QAScore -- An Unsupervised Unreferenced Metric for the Question Generation Evaluation

Question Generation (QG) aims to automate the task of composing questions for a passage with a set of chosen answers found within the passage. In recent years, the introduction of neural generation models has resulted in substantial improvements of automatically generated questions in terms of quality, especially compared to traditional approaches that employ manually crafted heuristics. However, the metrics commonly applied in QG evaluations have been criticized for their low agreement with human judgement. We therefore propose a new reference-free evaluation metric that has the potential to provide a better mechanism for evaluating QG systems, called QAScore. Instead of fine-tuning a language model to maximize its correlation with human judgements, QAScore evaluates a question by computing the cross entropy according to the probability that the language model can correctly generate the masked words in the answer to that question. Furthermore, we conduct a new crowd-sourcing human evaluation experiment for the QG evaluation to investigate how QAScore and other metrics can correlate with human judgements. Experiments show that QAScore obtains a stronger correlation with the results of our proposed human evaluation method compared to existing traditional word-overlap-based metrics such as BLEU and ROUGE, as well as the existing pretrained-model-based metric BERTScore.Comment: 19 pages, 5 figures, 7 table

A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-α therapy

BACKGROUND: Survivin is a member of the inhibitor-of-apoptosis (IAP) family which is widely expressed by many different cancers. Overexpression of survivin is associated with drug resistance in cancer cells, and reduced patient survival after chemotherapy and radiotherapy. Agents that antagonize the function of survivin hold promise for treating many forms of cancer. The purpose of this study was to investigate whether a cell-permeable dominant-negative survivin protein would demonstrate bioactivity against prostate and cervical cancer cells grown in three dimensional culture.RESULTS: A dominant-negative survivin (C84A) protein fused to the cell penetrating peptide poly-arginine (R9) was expressed in E. coli and purified by affinity chromatography. Western blot analysis revealed that dNSurR9-C84A penetrated into 3D-cultured HeLa and DU145 cancer cells, and a cell viability assay revealed it induced cancer cell death. It increased the activities of caspase-9 and caspase-3, and rendered DU145 cells sensitive to TNF-&alpha; via by a mechanism involving activation of caspase-8.CONCLUSIONS: The results demonstrate that antagonism of survivin function triggers the apoptosis of prostate and cervical cancer cells grown in 3D culture. It renders cancer cells sensitive to the proapoptotic affects of TNF-&alpha;, suggesting that survivin blocks the extrinsic pathway of apoptosis. Combination of the biologically active dNSurR9-C84A protein or other survivin antagonists with TNF-&alpha; therapy warrants consideration as an approach to cancer therapy.<br /

Overexpression of EPHB4 Is associated with poor survival of patients with gastric cancer

Background: Increased expression of erythropoietin-producing human hepatoma (EPHB4) leads to enhanced cell migration, growth and adhesion in tumor cells. However, little is known regarding the effects of EPHB4 in gastric cancer. The present study aimed to examine the clinical relevance of EPHB4 and its association with the prognosis of gastric cancer. Materials and Methods: EPHB4 transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues was determined using quantitative polymerase chain reaction and the results were statistically analyzed against patient clinicopathological data. AGS and HGC27 cell lines were transfected with EPHB4 siRNA and the effects examined by functional analysis. Results: EPHB4 mRNA levels in gastric cancer tissues were significantly elevated when compared to non-cancerous tissues (p=0.0110). Tissue samples from male patients exhibited lower expression than those from female patients (p=0.0110). Non-cardiac gastric tumors (fundus, corpus and pylorus) expressed a higher number of EPHB4 transcripts in comparison to cardiac gastric tumors (p<0.001). Increased expression of EPHB4 was significantly associated with poorer overall (p=0.0051) and progression-free (p=0.0262) survival. EPHB4 knockdown appeared to reduce post-wound migration of AGS cells (p=0.0057) and increase migration of HGC27 cells (p=0.0337). EPHB4 knockdown significantly increased adhesive ability in HGC27 (p<0.0001). Conclusion: The expression of EPHB4 was increased in gastric cancer and increased EPHB4 expression was correlated with poor survival. Knockdown of EPHB4 promoted adhesion and exerted diverse effects on migration of gastric cancer cells. Further investigations may highlight its predictive and therapeutic potential in gastric cancer

Psoriasin overexpression confers drug resistance to cisplatin by activating ERK in gastric cancer

Psoriasin, a member of the S100 multigenic family, which is aberrantly expressed in a variety of human tumors, is considered as an attractive molecular target for cancer treatment. The present study aimed to characterize the role of psoriasin in gastric cancer (GC), the associated pathways through which it contributes to cancer development and progression, and the effect of psoriasin on cellular response to pre-operative chemotherapy in patients with GC. Expression of psoriasin mRNA and protein were analyzed using quantitative polymerase chain reaction and immunohistochemistry of gastric cancer cohorts, respectively. Gastric cancer cell models with differential expression of psoriasin were generated using stable cell lines that overexpressed psoriasin. The in vitro biological functions of the cells in response to psoriasin overexpression and to chemotherapeutic agents were assessed using various cell-based assays. Psoriasin was overexpressed in patients with advanced GC, and high psoriasin levels led to poor clinical outcomes. Increasing psoriasin expression in GC cell lines promoted cell proliferation, migration and invasion in vitro. Furthermore, psoriasin overexpression caused alterations in the levels of epithelial-mesenchymal transition-associated proteins, and activated the extracellular signal-regulated kinase signaling pathway. Additionally, higher levels of psoriasin expression were significantly associated a lack of response to neoadjuvant chemotherapy in patients with GC. Psoriasin overexpression tended to decrease the sensitivity of GC cells to cisplatin, potentially by inhibiting apoptosis or increasing the S-phase population. Taken together, these results indicate that psoriasin may be a promising therapeutic target for GC treatment, and a potential molecular marker to predict patient response to pre-operative chemotherapy

EphB2 represents an independent prognostic marker in patients with gastric cancer and promotes tumour cell aggressiveness

Dysregulated expression of ephrin type-B receptor 2 (EphB2) has been linked with development and progression of solid tumours. In the current study we attempted to investigate the clinical relevance in GC and the effect of EphB2 expression on gastric cancer (GC) cells. EphB2 protein levels in GC and benign gastric tissues were determined using immunohistochemistry. EphB2 transcript expression in a GC cohort with GC tissue samples (n=171) and paired adjacent normal gastric tissues (n=97) was determined using qPCR. The EphB2 expression was over-activated using a CRISPR activator for the investigation of its cellular function. The expression levels of the EphB2 protein in the tumour tissues of tissue arrays were higher than the benign non-cancerous gastric tissues (P<0.05). EphB2 mRNA expression in GC tissues was also significantly elevated when compared with adjacent non-cancerous tissues (P<0.01). EphB2 activation promoted the migration and invasion abilities of the GC cell lines (P<0.01, respectively). In contrast, EphB2 activation significantly decreased the adhesion in GC cells (P<0.0001, respectively). The enrichment analysis of the correlated genes in a GC cohort indicates that EphB2 may function through mediating the cytokine-cytokine interaction, JAK-STAT and TP53 signaling pathways. In conclusion, EphB2 represents as a novel independent prognostic marker in GC. And activation of the EphB2 gene expression elevated the levels of migration and invasion, but suppressed adhesion of GC cells, indicating that EphB2 may act as a tumour promotor in GC. Our findings thus provide fundamental evidence for the consideration of the therapeutic potential of targeting EphB2 in GC

Neuroprotective Effects and Mechanism of β

Emerging evidence suggests that activated astrocytes play important roles in AD, and β-asarone, a major component of Acorus tatarinowii Schott, was shown to be a potential therapeutic candidate for AD. While our previous study found that β-asarone could improve the cognitive function of rats hippocampally injected with Aβ, the effects of β-asarone on astrocytes remain unclear, and this study aimed to investigate these effects. A rat model of Aβ1–42 (10 μg) was established, and the rats were intragastrically treated with β-asarone at doses of 10, 20, and 30 mg/kg or donepezil at a dose of 0.75 mg/kg. The sham and model groups were intragastrically injected with an equal volume of saline. Animals were sacrificed on the 28th day after administration of the drugs. In addition, a cellular model of Aβ1–42 (1.1 μM, 6 h) was established, and cells were treated with β-asarone at doses of 0, 2.06, 6.17, 18.5, 55.6, and 166.7 μg/mL. β-Asarone improved cognitive impairment, alleviated Aβ deposition and hippocampal damage, and inhibited GFAP, AQP4, IL-1β, and TNF-α expression. These results suggested that β-asarone could alleviate the symptoms of AD by protecting astrocytes, possibly by inhibiting TNF-α and IL-1β secretion and then downregulating AQP4 expression

Identification of cell death-related biomarkers and immune infiltration in ischemic stroke between male and female patients

BackgroundStroke is the second leading cause of death and the third leading cause of disability worldwide, with ischemic stroke (IS) being the most prevalent. A substantial number of irreversible brain cell death occur in the short term, leading to impairment or death in IS. Limiting the loss of brain cells is the primary therapy target and a significant clinical issue for IS therapy. Our study aims to establish the gender specificity pattern from immune cell infiltration and four kinds of cell-death perspectives to improve IS diagnosis and therapy.MethodsCombining and standardizing two IS datasets (GSE16561 and GSE22255) from the GEO database, we used the CIBERSORT algorithm to investigate and compare the immune cell infiltration in different groups and genders. Then, ferroptosis-related differently expressed genes (FRDEGs), pyroptosis-related DEGs (PRDEGs), anoikis-related DEGs (ARDEGs), and cuproptosis-related DEGs (CRDEGs) between the IS patient group and the healthy control group were identified in men and women, respectively. Machine learning (ML) was finally used to generate the disease prediction model for cell death-related DEGs (CDRDEGs) and to screen biomarkers related to cell death involved in IS.ResultsSignificant changes were observed in 4 types of immune cells in male IS patients and 10 types in female IS patients compared with healthy controls. In total, 10 FRDEGs, 11 PRDEGs, 3 ARDEGs, and 1 CRDEG were present in male IS patients, while 6 FRDEGs, 16 PRDEGs, 4 ARDEGs, and 1 CRDEG existed in female IS patients. ML techniques indicated that the best diagnostic model for both male and female patients was the support vector machine (SVM) for CDRDEG genes. SVM’s feature importance analysis demonstrated that SLC2A3, MMP9, C5AR1, ACSL1, and NLRP3 were the top five feature-important CDRDEGs in male IS patients. Meanwhile, the PDK4, SCL40A1, FAR1, CD163, and CD96 displayed their overwhelming influence on female IS patients.ConclusionThese findings contribute to a better knowledge of immune cell infiltration and their corresponding molecular mechanisms of cell death and offer distinct clinically relevant biological targets for IS patients of different genders

Clinical Evaluation of Targeted Arterial Infusion of Verapamil in the Interventional Chemotherapy of Primary Hepatocellular Carcinoma

This study evaluates the clinical effectiveness of targeted arterial infusion of verapamil in interventional treatment of primary hepatocellular carcinoma. For this purpose, in 273 patients with middle- or late-stage primary hepatocellular carcinoma, verapamil, IL-2, and chemotherapeutic agents were infused into the target tumor vasculature through femoral artery using Seldinger technique. The medications were infused as serial dilutions, and effectiveness was evaluated after two treatment cycles. Among these 273 patients, 76 cases showed clinical cure or significant improvement, 119 cases improved, 64 cases stabilized, while 14 cases progressed or deteriorated. In 238 patients, KPS score and body weights were stabilized. Regarding side effects, 99 patients (36.3%) developed leukopenia; 160 patients had gastrointestinal reactions (58.6%); 80 patients (29.3%) presented with elevated ALT/AST profile; and 65 cases (23.8%) had pyrexia; however, these side effects abated quickly. No elevations in BUN/Cr and/or allergic reactions were observed. Pre- and post-intervention cardiac function did not change in all the patients. No significant change was observed in ECG. Liver function was also improved after two cycles of treatment. It was concluded that verapamil management via targeted arterial infusion could effectively reverse the multidrug resistance in cancer cells in primary hepatocellular carcinoma patients and therefore enhanced the efficacy of chemotherapy

Comparison of corporate social responsibility programmes of large international and small national hotel operators in Southeast Asia

Although the concept of Corporate Social Responsibility (CSR) has been introduced in 1979, the service industry has just recently begun to adopt CSR programmes. This study seeks to identify, compare and investigate the differences of CSR programmes in Phuket, Thailand as conducted by the Holiday Inn Phuket, which is managed by a large international hotel operator, the InterContinental Hotels Group (IHG), and the Centara Grand Beach Resort Phuket, which is managed by, a small national hotel operator, the Centara Hotels and Resorts Group (CHRG). Economic, social and environmental indicators have been selected from the Global Reporting Initiative (GRI) 3.1 guidelines and are used for the comparison of the CSR programmes in this study. IHG has guidelines, frameworks and systems at the corporate level for the individual properties to use and follow. Holiday Inn Phuket contributed to the community through donations to establish Happy Home, a children’s shelter, which is now converted to a learning centre due to changes in the Thai legislation. Holiday Inn Phuket has efforts to reduce energy consumption and promote recycling but is more focused on social initiatives, such as donations to schools and to Happy Home. CHRG engages external vendors for frameworks and guidelines to develop its CSR programmes. Centara Grand has environmental initiatives that reduce energy and water consumption. Centara Grand donates to the community and is involved in community projects together with other hotels under the Centara brand. The majority of the employees in both hotels are Thais but there are more expatriates in Centara Grand’s senior management than Holiday Inn Phuket’s. Both IHG and CHRG provide a high level of flexibility for individual properties to conduct their own initiatives, especially for social initiatives.BUSINES