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Background: Ovarian cancer is a difficult and lethal illness that requires early detection and precise classification for effective therapy. Microarray technology has permitted the simultaneous assessment of hundreds of genes' expression levels, yielding important insights into the molecular pathways driving ovarian cancer. To reduce computational complexity and improve accuracy, choosing the most likely differential genes to explain the impacts of ovarian cancer is necessary. Medical datasets, including those related to ovarian cancer, are often limited in size due to privacy concerns, data collection challenges, and the rarity of certain conditions. Data augmentation allows researchers to expand the dataset, providing a larger and more diverse set of examples for model training. Recent advances in machine learning and bioinformatics have shown promise in improving ovarian cancer classification based on gene information. Methods: In this paper, we present an ensemble algorithm based on gene selection, data augmentation, and boosting approaches for ovarian cancer classification. In the proposed approach, the initial genetic data were first subjected to feature selection. Results: The target genes were screened and combined with data augmentation and ensemble boosting algorithms. From the results, the chosen ten genes could accurately classify ovarian cancer at 98.21%. Conclusions: We further show that the proposed algorithm based on clustering approaches is effective for real-world ovarian cancer data, with 100% accuracy and strong performance in distinguishing between distinct ovarian cancer subtypes. The proposed algorithm may help doctors identify ovarian cancer patients early and develop individualized treatment plans. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the potential bioactive compounds from Phyllanthus emblica L. fruit. Methods: Acetone extracts (60%) of P emblica fruit were dissolved in water and fractionated sequentially with light petroleum and ethyl acetate (EtOAc). The water fraction was separated using Sephadex LH-20 and the isolated compounds were purified by preparative high-performance liquid chromatography. The structures of the isolated compounds were determined through HR-ESI-MS and spectroscopic methods, including 1D- and 2D-NMR, and the antioxidant abilities of the isolates were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Results: Three new phenolic compounds, mucic acid 1-ethyl ester 3- O -gallate (1), mucic acid 6-methyl ester 3- O -gallate (2), and mucic acid 6-ethyl ester 2- O -gallate (3), together with 4 known compounds (4 - 7), were isolated from P emblica fruit. All phenolics exhibited potent antioxidant abilities (DPPH: IC50 7.5-13.2 µM; ABTS: 1.12-2.84 µM Trolox/µM; FRAP: 1.11-2.26 µM Fe2+/µM). Conclusions: Our research contributes to the growing body of evidence demonstrating the benefits of P emblica for health and supports the functional food and nutraceutical applications of the fruit. [ABSTRACT FROM AUTHOR]

Pulmonary sarcomatoid carcinoma (PSC) is an aggressive and poorly differentiated type of non-small cell lung carcinoma. Because of the rarity of PSC, the efficacy and toxicity of immunotherapy remain unclear. Hence, the aim of this study was to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) for the treatment of advanced PSC. The study cohort was limited to 33 patients with pathologically confirmed PSC treated with ICIs in four hospitals in China from March 2018 to March 2022. Expression of programmed death ligand 1 (PD-L1) was detected by immunohistochemical analysis. Categorical variables were compared with the Fisher exact test and survival analysis was conducted with the Kaplan-Meier method. Of the 33 PSC patients, 8 (24.2%) received monotherapy with ICIs and 25 (75.8%) received combination therapy with ICIs. The objective response rate (ORR) and disease control rate (DCR) were 36.4% and 78.8%, respectively. The median durations of progression-free survival (PFS) and overall survival (OS) were 6.07 and 21.33 months, respectively. PD-L1 status in 16 available samples was assessed, which included 30.3% PD-L1-positive patients. The ORRs for PD-L1-positive vs. -negative patients were 50.0% and 90.0%, the DCR was 33.3% and 83.3%, and the median PFS was 17.50 and 6.07 months, respectively (p=0.812). The median OS was not reached in PD-L1-positive and -negative patients (p=0.655). The incidence of immune-related adverse (irAEs) was 48.5% and mainly included grade 1 or 2 (39.4%), while the incidence of grade 3 or 4 was 9.1%. Pneumonia (9.1%) and skin rash (9.1%) were the most frequent irAEs. Immunotherapy with ICIs was a promising regimen to improve the prognosis of patients with advanced PSC. [ABSTRACT FROM AUTHOR]

APAP is one of the most commonly used antipyretic and pain medications, but excessive use can cause liver toxicity and damage. 3,4-dihydroxyphenylethyl alcohol glycoside (DAG) is a component isolated from Sargentodoxa cuneata known to have anti-apoptotic, anti-oxidation and anti-inflammatory effects. However, the effects of DAG on acute liver failure (ALF) are largely unknown. The purpose of this study is to study the protective effects and mechanism of DAG on APAP-induced ALF in mice. We established an ALF model in adult male pathogen-free C57BL/6 mice treated with APAP (300 mg/kg) by intraperitoneal injection and resolved by 24 h. Hematoxylin and eosin (HE) staining was used to evaluate the pathological changes in mouse liver tissue. The infiltration of neutrophils in liver tissue and reactive oxygen species (ROS) in AML12 cells were analyzed by flow cytometry. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were analyzed using relevant kits. Our results show that DAG reduced APAP-induced serum ALT and AST levels, histopathological changes, liver neutrophil infiltration and proinflammatory cytokines production, also attenuated the accumulation of MDA and the exhaustion of GSH, CAT and SOD. In vitro experiment indicated that DAG dose-dependently inhibited APAP-induced the levels of pro-inflammatory factors (IL-1β and IL18), and reactive oxygen species (ROS) and preventing GSH depletion in mouse AML12 hepatocytes. More interestingly, DAG inhibited the expression of ERK, HO-1, NLRP3, Caspase1 (p20) and Gasdermin-D and upregulated the expression of GPX4 in liver tissues and AML12hepatocytes. Therefore, our results indicate that DAG may act as a potential agent to treat ALF induced by APAP by inhibiting hepatocyte ferroptosis and pyroptosis. [ABSTRACT FROM AUTHOR]

Alismatis Rhizoma decoction (ARD), comprised of Alisma plantago-aquatica subsp. orientale (Sam.) Sam and Atractylodes macrocephala Koidz. at a ratio of 5 : 2, is a classic traditional Chinese medicine (TCM) formula with successful clinical hypolipidemic effect. This paper aimed to explore the major bioactive compounds and potential mechanism of ARD in the treatment of hyperlipidemia on the basis of spectrum-effect analysis and molecular docking. Nine ARD samples with varying ratios of the constituent herbs were prepared and analyzed by UPLC-Q-TOF/MS to obtain the chemical spectra. Then, the lipid-lowering ability of the nine samples was tested in an oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). Grey relational analysis and partial least squares regression analysis were then performed to determine the correlation between the chemical spectrums and lipid-lowering efficacies of ARD. The potential mechanisms of the effective compounds were investigated by docking with the farnesoid X receptor (FXR) protein. The results indicated that alisol B 23-acetate, alisol C 23-acetate, and alisol B appeared to be the core effective components on hyperlipidemia in ARD. Molecular docking further demonstrated that all three compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of ARD for treating hyperlipidemia from a perspective of different compatibility, providing a new and feasible reference for the research of TCM formulas such as ARD. [ABSTRACT FROM AUTHOR]

Purpose: The great efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been identified in patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, it has not yet been established in postoperative adjuvant therapy. Patients and methods: To compare the prognosis and toxicity of EGFR-TKI-based adjuvant therapy and non-EGFR-TKI-based adjuvant therapy in resected NSCLC with sensitive EGFR mutations, we performed this meta-analysis of all eligible randomized controlled trials (RCTs). Results: A comprehensive literature search of electronic databases (from inception to December 31, 2017) was performed. Additionally, abstracts presented at the American Society of Clinical Oncology conferences and World Conference on Lung Cancer held between January 2000 and November 2017 were searched to identify relevant trials. Disease-free survival (DFS), overall survival (OS), and grade 3 or 4 toxicities were analyzed. Five RCTs were selected, and 560 participants were included. This meta-analysis demonstrated that EGFR-TKI-based adjuvant therapy was associated with better DFS compared with non-EGFR-TKI-based therapy (HR =0.52, 95% CI 0.34–0.78, P=0.002). Pooled estimate has showed the trend of superiority of EGFR-TKI-based therapy in the aspect of OS (HR =0.65, 95% CI 0.22–1.91, P=0.43); however, the difference was not significant. The incidence rate of grade 3–4 toxicities of EGFR-TKI-based regimens was significantly higher for rash (OR =10.17, 95% CI 2.37–43.63, P=0.002) but lower for vomiting (OR =0.08, 95% CI 0.01–0.61, P=0.02). Conclusion: EGFR-TKI-based therapy was associated with better DFS compared with non-EGFR-TKI-based adjuvant therapy in patients with NSCLC harboring EGFR mutations. A trend was found that EGFR-TKI-based regimen improved the OS, though the difference was not significant. Although more OS data are needed, EGFR-TKI-based treatment has the potential to be an alternative of adjuvant therapy for NSCLC with a sensitive EGFR mutation. [ABSTRACT FROM AUTHOR]

The article focuses on the decision of the U.S. Supreme Court in the case Elonis v. United States wherein the Court reversed a conviction for making online threats over the social media platform Facebook. It mentions that ambiguity in the intent requirement with the ease with which true threats can be made in the Internet age.

This paper considers adaptive neural control for a class of uncertain saturated nonlinear systems. To overcome the problem of “explosion of complexity" that exists in the traditional backstepping design, dynamic surface technique is utilized to avoid the repeated differentiations of virtual controllers. Novel truncated adaptation technique is proposed to attenuate the effect cause by input saturation. Radial basis function (RBF) neural networks (NNs) are used to online approximate uncertain system dynamics. Auxiliary signals generated by properly designed auxiliary system are used to truncate the training signal of RBF NNs when input saturation happens. The stability of closed-loop system is guaranteed and proved using Lyapunov stability theorem. The tracking error can be made to arbitrarily small by tuning design parameter in an explicit way even with input saturation in effect, and the compact sets that steady tracking error and transient tracking error are confined in are given, which are characterized by design parameters. Simulation results are presented to verify the effectiveness of the proposed control scheme. [ABSTRACT FROM AUTHOR]

Objective: The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer. Methods: A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed. Results: A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI]  = 0.32–0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25–0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41–0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29–3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications. Conclusion: CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors. [ABSTRACT FROM AUTHOR]

To compare the efficacy, prognosis, and toxicity of S-1-based with fluorouracil (5-FU)-based chemotherapy in patients with advanced gastric cancer (AGC) as first-line treatment, we performed this meta-analysis of all eligible randomized controlled trials (RCTs). A comprehensive literature search of electronic databases (up to February 20, 2014) was performed. Additionally, abstracts presented at the American Society of Clinical Oncology (ASCO) conferences held between January 2000 and February 2014 were searched to identify relevant trials. Overall response rate (ORR), time to treatment failure (TTF), overall survival (OS), and grade 3 or 4 toxicities were analyzed. Six RCTs with 2,264 patients of AGC were included. Meta-analysis demonstrated that S-1-based therapy was associated with better OS compared with 5-FU-based therapy (hazard ratio (HR) = 0.80, 95 % confidence interval (CI) 0.80-0.99, P = 0.03). Pooled estimate has showed the trend of superiority of S-1-based therapy in the aspect of ORR (odds ratio (OR) = 1.55, 95 % CI 0.87-2.77, P = 0.14) and TTF (HR = 0.73, 95 % CI 0.53-1.00, P = 0.05), but the difference was not significant. The incidence of toxicities of 5-FU-based regimens was significantly higher for thrombocytopenia (OR = 0.60, 95 % CI 0.42-0.88, P = 0.008) and stomatitis (OR = 0.22, 0, 95 % CI 0.05-0.9, P = 0.03). Based on the published studies, S-1-based therapy was superior to 5-FU-based therapy in OS and safety profile as first-line treatment in AGC. It was prone to improving ORR and TTF, though the difference was not significant. More high-quality randomized controlled trials should be performed to provide more information in comparing these two regimens. [ABSTRACT FROM AUTHOR]

Background: The management of limited-disease esophageal small cell carcinoma is not well defined, and the role of surgery is still controversial. We aim to determine the optimal treatment strategy in limited-disease of esophageal small cell carcinoma. Methods and Findings: We conducted a retrospective review of 141 patients with limited-disease esophageal small cell carcinoma from 3 institutions in China who underwent treatment between July 1994 and September 2008, July 1994 and July 2011, and June 2004 and December 2010, respectively. The survival rate was calculated by the Kaplan-Meier method, and the log-rank test was used to assess the survival differences between the groups. Cox proportional hazards model were used to further determine the independent factors impacting overall survival. The median survival time was 16.1 months for the entire cohort of patients, with a 5-year survival rate of 6.7%. The median survival times for surgery alone, surgery combined with chemotherapy, surgery combined with radiotherapy, surgery combined with chemotherapy and radiotherapy, chemotherapy plus radiotherapy, and chemotherapy alone were 18.0 months, 15.0 months, 23.0 months, 25.0 months, 17.1 months, and 6.1 months, respectively; the corresponding 5-year survival rates were 0%, 15.4%, 0%, 38.9%, 0%, and 0%, respectively. For the 105 patients who underwent R0 resection, the median disease-free survival time was 12.0 months, with a 95% confidence interval of 9.5 months to 14.5 months. The multivariate Cox regression analysis demonstrated that advanced pathological staging (p = 0.003), and pure esophageal small cell carcinoma (p = 0.035) were independent factors decreasing overall survival. Conclusions: Our data suggested that multidisciplinary modalities achieved encouraging long-term survival in patients with resectable limited-disease of esophageal small cell carcinoma. [ABSTRACT FROM AUTHOR]