Microfluidic Shape Analysis of Non-spherical Graphite for Li-Ion Batteries via Viscoelastic Particle Focusing.

The size and shape of graphite, which is a popular active anode material for lithium-ion batteries (LIBs), significantly affect the electrochemical performance of LIBs and the rheological properties of the electrode slurries used in battery manufacturing. However, the accurate characterization of its size and shape remains challenging. In this study, the edge plane of graphite in a cross-slot microchannel via viscoelastic particle focusing is characterized. It is reported that the graphite particles are aligned in a direction that shows the edge plane by a planar extensional flow field at the stagnation point of the cross-slot region. Accurate quantification of the edge size and shape for both spheroidized natural and ball-milled graphite is achieved when aligned in this manner. Ball-milled graphite has a smaller circularity and higher aspect ratio than natural graphite, indicating a more plate-like shape. The effects of these differences in graphite shape and size on the rheological properties of the electrode slurry, the structure of the coated electrodes, and electrochemical performance are investigated. This method can contribute to the quality control of graphite for the mass production of LIBs and enhance the electrochemical performance of LIBs.

Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men.

BACKGROUND: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics. METHODS: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort. RESULTS: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799). CONCLUSIONS: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.

Efficient data labeling strategies for automated muscle segmentation in lower leg MRIs of Charcot-Marie-Tooth disease patients.

We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies. The effect of leveraging unlabeled data on segmentation performance was evaluated by comparing the performances of few-supervised, semi-supervised (mean teacher model), and fully-supervised learning models. We employed a 2D U-Net architecture and assessed its performance by comparing the average Dice coefficients (ADC) using paired t-tests with Bonferroni correction. Among few-supervised models utilizing 10% labeled data, labeling three slices (the uppermost, central, and lowermost slices) per subject exhibited a significantly higher ADC (90.84±3.46%) compared with other strategies using a single image slice per subject (uppermost, 87.79±4.41%; central, 89.42±4.07%; lowermost, 89.29±4.71%, p < 0.0001) or all slices per subject (85.97±9.82%, p < 0.0001). Moreover, semi-supervised learning significantly enhanced the segmentation performance. The semi-supervised model using the three-slices strategy showed the highest segmentation performance (91.03±3.67%) among 10% labeled set models. Fully-supervised model showed an ADC of 91.39±3.76. A three-slice-based labeling strategy for ground truth segmentation is the most efficient method for developing automated muscle segmentation models of CMT lower leg MRI. Additionally, semi-supervised learning with unlabeled data significantly enhances segmentation performance.

Deoxybouvardin targets EGFR, MET, and AKT signaling to suppress non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) remains a significant challenge, as it is one of the leading causes of cancer-related deaths, and the development of resistance to anticancer therapy makes it difficult to treat. In this study, we investigated the anticancer mechanism of deoxybouvardin (DB), a cyclic hexapeptide, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. DB inhibited the viability and growth of HCC827 cells in a concentration- and time-dependent manner. In vitro kinase assay showed DB inhibited epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition (MET), and AKT, and their phosphorylation was suppressed in HCC827 cells treated with DB. A molecular docking model suggested that DB interacts with these kinases in the ATP-binding pockets. DB induces ROS generation and cell cycle arrest. DB treatment of HCC827 cells leads to mitochondrial membrane depolarization. The induction of apoptosis through caspase activation was confirmed by Z-VAD-FMK treatment. Taken together, DB inhibited the growth of both GEF-sensitive and GEF-resistant NSCLC cells by targeting EGFR, MET, and AKT and inducing ROS generation and caspase activation. Further studies on DB can improve the treatment of chemotherapy-resistant NSCLC through the development of effective DB-based anticancer agents.

Perceptions of organization, job attitudes, challenges, and solutions among medical school administrative staff.

PURPOSE: Staff is essential to the university's efficient administrative operations, which are critical for education, research, and service. Medical schools, often independent, need specialized administrative elements. This study explores how medical school staff perceives the organization using the Six-Box model and evaluates their perceived organizational support, job satisfaction, and organizational commitment based on the concept of job attitudes. METHODS: This study employs a mixed-methods approach, integrating quantitative and qualitative data via a convergent parallel design. It simultaneously collects and analyzes data from a survey and consensus workshop for medical school staff. The survey data were statistically analyzed (IBM SPSS ver. 25.0; IBM Corp., USA), and the workshop discussions were subjected to content analysis. The findings combined provide a comprehensive understanding of the medical school administrative system. RESULTS: Quantitative analysis revealed purpose (3.80) as the highest-rated organizational perception and rewards (2.72) as the lowest. Similarly, job satisfaction was highest (3.63) in job attitudes, while perceived organizational support (2.96) was the lowest. Group differences were observed by gender, enrollment capacity, and contract type (p<0.05). In qualitative research, keywords appeared in relation to their experiences within the medical school organization, encompassing doctor training, emotional responses, administrative features, personal attributes, and cultural influences. Overload, faculty issues, and communication gaps are obstacles. Strategies for overcoming these challenges focus on improving staff treatment, resource allocation, training, and communication channels. CONCLUSION: This study was conducted to explore a broad understanding of the administration of medical schools. Findings suggest challenges with workload, communication, and organizational support. We propose a dedicated medical school administrative system, improved work conditions, and enhanced communication.

Analysis of the current status of interview evaluations in Korean medical schools and professors' perceptions of the interview evaluations process.

PURPOSE: This study aimed to investigate the overall operational status of medical school admission interview evaluations in South Korea and explore the operational experience of universities conducting interview evaluations. METHODS: This study used a mixed-methods approach, combining quantitative and qualitative methods. Through a nationwide survey and data collection from 39 medical schools, the quantitative analysis explored interview evaluations procedures, the purpose of the interview evaluations, and the competencies expected of medical school freshmen. Concurrently, qualitative data were obtained through focus group discussions with 12 professors from 10 medical schools, providing in-depth insights into the operational experiences and challenges faced during interview evaluations. RESULTS: In the quantitative data, interview evaluations were most prevalent in the "comprehensive school records screening" for rolling admissions (85.5%), but less common in regular admissions (18.6%). Private schools (64.2%) showed a statistically significant higher proportion of interview admissions than public schools (11.1%) in the "high school grades focused admission" (p<0.01). Metropolitan areas (50.0%) conducted interview evaluations more frequently than non-metropolitan areas (11.1%) in the "College Scholastic Ability Test-focused admissions" (p<0.05). In the qualitative data, professors recognize the dominant role of "negative selection" in filtering out unsuitable candidates. Challenges in maintaining a consistent evaluator pool and team-based question development were acknowledged. Strategies, such as seeking student feedback for question improvement and conducting study meetings for interviewer preparation are essential. CONCLUSION: This study illuminates the operation of admissions interview evaluations in South Korea, revealing variations across regions and admissions types. These findings offer insights for enhancing medical school admission processes, guiding future research and policy.

Effect of Chicken Age on Proliferation and Differentiation Abilities of Muscle Stem Cells and Nutritional Characteristics of Cultured Meat Tissue.

This study aimed to investigate effects of chicken age on proliferation and differentiation capacity of muscle satellite cells (MSCs) and to determine total amino acid contents of cultured meat (CM) produced. Chicken MSCs (cMSCs) were isolated from hindlimb muscles of broiler chickens at 5-week-old (5W) and 19-embryonic-day (19ED), respectively. Proliferation abilities (population doubling time and cell counting kit 8) of cMSCs from 19ED were significantly higher than those from 5W (p<0.05). Likewise, both myotube formation area and expression of myosin heavy chain heavy of cMSCs from 19ED were significantly higher than those from 5W (p<0.05). After cMSCs were serially subcultured for long-term cultivation in 2D flasks to produce cultured meat tissue (CMT), total amino acid contents of CMT showed no significant difference between 5W and 19ED chickens (p>0.05). This finding suggests that cMSCs from chicken embryos are more suitable for improving the production efficiency of CM than those derived from young chickens.

Aspirin Monotherapy vs No Antiplatelet Therapy in Stable Patients With Coronary Stents Undergoing Low-to-Intermediate Risk Noncardiac Surgery.

BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

Quantification of glutathione and its associated spontaneous neuronal activity in major depressive disorder and obsessive-compulsive disorder.

BACKGROUND: Glutathione (GSH) is a crucial antioxidant in the human brain. Although proton magnetic resonance spectroscopy (MRS) using the MEscher-GArwood Point RESolved Spectroscopy (MEGA-PRESS) sequence is highly recommended, limited literature has measured cortical GSH using this method in major psychiatric disorders. METHODS: By combining MRS using the MEGA-PRESS and resting-state functional magnetic resonance imaging, we quantified brain GSH and glutamate in the medial prefrontal cortex (mPFC) and precuneus and explore relationships between the GSH levels and intrinsic neuronal activity as well as clinical symptoms among the three groups of healthy controls (HCs, N=30), major depressive disorder (MDD, N=28), and obsessive-compulsive disorder (OCD, N=28). RESULTS: GSH concentrations were lower in both the mPFC and precuneus in both the MDD and OCD groups compared to HCs. In HCs, positive correlations were noted between the GSH and glutamate levels, and between GSH and fractional amplitude of low-frequency fluctuations (fALFF) in both regions. However, while these correlations were absent in both patient groups, they showed a weak positive correlation between glutamate and fALFF values. Moreover, GSH levels negatively correlated with depressive and compulsive symptoms in MDD and OCD, respectively. CONCLUSIONS: These findings suggest that reduced GSH levels and an imbalance between GSH and glutamate could increase oxidative stress and alter neurotransmitter signaling, leading to disruptions in GSH-related neurochemical-neuronal coupling and psychopathologies across MDD and OCD. Understanding these mechanisms could provide valuable insights into the underlying processes of these disorders, potentially becoming a springboard for future directions and advancing our knowledge of their neurobiological foundations.

Disrupted cognitive network revealed by task-induced brain entropy in schizophrenia.

Brain entropy (BEN), which measures the amount of information in brain activity, provides a novel perspective for evaluating brain function. Recent studies using resting-state functional magnetic resonance imaging (fMRI) have shown that BEN during rest can help characterize brain function alterations in schizophrenia (SCZ). However, there is a lack of research on BEN using task-evoked fMRI to explore task-dependent cognitive deficits in SCZ. In this study, we evaluate whether the reduced working memory (WM) capacity in SCZ is possibly associated with dynamic changes in task BEN during tasks with high cognitive demands. We analyzed data from 15 patients with SCZ and 15 healthy controls (HC), calculating task BEN from their N-back task fMRI scans. We then examined correlations between task BEN values, clinical symptoms, 2-back task performance, and neuropsychological test scores. Patients with SCZ exhibited significantly reduced task BEN in the cerebellum, hippocampus, parahippocampal gyrus, thalamus, and the middle and superior frontal gyrus (MFG and SFG) compared to HC. In HC, significant positive correlations were observed between task BEN and 2-back accuracy in several brain regions, including the MFG and SFG; such correlations were absent in patients with SCZ. Additionally, task BEN was negatively associated with scores for both positive and negative symptoms in areas including the parahippocampal gyrus among patients with SCZ. In conclusion, our findings indicate that a reduction in BEN within prefrontal and hippocampal regions during cognitively demanding tasks may serve as a neuroimaging marker for SCZ.

Fuzzy clustering of 24-2 visual field patterns can detect glaucoma progression.

PURPOSE: To represent 24-2 visual field (VF) losses of individual patients using a hybrid approach of archetypal analysis (AA) and fuzzy c-means (FCM) clustering. METHODS: In this multicenter retrospective study, we classified characteristic patterns of 24-2 VF using AA and decomposed them with FCM clustering. We predicted the change in mean deviation (MD) through supervised machine learning from decomposition coefficient change. In addition, we compared the areas under the receiver operating characteristic curves (AUCs) of the decomposition coefficient slopes to detect VF progression using three criteria: MD slope, Visual Field Index slope, and pointwise linear regression analysis. RESULTS: We identified 16 characteristic patterns (archetypes or ATs) of 24-2 VF from 132,938 VFs of 18,033 participants using AA. The hybrid approach using FCM revealed a lower mean squared error and greater correlation coefficient than the AA single approach for predicting MD change (all P ≤ 0.001). Three of 16 AUCs of the FCM decomposition coefficient slopes outperformed the AA decomposition coefficient slopes in detecting VF progression for all three criteria (AT5, superior altitudinal defect; AT10, double arcuate defect; AT13, total loss) (all P ≤ 0.028). CONCLUSION: A hybrid approach combining AA and FCM to analyze 24-2 VF can visualize VF tests in characteristic patterns and enhance detection of VF progression with lossless decomposition.

Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea.

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Automated Association for Osteosynthesis Foundation and Orthopedic Trauma Association classification of pelvic fractures on pelvic radiographs using deep learning.

High-energy impacts, like vehicle crashes or falls, can lead to pelvic ring injuries. Rapid diagnosis and treatment are crucial due to the risks of severe bleeding and organ damage. Pelvic radiography promptly assesses fracture extent and location, but struggles to diagnose bleeding. The AO/OTA classification system grades pelvic instability, but its complexity limits its use in emergency settings. This study develops and evaluates a deep learning algorithm to classify pelvic fractures on radiographs per the AO/OTA system. Pelvic radiographs of 773 patients with pelvic fractures and 167 patients without pelvic fractures were retrospectively analyzed at a single center. Pelvic fractures were classified into types A, B, and C using medical records categorized by an orthopedic surgeon according to the AO/OTA classification system. Accuracy, Dice Similarity Coefficient (DSC), and F1 score were measured to evaluate the diagnostic performance of the deep learning algorithms. The segmentation model showed high performance with 0.98 accuracy and 0.96-0.97 DSC. The AO/OTA classification model demonstrated effective performance with a 0.47-0.80 F1 score and 0.69-0.88 accuracy. Additionally, the classification model had a macro average of 0.77-0.94. Performance evaluation of the models showed relatively favorable results, which can aid in early classification of pelvic fractures.

Increased coherence predicts medical refractoriness in patients with temporal lobe epilepsy on monotherapy.

Among patients with epilepsy, 30-40% experience recurrent seizures even after adequate antiseizure medications therapies, making them refractory. The early identification of refractory epilepsy is important to provide timely surgical treatment for these patients. In this study, we analyze interictal electroencephalography (EEG) data to predict drug refractoriness in patients with temporal lobe epilepsy (TLE) who were treated with monotherapy at the time of the first EEG acquisition. Various EEG features were extracted, including statistical measurements and interchannel coherence. Feature selection was performed to identify the optimal features, and classification was conducted using different classifiers. Functional connectivity and graph theory measurements were calculated to identify characteristics of refractory TLE. Among the 48 participants, 34 (70.8%) were responsive, while 14 (29.2%) were refractory over a mean follow-up duration of 38.5 months. Coherence feature within the gamma frequency band exhibited the most favorable performance. The light gradient boosting model, employing the mutual information filter-based feature selection method, demonstrated the highest performance (AUROC = 0.821). Compared to the responsive group, interchannel coherence displayed higher values in the refractory group. Interestingly, graph theory measurements using EEG coherence exhibited higher values in the refractory group than in the responsive group. Our study has demonstrated a promising method for the early identification of refractory TLE utilizing machine learning algorithms.

Rapid quantitative high-throughput mouse embryoid body model for embryotoxicity assessment.

Individuals are exposed to a wide arrays of hazardous chemicals on a daily basis through various routes, many of which have not undergone comprehensive toxicity assessments. While traditional developmental toxicity tests involving pregnant animals are known for their reliability, they are also associated with high costs and time requirements. Consequently, there is an urgent demand for alternative, cost-efficient, and rapid in vitro testing methods. This study aims to address the challenges related to automating and streamlining the screening of early developmental toxicity of chemicals by introducing a mouse embryoid body test (EBT) model in a 384-ultra low attachment well format. Embryoid bodies (EBs) generated in this format were characterized by a spontaneous differentiation trajectory into cardiac mesoderm by as analyzed by RNA-seq. Assessing prediction accuracy using reference compounds suggested in the ICH S5(R3) guideline and prior studies resulted in the establishment of the acceptance criteria and applicability domain of the EBT model. The results indicated an 84.38% accuracy in predicting the developmental toxicity of 23 positive and 9 negative reference compounds, with an optimized cutoff threshold of 750 µM. Overall, the developed EBT model presents a promising approach for more rapid, high-throughput chemical screening, thereby facilitating well-informed decision-making in environmental management and safety assessments.

Improving Patient Safety and Care Quality Through a "Speaking-Up" Climate: The Mediating Role of Situation Monitoring.

Purpose: In healthcare settings, a climate that encourages speaking up among staff is believed to enhance patient safety and quality of care. However, the specific mechanisms of this relationship remain underexplored. Particularly, there is a need to understand how components of teamwork, such as situation monitoring, can be linked to the impact of a speaking-up climate on relevant outcomes. This study aimed to investigate the direct and indirect effects of a speaking-up climate on patient safety and quality of care using situation monitoring as a potential mediator. Patients and Methods: This cross-sectional study used survey data from 380 staff nurses who provided direct patient care at three Korean hospitals. Structural equation modeling was utilized to test a hypothesized mediation model using Mplus 7.0. Results: Our data analysis confirmed the partial mediation model. As hypothesized, a speaking-up climate directly improved patient safety (ß = 0.384, p < 0.001) and quality of care (ß = 0.393, p < 0.001). Also, we found that indirect effects of a speaking-up climate on patient safety (ß = 0.224, p < 0.001) and quality of care (ß = 0.186, p = 0.005) through situation monitoring were significant. These results indicate that situation monitoring was found to significantly mediate the relationship between a speaking-up climate, patient safety, and quality of care. Conclusion: Our study demonstrates that the positive impact of a speaking-up climate extends beyond improving nurses' speaking up. Further, fostering a speaking-up climate can significantly improve patient safety and quality of care, and situation monitoring has a critical role in this relationship. These findings contribute to understanding how encouraging a speaking-up climate could benefit patient safety and care quality in healthcare organizations.

Prognostic implication of extra-pancreatic organ invasion in resectable pancreas ductal adenocarcinoma in the pancreas tail.

OBJECTIVES: To assess the prognostic significance of extra-pancreatic organ invasion in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreas tail. MATERIALS & METHODS: This retrospective study included patients with resectable PDAC in the pancreas tail who received upfront surgery between 2014 and 2020 at a tertiary institution. Preoperative pancreas protocol computed tomography (CT) scans evaluated tumor size, peripancreatic tumor infiltration, suspicious metastatic lymph nodes, and extra-pancreatic organ invasion. The influence of extra-pancreatic organ invasion, detected by CT or postoperative pathology, on pathologic resection margin status was evaluated using logistic regression. The impact on recurrence-free survival (RFS) was analyzed using multivariable Cox proportional hazard models (clinical-CT and clinical-pathologic). RESULTS: The study included 158 patients (mean age, 65 years ± 8.8 standard deviation; 93 men). Extra-pancreatic organ invasion identified by either CT (p = 0.92) or pathology (p = 0.99) was not associated with a positive resection margin. Neither CT (p = 0.42) nor pathological (p = 0.64) extra-pancreatic organ invasion independently correlated with RFS. Independent predictors for RFS included suspicious metastatic lymph node (hazard ratio [HR], 2.05; 95 % confidence interval [CI], 1.08-3.9; p = 0.03) on CT in the clinical-CT model, pathological T stage (HR, 2.97; 95 % confidence interval [CI], 1.39-6.35; p = 0.005 for T2 and HR, 3.78; 95 % CI, 1.64-8.76; p = 0.002 for T3) and adjuvant therapy (HR, 0.62; 95 % confidence interval [CI], 0.42-0.92; p = 0.02) in the clinical-pathologic model. CONCLUSION: Extra-pancreatic organ invasion does not independently influence pathologic resection margin status and RFS in patients with resectable PDAC in the pancreas tail after curative-intent resection; therefore, it should not be considered a high-risk factor.

Predictive biomarkers for embryotoxicity: a machine learning approach to mitigating multicollinearity in RNA-Seq.

Multicollinearity, characterized by significant co-expression patterns among genes, often occurs in high-throughput expression data, potentially impacting the predictive model's reliability. This study examined multicollinearity among closely related genes, particularly in RNA-Seq data obtained from embryoid bodies (EB) exposed to 5-fluorouracil perturbation to identify genes associated with embryotoxicity. Six genes-Dppa5a, Gdf3, Zfp42, Meis1, Hoxa2, and Hoxb1-emerged as candidates based on domain knowledge and were validated using qPCR in EBs perturbed by 39 test substances. We conducted correlation studies and utilized the variance inflation factor (VIF) to examine the existence of multicollinearity among the genes. Recursive feature elimination with cross-validation (RFECV) ranked Zfp42 and Hoxb1 as the top two among the seven features considered, identifying them as potential early embryotoxicity assessment biomarkers. As a result, a t test assessing the statistical significance of this two-feature prediction model yielded a p value of 0.0044, confirming the successful reduction of redundancies and multicollinearity through RFECV. Our study presents a systematic methodology for using machine learning techniques in transcriptomics data analysis, enhancing the discovery of potential reporter gene candidates for embryotoxicity screening research, and improving the predictive model's predictive accuracy and feasibility while reducing financial and time constraints.

Exocyst stimulates multiple steps of exocytic SNARE complex assembly and vesicle fusion.

Exocyst is a large multisubunit tethering complex essential for targeting and fusion of secretory vesicles in eukaryotic cells. Although the assembled exocyst complex has been proposed to tether vesicles to the plasma membrane and activate soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) for membrane fusion, the key biochemical steps that exocyst stimulates in SNARE-mediated fusion are undetermined. Here we use a combination of single-molecule and bulk fluorescence assays to investigate the roles of purified octameric yeast exocyst complexes in a reconstituted yeast exocytic SNARE assembly and vesicle fusion system. Exocyst had stimulatory roles in multiple distinct steps ranging from SNARE protein activation to binary and ternary complex assembly. Importantly, exocyst had a downstream role in driving membrane fusion and full content mixing of vesicle lumens. Our data suggest that exocyst provides extensive chaperoning functions across the entire process of SNARE complex assembly and fusion, thereby governing exocytosis at multiple steps.