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Therapeutic Efficacy of YH35324 on FcεRIα-Mediated Mast Cell/Basophil Activation
No full textPURPOSE: Immunoglobulin E (IgE) induces mast cell/basophil activation by binding with FcepsilonRIalpha and contributes to the development of allergic disease, in which targeting IgE has been considered an effective therapeutic strategy. YH35324 (YH) is a new hybrid protein with an extracellular domain consisting of FcepsilonRIalpha, and its pharmacodynamic effect and safety were validated. This study aimed to evaluate the therapeutic potential of YH as an anti-IgE immunomodulator compared with omalizumab (Oma). METHODS: To evaluate the in vitro efficacy of YH in human mast cells, YH was treated with various methods, and the changes were confirmed through flow cytometry, immunoblot analysis, and immunocytochemistry. To evaluate the ex vivo efficacy of YH, the expression of FcepsilonRIalpha on the surface of blood basophils was measured in 64 subjects with allergic diseases by flow cytometry. Serum soluble FcepsilonRIalpha, CD23, and Mas-Related G-Protein Coupled Receptor Member X2 levels were measured by enzyme-linked immunosorbent assay. RESULTS: The YH-administered group exhibited significantly lower expression of FcepsilonRIalpha on peripheral basophils compared to the Oma-administered group up to 14 days post-administration. YH directly suppressed FcepsilonRIalpha expression on the surface of LAD2 cells, as it was bound to IgE-unbound FcepsilonRIalpha and migrated into the cells by actin-dependent endocytosis, then was recycled by FcRn binding in the lysosome in vitro. Serum soluble FcepsilonRIalpha levels were increased in the YH-administered group compared to the other groups and showed a positive correlation with serum-free IgE. CONCLUSIONS: YH represents a new therapeutic agent for IgE-mediated allergic disease. Further studies are needed to evaluate its additional effects on the FcepsilonRIalpha-mediated autoimmune mechanism
The impact of an empathy education programme on empathy, communication skills and emotional competency in nursing students: A quasi-experimental study
No full textAIMS: This study aimed to evaluate the impact of an empathy education programme on the empathy, communication skills and emotional competency of fourth-year undergraduate nursing students in Korea. BACKGROUND: Empathy is crucial for building rapport with patients and supporting person-centred care. There is a need to integrate a sustainable empathy education programme into the nursing curriculum. DESIGN: This quasi-experimental study assigned 50 fourth-year nursing students from two universities in Korea to experimental and control groups. METHODS: The experimental group was exposed to an 8-week empathy programme, with 90-minute weekly sessions. The program included self-understanding, understanding others and therapeutic communication skills. Data were collected via questionnaires on empathy, communication skills and emotional competency at baseline, post-test and follow-up. RESULTS: The experimental group showed significant improvements in empathy, communication skills and emotional competency, with a sustained impact at the four-week follow-up. CONCLUSION: The empathy education programme effectively enhanced empathy, communication and emotional competency in nursing students, serving as a valuable educational tool at the undergraduate level
The association between commissural height and graft size selection in valve-sparing aortic root replacement
No full textOBJECTIVES: For selecting graft sizes in valve-sparing aortic root replacement (VSARR), commissural height is often referenced as a fixed variable; however, it may be affected by the diameter of the graft implanted. Using a novel aortic root sizer, we explored whether commissural height interacts with graft size. METHODS: The novel sizer is a semi-translucent, rigid tube that is applied externally on the trimmed aortic root. It has 3 longitudinal slits with 120 degrees orientation, which allows suspending the commissural stitches, symmetrically. The sizer is intended to identify the best graft size for a given anatomy by applying sizers of differing internal diameters, by which the quality of coaptation is inspected. Furthermore, each commissural slit is embedded with a ruler that allows measuring commissural heights. Using 5 normal porcine aortic roots with various annular diameters (23-31mm), we applied the 6 sizers in varying diameters (26, 28, 30, 32, 34 and 36 mm) on each of the root. We examined the correlations between the commissural height and baseline anatomical parameters and diameter of the sizer. RESULTS: The commissural height correlated positively with annular dimension (r = 0.55, P = 0.002), free-edge length (r = 0.54, P = 0.002), geometric height (r = 0.51, P = 0.004) and negatively with diameter of the sizer (r = -0.75, P = 0.002). Binary linear regression models validated that the sizer's diameter negatively correlated with the commissural height after adjustments with each of the anatomical parameters (R2, 0.83-0.87; P < 0.001 for all). CONCLUSION: Commissural height is not a fixed factor, but it interacts with the native aortic root size and the dimension of the implanted graft in VSARR
Diagnostic Accuracy and Clinical Value of a Domain-specific Multimodal Generative AI Model for Chest Radiograph Report Generation
No full textBackground: Generative artificial intelligence (AI) is anticipated to alter radiology workflows, requiring a clinical value assessment for frequent examinations like chest radiograph interpretation. Purpose: To develop and evaluate the diagnostic accuracy and clinical value of a domain-specific multimodal generative AI model for providing preliminary interpretations of chest radiographs. Materials and Methods: For training, consecutive radiograph-report pairs from frontal chest radiography were retrospectively collected from 42 hospitals (2005-2023). The trained domain-specific AI model generated radiology reports for the radiographs. The test set included public datasets (PadChest, Open-i, VinDr-CXR, and MIMIC-CXR-JPG) and radiographs excluded from training. The sensitivity and specificity of the model-generated reports for 13 radiographic findings, compared with radiologist annotations (reference standard), were calculated (with 95% CIs). Four radiologists evaluated the subjective quality of the reports in terms of acceptability, agreement score, quality score, and comparative ranking of reports from (a) the domain-specific AI model, (b) radiologists, and (c) a general-purpose large language model (GPT-4Vision). Acceptability was defined as whether the radiologist would endorse the report as their own without changes. Agreement scores from 1 (clinically significant discrepancy) to 5 (complete agreement) were assigned using RADPEER; quality scores were on a 5-point Likert scale from 1 (very poor) to 5 (excellent). Results: A total of 8 838 719 radiograph-report pairs (training) and 2145 radiographs (testing) were included (anonymized with respect to sex and gender). Reports generated by the domain-specific AI model demonstrated high sensitivity for detecting two critical radiographic findings: 95.3% (181 of 190) for pneumothorax and 92.6% (138 of 149) for subcutaneous emphysema. Acceptance rate, evaluated by four radiologists, was 70.5% (6047 of 8680), 73.3% (6288 of 8580), and 29.6% (2536 of 8580) for model-generated, radiologist, and GPT-4Vision reports, respectively. Agreement scores were highest for the model-generated reports (median = 4 [IQR, 3-5]) and lowest for GPT-4Vision reports (median = 1 [IQR, 1-3]; P < .001). Quality scores were also highest for the model-generated reports (median = 4 [IQR, 3-5]) and lowest for the GPT-4Vision reports (median = 2 [IQR, 1-3]; P < .001). From the ranking analysis, model-generated reports were most frequently ranked the highest (60.0%; 5146 of 8580), and GPT-4Vision reports were most frequently ranked the lowest (73.6%; 6312 of 8580). Conclusion: A domain-specific multimodal generative AI model demonstrated potential for high diagnostic accuracy and clinical value in providing preliminary interpretations of chest radiographs for radiologists
Correction: Gastric emptying time and its correlation with cardiac MIBG in body-first and brain-first subtype Parkinson’s disease
No full textImpacts of Tricuspid Regurgitation and Concomitant Tricuspid Surgery in Aortic Valve Replacement
No full textBACKGROUND: Recent studies on the effects of preoperative tricuspid regurgitation (TR) severity and concomitant tricuspid valve (TV) surgery in patients undergoing aortic valve replacement (AVR) have yielded conflicting results, complicating the decision making on concomitant TV surgery in AVR. OBJECTIVES: The purpose of this study was to investigate the impact of preoperative TR severity on outcomes of AVR and to assess the impact of concomitant TV surgery. METHODS: Patients who underwent AVR from 2000 to 2022 were included. The primary outcome was all-cause mortality, and the secondary outcome was a composite of mortality, TV-related reoperation, stroke, and heart failure. For patients with moderate TR, the impact of TV surgery was analyzed using the inverse probability of treatment weighting to address for selection bias. RESULTS: A total of 2,679 consecutive patients (median 7.22 years, Q1-Q3: 4.21-11.83 years) constituted the study cohort. At baseline, TR severity was none-to-trivial, mild, moderate, and severe in 1,688 (63.0%), 731 (27.3%), 215 (8.0%), and 45 (1.7%) patients, respectively. Clinical outcomes demonstrated significant disparities depending on baseline TR severity (P for trend < 0.001). After adjusting for potential covariates, TV surgery did not affect overall survival among patients with moderate TR (HR: 0.57; 95% CI: 0.21-1.50). However, the TV surgery group exhibited a favorable composite outcome and lower TV-related reoperation rate (HR: 0.37; 95% CI: 0.15-0.92, and subdistribution HR: 0.07; 95% CI: 0.01-0.63, respectively). CONCLUSIONS: In patients who underwent AVR, baseline TR severity correlated with unfavorable clinical outcomes. Concomitant TV surgery reduced the rate of TV-related reoperations, but not mortality, among patients with moderate TR
Domain Adaptive Deep Learning for Advanced Otoscope
No full textLow-resource endoscope devices are currently increasing in number. However, despite the expectation that these devices could be used in regions with inadequate medical infrastructure, they are not easily utilized due to the limitation that professional medical personnel must be present in those areas. To overcome this shortcoming, we propose an AI that overcomes generalization issues using a deep learning model through domain adaptation. This approach is expected to enable disease screening via endoscopy even in areas with insufficient medical infrastructure
HDAC6 inhibition upregulates endothelial SOD3 expression via Sp1 acetylation and attenuates angiotensin II-induced hypertension
No full textExtracellular superoxide dismutase (SOD3) plays an important role in maintaining vascular redox homeostasis by eliminating superoxides. The angiotensin II (AngII) peptide mediates vasoconstriction in part via reactive oxygen species (ROS) but has pathologic effects when elevated in adults. Histone deacetylase 6 (HDAC6) modulates the acetylation of non-histone substrates and is associated with hypertensive disorders. Here, we investigated the potential regulation of SOD3 by HDAC6 in human aortic endothelial cells (HAECs) and its implications for AngII-induced oxidative stress and hypertension. HDAC6 inhibition (via the specific inhibitor tubastatin A (TubA), gene knockdown, or a deacetylase activity-deficient mutant) significantly increased SOD3 protein and mRNA expression but did not affect SOD1 or SOD2 protein levels. Conversely, AngII downregulated SOD3 levels and increased ROS and superoxide levels; these effects were antagonized by TubA. We confirmed that the transcription factor Sp1 mediates TubA-induced as well as basal SOD3 expression. Notably, TubA strongly augmented Sp1 acetylation at lysine 703, which activated Sp1 binding to the proximal SOD3 promoter region and, consequently, SOD3 expression. Alternatively, AngII decreased Sp1 acetylation, and TubA-mediated SOD3 induction was reduced upon overexpression of an acetylation-resistant Sp1 mutant (K703R) compared to that by the wild-type protein. Consistent with these findings, aortic SOD3 expression was significantly higher in HDAC6-deficient mice than in wild-type mice. Moreover, AngII infusion-mediated blood pressure elevation was reduced in HDAC6-deficient mice compared with that in wild-type mice. Collectively, our results suggest that HDAC6 inhibition leads to SOD3 upregulation by enhancing Sp1 acetylation in HAECs, thereby mitigating AngII-induced oxidative stress and hypertension
Clinicopathological Factors Affecting Stomach Preservation Following Laparoscopic Sentinel Node Navigation Surgery in Patients with Early Gastric Cancer: A Secondary Analysis of the Multicenter Randomized Phase III SENORITA Trial
No full textBACKGROUND: The SENORITA phase III trial demonstrated the effectiveness of laparoscopic sentinel node navigation surgery (LSNNS) in preserving stomach function for patients with early gastric cancer (EGC), although some patients experienced surgical failure or recurrence. The purpose of this study was to analyze patients' clinicopathologic features from the SENORITA trial who were allocated to LSNNS with stomach-preserving surgery but ultimately did not preserve stomach or experienced recurrence. PATIENTS AND METHODS: Patients were categorized into two groups: the failure group (stomach preservation failure or cancer recurrence after LSNNS) and the success group (stomach preservation without recurrence following LSNNS). This study analyzed the detailed clinicopathologic characteristics of patients in the failure group from the SENORITA trial. RESULTS: Among 258 patients who underwent LSNNS, 193 patients (74.8%) achieved stomach preservation, while 65 patients (25.2%) failed to preserve. Intraoperative failure was the most common cause of unsuccessful stomach preservation, occurring in 35 of 65 cases (53.8%). Advanced pathological TNM stage was the only independent risk factor by multivariate analysis, with stage IB and IIA patients showing 5.9- and 45.0-fold higher failure risks. The main causes of failure included sentinel basin detection failure, metastatic lymph nodes, positive tumors at resection margins, and complications. The failure group also included five cases of gastric cancer recurrence following LSNNS. CONCLUSION: Accurate preoperative staging and patient selection are crucial for optimizing LSNNS outcomes. Ensuring precise resection with an adequate number of harvested sentinel basin nodes is essential to succeed the stomach-preserving surgery
Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin
No full textBACKGROUND: Synphilin-1 has been studied extensively in the context of Parkinson's disease pathology. However, the biophysical functions of synphilin-1 remain unexplored. To investigate its novel functionalities herein, cellular traction force and rigidity sensing ability are analyzed based on synphilin-1 overexpression using elastomeric pillar arrays and substrates of varying stiffness. Molecular changes are analyzed using RNA sequencing-based transcriptomic and liquid chromatography-tandem mass spectrometry-based proteomic analyses. RESULTS: Synphilin-1 overexpression reduces cell area, with a decline of local contraction on elastomeric pillar arrays. Cells overexpressing synphilin-1 exhibit an impaired ability to respond to substrate rigidity; however, synphilin-1 knockdown restores rigidity sensing abilities. Integrated omics analysis and in silico prediction corroborate the phenotypic alterations induced by synphilin-1 overexpression at a biophysical level. Zyxin emerges as a novel synphilin-1 binding protein, and synphilin-1 overexpression reduces the nuclear translocation of yes-associated protein. CONCLUSION: These findings provide novel insights into the biophysical functions of synphilin-1, suggesting a potential protective role to the altered extracellular matrix, which may be relevant to neurodegenerative conditions such as Parkinson's disease