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Lung cancer is considered the number one cause of cancer-related deaths worldwide. Although current treatments initially reduce the lung cancer burden, relapse occurs in most cases; the major causes of mortality are drug resistance and cancer stemness. Recent investigations have provided evidence that shikonin generates various bioactivities related to the treatment of cancer. We used shikonin to treat multi-resistant non-small lung cancer cells (DOC-resistant A549/D16, VCR-resistant A549/V16 cells) and defined the anti-cancer efficacy of shikonin. Our results showed shikonin induces apoptosis in these ABCB1-dependent and independent chemoresistance cancer sublines. Furthermore, we found that low doses of shikonin inhibit the proliferation of lung cancer stem-like cells by inhibiting spheroid formation. Concomitantly, the mRNA level and protein of stemness genes (Nanog and Oct4) were repressed significantly on both sublines. Shikonin reduces the phosphorylated Akt and p70s6k levels, indicating that the PI3K/Akt/mTOR signaling pathway is downregulated by shikonin. We further applied several signaling pathway inhibitors that have been used in anti-cancer clinical trials to test whether shikonin is suitable as a sensitizer for various signaling pathway inhibitors. In these experiments, we found that low doses shikonin and dual PI3K-mTOR inhibitor (BEZ235) have a synergistic effect that inhibits the spheroid formation from chemoresistant lung cancer sublines. Inhibiting the proliferation of lung cancer stem cells is believed to reduce the recurrence of lung cancer; therefore, shikonin's anti-drug resistance and anti-cancer stem cell activities make it a highly interesting molecule for future combined lung cancer therapy. [ABSTRACT FROM AUTHOR]

(1) Background: We aimed to evaluate the risk of hepatitis B virus (HBV) reactivation in lung cancer patients treated with tyrosine kinase inhibitor (TKI), particularly in those with resolved HBV infection. (2) Methods: In this retrospective hospital-based cohort study, we screened all lung cancer patients with positive hepatitis B core antibodies (anti-HBc) receiving systemic antineoplastic treatment during the period from January 2011 to December 2020. Cumulative incidences of HBV reactivation, and their hazard ratios (HRs), were evaluated after adjusting patient mortality as a competing risk. (3) Results: Among 1960 anti-HBc-positive patients receiving systemic therapy, 366 were HBsAg-positive and 1594 were HBsAg-negative. In HBsAg-positive patients without prophylactic NUC, 3-year cumulative incidences of HBV reactivation were similar between patients receiving chemotherapy and patients receiving TKI (15.0%, 95% confidence interval (CI): 0–31.2% vs. 21.2%, 95% CI: 10.8–31.7%; p = 0.680). Likewise, 3-year cumulative incidences of HBV-related hepatitis were similar between the two groups (chemotherapy vs. TKI: 15.0%, 95% CI: 0–31.2% vs. 9.3%, 95% CI: 2.8–15.7%; p = 0.441). In 521 HBsAg-negative TKI users, the 3-year cumulative incidence of HBV reactivation was only 0.6% (95% CI: 0.0–1.9%). From multivariable regression analysis, we found that the only independent risk factor for HBV reactivation in TKI users was HBsAg positivity (HR 53.8, 95% CI: 7.0–412.9; p < 0.001). (4) Conclusion: Due to high risks of HBV reactivation in HBsAg-positive TKI users, NUC prophylaxis can be considered. However, in patients with resolved HBV infection, such risks are lower, and therefore regular monitoring is recommended. [ABSTRACT FROM AUTHOR]

This study aimed to challenge chemoresistance by curcumin (CUR) with drug-selected human lung cancer A549 sublines that continuously proliferate in the present of docetaxel (DOC) and vincristine (VCR). Their sensitivities to CUR were measured by MTT assay and the particular intracellular reactive oxygen species (ROS) was detected by fluorescence activated cell sorting (FACS) analysis. Apoptosis was analyzed by Annexin V assay of the flow cytometry. Inhibitors and RNA interference were used to examine the signaling pathway regulated by the kinases. The obtained data demonstrated that CUR induces chemoresistant cell apoptosis by generating ROS and application of N-acetylcysteine (NAC) blocks ROS production, resulting in apoptosis suppression. Phosphorylation of extracellular regulated kinase (ERK), p38 MAPK, and eIF-2α were increased but c-Jun N-terminal kinase (JNK) did not increase when chemoresistant cells were treated with CUR. Downregulation of ERK and p38 MAPK phosphorylation by their inhibitors had no effect on CUR-induced apoptosis. Interestingly, the knockdown of p38 MAPK with shRNA significantly reduced CUR-induced apoptosis on the chemoresistant sublines. Phosphorylation of the eIF-2α protein was inhibited when p38 MAPK was knocked down in DOC-resistant A549 cells, but a high level of phosphorylated eIF-2α protein remained on the VCR-resistant A549 cells when p38 MAPK was knocked down. These data confirmed that CUR-augmented ROS potently induced apoptosis via upregulated p38 MAPK phosphorylation. Therefore, activated p38 MAPK is considered a pro-apoptotic signal for CUR-induced apoptosis of chemoresistant human lung cancer cells. [ABSTRACT FROM AUTHOR]

Background and Objectives: Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is one of the standard-of-care therapies in patients with EGFR-mutant lung adenocarcinoma; however, acquired resistance inevitably developed. Despite the proposition of histological transformation being one of the resistance mechanisms, its incidence and influence on outcome remain unclear. Materials and Methods: This was a retrospective study conducted at Taichung Veterans General Hospital on patients with advanced EGFR-mutant lung adenocarcinoma receiving the third-generation EGFR-TKI. Only patients receiving rebiopsy were included in the analysis. Results: A total of 55 patients were studied. Eight patients (14.5%) showed histological transformation, including three small cell carcinoma, three squamous cell carcinoma, one large cell neuroendocrine carcinoma, and one with a mixture of adenocarcinoma and squamous cell carcinoma components. The median treatment duration of the third-generation EGFR-TKI before rebiopsy was numerically longer in patients with histological transformation than those without (16.0 vs. 10.9 months). Both the overall survival time from the start of third-generation EGFR-TKI initiation (30.8 vs. 41.2 months) and from rebiopsy (6.6 vs. 12.9 months) to mortality were numerically shorter amongst the transformed population. All patients in the transformed group did not respond to the next line of systemic treatment. One patient with histological transformation receiving local treatment for the metastatic site had a longer overall survival. Conclusions: Repeating biopsy to identify histological transformation should be considered in patients with progression to the third-generation EGFR-TKI. Histological transformations could contribute to the acquired resistance with the implication of a worse prognosis. Further studies are needed to determine the optimal therapy for these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Leptomeningeal metastasis (LM) is a devastating complication of lung cancer, with a generally poor outcome. We conduct the present study to evaluate the association between clinical presentations, brain images, tumor cell counts of the cerebrospinal fluid (CSF), and the epidermal growth factor receptor (EGFR) mutation detection rate in CSF among EGFR-mutant lung adenocarcinoma patients with LM and accessed the influence of the timing of LM occurrence on patient outcomes. Tumor cell numbers were semi-quantified according to tumor cells per high power field of CSF cytological slides. Radiological burden was assessed using a four-point scoring system, which evaluated LM-involved areas on brain magnetic resonance imaging. Our results suggest the association between the radiological severity score of LM, CSF tumor cell counts, and EGFR mutation detection rate in CSF. Furthermore, LM prior to first-line EGFR-tyrosine kinase inhibitor treatment was associated with an independently worse outcome. Background: We aim to evaluate the influence of the timing of leptomeningeal metastasis (LM) occurrence on the outcome of EGFR-mutant lung adenocarcinoma and to explore the predictors of detectable EGFR mutation in the cerebrospinal fluid (CSF). Methods: EGFR-mutant lung adenocarcinoma patients with cytologically confirmed LM were included for analysis. EGFR mutation in CSF was detected by MALDI-TOF MS plus PNA. Results: A total of 43 patients was analyzed. Of them, 8 (18.6%) were diagnosed with LM prior to first-line EGFR-TKI treatment (early onset), while 35 patients (81.4%) developed LM after first-line EGFR-TKI treatment (late onset). Multivariate analysis suggested that both late-onset LM (aHR 0.31 (95% CI 0.10–0.94), p = 0.038) and a history of third-generation EGFR-TKI treatment (aHR 0.24 (95% CI 0.09–0.67), p = 0.006) independently predicted a favorable outcome. EGFR mutation detection sensitivity in CSF was 81.4%. The radiological burden of LM significantly correlated with CSF tumor cell counts (p = 0.013) with higher CSF tumor cell counts predicting a higher detection sensitivity of EGFR mutation (p = 0.042). Conclusions: Early onset LM was an independently poor prognostic factor. A higher radiological severity score of LM could predict higher tumor cell counts in CSF, which in turn were associated with a higher detection rate of EGFR mutation. [ABSTRACT FROM AUTHOR]

In recent years, Taiwan's government has focused on policies regarding offshore wind farming near the Indo-Pacific humpback dolphin habitat, where marine mammal observation is a critical consideration. The present research developed an algorithm called National Taiwan University Passive Acoustic Monitoring (NTU_PAM) to assist marine mammal observers (MMOs). The algorithm performs whistle detection processing and whistle localization. Whistle detection processing is based on image processing and whistle feature extraction; whistle localization is based on the time difference of arrival (TDOA) method. To test the whistle detection performance, we used the same data to compare NTU_PAM and the widely used software PAMGuard. To test whistle localization, we designed a real field experiment where a sound source projected simulated whistles, which were then recorded by several hydrophone stations. The data were analyzed to locate the moving path of the source. The results show that localization accuracy was higher when the sound source position was in the detection region composed of hydrophone stations. This paper provides a method for MMOs to conveniently observe the migration path and population dynamics of cetaceans without ecological disturbance. [ABSTRACT FROM AUTHOR]

Many studies have shown that the weather greatly affects the tourist count. Understanding weather information, climate change, and how they influence the tourist count in different tourist seasons (peak season, second peak season, off season) can help park planners and managers to analyze the opportunities and risks caused by climate change. This study aimed to predict the visitor count through information on the number of visitors and the weather day for three tourist seasons in a 12-month period. The study was conducted in the Huisun Forest Park of Taiwan based on the peak season (February, July, August, and October), the second peak season (January, April, May, November, and December), and the off-season (March, June, and September), using weather factors and virtual factors (such as whether it is a weekend or not) to establish three multivariate regression models for predicting the daily visitor count. This study assessed the impact of climate change on the visitor count and analyzed possible scenarios of climate change using representative concentration pathways (RCPs), as stated in the fifth assessment report of the Intergovernmental Panel on Climate Change (IPCC). The results of this study indicated that the impacts of weather factors on the visitor count is the same for the peak season and the off season. The temperature and relative humidity have a significant impact on the visitor count, and precipitation is not significant. In the second peak season, only the temperature has a significant impact on the visitor count. The relative humidity and precipitation are not significant. The temperature is the most influential factor in all three seasons, and has the highest influence on the peak season, followed by the low season, and then the second peak season. In addition, the number of visitors in Huisun Forest Park is on the rise, according to an analysis of various climate change scenarios (RCP2.6, RCP4.5, RCP6.0, RCP8.5). The results of this study can be used as a reference by forest park managers and future researchers. It is noted that the results were based on the current economic and political situation. The worsening of the entire world situation could break the relationships. [ABSTRACT FROM AUTHOR]

Stereo vision utilizes two cameras to acquire two respective images, and then determines the depth map by calculating the disparity between two images. In general, object segmentation and stereo matching are some of the important technologies that are often used in establishing stereo vision systems. In this study, we implement a highly efficient self-organizing map (SOM) neural network hardware accelerator as unsupervised color segmentation for real-time stereo imaging. The stereo imaging system is established by pipelined, hierarchical architecture, which includes an SOM neural network module, a connected component labeling module, and a sum-of-absolute-difference-based stereo matching module. The experiment is conducted on a hardware resources-constrained embedded system. The performance of stereo imaging system is able to achieve 13.8 frames per second of 640 × 480 resolution color images. [ABSTRACT FROM AUTHOR]