• Journal of Genetic Medicine
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• v.7 no.1
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• pp.24-36
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• 2010

Colorectal cancer is one of the most steeply increasing malignancies in Korea. Among 398,824 new patients recorded by the Korea Central Cancer Registry between 2003 and 2005, 47,915 cases involved colorectal cancers, accounting for 12.0 % of all malignancies. In 2002, total number of colorectal cancer cases had accounted for 11.2 % of all malignancies. Hereditary syndromes are the source of approximately 5% to 15% of overall colorectal cancer cases. Hereditary colorectal cancers are divided into two types: hereditary nonpolyposis colorectal cancer (HNPCC), and cancers associated with hereditary colorectal polyposis, including familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, juvenile polyposis, and the recently reported hMutYH (MYH)-associated polyposis (MAP). Hereditary colorectal cancers have unique clinical features distinct from sporadic cancer because these are due to germline mutations of the causative genes; (i) early age-of-onset of cancer, (ii) frequent association with synchronous or metachronous tumors, (iii) frequent association with extracolonic manifestations. The management strategy for patients with hereditary colorectal cancer is quite different from that for sporadic cancer. Furthermore, screening, genetic counseling, and surveillance for at-risk familial member are also important. A well-organized registry can plays a central role in the surveillance and management of families affected by hereditary colorectal cancers. Here, we discuss each type of hereditary colorectal cancer, focusing on the clinical and genetic characteristics, management, genetic screening, and surveillance.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1478-1487
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• 2019

Ulcerative colitis (UC), a chronic inflammatory bowel disease, substantially impacts patients' health-related quality of life. In this study, an effective strategy for discovering high-efficiency probiotics has been developed. First, in order to survive in the conditions of the stomach and intestine, high bile salt-resistant and strong acid-resistant strains were screened out from the fecal flora of healthy adults. Next, the probiotic candidates were rescreened by examining the induction ability of IL-10 (anti-inflammatory factor) production in dextran sodium sulfate (DSS)-induced colitis mice, and Lactobacillus sakei 07 (L07) was identified and selected as probiotic P. In the end, fourteen bifidobacterium strains isolated from stools of healthy males were examined for their antimicrobial activity. Bifidobacterium bifidum B10 (73.75% inhibition rate) was selected as probiotic B. Moreover, the colonic IL-6 and $TNF-{\alpha}$ expression of the DSS-induced colitis mice treated with L. sakei 07 (L07) - B. bifidum B10 combination (PB) significantly decreased and the IL-10 expression was up-regulated by PB compared to the DSS group. Furthermore, Bacteroidetes and Actinobacteria decreased and Firmicutes increased in the DSS group mice, significantly. More interestingly, the intestinal flora biodiversity of DSS colitis mice was increased by PB. Of those, the level of B. bifidum increased significantly. The Bacteriodetes/Firmicutes (B/F) ratio increased, and the concentration of homocysteine and LPS in plasma was down-regulated by PB in the DSS-induced colitis mice. Upon administration of PB, the intestinal permeability of the the DSS-induced colitis mice was decreased by approximately 2.01-fold. This method is expected to be used in high-throughput screening of the probiotics against colitis. In addition, the L. sakei 07 - B. bifidum B10 combination holds potential in UC remission by immunomodulatory and gut microbiota modulation.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.427-434
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• 2022

The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.

• Archives of Plastic Surgery
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• v.49 no.2
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• pp.184-194
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• 2022

The face and the external nose define an individual's physical appearance. Nasal deformities can cause facial disfigurement along with unwanted psychological repercussions. Nasal deformities range in severity, with the most severe cases being indications for a rhinectomy, due to the complexity of the nasal defect. According to published literature, there is no consensus among otolaryngologists and plastic surgeons on which technique or flap use is preferred in terms of complications, aesthetic outcome, or patient satisfaction. The goal of this study is to provide a comprehensive analysis of published studies on nasal reconstruction following rhinectomy. Using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines for writing systematic reviews, a systematic review was conducted. Four databases were searched using a search strategy. These articles were then imported into the COVIDENCE software and went screening and thorough article review. After screening 2,237 articles, 23 studies were then extracted for data collection analysis. We collected data from 12 case series, 4 case studies, 1 prospective case series, and 4 retrospective chart review studies. The most commonly reported flaps were forehead flaps, superior extended nasal myocutaneous island, forearm free flaps, anterolateral thigh (ALT) free flap, medial femoral condyle free flap (n = 8), and zygomaticus implants (n = 6), and retained nasal prosthesis. Although not specifically indicated by a certain number, the most common indication for the rhinectomy was malignancy, followed by traumas, postsurgical complications, radionecrosis, and congenital nasal malformations.

• Korea Journal of Hospital Management
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• v.1 no.1
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• pp.108-135
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• 1996

This paper investigates the current feature of management strategy of hospitals in Korea, and examines the relationships between adoption of a particular strategic orientation and the hospitals environmental and organizational characteristics, strategic behaviors and management improvement activities, and financial performance. Data were collected from CEOs of 88 hospitals among 650 hospitals for a 13.5% response rate using the self-administered questionnaire by mail survey. The major findings that obtained are as follows: 1. Only 37.2% of response hospitals carried out strategic planning, Most of these hospitals established the first strategic planning in 1991(81.3%) and renovated strategic planning by 4 or 5 years(56.3%), and modified strategic planning with flexibility(59.4%). Most strategic plans were documented, but informalized(68.8%). And only 29.0% of these hospitals had independent planning division. 2. Hospital services that CEOs assessed rank ordered for their impact on profitability are as follows: i)diagnostic ultrasound facility, computerized tomography scanner, obstetric inpatient unit, therapeutic X-ray, and physical therapy at present. ii)diagnostic ultrasound facility, physical therapy, computerized tomography scanner, emergency department, and health screening at future. And the services rank ordered that CEOs hoped to introduce are as follows: emergency department, physical therapy, health screening, volunteer services, and computerized tomography scanner. 3. Using a typology developed by Miles and Snow(l978), the strategic orientation of response hospitals are shifting significantly from defenders in the past to analyzers in the present, and to prospectors in the future(p<.01). 4. With regard to hospital environmental and organizational characteristics such as ownership, physician training, location, bed size, and hospital management training career and specialty of CEOs, the four strategic orientation archetypes varied not significantly. But, hospitals with a analyser orientation in the present and a reactor orientation in the future perceived competition significantly higher than the other three archetypes(p<.05). 5. The four archetypes rank ordered in terms of appling strategic behaviors and management improvement activities are as follows: prospector, analyzer, reactor, and defender. 6. The four archetypes differed significantly in terms of their financial performance using revenue per bed(p<.05). Reactors and prospectors in terms of total revenue per bed, prospectors in terms of outpatient revenue per bed, and reactors and prospectors in terms of inpatient revenue per bed had the best performance.

• Mass Spectrometry Letters
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• v.8 no.2
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• pp.39-43
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• 2017

Meldonium is a drug for treating ischemia by expanding the arteries but it can also enhance the performance of sports players. The World Anti-Doping Agency (WADA) has included it in the list of prohibited substances since 2016. Meldonium is one of the challenging substances for anti-doping testing because it is difficult to recover by general liquid-liquid or solid phase extraction due to its permanent charge and high polarity. Therefore, high-performance liquid chromatography (HPLC) is currently used by injecting a diluted urine sample (known as the "dilute-and-shoot" strategy). There is no loss of target compounds in the extraction/cleanup procedure but its high matrix effect could interfere in their separation or detection from the endogenous urinary compounds. We report a single method using high-resolution mass spectrometry that can be used for both screening and confirmation, which follows the "dilute-and-shoot" strategy. In this method, the endogenous compounds' interfering peaks in the mass spectrum are separated at a high resolution of FWHM 140,000, and the results are suitable for substance detection following the WADA guidelines. The interferences in the obtained mass spectrum of the urine matrix are identified as acetylcholine, lysine, and glutamine by further analysis and database searching. Validation of the method is performed in routine anti-doping testing, and the limit of detection is 50 ng/mL. This method uses simple sample preparation and a general reverse phase HPLC column, and it can be easily applied to other substances.

• KSBB Journal
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• v.20 no.5 s.94
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• pp.376-382
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• 2005

Avermectin (AVM) $B_{1a}$ produced by Streptomyces avermitilis via polyketide pathway is a secondary metabolite with powerful anthelmintic and insecticidal activities, thus being used as an efficient agent in the field of agriculture and animal health. It has been reported that a precursor for AVM $B_{1a}$ biosynthesis was isoleucine and the biosynthetic pathway of AVM $B_{1a}$ was closely similar to that of fatty acid. Based on understanding of the biosynthetic pathway of AVM $B_{1a}$, we intended to screen various mutants resistant against O-methyl threonine (OMT), an isoleucine-anti metabolite, and/or mutants resistant against p-fluoro phenoxy acetic acid (pFAC), an inhibitor of fatty acid biosynthesis. It was inferred that these mutants could produce AVM $B_{1a}$ more efficiently, due to the acquired capability of not only overproducing isoleucine intracellularly but also channelling metabolized carbon-sources into the polyketide pathway, thus leading to enhanced biosynthesis of AVM $B_{1a}$. The resulting mutant (PFA-1 strain) resistant against 100 ppm of pFAC was able to produce approximately 42 fold higher amount of AVM $B_{1a}$ compared to the parallel mother strain (4,200 vs. 100 units/l). In addition, through the process of continuous strain improvement program carried out by gradually increasing the OMT concentration, it was possible to obtain a more attractive mutant with greater AVM $B_{1a}$ production capacity (9,000 units/l). Notable was that significantly higher producer (12,000 units/l) could be selected through further screening of the resistant mutants, this time, to even higher concentration of PFAC. Meanwhile, through the analysis of AVM Bla production histograms (i.e., number of strains according to their AVM $B_{1a}$ biosynthetic ability) for the earlier strains in comparison with the high producers having the characteristics of resistance to OMT and pFAC, it was found that production stability of the high-yielding producers were remarkably improved, as demonstrated by the fact that larger proportion of the mutated strains had greater capability of AVM $B_{1a}$ biosynthesis ($71\%$ in the range between 5,000 and 7,000 units/L; $47\%$ in the range between 6,000 and 7,000 units/l). Based on these consequences, it was concluded that the rational screening strategy based on the understanding of the biosynthetic pathway of AVM $B_{1a}$ was very effective in obtaining high-yielding mutants with the features of enhanced production stability.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.2
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• pp.57-61
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• 2016

Isovaleric acidemia (IVA) is an autosomal recessively inherited organic acid disorder due to a defect of the enzyme isovaleryl-CoA dehydrogenase in the leucine metabolic pathway. Deficiency of this enzyme results in the accumulation of derivatives of isovaleryl-CoA. In acute illness in IVA, isovaleric acid and its derivatives accumulate and profound metabolic acidosis with ketosis, characteristic pungent body odor, hypoglycemia, and hyperammonemia can be developed. Additionally, recurrent vomiting, failure to thrive, developmental delay, epilepsy and mental retardation are chronic presenting symptoms and signs for IVA. On the result of newborn screening for inherited metabolic disorders, increased levels of isovalerylcarnitine (C5) are shown. However, C5 elevation can be accompanied with short/branched-chain acyl-CoA dehydrogenase (SBCAD) and therapy with certain antibiotics containing pivalic acid. Quantitative measurement of organic acids in urine and acylcarnitine profiles in plasma are necessary to differential diagnosis. Molecular genetic analysis of the IVD gene for IVA and ACADSB is also helpful to confirm IVA and SBCAD deficiency, respectively. Considering that IVA can be associated with significant morbidity and mortality at acute presentation of metabolic crisis, early diagnosis prior to the onset of symptoms by newborn screening enable to introduction of early treatment and prevention of acute and chronic complications.

• Journal of Microbiology and Biotechnology
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• v.12 no.1
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• pp.121-129
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• 2002

Using recombinant Chinese hamster ovary (CHO) cells, strategies for developing high producers for the recombinant human Transforming Growth $Factor-{\beta}1$ ($TGF-{\beta}1$) protein are proposed and their physiological characteristics in cell cultures were investigated. $TGF-{\beta}1$ is a pleiotrophic polypeptide involved in various biological activities, including cell growth, differentiation, and deposition of extracellular matrix proteins. The CHO cells included human $TGF-{\beta}1$ cDNA in conjunction with a dihydrofolate reductase (DHFR) gene, which was cotransfected into the cells to amplify the transfected $TGF-{\beta}1$ cDNA. As a first-round screening of the transfected cells, a relatively high $TGF-{\beta}1$-producing cell line was selected, and then, it acquired a resistance to increasing concentrations of methotrexate (MTX) up to $60{\mu}M$,resulting in a significant improvement in its $TGF-{\beta}1$ biosynthetic ability. After applying a monoclonal selection strategy to the MTX-resistant cells, more productive cells were screened, including the APP-3, App-5, and App-8 cell lines. These high producers were compared with two other cell lines (AP-l cell line without amplification of transfected $TGF-{\beta}1$ cDNA and nontransfectant of $TGF-{\beta}1$ cDNA) in terms of cell growth, $TGF-{\beta}1$ productivity, sugar uptake, and byproduct formation, in the presence or absence of MTX in the culture medium. Consequently, both monoclonal selection as well as an investigation of the physiological characteristics were found to be needed for the efficient screening of higher $TGF-{\beta}1$ producers, even after the transfection and amplification of the transfected gene.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3645-3651
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• 2012

Conventional pap smear (CPS) examination has been the mainstay for early detection of cervical cancer. However, its widespread use has not been possible due to the inherent limitations, like presence of obscuring blood and inflammation, reducing its sensitivity considerably. Automated methods in use in developed countries may not be affordable in the developing countries due to paucity of resources. On the other hand, manual liquid based cytology (MLBC) is a technique that is cost effective and improves detection of precursor lesions and specimen adequacy. Therefore the aim of the study was to compare the utility of MLBC with that of CPS in cervical cancer screening. A prospective study of 100 cases through MLBC and CPS was conducted from October 2009 to July 2010, in a Medical College in India, by two independent pathologists and correlated with histopathology (22 cases). Morphological features as seen through MLBC and CPS were compared. Subsequently, all the cases were grouped based on cytological diagnosis according to two methods into 10 groups and a subjective comparison was made. In order to compare the validity of MLBC with CPS in case of major diagnoses, sensitivity and specificity of the two methods were estimated considering histological examination as the gold standard. Increased detection rate with MLBC was 150%. The concordance rate by LBC/histopathology v/s CPS/histopathology was also improved (86% vs 77%) The percentage agreement by the two methods was 68%. MLBC was more sensitive in diagnosis of LSIL and more specific in the diagnosis of inflammation. Thus, MLBC was found to be better than CPS in diagnosis of precursor lesions. It provided better morphology with increased detection of abnormalities and preservation of specimen for cell block and ancillary studies like immunocytochemistry and HPV detection. Therefore, it can be used as alternative strategy for cervical cancer prevention in limited resource settings.