The Prognostic Value of Positron Emission Tomography/Computed Tomography in Clinical Stage I Lung Cancer Patients: A Propensity-Match Analysis.

Background: The application of positron emission tomography/computed tomography (PET/CT) helps provide accurate clinical staging for lung cancer patients. However, the effects and trends in early-stage lung cancer remain unclear. The aim of this study was to compare differences between clinical stage I lung cancer patients who received PET/CT for staging and those who did not. Methods: Data were obtained from the Taiwan Society of Cancer Registry. There were 6587 clinical stage I lung cancer patients between 2009 and 2014 analyzed in this study. We compared the characteristics of the PET/CT and no PET/CT groups. After propensity score matching, it resulted in both groups having 2649 patients. We measured the overall survival rates of all clinical stage I lung cancer patients and the overall survival rates of patients with PET/CT and without PET/CT. Results: The 1-, 3-, and 5-year survival rates of all clinical stage I lung cancer patients were 97.2%, 88.2%, and 79.0%, respectively. Patients with a larger tumor size tended to receive PET/CT for staging (stage Ib: 38.25% vs. 27.82%, p < 0.0001) and a larger resection (lobectomy: 74.62% vs. 66.61%, p < 0.0001). The 5-year survival rates were 79.8% in the PET/CT group and 78.2% in the no PET/CT group after propensity score matching (p = 0.6528). Conclusions: For clinical stage I lung cancer in Taiwan, patients with larger tumor sizes tend to have PET/CT for staging. Although PET/CT provided more precise clinical staging, these patients still received larger resections and had more pathological migration. However, there was no overall survival rate benefit after PET/CT.

Allosteric strand displacement isothermal amplification for the visual detection of Toxoplasma gondii in 30 minutes.

Early detection of Toxoplasma gondii (T. gondii) is critical due to a lack of effective treatment for toxoplasmosis.This study established a simple, cost-effective, and rapid colorimetric detection method for T. gondii. The entire testing process, from sample collection to results, takes only 0.5 h. These characteristics fulfill the demands of researchers seeking rapid target detection with minimal equipment reliance. For genomic extraction, this study evaluated the ability of two filter papers to capture genomes. A rapid genomic extraction device combined with the two filter papers was designed to simplify the genomic extraction process, which was completed within 10 min and increased the detection sensitivity tenfold. The method utilized a simplified primer design for isothermal amplification, namely allosteric strand displacement (ASD), and employed an underutilized commercial color indicator, Bromothymol Blue (BTB), for signal output. Compared with other reported indicators, BTB exhibited a more pronounced color change, shifting from blue to yellow in positive samples, facilitating easier visual differentiation. The reaction was completed in 20 min with a limit of detection (LOD) as low as 0.014 T. gondii per microliter.

Acupuncture for ventilator-dependent patients at a hospital-based respiratory care center: A randomized controlled trial.

Background: In intensive care units, mechanical ventilation is an important therapy to help patients with dyspnea. However, long-term ventilator dependence would consume huge medical resources and increase the risk of morbidity and mortality. The aim of the study was to examine the efficacy of the acupuncture combined with western medical care on ventilator parameters in ventilator-dependent patients. Methods: In this clinical trial, 80 ventilator-dependent patients aged 20 to 80 years old were randomly assigned to acupuncture group and control group in the respiratory care center (RCC) of Changhua Christian Hospital. Besides regular medical care and therapy, participants in the acupuncture group received acupuncture therapy at the same 17 acu-points for 20 minutes once a day, a total of 12 sessions. The ventilator parameters were recorded to evaluate the respiratory efficiency for all participants. The primary outcome was rapid shallow breathing index (RSBI), and secondary outcomes were respiratory rate (RR), tidal volume (TV) and ventilation per minute (MV). Results: Though there was no significant difference in the parameter between the acupuncture group and the control group, we found the trend of decreasing RSBI in the acupuncture group. In subgroup analyses, the mean of RSBI significantly decreased 16.02 (with the SD in 60.84) in acupuncture group, while it increased 17.84 (with the SD in 39.38) in control group (p=0.036) after 12 sessions. Conclusion: Acupuncture treatment can improve breathing ability of patients with respirator dependence in respiratory care center.

A turn-on signal biosensor for cadmium(II) based on DNAzyme and stem-loop qPCR.

Cadmium is a heavy metal that is exceedingly hazardous to humans and can enter the body through tainted food or drink, causing severe harm. It is critical to develop a technology for detecting cadmium in food and water that is sensitive and accurate. One such approach, which employs nucleases, is uncommon. A cadmium(II) turn-on biosensor was successfully created in this work using repetitive cleavage of certain specific nucleases for signal conversion and sophisticated stem-loop qPCR (quantitative polymerase chain reaction) for quick signal amplification and output. The method has strong selectivity and sensitivity for precise quantification, with a detection limit of 6 nmol L-1, i.e. 0.948 g L-1, which is far lower than the 5.0 g L-1 set by the United States Environmental Protection Agency, and it also operates well in retail rice samples.

Current Progress of COPD Early Detection: Key Points and Novel Strategies.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, with approximately 70% to 80% of adults with COPD being undiagnosed. Patients with undiagnosed COPD are at increased risk of poor outcomes and a worsened quality of life, making early detection a crucial strategy to mitigate the impact of COPD and reduce the burden on healthcare systems. In the past decade, increased interest has been focused on the development of effective strategies and instrument for COPD early detection. However, identifying undiagnosed cases of COPD is still challenging. Both screening and case-finding approaches have been adopted to identify undiagnosed COPD, with case-finding being recommended by the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline and the updated United States Preventive Services Task Force (USPTF) recommendation. Nonetheless, the approaches, criteria, and instruments used for early detection of COPD are varied. However, advances in the taxonomy and risk factors of COPD are continuously being investigated. It is important to continuously assess the current state of knowledge on COPD early detection, given the challenges associated with identifying undiagnosed COPD. This review aims to highlight recent advances in early detection of COPD. To discuss the current challenge and opportunity in COPD early detection, providing an overview of existing literature on COPD case-finding strategies, including the approaches, criteria for subjects, and instruments. The review also summarizes the current progress in COPD case-findings and proposes a COPD case-finding flowchart as an efficient method for identifying at risk COPD patients.

The impact of the duration of the integrated disease management program on COPD-related outcomes.

BACKGROUND: The aim of this study is to assess the impact of the duration of the integrated disease management (IDM) program on COPD-related outcomes in real-world setting. METHODS: A retrospective cohort study among 3771 patients with COPD who had regularly completed 4 visits of IDM program within 1 year between April 1, 2017 and December 31, 2018. CAT score as the primary outcome used to investigate the association between IDM intervention duration and improvement in CAT score. Change in CAT score from baseline to each follow-up visit determined by using least-squares means (LSMeans) approach. The cut-off value of IDM duration for improving the CAT score was determined by the Youden index. Logistic regression was used to analyze the relationship between IDM intervention duration and MCID (the minimal clinically important difference) improvement in CAT score and the factor associated CAT improvement. Risks of COPD exacerbation events (COPD-related ED visit and COPD-related hospitalization) were estimated by using the cumulative incidence curve and Cox proportional hazards models. RESULT: Among 3771 enrolled COPD patients, the majority of the study cohort were males (91.51%) and 42.7% of patients had CAT score of ≥ 10 at baseline. The mean of age was 71.47 years and the mean CAT at baseline were 10.49. The mean change from baseline in CAT score was - 0.87, - 1.19, - 1.23 and - 1.40 at 3-, 6-, 9- and 12 month follow-up (p < 0.0001 for all visits), respectively. Statistically significantly lower likelihood of achieving MCID improvement in CAT were observed at 3- and 6 month compared to 9 month (at 3 month: OR: 0.720, 95% CI 0.655-0.791; at 6 month: OR: 0.905, 95% CI 0.825-0.922). And only a modest increase likelihood of achieving MCID improvement in CAT at 12 month (OR: 1.097, 95% CI 1.001-1.201) compared with 9-month follow-up. In logistic regression on the entire cohort, CAT MCID improvement was most associated with baseline CAT scores ≥ 10, followed by frequent exacerbation in previous year (> 2 episodes/year), wheezing, and GOLD B or D at baseline. In baseline CAT ≥ 10 group, patients were more likely to achieve CAT MCID improvement and had greater decreases from baseline in CAT score observed at 3-, 6-, 9-, and 12 month compared with baseline CAT score < 10 group (all p < 0.0001). Moreover, in CAT ≥ 10 groups, patients who achieved CAT MCID improvement had lower risk of subsequent COPD exacerbation events (COPD-related ED visit: aHR: 1.196, 95% CI 0.985-1.453, p = 0.0713; COPD-related hospitalization: aHR: 1.529, 95% CI 1.215-1.924, p = 0.0003) when compared to those without. CONCLUSION: This is the first real-world study indicating the association between COPD IDM intervention duration and COPD-related outcomes. From 3 to 12 month follow-up results showed that continued improvement over time in COPD-specific health status, particularly in patients with baseline CAT score of ≥ 10. Furthermore, a reduction of the risk of subsequent COPD exacerbations were observed in patients with CAT MCID improvement.

Coordination-Driven One-Step Rapid Self-Assembly Synthesis of Dual-Functional Ag@Pt Nanozyme.

Realizing high-precise and adjustable regulation of engineering nanozyme is important in nanotechnology. Here, Ag@Pt nanozymes with excellent peroxidase-like and antibacterial effects are designed and synthesized by nucleic acid and metal ions coordination-driven one-step rapid self-assembly. The adjustable NA-Ag@Pt nanozyme is synthesized within 4 min using single-stranded nucleic acid as templates, and peroxidase-like enhancing FNA-Ag@Pt nanozyme is received by regulating functional nucleic acids (FNA) based on NA-Ag@Pt nanozyme. Both Ag@Pt nanozymes that are developed not only has simple and general synthesis approaches, but also can produce artificial precise adjustment and possess dual-functional. Moreover, when lead ion-specific aptamers as FNA are introduced to NA-Ag@Pt nanozyme, the Pb2+ aptasensor is successfully constructed by increasing electron conversion efficiency and improving the specificity of nanozyme. In addition, both nanozyme has good antibacterial properties, with ~100% and ~85% antibacterial efficiency against Escherichia coli and Staphylococcus aureus, respectively. This work provides a synthesis method of novelty dual-functional Ag@Pt nanozymes and successful application in metal ions detection and antibacterial agents.

Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects.

Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.

Toehold-mediated biosensors: Types, mechanisms and biosensing strategies.

Toehold-mediated strand displacement (TMSD) reactions between double-stranded DNA and single-stranded oligonucleotides, which use a toehold structure as a switch, enable DNA rehybridization in a fast, base-to-base, programmable and controlled manner. TMSD offers numerous advantages, as reactions are enzyme-free, highly efficient, isothermal and cost-effective. Consequently, TMSD-based reaction systems have attracted great interest from researchers in the last two decades as they become increasingly diverse, versatile and robust, and have been widely used in biochemical sensing and medical diagnosis. In this review, we provide a comprehensive overview of TMSD reactions and their applications in biosensors. The six current TMSD reaction types are generalized according to their various modes of action and nucleic acid conformations. Reaction mechanisms via three major thermodynamic driving forces are explained, along with their dynamic affecting factors, and seven toehold-mediated biosensing strategies are summarized. Furthermore, TMSD-reaction biodetection and bioimaging applications are discussed and, finally, several current challenges and perspectives in the field are considered.

Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: a multicentre study.

BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.

Safety and effectiveness of transdermal buprenorphine in cancer pain: An observational study in Taiwan (SOOTHE).

AIM: Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population. METHODS: This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs). RESULTS: A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p < .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain. CONCLUSION: This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831).

Blood monocyte levels predict the risk of acute exacerbations of chronic obstructive pulmonary disease: a retrospective case-control study.

Monocytes were critical cells in the innate immune system. Monocyte recruitment to the lungs is a crucial process of pathophysiology in chronic obstructive pulmonary disease (COPD). Current evidence on the association between the occurrence of acute exacerbations of COPD (AECOPD) and monocytes was unclear. This study aimed to examine whether blood monocytes are associated with the occurrence of AECOPD and to determine the specific blood monocyte level to predict AECOPD. A retrospective case-control study was conducted at Changhua Christian Hospital. A total of 444 eligible patients with COPD were included between January 2017 and December 2019. Restricted cubic splines were used to analyze the nonlinear relationships between continuous white blood cell values and the occurrence of AECOPD. The association between monocytes and the occurrence of AECOPD was assessed using the logistic, lasso, and ridge regression models. Restricted cubic splines revealed nonlinear associations among the monocyte level, the continuous value of the eosinophil-to-lymphocyte ratio, and the occurrence of AECOPD. The lowest risk of occurrence of AECOPD ranged from 7.4 to 10%; < 7.4% with an absolute count < 0.62 or > 10% indicated significant risk. No significant association was noted between the eosinophil-to-lymphocyte ratio categories in the tertiles (< 0.049, 0.049 to < 0.122, and ≥ 0.122) and the risk of AECOPD. A significantly higher risk was noted in the association of the occurrence of AECOPD with the CAT score; mMRC score; wheezing cough; preexisting chronic pulmonary disease; hypertension and malignancy; use of dual- and triple, and oral long-acting bronchodilators for COPD treatment; and WBC count. We reported a nonlinear relationship between monocytes and the occurrence of AECOPD. Patients with monocyte percentage of > 10% or < 7.4% with an absolute count < 0.62 had higher risk of occurrence of AECOPD. Overall, our study demonstrated the specific value of monocytes in identifying high risks of the occurrence of AECOPD; this value is an easy-to-obtain, inexpensive biomarker in patients with AECOPD and should be further investigated in future prospective clinical studies.

The Effectiveness and Tolerability of Glycopyrronium for Patients with Chronic Obstructive Pulmonary Disease in a Clinical Setting: GLARE-Taiwan.

Glycopyrronium (GLY) is a pharmacological maintenance treatment for chronic obstructive pulmonary disease (COPD). However, its effectiveness and tolerability for COPD patients in routine clinical practice have not been well-investigated. This study aimed to assess the effectiveness of GLY on health-related quality of life and its safety in patients with COPD in a routine clinical care setting. This multi-center, prospective, six-month observational study recruited patients diagnosed with COPD and treated with GLY at three medical centers in central Taiwan. The full analysis set (n = 102) had a significant improvement in the Clinical COPD Questionnaire total (mean ± SD = −0.39 ± 0.90, p = 0.002), symptoms (mean ± SD = −0.61 ± 0.90, p < 0.001) and mental state scores (mean ± SD = −0.54 ± 1.72, p = 0.021) but not the functional state score (mean ± SD = −0.10 ± 1.15, p = 0.529). During the observational period, 58 patients (52.73%) experienced adverse events; only one adverse event (dizziness) was suspected to be related to the study drug. Three patients (2.73%) discontinued the study and GLY treatment because of an adverse event. One patient (0.91%) died during the study period because of a cerebral infarction, which was judged to be not associated with GLY treatment. In conclusion, GLY could be effective in improving the health status and is safe for patients with COPD in a real-life setting.

Nano-gold-enhanced LAMP method for qualitative visual detection of Salmonella in milk.

Since Salmonella can cause foodborne disease and public health safety issues and requires a robust, rapid, on-site detection method, a novel visual qualitative method with nano-gold-enhanced loop-mediated isothermal amplification (LAMP) reaction was established for detecting Salmonella in an integrated tube. During the experiment, nano-gold were used to enhance LAMP amplification, improving amplification efficiency and shortening the reaction time to within 30 min. Visual qualitative detection is achieved via negative staining, involving the addition of CuSO4 to the final products of the LAMP reaction. Ring-like white accumulation occurs in the absence of Salmonella targets but not when they are present. After completing the LAMP reaction, the integration tube was shaken gently for 1 min to observe the liquid phase system changes, realizing the closed tube detection of Salmonella. The process resolved the challenge presented by cross-contamination, false positives, and nonspecific amplification during the LAMP reaction. This method was used to detect Salmonella in milk, further highlighting its prospects in the field of rapid food safety detection.

The Mediating Effect of Cytokines on the Association between Fungal Sensitization and Poor Clinical Outcome in Asthma.

Sensitization to fungal allergens is one of the proposed phenotypes in asthma. An association between fungal sensitization and worse clinical outcomes is apparent. Moreover, fungal sensitization in asthma that is associated with different type of immunological mechanism has been reported. How the role of cytokines mediates the association between fungal sensitization and poorer asthmatic outcomes remains unclear. We aimed to determine role of cytokines in the relationship between fungal sensitization and worse clinical outcomes in asthma. METHOD: We conducted a prospective study to recruit adult patients with asthma. Data including age, sex, height, weight, smoking history, medication, emergency visit and admission, pulmonary function testing result, and Asthma Control Test (ACT) scores were collected. We used the automated BioIC method to measure fungal allergen sIgE in sera. Serum levels of Interleukin (IL) -4, IL-13, IL-6, IL-9, IL-10, IL-17 A, IL-22, Interferon (IFN) -γ, Immunoglobulin E (IgE), Tumor necrosis factor-α (TNF-α), and Transforming growth factor-ß (TGF-ß) were measured using ELISA. RESULT: IL-6 and IL-17A had a significant positive correlation between sensitization and most fungi species compared to IgE. Sensitization to Candida albicans had strongly positive association both with IL-6 and IL-17A. However, only IL-17A had significant relationship with ED visit times. The mediation analysis result indicates that IL-17A had a significant positively mediating effect (ME) on the association between Candida albicans and ED visit times. CONCLUSION: IL-17A is a potential mediator to link Candida albicans sensitization and ED visits for asthma. We suggest that patients with fungal sensitization, such as Candida albicans, have poorer outcomes associated with Th17-mediated immune response rather than Th2.

Comparison of recurrence risk between patients with clinically node-positive and -negative stage I non-small cell lung cancer following surgery: A propensity score matching analysis.

BACKGROUND: Identifying patients with stage I non-small cell lung cancer (NSCLC) at increased risk of tumor recurrence following surgery remains a major challenge. The current study aimed to compare disease-free survival (DFS) rates after surgery between patients with clinically node-positive (cN+) and -negative (cN0) stage I NSCLC. METHODS: Patients with pathological stage I resected NSCLC were identified from the lung cancer database of Changhua Christian Hospital in Taiwan. Patients with clinical N status 1 or 2 and pathological N status 0 were identified as the cN+/pN0 cohort, whereas others were identified as the cN0/pN0 cohort. Propensity score matching (PSM) was used to balance the baseline characteristics between both cohorts. Kaplan-Meier method and Cox proportional hazards model were used to evaluate DFS. RESULTS: From January 2010 to July 2019, 754 eligible patients were enrolled into the study, among whom 41 (5.4%) were cN+/pN0. The median follow-up time was 43.4 months. Before PSM, the 5-year DFS rate was 79.0% and 90.3% in cN+/pN0 and cN0/pN0 cohorts (log-rank test, p = 0.009), respectively. After a 1:4 PSM, multivariate analysis showed that the cN+/pN0 cohort still had a poorer DFS compared to the cN0/pN0 cohort in (hazard ratio, 3.17; p = 0.040). CONCLUSION: Among patients with stage I resected NSCLC, cN+ patients had a worse DFS compared to cN0 patients. Surgeons should therefore consider more aggressive adjuvant therapy or frequent follow-up in patients with surgically resected stage I NSCLC with cN+ status.

Pendulone induces apoptosis via the ROS-mediated ER-stress pathway in human non-small cell lung cancer cells.

PURPOSE: Pendulone, an isoflavone compound, is known to act against human cancer cells. However, its role in human non-small cell lung cancer (NSCLC) and the exact molecular mechanisms of action have never been reported. METHODS: We investigated the effects of pendulone on cell proliferation and apoptosis in human NSCLC H1299 cells. Cell viability was examined using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay. Flow cytometry was employed to evaluate apoptotic indices such as the cell cycle, mitochondrial membrane potential, cytochrome c release, caspase activity, and death receptor expression. The expression of proteins related to the cell cycle and apoptosis were analyzed by Western blot analysis. RESULTS: Pendulone significantly decreased H1299 cell viability by inducing endoplasmic reticulum (ER) stress through the accumulation of reactive oxygen species (ROS). Pendulone induced the expression of ER stress-associated proteins, such as ATF4 and CHOP, which promoted the expression of death receptors. Activation of caspase 8 induced extrinsic pathway apoptosis. Pendulone also caused the loss of mitochondrial membrane potential, inhibited the anti-apoptotic proteins BCL-2 and activated the pro-apoptotic protein BAX, which promoted the release of cytochrome c to activate caspase 9. Antioxidant N-acetylcysteine (NAC), with its ROS-suppressive property, reversed pendulone-induced ER stress and cell apoptosis. CONCLUSION: Our findings provide evidence that pendulone induces apoptosis by inducing ER stress through ROS accumulation and mitochondrial dysfunction in NSCLC cell lines.

Explainable Machine Learning Model for Predicting First-Time Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level. METHODS: We conducted a retrospective case-control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model's decisions. RESULTS: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745-0.921] and AUC = 0.836 [95% CI 0.757-0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was <0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD. CONCLUSIONS: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model's decision-making process.

Video-Assisted Thoracoscopic Surgery in Community-Acquired Thoracic Empyema: Analysis of Risk Factors for Mortality.

Background: Thoracic empyema is a disease with high mortality and morbidity. Video-assisted thoracoscopic surgery (VATS) is recommended to treat advanced stage empyema. The purpose of this study was to explore risk factors associated with post-surgery mortality for community-acquired empyema. Patients and Methods: We retrospectively reviewed 440 patients who received VATS for community-acquired empyema, higher than stage 2, in a tertiary medical center in Taiwan. Patients' age, comorbidities, pleural effusion analysis, and post-surgery outcome were compiled. Cox regression model for survival was applied to identify risk factors of 90-day death after surgery. Results: Fifty-three patients (12.05%) had died within 90 days post-surgery. The risk factors of mortality were advanced age (hazard ratio [HR], 1.027; 95% confidence interval [CI], 1.001-1.052), chronic kidney disease (HR, 5.322; 95% CI, 2.635-10.746), cancer (HR, 6.038; 95% CI, 2.737-13.321), pleural effusion pH ≤7 (HR, 2.61; 95% CI, 1.344-5.069), pleural effusion protein ≤4 (HR, 2.021; 95% CI, 1.035-3.947), and late surgery (HR, 3.014; 95% CI, 1.595-5.696). The 90-day mortality in the early surgery group versus the late group was 6.85% versus 26.05%. The increased mortality risk from late surgery was observed in most subgroups, except for patients who were female, had chronic renal disease, and had coronary artery disease. Conclusions: Patients who are elderly, have chronic kidney disease, cancer history, low pleural effusion pH, low pleural effusion protein, and late surgery are associated with post-surgery mortality for community-acquired advanced empyema. Early VATS surgery for advanced empyema or treatment failure of chest tube drainage appears to beneficial and is recommended.