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Fracture Incidence and Mortality in Kidney Transplant Recipients Compared to Waitlisted Dialysis Patients : A Single-Center retrospective analalysis
No full text소개
신장 이식은 투석에 비해 생존율을 높이지만, 이식 환자에서 장기적인 골 건강 문제는 여전히 중요한 과제입니다. 만성 신장병-미네랄 뼈 질환(CKD-MBD)은 골절 위험을 크게 높이며, 이식 후에 도 신장 이식 환자(KTR)들은 특히 이식 첫 해에 빠른 골 손실과 높은 골절 위험을 경험합니다. 이는 미네랄 대사 변화와 면역억제제의 영향 때문입니다. 이식 전 골감소증이나 골다공증이 있으면 이식 후 골절 위험이 더 커집니다. 본 연구는 한국의 신장 이식 환자와 이식 대기 중인 투석 환자에서 골절 발생률과 전체 사망률을 비교하여, 이식이 골 건강과 생존에 미치는 영향을 평가하고자 합니다.
방법
연구 설계 및 대상:
이 후향적 코호트 연구는 1998년 1월부터 2019년 12월까지 울산대학교병원에서 신장 이식을 받은 504명을 포함하였습니다. 데이터는 전자의무기록에서 수집되어 익명화되었으며, IRB 승인을 받았습니다.
기본 특성:
수집된 정보에는 인구학적 자료, 동반 질환, 만성 신장병 원인, 이식 전 투석 이력, 면역학적 지표(ABO, HLA, PRA, 교차반응), 공여자 정보, 약물 복용 이력, 검사실 결과가 포함되었습니다.
근골격계 사건:
골절 발생은 영상의학 보고서에서 ‘골절’이 언급된 경우로 정의하였으며, 늑골 및 오래된 골절은 제외하였습니다. 골밀도(BMD)는 이식 전후 요추와 고관절에서 DXA로 측정하였으나, 후향적으로 얻은 자료이고 측정 시점이 환자마다 다양해 분석에 적합하지 않아 환자 특성 및 통계 분석에서 제외하였습니다. 영상 보고서에 명시된 신규 골절만을 기록하였습니다.
사망:
사망 일자와 원인(감염, 심혈관/뇌혈관 질환, 악성종양, 기타)을 기록하였습니다.
통계 분석:
기술 통계를 통해 자료를 요약하였고, 골절 유무에 따른 비교, 다변량 분석, 생존 분석(Cox 회귀 포함)을 계획하였습니다. 통계적 유의성은 P<0.05로 정의하였으며, 분석은 적절한 소프트웨어(SPSS 또는 R)를 사용하였습니다.
결과
울산대학교병원 신장 이식 수혜자 600명 중 임상 및 영상 자료가 완전한 504명을 분석하였습니다. 평균 연령은 46.7세였고, 남성이 58.1%를 차지했습니다. 이식 전 신대체요법은 혈액투석이 가장 많았으며(67%), 생체이식이 53%로 사체이식보다 약간 많았습니다. 면역억제 유도요법으로는 basiliximab이 가장 많이 사용되었고, tacrolimus가 주요 칼시뉴린 억제제로 사용되었습니다. 당뇨병은 29%에서 동반되었습니다. 추적관찰 기간 동안 골절은 9.1%에서 발생했습니다.
다변량 Cox 회귀분석 결과, 골절은 사망률과 유의한 관련이 없었습니다(HR 2.03, p=0.244). 수혜자 연령이 높을수록 사망 위험이 증가했고, tacrolimus 사용은 cyclosporine에 비해 사망률을 유의하게 낮췄습니다. 성별, 투석 종류, 공여자 유형, 공여자 연령 등은 사망률에 유의한 영향을 미치지 않았습니다.
신장이식 대기 중인 투석 환자 423명 중 12.5%에서 골절이 발생했습니다. 골절 유무에 따라 연령, 성별, ESRD 원인, 과거 이식 여부, 혈액형, 등록 시기 등 기초 특성에 유의한 차이는 없었습니다.
Cox 회귀분석에서 이전 신장이식력이 사망 위험을 크게 높였고, 65세 이상 고령은 오히려 사망 위험을 낮추는 결과를 보였습니다. 골절, 성별, 혈액형, 등록 시기는 사망률과 유의한 연관이 없었습니다.
고찰
이 단일기관 후향적 연구는 신장이식 환자 504명과 이식 대기 투석 환자 423명을 비교하여 골절 발생률과 사망률에 미치는 영향을 평가했습니다. 골절 발생률은 이식 환자(9%)와 대기 투석 환자(12%) 간에 유의한 차이가 없었습니다. 골절은 두 집단 모두에서 사망률의 독립적 예측인자가 아니었으며, 연령이 사망 위험에 더 큰 영향을 미쳤습니다. Tacrolimus 사용은 cyclosporine에 비해 이식 환자 생존율을 높였습니다. 기존 연구와 마찬가지로, 이식만으로 골절 위험이 크게 감소하지 않으며, 이식 후에도 골 건강 관리가 매우 중요함을 시사합니다. 본 연구는 후향적 단일기관 연구라는 한계와 골절 과소진단 가능성을 가지고 있습니다. 결론적으로, 신장이식의 생존 이득은 골절 위험 감소와 직접적으로 연관되지 않으며, 이식 환자와 투석 환자 모두에서 적극적인 골 건강 관리가 필요합니다.|Background: Kidney transplantation (KT) confers substantial survival advantages over dialysis for patients with end-stage renal disease (ESRD), yet persistent bone health issues remain a significant concern. Both dialysis patients and kidney transplant recipients (KTRs) face a markedly increased risk of fractures compared to the general population, largely due to chronic kidney disease-mineral bone disorder (CKD-MBD), longstanding hyperparathyroidism, and the effects of immunosuppressive therapy. Whether KT reduces fracture risk or fracture-related mortality compared to remaining on dialysis is not well established.
Methods: In this retrospective, single-center cohort study, we compared the incidence of fractures and all-cause mortality between 504 KTRs and 423 waitlisted dialysis patients at a tertiary hospital in South Korea from 1998 to 2019. Fracture events were identified through systematic review of radiologic reports, and mortality data were extracted from medical records. Multivariate Cox regression analyses were performed to identify independent predictors of mortality, including fracture events as a covariate.
Results: The incidence of fractures did not differ significantly between KTRs (9.1%) and waitlisted dialysis patients (12.5%). Fracture events were not significantly associated with increased mortality in either group (KTRs: hazard ratio [HR] 2.03, 95% confidence interval [CI] 0.62–6.67, p=0.24; dialysis: HR 0.97, 95% CI 0.12–8.08, p=0.98). Age was the strongest predictor of mortality in both cohorts, while the use of tacrolimus as a calcineurin inhibitor was associated with reduced mortality risk compared to cyclosporine in KTRs (HR 0.18, 95% CI 0.05–0.66, p=0.009). Other factors, including sex, dialysis modality, donor type, and donor age, were not independently associated with mortality.
Conclusions: KTRs continue to experience a fracture risk comparable to that of waitlisted dialysis patients, and fractures did not significantly affect survival in either group during the follow-up period. These findings suggest that the survival benefits of KT are driven primarily by factors other than reductions in fracture-related complications. Clinicians should maintain vigilant bone health management in KTRs, as transplantation alone does not eliminate the elevated fracture risk associated with advanced CKD. Further multicenter and prospective studies are warranted to clarify the long-term skeletal outcomes after KT.Maste
Prediction of long-term creep settlement using CRS experiment
No full textCRS 실험을 이용한 장기크리프 침하량 예측 蔚山大學校 大學院 建設環境工學科 최근 국내외적으로 해저도시나 신공항과 같은 해저에 인프라 건설을 하면서 과거에 응 력을 거의 받지 않은 점토의 연약지반 침하 발생에 대한 문제점이 중요시되고 있다. 그러 나 현재 국내외의 연구에서는 실험적, 수치 해석적으로 미비한 실정이다. 따라서 본 연구 에서는 CRS 시험 결과를 통해 유효응력 변화, OCR의 변화에 따른 크리프 거동을 분석 하고 보다 나은 크리프 모델을 개발하여 크리프 예측 방법을 제안하고자 한다. 이번 연구에서 두가지 실험을 실행하였습니다. 시료의 하중을 가함으로써 하중변화에 대한 간극비, 압밀계수, 압축계수의 관계를 산정하는 압밀크리프시험과 배압을 이용하여 시료를 완전히 포화시킨 상태에서 시간에 대한 변형률을 일정하게 주어 시료하단의 과잉 간극수압을 측정하는 CRS 시험을 하였습니다. 이번 실험에서는 벤토나이트와 풍화토를 혼합한 시료를 사용하였으며, 압밀 크리프 시험과 CRS 시험을 비교하여 다른 조건에서 의 OCR과 stress level을 고려하였을 때, Isotache concept에서의 경향성을 확인할 수 있 었습니다. 이번 연구에서는 변형률 속도와 OCR에 대한 CRS시험을 통하여 점토의 크리프 현상을 해석할수 있는 크리프 모델을 제안 하고자 한다. 본 연구에서 제안하는 크리프 모델은 3 요소(Three-Element) 모델을 기반으로 유한차분법 해석을 적용하여 유동학적 모델을 제 시 하였다.Maste
The Rain Ritual of Excavating Graves and Folk Consciousness during the Japanese Colonial Period
No full text굴묘기우는 명당에 몰래 묻은 무덤을 파헤치고, 시체를 드러내어 비를 기원하던 행위였다. 이는 명당에 조상의 시신을 묻으면 후손에게 발복하여 부귀공명을 누리지만 인근 지역은 재앙 또는 극심한 가뭄이 발생한다는 속신(俗信)에 따라 생겨난 풍습으로, 명당 인 근 지역 주민 수백, 수천 명이 모여서 행하는 집단행위로 나타났다.
굴묘기우는 비윤리성과 범법성 때문에 통치 권력 주도로는 불가능했으며, 대부분 민중의 자발적 참여로 일어났다. 따라서 굴묘기우는 일제시기 식민 통치 아래 살아가는 피지배층의 의식과 대응 양태를 세밀하게 살필 수 있는 미시적 사건으로서 중요한 의의를 지닌다. 또한 이 풍습은 기존의 사회 구조(유교적 금기, 법)가 극심한 가뭄에 직면했을 때 민중이 형성한 공동체가 주도하여 반구조적 행위를 실행한 상징적 사건으로도 이해할 수 있다.
1938년에 조선총독부 총독관방이 펴낸 『석전·기우·안택』에서는 조선의 민간에서 행한 기우제 유형을 크게 7가지로 나누었는데, 불 지르기, 물병 거꾸로 매달기, 시장 옮기기, 용 만들기, 줄다리기, 신성한 곳 더럽히기, 암장(暗葬) 파헤치기가 있다. 굴묘기우는 가뭄의 원 인을 몰래 묻은 무덤에서 찾는다. 조선의 유교 사회에서 무덤을 함부로 파헤치는 행위는 후손의 삶 전체를 위협할 수 있는 중대한 행위로 여겨졌다. 나아가 조상에 대한 예(禮)를 훼손하고 사회의 윤리 질서를 파괴하는 반사회적 범죄로 간주되었다. 이와 같은 관념 아래 굴 묘는 철저히 금기시되었으며, 법적으로 처벌의 대상이었다.
굴묘기우는 행정 단위의 지역뿐 아니라, 풍수지리적으로 주산(主山)을 공유하는 광범위한 지역의 연대와 집단행동을 보여준다. 또한 전통적으로 의례는 대체로 남성 중심으로 운영하였던데 반해, 굴묘기우에는 유독 여성들이 적극적으로 참여한 점도 주목할 만하다.
굴묘기우는 근대 지식인과 식민 권력의 관점에서 볼 때 불합리하고 타파해야 할 미신이었다. 그러나 전통적 경험과 신념을 중시하던 농촌 민중에게는 여전히 직접적이고 설득력 있는 가뭄의 해결책이었다. 그래서 농촌사회의 네트워크를 매개로 순식간에 절대다수의 인원 이 결집하여 가까스로 굴묘하고, 문제를 해결했다며 스스로 만족하였다. 재난으로 치안이 불안정한 상황에서 식민 권력 역시 이러한 사회 안정 기능을 인지한 듯, 굴묘를 강압적으로 통제하지 못하고, 일부 허용하거나 묵인했던 측면도 있었다.
굴묘기우에서 특징적으로 드러나는 민중의식은 풍수적 인식, 주술적 폭력성, 자율성과 주체성, 공동체 중심 상호의존과 연대, 여성의 실행력 등이다. 이것은 위기 상황에 직면한 민중의 생존을 위한 방어기제로 작용했다. 굴묘기우는 단순히 기괴한 풍습이 아니라, 재난 상황에서 농촌 공동체의 안녕을 위해 민중이 자발적으로 실행한 생존 전략으로 사회 통합의 수단이었으며 상징적인 집단행위였다.
주제어: 가뭄, 기우제, 암장(暗葬), 분묘 발굴, 굴총, 굴묘기우, 민중의식Maste
Transferrin induces ferroptosis in the in vitro model of myocardial ischemia-reperfusion injury
No full textCurrently, the most important treatment modality for myocardial infarction caused by ischemia is the restoration of perfusion. However, abrupt cell death occurs immediately after reperfusion, which is called reperfusion injury. It is considered preventable because it occurs during treatment period in the hospital. Therefore, numerous studies to reduce reperfusion injury or to elucidate the mechanisms of it have been actively implemented. However, only limited treatment modalities are applied to reduce reperfusion injury. One of the hindrances of its studies is the lack of reliable in vitro model. Therefore, this study aimed to establish the optimal reperfusion injury in vitro model based on pathophysiology of ischemia-reperfusion. On the other hand, iron dependent necrosis, ferroptosis is related with reperfusion injury. Although it has been studied that iron chelators would reduce reperfusion injury, the mechanism of iron induced reperfusion injury remains to be studied. One of the most important factors about iron homeostasis is transferrin. Cells obtain iron mainly via transferrin uptake. In this study, it was also aimed to study the effect of transferrin on reperfusion injury and to demonstrate the mechanism of ferroptosis induced by simulated reperfusion in the established in vitro model. Currently, oxygen-glucose deprivation (OGD) model is widely used to simulate ischemia-reperfusion in vitro. Serum deprivation is generally combined with glucose deprivation as serum also contains glucose. However, cell viability was significantly decreased by serum deprivation itself. On the other hand, reperfusion injury was not apparent after simulated ischemia with 1% fetal bovine serum (FBS), even after combining acidosis and glucose/glutamine deprivation. To overcome these obstacles, dialyzed FBS was used. Although cell viability was also decreased when 10% dialyzed FBS was used compared to that with 10% FBS, cell viability was improved compared to that with serum deprivation or 1% FBS conditions. Moreover, reperfusion injury occurred obviously by simulated reperfusion after OGD with 10% dialyzed FBS. Both glucose and glutamine deprivation during simulated ischemia augmented LDH release after simulated reperfusion. Additionally, to reflect pH paradox that is cell death resulting from rapid pH normalization by reperfusion, simulated ischemia was performed with hypoxia with lactic acidosis. After simulated ischemia with hypoxia with lactic acidosis, reperfusion injury was apparently observed after simulated reperfusion. Among the models used in the study, in order to focus on reperfusion injury, it was decided to use hypoxia with acidosis condition to simulate ischemia, because less cell death occurred during simulated ischemia. To elucidate the mechanism of iron metabolism after reperfusion in the established in vitro model, research on transferrin was conducted. Before simulated ischemia, cells were treated with chlorazol black, which leads to degradation of transferrin receptor. With chlorazol black pre-treatment, labile iron signal was decreased after simulated ischemia, and reperfusion damage was decreased. Additional experiment was performed using saturated or depleted transferrin iron in dialyzed FBS. With saturated transferrin, reperfusion injury was increased. With depleted transferrin iron, reperfusion damage was decreased. Finally, with high dose of apo-transferrin, which is known to reduce the iron uptake, the intracellular labile iron level was significantly decreased after simulated ischemia and reperfusion injury was also significantly decreased. In conclusion, the optimal reperfusion injury in vitro model was established, which reflects pathophysiology of ischemia-reperfusion. Ferroptosis which occurred by reperfusion in the model was caused by iron originated from transferrin during simulated ischemia.Docto
A Study on the Process Characteristics and Design of High-precise 3D Printing Dispensing System for Semiconductor Packaging Application
No full text본 연구에서는 에어로졸 3D 프린팅 방식(A3DP) 은 반도체 패키징 및 소형 집 적화되는 전자부품에 적합하며, 미세 해상도로 선을 그릴 수 우수한 성능을 가 진다. 이에 국산화하고, 공정 성능을 평가하고, 반도체용 시스템으로 개발하였 고, 본 기기에 맞게 공정을 연구하여, 기존 외산 장비와 비교하여, 국산화 장비 의 성능 입증은 기존의 문헌을 참조하여 진행하였다. 반도체 생산에 적용하기 위하여 반도체 디스펜싱 장비에 적용하여, 반도체 제조 공정에 사용을 하게 한 것은 획기적인 생산 방식의 변화를 가져올 것이다. 장비의 설계는 기존 문헌을 기반으로 설계되었고, 국내에 없는 새로운 부품 설계 및 고정밀 가공을 진행하였다. 공압제어 소프트웨어와 G-code 방식 구동 SW 는 직접 제작하고, 추가적으로 산업에 필요한 반도체 패키징 저작 도구와 연결이 되고, 필요 부분은 추가적으로 개발하였다. 국산화 에어로졸 시스템은 뉴메틱 아토마이저로 개발되었고, 캐리어 가스를 활용하여, 에어로졸을 만들고, 가상임펙터를 통해 관성을 이용하여 분리하여, 직진성이 있는 에어로졸을 걸러내서, 초정밀 노즐로 분사하는 방식으로 공정을 구성하였다. 여러 가지 공정 변수에 대한 토출 결과물에 대한 공정 연구 진행 하였다. 하드웨어적으로 CNC 방식의 제어 장치를 개발하였으며, 반도체 패키징에서 쉽게 사용하게 디스펜싱 설비에 에어로졸 시스템을 적용함으로써, 원하는 위치 에, 은나노 잉크, 폴리머 전도성 잉크를 활용하여 정밀한 미세 선폭 패터닝을 구현하였으며,전기로에서 잉크를 소결하여, 전기적 성질에 대한 연구를 수행하 였다. 공정 부분에서는 은나노 잉크에 대한 각 온도에 따른 소결 후의 상태를 SEM 이미지로 하여, 결정 구조를 분석한 결과, 소결에 적합한 온도는 200 도 이상으로 관찰을 하였고, 두께와 전기전도도 상관 관계 분석하여, 반복 횟수, 인쇄 속도에 대한 전도도의 관계를 규명하였고, 선폭 (Area, Dia) 저항값(ohm) 과 반비례 관계임을 확인할 수 있었다. 연구의 결과에 따라, 원하는 회로 부분에 효율적인 Direct Writing 하게 되어, 고정밀 반도체 첨단 패키징의 정전기 차폐, 와이어 본딩 기술을 대체하여 3D /2.5D 패키징, 안테나 패키징 등 반도체 산업 현장에서의 설계 요구에 따른 요 구 사항 해결하고, 에어로졸 활용을 실제적으로 입증하였으며, 향후, 여러 응용 분야에서 활용할 수 있게 하였다. With pride and affection to my beloved wife Sang Mi Park, for her endless support and for being the perfect mother to our lovely and very sparkly sun Won Jae and daughter Ji HyunDocto
Task Offloading, Resource Allocation, and UAV Trajectory Planning in Multi-access Edge Computing-enabled UAV Networks for Emergency Response
No full textNatural and human-induced disasters cause significant loss of life, property damage, and economic disruption annually. Effective emergency response operations are crucial for mit- igating these impacts, involving activities such as locating trapped individuals, identifying evacuation routes, and gathering geospatial data for damage assessment. Unmanned aerial vehicles (UAVs) have emerged as valuable tools in these operations, performing tasks like image processing and deep learning-based object detection to accelerate rescue missions and damage evaluation. However, these computationally intensive tasks strain UAVs’ lim- ited onboard resources, potentially leading to operational delays or failures in time-critical emergency scenarios. To overcome these resource limitations, multi-access edge computing (MEC) enables UAVs to offload computational tasks to more powerful edge servers. However, in disaster- affected areas, transmitting tasks from UAVs to traditional base stations can introduce delays due to factors such as long transmission distances and infrastructure damage. Deploying UAVs with higher computational capacity near disaster sites as aerial base stations and MEC service providers can facilitate rapid response operations, forming UAV-aided MEC systems. However, existing researches on UAV-assisted MEC often overlook practical constraints, including that a UAV can not perform all types of tasks since it has limitations on memory, available software, central processing unit (CPU), and graphics processing unit (GPU), and the benefits of combined CPU-GPU processing for deep learning applications. To address these limitations, we first propose a messy genetic algorithm-based task offloading framework (mGATO) that jointly optimizes task offloading decisions, transmission power allocation, and computational resource allocation in a UAV network consisting of UAV mother-ships with MEC servers (UMECs), UAV scouts, and ground stations. Our framework considers the limitations on the type of tasks a UAV can perform and incorporates both CPU and GPU processing along with other constraints such as the resource budget of UAVs, and formulates the task offloading, power, and computational resource allocation problem as a mixed-integer nonlinear programming (MINLP) problem. Then, to solve the problem, a modified messy genetic algorithm-based task offloading, power, and computational resource allocation (mGA-TPR) algorithm is developed with the aim of minimizing the weighted sum of maximum energy consumption ratio and task execution latency ratio to ensure equitable resource utilization. Despite mGATO’s effectiveness, it lacks adaptability to environmental variations, requir- ing re-execution whenever parameters change and potentially introducing longer decision- making times. Additionally, its meta-heuristic approach is prone to local optima due to diminishing genetic diversity, and its focus on total latency might lead to uneven task ex- ecution times among users. Addressing these limitations, we proposed a soft actor-critic (SAC)-based task offloading framework (SACTO) that efficiently adapts to dynamic envi- ronments through continuous learning. In SACTO, the task offloading, power, and computa- tional resource allocation problem is formulated as a MINLP problem similar to the mGATO (where the objective is to minimize the maximum energy consumption ratio, maximum task execution latency ratio, and total system energy), and a SAC-based task offloading and re- source (transmission power and computational resource) allocation (SATORA) algorithm is developed to find the solutions while avoiding local optima through continuous environment exploration. While SACTO optimizes task offloading and resource allocation, the trajectories of UMECs significantly affect task execution time and energy consumption. Therefore, we extend our work to include trajectory planning with our soft actor-critic-based trajectory planning and task offloading framework (SACTT). Unlike existing studies that primarily consider rotary-wing UAVs as aerial MEC servers, in SACTT, fixed-wing UAVs are em- ployed as UMECs for their superior flight endurance, speed, and payload capacity. Moreover, SACTT incorporates often-overlooked minimum turning radius constraints for fixed-wing UAVs (which directly affect energy consumption and task execution time) along with other movement constraints, such as maximum velocity and minimum distance between UMECs. We propose both a particle swarm optimization-based solution (i.e., P-TTR) and a deep re- inforcement learning approach (i.e., S-TTR) that generalizes to time-varying environments for real-time emergency response operations. Experimental evaluations demonstrate that our proposed frameworks significantly en- hance the efficiency of UAV-aided emergency response through improved resource utilization, reduced latency, and optimized energy consumption across diverse operational scenarios.Docto
Numerical investigation of combustion and emission characteristics of ammonia-diesel dual fuel compression ignition engine
No full textThis study proposes a dual-fuel approach combining diesel and ammonia in a single-cylinder compression ignition engine to reduce harmful emissions from internal combustion. Diesel is directly injected into the combustion chamber, while ammonia is introduced through the intake manifold with intake air. In this study, injection timing and the percentage of ammonia energy fraction was varied. A computational fluid dynamics (CFD) model simulates the combustion and emission processes to assess the impact of varying diesel injection timings and ammonia energy contributions. Findings indicate that as ammonia content increases, the engine experiences reductions in peak in-cylinder pressure, temperature, heat release rate, as well as overall efficiency and power output. Emission results suggest that greater ammonia usage leads to a reduction in soot, carbon monoxide, carbon dioxide and unburned hydrocarbons, though a slight increase in nitrogen oxides emissions is observed.Maste
Classification of Patient-Derived Normal Airway Organoids from Heavy and Never smokers : Potential in vitro precancerous models
No full textCigarette smoking is a major risk factor for lung cancer and is associated with distinct histologic subtypes, including adenocarcinoma and squamous cell carcinoma (SCC). Among 156 normal lung organoids derived from donors stratified by smoking status, we identified a subset exhibiting abnormal phenotypes that diverged from typical airway and alveolar differentiation.
To clarify group-specific patterns, we selected 33 lines from never smokers exhibiting distinct proximal and distal airway features, along with 22 SqM-like lines from heavy smokers and 15 AAH-like lines primarily from never and light smokers. From these, representative subsets (n = 5 per group) were chosen for detailed immunophenotypic analysis.
Organoids from heavy smokers exhibited squamous metaplasia-like features, including solid or multicystic morphologies, basal cell disorganization, and strong expression of basal markers (P40, CK5/6), accompanied by loss of terminal respiratory unit differentiation and secretory markers (TTF-1, MUC5AC, MUC1). These abnormalities were observed under both proximal (conducting airway) and distal (terminal respiratory) differentiation conditions, indicating widespread epithelial disruption suggestive of field cancerization and early squamous cell carcinoma-like changes.
In contrast, a subset of organoids derived from never and light smokers resembled atypical adenomatous hyperplasia (AAH), forming uniform, monolayered cystic structures with strong, polarized TTF-1 expression. These AAH-like organoids expanded over passages, suggesting a slow-cycling yet clonally stable population reflective of early adenocarcinoma pathogenesis.
Together, our findings demonstrate that lung organoids retain smoking history-dependent phenotypic memory and can model early divergent trajectories of lung cancer development. A multi-marker classification framework integrating morphological and immunophenotypic features may provide a useful approach for identifying preneoplastic states in vitro.Maste
Clinical Features by Genetic Heterogeneity of Autosomal Dominant Retinitis Pigmentosa
No full textIntroduction : This study aims to analyze the clinical characteristics and progression of autosomal dominant retinitis pigmentosa (adRP) by causative gene mutations and fundus autofluorescence (FAF) patterns. Method : Retrospective analysis of RP patients diagnosed via next-generation sequencing. Patients were categorized based on genetic mutations and FAF imaging patterns. We measured visual acuity, hyperautofluorescent (HyperAF) ring area, and ellipsoid zone (EZ) area across different ages. Result : Among 37 patients with adRP who met the inclusion criteria, RHO mutations were the most common cause (27.0%), followed by PRPF31 (21.6%) and RP1 (18.9%) mutation. In terms of FAF patterns, the paracentral pattern was the most frequent at 51.3%, followed by peripheral (21.6%) and posterior pole patterns (8.1%). The paracentral pattern showed early constriction of the EZ and hyperAF ring compared to the peripheral pattern. Visual impairment progressed at different rates depending on the causal gene, even within the same pattern; particularly, in the paracentral pattern, patients with PRPF31 mutations exhibited central vision loss starting in their 40s, indicating an earlier progression compared to other mutations within the same pattern. By causal gene, the frequently observed FAF types varied. In the case of PRPF31 mutations, all seven patients, except for one who had extensive retinal involvement, exhibited the paracentral pattern. The sectoral pattern was only found in RHO mutations, while the preserved para-arteriolar retinal pigment epithelium pattern was only observed in patients with CRB1 mutations. Conclusion : In this study, we observed that in autosomal dominant retinitis pigmentosa in Korea, there are characteristic progression patterns in objective indicators such as visual acuity, the ellipsoid zone and hyperfluorescent ring area by autofluorescence imaging patterns. Additionally, we found that even within the same pattern, there were differences in the degree of progression based on the causal gene, indicating the potential for predicting prognosis based on FAF patterns and causal gene mutations. Keywords : Retinitis pigmentosa, Inherited retinal disease, Fundus autofluorescence photographyMaste
Association between serologic biomarkers of hepatic fibrosis and graft outcomes in kidney transplantation recipients
No full textBackground: Although studies have suggested that metabolic risk profiles are prognostic factors in kidney transplantation recipients (KTRs), the prognostic value of liver fibrosis, a known surrogate of metabolic risk, in KTRs remains to be elucidated. The objective of this study was to investigate the association between non-invasive liver biomarkers used to assess hepatic fibrotic burden and graft outcomes in KTRs. Methods: A total of 3,092 patients who underwent deceased or living donor kidney transplantation (KT) between January 2000 and December 2022 were enrolled. Postoperative hepatic fibrotic burdens of KTRs were assessed using the Fibrosis-4 (FIB-4) score and the non- alcoholic fatty liver disease fibrosis score (NFS). The primary outcome was a composite of 50% estimated glomerular filtration rate (eGFR) decline and graft failure. Secondary outcomes included individual outcomes of 50% eGFR decline, graft failure, and acute rejection. Results: For the primary outcome, during a mean follow-up of 6.0 years, the composite outcome occurred in 519 (16.8%) participants. When stratified into three groups according to FIB-4 score categories, the highest score group (FIB-4 ≥2.67) had a 2.05-fold (95% confidence interval [CI], 1.44-2.91; P <0.001) higher risk of the composite outcome compared to the lowest score group (FIB-4 <1.30). Furthermore, the highest score group showed higher risk of the secondary outcomes, with hazard ratios (95% CI) of 1.75 (1.16-2.66), 1.62 (1.06- 2.46), and 2.23 (1.43-3.46) for 50% eGFR decline, acute rejection and graft failure, respectively. Similar findings were observed for NFS. Conclusions: Higher hepatic fibrotic burdens were associated with unfavorable graft outcomes in KTRs. Keywords: Chronic kidney disease; kidney transplantation; liver fibrosis; metabolic dysfunction-associated steatotic liver diseaseDocto