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Sphingosylphosphorylcholine Promotes Th9 Cell Differentiation Through Regulation of Smad3, STAT5, and β-Catenin Pathways
No full textSphingosylphosphorylcholine (SPC) is one of sphingomyelin-derived sphingolipids. SPC levels are increased in ascitic fluids of ovarian cancer patients and stratum corneum of atopic dermatitis (AD) patients. SPC has antitumor activity against several cancer cells by reducing proliferation and migration and increasing apoptosis in vitro. SPC can also cause scratching, potentially exacerbating symptoms of AD. However, the role of SPC in modulating immune responses, particularly in the differentiation of Th9 cells, which carry the most powerful antitumor activity among CD4+ T cells, has yet to be investigated. In this study, we found that SPC is another inducer of Th9 cell differentiation by replicating TGF-β. SPC upregulated Smad3, STAT5, and β-catenin signaling pathways. Increased Smad3 and STAT5 signaling pathways by SPC promoted the differentiation of Th9 cells and increased β-catenin signaling pathway resulted in a less-exhausted, memory-like phenotype of Th9 cells. Increased Smad3, STAT5 and β-catenin signaling pathways by SPC were mediated by increased mitochondrial ROS. These results suggest that SPC is an important endogenous inducer of Th9 cell differentiation and may be one of the targets for treating Th9-related diseases, and that enhancing Th9 differentiation by SPC may be helpful in adoptive T cell therapy for cancer treatment
The Efficacy and Safety of NOAC in Very Elderly Atrial Fibrillation Patients: Data From the Korean National Health Insurance Cohort Registry
No full textBackground and Objectives: We investigated the clinical benefit of anticoagulation with non-vitamin K antagonist oral anticoagulant (NOAC) in very elderly atrial fibrillation (AF) patients through national healthcare insurance registry. Methods: Clinical data was acquired from the National Health Insurance Service of south Korea. Medical records of 862,935 patients who were diagnosed with AF from 2015 to 2020 were collected for analysis. Patients under the age of 85, prior history of intracranial hemorrhage, gastrointestinal bleeding and prior prescription days of aspirin, warfarin or NOAC exceeding 90 along with follow up period less than 90 days were excluded. Results: A total of 10,625 patients were eligible for analysis. Patients with oral anticoagulant (hazard ratio [HR], 0.60, 95% confidence interval [CI], 0.53–0.69, p<0.001) showed higher efficacy regarding cerebrovascular accident (CVA) compared to aspirin (HR, 0.84, 95% CI, 0.74–0.95, p=0.008) and no treatment group. Individual comparison of NOAC and aspirin via propensity score matching showed that patients with NOAC (HR, 0.71, 95% CI, 0.61–0.85, p<0.001) showed higher event free survival regarding CVA compared to aspirin. Bleeding risk was also higher for NOAC (HR, 1.28, 95% CI, 1.07–1.56, p=0.006) group but did not result in commensurate increase in mortality (HR, 0.60, 95% CI, 0.45–0.81, p<0.001). Conclusions: Anticoagulation with NOAC in very elderly patient showed higher event free survival regarding CVA. Despite having higher event rate of bleeding, eventual death was lower for NOAC
Rétinites virales
No full textViruses belonging to the herpes family group, including HSV (herpes simplex virus) 1 and 2, VZV (varicella zoster virus) and CMV (cytomegalovirus) are the leading causes of necrotizing retinitis. These viral retinal necroses generally manifest in three forms, depending on the patient's immune status: acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN) and CMV retinitis. Although specific, effective drug treatments are available today, early treatment initiation is essential to avoid sight-threatening complications. © 2024 Elsevier Masson SAS; Les virus du groupe herpès, tels que l'HSV (herpès simplex virus) 1 et 2, le VZV (varicella zoster virus) et le CMV (cytomégalovirus) peuvent provoquer des rétinites nécrosantes susceptibles de causer la cécité. Ces nécroses rétiniennes virales (NRV) se manifestent généralement sous trois formes suivant l’état immunitaire du patient: la nécrose rétinienne aiguë (ARN), la nécrose rétinienne externe progressive (PORN) et la rétinite à CMV. Bien que des traitements médicamenteux spécifiques et efficaces soient disponibles aujourd'hui, la précocité de l'instauration des traitements est essentielle pour améliorer le pronostic
Emergence of resistance to last-resort antimicrobials in bacteremia patients: A multicenter analysis of bloodstream pathogens in Korea
Get PDFThis study retrospectively reviewed the microbiological and clinical characteristics of patients diagnosed with bacteremia. Results from the first positive blood cultures were consecutively collected from July 2022 to June 2023 at a public secondary hospital, a university-affiliated tertiary hospital, and a university-affiliated secondary hospital in the Seoul metropolitan area. Antibiotic spectrum coverage (ASC) scores were calculated on the day the blood culture was performed (B0) and on two days after the blood culture results were reported (R+2). A total of 3,397 isolates were collected from 3,094 patients. Among these, 949 isolates obtained from 893 patients were classified as multidrug-resistant organisms (MDRO), including 170 imipenem-resistant gram-negative bacteria, 714 methicillin-resistant staphylococci, and 65 vancomycin-resistant enterococci. Interestingly, 13 and 42 gram-positive isolates were resistant to linezolid and quinupristin/dalfopristin, respectively. Moreover, 44 and 181 gram-negative isolates were resistant to amikacin and tigecycline, respectively. The proportion of ASC scores corresponding to broad or extremely broad-spectrum coverage was not significantly different between MDRO and non-MDRO groups at B0 (p = 0.0925). However, it increased in the MDRO group at R+2 (p <0.001). This study found that resistance to last-resort antimicrobials is emerging. Therefore, developing and incorporating molecular diagnostics using a wide range of resistance targets may facilitate rapid, tailored antimicrobial treatments
A Multi-label Artificial Intelligence Approach for Improving Breast Cancer Detection With Mammographic Image Analysis
Get PDFBackground/Aim: Breast cancer remains a major global health concern. This study aimed to develop a deep-learning-based artificial intelligence (AI) model that predicts the malignancy of mammographic lesions and reduces unnecessary biopsies in patients with breast cancer. Patients and Methods: In this retrospective study, we used deep-learning-based AI to predict whether lesions in mammographic images are malignant. The AI model learned the malignancy as well as margins and shapes of mass lesions through multi-label training, similar to the diagnostic process of a radiologist. We used the Curated Breast Imaging Subset of Digital Database for Screening Mammography. This dataset includes annotations for mass lesions, and we developed an algorithm to determine the exact location of the lesions for accurate classification. A multi-label classification approach enabled the model to recognize malignancy and lesion attributes. Results: Our multi-label classification model, trained on both lesion shape and margin, demonstrated superior performance compared with models trained solely on malignancy. Gradient-weighted class activation mapping analysis revealed that by considering the margin and shape, the model assigned higher importance to border areas and analyzed pixels more uniformly when classifying malignant lesions. This approach improved diagnostic accuracy, particularly in challenging cases, such as American College of Radiology Breast Imaging-Reporting and Data System categories 3 and 4, where the breast density exceeded 50%. Conclusion: This study highlights the potential of AI in improving the diagnosis of breast cancer. By integrating advanced techniques and modern neural network designs, we developed an AI model with enhanced accuracy for mammographic image analysis
Challenges and considerations in multi-epitope vaccine design surrounding toll-like receptors
No full textEpitope-based peptide vaccines elicit targeted immune responses, making them effective for diseases requiring focused immune activation, such as targeting cancer-associated antigens. Strategies like peptide cocktails and mRNA-based epitope vaccines have revolutionized the field; however, the term ‘multi-epitope peptide vaccine’ has been overextended, especially concerning the use of toll-like receptors (TLRs), their ligands, and peptide linkers. TLRs are often conflated with T cell receptors (TCRs) and B cell receptors (BCRs), which recognize immunogenic peptides within vaccines. This Opinion clarifies the role of TLRs and highlights challenges linked to their indiscriminate use in multi-epitope vaccine design. While peptide linkers are crucial in creating multivalent vaccines, their unsupervised application is increasing and warrants attention. After highlighting their role in advancing peptide vaccines, we discuss critical factors in linker implementation and caution against their misuse, which could undermine vaccines’ efficacy
High Risk of Non-Melanoma Skin Cancer in Actinic Keratosis Patients with Skin of Color: A Nationwide Register-Based Cohort Study
No full textINTRODUCTION: Actinic keratoses (AKs) are rough, scaly patches from UV exposure, increasing the risk of non-melanoma skin cancer (NMSC). This study examines AK incidence in Korea and its role as a risk factor for NMSC. METHODS: A retrospective nationwide register-based cohort study analyzed 2,917 AK patients and 14,585 controls from 2002 to 2019. Patients diagnosed with AK were followed until NMSC occurrence, death, emigration, or December 2019. RESULTS: AK incidence reached 44.8 per 100,000 person-years in 2019. The adjusted hazard ratio for NMSC in AK patients was 8.91 (95% confidence interval, 5.72-13.90). Higher NMSC risk was observed in female AK patients, those under 60 years, and those with lower income levels. The 16-year cumulative incidence of NMSC was 4.19% in AK patients versus 0.44% in controls. CONCLUSION: AK significantly increases the risk of NMSC in Koreans, highlighting the need for tailored surveillance and treatment strategies
Autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases
No full textObjectives: The primary objective of this study was to explore relationship between autoimmunity and epithelial dysplasia in patients with oral lichenoid diseases. Materials and Methods: A total of 66 patients with oral lichen planus (OLP), 35 with oral lichenoid lesion (OLL), and 85 with oral lichenoid drug reaction (OLDR) were enrolled. OLP, OLL, and OLDR were diagnosed following the definitions of the modified World Health Organization criteria, except for the absence of epithelial dysplasia. All patients underwent diagnostic incisional biopsy and adjunctive direct immunofluorescence assays. An indirect immunofluorescence assay was conducted to determine the antinuclear antibody (ANA) positivity. Results: OLP and OLDR patients with epithelial dysplasia demonstrated higher prevalence of serum ANA positivity compared to those without epithelial dysplasia. Elevated serum levels of high sensitivity-C reactive proteins were observed in the OLP, OLL, and OLDR patients with epithelial dysplasia. In the DIF analysis, patients with epithelial dysplasia in the OLP exhibited a higher prevalence of C3 deposition in the basement membrane zone. Conclusions: This study proposed that autoimmunity may contribute to elevating levels of focal and chronic systemic inflammation, potentially influencing abnormal wound healing and development of dysplastic changes in the oral epithelium among patients with oral lichenoid disease
Biological Function Analysis of MicroRNAs and Proteins in the Cerebrospinal Fluid of Patients with Parkinson’s Disease
Get PDFParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by alpha-synuclein aggregation into Lewy bodies in the neurons. Cerebrospinal fluid (CSF) is considered the most suited source for investigating PD pathogenesis and identifying biomarkers. While microRNA (miRNA) profiling can aid in the investigation of post-transcriptional regulation in neurodegenerative diseases, information on miRNAs in the CSF of patients with PD remains limited. This review combines miRNA analysis with proteomic profiling to explore the collective impact of CSF miRNAs on the neurodegenerative mechanisms in PD. We constructed separate networks for altered miRNAs and proteomes using a bioinformatics method. Altered miRNAs were poorly linked to biological functions owing to limited information; however, changes in protein expression were strongly associated with biological functions. Subsequently, the networks were integrated for further analysis. In silico prediction from the integrated network revealed relationships between miRNAs and proteins, highlighting increased reactive oxygen species generation, neuronal loss, and neurodegeneration and suppressed ATP synthesis, mitochondrial function, and neurotransmitter release in PD. The approach suggests the potential of miRNAs as biomarkers for critical mechanisms underlying PD. The combined strategy could enhance our understanding of the complex biochemical networks of miRNAs in PD and support the development of diagnostic and therapeutic strategies for precision medicine
간호대학생을 위한 사례기반의 환자안전역량 강화프로그램 개발 및 효과
No full textDoctorⅠ. 서 론 1
A. 연구의 필요성 1
B. 연구의 목적 4
C. 연구의 가설 5
D. 용어의 정의 6
Ⅱ. 문헌고찰 10
A. 환자안전과 환자안전역량 10
B. 사례기반학습과 웹 기반 교육 14
C. 계획적 행위이론 20
Ⅲ. 개념적 기틀 24
Ⅳ. 연구방법 27
A. 사례기반의 환자안전역량 강화프로그램 개발 27
B. 사례기반의 환자안전역량 강화프로그램 효과 검증 41
1. 연구설계 41
2. 연구대상자 42
3. 연구도구 44
4. 자료수집 방법 47
5. 연구진행 절차 48
6. 연구자의 준비 51
7. 윤리적 고려 51
8. 내외적 타당도 52
9. 자료분석 방법 53
Ⅴ. 연구결과 54
A. 실험군과 대조군의 사전 동질성 검사 54
B. 연구의 가설 검증 58
Ⅵ. 논의 72
A. 간호대학생을 위한 사례기반의 환자안전역량 강화프로그램 개발 72
B. 간호대학생을 사례기반의 환자안전역량 강화프로그램 효과 검증 76
C. 연구의 제한점 87
D. 연구의 의의 87
Ⅶ. 결론 및 제언 89
A. 결론 89
B. 제언 90
참고문헌 91
부록 106
ABSTRACT 14