco-friendly, beneficial, and productive aspects.
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http://dx.doi.org/10.1016/j.envres.2021.111757DOI Listing
September 2021

Low alanine aminotransferase as a risk factor for chronic obstructive pulmonary disease in males.

Sci Rep 2021 07 21;11(1):14829. Epub 2021 Jul 21.

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-ro, Gangnam-gu, Seoul, 06273, Korea.

Alanine aminotransferase (ALT) levels reflect skeletal muscle volume and general performance, which are associated with chronic obstructive pulmonary disease (COPD) development and prognosis. This study aimed to investigate ALT levels as a risk factor for COPD development. This 13-year population-based retrospective observational cohort study included 422,452 participants for analysis. We classified groups according to the baseline ALT levels (groups 1-5: ALT (IU/L) < 10; 10-19; 20-29; 30-39; and ≥ 40, respectively). The incidence of COPD was the highest in group 1, decreasing as the group number increased in males, but not in females. The Cox regression analysis in males revealed that a lower ALT level, as a continuous variable, was a significant risk factor for COPD development [univariable, hazard ratio (HR): 0.992, 95% confidence interval (CI): 0.991-0.994; multivariable, HR: 0.998, 95% CI: 0.996-0.999]. In addition, COPD was more likely to develop in the lower ALT level groups (groups 1-4; < 40 IU/L), than in the highest ALT level group (group 5; ≥ 40 IU/L) (univariable, HR: 1.341, 95% CI: 1.263-1.424; multivariable, HR: 1.097, 95% CI: 1.030-1.168). Our findings suggest that males with low ALT levels should be carefully monitored for COPD development.
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http://dx.doi.org/10.1038/s41598-021-94385-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295341PMC
July 2021

Variable effects of underlying diseases on the prognosis of patients with COVID-19.

PLoS One 2021 19;16(7):e0254258. Epub 2021 Jul 19.

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Underlying diseases might be risk factors for poor prognosis in patients with coronavirus disease (COVID-19); however, we still do not know whether these diseases are independent factors affecting prognosis, which type of underlying diseases are risk factors, and which type of clinical outcomes are affected. We retrospectively reviewed cohort data from 7,590 de-identified patients with COVID-19 who were diagnosed using severe acute respiratory syndrome-coronavirus-2 RNA polymerase chain reaction test up to May 15, 2020. We used linked-medical claims data provided by the Health Insurance Review and Assessment Service in South Korea. Underlying diseases were identified using the diagnostic codes in the patients' files from January 1, 2019 to December 31, 2019. The total mortality rate was 3.0% in patients with COVID-19. After adjusting for age, sex, and concomitant chronic conditions, we found that congestive heart failure, chronic pulmonary diseases, diabetes without chronic complications, renal diseases, and malignancy were factors that significantly increased the cost of treatment. Cerebrovascular disease, chronic pulmonary disease, and paralysis were found to be independent factors significant in prolonging hospital stay. Diabetes with chronic complications was independently associated with intensive care unit admission. In addition, underlying congestive heart failure (odds ratio [OR], 1.724; P = 0.003), dementia (OR, 1.598; P = 0.012), diabetes with and without chronic complications (OR, 1.821; P = 0.002 and OR, 1.518; P = 0.022, respectively), renal disease (OR, 2.299; P = 0.002), and malignancy (OR, 1.529; P = 0.039) were significant factors associated with death, even after adjustments. Underlying diseases were significant independent factors of the poor prognosis in patients with COVID-19. The effects were variable according to the type of underlying disease and clinical outcome. Therefore, patients with COVID-19 with underlying diseases should be monitored more closely because they are more at risk of a poor prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254258PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289057PMC
July 2021

Pearls & Oy-sters: Cerebral Microbleeds Caused by Adrenocortical Adenoma-Related Primary Aldosteronism.

Neurology 2021 05 7;96(20):960-962. Epub 2021 Apr 7.

From the Departments of Neurology (S.M.L., S.Y.M.), Endocrinology (Y.J.C.), Ophthalmology (K.L.), Thyroid Endocrinology Surgery (H.K.K.), Cardiology (J.-S.P.), Neurosurgery (Y.C.L.), and Pathology (J.-H.K.), Ajou University School of Medicine; and Department of Medical Sciences (S.M.L.), Graduate School of Ajou University, Suwon, Republic of Korea.

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http://dx.doi.org/10.1212/WNL.0000000000011934DOI Listing
May 2021

Effects of circuit training or a nutritional intervention on body mass index and other cardiometabolic outcomes in children and adolescents with overweight or obesity.

PLoS One 2021 28;16(1):e0245875. Epub 2021 Jan 28.

Department of Family Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Republic of Korea.

Objective: We aimed to assess the effectiveness of the first 6 months of a 24 month multidisciplinary intervention program including circuit training and a balanced diet in children and adolescents with obesity.

Methods: A quasi-experimental intervention trial included 242 participants (age [mean±standard deviation]: 11.3±2.06 years, 97 girls) of at least 85th percentile of age- and sex-specific body mass index (BMI). Participants were grouped into three to receive usual care (usual care group), exercise intervention with circuit training (exercise group), or intensive nutritional and feedback intervention with a balanced diet (nutritional group). Primary outcome was BMI z-score, while secondary outcomes included body composition, cardiometabolic risk markers, nutrition, and physical fitness.

Results: Among the participants, 80.6% had a BMI ≥ the 97th percentile for age and sex. The BMI z-score of the overall completers decreased by about 0.080 after 6 months of intervention (p < 0.001). After the intervention, both exercise and nutritional groups had significantly lower BMI z-scores than the baseline data by about 0.14 and 0.075, respectively (p < 0.05). Significant group by time interaction effects were observed between exercise versus usual care group in BMI z-score (β, -0.11; 95% confidence interval (CI), -0.20 to -0.023) and adiponectin (β, 1.31; 95% CI, 1.08 to 1.58); and between nutritional versus usual care group in waist circumference (β, -3.47; 95% CI, -6.06 to -0.89). No statistically significant differences were observed in any of the other secondary outcomes assessed.

Conclusion: Multidisciplinary intervention including circuit training and a balanced diet for children and adolescents with obesity reduced the BMI z-score and improved cardiometabolic risk markers such as adiponectin and waist circumference.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245875PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842905PMC
June 2021

The secular trends in the use of medications for osteoporosis in South Korea using Intercontinental Medical Statistics Health Sales Audit 2006-2018.

Osteoporos Sarcopenia 2020 Dec 3;6(4):185-190. Epub 2020 Dec 3.

Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea.

Objectives: Osteoporosis medications are widely available in South Korea, and well reimbursed by the Government Health Insurance; however, some expensive drugs are not reimbursed. The prescription of anti-osteoporosis drugs (AODs) are increasing for the elderly and for postmenopausal women. We investigate the secular trends of AODs in South Korea.

Methods: We used the Intercontinental Medical Statistics Health Sales Audit between January 1, 2006 and December 31, 2018. We analyzed the total sales costs and market share of AODs including bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone (PTH), calcitonins, and denosumab using the number of days of therapy (DOT). Changes of prescription patterns including original versus generic drugs, vitamin D combination, and types of medical institutions were also analyzed.

Results: Bisphosphonates were the most frequently used drug during the study period although its DOT declined from 92.5% in 2008 to 80.0% in 2018. SERMs were the second-most used medication, and has maintained around 13% since 2015. The proportion of calcitonins has decreased since 2011, mainly due to malignancy risk. In contrast, the DOT of PTH and denosumab increased to 0.8% and 4.7% in 2018, respectively. The use of generics, vitamin D combination, and intravenous bisphosphonates has been increasing throughout the study period.

Conclusions: Prescription patterns using DOT are changing probably due to the increase in older adult patients and severely osteoporotic patients. There are other issues including safety and the launching of new drugs.
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http://dx.doi.org/10.1016/j.afos.2020.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783074PMC
December 2020

Rapid Diagnosis of Coronavirus by RNA-Directed RNA Transcription Using an Engineered RNA-based Platform.

Nano Lett 2021 01 4;21(1):462-468. Epub 2021 Jan 4.

Department of Chemical Engineering, University of Seoul, 163 Seoulsiripdaero, Dongdaemungu, Seoul 02504, Republic of Korea.

A coronavirus disease (COVID-19) outbreak associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading widely through person-to-person transmission. Various detection approaches have been developed involving quantitative polymerase chain reaction (qPCR) methods, CRISPR-based systems, and direct targeting of specific coronavirus proteins. However, there have only been a few reports on the detection of RNA-dependent RNA polymerase (RdRP), the primer-independent RNA-replicable protein produced by the RNA genes of coronavirus. Here, we introduce a novel diagnostic methodology for COVID-19 using the RNA-directed and RNA replicable function of RdRP. We devised an RNA platform for RdRP-induced transcription (RPRIT) that includes an RNA template that can be directly transcribed by RdRP. By utilizing RPRIT, the presence of RdRP can be readily confirmed within 30 min using isothermal incubation without PCR. This RdRP detection method can provide a new route for rapid diagnosis of RNA virus-infected patients.
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http://dx.doi.org/10.1021/acs.nanolett.0c03917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805305PMC
January 2021

6,8-Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53.

Environ Toxicol 2021 May 31;36(5):914-925. Epub 2020 Dec 31.

Department of Bio and Chemical Engineering, Hongik University, Sejong, South Korea.

6,8-Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8-diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8-diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8-Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose- and time-dependent manner. A 40 μM of 6,8-diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8-diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8-diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen-activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8-diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N-acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8-diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8-diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8-diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS.
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http://dx.doi.org/10.1002/tox.23093DOI Listing
May 2021

Metabolic Engineering of Extremophilic Bacterium for the Production of the Novel Carotenoid Deinoxanthin.

Microorganisms 2020 Dec 25;9(1). Epub 2020 Dec 25.

School of Environmental Engineering, University of Seoul, Seoul 02504, Korea.

Deinoxanthin, a xanthophyll derived from species, is a unique organic compound that provides greater antioxidant effects compared to other carotenoids due to its superior scavenging activity against singlet oxygen and hydrogen peroxide. Therefore, it has attracted significant attention as a next-generation organic compound that has great potential as a natural ingredient in a food supplements. Although the microbial identification of deinoxanthin has been identified, mass production has not yet been achieved. Here, we report, for the first time, the development of an engineered extremophilic microorganism, strain R1, that is capable of producing deinoxanthin through rational metabolic engineering and process optimization. The genes and were first introduced into the genome to reinforce the metabolic flux towards deinoxanthin. The optimal temperature was then identified through a comparative analysis of the mRNA expression of the two genes, while the carbon source was further optimized to increase deinoxanthin production. The final engineered strain R1 was able to produce 394 ± 17.6 mg/L (102 ± 11.1 mg/g DCW) of deinoxanthin with a yield of 40.4 ± 1.2 mg/g sucrose and a productivity of 8.4 ± 0.2 mg/L/h from 10 g/L of sucrose. The final engineered strain and the strategies developed in the present study can act as the foundation for the industrial application of extremophilic microorganisms.
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http://dx.doi.org/10.3390/microorganisms9010044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823818PMC
December 2020

IN REPLY.

Anesth Pain Med (Seoul) 2020 Jan;15(1):130

Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju, Korea.

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http://dx.doi.org/10.17085/apm.2020.15.1.130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713859PMC
January 2020

Reactive oxygen species modulator 1 expression predicts lymph node metastasis and survival in early-stage non-small cell lung cancer.

PLoS One 2020 1;15(12):e0239670. Epub 2020 Dec 1.

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Reactive oxygen species modulator 1 (romo1) causes cell hyperplasia and promotes cancer cell invasion. Based recent studies, the overexpression of romo1 is associated with lymphatic metastasis and poor prognosis in lung cancer. We aimed to evaluate associations between romo1 expression and lymph node metastasis in non-small cell lung cancer (NSCLC). Clinical data and pathological results were retrospectively reviewed for 98 subjects diagnosed with NSCLC and who underwent surgical biopsy between 1994 and 2009. A total 98 tumor specimens were analyzed. The romo1 H score was correlated with stage and was significantly higher in subjects with lymph node metastasis than in those without metastasis (173 vs 116; P < 0.05). The area (%) of grade 1 expression was significantly smaller (19.5 vs 37.0; P = 0.005) and the area of grade 3 expression was significantly larger (27.9 vs 6.00; P < 0.001) in subjects with lymph node metastasis than in those without metastasis. In stage I patients, disease free survival (DFS) (191 ± 18.8 vs. 75.6 ± 22.4 months, P = 0.004) was significantly longer in the low romo1 group than in the high romo1 group. A multivariate analysis showed a significant association between high romo1 expression and poor DFS (hazard ratio 5.59, 95 confidence interval, 1.54-20.3, P = 0.009). These findings support the prognostic value of romo1 in NSCLC, especially in stage I.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239670PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707601PMC
January 2021

FEF Values in Patients with Normal Lung Function Can Predict the Development of Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 12;15:2913-2921. Epub 2020 Nov 12.

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: The forced mid-expiratory flow (FEF) value is a potentially sensitive marker of obstructive peripheral airflow. We aimed to assess whether FEF can be an early predictor of chronic obstructive pulmonary disease (COPD).

Patients And Methods: Between July 1, 2007 and June 31, 2009, we identified 3624 patients who underwent a pulmonary function test (PFT) in Gangnam Severance Hospital. We selected 307 patients aged over 40 years without COPD who had normal PFT results at baseline and who had follow-up PFT records more than 1 year later. A FEF z-score less than -0.8435 was considered low. We defined COPD as a forced expiratory volume in one second/forced vital capacity value of less than 0.7 before July 31, 2019.

Results: Among 307 patients, 91 (29.6%) had low FEF at baseline. After 10 years, the incidence rate of COPD in the low FEF group was significantly higher than that in the normal FEF group (41.8% vs 7.4%; <0.001). The Cox proportional hazard model showed that age (hazard ratio [HR] 1.09; -value<0.001), smoking status (occasional smoker HR, 4.59; -value<0.001 and long-term smoker HR, 2.18; -value=0.023), and low FEF (HR, 3.31; -value<0.001) were predictive factors for the development of COPD.

Conclusion: The FEF value in patients with normal lung function is a useful predictor for the development of COPD. We should carefully monitor patients who present with low FEF values, even if they have normal lung function.
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http://dx.doi.org/10.2147/COPD.S261732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669499PMC
June 2021

Extremophilic Microorganisms for the Treatment of Toxic Pollutants in the Environment.

Molecules 2020 Oct 23;25(21). Epub 2020 Oct 23.

School of Environmental Engineering, University of Seoul, Seoul 02504, Korea.

As concerns about the substantial effect of various hazardous toxic pollutants on the environment and public health are increasing, the development of effective and sustainable treatment methods is urgently needed. In particular, the remediation of toxic components such as radioactive waste, toxic heavy metals, and other harmful substances under extreme conditions is quite difficult due to their restricted accessibility. Thus, novel treatment methods for the removal of toxic pollutants using extremophilic microorganisms that can thrive under extreme conditions have been investigated during the past several decades. In this review, recent trends in bioremediation using extremophilic microorganisms and related approaches to develop them are reviewed, with relevant examples and perspectives.
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http://dx.doi.org/10.3390/molecules25214916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660605PMC
October 2020

Incidental Lung Cancer of Explanted Lungs from Lung Transplant Recipients: Incidence, Characteristics, and 5-Year Survival.

Yonsei Med J 2020 Nov;61(11):958-964

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Recent history of malignancy without 5-year disease-free interval is an absolute contraindication for lung transplantation (LTx). However, in rare cases, lung cancer may be incidentally diagnosed in the explanted lung of recipients. We evaluated the prevalence, 5-year survival, and prognosis of incidental lung cancer after LTx.

Materials And Methods: Medical records of patients who underwent LTx at Severance Hospital between January 1, 2012 and June 30, 2019 were reviewed. Patients with incidental lung cancer were included, and those with histologically proven pre-transplant lung cancer were excluded.

Results: Of the 247 patients who underwent LTx, 6 (2.4%) were diagnosed with incidental lung cancer. Interstitial lung disease (ILD) was the underlying lung disease in all patients. The median interval from the last preoperative computed tomography (CT) screening to LTx was 26 days. The most common histological type of incidental lung cancer was adenocarcinoma (n=4, 66.7%). All Stage IV cases were misdiagnosed as fibrosis on preoperative chest CT. Patients with incidental lung cancer showed lower 5-year survival than those without malignancy (median survival: 8.5 months vs. not reached, =0.047, respectively). Patients with Stage III or IV demonstrated lower 5-year survival than those with Stage I or II and those without malignancy (median survival: 5 months, 19 months, and not reached, respectively, =0.011).

Conclusion: Multidisciplinary preoperative screening and serial imaging studies within short intervals are required to differentiate lung malignancy from fibrotic foci. Furthermore, active pathologic examination of suspicious lung lesions is required in patients at high risk for lung cancer.
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http://dx.doi.org/10.3349/ymj.2020.61.11.958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593106PMC
November 2020

Enhanced Lycopene Production by UV-C Irradiation in Radiation-Resistant R1.

J Microbiol Biotechnol 2020 Dec;30(12):1937-1943

School of Environmental Engineering, University of Seoul, Seoul 02504, Republic of Korea.

Although classical metabolic engineering strategies have succeeded in developing microbial strains capable of producing desired bioproducts, metabolic imbalance resulting from extensive genetic manipulation often leads to decreased productivity. Thus, abiotic strategies for improving microbial production performance can be an alternative to overcome drawbacks arising from intensive metabolic engineering. Herein, we report a promising abiotic method for enhancing lycopene production by UV-C irradiation using a radiation-resistant Δ/ R1 strain. First, the onset of UV irradiation was determined through analysis of the expression of 11 genes mainly involved in the carotenoid biosynthetic pathway in the Δ/ R1 strain. Second, the effects of different UV wavelengths (UV-A, UV-B, and UV-C) on lycopene production were investigated. UV-C irradiation induced the highest production, resulting in a 69.9% increase in lycopene content [64.2 ± 3.2 mg/g dry cell weight (DCW)]. Extended UV-C irradiation further enhanced lycopene content up to 73.9 ± 2.3 mg/g DCW, a 95.5% increase compared to production without UV-C irradiation (37.8 ± 0.7 mg/g DCW).
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http://dx.doi.org/10.4014/jmb.2009.09013DOI Listing
December 2020

Effect of asthma and asthma medication on the prognosis of patients with COVID-19.

Eur Respir J 2021 03 4;57(3). Epub 2021 Mar 4.

Dept of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide rapidly. However, the effects of asthma, asthma medication and asthma severity on the clinical outcomes of COVID-19 have not yet been established.

Methods: The study included 7590 de-identified patients, who were confirmed to have COVID-19 using the severe acute respiratory syndrome coronavirus 2 RNA-PCR tests conducted up to May 15, 2020; we used the linked-medical claims data provided by the Health Insurance Review and Assessment Service. Asthma and asthma severity (steps suggested by the Global Initiative for Asthma) were defined using the diagnostic code and history of asthma medication usage.

Results: Among 7590 COVID-19 patients, 218 (2.9%) had underlying asthma. The total medical cost associated with COVID-19 patients with underlying asthma was significantly higher than that of other patients. Mortality rate for COVID-19 patients with underlying asthma (7.8%) was significantly higher than that of other patients (2.8%; p<0.001). However, asthma was not an independent risk factor for the clinical outcomes of COVID-19 after adjustment, nor did asthma medication use and asthma severity affect the clinical outcomes of COVID-19. However, use of oral short-acting β-agonists was an independent factor to increase the total medical cost burden. Patients with step 5 asthma showed significant prolonged duration of admission compared to those with step 1 asthma in both univariate and multivariate analysis.

Conclusions: Asthma led to poor outcomes of COVID-19; however, underlying asthma, use of asthma medication and asthma severity were not independent factors for poor clinical outcomes of COVID-19, generally.
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http://dx.doi.org/10.1183/13993003.02226-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518077PMC
March 2021

Team-based primary care program for disabled people and changes in rate of unmet health care needs.

Fam Pract 2021 03;38(2):95-102

Policy Bureau, Cooperative Institute for Health Plus, Ansan, Republic of Korea.

Background: Few studies have been conducted on the application of specific and practical methods, such as interventions, for reducing the unmet health care needs (UHCN) of disabled people.

Objectives: The study aims to evaluate the impact of the team-based primary care program (TPCP) for disabled people on UHCN.

Method: In 2017, we surveyed 696 disabled people who were enrolled in the TPCP at one of the 11 institutions belonging to the Korea Health Welfare Social Cooperative Federation from 2015 to 2017 to assess their unmet needs before and after enrolment. We conducted a logistic regression analysis before and after the program to evaluate the relationship between participation period and unmet needs after adjusting for physician type, gender, age, drinking, monthly income, disability type, personal assistance services and living alone.

Result: After using the service, the proportion of disabled people with unmet needs decreased from 42.9% to 20.4% for a medical doctor and 43.6% to 18.6% for a Korean medical (KM) doctor. After adjusting for related factors and stratifying with type of physician, the proportion of disabled people with unmet needs decreased significantly in response to the participation period for the medical doctor-involved program (P-trend < 0.001); this was not observed in the KM counterpart (P-trend = 0.6).

Conclusion: The TPCP for disabled people provides disease prevention, health care and health promotion activities and is crucial for solving the unmet needs.
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http://dx.doi.org/10.1093/fampra/cmaa089DOI Listing
March 2021

Prediction model for hyperprogressive disease in non-small cell lung cancer treated with immune checkpoint inhibitors.

Thorac Cancer 2020 10 11;11(10):2793-2803. Epub 2020 Aug 11.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Background: Hyperprogressive disease (HPD) is a paradoxical acceleration of tumor growth after immune checkpoint inhibitor (ICI) treatment. This study aimed to identify the risk factors and to present a predictive model for HPD in patients treated with ICIs.

Methods: A total of 78 non-small cell lung cancer (NSCLC) cases, treated with at least two cycles of ICIs who underwent computed tomography (CT) for response assessment were recruited into the study from January 2016 to August 2019. HPD was defined by the following criteria: (i) time-to-treatment failure <2 months; (ii) a 50% increase in the sum of target lesion diameters; (iii) new development of at least two lesions in an already involved organ; (iv) appearance of a new organ lesion; and (v) a decrease in ECOG PS 2.

Results: Of the 78 total patients, 15 (19.2%) had HPD. The risk factors of HPD were age; primary lesion size; and metastases in the contralateral lung, pleura, liver, and bone in multivariable logistic regression (odds ratio [OR]; 0.9038, 1.6619, 28.5913, 23.8264, 14.5711, and 20.1533, respectively, all P-values < 0.05). By using these risk factors, we developed a prediction model for HPD and the area under the receiver operating characteristic curve of the model was 0.9556 (95% confidence interval [CI]: 0.9133-0.9978).

Conclusions: HPD is relatively common and associated with a grave clinical outcome, requiring a careful monitoring in lung cancer patients treated with ICIs. Moreover, risk factors such as age, size of tumor and number of various metastatic lesions should be taken into consideration before ICI administration.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Age, primary lesion size, and number of metastases are risk factors of HPD. HPD is strongly associated with poor prognosis. HPD during ICI use needs comprehensive monitoring.

What This Study Adds: This is the first study to develop a prediction model. The area under the curve of the prediction model for HPD was 0.9556.
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http://dx.doi.org/10.1111/1759-7714.13594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529559PMC
October 2020

Trabecular bone score may indicate chronic kidney disease-mineral and bone disorder (CKD-MBD) phenotypes in hemodialysis patients: a prospective observational study.

BMC Nephrol 2020 07 25;21(1):299. Epub 2020 Jul 25.

Department of Nephrology, Ajou University School of Medicine, Suwon, South Korea.

Background: In the general population, the trabecular bone score (TBS) represents the bone microarchitecture and predicts fracture risk independent of bone mineral density (BMD). A few studies reported that TBS is significantly reduced in dialysis patients. Chronic kidney disease-mineral and bone disorder (CKD-MBD) are accompanied by increased fracture risk, cardiovascular morbidity, and mortality. We investigated whether TBS is associated with comorbidity related to CKD-MBD or frailty in hemodialysis patients.

Methods: In this prospective observational study, TBS was obtained using the TBS iNsight software program (Med-Imaps) with BMD dual energy x-ray absorptiometry (DXA) images (L1-L4) from prevalent hemodialysis patients. A Tilburg frailty indicator was used to evaluate frailty, and hand grip strength and bio-impedance (InBody) were measured. A patient-generated subjective global assessment (PG-SGA) was used for nutritional assessment. The history of cardiovascular events (CVE) and demographic, clinical, laboratory, and biomarker data were collated. We then followed up patients for the occurrence of CKD-MBD related complications.

Results: We enrolled 57 patients in total. The mean age was 56.8 ± 15.9 years (50.9% female). Prevalence of Diabetes mellitus (DM) was 40.4% and CVE was 36.8%. Mean TBS was 1.44 ± 0.10. TBS significantly reduced in the CVE group (1.38 ± 0.08 vs. 1.48 ± 0.10, p <  0.001). Multivariable regression analysis was conducted adjusting for age, sex, dialysis vintage, DM, CVE, albumin, intact parathyroid hormone, fibroblast growth factor 23, handgrip strength, and phosphate binder dose. Age (ß = - 0.030; p = 0.001) and CVE (ß = - 0.055; p = 0.024) were significant predictors of TBS. During the follow up period after TBS measurements (about 20 months), four deaths, seven incident fractures, and six new onset CVE were recorded. Lower TBS was associated with mortality (p = 0.049) or new onset fracture (p = 0.007, by log-rank test).

Conclusion: Lower TBS was independently associated with increased age and CVE prevalence in hemodialysis patients. Mortality and fracture incidence were significantly higher in patients with lower TBS values. These findings suggest that TBS may indicate a phenotype of frailty and also a CKD-MBD phenotype reciprocal to CVE.
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http://dx.doi.org/10.1186/s12882-020-01944-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382149PMC
July 2020

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Endocrinol Metab (Seoul) 2020 06 24;35(2):272-287. Epub 2020 Jun 24.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.
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http://dx.doi.org/10.3803/EnM.2020.35.2.272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386113PMC
June 2020

Leucine-Enriched Protein Supplementation Increases Lean Body Mass in Healthy Korean Adults Aged 50 Years and Older: A Randomized, Double-Blind, Placebo-Controlled Trial.

Nutrients 2020 Jun 18;12(6). Epub 2020 Jun 18.

Department of Medical Nutrition, Kyung Hee University, Yong-in 17104, Korea.

Early prevention of sarcopenia could be an important strategy for muscle retention, but most studies have focused on subjects aged 65 or older. Therefore, in this study we investigated the effects of leucine-enriched protein supplementation on muscle condition in a sample including late middle-aged adults. A 12-week intervention was performed for 120 healthy community-dwelling adults by providing either leucine-enriched protein supplement [leucine 3 g, protein mixture (casein 50% + whey 40% + soy 10%) 17 g, vitamin D 800IU (20 µg), calcium 300 mg, fat 1.1 g, carbohydrate 2.5 g] or isocaloric carbohydrate supplement twice per day. Appendicular skeletal muscle mass index (ASMI) and lean body mass (LBM) were measured by dual-energy X-ray absorptiometry. A total of 111 participants completed the study, with a dropout rate of 9.2%. LBM normalized by height and body weight (LBM/Wt) was significantly increased ( < 0.001) in the intervention group (0 wk: 633.9 ± 8.5 vs. 12 wk 636.9 ± 8.4 in the intervention group; 0 wk: 638.6 ± 8.3 vs. 12 wk: 632.9 ± 8.1 in the control group). In subgroup analyses, significant differences remained only in subjects between 50 and 64 years of age. We concluded that leucine-enriched protein supplementation can have beneficial effects by preventing muscle loss, mainly for late middle-aged adults.
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http://dx.doi.org/10.3390/nu12061816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353448PMC
June 2020

Case report: nosocomial fungemia caused by Candida diddensiae.

BMC Infect Dis 2020 May 27;20(1):377. Epub 2020 May 27.

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.

Background: Candida diddensiae, a yeast found in olive oil, is considered non-pathogenic to humans. Here, we describe the first case of fungemia caused by C. diddensiae in a hospitalized patient with underlying diseases.

Case Presentation: A 62-year-old woman was admitted because of multiple contusions due to repeated falls and generalized weakness. She presented with chronic leukopenia due to systemic lupus erythematosus, and multiple cranial nerve neuropathies due to a recurring chordoma. She was given a lipid emulsion containing total parenteral nutrition (TPN) starting on the day of admission. Broad-spectrum antibiotics had been administered during her last hospital stay and from day 8 of this hospitalization. However, no central venous catheter was used during this hospital stay. Blood cultures obtained on hospital days 17, 23, and 24 yielded the same yeast, which was identified as C. diddensiae via sequence analyses of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. In vitro susceptibility testing showed that the minimum inhibitory concentration of fluconazole for all isolates was 8 μg/mL. On day 23, TPN was discontinued and fluconazole therapy was started. Blood cultures obtained on day 26 were negative. The fluconazole therapy was replaced with micafungin on day 26 and the patient exhibited improvements.

Conclusion: The use of lipid TPN may potentially contribute to the occurrence of nosocomial fungemia by C. diddensiae, an unusual Candida species.
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http://dx.doi.org/10.1186/s12879-020-05095-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251903PMC
May 2020
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