Publications by authors named "Jin Yoo"

246 Publications

Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties.

ACS Macro Lett 2021 12 15;10(12):1510-1516. Epub 2021 Nov 15.

Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47907, United States of America.

Extensive studies have been conducted to elucidate the effects of such parameters as molecular weight, polydispersity, and composition on the controlled release properties of poly(d,l-lactic--glycolic acid) (PLGA). However, studies dealing with the effect of monomer sequence distribution have been sparse mainly because of the difficulty of precisely controlling the monomer sequence in PLGA. Herein, we present a semibatch copolymerization strategy that enables the production of statistically sequence-controlled "uniform PLGA" polymers through control of the rate of comonomer addition. Using this method, a series of PEG-PLGA samples having a comparable molecular weight and composition but different sequence distributions (uniform vs gradient) were prepared. The properties of these materials (PEG crystallization/melting, hygroscopicity, aqueous sol-gel transition, drug release kinetics) were found to significantly vary, demonstrating that sequence control only at the statistical level still significantly influences the properties of PLGA. Most notably, uniform PLGA exhibited the more sustained drug release behavior compared to gradient PLGA.
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http://dx.doi.org/10.1021/acsmacrolett.1c00637DOI Listing
December 2021

Synthesis, Structural, and Mechanical Behavior of -Ca(PO)-ZrO Composites Induced by Elevated Thermal Treatments.

Materials (Basel) 2022 Apr 17;15(8). Epub 2022 Apr 17.

Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, Korea.

Biocompatible -Ca(PO) and mechanically stable ZrO composites are currently being combined to overcome the demerits of the individual components. A series of five composites were synthesized using an aqueous precipitation technique. Their structural and mechanical stability was examined through X-ray diffraction, Rietveld refinement, FTIR, Raman spectroscopy, high-resolution scanning electron microscopy, and nanoindentation. The characterization results confirmed the formation of -Ca(PO)--ZrO composites at 1100 °C. Heat treatment above 900 °C resulted in the degradation of the composites because of cationic interdiffusion between Ca ions and O vacancy in Zr ions. Sequential thermal treatments correspond to four different fractional phases: calcium-deficient apatite, -Ca(PO), -ZrO, and -ZrO. The morphological features confirm in situ synthesis, which reveals abnormal grain growth with voids caused by the upsurge in ZrO content. The mechanical stability data indicate significant variation in Young's modulus and hardness throughout the composite.
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http://dx.doi.org/10.3390/ma15082924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029194PMC
April 2022

Viable SARS-CoV-2 shedding under remdesivir and dexamethasone treatment.

J Infect 2022 Jun 26;84(6):834-872. Epub 2022 Mar 26.

Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2022.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957381PMC
June 2022

Lower Dietary Calcium Intake is Associated with a Higher Risk of Mortality in Korean Adults.

J Acad Nutr Diet 2022 Feb 24. Epub 2022 Feb 24.

Department of Food and Nutrition, Seoul National University Seoul, Republic of Korea. Electronic address:

Background: Calcium, one of the most abundant minerals in the human body, has a pivotal role in human physiology. However, only a few studies have examined the association of dietary calcium intake with mortality in a population with low calcium intake.

Objective: The aim of this study was to examine the association of dietary calcium intake with risk of all-cause and cause-specific mortality among Korean adults with low calcium intake.

Design: This study was a prospective cohort study.

Participants/setting: The analysis was conducted using data from 44,327 eligible Korean adults aged 19 years and older who participated in the Korea National Health and Nutrition Examination Survey 2007-2015. Dietary calcium intake was assessed using 1-day 24-hour recall data.

Main Outcome Measures: The main outcomes of this study were mortality from all causes, cancer, cardiovascular disease, respiratory disease, and all other causes combined. The outcome was ascertained through linkage to the death registry compiled by Statistics Korea with the use of the resident registration number.

Statistical Analyses Performed: Weighted Cox proportional hazard models were used to estimate the hazard ratios and 95% CIs of the all-cause and cause-specific mortality according to dietary calcium intake.

Results: During a mean follow-up of 7.28 person-years, 1,889 deaths were ascertained. After multivariable adjustment, the hazard ratios for all-cause mortality for the second quintile to the highest quintile of dietary calcium intake, respectively, compared with the first quintile were 0.86 (95% CI 0.73 to 1.00), 0.82 (95% CI 0.69 to 0.98), 0.85 (95% CI 0.69 to 1.03), and 0.78 (95% CI 0.64 to 0.96) (P for trend from the lowest to the highest quintile = .04). There were no statistically significant associations between dietary calcium intake and risk of mortality from cancer, cardiovascular, or respiratory disease.

Conclusions: In this large prospective cohort study of Korean adults, lower dietary calcium intake was associated with a higher risk of all-cause mortality.
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http://dx.doi.org/10.1016/j.jand.2022.02.012DOI Listing
February 2022

Imaging and Clinical Features of COVID-19 Breakthrough Infections: A Multicenter Study.

Radiology 2022 Jun 1;303(3):682-692. Epub 2022 Feb 1.

From the Department of Radiology, Chonnam National University Hospital, Gwangju, Korea (J.E.L., Y.H.K.); Department of Radiology and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea (M.H., Y.J.J.); Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (M.J.C.); Department of Radiology, Namwon Medical Center, Namwon, Korea (B.H.S.); Department of Radiology, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea (K.J.C.); and Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea (J.Y.Y.).

Background Since vaccines against COVID-19 became available, rare breakthrough infections have been reported despite their high efficacies. Purpose To evaluate the clinical and imaging characteristics of patients with COVID-19 breakthrough infections and compare them with those of unvaccinated patients with COVID-19. Materials and Methods In this retrospective multicenter cohort study, the authors analyzed patient (aged ≥18 years) data from three centers that were registered in an open data repository for COVID-19 between June and August 2021. Hospitalized patients with baseline chest radiographs were divided into three groups according to their vaccination status. Differences between clinical and imaging features were analyzed using the Pearson χ test, Fisher exact test, and analysis of variance. Univariable and multivariable logistic regression analyses were used to evaluate associations between clinical factors, including vaccination status and clinical outcomes. Results Of the 761 hospitalized patients with COVID-19, the mean age was 47 years and 385 (51%) were women; 47 patients (6%) were fully vaccinated (breakthrough infection), 127 (17%) were partially vaccinated, and 587 (77%) were unvaccinated. Of the 761 patients, 412 (54%) underwent chest CT during hospitalization. Among the patients who underwent CT, the proportions without pneumonia were 22% of unvaccinated patients (71 of 326), 30% of partially vaccinated patients (19 of 64), and 59% of fully vaccinated patients (13 of 22) ( < .001). Fully vaccinated status was associated with a lower risk of requiring supplemental oxygen (odds ratio [OR], 0.24 [95% CI: 0.09, 0.64; = .005]) and lower risk of intensive care unit admission (OR, 0.08 [95% CI: 0.09, 0.78; = .02]) compared with unvaccinated status. Conclusion Patients with COVID-19 breakthrough infections had a significantly higher proportion of CT scans without pneumonia compared with unvaccinated patients. Vaccinated patients with breakthrough infections had a lower likelihood of requiring supplemental oxygen and intensive care unit admission. © RSNA, 2022 See also the editorial by Schiebler and Bluemke in this issue.
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http://dx.doi.org/10.1148/radiol.213072DOI Listing
June 2022

Enhanced Chemodynamic Therapy by Cu-Fe Peroxide Nanoparticles: Tumor Microenvironment-Mediated Synergistic Fenton Reaction.

ACS Nano 2022 02 26;16(2):2535-2545. Epub 2022 Jan 26.

Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea.

An urgent need in chemodynamic therapy (CDT) is to achieve high Fenton catalytic efficiency at small doses of CDT agents. However, simple general promotion of the Fenton reaction increases the risk of damaging normal cells along with the cancer cells. Therefore, a tailored strategy to selectively enhance the Fenton reactivity in tumors, for example, by taking advantage of the characteristics of the tumor microenvironment (TME), is in high demand. Herein, a heterogeneous CDT system based on copper-iron peroxide nanoparticles (CFp NPs) is designed for TME-mediated synergistic therapy. CFp NPs degrade under the mildly acidic conditions of TME, self-supply HO, and the released Cu and Fe ions, with their larger portions at lower oxidation states, cooperatively facilitate hydroxyl radical production through a highly efficient catalytic loop to achieve an excellent tumor therapeutic efficacy. This is distinct from previous heterogeneous CDT systems in that the synergism is closely coupled with the Cu-assisted conversion of Fe to Fe rather than their independent actions. As a result, almost complete ablation of tumors at a minimal treatment dose is demonstrated without the aid of any other therapeutic modality. Furthermore, CFp NPs generate O during the catalysis and exhibit a TME-responsive T magnetic resonance imaging contrast enhancement, which are useful for alleviating hypoxia and monitoring of tumors, respectively.
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http://dx.doi.org/10.1021/acsnano.1c09171DOI Listing
February 2022

Clinical Factors Associated with Cavitary Tuberculosis and Its Treatment Outcomes.

J Pers Med 2021 Oct 25;11(11). Epub 2021 Oct 25.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju 28644, Korea.

Cavitary pulmonary tuberculosis (TB) is associated with poor outcomes, treatment recurrence, higher transmission rates, and the development of drug resistance. However, reports on its clinical characteristics, associated factors, and treatment outcomes are lacking. Hence, this study sought to evaluate the clinical factors associated with cavitary pulmonary TB and its treatment outcomes. We retrospectively evaluated 410 patients with drug-susceptible pulmonary TB in a university hospital in Korea between 2014 and 2019. To evaluate the factors associated with cavitary TB, multivariable logistic regression was performed with adjustments for potential confounders. We also compared the treatment outcomes between patients with cavitary TB and those without cavitary TB. Of the 410 patients, 244 (59.5%) had non-cavitary TB and 166 (40.5%) had cavitary TB. Multivariable logistic analysis with forward selection method showed that body mass index (BMI) (adjusted OR = 0.88, 95% CI: 0.81-0.97), previous history of TB (adjusted OR = 3.45, 95% CI: 1.24-9.59), ex- or current smoker (adjusted OR = 1.77, 95% CI: 1.01-3.13), diabetes mellitus (adjusted OR = 2.72, 95% CI: 1.36-5.44), and positive results on the initial sputum acid-fast bacilli (AFB) smear (adjusted OR = 2.24, 95% CI: 1.26-3.98) were significantly associated with cavitary TB. Although treatment duration was significantly longer in patients with cavitary TB than in those with non-cavitary TB (248 (102-370 days) vs. 202 (98-336 days), < 0.001), the recurrence rate after successful treatment was significantly higher in the patients with cavitary TB than in those with non-cavitary TB (0.4% vs. 3.0% = 0.042). In conclusion, ex- or current smoker, lower BMI, previous history of TB, diabetes mellitus, and positivity of the initial AFB smear were associated with cavitary TB. The patients with cavitary TB had more AFB culture-positive results at 2 months, longer treatment duration, and higher recurrence rates than those with non-cavitary TB.
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http://dx.doi.org/10.3390/jpm11111081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622689PMC
October 2021

Association of coffee drinking with all-cause and cause-specific mortality in over 190,000 individuals: data from two prospective studies.

Int J Food Sci Nutr 2022 Jun 15;73(4):513-521. Epub 2021 Nov 15.

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

We examined the association of coffee drinking with all-cause and cause-specific mortality in a pooled analysis of two Korean prospective cohort studies: The Korea National Health and Nutrition Examination Survey and the Korean Genome and Epidemiology Study. We included 192,222 participants, and a total of 6057 deaths were documented. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), and the HRs were combined using a random-effects model. Coffee drinking was associated with a lower risk of all-cause mortality [HR (95% CI) = 0.84 (0.77-0.92), for ≥3 cups/day of coffee drinking versus non-drinkers; for trend = 0.004]. We observed the potential benefit of coffee drinking for mortality due to cardiovascular disease, respiratory disease, and diabetes, but not for cancer mortality. Overall, we found that moderate coffee drinking was associated with a lower risk of death in population-based cohort analysis of Korean adults.
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http://dx.doi.org/10.1080/09637486.2021.2002829DOI Listing
June 2022

Antifreeze and Rheological Properties of Injectable Triblock Copolymer Hydrogels with Supramolecular Junctions.

Macromol Rapid Commun 2021 Nov 5:e2100618. Epub 2021 Nov 5.

The National Creative Research Initiative Center for Intelligent Hybrids, Department of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

ABC triblock copolymers composed of hydrophobic poly(ε-caprolactone) (PCL), zwitterionic poly(carboxybetaine methacrylate) midblock, and P(PEGMA-UPy ) containing supramolecular ureidopyrimidinone moieties, poly(ε-caprolactone-block-carboxybetaine methacrylate-block-[poly(ethylene glycol) methyl ether methacrylate-co-(α-methacryloyl-ω-(6-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)hexylcarbamoyloxy)poly(ethylene glycol))]), are investigated to achieve multifunctional antifreeze hydrogels. The PCL and P(PEGMA-UPy ) blocks induce the formation of physical network with a hierarchical nanostructure comprising hydrophobic PCL cores and supramolecular junctions, respectively. The super-hydrophilic nature of polyzwitterion midblocks and the confinement effect of the supramolecular junctions enhance the antifreeze performance, where the majority of water molecules remains supercooled below sub-zero temperature. The hydrogel relaxation characterized over a wide range of timescale reveals that the facile dynamics of the supramolecular junctions lead to the self-healing and injectability of the hydrogels. In conjunction with the biodegradable PCL cores, the antifreeze and rheological characteristics of the triblock copolymer hydrogels provide significant potential to use for cryo-preservable and bio-injectable drug storage and delivery.
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http://dx.doi.org/10.1002/marc.202100618DOI Listing
November 2021

Azidothymidine Downregulates Insulin-Like Growth Factor-1 Induced Lipogenesis by Suppressing Mitochondrial Biogenesis and Mitophagy in Immortalized Human Sebocytes.

Ann Dermatol 2021 Oct 8;33(5):425-431. Epub 2021 Sep 8.

Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.

Background: Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile.

Objective: To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulinlike growth factor (IGF)-1-induced lipid synthesis in sebocytes.

Methods: Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated.

Results: TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptorgamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes.

Conclusion: These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.
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http://dx.doi.org/10.5021/ad.2021.33.5.425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460479PMC
October 2021

Technical Feasibility, Outcomes, and Patient Satisfaction After Needlescopic and Laparoscopic Bariatric Surgery: a Randomized Study.

Obes Surg 2021 11 4;31(11):5085-5091. Epub 2021 Sep 4.

School of Medicine, Department of Surgery, Duke University, 407 Crutchfield St, Durham, NC, 27704, USA.

Background: Needlescopic instruments create a 3-mm incision and may result in less pain and superior cosmesis. There is limited understanding of the effectiveness of needlescopic instruments in patients with a body mass index (BMI) > 35 kg/m. We report perioperative outcomes and perception of body image with use of needlescopic instruments after bariatric surgery.

Methods: Laparoscopic bariatric procedures were performed on 30 adults at a single academic medical center from January to December 2017. Patients were randomized to conventional laparoscopy (LAP) or needlescopic (NEED) surgery. The Multidimensional Body-Self Relations Questionnaire (MBSRQ) and Patient Scar Assessment Questionnaire (PSAQ) were completed at 6 months and 1 year. Univariate analysis was performed on perioperative outcomes and survey scores.

Results: Surgery was completed on patients in the LAP group (N = 13) and compared to the NEED group (N = 17). The mean BMI was 41.4 kg/m2 LAP and 41.1 kg/m2 NEED. The most common procedure was Roux-en-Y gastric bypass (RYGB), with 13 RYGB in LAP and 12 RYGB in NEED (P = 0.76).The operative time was not significantly different between the LAP and the NEED group (209.5 ± 66.1 vs 181.9 ± 58.1 min, P = 0.48). There was no leak or mortality in the 30-day follow-up period. Within MBSRQ, the patient's appearance self-evaluation score was similar between LAP and NEED (2.5 ± 0.6 vs 2.4 ± 0.6, P = 0.61). Within PSAQ, the mean satisfaction score for incision appearance was also similar between LAP and NEED (16.1± 2.9 vs 15.4 ± 4.6, P = 0.85). Incision-related perceptions remained consistent at 6 months and 1 year after bariatric surgery.

Conclusions: Needlescopic instruments are safe and a viable alternative to use during bariatric surgery. Appearance and perception of scar were similar between groups. Further studies with needlescopic instruments should include patients with a BMI > 35 kg/m and compare additional factors associated with body image.
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http://dx.doi.org/10.1007/s11695-021-05675-5DOI Listing
November 2021

Additive Fabrication and Characterization of Biomimetic Composite Bone Scaffolds with High Hydroxyapatite Content.

Gels 2021 Jul 23;7(3). Epub 2021 Jul 23.

Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, Korea.

With the increased incidence of bone defects following trauma or diseases in recent years, three-dimensional porous scaffolds fabricated using bioprinting technologies have been widely explored as effective alternatives to conventional bone grafts, which provide cell-friendly microenvironments promoting bone repair and regeneration. However, the limited use of biomaterials poses a significant challenge to the robust and accurate fabrication of bioprinted bone scaffolds that enable effective regeneration of the target tissues. Although bioceramic/polymer composites can provide tunable biomimetic conditions, their effects on the bioprinting process are unclear. Thus, in this study, we fabricated hydroxyapatite (HA)/gelatin composite scaffolds containing large weight fractions of HA using extrusion-based bioprinting, with the aim to provide an adequate biomimetic environment for bone tissue regeneration with compositional and mechanical similarity to the natural bone matrix. The overall features of the bioprinted HA/gelatin composite scaffolds, including rheological, morphological, physicochemical, mechanical, and biological properties, were quantitatively assessed to determine the optimal conditions for both fabrication and therapeutic efficiency. The present results show that the bioprinted bioceramic/hydrogel scaffolds possess excellent shape fidelity; mechanical strength comparable to that of native bone; and enhanced bioactivity in terms of cell proliferation, attachment, and osteogenic differentiation. This study provides a suitable alternative direction for the fabrication of bioceramic/hydrogel-based scaffolds for bone repair based on bioprinting.
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http://dx.doi.org/10.3390/gels7030100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395852PMC
July 2021

Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea.

J Korean Med Sci 2021 Aug 9;36(31):e223. Epub 2021 Aug 9.

Department of Neurosurgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.
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http://dx.doi.org/10.3346/jkms.2021.36.e223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352786PMC
August 2021

Multilayered Cell Sheets of Cardiac Reprogrammed Cells for the Evaluation of Drug Cytotoxicity.

Tissue Eng Regen Med 2021 10 12;18(5):807-818. Epub 2021 Jul 12.

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Background: Various cell-culture systems have been used to evaluate drug toxicity in vitro. However, factors that affect cytotoxicity outcomes in drug toxicity evaluation systems remain elusive. In this study, we used multilayered sheets of cardiac-mimetic cells, which were reprogrammed from human fibroblasts, to investigate the effects of the layer number on drug cytotoxicity outcomes.

Methods: Cell sheets of cardiac-mimetic cells were fabricated by reprogramming of human fibroblasts into cardiac-mimetic cells via coculture with cardiac cells and electric stimulation, as previously described. Double-layered cell sheets were prepared by stacking the cell sheets. The mono- and double-layered cell sheets were treated with 5-fluorouracil (5-FU), an anticancer drug, in vitro. Subsequently, apoptosis and lipid peroxidation were analyzed. Furthermore, effects of cardiac-mimetic cell density on cytotoxicity outcomes were evaluated by culturing cells in monolayer at various cell densities.

Results: The double-layered cell sheets exhibited lower cytotoxicity in terms of apoptosis and lipid peroxidation than the mono-layered sheets at the same 5-FU dose. In addition, the double-layered cell sheets showed better preservation of mitochondrial function and plasma membrane integrity than the monolayer sheets. The lower cytotoxicity outcomes in the double-layered cell sheets may be due to the higher intercellular interactions, as the cytotoxicity of 5-FU decreased with cell density in monolayer cultures of cardiac-mimetic cells.

Conclusion: The layer number of cardiac-mimetic cell sheets affects drug cytotoxicity outcomes in drug toxicity tests. The in vitro cellular configuration that more closely mimics the in vivo configuration in the evaluation systems seems to exhibit lower cytotoxicity in response to drug.
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http://dx.doi.org/10.1007/s13770-021-00363-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440721PMC
October 2021

Correction to: Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.

J Transl Med 2021 Jun 21;19(1):266. Epub 2021 Jun 21.

Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.

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http://dx.doi.org/10.1186/s12967-021-02916-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218406PMC
June 2021

Activation of Nrf2/HO-1 by Peptide YD1 Attenuates Inflammatory Symptoms through Suppression of TLR4/MYyD88/NF-κB Signaling Cascade.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju 501-759, Korea.

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.
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http://dx.doi.org/10.3390/ijms22105161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152960PMC
May 2021

Association Between Visit-to-Visit Fasting Plasma Glucose Variability and Osteoporotic Fractures in Nondiabetic Subjects.

J Clin Endocrinol Metab 2021 08;106(9):e3449-e3460

Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

Context: Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes.

Objective: We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes.

Methods: Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM).

Results: Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results.

Conclusion: FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.
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http://dx.doi.org/10.1210/clinem/dgab370DOI Listing
August 2021

Fenofibrate, a PPARα agonist, reduces hepatic fat accumulation through the upregulation of TFEB-mediated lipophagy.

Metabolism 2021 07 11;120:154798. Epub 2021 May 11.

Department of Endocrinology and Metabolism, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Recent studies have shown that dysregulation of autophagy is involved in the development of nonalcoholic fatty liver disease (NAFLD). Transcription factors E3 (TFE3) and EB (TFEB) are master regulators of the transcriptional response of basic cellular processes such as lysosomal biogenesis and autophagy. Here, we investigated the role of fenofibrate, a PPARα agonist, in promotion of intracellular lipid clearance by upregulation of TFEB/TFE3.

Methods: We investigated whether the effects of fenofibrate on livers were dependent on TFEB in high fat diet (HFD)-fed mice and in vivo Tfeb knockdown mice. These mice were analyzed for characteristics of obesity and diabetes; the effects of fenofibrate on hepatic fat content, glucose sensitivity, insulin resistance, and autophagy functional dependence on TFEB were investigated. HepG2, Hep3B, TSC2 and tsc2 MEFs, tfeb wild type- and tfeb knockout-HeLa cells were used for in vitro experiments.

Results: Fenofibrate treatment activated autophagy and TFEB/TFE3 and reduced hepatic fat accumulation in an mTOR-independent manner. Knockdown of TFEB offset the effects of fenofibrate on autophagy and hepatic fat accumulation. In addition, fenofibrate treatment induced lysosomal Ca release through mucolipin 1, activated calcineurin and the CaMKKβ-AMPK-ULK1 pathway, subsequently promoted TFEB and TFE3 dephosphorylation and nuclear translocation. Treatment with calcium chelator or knockdown of mucolipin 1 in hepatocytes offset the effects of fenofibrate treatment on autophagy and hepatic fat accumulation.

Conclusion: Activation of PPARα ameliorates hepatic fat accumulation via activation of TFEB and lipophagy induction. Lysosomal calcium signaling appears to play a critical role in this process. In addition, activation of TFEB by modulating nuclear receptors including PPARα with currently available drugs or new molecules might be a therapeutic target for treatment of NAFLD and other cardiometabolic diseases.
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http://dx.doi.org/10.1016/j.metabol.2021.154798DOI Listing
July 2021

Risk Factors of Outcomes of COVID-19 Patients in Korea: Focus on Early Symptoms.

J Korean Med Sci 2021 May 10;36(18):e132. Epub 2021 May 10.

Department of Urology, Kyung Hee University School of Medicine, Seoul, Korea.

Background: Coronavirus disease 2019 (COVID-19) has spread around the globe, and it is important to determine the risk factors of death in the general population. Our study aimed to determine the risk factors of death and severe illness requiring supplemental oxygen therapy based on the demographic and clinical characteristics of COVID-19 patients in Korea.

Methods: In this study, we used data provided by the Korea Disease Control and Prevention Agency (KDCA) and analyzed a total of 5,068 patients with COVID-19, excluding 19 pregnant women and 544 individuals with missing data. We performed logistic regression analysis to determine the impact of early symptoms on survival and severe disease. Logistic regression models included sex, age, number of comorbidities, symptoms on admission, blood pressure, heart rate, and body temperature as explanatory variables, and death and oxygen therapy as outcome variables.

Results: Logistic regression analyses revealed that the male sex, older age (≥ 60 years), higher number of comorbidities, presence of symptoms on admission, heart rate ≥ 120 bpm, and body temperature ≥ 37.5°C presented with higher risk of in-hospital death and oxygen therapy requirement. Conversely, rhinorrhea and headache were associated with a low risk of death and oxygen therapy requirement. The findings showed that cough, sputum, and fever were the most common symptoms on admission, while 25.3% of patients with COVID-19 were asymptomatic.

Conclusion: COVID-19 patients with high-risk early symptoms on admission, such as dyspnea and altered mental status, and those without low-risk symptoms of rhinorrhea and headache should be included in priority treatment groups.
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http://dx.doi.org/10.3346/jkms.2021.36.e132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111043PMC
May 2021

Allopurinol ameliorates high fructose diet induced hepatic steatosis in diabetic rats through modulation of lipid metabolism, inflammation, and ER stress pathway.

Sci Rep 2021 05 10;11(1):9894. Epub 2021 May 10.

Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, #892 Dongnam-ro, Gangdong-gu, Seoul, 05278, Korea.

Excess fructose consumption contributes to development obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). Uric acid (UA), a metabolite of fructose metabolism, may have a direct role in development of NAFLD, with unclear mechanism. This study aimed to evaluate role of fructose and UA in NAFLD and explore mechanisms of allopurinol (Allo, a UA lowering medication) on NAFLD in Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed a high fructose diet (HFrD), with Long-Evans Tokushima Otsuka (LETO) rats used as a control. There were six groups: LETO, LETO-Allo, OLETF, OLETF-Allo, OLETF-HFrD, and OLETF-HFrD-Allo. HFrD significantly increased body weight, epididymal fat weight, and serum concentrations of UA, cholesterol, triglyceride, HbA1c, hepatic enzymes, HOMA-IR, fasting insulin, and two hour-glucose after intraperitoneal glucose tolerance tests, as well as NAFLD activity score of liver, compared to the OLETF group. Allopurinol treatment significantly reduced hepatic steatosis, epididymal fat, serum UA, HOMA-IR, hepatic enzyme levels, and cholesterol in the OLETF-HFrD-Allo group. Additionally, allopurinol significantly downregulated expression of lipogenic genes, upregulated lipid oxidation genes, downregulated hepatic pro-inflammatory cytokine genes, and decreased ER-stress induced protein expression, in comparison with the OLETF-HFrD group. In conclusion, allopurinol ameliorates HFrD-induced hepatic steatosis through modulation of hepatic lipid metabolism, inflammation, and ER stress pathway. UA may have a direct role in development of fructose-induced hepatic steatosis, and allopurinol could be a candidate for prevention or treatment of NAFLD.
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http://dx.doi.org/10.1038/s41598-021-88872-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110790PMC
May 2021

3D Printed Porous Methacrylate/Silica Hybrid Scaffold for Bone Substitution.

Adv Healthc Mater 2021 06 5;10(12):e2100117. Epub 2021 May 5.

Department of Materials, Imperial College London, London, SW7 2AZ, United Kingdom.

Inorganic-organic hybrid biomaterials made with star polymer poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate) and silica which show promising mechanical properties, are 3D printed as bone substitutes for the first time, by direct ink writing of the sol. Three different inorganic:organic ratios of poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate)-star-SiO hybrid inks are printed with pore channels in the range of 100-200 µm. Mechanical properties of the 3D printed scaffolds fall within the range of trabecular bone, and MC3T3 pre-osteoblast cells are able to adhere to the scaffolds in vitro, regardless of their compositions. Osteogenic and angiogenic properties of the hybrid scaffolds are shown using a rat calvarial defect model. Hybrid scaffolds with 40:60 inorganic:organic composition are able to instigate new vascularized bone formation within its pore channels and polarize macrophages toward M2 phenotype. 3D printing inorganic-organic hybrids with sophisticated polymer structure opens up possibilities to produce novel bone graft materials.
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http://dx.doi.org/10.1002/adhm.202100117DOI Listing
June 2021

Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.

J Transl Med 2021 05 4;19(1):192. Epub 2021 May 4.

Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.

Scleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α play important roles in the pathogenesis of scleroderma. Because metformin, a medication used to treat diabetes, has effective immunoregulatory functions, we investigated its therapeutic function in scleroderma. Mice in a model of bleomycin-induced scleroderma were treated with metformin for 2 weeks. Histological assessment demonstrated protective effects of metformin against scleroderma. Metformin decreased the expression of pro-inflammatory factors in dermal tissue and lymphocytes. It also decreased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) and fibrosis-inducing molecules both in vivo and in vitro. These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1β, IL-6, and TNF-α. To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment. These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.
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http://dx.doi.org/10.1186/s12967-021-02860-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097822PMC
May 2021

Novel Anti-Inflammatory Effects of Brimonidine on -Induced Inflammatory Reaction.

Ann Dermatol 2020 Aug 30;32(4):342-344. Epub 2020 Jun 30.

Department of Dermatology, School of Medicine, Kyungpook National University, Daegu, Korea.

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http://dx.doi.org/10.5021/ad.2020.32.4.342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992652PMC
August 2020

Sarcoidosis during treatment of pulmonary tuberculosis: a rare case report and review of the literature.

J Int Med Res 2021 Apr;49(4):3000605211001632

Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea.

The coexistence of pulmonary tuberculosis and pulmonary sarcoidosis is rare. Further, the morphological features of pulmonary tuberculosis with comorbid pulmonary sarcoidosis are similar to those of tuberculosis alone. There are obvious clinical, histological, and radiological similarities between sarcoidosis and tuberculosis, which makes differential diagnosis very challenging, particularly in countries with a high burden of tuberculosis. Here, a rare case of computed tomography (CT) findings of sarcoidosis that developed during tuberculosis treatment is reported. The 46-year-old male patient had no significant symptoms and was undergoing treatment for infection. Chest CT revealed enlargement of multiple lymph nodes, without cystic or necrotic changes, in the mediastinum and both hili, and post-infectious changes consistent with the sequelae of tuberculosis infection in the left upper lobe. Chest radiographic evidence was accompanied by compatible clinical features and noncaseating granulomas on biopsy. As the patient was clinically stable, corticosteroid treatment was not initiated. To date, the patient remains without specific symptoms and outpatient follow-ups continue. Although rare, sarcoidosis may occur during treatment of pulmonary tuberculosis, and requires attention for diagnosis and treatment. The present case draws a radiological picture of how tuberculosis evolved to sarcoidosis.
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http://dx.doi.org/10.1177/03000605211001632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059043PMC
April 2021

Large-Scale Survey Data Analysis with Penalized Regression: A Monte Carlo Simulation on Missing Categorical Predictors.

Multivariate Behav Res 2021 Mar 11:1-29. Epub 2021 Mar 11.

Department of Education, Korea National University of Education.

With the advent of the big data era, machine learning methods have evolved and proliferated. This study focused on penalized regression, a procedure that builds interpretive prediction models among machine learning methods. In particular, penalized regression coupled with large-scale data can explore hundreds or thousands of variables in one statistical model without convergence problems and identify yet uninvestigated important predictors. As one of the first Monte Carlo simulation studies to investigate predictive modeling with missing categorical predictors in the context of social science research, this study endeavored to emulate real social science large-scale data. Likert-scaled variables were simulated as well as multiple-category and count variables. Due to the inclusion of the categorical predictors in modeling, penalized regression methods that consider the grouping effect were employed such as group Mnet. We also examined the applicability of the simulation conditions with a real large-scale dataset that the simulation study referenced. Particularly, the study presented selection counts of variables after multiple iterations of modeling in order to consider the bias resulting from data-splitting in model validation. Selection counts turned out to be a necessary tool when variable selection is of research interest. Efforts to utilize large-scale data to the fullest appear to offer a valid approach to mitigate the effect of nonignorable missingness. Overall, penalized regression which assumes linearity is a viable method to analyze social science large-scale survey data.
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http://dx.doi.org/10.1080/00273171.2021.1891856DOI Listing
March 2021

Prognostic Implications of CT Feature Analysis in Patients with COVID-19: a Nationwide Cohort Study.

J Korean Med Sci 2021 Mar 1;36(8):e51. Epub 2021 Mar 1.

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Few studies have classified chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) and analyzed their correlations with prognosis. The present study aimed to evaluate retrospectively the clinical and chest CT findings of COVID-19 and to analyze CT findings and determine their relationships with clinical severity.

Methods: Chest CT and clinical features of 271 COVID-19 patients were assessed. The presence of CT findings and distribution of parenchymal abnormalities were evaluated, and CT patterns were classified as bronchopneumonia, organizing pneumonia (OP), or diffuse alveolar damage (DAD). Total extents were assessed using a visual scoring system and artificial intelligence software. Patients were allocated to two groups based on clinical outcomes, that is, to a severe group (requiring O₂ therapy or mechanical ventilation, n = 55) or a mild group (not requiring O₂ therapy or mechanical ventilation, n = 216). Clinical and CT features of these two groups were compared and univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors.

Results: Age, lymphocyte count, levels of C-reactive protein, and procalcitonin were significantly different in the two groups. Forty-five of the 271 patients had normal chest CT findings. The most common CT findings among the remaining 226 patients were ground-glass opacity (98%), followed by consolidation (53%). CT findings were classified as OP (93%), DAD (4%), or bronchopneumonia (3%) and all nine patients with DAD pattern were included in the severe group. Uivariate and multivariate analyses showed an elevated procalcitonin (odds ratio [OR], 2.521; 95% confidence interval [CI], 1.001-6.303, = 0.048), and higher visual CT scores (OR, 1.137; 95% CI, 1.042-1.236; = 0.003) or higher total extent by AI measurement (OR, 1.048; 95% CI, 1.020-1.076; < 0.001) were significantly associated with a severe clinical course.

Conclusion: CT findings of COVID-19 pneumonia can be classified into OP, DAD, or bronchopneumonia patterns and all patients with DAD pattern were included in severe group. Elevated inflammatory markers and higher CT scores were found to be significant predictors of poor prognosis in patients with COVID-19 pneumonia.
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http://dx.doi.org/10.3346/jkms.2021.36.e51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921372PMC
March 2021

Gastrointestinal mucosal damage in patients with COVID-19 undergoing endoscopy: an international multicentre study.

BMJ Open Gastroenterol 2021 02;8(1)

Department of Gastroenterology, Newcastle upon Tyne hospitals NHS Trust, Newcastle upon Tyne, UK.

Background: Although evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported.

Aims: We aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19.

Methods: All consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ or Fisher's exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors.

Results: Between February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58-74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69-86.87)) and presence of GI symptoms (OR=6.17 (1.13-33.67)) were independently associated with major abnormalities at multivariate analysis.

Conclusion: In this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy.

Trial Registration Number: ClinicalTrial.gov (ID: NCT04318366).
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http://dx.doi.org/10.1136/bmjgast-2020-000578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907837PMC
February 2021

Development of a deep learning-based algorithm for the automatic detection and quantification of aortic valve calcium.

Eur J Radiol 2021 Apr 6;137:109582. Epub 2021 Feb 6.

Department of Radiology, Center for Clinical Imaging Data Science, Research Institute of Radiological Sciences, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: We aimed to develop a deep learning (DL)-based algorithm for automated quantification of aortic valve calcium (AVC) from non-enhanced electrocardiogram-gated cardiac CT scans and compare performance of DL-measured AVC volume and Agatston score with those of visual gradings by radiologist readers for classification of AVC severity.

Method: A total of 589 CT examinations performed at a single center between March 2010 and August 2017 were retrospectively included. The DL algorithm was designed to segment AVC and to quantify AVC volume, and Agatston score was calculated using attenuation values. Manually measured AVC volume and Agatston score were used as ground truth. To validate AVC segmentation performance, the Dice coefficient was calculated. For observer performance testing, four radiologists determined AVC grade in two reading rounds. The diagnostic performance of DL-measured AVC volume and Agaston score for classifying severe AVC was compared with that of each reader's assessment.

Results: After applying the DL algorithm, the Dice coefficient score was 0.807. In patients with AVC, accuracy of DL-measured AVC volume for AVC grading was 97.0 % with area under the curve (AUC) of 0.964 (95 % confidence interval [CI] 0.923-1) in the test set, which was better than the radiologist readers (accuracy 69.7 %-91.9 %, AUC 0.762-0.923) with manually measured AVC volume as ground truth. When manually measured AVC Agatston score was used as ground truth, accuracy of DL-measured AVC Agatston score for AVC grading was 92.9 % with AUC of 0.933 (95 % CI 0.885-0.981) in the test set, which was also better than the radiologist readers (accuracy 77.8-89.9 %, AUC 0.791-0.903).

Conclusions: DL-based automated AVC quantification may be comparable with manual measurements. The diagnostic performance of the DL-measured AVC volume and Agatston score for classification of severe AVC outperforms radiologist readers.
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http://dx.doi.org/10.1016/j.ejrad.2021.109582DOI Listing
April 2021

What We Do Know and Do Not Yet Know about COVID-19 Vaccines as of the Beginning of the Year 2021.

Authors:
Jin Hong Yoo

J Korean Med Sci 2021 Feb 8;36(6):e54. Epub 2021 Feb 8.

Division of Infectious Diseases, Department of Internal Medicine, Bucheon St. Mary's Hospital, Bucheon, Korea.

Coronavirus disease 2019 (COVID-19), which started at the end of 2019 and has spread worldwide, has remained unabated in 2021. Since non-pharmaceutical interventions including social distancing are facing limitations in controlling COVID-19, additional absolute means to change the trend are necessary. To this end, coronavirus-specific antiviral drugs and vaccines are urgently needed, but for now, the priority is to promote herd immunity through extensive nationwide vaccination campaign. In addition to the vaccines based on the conventional technology such inactivated or killed virus or protein subunit vaccines, several vaccines on the new technological platforms, for example, nucleic acids-based vaccines delivered by viral carriers, nanoparticles, or plasmids as a medium were introduced in this pandemic. In addition to achieving sufficient herd immunity with vaccination, the development of antiviral treatments that work specifically against COVID-19 will also be necessary to terminate the epidemic completely.
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http://dx.doi.org/10.3346/jkms.2021.36.e54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870421PMC
February 2021

Phenomenology of the Initial Burst Release of Drugs from PLGA Microparticles.

ACS Biomater Sci Eng 2020 11 9;6(11):6053-6062. Epub 2020 Oct 9.

Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47907, United States of America.

Poly(lactic--glycolic acid) (PLGA) is the most prevalent polymer drug delivery vehicle in use today. There are about 20 commercialized drug products in which PLGA is used as an excipient. In more than half of these formulations, PLGA is used in the form of microparticles (with sizes in the range between 60 nm and 100 μm). The primary role of PLGA is to control the kinetics of drug release toward achieving sustained release of the drug. Unfortunately, most drug-loaded PLGA microparticles exhibit a common drawback: an initial uncontrolled burst of the drug. After 30 years of utilization of PLGA in controlled drug delivery systems, this initial burst drug release still remains an unresolved challenge. In this Review, we present a summary of the proposed mechanisms responsible for this phenomenon and the known factors affecting the burst release process. Also, we discuss examples of recent efforts made to reduce the initial burst release of the drug from PLGA particles.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01228DOI Listing
November 2020
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