Integrating EEG and Ensemble Learning for Accurate Grading and Quantification of Generalized Anxiety Disorder: A Novel Diagnostic Approach.

Current assessments for generalized anxiety disorder (GAD) are often subjective and do not rely on a standardized measure to evaluate the GAD across its severity levels. The lack of objective and multi-level quantitative diagnostic criteria poses as a significant challenge for individualized treatment strategies. To address this need, this study aims to establish a GAD grading and quantification diagnostic model by integrating an electroencephalogram (EEG) and ensemble learning. In this context, a total of 39 normal subjects and 80 GAD patients were recruited and divided into four groups: normal control, mild GAD, moderate GAD, and severe GAD. Ten minutes resting state EEG data were collected for every subject. Functional connectivity features were extracted from each EEG segment with different time windows. Then, ensemble learning was employed for GAD classification studies and brain mechanism analysis. Hence, the results showed that the Catboost model with a 10 s time window achieved an impressive 98.1% accuracy for four-level classification. Particularly, it was found that those functional connections situated between the frontal and temporal lobes were significantly more abundant than in other regions, with the beta rhythm being the most prominent. The analysis framework and findings of this study provide substantial evidence for the applications of artificial intelligence in the clinical diagnosis of GAD.

Association Between Red Blood Cell Distribution Width and Coronary Calcification in Patients Referred for Invasive Coronary Angiography.

This study aimed to determine whether red cell distribution width (RDW) is associated with coronary calcification. A total of 4796 patients who underwent coronary computed tomography angiography and subsequent invasive coronary angiography were consecutively enrolled. Coronary artery calcium score (CACS), demographic, clinical, and laboratory data were collected from electronic medical records. RDW were expressed in two forms, as a coefficient of variation (CV) or as a standard deviation (SD). Multivariable ordinal logistic regression was used to investigate the association of RDW with CACS grades (CACS 0-99, 100-399, 400-999, and >1000). A significant association was found between elevated RDW-SD and higher CACS grades after full adjustment (adjusted OR per 1-SD increase: 1.11, 95% CI: 1.05-1.18; P < .001), while no significant association was found between RDW-CV and CACS grades. When RDW-SD was analyzed as a categorical variable, it was primarily the 4th quartile of RDW-SD that was associated with elevated CACS grades compared with the 1st quartile (adjusted OR: 1.25, 95% CI: 1.07-1.46; P = .006), while the 2nd and 3rd quartiles showed no significantly higher risk. RDW-SD is a more robust biomarker for coronary calcification compared with RDW-CV.

Machine learning-based coronary artery calcium score predicted from clinical variables as a prognostic indicator in patients referred for invasive coronary angiography.

OBJECTIVES: Utilising readily available clinical variables, we aimed to develop and validate a novel machine learning (ML) model to predict severe coronary calcification, and further assessed its prognostic significance. METHODS: This retrospective study enrolled patients who underwent coronary CT angiography and subsequent invasive coronary angiography. Multiple ML algorithms were used to train the models for predicting severe coronary calcification (cardiac CT-measured coronary artery calcium [CT-CAC] score ≥ 400). The ML-based CAC (ML-CAC) score derived from the ML predictive probability was stratified into quartiles for prognostic analysis. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Overall, 5785 patients were divided into training (80%) and test sets (20%). For clinical practicability, we selected the nine-feature support vector machine model with good and satisfactory performance regarding both discrimination and calibration based on five repetitions of the 10-fold cross-validation in the training set (mean AUC = 0.715, Brier score = 0.202), and based on the test in the test set (AUC = 0.753, Brier score = 0.191). In the test set cohort (n = 1137), the primary endpoint was observed in 50 (4.4%) patients during a median 2.8 years' follow-up. The ML-CAC system was significantly associated with an increased risk of the primary endpoint (adjusted hazard ratio for trend 2.26, 95% CI 1.35-3.79, p = 0.002). There was no significant difference in the prognostic value between the ML-CAC and CT-CAC systems (C-index, 0.67 vs. 0.69; p = 0.618). CONCLUSION: ML-CAC score predicted from clinical variables can serve as a novel prognostic indicator in patients referred for invasive coronary angiography. CLINICAL RELEVANCE STATEMENT: In patients referred for invasive coronary angiography who have not undergone preoperative CT-measured coronary artery calcium scoring, machine learning-based coronary artery calcium score assessment can serve as an alternative for predicting the prognosis. KEY POINTS: • The coronary artery calcium (CAC) score, a solid prognostic indicator, can be predicted using non-CT methods. • We developed a machine learning (ML)-CAC model utilising nine clinical variables to predict severe coronary calcification. • The ML-CAC system offers significant prognostic value in patients referred for invasive coronary angiography.

Association of serum thyroid hormone and coronary artery calcification in patients who underwent invasive coronary angiography: an observational study.

BACKGROUND: Thyroid hormones (TH) are known to have a range of effects on the cardiovascular system. However, there is still controversy regarding the relationship between thyroid function and coronary artery calcification (CAC). The purpose of this paper is to investigate the relationship between TH and CAC, especially severe CAC, in patients who underwent invasive coronary angiography (ICA). This may provide further insights into the potential role of TH in the development and progression of cardiovascular disease. METHOD: This observational study included 4221 patients who underwent ICA after completing CTA in a single center. We collected demographic, clinical, and laboratory data from electronic medical records and measured CAC scores via non-contrast cardiac CT. RESULT: The study found that there is a negative correlation between the CAC score and FT3 level, even after adjusting for potential confounding factors, but there was no correlation between the CAC score and FT4 or TSH. When categorized into quartiles, the highest quartile of FT3 was associated with a decrease (ß = -104.37, 95%CI: -172.54, -36.21) in calcification score compared to the lowest quartile. This correlation was more significant in the subgroup of individuals with diabetes or hypertension. CONCLUSION: The study found a negative correlation between FT3 and CAC in patients who underwent ICA. The correlation was consistent with other studies and may suggest that low levels of FT3 are associated with severe CAC. The study may provide new evidence for future research on CAC and potential therapeutic approaches.

Fibroblast growth factor 21 inhibits vascular calcification by ameliorating oxidative stress of vascular smooth muscle cells.

Vascular calcification is very common in clinical. Severe vascular calcification is related to the occurrence of adverse events. Oxidative stress (OS) plays a pathophysiological role in the formation of vascular calcification. Previous studies have demonstrated that fibroblast growth factor 21(FGF21) could inhibit vascular calcification both in vivo and in vitro. FGF21 has also been proved to promote the recovery of superoxide dismutase (SOD) and thereby alleviate OS. Thus, our assumption was that FGF21 inhibit vascular calcification partly by restoring the level of antioxidant SOD and reducing OS. In this study, we established the vascular calcification by 5/6 nephrectomy plus high phosphate diet chronic kidney disease (CKD) model. The results showed the receptor of FGF21, fibroblast growth factor receptor 1 (FGFR1) and ßKlotho in the aorta increased in CKD group, and mainly located in the media of the artery. Ulteriorly, immunofluorescence (IF) and IHC staining showed that FGFR1 and ßKlotho mainly existed in arterial vascular smooth muscle cells (VSMCs). When FGF21 was knock out, the calcification was more severe in FGF21 KO + CKD mice, compared to wild type (WT)+ CKD mice. The transcriptional level of vascular calcification-related genes was significantly higher in FGF21 KO mice than control group. The dihydroethidium (DHE) staining reactive oxygen species (ROS) level in the CKD group was higher compared to the control group, but lower in FGF21 KO + CKD group, and the transcriptional level of SOD1 and SOD2 in FGF21 KO + CKD group was significantly higher than that in CKD group. In conclusion, FGF21 could inhibit vascular calcification, partly by restoring the level of antioxidant SOD and reducing vascular oxidative stress. This study provides further evidence for FGF21 as a candidate drug for cardiovascular protective agents.

Possible effects of fibroblast growth factor 21 on vascular calcification via suppressing activating transcription factor 4 mediated apoptosis and osteogenic transformation in rats.

Vascular calcification (VC), a significant risk factor of many cardio-cerebral vascular diseases, is a perplexing issue with no effective treatment in clinical work up to now. Endoplasmic reticulum stress (ERS) mediated apoptosis has been proved to be a significant mechanism for initiating VC process. Activating transcription factor 4 (ATF4), a key transcription factor of ERS, is most closely associated with VC. Fibroblast growth factor 21 (FGF21), an atypical member of the FGFs family, has a protective biological function in various metabolic diseases by ERS pathways. However, the possible effects of FGF21 on VC by regulating ERS, especially through the ATF4 pathway, is still unclear. Our research provides the first evidence that exogenous FGF21 treatment can alleviate the vitamin D3 plus nicotine-induced VC at least in part via suppressing ATF4 mediated apoptosis and osteogenic transformation in rats.

Medication reconciliation role and value in Alzheimer's disease treatment.

BACKGROUND: With the continuous increase of Alzheimer's disease (AD), it is also imminent to treat patients with AD for medication reconciliation. OBJECTIVE: To explore the role and value of medication reconciliation in AD treatment. METHODS: 100 patients over 65 years of age diagnosed with AD were randomly separated into two groups: conventional treatment and medication reforming. The list of medical orders of all subjects was obtained within 24 hours after admission with Beers criteria, STOPP/START criteria, and Chinese Pharmacopoeia used as the MED intervention criteria. Medication reconciliation was performed at 2 weeks, 1 month, and 2 months after hospital admission. The number of medications prescribed, the quantity of the medication, medication error rate, therapeutic effect, adverse drug reactions, and satisfaction levels of family members and main caregivers were compared between the two groups. RESULTS: After the intervention, the types and amount of medication in the MED group were less compared to the CON group along with a reduced medication deviation rate. The Mini-mental state examination (MMSE) score and the proportion of well-nourished patients in the MED group were higher than those in the CON group. It was also observed that the physical self-care ability score and the proportion of patients with abnormal swallowing were lower when in comparison with the CON group. The incidence of adverse drug reactions in the MED group was lower than that in the CON group. However, the satisfaction rate was higher than that in the CON group. CONCLUSION: Medication reconciliation can reduce the medication deviation in AD patients.

Lesion characteristics and procedural complications of chronic total occlusion percutaneous coronary intervention in patients with prior bypass surgery: A meta-analysis.

Coronary artery bypass graft (CABG) accelerates the prevalence of native coronary chronic total occlusion (CTO), and this kind of CTO shows extensive challenging and complex atherosclerotic pathology. As a result, the procedural success rate of percutaneous coronary intervention (PCI) is inferior to another kind of lesions. The present meta-analysis aims to compare the lesion characteristics and procedural complications of CTO-PCI in patients with or without prior CABG. A total of 8 studies, comprising of 13439 patients, published from inception to August 2021 were included in this meta-analysis. Results were pooled using random effects model and are presented as odds ratio (OR) with 95% confidence intervals (95% CIs). From the 13439 patients enrolled, 3349 (24.9%) patients had previous CABG and 10090 (75.1%) formed the control group in our analysis. For the clinical characteristic, compared to the non-CABG patients, prior CABG patients were older (OR, 3.98; 95% CI, 3.19-4.78; p < .001; I2 = 72%), had more male (OR, 1.30; 95% CI, 1.14-1.49; p < .001; I2 = 6%), diabetes mellitus (OR, 1.54; 95% CI, 1.36-1.73; p < .001; I2 = 37%), dyslipidemia (OR, 1.89; 95% CI, 1.33-2.69; p < .001; I2 = 81%), hypertension (OR, 1.88; 95% CI, 1.46-2.41; p < .001; I2 = 71%), previous myocardial infarction (OR, 1.94; 95% CI, 1.48-2.56; p < .001; I2 = 85%), and previous PCI (OR, 1.74; 95% CI, 1.52-1.98; p < .001; I2 = 22%). Non-CABG patents had more current smoker (OR, .45; 95% CI, 0.27-0.74; p < .001; I2 = 91%). BMI (OR, -0.01; 95% CI, -0.07-0.06; p = .85; I2 = 36%) were similar in both groups. For lesions location, the right coronary artery (RCA) was predominant target vessel in both groups (50.5% vs 48.7%; p＝.49), although, the left circumflex (LCX) was more frequently CTO in the prior CABG group (27.3% vs 18.9%; p＜.01), while left anterior descending artery (LAD) in non-CABG ones (16.0% vs 29.1%; p＜0.01). For lesions characteristics, prior CABG patients had more blunt stump (OR, 1.71; 95% CI, 1.46-2.00; p < .001; I2 = 40%), proximal cap ambiguity (OR, 1.45; 95% CI, 1.28-1.64; p < .001; I2 = 0.0%), severe calcifications (OR, 2.91; 95% CI, 2.19-3.86; p < .001; I2 = 83%), more bending (OR, 3.07; 95% CI, 2.61-3.62; p < .001; I2 = 0%), lesion length > 20 mm (OR, 1.59; 95% CI, 1.10-2.29; p = .01; I2 = 83%), inadequate distal landing zone (OR, 1.95; 95% CI, 1.75-2.18; p＜.001; I2 = 0.0%), distal cap at bifurcation (OR, 1.65; 95% CI, 1.46-1.88; p < .001; I2 = 0.0%), and higher J-CTO score (SMD, 0.52; 95% CI, 0.42-0.63; p < .001; I2 = 65%). But side branch at proximal entry (OR, 0.88; 95% CI, 0.72-1.07; p = .21; I2 = 45%), in-stent CTO (OR, 0.99; 95% CI, 0.86-1.14; p = .88; I2 = 0.0%), lack of interventional collaterals (OR, 0.80; 95% CI, 0.55-1.15; p = .23; I2 = 78%), and previously failed attempt (OR, 0.73; 95% CI, 0.48-1.11; p = .14; I2 = 89%) were similar in both groups. For complication, prior CABG patients had more perforation with need for intervention (OR, 1.91; 95% CI, 1.36-2.69; p < 0.001; I2 = 34%), contrast-induced nephropathy (OR, 3.40; 95% CI, 1.31-8.78; p = .01; I2 = 0.0%). Non-CABG patents had more tamponade (OR, 0.25; 95% CI, 0.09-0.72; p = .01; I2 = 0.0%), and the major bleeding complication (OR, 1.18; 95% CI, 0.57-2.44; p = .65; I2 = 0%) were no significant difference in both groups. In conclusion, Patients with prior CABG undergoing CTO-PCI have more complex lesion characteristics, though procedural complication rates were comparable.

Discovery and identification of new non-ATP competitive FGFR1 inhibitors with therapeutic potential on non-small-cell lung cancer.

Fibroblast growth factor receptor (FGFR) tyrosine kinases have been regarded as a target for cancer treatment, and there is much interest in inhibiting FGF/FGFR signaling by small molecules as a therapeutic approach to cancer. Generally, inhibitors mimics ATP structure and block the binding between ATP and FGFR kinase. Here, two novel, non-ATP-competitive, selective, irreversible FGFR1 inhibitors, A114 and A117, were identified via kinase inhibitory assay from 156 synthetic bisaryl-1,4-dien-3-one derivatives. A "DFG-OUT" inactive conformation binding mode with FGFR1 was predicted by molecular docking. A114 and A117 showed significant anti-tumor activity both in vitro and in vivo via targeting FGFR1.

Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells.

BACKGROUND: Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy. METHODS: A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated. RESULTS: B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo. CONCLUSIONS: A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC.

Synthesis and biological evaluation of novel thiazolidinone derivatives as potential anti-inflammatory agents.

The modulation of pro-inflammatory cytokines provides a target for controlling inflammatory diseases and attracts much attention in current anti-inflammatory drug development. Here, four series of thiazolidinone derivatives were synthesized and screened for anti-inflammatory activities. A majority of these compounds showed excellent inhibition on the expression of TNF-α and IL-6 in LPS-stimulated macrophages. Discussions are given regarding the structure-activity relationships. Compounds 12d and 12h inhibited LPS-induced TNF-α and IL-6 release in a dose-dependent manner. Furthermore, 12d exhibited a significant protection against LPS-induced septic death in mouse model. Together, these data present a series of new thiazolidinones with potential therapeutic effects in acute inflammatory diseases and they could be important leads in the continuing anti-inflammatory drug research.

Ethyl 7-methyl-2-((1-methyl-1H-pyrrol-2-yl)methyl-ene)-3-oxo-5-phenyl-3,5-dihydro-2H-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.

In the structure of the title compound, C(22)H(21)N(3)O(3)S, the thia-zole ring forms dihedral angles of 88.83 (7) and 9.39 (9)°, respectively, with the benzene and pyrrole rings. The dihydro-pyrimidine ring adopts a flattened boat conformation. The olefinic double bond is in a Z conformation.