Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

Using Bidirectional Encoder Representations from Transformers (BERT) to predict criminal charges and sentences from Taiwanese court judgments.

People unfamiliar with the law may not know what kind of behavior is considered criminal behavior or the lengths of sentences tied to those behaviors. This study used criminal judgments from the district court in Taiwan to predict the type of crime and sentence length that would be determined. This study pioneers using Taiwanese criminal judgments as a dataset and proposes improvements based on Bidirectional Encoder Representations from Transformers (BERT). This study is divided into two parts: criminal charges prediction and sentence prediction. Injury and public endangerment judgments were used as training data to predict sentences. This study also proposes an effective solution to BERT's 512-token limit. The results show that using the BERT model to train Taiwanese criminal judgments is feasible. Accuracy reached 98.95% in predicting criminal charges and 72.37% in predicting the sentence in injury trials, and 80.93% in predicting the sentence in public endangerment trials.

The role of the basal forebrain in general anesthesia.

The basal forebrain is a group of nerve nuclei on the ventral side of the ventral ganglion, composed of γ-aminobutyric acid neurons, glutamatergic neurons, cholinergic neurons, and orexigenic neurons. Previous studies have focused on the involvement of the basal forebrain in regulating reward, learning, movement, sleep-awakening, and other neurobiological behaviors, but its role in the regulation of general anesthesia has not been systematically elucidated. Therefore, the different neuronal subtypes in the basal forebrain and projection pathways in general anesthesia will be discussed in this paper. In this paper, we aim to determine and elaborate on the role of the basal forebrain in general anesthesia and the development of theoretical research and provide a new theory.

Does tourism market diversification matter for CO2 emissions? evidence from Singapore.

This research analyzed the effect of tourism market diversification on Singapore's CO2 emissions by measuring the level of concentration of source countries in a foreign tourist basket of Singapore using a Herfindahl-Hirschman index. Our results indicated that the index fell over the period 1978-2020, which means the diversification of source countries of Singapore's foreign tourists increased. By applying the recent bootstrap and quantile ARDL models, we found that tourism market diversification and inward FDI act as stumbling blocks to CO2 emissions. In contrast, economic growth and primary energy consumption increase CO2 emissions. Policy implications are presented and discussed.

A Robust, Fully Automatic Detection Method and Calculation Technique of Midline Shift in Intracranial Hemorrhage and Its Clinical Application.

A midline shift (MLS) is an important clinical indicator for intracranial hemorrhage. In this study, we proposed a robust, fully automatic neural network-based model for the detection of MLS and compared it with MLSs drawn by clinicians; we also evaluated the clinical applications of the fully automatic model. We recruited 300 consecutive non-contrast CT scans consisting of 7269 slices in this study. Six different types of hemorrhage were included. The automatic detection of MLS was based on modified Keypoint R-CNN with keypoint detection followed by training on the ResNet-FPN-50 backbone. The results were further compared with manually drawn outcomes and manually defined keypoint calculations. Clinical parameters, including Glasgow coma scale (GCS), Glasgow outcome scale (GOS), and 30-day mortality, were also analyzed. The mean absolute error for the automatic detection of an MLS was 0.936 mm compared with the ground truth. The interclass correlation was 0.9899 between the automatic method and MLS drawn by different clinicians. There was high sensitivity and specificity in the detection of MLS at 2 mm (91.7%, 80%) and 5 mm (87.5%, 96.7%) and MLSs greater than 10 mm (85.7%, 97.7%). MLS showed a significant association with initial poor GCS and GCS on day 7 and was inversely correlated with poor 30-day GOS (p < 0.001). In conclusion, automatic detection and calculation of MLS can provide an accurate, robust method for MLS measurement that is clinically comparable to the manually drawn method.

Remarkably enhanced photovoltaic effects and first-principles calculations in neodymium doped BiFeO3.

Remarkably enhanced photovoltaic effects have been observed in the heterostructures of p-type A-site Nd3+-doped BiFeO3 (Bi0.9375Nd0.0625)FeO3 (or BFONd) polycrystalline ceramics and the n-type ITO thin film. The maximum power conversion is ~0.82%, which is larger than 0.015% in BiFeO3 (BFO) under blue-ultraviolet irradiation of wavelength λ = 405 nm. The current-voltage (I-V) characteristic curve suggests a p-n junction interface between the ITO thin film and BFO (or BFONd) ceramics. The band gaps calculated from first-principles for BFO and BFONd are respectively 2.25 eV and 2.23 eV, which are consistent with the experimental direct band gaps of 2.24 eV and 2.20 eV measured by optical transmission spectra. The reduction of the band gap in BFONd can be explained by the lower electronic Fermi level due to acceptor states revealed by first-principles calculations. The optical calculations show a larger absorption coefficient in BFONd than in BFO.

New flavan and benzil isolated from Fissistigma latifolium.

Further investigation of the methanolic extract of Fissistigma latifolium resulted in two new compounds whose structures were assigned as 2,5,6,7-tetramethoxyflavan (1) and 2'-hydroxy-4',5',6'-trimethoxybenzil (2). These two compounds were determined on the basis of chemical and spectroscopic evidences. Compound 2 is the first report of benzil from Fissistigma species. 2,5,6,7-Tetramethoxyflavan (1) showed a potent inhibitory effect on superoxide anion production in formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)/cytochalasin B (CB)-activated human neutrophils.

The first bis-retrochalcone from Fissistigma latifolium.

Two novel chalconoids, [3-3'']bi-2-hydroxy-4,5,6-trimethoxydihydrochalcone (1) and 4,6-dimethoxy-2,5-quinodihydrochalcone (2), and twelve known compounds were isolated from the methanolic extract of Fissistigma latifolium (Dun.) Merr. The structures of all compounds were determined by spectroscopic methods. Of these, compounds 1, 2, and 2-hydroxy-4,5,6-trimethoxydihydrochalcone (10) belong to an uncommon group of chalconoids, the retrochalcones. Compound 1 is the first bis-retrochalcone to be reported, and compound 2 is a quinoretrochalcone. Furthermore, 2 showed activity against the MDA-MB-231 human breast cancer cell line with an IC (50) value of 7.1 µM.