• Journal of Veterinary Clinics
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• v.23 no.2
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• pp.105-110
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• 2006

A three-layer, feed-forward artificial neural network (ANN) with sixteen input neurons, three hidden neurons, and one output neuron was developed to identify the presence of infectious bronchitis (IB) infection as early as possible in laying hen flocks. Retrospective data from flocks that enrolled IB surveillance program between May 2003 and November 2005 were used to build the ANN. Data set of 86 flocks was divided randomly into two sets: 77 cases for training set and 9 cases for testing set. Input factors were 16 epidemiological findings including characteristics of the layer house, management practice, flock size, and the output was either presence or absence of IB. ANN was trained using training set with a back-propagation algorithm and test set was used to determine the network's capability to predict outcomes that it has never seen. Diagnostic performance of the trained network was evaluated by constructing receiver operating characteristic (ROC) curve with the area under the curve (AUC), which were also used to determine the best positivity criterion for the model. Several different ANNs with different structures were created. The best-fitted trained network, IBV_D1, was able to predict IB in 73 cases out of 77 (diagnostic accuracy 94.8%) in the training set. Sensitivity and specificity of the trained neural network was 95.5% (42/44, 95% CI, 84.5-99.4) and 93.9% (31/33, 95% CI, 79.8-99.3), respectively. For testing set, AVC of the ROC curve for the IBV_D1 network was 0.948 (SE=0.086, 95% CI 0.592-0.961) in recognizing IB infection status accurately. At a criterion of 0.7149, the diagnostic accuracy was the highest with a 88.9% with the highest sensitivity of 100%. With this value of sensitivity and specificity together with assumed 44% of IB prevalence, IBV_D1 network showed a PPV of 80% and an NPV of 100%. Based on these findings, the authors conclude that neural network can be successfully applied to the development of a screening model for identifying IB infection in laying hen flocks.

• The Korean Society of Law and Medicine
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• v.21 no.1
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• pp.223-259
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• 2020

With COVID-19 spreading rapidly around the world, research and development issues on treatments and vaccines for the virus are of high interest. Among them, Remdesivir was the first to show noticeable therapeutic effects and began clinical trials, with each country authorizing the use of the drug through emergency approval. However, Gilead Co., Ltd., the developer of Remdesivir, received a lot of criticism from civic groups for submitting the application for the marketing authorization as an orphan drug. This is because when a new drug got a marketing authorization as an orphan drug could be granted an exclusive status for seven year. The long-term exclusive status of an orphan drug comes from the policy purpose of motivating pharmaceutical companies to develop treatment opportunities for patients suffering from rare diseases, which was not appropriate to apply to infectious disease treatments. This paper provides a review of the problems and improvement directions of the domestic system through comparative legal consideration against the United States, Europe and Japan for the statutes which give exclusive status to medicines. The domestic system has a fundamental problem that it does not have explicit provisions in the statute in the manner of granting exclusive status, and that it uses the review system to give it exclusive status indirectly. In addition, in the case of orphan drugs, the "Rare Diseases Management Act" and the "Regulations on Examination of Items Permission and Reporting of Drugs" provide overlapping review periods, and despite the relatively long monopoly period, there seems to be no check clause to recover exclusive status in the event of a change in circumstances. Given that biopharmaceuticals are difficult to obtain patents, the lack of such provisions is a pity of domestic legislation, although granting exclusive rights may be a great motivation to induce drug development. In the United States, given that the first biosimilar also has a one-year monopoly period, it can be interpreted that domestic legislation is quite strictly limited to granting exclusive status to biopharmaceuticals. The need for improvement of the domestic system will be recognized in that it could undermine local pharmaceutical companies' willingness to develop biopharmaceuticals in the future, and in that it is also necessary to harmonize international regulations. Taking advantage of the emergence of COVID-19 as an opportunity, we look again at the problems of the domestic system that grants exclusive rights to medicines and hope that an overall revision of the relevant legislation will be made to establish a unified legal basis.

• Journal of Plant Biotechnology
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• v.43 no.3
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• pp.261-271
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• 2016

Citrus is an economically important fruit crop widely growing worldwide. However, citrus production largely depends on natural hybrid selection and bud sport mutation. Unique botanical features including long juvenility, polyembryony, and QTL that controls major agronomic traits can hinder the development of superior variety by conventional breeding. Diverse factors including drastic changes of citrus production environment due to global warming and changes in market trends require systematic molecular breeding program for early selection of elite candidates with target traits, sustainable production of high quality fruits, cultivar diversification, and cost-effective breeding. Since the construction of the first genetic linkage map using isozymes, citrus scientists have constructed linkage maps using various DNA-based markers and developed molecular markers related to biotic and abiotic stresses, polyembryony, fruit coloration, seedlessness, male sterility, acidless, morphology, fruit quality, seed number, yield, early fruit setting traits, and QTL mapping on genetic maps. Genes closely related to CTV resistance and flesh color have been cloned. SSR markers for identifying zygotic and nucellar individuals will contribute to cost-effective breeding. The two high quality citrus reference genomes recently released are being efficiently used for genomics-based molecular breeding such as construction of reference linkage/physical maps and comparative genome mapping. In the near future, the development of DNA molecular markers tightly linked to various agronomic traits and the cloning of useful and/or variant genes will be accelerated through comparative genome analysis using citrus core collection and genome-wide approaches such as genotyping-by-sequencing and genome wide association study.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.183-193
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• 2009

Purpose: Rotaviruses, noroviruses, astroviruses, and enteric adenoviruses cause acute gastroenteritis (AGE) in children. Some children with AGE have afebrile convulsions associated with viral gastroenteritis. The purpose of this study was to detect and genotype viruses from children with AGE or benign infantile seizures associated with mild gastroenteritis (BIS-MG). Methods: Between August 2004 and June 2005, 311 children with AGE were included. Four viral agents, including rotavirus, norovirus, astrovirus, and adenovirus, were analyzed from stool specimens of each patient using the latex agglutination method, enzyme immunoassay, and reverse transcriptase polymerase chain reaction. Genotyping of each virus was performed in 217 of the 311 children. Results: Among 217 children (male, 121; female, 96; mean age, 20.6${\pm}$15.4 months), rotavirus was detected in 109 (50.2%), norovirus in 28 (12.9%), adenovirus in 13 (6.0%), and astrovirus in 2 children (0.9%). Genotyping of rotavirus revealed positive results in 97 children; P[8]G3 in 36, P[4]G2 in 21, P[6]G4 in 10, P[4]G4 in 9, P[8]G9 in 6, P[8]G1 in 6, P[4]G3 in 4, P[4]G9 in 3, and P[6]G2 in 2. Genotyping of norovirus showed GII-4 in 27 of 28 children and GII-6 in 1 child. Sixteen children were diagnosed with BIS-MG. Rotavirus was detected in 13 of 16 children with BIS-MG, and norovirus in 2 children. Genotyping of rotavirus detected in children with BIS-MG revealed P[8]G3 in 6 children, P[4]G2 in 2 children, and P[4]G9 in 1 child. Conclusion: Analysis of viruses from stool specimens indicates that both rotavirus and norovirus are the main viruses related to BIS-MG in children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.199-206
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• 2009

Purpose: To analyze the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after liver transplantation in children. Methods: From January 1988 to June 2009, we retrospectively reviewed the medical records of 8 PTLD cases among 148 pediatric patients underwent liver transplantation. The age at transplantation, time of presentation after transplantation, clinical manifestations, histologic diagnosis, results of EBV (Epstein-Barr virus) assessments, managements and outcomes of PTLD were investigated. Results: The prevalence of PTLD in liver transplant pediatric recipients was 5.4% (8 of 148). The mean age of patients was 25.4${\pm}$21.3 months (range 10 to 67 months). Seven of 8 patients (87.5%) underwent liver transplantation before 1 year of age. The common clinical presentations were persistent fever (8 of 8, 100%) and bloody diarrhea (6 of 8, 75%). PTLD was diagnosed with gastrointestinal endoscopic biopsies in five patients and surgical biopsies in three. Histologic findings showed early lesion in three patients, polymorphic in two, and monomorphic in three. Burkitt lymphoma and lymphoblastic lymphoma were found in two of 3 monomorphic patients. Seven of 8 patients were found with EBV-positive. Eight patients were treated with dose reduction of immunosuppressants and infusion of ganciclovir. Rituximab was added to four patients. PTLD were successfully managed in all patients except one who died of sepsis during chemotherapy. Conclusion: Major risk factor of PTLD was to undergo liver transplantation before 1 year of age. Continuous monitoring for EBV viral load and gastrointestinal endoscopic biopsy may be useful to early detection of PTLD.

• Pediatric Infection and Vaccine
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• v.24 no.1
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• pp.16-22
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• 2017

Purpose: We suspect there is a difference in the clinical manifestations and treatment response to antiviral drugs for influenza A and B. This study was conducted to investigate this difference. Methods: We collected information on pediatric patients, infected with the influenza virus, admitted to Dongguk University Ilsan Hospital from October 2013 to May 2015. We investigated the clinical manifestations of influenza and differences in treatment response to oseltamivir treatment for the two types of influenza. Results: A total of 138 patients were included. The mean age was $3.5{\pm}4.0$ years. When comparing the diseases associated with influenza A and B, croup (19.2% vs. 1.7%, P=0.001) was more common with influenza A infection. Myositis (0% vs. 6.7%, P=0.021) and gastroenteritis (29.5% vs. 46.7%, P=0.038) were more common with influenza B infection. When comparing the total fever duration from the start of oseltamivir administration, patients treated with oseltamivir within 2 days of fever had the shortest duration. Among the patients treated with oseltamivir, the duration of fever, after the start of oseltamivir treatment, for was shorter for influenza A infection than for influenza B infection ($16.0{\pm}19.1$ hours vs. $28.9{\pm}27.9$ hours, P=0.006). Conclusions: There appear to be differences in the accompanying diseases and antiviral medication responses between the two types of influenza. It is important to administer oseltamivir within 2 days of fever.

• The Korean Journal of Nuclear Medicine Technology
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• v.15 no.1
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• pp.121-125
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• 2011

Purpose: The DNA-type virus HBV, discovered by D. Dane and others in 1976, is approximately 42nm big and known as the main cause of liver-related diseases around the world. HBsAg has 4 kinds of subtypes including adw, adr, ayw and ayr and besides common antigen factor a, there are d, y, r, w. From the methods of serologically testing HBV, IRMA, EIA and CLIa were developed for testing HBsAg and are being used in examining the surface antigen of HBV. In this study, among the methods for testing HBV, the recently developed RIAKEY Ultrasensitive HBsAg IRMA kit's sensitivity level and performance in detection of mutant forms were measured and compared with CLIA. Materials and methods: Two certified reference materials, which are WHO 1st International Standard 1985(80/549) and WHO 2nd International Standard 2003(00/588. subtype adw2, genotypeA), were used in the examination and the sensitivity level was measured by diluting these materials from 0.08 IU/ml to 0.005 IU/ml. The materials for examining the detection of mutant forms included 9 kinds of subtype 'ad' and one kind of subtype 'ay' purchased from DSI company. Also, with the use of positive and negative samples, they was compared with CLIA. Result: Ultrasensitive HBsAg kit based on IRMA method showed the detection of up to 0.01 IU/ml not only for WHO 1st International Standard 1985(80/549) but also for WHO 2nd International Standard 2003(00/588. subtype adw2, genotypeA) and the sensitivity level was measured as 0.01 IU/ml by WHO standard. In testing the performance for detection of mutant forms, the 9 kinds of subtype 'ad' and one kind of subtype 'ay' mutant materials were detected, demonstrating the capacity of detecting various types of mutant forms. Conclusions: With the clinical importance of sensitivity level and performance in detection of mutant forms increasing in the field of HBsAg diagnosis, the examination of IRMA's effectiveness using RIA method in the aspects of the sensitivity level and performance in detection of mutant forms was carried out and its result is as follows. The sensitivity level was measured as 0.01 IU/ml by WHO standard and it was possible to measure various types of mutant forms with high sensitivity. Thus it is suggested that more speedy and accurate reports could be produced from a nuclear medicine laboratory for clinical practitioners requiring results of various situations.

• Journal of The Korean Society of Grassland and Forage Science
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• v.35 no.1
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• pp.57-62
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• 2015

"Nokyang" (Hordeum vulgare L.), a new whole-crop silage barley cultivar, was developed by the breeding team at the Department of Rice and Winter Cereal Crop, National Institute of Crop Science, RDA, Korea in 2012. It was derived from combining "Nagyoung" and breeding line "SB77368-B-145". Among the combinations made in 2001, a promising line, "SB01T2017", showed good characteristics in terms of potential forage yield in the yield trial at Iksan from 2007 to 2009. In 2009, the promising line was designated as "Iksan457" and placed in regional yield trials at six locations around Korea for three years from 2010 to 2012, and was released under the name of "Nokyang." It has the growth habit of a group III creeping plant type, with a light-green leaf and common spike. Its average heading and maturing dates were on May 6 and June 4, respectively, which were later than cultivar "Youngyang." "Nokyang" also showed strong winter hardiness, and a resistance to shattering and barley yellow mosaic virus (BaYMV) similar to those of the check cultivar. The best thing among the traits of one is a new good quality with the plant green at the latter growing period. The average forage dry matter (DM) yields in the regional yield trial were about 12.8 and 11.5 MT $ha^{-1}$ in upland and paddy field, respectively, which were higher than those of the check cultivar, by 7% and 2%, respectively. This cultivar would be suitable for an area of the Korean peninsula where the daily minimum temperature in January is above $-8^{\circ}C$.

• Journal of The Korean Society of Grassland and Forage Science
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• v.39 no.4
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• pp.243-249
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• 2019

A barley(Hordeum vulgare L.) cultivar 'Youjin' with hooded spike type having good silage quality was developed at National Institute of Crop Science, RDA in 2016. 'Youjin' showed both high yielding and cold resistance through the preliminary and advanced yield trials(PYT, AYT) from 2012 to 2013. We conducted regional yield trials(RYT) of 'Youjin' in six locations around Korea for three years from 2014 to 2016. It had erect plant type, growth habit of II, the green leaf and hooded awn type. In the paddy field its heading date was April 24 and the maturing date was May 25. Plant height was 99 cm and the number of spikes per ㎡ was 696. It has high rate of leaf blades, resistance to BaYMV(Barley Yellow Mosiac Virus) and good winter hardiness. The average dry matter of Youjin was about 17.2 MT ha^-1 in the field. And feed quality of 'Youjin' was 10.6% of crude protein content, 24.8% of ADF(Acid Detergent Fiber), 43.5 % of NDF(Neutral Detergent Fiber), 69.1% of TDN(Total Digestible Nutrients). And also 'Youjin' had grade I of silage quality.

• Pediatric Infection and Vaccine
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• v.11 no.2
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• pp.176-182
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• 2004

Purpose : The etiologic agents of aseptic meningitis remain mostly unknown due to difficulty of viral culture and identification. There was an outbreak of aseptic meningitis in northern area of Seoul from June to August, 2002. We report the clinical features, laboratory data and causative viruses on 196 children with aseptic meningitis during this period. Methods : We retrospectively studied about clinical manifestations and laboratory findings 196 patients diagnosed as aseptic meningitis at Sanggye-Paik hospital. Virus isolation and serotype identification were performed by cell culture and reverse transcription polymerase chain reaction(RT-PCR) of the cerebrospinal fluid. Results : The male to female ratio was 1.39 : 1 and the mean age was 5.8+3 years. The clinical manifestations were fever, headache and vomiting. It occurred mostly in June, July and August. The numbers of peripheral blood leukocytes were $4,800{\sim}24,360/mm^3$. On cerebrospinal fluid examinations, leukocytes were in range of 10~2,000(mean 105)/$mm^3$, protein level in range of 15~171(mean 41.4) mg/dL and glucose level from 16~97(mean 57.9) mg/dL. Viral culture of cerebrospinal fluid showed 3 cases of Echovirus 9, 1 case of 25 and 30. In stool culture, 2 cases of Echovirus 6, 2 cases of Echovirus 13 and 1 case of Echovirus 30 were isolated. Conclusion : The etiologic viruses of the aseptic meningitis in northern area of Seoul in 2002 are presumed to be Echovirus 6, 9, 13, 25, 30.