Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG)

The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of ITGB3 was the most common, followed by c.2333A>C (p.Gln778Pro) of ITGB2B. Known variants of GT, including c.917A>C (p.His306Pro) of ITGB3 and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of ITGA2B, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of ITGB3 and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of ITGA2B, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel RASGRP2 variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.ope

A Study of Underwater Acoustic Communication for High Speed Data Transmission

Recently, the necessity of underwater acoustic comunication increase, and demands for transmitting and receiving various data such as voice or high resolution data are increasing as well. However, the performance of underwater acoustic communication is influenced on underwater channel characteristic. Many obstacles exist in underwater acoustic communication. Especially, an important feature of the underwater acoustic communication is multipath propagation and Doppler spread cause by the surface and bottom reflections. Orthogonal Frequency Division Multiplexing(OFDM) technique for mitigating of multipath fading is central to improving the performance of underwater acoustic communication system. Conventional OFDM system uses a fixed-length Cyclic Prefix(CP) to mitigate Inter-Symbol Interferences (ISI) caused by underwater channel delay spreading. CP length may cause considerable performance degradation when it is less than the channel Root-Mean-Square (RMS) delay spread or decrease the system power and spectrum efficiency when it is much larger than the channel RMS delay spread. This thesis proposed to variable CP length to adapt variation of channel delay spread. Adaptive OFDM utilizes the preamble or pilot symbol of each OFDM packet to estimate the channel RMS delay spread and then uses a criterion to calculate the CP length. In this thesis, the performance of the conventional OFDM and the adaptive OFDM system are compared in Underwater Acoustic Communication System. The thesis compared the original image data with demodulated image data. Futhermore, this thesis also compare the multi-carrier underwater acoustic communication system with single-carrier underwater acoustic communication system. As a result, this thesis shows that the improvement of bit rate is about 20% compared with conventional method.제 1 장 서론 = 1 제 2 장 수중 음향 통신 채널 특성 = 4 제 2-1 절 수중 채널 특성 = 4 제 2-2 절 수중 음향 통신 오차 유발 요인 분석 = 5 2-2-1. 전달 손실(Path-Loss) = 6 2-2-2. 다중 경로(Multi-Path) = 6 2-2-3. 도플러 확산(Doppler spread) = 7 2-2-4. 잡음(Noise) = 7 제 3 장 OFDM 전송 시스템 = 9 제 3-1절 OFDM 전송 시스템 = 9 제 3-2 절 보호구간 = 12 제 3-3 절 동기화 = 14 3-3-1. 프리앰블 = 14 제 3-4 절 OFDM 수신기 = 18 3-4-1. 패킷 검파 = 18 제 3-5 절 시뮬레이션을 통한 성능 평가 = 20 3-5-1. 수중 시뮬레이션 환경 = 20 3-5-2. 수중 시뮬레이션 = 21 제 4 장 가변 보호구간을 갖는 OFDM 시스템 = 23 제 4-1 절 채널 추정 = 24 4-1-1. 프리앰블을 사용한 채널 추정 = 24 4-1-2. 파일럿 심벌을 사용한 채널 추정 = 25 제 4-2 절 RMS 지연확산 추정 = 26 제 4-3 절 시뮬레이션을 통한 성능 평가 = 27 제 5 장 수중에서 OFDM 통신의 실험 및 분석 = 29 제 5-1 절 수중 음향 통신 환경 = 31 제 5-2 절 패킷 검파 = 33 제 5-3절 QPSK 수신신호의 복조 = 35 제 5-4절 OFDM 수신신호의 복조 = 36 제 5-5 절 가변 보호구간을 가지는 OFDM 수신신호의 복조 = 36 제 6 장 결론 = 38 참고문헌 = 4

Joint Health Status in Hemophilia Patients Using Hemophilia Joing Health Score and Pettersson Score

Background: Comprehensive clinical and radiologic follow-up is needed to preserve joint functions and quality of life in hemophilia using clinimetric tools such as Hemophilia joint health score (HJHS) or Pettersson score (PS). We investigated the joint health status evaluated using the tools in Korean hemophilia patients. Methods: We reviewed retrospectively medical records to collect clinical parameters, HJHS and PS, who were followed up in Severance Hospital, Seoul, Korea. The correlation between HJHS and PS, and the effect of the prophylaxis for hemophilia on the outcomes measured with the scores were evaluated. The prophylaxis proportion (PP) was calculated as the proportion of prophylaxis duration to each patient’s life time. Results: Total of 28 patients with severe hemophilia were enrolled. Twelve patients (42.8%) were less than 20 years old. Total of 23 patients had experienced prophylaxis during their lives, and median PP was 39.7%. There was significant correlation between HJHS and PS (P＜0.001). Each score was positively correlated with patient’s age (P＜0.001). PP was negatively correlated with either HJHS or PS (P＜0.001, respectively). There was significant correlation between either HJHS or PS and the PP in the group of patients ＜20 years old, but there was no correlation in the group of ＞20 years old. Conclusion: HJHS and PS were positively correlated. Each score increased as the patient’s age increased. The prophylaxis had protective effect on joint health. The prospective evaluation of HJHS and PS will be needed to prove the effect of proper management on the joint health status.ope

Metal doping effects in cycle ability and efficiency of SiOx lithium-ion battery anodes

실리콘 산화물 (SiOx, x ≈ 1)은 기존 흑연에 비해 높은 이론용량을 가지고 있어 차세대 리튬이온 이차전지 음극재로써 각광받고 있는 물질이다. 하지만 이러한 큰 용량에도 불구하고 기존 흑연에 비해 낮은 초기 충·방전 효율은 상용화하는데 큰 걸림돌이 되고 있다. 이러한 문제점을 해결하기 위해서, 본 연구에서는 물리 증기 증착법(Physical Vapor Deposition, PVD)를 통해 대량으로 마그네슘을 도핑한 새로운 물질의 합성을 성공적으로 해냈다. 마그네슘은 실리콘 산화물과 반응해 실리콘과 전기화학적으로 반응하지 않는 마그네슘실리케이트를 만들어 초기 충·방전 효율을 증가시킨다. 또한, 마그네슘 도핑 구성은 수명 특성과 전기전도성을 향상하게 하는 데 중요한 역할을 한다. 본 연구는 전극부터 입자 내부까지의 다중 스케일 분석을 통해 충·방전 시 일어나는 실리콘 산화물 입자 내부의 형태 변화와 수명 특성과 연관이 있는지 통찰하였다. 마그네슘의 도핑 함량에 따라 실리콘 도메인 크기가 초기 및 충·방전 후 상태에 영향을 끼친 것으로 확인됐다. 이 연구를 통해 마그네슘이 8% 함유된 샘플에서 용량, 효율, 그리고 수명 특성에 있어서 가장 좋은 균형성을 가지고 있는 것을 확인했다. 특정한 마그네슘실리케이트 상이 많은 충·방전을 거쳤을 때, 다른 상과 균일하게 섞이는 모습이 관찰됐다. 이 결과로 실리콘 도메인의 크기가 작아짐에 따라 수명 특성이 다른 배치보다 월등하다는 것을 보였다. 이러한 연구는 실리콘 산화물을 효율을 높이려 다른 금속을 첨가하여 합금(alloy)을 만들 때, 적절한 조합이 최상의 성능을 보여주고 있음을 시사한다.제 1 장 서 론 1 제 2 장 문헌연구 3 2.1 리튬이온이차전지 3 2.1.1 시스템 3 2.1.2 실리콘(silicon)기반 음극소재 4 2.2 초기효율 향상방법 8 2.2.1 Prelithiation 8 2.2.2 산소함량제어 8 2.2.3 금속도핑 10 2.2.4 마그네슘 도핑 11 제 3 장 실험방법 12 3.1 합성 및 특성분석 12 3.1.1 합성방법 12 3.1.2 물질함량 분석 12 3.1.3 X-ray 분석 14 3.1.4 전자현미경 분석 14 3.2 전기화학분석 15 3.2.1 코인셀 반쪽전지 제작 15 3.2.2 전기화학 테스트 15 3.3 소재열화분석 17 3.3.1 코인셀 분해 및 전극 획득 17 3.3.2 X-ray 분석 17 3.3.3 전자현미경 분석 17 제 4 장 결과 및 고찰 19 4.1 입자특성분석 19 4.1.1 겉보기 특징 및 구조분석 19 4.1.2 XPS 결과 21 4.2 전기화학분석 25 4.2.1 전지성능 평가 25 4.2.2 도핑에 따른 이론용량 28 4.3 소재열화분석 31 4.3.1 전극두께 및 구조변화 분석 31 4.3.2 입자내부의 열화분석 34 제 5 장 결론 47 참고문헌 48 Abstract 52석

Trends in contralateral prophylactic mastectomy rate according to clinicopathologic and socioeconomic status

PURPOSE: There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) among women diagnosed with unilateral breast cancer or mutations in BRCA1 or BRCA2 to reduce the occurrence of contralateral breast cancer. This study aimed to examine trends in the CPM rate according to clinicopathologic and socioeconomic status at a single institution in Korea. METHODS: This study included 128 patients with mutations in BRCA1 or BRCA2. Patients were divided into a CPM group (n = 8) and a non-CPM group (n = 120) between May 2013 and March 2016. The main outcome variables, including epidemiology, clinical features, socioeconomic status, and tumor characteristics, were analyzed. RESULTS: A total of 8 CPMs were performed among 128 patients. All CPM patients were married. The proportion of professional working women was higher in the CPM group (P = 0.049). Most patients who underwent CPM graduated college, compared to less than a third of the non-CPM group (P = 0.013). The CPM group had a higher rate of visits to the Hereditary Breast and Ovarian Cancer (HBOC) clinic (P = 0.021). The risk-reducing salpingo-oophorectomy (RRSO) rate was significantly higher in the CPM group (P < 0.01). CONCLUSION: CPM rates were significantly different according to socioeconomic status. The CPM rate tends to increase in highly educated and professional working women. The socioeconomic status of patients is an important factor in the decision to participate in the HBOC clinic and undergo CPM or RRSO.ope

Superimposed Pilot에 의해 향상된 Throughput을 갖는 수중음향통신에 관한 연구

Recently, the necessity of underwater acoustic communication increase, and demands for transmitting and receiving various data such as voice or high resolution data are increasing as well. However, the performance of underwater acoustic communication is influenced on underwater channel characteristic. Many obstacles exist in underwater acoustic communication. The performance of coherent acoustic communication systems is highly dependent upon channel characteristics including multipath, spatial and temporal coherence, Doppler effects and ambient noise. An important feature of the process of the sound field formation in oceanic waveguide is the interference caused by the surface and bottom reflections and by the layered structure of the water bulk. This means multipath effect. The interference effects lead to the ISI (Inter-Symbol-Interference). The performance of underwater acoustic communication is sensitive to the ISI due to multipath signal propagation. A popular technique to maintain coherent demodulation of digital modulation schemes is known as pilot-symbol-assisted channel estimation. The main idea of pilot-symbol-assisted channel estimation is to add known pilot symbols (or training symbols) into a data stream. In this paper, I verify the performance of acoustic communication based on pilot-symbol-assisted channel estimation technique through the sea trial. However, receiver for channel estimation must satisfy the condition that pilot symbol length is longer than the delay spread. If the delay spread is longer than pilot symbol length, data demodulation is impossible because equalizer has not optimized tap coefficient and in the opposition case. And in the opposition case, it obtains a good performance but generates an overhead and decrease data rate. This thesis proposed underwater acoustic communication using channel estimation based on superimposed pilot for decrease an overhead. Channel estimation technique based on superimposed pilot transmit the data symbol and pilot symbol in same time and same frequency. In the superimposed pilot channel estimation, the receiver correlates the received signal with the pilot symbol, and obtains the channel estimate. The system with the superimposed channel estimation has a high spectral efficiency because of the simultaneous transmission of the pilot symbol and the data symbol. Especially, superimposed pilot technique is possible to estimate the time-variant channel without additional overhead and increase the data rate. In this thesis, the performance of the conventional pilot-symbol-assisted channel estimation and the superimposed pilot channel estimation was compared in underwater acoustic communication system. Furthermore, the thesis compares the performance according to the superimposed pilot length and power. As a result, minimize the overhead of underwater communication system and increase the data rate about 10 % ~ 30%.List of Tables iii List of Figures iv Abbreviation vii Abstract ix 제 1 장 서론 1 1.1 연구 배경 1 1.2 연구 목적 5 1.3 논문 구성 6 제 2 장 수중 음향 채널 특성 8 2.1 신호 감쇠 9 2.1.1 확산 손실 9 2.1.2 흡수 손실 10 2.1.3 전달 손실 11 2.2 다중 경로 13 2.3 도플러 효과 16 2.4 잡음 16 2.4.1 주변 잡음 17 2.4.2 인공 잡음 17 제 3 장 수중음향통신 시스템 구성 및 성능 19 3.1 전송 기법에 따른 성능 분석 19 3.1.1 QPSK(Quadrature Phase Shift Keying) 19 3.1.2 OFDM(Orthogonal Frequency Division Multiplexing) 22 3.1.3 대역확산(Spread Spectrum) 기법 26 3.2 수신기 구성 30 3.2.1 시간 동기 오차 회복(Timing Offset Recovery) 31 3.2.2 주파수 동기 오차 회복(Frequency Offset Recovery) 33 3.2.3 등화기(Equalizer) 40 3.3 해상시험 및 분석 50 3.3.1 고속데이터 전송기법의 해상시험 결과 및 분석 50 3.3.2 전송거리 증가를 위한 전송기법의 해상시험 결과 및 분석 56 제 4 장 Superimposed Pilot을 이용한 수중음향통신 시스템 76 4.1 파일럿 심벌 전송길이에 따른 성능 변화 76 4.2 Superimposed pilot을 이용한 채널 추정 기법 82 제 5 장 시험 및 고찰 89 5.1 모의시험 및 분석 89 5.1.1 모의 수중채널 환경 89 5.1.2 모의시험 결과 분석 92 5.2 해상시험 및 분석 99 제 6 장 결론 105 참고문헌 10

Differentiation between Clear Cell Sarcoma of the Kidney and Wilms' Tumor with CT

Objective: Clear cell sarcoma of the kidney (CCSK) is the second-most common but extremely rare primary renal malignancy in children after Wilms' tumor. The aims of this study were to evaluate the imaging features that could distinguish between CCSK and Wilms' tumor and to assess the features with diagnostic value for identifying CCSK. Materials and methods: We reviewed the initial contrast-enhanced abdominal-pelvic CT scans of children with CCSK and Wilms' tumor between 2010 to 2019. Fifty-eight children (32 males and 26 females; age, 0.3-10 years), 7 with CCSK, and 51 with Wilms' tumor, were included. The maximum tumor diameter, presence of engorged perinephric vessels, maximum density of the tumor (Tmax) of the enhancing solid portion, paraspinal muscle, contralateral renal vein density, and density ratios (Tmax/muscle and Tmax/vein) were analyzed on the renal parenchymal phase of contrast-enhanced CT. Fisher's exact tests and Mann-Whitney U tests were conducted to analyze the categorical and continuous variables, respectively. Logistic regression and receiver operating characteristic curve analyses were also performed. Results: The age, sex, and tumor diameter did not differ between the two groups. Engorged perinephric vessels were more common in patients in the CCSK group (71% [5/7] vs. 16% [8/51], p = 0.005). Tmax (median, 148.0 vs. 111.0 Hounsfield unit, p = 0.004), Tmax/muscle (median, 2.64 vs. 1.67, p = 0.002), and Tmax/vein (median, 0.94 vs. 0.59, p = 0.002) were higher in the CCSK compared to the Wilms' group. Multiple logistic regression revealed that engorged vessels (odds ratio 13.615; 95% confidence interval [CI], 1.770-104.730) and Tmax/muscle (odds ratio 5.881; 95% CI, 1.337-25.871) were significant predictors of CCSK. The cutoff values of Tmax/muscle (86% sensitivity, 77% specificity) and Tmax/vein (71% sensitivity, 86% specificity) for the diagnosis of CCSK were 1.97 and 0.76, respectively. Conclusion: Perinephric vessel engorgement and greater tumor enhancement (Tmax/muscle > 1.97 or Tmax/vein > 0.76) are helpful for differentiating between CCSK and Wilms' tumor in children aged below 10 years.ope

Characteristics and Outcomes of Second Malignant Neoplasms after Childhood Cancer Treatment: Multi-Center Retrospective Survey

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.ope

Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea

Purpose: Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. Materials and methods: In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. Results: Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. Conclusion: Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.ope

Endoscopic papillary large balloon dilation: guidelines for pursuing zero mortality.

Since endoscopic papillary large balloon dilation (EPLBD) is used to treat benign disease and as a substitute for conventional methods, such as endoscopic sphincterotomy plus endoscopic mechanical lithotripsy, we should aim for zero mortality. This review defines EPLBD and suggests guidelines for its use based on a review of published articles and our large-scale multicenter retrospective review.ope