Publications by authors named "Young Jae Lee"

144 Publications

New Surgical Technique for Robotic Myomectomy: Continuous Locking Suture on Myoma (LSOM) Technique.

J Clin Med 2021 Feb 8;10(4). Epub 2021 Feb 8.

Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Seoul Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Robot-assisted laparoscopic myomectomy (RALM) has broadened the indications even in complex myomas. However, the high cost of RALM remains the main disadvantage. Therefore, a surgical technique that can reduce the cost of RALM and still has the advantages of robotic surgery is required. We propose a "locking suture on myoma (LSOM)" technique and compared the operative and perioperative outcomes of patients who underwent RALM with or without the LSOM technique. We included 337 patients who underwent RALM with ( = 160) or without ( = 177) the LSOM technique between March 2019 and August 2020. The LSOM group had low parity and gravidity, with a low rate of Cesarean sections. Myoma type was not different between the groups; however, patients in the LSOM group had larger, heavier, and higher number of myomas, although fewer patients had multiple myomas and were discharged earlier. Total operating time, estimated blood loss, pre- and postoperative hemoglobin levels, transfusion rate, and postoperative fever were not different between the two groups. In conclusion, the LSOM technique may be a viable surgical option for myomas, as it can reduce the cost of RALM by obviating the need for robotic Tenaculum forceps.
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http://dx.doi.org/10.3390/jcm10040654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914728PMC
February 2021

Phase imaging with computational specificity (PICS) for measuring dry mass changes in sub-cellular compartments.

Nat Commun 2020 12 7;11(1):6256. Epub 2020 Dec 7.

Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Due to its specificity, fluorescence microscopy has become a quintessential imaging tool in cell biology. However, photobleaching, phototoxicity, and related artifacts continue to limit fluorescence microscopy's utility. Recently, it has been shown that artificial intelligence (AI) can transform one form of contrast into another. We present phase imaging with computational specificity (PICS), a combination of quantitative phase imaging and AI, which provides information about unlabeled live cells with high specificity. Our imaging system allows for automatic training, while inference is built into the acquisition software and runs in real-time. Applying the computed fluorescence maps back to the quantitative phase imaging (QPI) data, we measured the growth of both nuclei and cytoplasm independently, over many days, without loss of viability. Using a QPI method that suppresses multiple scattering, we measured the dry mass content of individual cell nuclei within spheroids. In its current implementation, PICS offers a versatile quantitative technique for continuous simultaneous monitoring of individual cellular components in biological applications where long-term label-free imaging is desirable.
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http://dx.doi.org/10.1038/s41467-020-20062-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721808PMC
December 2020

Anti-inflammatory effect of sulforaphane on LPS-stimulated RAW 264.7 cells and ob/ob mice.

J Vet Sci 2020 Nov;21(6):e91

College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea.

Background: Sulforaphane (SFN) is an isothiocyanate compound present in cruciferous vegetables. Although the anti-inflammatory effects of SFN have been reported, the precise mechanism related to the inflammatory genes is poorly understood.

Objectives: This study examined the relationship between the anti-inflammatory effects of SFN and the differential gene expression pattern in SFN treated ob/ob mice.

Methods: Nitric oxide (NO) level was measured using a Griess assay. The inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were analyzed by Western blot analysis. Pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing analysis was performed to evaluate the differential gene expression in the liver of ob/ob mice.

Results: The SFN treatment significantly attenuated the iNOS and COX-2 expression levels and inhibited NO, TNF-α, IL-1β, and IL-6 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA sequencing analysis showed that the expression levels of 28 genes related to inflammation were up-regulated (> 2-fold), and six genes were down-regulated (< 0.6-fold) in the control ob/ob mice compared to normal mice. In contrast, the gene expression levels were restored to the normal level by SFN. The protein-protein interaction (PPI) network showed that chemokine ligand (Cxcl14, Ccl1, Ccl3, Ccl4, Ccl17) and chemokine receptor (Ccr3, Cxcr1, Ccr10) were located in close proximity and formed a "functional cluster" in the middle of the network.

Conclusions: The overall results suggest that SFN has a potent anti-inflammatory effect by normalizing the expression levels of the genes related to inflammation that were perturbed in ob/ob mice.
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http://dx.doi.org/10.4142/jvs.2020.21.e91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710464PMC
November 2020

Robot-Assisted Laparoscopic Myomectomy versus Abdominal Myomectomy for Large Myomas Sized over 10 cm or Weighing 250 g.

Yonsei Med J 2020 Dec;61(12):1054-1059

Department of Obstetrics & Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Here, we compared the operative and perioperative outcomes between robot-assisted laparoscopic myomectomy (RALM) and abdominal myomectomy (AM) in patients with large (>10 cm) or heavy myomas (>250 g).

Materials And Methods: We included 278 patients who underwent multi-port RALM (n=126) or AM (n=151) for large or heavy myomas in a tertiary care hospital between April 2019 and June 2020. The t-test, chi-square, Bonferroni's test, and multiple linear regression were used.

Results: No differences were observed in age, body mass index, parity, or history of pelvic surgery between the two groups. Myoma diameters were not different (10.8±2.52 cm vs. 11.2±3.0 cm, =0.233), but myomas were lighter in the RALM group than in the AM group (444.6±283.14 g vs. 604.68±368.35 g, respectively, =0.001). The RALM group had a higher proportion of subserosal myomas, fewer myomas, fewer large myomas over >3 cm, lighter myomas, and longer total operating time. However, the RALM group also had shorter hospital stay and fewer short-term complications. Estimated blood loss (EBL) was not different between the two groups. The number of removed myomas was the most significant factor (coefficient=10.89, <0.0001) affecting the EBL.

Conclusion: RALM is a feasible myomectomy technique even for large or heavy myomas. RALM patients tend to have shorter hospital stays and fewer postoperative fevers within 48 hours. However, RALM has longer total operating time.
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http://dx.doi.org/10.3349/ymj.2020.61.12.1054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700878PMC
December 2020

Quantifying myelin content in brain tissue using color Spatial Light Interference Microscopy (cSLIM).

PLoS One 2020 19;15(11):e0241084. Epub 2020 Nov 19.

Quantitative Light Imaging Laboratory, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

Deficient myelination of the brain is associated with neurodevelopmental delays, particularly in high-risk infants, such as those born small in relation to their gestational age (SGA). New methods are needed to further study this condition. Here, we employ Color Spatial Light Interference Microscopy (cSLIM), which uses a brightfield objective and RGB camera to generate pathlength-maps with nanoscale sensitivity in conjunction with a regular brightfield image. Using tissue sections stained with Luxol Fast Blue, the myelin structures were segmented from a brightfield image. Using a binary mask, those portions were quantitatively analyzed in the corresponding phase maps. We first used the CLARITY method to remove tissue lipids and validate the sensitivity of cSLIM to lipid content. We then applied cSLIM to brain histology slices. These specimens are from a previous MRI study, which demonstrated that appropriate for gestational age (AGA) piglets have increased internal capsule myelination (ICM) compared to small for gestational age (SGA) piglets and that a hydrolyzed fat diet improved ICM in both. The identity of samples was blinded until after statistical analyses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241084PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676665PMC
December 2020

Identifying patterns in the multitrophic community and food-web structure of a low-turbidity temperate estuarine bay.

Sci Rep 2020 10 6;10(1):16637. Epub 2020 Oct 6.

School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.

Food web dynamics outline the ecosystem processes that regulate community structure. Challenges in the approaches used to capture topological descriptions of food webs arise due to the difficulties in collecting extensive empirical data with temporal and spatial variations in community structure and predator-prey interactions. Here, we use a Kohonen self-organizing map algorithm (as a measure of community pattern) and stable isotope-mixing models (as a measure of trophic interaction) to identify food web patterns across a low-turbidity water channel of a temperate estuarine-coastal continuum. We find a spatial difference in the patterns of community compositions between the estuarine and deep-bay channels and a seasonal difference in the plankton pattern but less in the macrobenthos and nekton communities. Dietary mixing models of co-occurring dominant taxa reveal site-specific but unchanging food web topologies and the prominent role of phytoplankton in the trophic base of pelagic and prevalent-detrital benthic pathways. Our approach provides realistic frameworks for linking key nodes from producers to predators in trophic networks.
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http://dx.doi.org/10.1038/s41598-020-73628-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538895PMC
October 2020

Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19.

Sci Rep 2020 10 1;10(1):16200. Epub 2020 Oct 1.

Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, 28159, Chungcheongbuk-do, Republic of Korea.

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 10-, 10- and 10-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.
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http://dx.doi.org/10.1038/s41598-020-72879-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530981PMC
October 2020

Prevalence and clinical features of bone morphogenetic protein receptor type 2 mutation in Korean idiopathic pulmonary arterial hypertension patients: The PILGRIM explorative cohort.

PLoS One 2020 23;15(9):e0238698. Epub 2020 Sep 23.

Department of Cardiovascular Medicine, Gachon University Gil Medical Center, Incheon, Korea.

Background: Pulmonary arterial hypertension (PAH) is a progressive chronic disease with poor outcomes. One reason for poor prognosis is the lack of understanding regarding individual variability in response to treatment. Idiopathic PAH (IPAH) patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations have distinct phenotypes that are crucial for individualized therapy but evidence regarding their prevalence and clinical features in the Korean population is lacking. Therefore, the present study aimed to screen Korean IPAH patients for BMPR2 mutations and analyze their clinical phenotypes.

Methods: We enrolled 73 unrelated IPAH patients for BMPR2 mutation screening between March 2010 to November 2015 from 11 hospitals in Korea. Thirty-three lineal family members from 6 families of BMPR2 mutation carriers were also screened.

Results: Among 73 patients, 16 (22%) had BMPR2 mutations. Mutation carriers were younger (27 vs. 47 years; p = 0.02) and had a higher mean pulmonary arterial pressure (mPAP) than non-carriers (64 vs. 51 mmHg; p<0.05). Of the 16 individuals with mutations, 5 deletion, 2 splice-site, 6 nonsense, and 3 missense mutations were found, among which, 9 were newly identified mutation types. Patients less than 30 years old had more BMPR2 mutations (44 vs. 14%; p = 0.04) and a higher mPAP (64 vs. 50 mmHg; p = 0.04) compared with those equaled to or over 30 years old. There were no differences in hemodynamic profiles or the proportion of BMPR2 mutation carriers between groups according to sex.

Conclusion: The prevalence of BMPR2 mutations in Korean IPAH patients was 22%. Mutation carriers were younger and had a poorer hemodynamic profile compared with the non-carriers.

Clinical Trial Registration: Clinicaltrials.gov NCT01054105.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238698PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510973PMC
October 2020

Network science characteristics of brain-derived neuronal cultures deciphered from quantitative phase imaging data.

Sci Rep 2020 09 15;10(1):15078. Epub 2020 Sep 15.

Ming Hsieh Department of Electrical and Computer Engineering, University of Southern California, Los Angeles, CA, 90007, USA.

Understanding the mechanisms by which neurons create or suppress connections to enable communication in brain-derived neuronal cultures can inform how learning, cognition and creative behavior emerge. While prior studies have shown that neuronal cultures possess self-organizing criticality properties, we further demonstrate that in vitro brain-derived neuronal cultures exhibit a self-optimization phenomenon. More precisely, we analyze the multiscale neural growth data obtained from label-free quantitative microscopic imaging experiments and reconstruct the in vitro neuronal culture networks (microscale) and neuronal culture cluster networks (mesoscale). We investigate the structure and evolution of neuronal culture networks and neuronal culture cluster networks by estimating the importance of each network node and their information flow. By analyzing the degree-, closeness-, and betweenness-centrality, the node-to-node degree distribution (informing on neuronal interconnection phenomena), the clustering coefficient/transitivity (assessing the "small-world" properties), and the multifractal spectrum, we demonstrate that murine neurons exhibit self-optimizing behavior over time with topological characteristics distinct from existing complex network models. The time-evolving interconnection among murine neurons optimizes the network information flow, network robustness, and self-organization degree. These findings have complex implications for modeling neuronal cultures and potentially on how to design biological inspired artificial intelligence.
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http://dx.doi.org/10.1038/s41598-020-72013-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492189PMC
September 2020

Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Stability in Multiple Water Matrices.

J Korean Med Sci 2020 09 14. Epub 2020 Sep 14.

Division of Viral Disease Research, Center for Infectious Diseases Research, National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Korea.

The advent of the global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates a thorough study of the stability and transmissibility in the environment. We characterized the stability of SARS-CoV-2 in three water matrices: fresh, tap, and seawater. The minimum infective dose of SARS-CoV-2 in Vero cells was confirmed to be 10³ PFU/mL. The stability of SARS-CoV-2 varied according to the water matrix: infective SARS-CoV-2 was undetectable after treatment with fresh water and seawater, but remained detectable for 2 days in tap water, when starting with an initial concentration of 10⁴ PFU/mL. When the starting concentration was increased to 10⁵ PFU/mL, a similar trend was observed. In addition, viral RNA persisted longer than infectious virus in all water matrices. This study was conducted in stagnant water containing a significantly high titer of virus, thus, human-to-human transmission of SARS-CoV-2 through the actual aquatic environment is expected to be rare.
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September 2020

Enhanced Arsenic (III and V) Removal in Anoxic Environments by Hierarchically Structured Citrate/FeCO Nanocomposites.

Nanomaterials (Basel) 2020 Sep 8;10(9). Epub 2020 Sep 8.

Department of Earth and Environmental Sciences, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea.

Novel citrate/FeCO nanocomposites (CF-NCs) were synthesized for effective arsenic (III and V) sorption with constant addition of Fe into HCO solution in the presence of citrate. This paper is the first report on the formation of CF-NCs, and in this study we investigate the mechanisms of arsenic uptake by the sorbent under anoxic conditions through various solid- and liquid-phase spectroscopic methods, including X-ray absorption spectroscopy. In CF-NCs, citrate was found to be incorporated into the structure of siderite (up to 17.94%) through (Fecitrate) complexes. The crystal morphology of rhombohedral siderite was changed into hierarchically nanostructured spherical aggregates composed of several sheet-like crystals, which improved the surface reactivity in the presence of sufficient citrate. Compared to pure siderite (15.2%), enhanced removal of As(III) in the range of 19.3% to 88.2% was observed, depending on the amount of incorporated citrate. The maximum sorption capacities of CF-NCs for As(III) and As(V) were 188.97 and 290.22 mg/g, respectively, which are much higher than those of previously reported siderite-based adsorbents. It was found that arsenic (III and V) sorption on CF-NCs occurred via bidentate corner-sharing surface complexation, predominantly without changes in the arsenic oxidation states. These results suggest that arsenic (III and V) can be attenuated by siderite in anoxic environments, and this attenuation can be even more effective when siderite is modified by incorporation of organic compounds such as citrate.
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http://dx.doi.org/10.3390/nano10091773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558564PMC
September 2020

Integrated Highway Safety Information System (HSIS) datasets by means of a Roadway Safety Data Integrator (RSDI) tool.

Data Brief 2020 Oct 7;32:106154. Epub 2020 Aug 7.

Software Developer, NorthSoft, Baltimore, MD, United States.

The datasets and tool presented in this article are related to the research article entitled "Improving crash predictability of the through optimizing local calibration process" (Dadvar et al., 2020) [1], in which these datasets were used to investigate alternative local calibration methods for the (HSM) [2] local application. The datasets are integrated Highway Safety Information System (HSIS) [3] state-wide rural two-lane, two-way roads (R2U) data from states of Illinois and Washington. The HSIS is a database that maintains motor vehicle crash data, roadway inventory, and traffic volume data for several US states. It is an excellent source of data to highway safety research and can be used to investigate many research questions. However, to prepare an analysis-ready roadway safety dataset based on the HSIS or any databases that store the relevant data in multiple different datasets, the researchers should integrate multiple datasets, merge or unmerge and remove certain inconsistent records, and finally clean the integrated dataset. The HSIS staff is usually accommodating and eager to help, but sometimes the nature of data needs is complicated and laborious. A tool named Roadway Safety Data Integrator (RSDI) was developed for combining, segmenting, and selecting homogeneous (unchanged during the study period for certain variables of interest) HSIS roadway segments and also crash assignment by desired crash attributes (e.g., crash severity or type). The RSDI tool can be helpful for integrating different safety-related datasets such as roadway inventory (including grade, curve, and other subsets), traffic volume, and motor vehicle crash data; also, it can do required segmentation and identify the homogeneous roadway segments over the desired years of study that are the basis for development and calibration of the HSM predictive models. The shared datasets contain homogeneous roadway segments, geometric details, and crash data for six years from Illinois (2005-10) and Washington (2010-15). The datasets and RSDI tool would be important sources generally for investigating highway safety research questions and in particular, for HSM-related analyses. The RSDI tool can be used for similar purposes and it is not limited to the HSIS data. It can be used for segmentation and finding homogeneous segments of any datasets that follow linear referencing. The datasets and RSDI tool are hosted in the Mendeley Data repository [4].
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http://dx.doi.org/10.1016/j.dib.2020.106154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452693PMC
October 2020

Wolf phase tomography (WPT) of transparent structures using partially coherent illumination.

Light Sci Appl 2020 19;9:142. Epub 2020 Aug 19.

Quantitative Light Imaging Laboratory, Beckman Institute for Advanced Science and Technology, Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 USA.

In 1969, Emil Wolf proposed diffraction tomography using coherent holographic imaging to extract 3D information from transparent, inhomogeneous objects. In the same era, the Wolf equations were first used to describe the propagation correlations associated with partially coherent fields. Combining these two concepts, we present Wolf phase tomography (WPT), which is a method for performing diffraction tomography using partially coherent fields. WPT reconstruction works directly in the space-time domain, without the need for Fourier transformation, and decouples the refractive index (RI) distribution from the thickness of the sample. We demonstrate the WPT principle using the data acquired by a quantitative-phase-imaging method that upgrades an existing phase-contrast microscope by introducing controlled phase shifts between the incident and scattered fields. The illumination field in WPT is partially spatially coherent (emerging from a ring-shaped pupil function) and of low temporal coherence (white light), and as such, it is well suited for the Wolf equations. From three intensity measurements corresponding to different phase-contrast frames, the 3D RI distribution is obtained immediately by computing the Laplacian and second time derivative of the measured complex correlation function. We validate WPT with measurements of standard samples (microbeads), spermatozoa, and live neural cultures. The high throughput and simplicity of this method enables the study of 3D, dynamic events in living cells across the entire multiwell plate, with an RI sensitivity on the order of 10.
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http://dx.doi.org/10.1038/s41377-020-00379-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438521PMC
August 2020

Performance evaluation of an amplicon-based next-generation sequencing panel for BRCA1 and BRCA2 variant detection.

J Clin Lab Anal 2020 Dec 19;34(12):e23524. Epub 2020 Aug 19.

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: As next-generation sequencing (NGS) technology matures, various amplicon-based NGS tests for BRCA1/2 genotyping have been introduced. This study was designed to evaluate an NGS test using a newly released amplicon-based panel, AmpliSeq for Illumina BRCA Panel (AmpliSeq panel), for detection of clinically significant BRCA variants, and to compare it to another amplicon-based NGS test confirmed by Sanger sequencing.

Methods: We reviewed BRCA test results done by NGS using the TruSeq Custom Amplicon kit from patients suspected of hereditary breast/ovarian cancer syndrome (HBOC) in 2018. Of those, 96 residual samples with 100 clinically significant variants were included in this study using predefined criteria: 100 variants were distributed throughout the BRCA1 and BRCA2 genes. All target variants were confirmed by Sanger sequencing. Duplicate NGS testing of these samples was performed using the AmpliSeq panel, and the concordance of results from the two amplicon-based NGS tests was assessed.

Results: Ninety-nine of 100 variants were detected in duplicate BRCA1/2 genotyping using the AmpliSeq panel (sensitivity, 99%; specificity, 100%). In the discordant case, one variant (BRCA1 c.3627dupA) was found only in repeat 1, but not in repeat 2. Automated nomenclature of all variants, except for two indel variants, was in consensus with Human Genome Variation Society nomenclature.

Conclusion: Our findings confirm that the analytic performance of the AmpliSeq panel is satisfactory, with high sensitivity and specificity.
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http://dx.doi.org/10.1002/jcla.23524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755770PMC
December 2020

Applicability of weathered coal waste as a reactive material to prevent the spread of inorganic contaminants in groundwater.

Environ Sci Pollut Res Int 2020 Dec 12;27(36):45297-45310. Epub 2020 Aug 12.

Department of Earth and Environmental Sciences, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.

It is necessary to determine an environmentally friendly method of reusing the vast amount of coal waste that is generated during coal preparation. This study evaluates the applicability of using weathered coal waste in a permeable reactive barrier to prevent groundwater contamination. Coal waste, with different weathering degrees, was obtained from two coal mining sites in South Jeolla Province, Korea. The reactivities of the coal waste with inorganic contaminants, such as copper, cadmium, and arsenic, were examined in batch and column experiments. The batch experiment results indicate that the coal waste removal efficiencies of copper (99.8%) and cadmium (95.4%) were higher than those of arsenic (71.0%). The maximum adsorption capacities of coal waste for copper, cadmium, and arsenic calculated from the Langmuir isotherm model were 4.440 mg/g, 3.660 mg/g, and 0.718 mg/g, respectively. The equilibrium of adsorption was attained within 8 h. The column experiment results reveal that the coal waste effectively removed inorganic contaminants under flow-through conditions. Faster breakthrough times were observed in single solute system (As(V) = 19.3 PV, Cu(II) = 47.6 PV) compared with binary solute system (As(V) = 27.8 PV, Cu(II) = 65.4 PV). To confirm the applicability of using coal waste in a groundwater environment, its decontamination ability was analyzed at low concentrations and under various pH conditions. To examine the potential ecological risks in the subsurface environment, a test to determine acute toxicity to Daphnia magna and a toxic characteristic leaching procedure (TCLP) test were conducted. The coal waste was found to satisfy appropriate standards. The acute toxicity test also confirmed the ecological safety of using coal waste in a groundwater environment. The acceptably high capacity and fast kinetics of inorganic contaminant sorption by the coal waste indicate it could potentially be employed as a reactive material. The recycling and application of this abundant waste material will contribute to solving both coal waste disposal and water pollution problems.
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http://dx.doi.org/10.1007/s11356-020-10418-7DOI Listing
December 2020

Overexpression of Activin Receptor-Like Kinase 1 in Endothelial Cells Suppresses Development of Arteriovenous Malformations in Mouse Models of Hereditary Hemorrhagic Telangiectasia.

Circ Res 2020 Oct 31;127(9):1122-1137. Epub 2020 Jul 31.

Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville (Y.H.K., S.-w.C., S.P.O.).

Rationale: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease caused by mutations in , , or . Since proteins from all 3 HHT genes are components of signal transduction of TGF-β (transforming growth factor β) family members, it has been hypothesized that HHT is a disease caused by defects in the ENG-ALK1-SMAD4 linear signaling. However, in vivo evidence supporting this hypothesis is scarce.

Objective: We tested this hypothesis and investigated the therapeutic effects and potential risks of induced-ALK1 or -ENG overexpression (OE) for HHT.

Methods And Results: We generated a novel mouse allele (ROSA26) in which HA (human influenza hemagglutinin)-tagged ALK1 and bicistronic eGFP expression are induced by Cre activity. We examined whether ALK1-OE using the ROSA26 allele could suppress the development of arteriovenous malformations (AVMs) in wounded adult skin and developing retinas of - and -inducible knockout (iKO) mice. We also used a similar approach to investigate whether ENG-OE could rescue AVMs. Biochemical and immunofluorescence analyses confirmed the Cre-dependent OE of the ALK1-HA transgene. We could not detect any pathological signs in ALK1-OE mice up to 3 months after induction. ALK1-OE prevented the development of retinal AVMs and wound-induced skin AVMs in -iKO as well as -iKO mice. ALK1-OE normalized expression of SMAD and NOTCH target genes in ENG-deficient endothelial cells (ECs) and restored the effect of BMP9 (bone morphogenetic protein 9) on suppression of phosphor-AKT levels in these endothelial cells. On the other hand, ENG-OE could not inhibit the AVM development in -iKO models.

Conclusions: These data support the notion that ENG and ALK1 form a linear signaling pathway for the formation of a proper arteriovenous network during angiogenesis. We suggest that ALK1 OE or activation can be an effective therapeutic strategy for HHT. Further research is required to study whether this therapy could be translated into treatment for humans.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.316267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554133PMC
October 2020

Cell Fate Determination of Lymphatic Endothelial Cells.

Authors:
Young Jae Lee

Int J Mol Sci 2020 Jul 6;21(13). Epub 2020 Jul 6.

Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Korea.

The lymphatic vasculature, along with the blood vasculature, is a vascular system in our body that plays important functions in fluid homeostasis, dietary fat uptake, and immune responses. Defects in the lymphatic system are associated with various diseases such as lymphedema, atherosclerosis, fibrosis, obesity, and inflammation. The first step in lymphangiogenesis is determining the cell fate of lymphatic endothelial cells. Several genes involved in this commitment step have been identified using animal models, including genetically modified mice. This review provides an overview of these genes in the mammalian system and related human diseases.
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http://dx.doi.org/10.3390/ijms21134790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370169PMC
July 2020

Comparison of Risk of Ovarian Malignancy Algorithm and cancer antigen 125 to discriminate between benign ovarian tumor and early-stage ovarian cancer according to imaging tumor subtypes.

Oncol Lett 2020 Jul 14;20(1):931-938. Epub 2020 May 14.

Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.

The present study aimed to compare the accuracy of the Risk of Ovarian Malignancy Algorithm (ROMA) and cancer antigen (CA)125 to discriminate between benign ovarian tumors and early-stage ovarian cancer according to imaging tumor subtypes associated with post-operative histopathological findings. A total of 1,207 patients who were assessed using the ROMA test due to suspected early-stage ovarian cancer and underwent surgery at Asan Medical Center (Seoul, Korea) between September 2014 and March 2018 were identified. A total of 981 patients who met the inclusion criteria were included in the retrospective analysis. Among the 981 subjects, 816 had benign tumors, 90 had malignant tumors and 75 had borderline tumors. Of the patients diagnosed with ovarian cancer or borderline tumor, 47.3% were judged as high-risk by the ROMA test and 58.2% had CA125 levels of >35 U/ml. The specificity and accuracy of ROMA were higher compared with those of CA125 in pre-menopausal females. However, the superiority of the ROMA test in the identification of malignant ovarian tumors compared with CA125 was only observed in patients with endometriotic-type tumors but not in any of the other tumor subtypes. In the endometriotic type of ovarian tumor, the superiority of the ROMA test compared to CA125 was confirmed in triage of ovarian tumor. However, the sensitivity and specificity of ROMA and CA125 were similar for the other tumor types. Therefore, future development of better tumor-specific biomarkers for triage of ovarian tumor is required.
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http://dx.doi.org/10.3892/ol.2020.11629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285867PMC
July 2020

CXCL12 is required for stirrup-shaped stapes formation during mammalian middle ear development.

Dev Dyn 2020 09 2;249(9):1117-1126. Epub 2020 May 2.

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

Background: The mammalian middle ear comprises a chain of three ossicles-the malleus, incus, and stapes-each of which has a unique morphology for efficiently transmitting sound information. In particular, the stapes, which is attached to the inner ear, is stirrup-shaped with a head and base connected by two crural arches, forming the stapedial foramen, through which the stapedial artery passes. However, how the stapes acquires this critical stirrup shape for association with the stapedial artery during development is not clear.

Results: C-X-C motif chemokine ligand 12 (CXCL12) is a chemoattractant essential for cellular movement and angiogenesis. In Cxcl12 embryos, migration of neural crest cells into the prospective middle ear regions and their mesenchymal condensation to form the three ossicles proceed normally in correct alignment with each other and the inner ear. However, in the absence of CXCL12, the stapes loses its stirrup shape and instead exhibits a columnar shape lacking the crural arches and central hole. In addition, although the stapedial artery initially forms during early mesenchymal condensation of the stapes, it degenerates without CXCL12 function.

Conclusion: CXCL12 plays an essential role in establishing the stirrup-shaped architecture of the stapes, possibly by maintaining the stapedial foramen and stapedial artery throughout development.
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http://dx.doi.org/10.1002/dvdy.180DOI Listing
September 2020

High-phytate/low-calcium diet is a risk factor for crystal nephropathies, renal phosphate wasting, and bone loss.

Elife 2020 04 9;9. Epub 2020 Apr 9.

Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea.

Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.
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http://dx.doi.org/10.7554/eLife.52709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145417PMC
April 2020

GeneReader NGS System Is a Useful Sequencing Platform for Clinical Testing of and .

Ann Clin Lab Sci 2020 Jan;50(1):107-118

Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Although next-generation sequencing (NGS) is widely used for sequencing analysis, it involves a fragmented workflow along with complex bioinformatic analysis and interpretation. In this study, the performance characteristics and workflow of the GeneReader NGS System (QIAGEN), including sequencing, were evaluated. For genetic testing, we conducted library preparation, emulsion PCR, and sequencing. QCI Analyze software was used for read alignment, quality control, variant calling, and clinical report generation. GeneReader and Sanger sequencing utilized 63 patients with breast or ovarian cancer for comparison. Reproducibility, precision, variant calling, turnaround time, and hands-on time were evaluated. The read percentage in the on-target regions was 90.5%. More than 99.99% of target regions showed read depths ≥100x. Variants generated from GeneReader showed 100% accuracy compared to the Sanger sequencing results. Annotation with GeneReader showed >99.8% concordance with HGVS nomenclature. Single-nucleotide variations and indel variants showed 100% calling reproducibility; the precision for variant frequency showed a 0.3-3.6% coefficient of variation. Most processes involved hands-off time (3714 min, 88.6% of total run time). The GeneReader NGS System for and testing showed good analytical performance and a short hands-on time. Because of its integrated sample preparation for bioinformatic interpretation, this system is practical for clinical laboratories.
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January 2020

TMEM100 is a key factor for specification of lymphatic endothelial progenitors.

Angiogenesis 2020 08 28;23(3):339-355. Epub 2020 Feb 28.

Department of Physiology and Functional Genomics, College of Medicine, University of Florida, 1600 SW Archer Road, Room CG-20B, Gainesville, FL, USA.

Background: TMEM100 is identified as a downstream gene of bone morphogenetic protein 9 (BMP9) signaling via activin receptor-like kinase 1 (ALK1), which is known to participate in lymphangiogenesis as well as angiogenesis. TMEM100 has been shown to be important for blood vessel formation and maintenance, but its role in the development of lymphatic vasculature remains unknown. The objective is to investigate the role of TMEM100 in development of the lymphatic system.

Methods And Results: Global Tmem100 gene deletion was induced by tamoxifen on 10.5 days post-coitus. Tmem100-inducible knockout (iKO) embryos in embryonic days (E)14.5-16.5 exhibited edema and blood-filled enlarged lymphatics with misconnections between veins and lymphatic vessels. For a reciprocal approach, we have generated a novel mouse line in which TMEM100 overexpression (OE) can be induced in endothelial cells by intercrossing with Tie2-Cre driver. TMEM100-OE embryos at E12.5-14.5 exhibited edema with small size and number of lymphatic vessels, the exact opposite phenotypes of Tmem100-iKOs. In Tmem100-iKO embryos, the number of progenitors of lymphatic endothelial cells (LECs) in the cardinal vein was increased, while it was decreased in TMEM100-OE embryos. The activity of NOTCH signaling, which limits the number of progenitors of LECs in the cardinal vein, was decreased in Tmem100-iKO embryos, whereas it was increased in TMEM100-OE embryos.

Conclusion: TMEM100 plays an important role in the specification of LECs in the cardinal veins, at least in part, by regulating the NOTCH signaling.
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http://dx.doi.org/10.1007/s10456-020-09713-1DOI Listing
August 2020

Knockout Mouse Models for Peroxiredoxins.

Authors:
Young Jae Lee

Antioxidants (Basel) 2020 Feb 22;9(2). Epub 2020 Feb 22.

Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Korea.

Peroxiredoxins (PRDXs) are members of a highly conserved peroxidase family and maintain intracellular reactive oxygen species (ROS) homeostasis. The family members are expressed in most organisms and involved in various biological processes, such as cellular protection against ROS, inflammation, carcinogenesis, atherosclerosis, heart diseases, and metabolism. In mammals, six PRDX members have been identified and are subdivided into three subfamilies: typical 2-Cys (PRDX1, PRDX2, PRDX3, and PRDX4), atypical 2-Cys (PRDX5), and 1-Cys (PRDX6) subfamilies. Knockout mouse models of PRDXs have been developed to investigate their in vivo roles. This review presents an overview of the knockout mouse models of PRDXs with emphases on the biological and physiological changes of these model mice.
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http://dx.doi.org/10.3390/antiox9020182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070531PMC
February 2020

Influence of Annealing Atmosphere on the Characteristics of GaO/4H-SiC n-n Heterojunction Diodes.

Materials (Basel) 2020 Jan 16;13(2). Epub 2020 Jan 16.

Department of Electronic Materials Engineering, Kwangwoon University, 20 Kwangwoon-ro, Nowon-gu, Seoul 01897, Korea.

GaO/4H-SiC n-n isotype heterojunction diodes were fabricated by depositing GaO thin films by RF magnetron sputtering. The influence of annealing atmosphere on the film quality and electrical properties of GaO layers was investigated. X-ray diffraction (XRD) analysis showed a significant increase in the peak intensities of different faces of β-GaO {(-201), (-401) and (002)}. X-ray photoelectron spectroscopy (XPS) measurement showed that the atomic ratio of oxygen increases under high-temperature annealing. Moreover, an N-annealed diode exhibited a greater rectifying ratio and a lower thermal activation energy owing to the decrease in oxygen-related traps and vacancies on the GaO film and GaO-metal interface.
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http://dx.doi.org/10.3390/ma13020434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013600PMC
January 2020

Improving crash predictability of the Highway Safety Manual through optimizing local calibration process.

Accid Anal Prev 2020 Mar 10;136:105393. Epub 2020 Jan 10.

City & Regional Planning Program, Department of Graduate Built Environment Studies, School of Architecture and Planning, Morgan State University, 1700 E. Cold Spring Lane, Baltimore, MD 21251, United States. Electronic address:

The predictive method of the Highway Safety Manual (HSM) estimates crash frequency by applying an uncalibrated safety performance function (SPF) and a set of uncalibrated crash modification factors (CMFs) to each location individually; then the predicted crashes must be adjusted by a local calibration factor (LCF) at the aggregate level for at least 30-50 sites per SPF. Although this calibration procedure assures total predicted crashes will be localized, still the prediction of crashes for individual locations suffers from the aggregate localization process. An alternative approach of locally calibrating the HSM predictive method is proposed to improve prediction quality at individual locations while maintaining equality of total observed and total predicted crashes. The methodology incorporates multiple calibration factors for different components of the predictive method (SPF parameters and CMFs) rather than a single calibration factor as recommended by the HSM that only calibrates at the aggregate level. In the proposed method, the application of calibration factors expressed in both weight and power function better reflects the local conditions while still ensuring calibration at the aggregate level. The parameters are estimated through an optimization process of five different methods. Rural two-lane, two-way roads (R2U) data was used from the states of Maryland, Illinois, and Washington. A tool named "Roadway Safety Data Integrator (RSDI)" was developed for data preparation. Different Goodness-of-Fit measures along with CURE plots indicated that the proposed method performed significantly better than the HSM calibration method, calibration function (that will most likely be calibration process in the HSM 2 edition), calibrated Washington models (for the case of Washington data), and some alternative calibration methods suggested by past studies. Moreover, the results indicated that the additional parameters for CMFs could improve the prediction significantly; a previous study did not find this to be so due to data limitations, but we have improved the methodology and are not so limited. Application of the proposed approach can lead to more accurate identification of hot-spots and site-specific strategies. Considering the limitations of this study, some avenues for further research are discussed.
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http://dx.doi.org/10.1016/j.aap.2019.105393DOI Listing
March 2020

The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation.

PLoS One 2020 9;15(1):e0227516. Epub 2020 Jan 9.

Division of Viral Disease Research, Center for Infectious Diseases Research, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong, Republic of Korea.

Elucidating the genetic basis of influenza A viruses (IAVs) is important to understand which mutations will determine the virulence and the host range of mammals. Here, seasonal H3N2 influenza was adapted in mice by serial passage and four mutants, each carrying amino acid substitutions related to mouse adaptation in either the PB2, HA, NP, or NA protein, were generated. To confirm the contribution of each gene to enhanced pathogenicity and mouse adaptation, mice were inoculated with the respective variants, and virulence, replication, histopathology, and infectivity were examined. The virus harboring HA mutations displayed increased infection efficiency and replication competence, resulting in higher mortality in mice relative to those infected with wild-type virus. By contrast, the NP D34N mutation caused rapid and widespread infection in multiple organs without presenting virulent symptoms. Additionally, the PB2 F323L mutation presented delayed but elevated replication competence in the respiratory tract, whereas the S331R mutation in NA showed no considerable effects on mouse adaptation. These results suggested that mouse-adapted changes in HA are major factors in increased pathogenicity and that mutations in NP and PB2 also contribute to cross-species adaptability. Our findings offer a better understanding of the molecular basis for IAV pathogenicity and adaptation in a new host.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227516PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952113PMC
April 2020

Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function.

Cell Death Dis 2020 01 6;11(1):14. Epub 2020 Jan 6.

Department of Stem Cell & Regenerative Biotechnology, Humanized Pig Research Center (SRC), Konkuk University, Seoul, Gwangjin-gu, 05029, Republic of Korea.

Proper functioning of the lymphatic system is required for normal immune responses, fluid balance, and lipid reabsorption. Multiple regulatory mechanisms are employed to ensure the correct formation and function of lymphatic vessels; however, the epigenetic modulators and mechanisms involved in this process are poorly understood. Here, we assess the regulatory role of mouse Dot1l, a histone H3 lysine (K) 79 (H3K79) methyltransferase, in lymphatic formation. Genetic ablation of Dot1l in Tie2(+) endothelial cells (ECs), but not in Lyve1(+) or Prox1(+) lymphatic endothelial cells (LECs) or Vav1(+) definitive hematopoietic stem cells, leads to catastrophic lymphatic anomalies, including skin edema, blood-lymphatic mixing, and underdeveloped lymphatic valves and vessels in multiple organs. Remarkably, targeted Dot1l loss in Tie2(+) ECs leads to fully penetrant lymphatic aplasia, whereas Dot1l overexpression in the same cells results in partially hyperplastic lymphatics in the mesentery. Genetic studies reveal that Dot1l functions in c-Kit(+) hemogenic ECs during mesenteric lymphatic formation. Mechanistically, inactivation of Dot1l causes a reduction of both H3K79me2 levels and the expression of genes important for LEC development and function. Thus, our study establishes that Dot1l-mediated epigenetic priming and transcriptional regulation in LEC progenitors safeguard the proper lymphatic development and functioning of lymphatic vessels.
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http://dx.doi.org/10.1038/s41419-019-2201-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944698PMC
January 2020

Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer.

J Hum Genet 2020 Mar 6;65(3):209-220. Epub 2020 Jan 6.

Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.

The clinical utility of BRCA1/2 genotyping was recently extended from the selection of subjects at high risk for hereditary breast and ovary cancer to the identification of candidates for poly (ADP-ribose) polymerase (PARP) inhibitor treatment. This underscores the importance of accurate interpretation of BRCA1/2 genetic variants and of reducing the number of variants of uncertain significance (VUSs). Two recent studies by Findlay et al. and Starita et al. introduced high-throughput functional assays, and proactively analyzed variants in specific regions regardless of whether they had been previously observed. We retrospectively reviewed all BRCA1 and BRCA2 germline genetic test reports from patients with breast or ovarian cancer examined at Asan Medical Center (Seoul, Korea) between September 2011 and December 2018. Variants were assigned pathogenic or benign strong evidence codes according to the functional classification and were reclassified according to the ACMG/AMP 2015 guidelines. Among 3684 patients with available BRCA1 and BRCA2 germline genetic test reports, 429 unique variants (181 from BRCA1) were identified. Of 34 BRCA1 variants intersecting with the data reported by Findlay et al., three missense single-nucleotide variants from four patients (0.11%, 4/3684) were reclassified from VUSs to likely pathogenic variants. Four variants scored as functional were reclassified into benign or likely benign variants. Three variants that overlapped with the data reported by Starita et al. could not be reclassified. In conclusion, proactive high-throughput functional study data are useful for the reclassification of clinically observed VUSs. Integrating additional evidence, including functional assay results, may help reduce the number of VUSs.
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http://dx.doi.org/10.1038/s10038-019-0713-2DOI Listing
March 2020

Quantitative insights into major constituents contained in or released by electronic cigarettes: Propylene glycol, vegetable glycerin, and nicotine.

Sci Total Environ 2020 Feb 2;703:134567. Epub 2019 Nov 2.

Department of Environmental Engineering, Pukyong National University, 45 Yongso-ro, Busan 48513, Republic of Korea. Electronic address:

Generally, the liquid used in electronic cigarettes (E-cigarettes), which is also called E-liquid, is composed of propylene glycol (PG), vegetable glycerin (VG), and nicotine, with many other miscellaneous ingredients. E-liquid is consumed mainly in the form of aerosol via inhalation by the e-cigarette user. The amount and composition of the aerosol generated during its consumption depend on various factors. In this study, the three major constituents (PG, VG, and nicotine) of E-cigarettes were analyzed in both liquid and aerosol samples from 50 commercial products. Their concentrations in the liquid (and aerosol at 3.4 V) samples were 538 (4 6 7), 482 (4 4 9), and 8.75 mg g (7.91 mg g), respectively. The nicotine levels in the E-liquids measured in this study were normally 1.2 times greater than those specified by the manufacturers. Furthermore, the amount of liquid consumed increased proportionally as the voltage of the E- cigarette increased. The consumption rate of VG increased as the voltage of the E-cigarette increased, whereas that of PG and nicotine decreased. The results of our study confirm that the amounts of PG and VG generated through the use of E-cigarettes are noticeably larger than those from other tobacco products (such as traditional tobaccos and heat-not-burn products), although no such trend was evident in case of nicotine.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134567DOI Listing
February 2020

Minimally invasive salvage of infected breast tissue expanders: A continuous closed irrigation technique based on surface biofilm disruption.

J Plast Reconstr Aesthet Surg 2020 Feb 8;73(2):295-302. Epub 2019 Aug 8.

Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon, Gangnam, Seoul, Republic of Korea. Electronic address:

Background: Removal of the infected device has been the general treatment for device-associated infection in antibiotic failure. There have been anecdotal attempts to salvage infected medical devices by introducing a continuous closed irrigation system.

Objective: This study examines whether continuous closed irrigation of an infected device is a successful alternative to removal in patients with recalcitrant device-associated infection.

Methods: Patients who were diagnosed with recalcitrant periexpander infections during the course of expander-implant breast reconstruction from 2010 to 2018 were enrolled in a retrospective case-control study. Patients who failed antibiotics before 2017 underwent expander removal, but patients since 2017 underwent continuous closed irrigation of the infected expanders. Treatment details and clinical outcomes were compared. Rationale for expander irrigation was based on review of the current literature on biofilm research.

Results: During the study period, 21 out of the 1176 patients were diagnosed with periexpander infection recalcitrant to antibiotic therapy. Among the 21 patients, 16 underwent expander removal and five underwent expander irrigation. Clinical outcomes were comparable in terms of resolution of infection signs. The irrigation group showed fewer patients who abandoned reconstruction after infection treatment (removal = 11/16, irrigation = 1/5). Literature review revealed that expander irrigation might have induced hydrodynamic disruption of the biofilm structure.

Conclusion: Expander irrigation was less invasive than removal and effective in suppressing severe recalcitrant periexpander infection. Continuous closed irrigation of infected expander devices may be a successful antibiofilm strategy in treating device-associated infections in select patients.
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http://dx.doi.org/10.1016/j.bjps.2019.07.020DOI Listing
February 2020