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Identification of the Novel HLA-DQB1*06:432 Allele by Sequence-Based Typing
No full textHLA-DQB1*06:432 differs from HLA-DQB1*06:09:01:01 by a nonsynonymous nucleotide substitution in codon 186, changing Valine to Methionine
Study of Core Molecular Network Function in Critical Transition of Breast Cancer by the depletion of BRCA1
No full textBreast cancer is the most common cancer among women worldwide, and particularly, in cases where individuals inherit mutations associated with high-risk hereditary breast cancer, the likelihood of being diagnosed with breast cancer is known to increase by over 70%. For individuals within this high-risk group with genetic predispositions, apart from preventive mastectomies or regular screenings, there are currently no highly effective methods available to prevent the occurrence of cancer. In this paper, genes that play an important role in transition state changes in breast cancer tumurigenesis are selected,and determine how these genes affect the growth and development of breast cancer caused by BRCA1 depletion. For this purpose, we used the Crispr-Cas9 system to target 2 copies of BRCA1 and designed a mutant cell line in which BRCA1 was knocked out. In this cell line, we used the Tet-On inducible system to identify the estimated transition state time point and candidates acting at this time and confirmed their functions. After knock out BRCA1 and P53, BRCA1 expression decreased until 50 days, but then increased again. And it was confirmed that BRCA1 remained reduced even up to 110 days. In addition, as shown in the results analyzed from public data, we found that SMC2, XCL1, and FOS genes were transiently increased in the designed BRCA1 K.O cell line. It was confirmed that when SMC2 and XCL1 were knocked down at each expected transition state time point, cell proliferation was reduced by 50%. It suggested that XCL1 and SMC2 genes may act as promoters of gene proliferation, and it can be predicted that this increases when BRCA1 depletion occurs. However, the exact transition state point must be found and additional functional studies are needed. Through these results, we would like to molecularly identify transition state changes during the tumorigenesis with BRCA1 mutations in the high-risk group of hereditary cancer and propose preventive methods through this.Maste
Predicting early mortality in hemodialysis patients: a deep learning approach using a nationwide prospective cohort in South Korea
No full textEarly mortality after hemodialysis (HD) initiation significantly impacts the longevity of HD patients. This study aimed to quantify the effect sizes of risk factors on mortality using various machine learning approaches. A cohort of 3284 HD patients from the CRC-ESRD (2008-2014) was analyzed. Mortality risk models were validated using logistic regression, ridge regression, lasso regression, and decision trees, as well as ensemble methods like bagging and random forest. To better handle missing data and time-series variables, a recurrent neural network (RNN) with an autoencoder was also developed. Additionally, survival models predicting hazard ratios were employed using survival analysis techniques. The analysis included 1750 prevalent and 1534 incident HD patients (mean age 58.4 ± 13.6 years, 59.3% male). Over a median follow-up of 66.2 months, the overall mortality rate was 19.3%. Random forest models achieved an AUC of 0.8321 for first-year mortality prediction, which was further improved by the RNN with autoencoder (AUC 0.8357). The survival bagging model had the highest hazard ratio predictability (C-index 0.7756). A shorter dialysis duration (< 14.9 months) and high modified Charlson comorbidity index scores (7-9) were associated with hazard ratios up to 7.76 (C-index 0.7693). Comorbidities were more influential than age in predicting early mortality. Monitoring dialysis adequacy (KT/V), RAAS inhibitor use, and urine output is crucial for assessing early prognosis
Impact of One-Piece Fronto-Orbital Distraction Osteogenesis on Orbital Morphology and Strabismus Development in Unilateral Craniosynostosis
No full textBackground: Unicoronal craniosynostosis (UCS) is associated with orbital dysmorphologies that underlie ophthalmologic dysfunctions, such as strabismus. This study aimed to assess orbital dysmorphology in patients with UCS and how it changes after fronto-orbital distraction osteogenesis (FODO), and to analyze the features of new-onset strabismus.
Methods: A retrospective analysis was conducted on 19 patients with UCS who underwent FODO between May of 2008 and November of 2020. Ophthalmologic records and computed tomographic scans were reviewed. Seven parameters, including width, height, volume, and four-direction orbital angles were evaluated in patients with UCS and compared with those of age-matched control subjects.
Results: The superolateral angle and vertical angle of the ipsilateral orbit and the superomedial angle (SMA) of the contralateral orbit were more obtuse than those of the controls. Following FODO, the ipsilateral superolateral angle was decreased from 69.2 ± 5.4 degrees to 59.1 ± 4.2 degrees ( P = 0.001), and the contralateral SMA was decreased from 64.8 ± 5.8 degrees to 60.2 ± 6.0 degrees ( P = 0.003). Four of the 17 patients without strabismus in the preoperative period developed strabismus, and the horizontal type was the most common. Logistic regression analysis demonstrated a significant association between new-onset strabismus and SMA difference between both orbits (OR, 1.39; P = 0.041).
Conclusions: Orbital dysmorphology in the UCS is bilateral, and the orbital roofs are dysmorphic. The bilateral orbital roofs are lifted toward the fused coronal suture and can be improved after FODO. Horizontal strabismus, such as esotropia and exotropia, is common after FODO, and superomedial orbital roof asymmetry may play a role in its development
Diagnosis and Reclassification of Myelodysplastic Syndromes and Acute Myeloid Leukemia: Comparison Between the 2016 WHO 4th and 2022 WHO 5th/ICC Classifications
No full text배경: AML, MDS의 새로운 분류법을 포함한 혈액종양 전체에 걸친 새로이 개정된 WHO 5판 및 ICC 재분류법이 2022년에 도입되었다. 본 연구에서는 2016년 WHO 4판 분류법과 WHO 5차/ICC 분류법을 기준으로 하였을 때 MDS와 AML의 진단 및 재분류 차이를 비교, 분석하였다.
방법: 2019년 4월부터 2023년 6월까지 울산대학교병원에서 WHO 4판 분류법에 따라 MDS, AML로 진단받은 환자 246명을 대상으로 하였다. 이들을 대상으로 WHO 5판, ICC 분류법을 적용하여 환자의 진단을 재분류한 후 그 차이를 후향적으로 비교, 분석하였다.
결과: WHO 4판 분류법에 의해 MDS로 진단된 96명의 환자 중 5명(5.2%)의 환자가 WHO 5판 또는 ICC 분류법에 의해 AML로 재분류되었고, 이들은 동반된 세포 및 분자유전학적 이상 소견으로 인해 WHO 5판 분류법에서는 모두 AML로 진단이 변경되었으며, ICC 분류법에서는 2명의 MDS with EB-2 환자만 AML로 진단이 변경되었다. WHO 4판 분류법을 적용하였을 때 MDS로 진단된 환자 중 28.6%, 17.0%의 환자가 각각 WHO 5판 분류법, ICC 분류법을 적용하였을 때 MDS 진단의 세부 분류가 변경되었으며, 대부분 개정된 분류법에서 MDS 진단의 세부 분류에 SF3B1, biallelic TP53 mutation 등의 분자유전학적 검사 결과가 추가되어 발생하였고, 일부 환자는 WHO 5판 분류법에서 MDS-h, MDS-f 등 형태학적 소견이 진단에 추가되어서 발생하였다.
결론: MDS 및 AML의 진단에 WHO 5판 및 ICC 분류법을 적용할 때, 골수생검조직의 형태학적 소견, 세포 및 분자유전학적 검사의 TAT 단축이 진단 정확도 향상에 중요한 역할을 할 것으로 사료된다.
Background: In 2022, the World Health Organization (WHO) 5th and International Consensus Classification (ICC) classification of hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) was introduced. This study contrasted the diagnosis and reclassification of MDS and AML between the 2016 WHO 4th and WHO 5th/ICC classifications.
Methods: From April 2019 to June 2023, 246 MDS and AML patients diagnosed by the WHO 4th classification at the Ulsan University Hospital were included in this study. These patients were reclassified by the WHO 5th and ICC classification, and the differences were retrospectively compared and analyzed.
Results: Among 96 MDS patients diagnosed by the WHO 4th classification, 5 (5.2%) were reclassified to AML using the WHO 5th or ICC due to concomitant cytogenetic and molecular abnormalities. Only 2 patients initially diagnosed with MDS with excess blasts-2 (MDS-EB-2) were later diagnosed with AML by ICC classification. When the WHO 5th and ICC classifications were applied, 28.6% and 17.0%, respectively, of MDS patients diagnosed by the WHO 4th classification changed MDS subtypes, mostly due to the presence of molecular abnormalities such as SF3B1 and biallelic TP53 mutation at diagnosis. The MDS subtypes of certain patients also changed when the WHO 5th classification were applied due to the addition of the MDS-hypoplastic and MDS-fibrosis categories.
Conclusions: When applying the WHO 5th and ICC classifications for the diagnosis of MDS and AML, morphologic findings of bone marrow biopsy and reduction of turnaround time in cytogenetic and molecular genetic tests would be crucial in improving diagnostic accuracy
Effect of the Community-Based Chronic Disease Management Service Using Information and Communication Technology
No full text이 연구는 2023년 5월부터 12월까지 「ICT 기반 보건소 만성질환관리 서비스 실증연구 사업」 9개 참여보건소의 만성질환자 452명을 대상으로 모바일 헬스케어사업의 서비스 제공 체계 및 정보시스템을 이용하여 ICT 기반 만성질환관리 서비스를 현장에 적용하고 그 효과성을 평가하였다. 연구 대상은 참여보건소 관내 고혈압·당뇨병으로 진단받은 주민으로 하였고, 인슐린 치료를 하는 경우와 사전 디지털 리터러시 설문조사에서 1개 항목 이상 "전혀 동의하지 않는다"가 있는 경우는 대상자 선정에서 제외하였으며, 질환 진단 여부에 따라 고혈압군, 당뇨병군, 복합질환(고혈압 & 당뇨병)군으로 유형을 분류하였다. 대상자에게는 장비(혈압계, 혈당계 등) 지급 후 모바일 애플리케이션에 장비를 연동하여 최초·중간(3개월 후)·최종(6개월 후) 방문 검진 및 모바일 애플리케이션을 활용한 영양, 운동 집중상담과 주차별 건강정보, 복약 알림 등 24주 동안 맞춤형 건강관리 서비스를 제공하였고, 보건소 관리자 웹 프로그램을 통하여 대상자를 모니터링하였으며, 15개의 성과지표 분석을 통해 효과를 평가하였다. 연구 결과 사업 참여 3개월 후와 6개월 후의 건강행태 지표가 1개 이상이 개선된 대상자의 비율은 각각 2.2%p, 건강위험요인이 1개 이상 감소한 대상자의 비율은 6.7%p 증가하였고, 혈압 조절률은 1.0%p, 고혈압 관리율은 33.5%p, 당뇨병 관리율은 24.8%p가 증가하였으며, 복약순응도 개선율은 고혈압군 84.3%, 복합질환군 80.3%, 당뇨병군 76.2% 순이었다. 사업 참여 전·후의 건강위험요인 변화 분석 결과, 체중(kg), BMI(kg/m2), 수축기 혈압 및 이완기 혈압(mmHg), 허리둘레(cm), 공복혈당(mg/dL)이 감소하였고, HDL-콜레스테롤(mg/dL)은 높게 나타났으며, 통계적으로 유의미한 차이를 보였다(p<0.001). 건강행태 지표 개선에 영향을 미치는 서비스 요인 분석 결과, 건강행태 지표 1개 이상 개선은 활동량계 연동 횟수(p=0.049), 신체활동 집중상담 확인 건수(p=0.003) 및 영양 집중상담 확인 건수(p=0.005), 고혈압약 복약미션 실천 건수(p=0.020)가 있었으며, 만성질환관리에 영향을 미치는 서비스 요인의 경우, 혈압조절률 개선은 혈압계 연동 횟수(p=0.004), 신체활동 집중상담 확인 건수(p=0.026) 및 영양집중상담 확인 건수(p=0.049), 고혈압 관리율 개선에는 활동량계 및 혈압계 연동 횟수(p<0.001)와 고혈압약 복약미션 실천 건수(p=0.004), 당뇨병 관리율 개선에는 혈압계 연동 횟수(p=0.022) 및 혈당계 연동 횟수(p=0.017)가 영향을 미치는 요인이었으며, 모두 통계적으로 유의미한 차이를 보였다. 이 연구는 비교-대조군 연구가 아닌 서비스 전·후의 비교 연구라는 제한점은 있지만 연구결과에 근거하여 만성질환자를 대상으로 정보통신기술을 이용한 건강관리 서비스 제공이 건강행태 지표 개선, 건강위험요인 감소, 고혈압·당뇨병 관리 지표, 체중, 체질량지수, 중성지방, 혈압·혈당 개선 등 건강 수준 전반에 긍정적인 효과가 있음을 실증하였다.
Objective: This study aimed to empirically evaluate the effectiveness of chronic disease management services utilizing ICT for patients with chronic illnesses. Methods: From May to December, 2023, 452 people who were diagnosed with hypertension and diabetes at 9 participating public health centers were provided with customized health care services for 24 weeks, and 15 performance indicators were analyzed to evaluate their effectiveness. Results: Health behavior indicators and health risk factors decreased before and after participation in the project, blood pressure control rate, hypertension and diabetes management rate, medication compliance, weight, BMI, BP, WC, FBG, and HDL-cholesterol improved(p<0.001). Service factors that influence the improvement of health behaviors included the number of activity monitor transmissions(p=0.049), confirmed concentrated consultations on physical activity(p=0.003) and nutrition(p=0.005), and the adherence to medication missions for hypertension(p=0.020). As for service factors influencing chronic disease management, the improvement in blood pressure regulation rate was due to the number of times the blood pressure monitor was linked(p=0.004), and the number of confirmed intensive consultations on physical activity(p=0.026), and nutrition(p=0.049); the improvement in hypertension control rate was due to the number of times the activity monitor and blood pressure monitor were linked(p<0.001), and the number of hypertension medication missions carried out (p=0.004); and the improvement in diabetes control rate was due to the number of times the blood pressure monitor(p=0.022) and blood sugar system were linked(p=0.017). Conclusion: Although this study has limitations as a comparative study before and after the service, it has proved that chronic disease management using ICT has a positive effect on improvement of health behavior indicator, reduction of health risk factors, hypertension, diabetes management index, weight, BMI, TG, BP, FBG improvement
Approximating Intermediate Feature Maps of Self-Supervised Convolution Neural Network to Learn Hard Positive Representations in Chest Radiography
No full textRecent advances in contrastive learning have significantly improved the performance of deep learning models. In contrastive learning of medical images, dealing with positive representation is sometimes difficult because some strong augmentation techniques can disrupt contrastive learning owing to the subtle differences between other standardized CXRs compared to augmented positive pairs; therefore, additional efforts are required. In this study, we propose intermediate feature approximation (IFA) loss, which improves the performance of contrastive convolutional neural networks by focusing more on positive representations of CXRs without additional augmentations. The IFA loss encourages the feature maps of a query image and its positive pair to resemble each other by maximizing the cosine similarity between the intermediate feature outputs of the original data and the positive pairs. Therefore, we used the InfoNCE loss, which is commonly used loss to address negative representations, and the IFA loss, which addresses positive representations, together to improve the contrastive network. We evaluated the performance of the network using various downstream tasks, including classification, object detection, and a generative adversarial network (GAN) inversion task. The downstream task results demonstrated that IFA loss can improve the performance of effectively overcoming data imbalance and data scarcity; furthermore, it can serve as a perceptual loss encoder for GAN inversion. In addition, we have made our model publicly available to facilitate access and encourage further research and collaboration in the field
Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma
No full textPurpose: This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC).
Materials and methods: This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, ver. 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test.
Results: Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19 to 14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05 to 8.93; p=0.04), and the absence of arterial-phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18 to 18.47; p < 0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors.
Conclusion: In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors
The Effect of 3-Dimensional-Printed Sequential Dual Drug-Releasing Patch on the Capsule Formation Around the Silicone Implant in a Rat Model
No full textBackground
Implant-based breast reconstruction is associated with increased risk of early infection and late-stage capsular contracture.
Objectives
We evaluated the feasibility of a dual drug-releasing patch that enabled the controlled delivery of antibiotics and immunosuppressants in a temporally and spatially appropriate manner to the implant site.
Methods
The efficacy of a dual drug-releasing patch, which was 3-dimensional-printed (3D-printed) with tissue-derived biomaterial ink, was evaluated in rats with silicone implants. The groups included implant only (n = 10); implant plus bacterial inoculation (n = 14); implant, bacterial inoculation, and patch loaded with gentamycin placed on the ventral side of the implant (n = 10), and implant, bacterial inoculation, and patch loaded with gentamycin and triamcinolone acetonide (n = 9). Histologic and immunohistochemical analyses were performed 8 weeks after implantation.
Results
The 2 drugs were sequentially released from the dual drug-releasing patch and exhibited different release profiles. Compared to the animals with bacterial inoculation, those with the antibiotic-only and the dual drug-releasing patch exhibited thinner capsules and lower myofibroblast activity and inflammation, indicating better tissue integration and less foreign body response. These effects were more pronounced with the dual drug-releasing patch than with the antibiotic-only patch.
Conclusions
The 3D-printed dual drug-releasing patch effectively reduced inflammation and capsule formation in a rat model of silicone breast reconstruction. The beneficial effect of the dual drug-releasing patch was better than that of the antibiotic-only patch, indicating its therapeutic potential as a novel approach to preventing capsular contracture while reducing concerns of systemic side effects
Legal Review on the Introduction of a Dedicated Organization for Implementing Basic Income Security Programs
No full text확장일로에 있는 복지 수요와 다른 한편으로 지방분권의 강화라는 시대적 요청에 부응하기 위하여 지방자치단체에 대한 국가의 재정 부담을 확대하는 것이 우선 요청되고 있다. 현재 지방자치단체가 수행하고 있는 복지사무 가운데 기초생활급여 · 기초연금 · 아동수당 · 장애인연금 · 장애아동수당 · 양육수당 등의 제공은 대상 국민의 최저생활수준 보장을 지향하는 것이므로 지역의 개별 사정을 고려하지 않고 법률에서 정한 통일적 기준에 따라 전국에 시행되는 특성을 지닌다. 따라서 이러한 기초소득보장 성격의 사무에 대해서는 국가의 재정 부담 확대라는 재정적 관점의 대응을 넘어, 현재 지방자치단체의 사무로 수행되고 있는 사회복지전달체계를 개편하여 국가기관의 사무로 전환하는 방안을 모색하는 것이 의미 있을 것이다. 기초소득보장 사업은 각 사무별로 법률에 따라 수행기관과 사무의 내용 · 절차가 규율되기 때문에 여기에는 해당 법률의 개정이 필수적이다.
이 논문에서는 기초소득보장 사업을 국가사무로 전환할 경우 현행 행정조직법 및 행정작용법의 체계 속에서 어떤 틀로 자리 잡을 수 있을지를 법적 관점에서 검토하였다. 주로 중앙정부의 기능과 사무를 지방자치분권의 방향으로 조정하는 것을 모색하는 기존 논의의 상황에서, 반대로 현재의 지방 사무를 국가의 몫으로 돌리는 방향을 가정한 연구를 통하여 지방자치분권의 과제를 더욱 선명히 하는 역설적 효과도 기대할 수 있을 것이다.
To respond to the expanding demand for welfare and the era’s call for enhanced local autonomy, it is imperative to increase the national financial support for local governments. Currently, welfare services administered by local governments - such as basic livelihood benefits, basic pensions, disability pensions, disability child allowances, childcare subsidies, and child-rearing allowances - are aimed at ensuring a minimum standard of living for citizens across the country. Therefore, these services are implemented uniformly across regions according to legally defined standards, without consideration for local circumstances. Given this, it may be worthwhile to explore the possibility of restructuring the social welfare delivery system, currently managed by local governments, by shifting these basic income security services to be administered by state agencies rather than just expanding financial support from the national level. Since each service within the basic income security programs is governed by specific laws that regulate the implementing agencies, content, and procedures, amendments to the relevant legislation would be necessary.
This paper examines, from a legal perspective, the framework in which basic income security programs could be positioned as state-administered tasks within the current system of administrative organization law and administrative action law. Unlike existing discussions, which focus on adjusting the functions and tasks of the central government toward local autonomy, this study assumes the opposite approach - shifting local responsibilities to the national level. This approach might paradoxically sharpen the discourse on local autonomy issues