Computed tomography-based multi-organ radiomics nomogram model for predicting the risk of esophagogastric variceal bleeding in cirrhosis.

BACKGROUND: Radiomics has been used in the diagnosis of cirrhosis and prediction of its associated complications. However, most current studies predict the risk of esophageal variceal bleeding (EVB) based on image features at a single level, which results in incomplete data. Few studies have explored the use of global multi-organ radiomics for non-invasive prediction of EVB secondary to cirrhosis. AIM: To develop a model based on clinical and multi-organ radiomic features to predict the risk of first-instance secondary EVB in patients with cirrhosis. METHODS: In this study, 208 patients with cirrhosis were retrospectively evaluated and randomly split into training (n = 145) and validation (n = 63) cohorts. Three areas were chosen as regions of interest for extraction of multi-organ radiomic features: The whole liver, whole spleen, and lower esophagus-gastric fundus region. In the training cohort, radiomic score (Rad-score) was created by screening radiomic features using the inter-observer and intra-observer correlation coefficients and the least absolute shrinkage and selection operator method. Independent clinical risk factors were selected using multivariate logistic regression analyses. The radiomic features and clinical risk variables were combined to create a new radiomics-clinical model (RC model). The established models were validated using the validation cohort. RESULTS: The RC model yielded the best predictive performance and accurately predicted the EVB risk of patients with cirrhosis. Ascites, portal vein thrombosis, and plasma prothrombin time were identified as independent clinical risk factors. The area under the receiver operating characteristic curve (AUC) values for the RC model, Rad-score (liver + spleen + esophagus), Rad-score (liver), Rad-score (spleen), Rad-score (esophagus), and clinical model in the training cohort were 0.951, 0.930, 0.801, 0.831, 0.864, and 0.727, respectively. The corresponding AUC values in the validation cohort were 0.930, 0.886, 0.763, 0.792, 0.857, and 0.692. CONCLUSION: In patients with cirrhosis, combined multi-organ radiomics and clinical model can be used to non-invasively predict the probability of the first secondary EVB.

Recent Advances in Fibrous Materials for Hydroelectricity Generation.

Depleting fossil energy sources and conventional polluting power generation pose a threat to sustainable development. Hydroelectricity generation from ubiquitous and spontaneous phase transitions between liquid and gaseous water has been considered a promising strategy for mitigating the energy crisis. Fibrous materials with unique flexibility, processability, multifunctionality, and practicability have been widely applied for fibrous materials-based hydroelectricity generation (FHG). In this review, the power generation mechanisms, design principles, and electricity enhancement factors of FHG are first introduced. Then, the fabrication strategies and characteristics of varied constructions including 1D fiber, 1D yarn, 2D fabric, 2D membrane, 3D fibrous framework, and 3D fibrous gel are demonstrated. Afterward, the advanced functions of FHG during water harvesting, proton dissociation, ion separation, and charge accumulation processes are analyzed in detail. Moreover, the potential applications including power supply, energy storage, electrical sensor, and information expression are also discussed. Finally, some existing challenges are considered and prospects for future development are sincerely proposed.

Diabetes self-management education programs: Results from a nationwide population-based study on characteristics of participants, rating of programs and reasons for non-participation.

OBJECTIVE: Population-based studies of reasons for not participating in diabetes self-management education (DSME) are scarce. Therefore, we investigated what sociodemographic and disease-related factors are associated with participation in DSME, the reasons for not participating in DSME and how participants evaluate DSME. RESEARCH DESIGN AND METHODS: We used data from the nationwide survey "Disease knowledge and information needs-Diabetes mellitus 2017", which included a total of 1396 participants diagnosed with diabetes mellitus (diabetes; n = 394 DSME-participants, n = 1002 DSME-never-participants). Analyses used weighted logistic or multinominal regression analyses with bivariate and multivariable approaches. RESULTS: Participants were more likely to attend DSME if they had a medium (OR 1.82 [95%CI 1.21-2.73]),or high (OR 2.04 [95%CI 1.30-3.21]) level of education, had type 1 diabetes (OR 2.46 [1.24-4.90]) and insulin treatment (OR 1.96 [95%CI 1.33-2.90]). Participants were less likely to attend DSME if they lived in East Germany (OR 0.57 [95%CI 0.39-0.83]), had diabetes for >2 to 5 years (OR 0.52 [95%CI 0.31-0.88] compared to >5 years), did not agree that diabetes is a lifelong disease (OR 0.30 [95%CI 0.15-0.62], had never been encouraged by their physician to attend DSME (OR 0.19 [95%CI 0.13-0.27]) and were not familiar with disease management programs (OR 0.67 [95%CI 0.47-0.96]). The main reasons for non-participation were participant's personal perception that DSME was not necessary (26.6%), followed by lack of recommendation from treating physician (25.7%) and lack of information on DSME (20.7%). DSME-participants found DSME more helpful if they had a medium educational level (OR 2.06 [95%CI 1.10-3.89] ref: low level of education) and less helpful if they were never encouraged by their treatment team (OR 0.46 [95%CI 0.26-0.82]). DISCUSSION: Professionals treating persons with diabetes should encourage their patients to attend DSME and underline that diabetes is a lifelong disease. Overall, the majority of DSME participants rated DSME as helpful.

A nanocarbon-enabled hybridization strategy to construct pharmacologically cooperative therapeutics for augmented anticancer efficacy.

The drug design principles are of great value in developing nanomedicines with favorable functionalities. Herein we propose a nanocarbon-enabled hybridization strategy to construct a pharmacologically cooperative nanodrug for improved cancer therapy in the light of pharmacophore hybridization in medicinal chemistry and the synthetic principles of nanocarbons. An antioxidant defense pharmacological inhibitor and a co-nucleation precursor are structurally hybridized into nanodrugs (SCACDs) via forming carbon quantum dots. These SCACDs elicit dual enhanced bioactivities, including superior sonocatalytic activity that arose from the appropriate band structure of the pharmacophoric carbon cores, and more than an order of magnitude higher antioxidant defense inhibitory activity than the pharmacological inhibitor via conveying the bioactive pharmacophores from the molecular level to nanoscale. In vivo, SCACDs possess a long body retention and desirable biodistribution to eliminate melanoma cells at a very low injection dose. The present study provides a viable yet effective strategy for the development of pharmacologically cooperative nanodrugs to achieve remarkably improved therapeutic efficacy.

Difluorocarbene-Enabled Trifluoromethylation and Cyclization for the Synthesis of 3-(Trifluoromethyl)-4H-pyrans.

A three-component annulation reaction and trifluoromethylation for the construction of 3-(trifluoromethyl)-4H-pyrans using ß-CF3-1,3-enynes, BrCF2CO2Et, and sulfoxonium ylides as readily available substrates has been developed. This metal-free process involves two C-F bond cleavages of ß-CF3-1,3-enynes and a CF3 group generated in situ from BrCF2CO2Et. This method is applicable to the late-stage modification of pharmaceutically active molecules.

Investigating alterations of nutritional constituents, antioxidant abilities, and physicochemicals in aging processes of ginseng sprouts.

This study was the first to document the fluctuations of nutritional constituents, antioxidant capacities, and physicochemical characteristics during the aging processes of red ginseng sprouts (RGS) and black ginseng sprouts (BGS) from dried ginseng sprouts (DGS). Total ginsenoside levels differed with 54.72 (DGS) → 57.15 (RGS) and 6.98 (BGS) mg/g, specifically, ginsenoside F2 and Rd2 in RGS remarkably increased with 1.97 â†’ 5.88 and 2.41 â†’ 5.49 mg/g, respectively. Phenolics increased dramatically as 297.02 â†’ 1770.01 (6.0-fold); 1834.94 (6.2-fold) µg/g in DGS → RGS; BGS with abundance contents of benzoic acid (>15.3-fold), chlorogenic acid (>9.5-fold), and catechin (>4.2-fold), whereas amino acids markedly decreased (3686.81 â†’ 1505.00; 364.64 mg/100 g), with arginine showing a significant decrease. Moreover, beneficial factors (total phenolic content: TPC; total flavonoid content: TFC; maillard reaction products: MRP) displayed increase tendencies (approximately 2.0-fold) with BGS > RGS > DGS, and antioxidant patterns significantly increased with potential capacities as follows: ABTS (48.3: DGS → 65.8: RGS; 70.2 %: BGS) > DPPH (18.5 â†’ 44.6; 59.2 %) > hydroxyl (23.2 â†’ 35.4; 39.9 %) > FRAP (0.6 â†’ 1.8; 1.8 %) at 500 µg/mL. In particular, DNA protection exhibited excellent rates of 100 %, in the order of BGS (25 µg/mL) > RGS (50 µg/mL) > DGS (500 µg/mL). These findings suggest that processed ginseng sprouts can be excellent agents for natural antioxidants.

Comparison of primary and secondary metabolites and antioxidant activities by solid-state fermentation of Apios americana Medikus with different fungi.

This study compared the nutritional components, isoflavones, and antioxidant activities by solid-sate fermentation of Apios americana Medikus (AAM) with seven different fungi. The total fatty acid contents increased from 120.5 mg/100 g (unfermented AAM, UFAAM) to 242.0 to 3167.5 mg/100 g (fermented AAM, FAAM) with all fungi. In particular, the values of total fatty acids were highest (26.3-fold increase) in the FAAM with Monascus purpureus. The amount of total free amino acids increased from 591.69 mg/100 g (UFAAM) to 664.38 to 1603.07 mg/100 g after fermentation except for Monascus pilosus and Lentinula edodes. The total mineral contents increased evidently after fermentation with M. purpureus, F. velutipes, and Tricholoma matsutake (347.36 â†’ 588.29, 576.59, and 453.32 mg/100 g, respectively). The UFAAM predominated isoflavone glycosides, whereas glycoside forms were converted into aglycone forms after fermentation by fungi. The bioconversion rates of glycoside to aglycone were excellent in the FAAM with M. pilosus, M. purpureus, F. velutipes, and T. matsutake (0.01 â†’ 0.69, 0.50, 0.27, and 0.31 mg/g, respectively). Furthermore, the total phenolic contents, total flavonoid contents, and antioxidant activities by the abovementioned FAAM were high except for L.edodes. This FAAM can be used as a potential food and pharmaceutical materials.

SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.

Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.

Hippocampal Availability of the α7 Nicotinic Acetylcholine Receptor in Recent-Onset Psychosis.

Importance: Studies using human postmortem tissue and imaging with positron emission tomography (PET) support a low hippocampal availability of the α7 nicotinic acetylcholine receptor (α7-nAChR) in psychotic conditions, particularly in schizophrenia or schizoaffective disorder (nonaffective psychosis). If validated further, the finding may have implications for clinical diagnosis and treatment. Objective: To test for lower availability of the α7-nAChR in the hippocampus of individuals with recent-onset psychosis compared with healthy control individuals and its association with lower cognitive performance or higher psychotic symptom burden within recent-onset psychosis. Design, Setting, and Participants: In this cross-sectional study, healthy individuals without history of psychosis and patients within 10 years of a first onset of psychotic disorder were recruited from the greater Baltimore, Maryland, and Washington, DC, area. Fluorine 18-labeled ASEM ([18F] ASEM) PET data were acquired from participants enrolled between March 1, 2014, and July 31, 2023, from an academic research institution. Data acquired between March 1, 2014, and January 31, 2018 (n = 26), were published as a pilot study and were combined with new data acquired between January 1, 2019, and July 31, 2023 (n = 33). Main Outcome and Measures: Regional [18F]ASEM total distribution volume (VT) that measures α7-nAChR availability, global cognition composite score, and total scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Results: A total of 59 participants (30 women [51%]; mean [SD] age, 25.5 [5.2] years), including 35 with recent-onset psychosis and 24 healthy controls, completed the study. In age-adjusted analyses, lower hippocampal [18F]ASEM VT was found in individuals with recent-onset psychosis (mean [SE], 17.87 [0.60]) compared with healthy controls (mean [SE], 19.82 [0.73]) (P = .04). In addition, [18F]ASEM VT was lower in individuals with nonaffective psychosis (mean [SE], 16.30 [0.83]) compared with healthy controls (P = .006) or those with affective psychosis (mean [SE], 19.34 [0.80]) (P = .03). Across recent-onset psychosis and after controlling for age, lower hippocampal [18F]ASEM VT was associated with more positive (r = -0.44; P = .009) but not negative symptoms, and higher hippocampal VT was associated with better global cognition composite score (r = 0.38; P = .03). Conclusions and Relevance: In this cross-sectional study of individuals with recent-onset psychosis compared with healthy controls, a lower hippocampal α7-nAChR availability was found in recent-onset psychosis, and its availability was lower in those with nonaffective vs affective psychosis. Further study of the association between low availability of the α7-nAChR and recent-onset psychosis is warranted toward informing diagnostic or therapeutic strategies related to these findings.

Machine learning analysis of serum cholesterol's impact on knee osteoarthritis progression.

The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K-L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.