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Simple Summary: The demand for multitarget-directed anticancer agents has been steadily increasing, as cancer remains a leading cause of death worldwide. Dyrk and Clk kinases play crucial roles in cancer cell division and survival. Our study presents novel Dyrk1/Dyrk1B/Clk1 inhibitors, developed by modifying our previous class of Clk1 inhibitors. These potent new inhibitors successfully halted the division of cancer cells without impacting normal cells. Additionally, we examined the effect of these compounds on the cell cycle to identify the specific phase affected. Finally, our compounds demonstrated the ability to activate pathways that induce cell death in cancer cells. Numerous studies have reported that Dyrk1A, Dyrk1B, and Clk1 are overexpressed in multiple cancers, suggesting a role in malignant disease. Here, we introduce a novel class of group-selective kinase inhibitors targeting Dyrk1A, Dyrk1B, and Clk1. This was achieved by modifying our earlier selective Clk1 inhibitors, which were based on the 5-methoxybenzothiophene-2-carboxamide scaffold. By incorporating a 5-hydroxy group, we increased the potential for additional hydrogen bond interactions that broadened the inhibitory effect to include Dyrk1A and Dyrk1B kinases. Within this series, compounds 12 and 17 emerged as the most potent multi-kinase inhibitors against Dyrk1A, Dyrk1B, and Clk1. Furthermore, when assessed against the most closely related kinases also implicated in cancer, the frontrunner compounds revealed additional inhibitory activity against Haspin and Clk2. Compounds 12 and 17 displayed high potency across various cancer cell lines with minimal effect on non-tumor cells. By examining the effect of these inhibitors on cell cycle distribution, compound 17 retained cells in the G2/M phase and induced apoptosis. Compounds 12 and 17 could also increase levels of cleaved caspase-3 and Bax, while decreasing the expression of the antiapoptotic Bcl-2 protein. These findings support the further study and development of these compounds as novel anticancer therapeutics. [ABSTRACT FROM AUTHOR]

Virtual reality (VR) is a 3D space created by computer graphics technology and immersive devices. In addition to providing a new visual experience, users can also interact with others in the virtual world to address any of their needs. In recent years, the application of virtual reality in the field of education has attracted the attention of more and more people. This study combined virtual reality and concepts of spatial memory in wayfinding and memory palace to develop a VR memory maze learning system based on the seven large-scale expedition voyages of Zheng He (1405–1433) in the early Ming Dynasty of imperial China. The objective is to improve memory and efficiency in learning social science by correlating spatial information and organizational skills in the virtual environment. A teaching experiment has been conducted to explore its impacts on learning effectiveness, learning motivation, and cognitive load, as well as learners' technology acceptance of the VR system. The analysis results indicate that using the VR system for learning social science can improve learning effectiveness; it can also increase learning motivation and reduce cognitive load. The questionnaire results of the technology acceptance model analysis show that most learners were satisfied with various aspects of this system. [ABSTRACT FROM AUTHOR]

A continuous increase in follicular lymphoma has been observed in Taiwan, Japan, and South Korea over the last few decades. This study aimed to evaluate the difference in incidence trends of follicular lymphoma in Taiwan, Japan, and South Korea between 2001 and 2019. The data for the Taiwanese populations was obtained from the Taiwan Cancer Registry Database, and those for the Japanese and Korean population were retrieved from the Japan National Cancer Registry and some additional reports, both of which included population-based cancer registry data, from Japan and Korea. Follicular lymphoma accounted for 4231 cases from 2002–2019 in Taiwan, 3744 cases from 2001–2008 and 49,731 cases from 2014–2019 in Japan; and 1365 cases from 2001–2012 and 1244 cases from 2011–2016 in South Korea. The annual percentage change for each time period was 3.49% (95% confidence interval: 2.75–4.24%) in Taiwan, 12.66% (95% confidence interval [CI]: 9.59–15.81%) and 4.95% (95% CI: 2.14–7.84%) in Japan, and 5.72% (95% CI: 2.79–8.73%) and 7.93% (95% CI: −1.63–18.42%) in South Korea. Our study confirms that the increasing trends of follicular lymphoma incidence in Taiwan and Japan have been remarkable in recent years, especially the rapid increase in Japan between 2014 and 2019; however, there was no significant in-crease from 2011 to 2015 in South Korea. [ABSTRACT FROM AUTHOR]

Globally, there are over half a million new patients with head and neck squamous cell carcinomas (HNSCC) every year. The current therapeutic approaches to HNSCC are surgery and adjuvant radiotherapy. These approaches carry a high incidence of metastasis or recurrence from HNSCC cells' radioresistance. Recent studies have revealed that a combination with radiosensitizers can be used to improve the radioresistance in HNSCC; however, few agents are approved as radiosensitizers. The constitutive activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a vitally oncogenic type of signaling that promotes tumorigenesis, metastasis, and radiotherapy resistance in HNSCC. Pharmacological targeting of PI3K/AKT/mTOR signaling pathway is considered a promising strategy of radiosensitization in HNSCC. In this review, we summarize the oncogenic significance of PI3K/AKT/mTOR signaling in HNSCC with radiotherapy resistance and highlight the therapeutic potential of small molecule inhibitors against PI3K/AKT/mTOR signaling for the radiosensitization in HNSCC treatment. It provides a mechanistic framework for the development of new drugs for radiosensitization in HNSCC radiotherapy via targeting PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Surgery for acute mesenteric infarction (AMI) is associated with high mortality. This study aimed to generate a mortality prediction model to predict the 30-day mortality of surgery for AMI. We included patients ≥18 years who received bowel resection in treating AMI and randomly divided into the derivation and validation groups. After multivariable analysis, the 'Surgery for acute mesenteric infarction mortality score' (SAMIMS) system was generated and was including age >62-year-old (3 points), hemodialysis (2 points), congestive heart failure (1 point), peptic ulcer disease (1 point), diabetes (1 point), cerebrovascular disease (1 point), and severe liver disease (4 points). The 30-day-mortality rates in the derivation group were 4.4%, 13.4%, 24.5%, and 32.5% among very low (0 point), low (1–3 point(s)), intermediate (4–6 points), and high (7–13 points)-risk patients. Compared to the very-low-risk group, the low-risk (OR = 3.332), intermediate-risk (OR = 7.004), and high-risk groups (OR = 10.410, p < 0.001) exhibited higher odds of 30-day mortality. We identified similar results in the validation group. The areas under the ROC curve were 0.677 and 0.696 in the derivation and validation groups. Our prediction model, SAMIMS, allowed for the stratification of the patients' 30-day-mortality risk of surgery for acute mesenteric infarction. [ABSTRACT FROM AUTHOR]

In clinical practice, the Ishak Score system would be adopted to perform the evaluation of the grading and staging of hepatitis according to whether portal areas have fibrous expansion, bridging with other portal areas, or bridging with central veins. Based on these staging criteria, it is necessary to identify portal areas and central veins when performing the Ishak Score staging. The bile ducts have variant types and are very difficult to be detected under a single magnification, hence pathologists must observe bile ducts at different magnifications to obtain sufficient information. This pathologic examinations in routine clinical practice, however, would result in the labor intensive and expensive examination process. Therefore, the automatic quantitative analysis for pathologic examinations has had an increased demand and attracted significant attention recently. A multi-scale inputs of attention convolutional network is proposed in this study to simulate pathologists' examination procedure for observing bile ducts under different magnifications in liver biopsy. The proposed multi-scale attention network integrates cell-level information and adjacent structural feature information for bile duct segmentation. In addition, the attention mechanism of proposed model enables the network to focus the segmentation task on the input of high magnification, reducing the influence from low magnification input, but still helps to provide wider field of surrounding information. In comparison with existing models, including FCN, U-Net, SegNet, DeepLabv3 and DeepLabv3-plus, the experimental results demonstrated that the proposed model improved the segmentation performance on Masson bile duct segmentation task with 72.5% IOU and 84.1% F1-score. [ABSTRACT FROM AUTHOR]

Lymphatic metastasis is a biological procedure associated with the pathogenesis of several diseases, especially in tumor metastasis. Therefore, regulation of lymphangiogenesis has become a promising strategy for cancer therapy. In this study, we aimed to investigate the anti-lymphangiogenic effect of heteronemin (SP-1) isolated from the sponge Hyrtios sp. in vitro and in vivo. Human lymphatic endothelial cells (LECs) were utilized to evaluate the anti-lymphangiogenic effect of SP-1 in vitro. Molecular docking, western blotting, flow-cytometry, MTT and ELISA were performed to investigate the mechanism of action. For in vivo approaches, the transgenic (fli1:EGFP; gata1:DsRed) zebrafish and mouse ear sponges were used. Molecular docking studies showed that SP-1 is a potent vascular endothelial growth factor receptor 3 (VEGFR-3)-binding compound. Treatment of LEC with SP-1 reduced the phosphorylation of VEGFR-3. SP-1 suppressed the development of the thoracic duct in zebrafish and mouse lymphangiogenesis ear sponges in vivo. Mechanistically, SP-1 induced the cell cycle arrest of LECs in the G0/G1 phase and reduced the downstream of VEGFR-3, such as phosphorylated MEK/ERK and NF-κB. In addition, SP-1 inhibited LECs' tubulogenesis and migration through the ARF-1 and MMP-9/VE-cadherin/vimentin. Overall, anti-lymphangiogenic properties of SP-1 occur by downregulating the VEGFR-3 cascade, ARF-1 and MMP-9/VE-cadherin/vimentin. Collectively, these results proposed that SP-1 might be a potential candidate for the treatment of lymphangiogenesis-associated diseases. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the influence of social support on the survival outcomes of patients with nasopharyngeal carcinoma (NPC). We examined whether the combined proxy influenced whether patients were more likely to receive radiotherapy. Methodology: data were collected from the 18 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results database. The association between both insurance status and marital status and disease-specific survival rates were evaluated with a multivariate Cox proportional-hazards regression model to calculate the hazard ratios and associated confidence intervals. Odds ratio (OR) computed by logistic regression was also used to examine the relationship between the receipt of radiotherapy and insurance and marital status. Results: insured and uninsured patients differed significantly in T-stage, N-stage, M-stage, radiotherapy use, race, and marital status. The uninsured-non-married patients showed the lowest 5-year disease-specific survival rates. We further found unmarried patients with either Medicaid (OR, 0.40), or no insurance (OR, 0.24) had lower odds of receiving radiotherapy than those with insurance at diagnosis. Conclusions: uninsured-unmarried NPC patients had a significantly higher risk of distant metastasis at diagnosis, poorer 5-year disease-specific survival, and were less likely to receive radiotherapy than insured-married patients. [ABSTRACT FROM AUTHOR]

We hypothesized that sorafenib plus transarterial chemoembolization (TACE) would confer survival benefits over sorafenib alone for advanced hepatocellular carcinoma (aHCC). We investigated this while using the population-based All-Cancer Dataset to assemble a cohort (n = 3674; median age, 60; 83% men) of patients receiving sorafenib for aHCC (Child-Pugh A) with macro-vascular invasion or nodal/distant metastases. The patients were classified into the sorafenib-TACE group (n = 426) or the propensity score-matched sorafenib-alone group (n = 1686). All of the participants were followed up until death or the end of the study. Time-dependent Cox model and the Mantel–Byar test were used for survival analysis. During the median follow-ups of 221 and 133 days for the sorafenib-TACE and sorafenib-alone groups, 164 (39%) and 916 (54%) deaths occurred, respectively; the corresponding median overall survivals (OS) were 381 and 204 days, respectively (hazard ratio, HR: 0.74; 95% confidence interval, CI, 0.63–0.88; p = 0.021). The one-year and six-month OS were 53.5% and 80.3% in the sorafenib-TACE group and 32.4% and 54.4% in the sorafenib-alone group, respectively. The major complications were comparable between the two groups. The addition of TACE to sorafenib improves survival, with a 26% reduction in mortality. These findings provide strong real-world evidence that supports this combination strategy for eligible Child-Pugh A aHCC patients. [ABSTRACT FROM AUTHOR]