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Kidney Transplant Recipients Switching to Prolonged-Release Tacrolimus: Five-Year Real-World Clinical Outcomes From the CHORUS Study
No full textBACKGROUND Tacrolimus trough-level concentration variability and patient non-adherence are risk factors for poorer graft and patient survival. This study investigated long-term outcomes in kidney transplant recipients who were converted from twice-daily immediate-release tacrolimus to once-daily prolonged-release tacrolimus. MATERIAL AND METHODS CHORUS (NCT02555787) is a 5-year, real-world, prospective, global, non-interventional study. Kidney transplant recipients (KTRs; >/=18 years, N=4389) were grouped by post-transplant conversion timing (early converters [ECs], 6 months). The primary endpoint was the change from baseline in estimated glomerular filtration rate (eGFR) from conversion to 5 years. Secondary endpoints included tacrolimus dose and trough levels, clinical and biopsy-proven acute rejection (BPAR), graft and patient survival, emergence of donor-specific antibodies, and safety. RESULTS The full analysis set included 4028 patients (1060 ECs and 2968 LCs). Overall, eGFR remained stable 5 years after conversion, with a mean change from baseline of -1.4 (early converters, 3.4; late converters, -3.0) mL/min/1.73 m(2). Mean daily tacrolimus dose and trough levels remained stable 5 years after conversion. Clinically-diagnosed and BPAR-free survival 5-year estimates were 91.2% and 93.9%, respectively. Graft and patient 5-year survival estimates were 95.0% and 97.1%, respectively. Donor-specific antibodies (DSA) occurrence was observed in 4.9% of patients after conversion. Prolonged-release tacrolimus (PRT)-related adverse events were reported by 19.3% of patients and were the cause of discontinuation in 5.5% of patients. CONCLUSIONS In this large and diverse cohort of KTRs, conversion to PRT, independent of conversion timing, was effective and well tolerated in routine clinical practice, supporting its continued long-term use
Single-cell and spatial omics: exploring hypothalamic heterogeneity
No full textElucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements
The association between fronto-insular interaction and executive function during childhood and adolescence in a resting state fMRI study
No full textThe Insula is an area of the brain that plays a vital role in various functions, mainly several executive functions (EFs) during neurological development. Functional connectivity (FC) between the Frontal lobes and the Insula, the regions most commonly associated with EFs, is claimed to play an essential role in EFs. However, there is insufficient data on the relationship between the FC between the two brain regions and the EFs in childhood and adolescence. We investigate the relationship between the degree of functional connection between the Insula and the Frontal lobe and EFs in a sample of Korean children's and adolescent communities. Total 95 participants between the ages of 6 and 17 were recruited. An fMRI seed-based connectivity analysis was conducted with the Insula and all the Frontal lobe areas of interest. A partial correlation analysis of the Stroop and Children's Color Trails Test (CCTT) were performed to measure the overall EFs. One hundred eleven children and adolescents (average age 12.23) participated in the resting functional magnetic resonance imaging (rs-fMRI) study. The Stroop and CCTT tests found a strong positive correlation with the functional connection between the Insula and the Frontal lobes. In particular, this study confirmed that the solid functional connection between the Inferior front gyrus and the Insula is related to good linguistic ability and attention. The functional solid connection between the Prefrontal gyrus and the Insula is related to developed inhibition and cognitive flexibility
Job Characteristic Profiles and Presenteeism Among Shift Nurses: A Latent Profile Analysis Based on the Job Demands–Resources Model
No full textAIM(S): To investigate job characteristic profiles based on the job demands-resources (JD-R) model and the association between job characteristic profiles and presenteeism. DESIGN: Cross-sectional study. METHODS: Data were collected from shift nurses in South Korea in January 2023 using an online survey. This study included 544 nurses working in tertiary and general hospitals in South Korea. The participants were classified into four job characteristic profiles based on the JD-R model using latent profile analysis. Multiple logistic and linear regression analyses were performed to examine the association between job characteristic profiles and presenteeism. RESULTS: Four profiles were derived from the latent profile analysis: low strain-low motivation, high strain-low motivation, low strain-high motivation and high strain-high motivation. The high strain-low motivation, low strain-high motivation and high strain-high motivation groups were 1.74, 1.37 and 3.51 times more likely to experience presenteeism than the low strain-low motivation group respectively. The number of days worked while sick and the level of reduced job productivity was also the highest in the high strain-high motivation group. In addition, general health, multimorbidities and insomnia were significant factors affecting presenteeism, number of days worked while sick and productivity loss among shift nurses. CONCLUSIONS: This study found that even with higher levels of job resources, work environments with high levels of job demands were associated with higher rates of presenteeism. IMPACT: Study findings suggest that various strategies are needed to improve the physical and mental health of shift nurses, and create a healthy organisational environment by reducing excessive job demands to reduce presenteeism and increase productivity. REPORTING METHOD: STROBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution
청년 간호과학인 소통 플랫폼 구축을 위한 국내외 환경 분석
No full textPURPOSE: As nursing continues to advance through digital health, clinical specialization, and interdisciplinary research, early-career nurse scientists are central to advancing innovation. However, Korea lacks a structured platform to support their research, collaboration, and career development. This review aimed to identify the needs of early-career nurse scientists and examine international best practices to guide the creation of an effective communication platform. METHODS: This study involved a secondary analysis of the final report from the project "Establishment of a communication platform for young nursing scientists," carried out by the Korean Society of Nursing Science. The report comprises data from focus group interviews with domestic graduate students and early-career researchers, a literature review of international communication and support systems, and a global policy analysis related to young nursing scientists. Based on this report, the present review synthesizes key findings and draws implications for the development of a communication platform in Korea. RESULTS: International examples, such as grant writing programs, mentoring initiatives, and digital collaboration hubs, showed positive outcomes in strengthening research capacity and promoting the professional growth of nurse scientists. Based on these findings, key considerations for platform development include: (1) establishing clear leadership and a participatory governance model; (2) providing demand-driven content such as research guides, mentoring, and mental health resources; (3) implementing mechanisms to ensure sustainability, content quality, and user data protection; and (4) designing an integrated platform that fosters synergy across research, policy development, education, and global networking. CONCLUSION: A digital platform for early-career nurse scientists should function not merely as an information portal, but also as dynamic infrastructure for collaboration, mentorship, and growth. It is recommended that the Korean Society of Nursing Science spearhead this initiative, with governmental support, to enhance the research capacity and expand the global engagement of Korean nursing scientists
위산저하의 검사와 치료: 기능의학적 접근과 의미
No full textHypochlorhydria and achlorhydria, a condition of abnormally low and no gastric acid secretion, are often underdiagnosed due to its nonspecific symptoms and limited clinical awareness. Gastric acid plays a critical role in protein digestion, micronutrient absorption, and microbial defense. Functional medicine approaches emphasize the upstream causes and systemic impacts of hypochlorhydria, identifying its contribution to nutritional deficiencies, small intestinal bacterial overgrowth, and chronic gastrointestinal symptoms. This review explores the pathophysiology, diagnostic strategies—including serologic, endoscopic, and microbiome-based assessments—and root causes such as Helicobacter pylori infection, autoimmune gastritis, and medication-induced hypochlorhydria. Functional medicine interventions such as the 5R framework (remove, replace, reinoculate, repair, rebalance) offer a holistic model to restore gastric function and systemic health. Particular attention is given to the role of nutrient supplementation, targeted microbial therapies, and acid replacement strategies like betaine HCl. In addition to diagnostic accuracy, therapeutic timing is crucial to prevent irreversible mucosal atrophy and micronutrient depletion. Clinical implications extend to anemia, osteoporosis, vitamin B12 deficiency, and impaired methylation pathways. Functional medicine offers a unique paradigm to address these interconnected systems, presenting opportunities for both disease management and prevention.위저산증(hypochlorhydria)과 위무산증(achlorhydria)은 위산 분비가 비정상적으로 감소, 그리고 분비되지 않는 상태로, 비특이적인 증상과 낮은 임상의의 인식으로 인해 과소 평가되어 있다. 위산은 단백질 소화, 미량영양소 흡수, 병원균 방어에 있어 핵심적인 역할을 한다. 기능의학은 저위산증의 원인과 전신적 영향을 강조하여 저위산증이 영양소 결핍, 소장세균과증식(small intestinal bacterial overgrowth), 만성 위장관 증상 등에 어떻게 기여하는지 설명해 줄 수 있다. 본 종설에서는 저위산증의 병태생리에 대해서 소개하며 혈청학적, 내시경적, 미생물 확인을 통한 진단과정을 소개한다. 그리고 Helicobacter pylori 감염, 자가면역성 위염, 약물 유발성 저위산증 등 주요 원인에 대해 확인한다. 또한 기능의학에서 제시하는 5R 접근법(remove, replace, reinoculate, repair, rebalance)을 통해 베타인 HCl을 활용한 위산 보충 전략, 위장관효소 보충, 영양적 보충 등을 활용하여 위 기능과 전신건강을 회복시키는 통합적인 치료 모델을 상세히 소개하였다. 저위산증은 빈혈, 골다공증, 비타민 B12 결핍, 메틸화 대사 이상 등 다양한 임상적 함의와 연결되며, 저위산증의 조기 치료는 추가적인 위 점막 위축 및 미량영양소 결핍의 예방에 있어 매우 중요하다. 위산저하증에 대한 기능의학적 접근은 이런 상호 연관된 문제들을 통합적으로 다룰 수 있는 임상적 시각을 제공할 수 있다
Impact of a computed tomography-based artificial intelligence software on radiologists’ workflow for detecting acute intracranial hemorrhage
No full textPURPOSE: To assess the impact of a commercially available computed tomography (CT)-based artificial intelligence (AI) software for detecting acute intracranial hemorrhage (AIH) on radiologists' diagnostic performance and workflow in a real-world clinical setting. METHODS: This retrospective study included a total of 956 non-contrast brain CT scans obtained over a 70-day period, interpreted independently by 2 board-certified general radiologists. Of these, 541 scans were interpreted during the initial 35 days before the implementation of AI software, and the remaining 415 scans were interpreted during the subsequent 35 days, with reference to AIH probability scores generated by the software. To assess the software's impact on radiologists' performance in detecting AIH, performance before and after implementation was compared. Additionally, to evaluate the software's effect on radiologists' workflow, Kendall's Tau was used to assess the correlation between the daily chronological order of CT scans and the radiologists' reading order before and after implementation. The early diagnosis rate for AIH (defined as the proportion of AIH cases read within the first quartile by radiologists) and the median reading order of AIH cases were also compared before and after implementation. RESULTS: A total of 956 initial CT scans from 956 patients [mean age: 63.14 +/- 18.41 years; male patients: 447 (47%)] were included. There were no significant differences in accuracy [from 0.99 (95% confidence interval: 0.99-1.00) to 0.99 (0.98-1.00), P = 0.343], sensitivity [from 1.00 (0.99-1.00) to 1.00 (0.99-1.00), P = 0.859], or specificity [from 1.00 (0.99-1.00) to 0.99 (0.97-1.00), P = 0.252] following the implementation of the AI software. However, the daily correlation between the chronological order of CT scans and the radiologists' reading order significantly decreased [Kendall's Tau, from 0.61 (0.48-0.73) to 0.01 (0.00-0.26), P < 0.001]. Additionally, the early diagnosis rate significantly increased [from 0.49 (0.34-0.63) to 0.76 (0.60-0.93), P = 0.013], and the daily median reading order of AIH cases significantly decreased [from 7.25 (Q1-Q3: 3-10.75) to 1.5 (1-3), P < 0.001] after the implementation. CONCLUSION: After the implementation of CT-based AI software for detecting AIH, the radiologists' daily reading order was considerably reprioritized to allow more rapid interpretation of AIH cases without compromising diagnostic performance in a real-world clinical setting. CLINICAL SIGNIFICANCE: With the increasing number of CT scans and the growing burden on radiologists, optimizing the workflow for diagnosing AIH through CT-based AI software integration may enhance the prompt and efficient treatment of patients with AIH
Drug hypersensitivity reactions in children in clinical practice: A WAO Statement
No full textDrug hypersensitivity reactions (DHRs) in children and adolescents are less common than in adults but can have serious consequences if mismanaged. Mislabeling children as drug-allergic due to incomplete diagnostic evaluations leads to unnecessary medication restrictions, increased healthcare costs, and suboptimal treatment choices. This Statement from the World Allergy Organization (WAO) provides evidence-based recommendations for evaluating and managing pediatric DHRs, emphasizing accurate diagnosis through in vivo and in vitro testing, risk stratification, and personalized approaches. Antibiotics, particularly beta-lactams, and non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently implicated drugs, with non-immediate reactions, such as maculopapular exanthema, being the most common presentation. The document also addresses emerging concerns, including monoclonal antibody-induced anaphylaxis and drug-induced enterocolitis syndrome. It underscores the need for specialized care in allergy centers with expertise in pediatric populations and advocates for multidisciplinary programs to manage complex cases, such as chemotherapy hypersensitivity and perioperative drug allergy. By addressing diagnostic challenges and clinical uncertainties, this document aims to improve the management of DHRs in children, reduce mislabeling, and enhance patient outcomes worldwide
Apomorphine is a novel necroptosis inhibitor targeting mixed lineage kinase domain-like protein oligomerization
No full textNecroptosis, a form of programmed cell death, has emerged as a promising therapeutic target. Although several RIPK1 inhibitors have demonstrated favorable safety profiles in clinical trials, clinical translation of necroptosis-targeted therapies remains limited by modest efficacy, limited specificity, and species-specific activity of compounds such as necrosulfonamide (NSA). To resolve these challenges, this study identified a potential necroptosis inhibitor from a clinical drug library. Apomorphine (APO), a non-addictive morphine derivative used to treat Parkinson's disease, was found to inhibit necroptosis by sterically blocking key residues involved in mixed lineage kinase domain-like protein (MLKL) activation and oligomerization, as confirmed by nuclear magnetic resonance analysis. APO is redox sensitive and prone to auto-oxidation. The oxidized form of APO (Ox-APO) showed stronger binding to MLKL than the reduced form of APO (Re-APO), as demonstrated by surface plasmon resonance analysis. Ox-APO significantly ameliorated tissue damage in two murine necroptosis models: dextran sulfate sodium (DSS)-induced colitis and acetaminophen (APAP)-induced liver injury. Collectively, these data highlight the therapeutic potential of APO as a necroptosis-specific inhibitor in necroptosis-related diseases in both humans and mice