An optimized BRCA1/2 next-generation sequencing for different clinical sample types

OBJECTIVE: A simultaneous detection of germline and somatic mutations in ovarian cancer (OC) using tumor materials is considered to be cost-effective for BRCA1/2 testing. However, there are limited studies of the analytical performances according to various sample types. The aim of this study is to propose a strategy for routine BRCA1/2 next-generation sequencing (NGS) screening based on analytical performance according to different sample types. METHODS: We compared BRCA1/2 NGS screening assay using buffy coat, fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) from 130 samples. RESULTS: The rate of repeated tests in a total of buffy coat, FF and FFPE was 0%, 8%, and 34%, respectively. The accuracy of BRCA1/2 NGS testing was 100.0%, 99.9% and 99.9% in buffy coat, FFPE and FF, respectively. However, due to the presence of variant allele frequency (VAF) shifted heterozygous variants, tumor materials (FFPE and FF) showed lower sensitivity (95.5%-99.0%) than buffy coat (100%). Furthermore, FFPE showed 51.4% of the positive predictive value (PPV) on account of sequence artifacts. When performed in the post-filtration process, PPV was increased by approximately 20% in FFPE. Buffy coat showed 100% of sensitivity, specificity and accuracy in BRCA1/2 NGS test. CONCLUSIONS: On the comparison of the analytical performance according to different sample types, the buffy coat was not affected by sequencing artifacts and VAF shifted variants. Therefore, the blood test should be given priority in detecting germline BRCA1/2 mutation, and tumor materials could be suitable to detect somatic mutations in OC patients without identifying germline BRCA1/2 mutation.ope

Haplotype Structure of the UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene and Its Relationship to Serum Total Bilirubin Concentration in a Male Korean Population

ope

음소인지 교육이 한국 초등학교 EFL 학습자들의 듣기 이해 능력에 미치는 영향

학위논문(석사) -- 서울대학교대학원 : 사범대학 외국어교육과(영어전공), 2021.8. 이민서.Phonemic awareness is a prerequisite ability to process foreign language speech (McDowell & Lorch, 2008). When learners do not have adequate phonemic awareness of the target language, they may face difficulties decoding speech streams of the foreign language. A considerable amount of focus is on enhancing listening skills in traditional L2 classrooms, yet they are mostly taught in word and sentence levels. Although students learning English as a foreign language need to develop sufficient ability for phonemic awareness, efforts to integrate phonemic awareness instruction with listening drills and activities are lacking. Furthermore, the main interest of this thesis, phoneme awareness instruction, was conducted in several previous studies related to the reading instruction of English native language learners, but there was a dearth of studies on phoneme awareness and listening for Korean elementary school learners in the EFL environment. This study examines the efficacy of explicit phonemic awareness instructions on developing phonemic awareness and listening comprehension skills, by comparing the pre- and posttest progress made by participants enrolled in an English course at an elementary school in Korea. Furthermore, it examines whether there are varying effects among different proficiency groups. An experimental design was used to investigate the effectiveness of phonemic awareness instructions on 57 Korean EFL elementary school learners, which were sub-grouped into three proficiency levels. The phonemic awareness odd-one-out test and multiple-choice listening comprehension test are used to collect data about students’ level of phonemic awareness and listening comprehension skills. The intervention took four weeks of 19 sessions, consisted of 14 asynchronous online instructions and five reviewing sessions in the classroom. Target phonemes were predetermined thirteen consonants which the learners found difficult to distinguish. Results indicate a positive effect of the instruction and an implication for the L2 classrooms. First, a paired sample t-test illustrated that phonemic awareness instruction has significantly enhanced EFL learners’ phonemic awareness and listening comprehension skills small and medium effects (Cohen’s d = 0.37; 1.08). Secondly, a paired sample t-test within proficiency group demonstrated the lower level group has shown the largest improvement in their listening comprehension scores (Cohen’s d = 1.49). Thirdly, Pearson’s product-moment correlation revealed that there is a statistically significant positive correlation between phonemic awareness ability and listening comprehension skills of the participants in the pretests (Pearson’s correlation coefficient = .427**) and stronger relationships in the posttests (Pearson’s correlation coefficient = .479**). The conclusion can be drawn that students’ development of phonemic awareness positively correlates with their listening comprehension skills. Pedagogical implications for L2 classrooms are provided following a depth analysis of the research results.외국어의 음소 구분 능력은 외국어 발화 듣기를 처리하기 위한 전제 조건이며 학습자의 듣기 능력에 영향을 미치는 주요 요인으로 여겨져 왔다. 학습자가 목표 언어의 충분한 음소 인지 능력을 가지고 있지 않은 경우, 외국어 음성을 이해하기 어려울 수 있다. 기존의 L2 교실의 영어수업은 학생들의 듣기 능력 향상에 많은 초점이 맞춰져 있지만, 대부분의 경우 단어와 문장 수준에서 진행하고 있다. 이에 외국어로서 영어를 배우는 학생들은 그들의 외국어 음소 인지 능력을 충분히 발달시킬 필요가 있으나 음소 인지 수업을 듣기 활동과 통합하는 노력은 부족했다. 또한 선행 연구를 살펴보면 이 논문의 주요 관심사인 음소 인지 지도는 영어 모국어 학습자들의 독해 지도와 관련으로 한 연구로만 주로 연구 되었으며 EFL 환경의 한국 초등학교 학습자들을 대상으로 한 듣기 지도에 대한 연구는 많지 않았다. 따라서 본 연구는 명시적인 음소 인지 교육의 효과를 조사하기 위하여 57명의 한국의 초등학생 참여자들을 모집했다. 4주간의 교육 기간을 거쳐 참여자들의 음소 인지와 청해 시험의 사전, 사후 결과를 비교했다. 또한 다른 숙련도 그룹간에 다양한 효과가 있는지 여부를 확인하기 위하여 청해 사전 시험의 결과를 토대로 참여자들을 3개의 하위 집단으로 구분하여 실험 결과를 분석했다. 교육 기간은 19번의 수업으로 이루어졌으며 이 중 14회는 온라인 영상을 탑재하는 방법으로, 5회는 온라인에서 배운 내용을 교실에서 복습해 보는 수업으로 진행되었다. 교육 대상 음소는 파일럿 테스트를 통해 알아본, 한국인 초등학생 학습자들이 가장 어렵다고 느낀 13개의 자음으로 구성되었다. 본 연구의 결과는 다음과 같은 음소 인지 지도의 긍정적인 효과와 L2 교실에 미치는 영향을 보여준다. 첫째, 음소 인지 지도를 받은 EFL 학습자의 음소 인지 능력, 청해 실력은 모두 통계적으로 유의미한 향상을 보여주었다 (코헨의 효과 크기 d = 0.37; 1.08). 둘째, 시간에 따른 수준별 집단 별 교육의 효과를 비교 한 결과, 제일 낮은 수준의 그룹의 청해 점수가 가장 큰 효과 크기로 향상되었다는 것을 알 수 있었다 (코헨의 효과 크기 d = 1.49). 마지막으로, 참가자들의 음소 인지 능력은 청해 실력과 정적인 상관관계를 보이는 것으로 나타났으며 이는 사전 시험 (피어슨 상관 계수 = .427**)에서보다 사후 시험 (피어슨 상관 계수 = .479**)에서 더욱 높은 상관관계를 보여주었다. 본 연구의 결과는 외국어로서 영어를 학습하는 학습자들의 발음 교육과 듣기 지도를 위한 교육과정 수립에 참고 자료로 활용될 수 있으며 이에 따른 영어 교육학적 함의를 지닌다.CHAPTER 1. INTRODUCTION 1 1.1 Background of the Study 1 1.2 Purpose of the Study 3 1.3 Research Questions 5 1.4 Organization of the Thesis 5 CHAPTER 2. LITERATURE REVIEW 7 2.1 Phonemic Awareness 7 2.1.1 Definition of Phonemic Awareness 7 2.1.2 Phonemic Awareness in Relation to Phonological Awareness 9 2.1.3 Differences between Phonemic Awareness and Phonics 12 2.1.4 Phonological Processing Ability in Listening Process 16 2.2 The Relationship between Phonemic Awareness and L2 Listening Comprehension 18 2.3 Development of Phonemic Awareness 21 2.4 Phoneme Differences between L1 and L2 26 2.4.1 Phoneme Differences between Korean and English 26 2.4.2 English Consonants Chosen for this Study 29 2.5 Phonemic Awareness Intervention in L2 Classrooms 30 2.6 Listening Instructions in Traditional L2 Classrooms 35 2.7 Summary of the Chapter 37 CHAPTER 3. METHODOLOGY 38 3.1 Participants 39 3.2 Instruments 40 3.2.1 Pretest and Posttest 40 3.2.2 Experiment Materials 43 3.2.3 Treatment 49 3.3 Procedures 53 3.3.1 Pilot Study 53 3.3.2 Lesson Procedure of the Experimental Group 59 3.3.3 Post-survey and Interviews 63 3.4 Data Analysis 64 CHAPTER 4. RESULTS 67 4.1 Effects of Phonemic Awareness Instruction 68 4.1.1 Effects of Phonemic Awareness Instruction on Phonemic Awareness Development 68 4.1.2 Effects of Phonemic Awareness Instruction on Listening Comprehension 73 4.2 Comparison by Proficiency Groups 75 4.2.1 Results of a Paired Sample t-test within Group 76 4.2.2 Results of Correlation 79 4.3 Post Survey and Interviews 88 4.4 Summary of the Chapter 95 CHAPTER 5. DISCUSSION 96 5.1 Discussion on Effects of Phonemic Awareness Instruction 96 5.2 Effects of Phonemic Awareness Instruction between Proficiency Groups 99 5.3 Relationship between Phonemic Awareness and Listening Comprehension Skills 100 5.4 Discussion on Student Survey and Interviews 102 5.5 Summary of the Chapter 104 CHAPTER 6. CONCLUSION 106 6.1 Major Findings and Pedagogical Implications 106 6.2 Limitations and Suggestions for Future Research 109 REFERENCES 111 APPENDICES 120 ABSTRACT IN KOREAN 139석

A Population-Based Analysis of BRCA1/ 2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study

In this study, we performed a comprehensive analysis of BRCA1/2 variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in BRCA1 and BRCA2. This study included 5433 Korean participants who were tested for BRCA1/2 genes. The BRCA1/2 variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had BRCA1 or BRCA2 PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for BRCA2 VUS than those of BRCA1 VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1-73.6%) for BRCA1 and 58.3% (95% CI: 43.2-73.0%) for BRCA2 carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4-53.9%) for BRCA1 and 14.9% (95% CI: 7.4-28.5%) for BRCA2 carriers.ope

Detection of Anti-Extractable Nuclear Antigens in Patients with Systemic Rheumatic Disease via Fluorescence Enzyme Immunoassay and Its Clinical Utility

PURPOSE: Testing for autoantibodies to extractable nuclear antigens (ENAs) plays an important role in the diagnosis and management of systemic rheumatic disease. Currently, no gold standard tests are available for detecting anti-ENAs. To address this gap, we aimed to identify an assay that exhibits satisfactory diagnostic performance in the detection of five common anti-ENAs by comparing two commonly used assays, an automated fluorescent enzyme immunoassay (FEIA) and a microplate ELISA assay. MATERIALS AND METHODS: Sera from 100 patients with systemic rheumatic disease were collected and assayed with FEIA and microplate ELISA to detect anti-ENAs. Statistical analyses were performed to check the agreement rate between the two platforms using kappa coefficients. Analytical sensitivity and specificity for each assay were calculated. RESULTS: The concordance rates between ELISA and FEIA ranged from 89% for anti-RNP to 97% for anti-Scl-70, and the kappa coefficients of the two assays were in the range of 0.44 to 0.82. Between the two assays, a significant difference in sensitivity and specificity was seen only for anti-Sm and anti-RNP, respectively. CONCLUSION: In this study, FEIA and ELISA showed comparable efficiency for detecting anti-ENAs.ope

Relationship between Myelodysplastic Syndrome and Epstein-Barr Virus or Human Parvovirus Bl9 Infection

Background :The mechanisms responsible for the disturbed hematopoiesis in myelodysplastic syndrome (MDS) include the expansion of abnormal clones, defects in cellular differentiation and he perturbation in the production of hematopoietic regulatory factors. Recently, viral infection such as immunodeficiency virus is known to induce myelodysplasia. And viral infection evokes the production of several cytokines. Therefore, abnormal production of cyrokine may be a potential candidate for the pathogenesis of MDS after viral infections such as Epstein-Barr virus (EBV) and human parvovirus B19. Method :We investigated bone marrow aspiration slides from 17 patients with MDS referred for the bone marrow study, over a period from January, 1992 to April, 1996. To clarify the contribution of EBV and human parvovirus B19 infections to the pathogenesis of MDS, DNA-PCR for EBV and human parvovirus Bl9 was used. Result :The EBV and human parvovirus B19-PCR results were all negative in 17 patients with MDS. Conclusion :EBV and human parvovirus Bl9 infections may not be associated with the major pathogenesis of MDSope

Identification of a UGT1A1*37 Allele in a Korean Patient with Pancreatic Cancer

UDP-glucuronosyltransferase 1A1 (UGT1A1) is an enzyme that catalyzes glucuronidation of substances, including bilirubin and other drug metabo lites. Certain UGT1A1 polymorphisms reduce UGT1A1 activity, notably UGT1A1*28 contains thymine-adenine repeats in the TATA box of the promo tor region. Irinotecan, a chemotherapy agent for solid cancers, is converted in the body to an active metabolite, SN-28, and then excreted, after being conjugated with glucuronide by UGT1A1. If UGT1A1 activity decreases (e.g. UGT1A1*28), the risk of irinotecan toxicity increases, which can develop into severe neutropenia and diarrhea. UGT1A1*37, a rare allele that has never been found in Asians, was previously reported to be asso ciated with severe neutropenia by reducing UGT1A1 activity further than UGT1A1*28. In this study, we first detected UGT1A1*37 in a 69-year-old Korean woman diagnosed with pancreatic cancer and excluded irinotecan from her chemotherapy regimen, in consideration of the increased risk of toxicity, based on pre-treatment UGT1A1 genotyping.ope

Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines Part 2

Pharmacogenetics is a rapidly evolving field and the number of pharmacogenetic tests for clinical use is steadily increasing. However, incorrect or inadequate implementation of pharmacogenetic tests in clinical practice may result in a rise in medical costs and adverse outcomes in patients. This document suggests guidelines for the clinical application, interpretation, and reporting of pharmacogenetic test results based on a literature review and the collection of evidence-based expert opinions. The clinical laboratory practice guidelines encompass the clinical pharmacogenetic tests covered by public medical insurance in Korea. Technical, ethical, and regulatory issues related to clinical pharmacogenetic tests have also been addressed. In particular, this document comprises the following pharmacogenetic tests: CYP2C9 and VKORC1 for warfarin, CYP2C19 for clopidogrel, CYP2D6 for tricyclic antidepressants, codeine, tamoxifen, and atomoxetine, NAT2 for isoniazid, UGT1A1 for irinotecan, TPMT for thiopurines, EGFR for tyrosine kinase inhibitors, ERBB2 (HER2) for erb-b2 receptor tyrosine kinase 2-targeted therapy, and KRAS for anti-epidermal growth factor receptor drugs. These guidelines would help improve the usefulness of pharmacogenetic tests in routine clinical settings.ope

Down-Turner syndrome (45,X/47,XY,+21): case report and review

We report the case of a 3-yr-old boy with Down-Turner mosaicism and review the previous reports of Down-Turner syndrome with documented karyotyping and clinical features. The patient showed clinical features of Down syndrome without significant stigma of Turner syndrome. Cytogenetic analysis of peripheral blood preparations by using G-banding revealed mosaicism with 2 cell lines (45,X[29]/47,XY,+21[4]). FISH analysis revealed that 87.5% of the cells had monosomy X karyotype and 12.5% of the cells had XY karyotype; trisomy 21 was only detected in the Y-positive cells. We suggest that additional cells should be analyzed and molecular genetic studies should be conducted to rule out double aneuploidy when karyotypes with sex chromosome aneuploidies and mosaicism are encountered, as in our case of Down syndrome mosaic with sex chromosome aneuploidy.ope

A Cytogenetic Study of 130 Couples with Recurrent Spontaneous Abortion

Background :Chromosomal aberration of a couple can lead to recurrent miscarriage and it has been accounted for 2-10% of recurrent spontaneous abortions in the Caucasian population The purpose of this stuffy is to evaluate the frequency of chromosomal abnormalities in couples having fetal losses. We also attempted to define the relationship of those chromosome rearrangements with the presence or absence of stillborn fetus or malformed live child Method :A total of 130 couples with two or more spontaneous abortions were studied. Chromosome studios were performed on metaphases using standard peripheral lymphocyte culture technique Result :Ten (77%) chromosomal abnormalities were detected, 7 (5,4%) in women and 3 23%) in men. The chance of finding chromosomal abnormality in couples with stillborn fetus or malformed live child was higher than in couples with spontaneous abortions but no other adverse event, but the difference was not statistically significant. Conclusion :Cytogenetic analysis was indicated in couples with recurrent spontaneous abortions The chance of chromosomal abnormality in couples with stillborn fetus or malformed live child was higher.ope