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The prognostic significance of conversion into a shockable rhythm in patients who experienced out-of-hospital cardiac arrest (OHCA) with an initially nonshockable rhythm is controversial, perhaps due to the timing of rhythm conversion not being considered previously. We aimed to compare the different prognoses of patients with OHCA and early and late conversion of their rhythm into a shockable rhythm.This was a single-centre retrospective cohort study. We enrolled patients with OHCA who were sent to a medical centre in central Taiwan from 2016 to 2020. Patients18 years old, those with cardiac arrest due to trauma or a circumstantial cause, and those for whom resuscitation was not attempted were excluded. Patients were divided into two groups in accordance with presentation with an initially shockable rhythm. Those with an initially nonshockable rhythm were divided into three subgroups: early-conversion, late-conversion, and nonconversion groups. The primary outcome was the neurological functional status upon discharge from hospital.A total of 1645 patients with OHCA were included: initially shockable rhythm group, 339; early conversion group, 68; late-conversion group, 166; and nonconversion group, 1072. After adjustment, multivariate logistic regression revealed that a favourable neurological outcome was more common in the early conversion group than the nonconversion group (odds ratio [OR] 2.4; 95% confidence interval [CI], 1.1-5.3; p = 0.035), whereas the late-conversion group did not significantly differ from the nonconversion group (OR 0.5; 95% CI, 0.1-1.5; p = 0.211). The proportions of sustained return of spontaneous circulation and survival to discharge were also higher in the early conversion group than the late-conversion group (OR 2.9 95% CI 1.6-5.5, p = 0.001 and OR 4.5, 1.8-11.0, p = 0.001, respectively).In patients who experience OHCA and have an initially nonshockable rhythm, early conversion into a shockable rhythm resulted in a better prognosis, whereas late conversion was not significantly different from nonconversion.

Constitutive activation of the epidermal growth factor receptor (EGFR) signaling pathway is implicated in the initiation and progression of lung cancer. EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for nonsmall cell lung cancer (NSCLC) patients. However, acquired resistance to these agents remains a major obstacle for managing NSCLC. Here, we investigated a novel strategy to overcome EGFR TKI resistance by targeting the stanniocalcin 2 (STC2)-JUN-AXL pathway. We revealed that STC2 was expressed at significantly higher levels in EGFR TKI-resistant cells. Further, clinical analysis showed that STC2 expression was increased after the development of EGFR TKI resistance and that higher levels were correlated with shorter progression-free survival in EGFR TKI-treated lung cancer patients. Moreover, STC2 overexpression in EGFR TKI-sensitive cells resulted in EGFR TKI resistance. Conversely, genetic silencing of STC2 rendered EGFR TKI-resistant cells more sensitive to EGFR TKIs. Mechanically, STC2 enhanced AXL promoter activity by increasing the phosphorylation of c-Jun, which is an indispensable transcription factor that transactivates AXL. STC2 promoted activation of the JUN-AXL-extracellular signal-regulated kinase (ERK) signaling axis in lung cancer cells. Pharmacological or genetic inhibition of AXL-ERK activity inhibited STC2-mediated EGFR TKI resistance. We also demonstrated that PE2988 cells, a C797S-independent osimertinib-resistant primary cancer cell line from a lung cancer patient, responded to combined AXL inhibitor and osimertinib treatment. In conclusion, our research indicates that STC2 overexpression is important for acquired resistance to EGFR TKIs and that STC2-JUN-AXL-ERK signaling might be a potential therapeutic target to overcome resistance to EGFR TKIs.

From the back-end data system point of view, the primary personal information protection mechanism is to block the direct accessing of sensitive data. The possibility that sensitive data may be indirectly inferenced by public information, have not been addressed. In United States, there are cases and discussions about "Mosaic theory". And responsibilities of data holders were legally stated. But no known researches were invested to create a responsible mechanism. This research explores the functional dependencies, and compute risky column sets based on them. We can then process users’ queries and initiate protection operation if risky data are involved.

In the field of machine learning, cluster analysis has always been a very important technology for determining useful or implicit characteristics in the data. However, the current mainstream cluster analysis algorithms require comprehensive analysis of the overall data to obtain the best parameters in the algorithm. As a result, handling large-scale datasets would be difficult. This research proposes a distributed related clustering mechanism for Unsupervised Learning, which assumes that if adjacent data are similar, a group can be formed by relating to more data points. Therefore, when processing data, large-scale datasets can be distributed to multiple computers, and the correlation of any two datasets in each computer can be calculated simultaneously. Later, results are processed through aggregation and filtering before assembled into groups. This method would greatly reduce the pre-processing and execution time of the dataset; in practical application, it only needs to focus on how the relevance of the data is designed. In addition, the experimental results show the accuracy, applicability, and ease of use of this method.

Background EGFR-mutant lung cancer inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Objective To investigate the clinical relevance of microRNAs (miRNAs) in TKI therapy response and resistance. Methods We performed a miRNA PCR array analysis and used The Cancer Genome Atlas (TCGA) database to identify potential miRNAs related to EGFR TKIs resistance. We then correlated miRNA expression in 70 surgical and 50 malignant pleural effusion specimens with patient outcomes in those with non-small cell lung carcinoma. Molecular manipulation was performed in EGFR mutant lung cancer cells to assess the effect of miR-200c-3p on cell migratory ability and EGFR-TKI sensitivity. Results We identified miR-200c-3p and miR-203a-3p as potential EGFR TKI resistance regulators via their modulation of epithelial-to-mesenchymal transition (EMT). MiR-200c-3p and miR-203a-3p were down-regulated in EGFR TKI-resistant cell lines. Progression-free survival (PFS) with EGFR-TKI treatment of patients with high miR-200c-3p expression, but not miR-203a-3p, in the specimens was significantly longer than that of patients with low expression. MiR-200c-3p overexpression inhibited the EMT process in EGFR TKI resistance cell lines and promoted cell death. MiR-200c-3p silencing in EGFR TKI sensitive cell lines increased drug resistance. Conclusion MiR-200c-3p plays a role in sensitivity to EGFR TKIs via modulating EMT process.

We present the result of a search for orphan Gamma-Ray Burst (GRB) afterglows in the Pan-STARRS1 (PS1) COSMOS survey. There is extensive theoretical and observational evidence suggesting that GRBs are collimated jets; the direct observation of orphan GRB afterglows would further support this model. An optimal survey strategy is designed by coupling the PS1 survey with the Subaru/Hyper-Suprime-Cam (HSC) survey. The PS1 COSMOS survey, one of the survey fields in the PS1 Medium Deep Survey (PS1/MDS), searches a field of 7 deg$^2$ from December 2011 to January 2014, reaching a limiting magnitude R $\sim$ 23. The dense cadence of PS1/MDS is crucial for identifying transients, and the deep magnitude reached by the HSC survey (R $\sim$ 26) is important for evaluating potential GRB hosts. A transient classification method is employed to select potential orphan GRB afterglow candidates. After a thorough analysis of the transient and host galaxy properties, we conclude that there are no candidates in this survey field. The null result implies that the consideration of jet structures is essential for further orphan GRB afterglow surveys., Comment: Matches published version; 16 pages, 7 figures, 4 tables

A kinesin family member 5b (KIF5B)-MET proto-oncogene, receptor tyrosine kinase (MET) rearrangement was reported in patients with lung adenocarcinoma but its oncogenic function was not fully evaluated. We used one-step reverse transcription-polymerase chain reaction for RNA samples to screen for the KIF5B-MET fusion in 206 lung adenocarcinoma and 28 pulmonary sarcomatoid carcinoma patients. Genomic breakpoints of KIF5B-MET were determined by targeted next-generation sequencing. Soft agar colony formation assays, proliferation assays, and a xenograft mouse model were used to investigate its oncogenic activity. In addition, specific MET inhibitors were administered to evaluate their anti-tumor activities. A KIF5B-MET fusion variant in a patient with a mixed-type adenocarcinoma and sarcomatoid tumor was identified, and another case was found in a pulmonary sarcomatoid carcinoma patient. Both cases carried the same chimeric gene, a fusion between exons 1–24 of KIF5B and exons 15–21 of MET. KIF5B-MET-overexpressing cells exhibited significantly increased proliferation and colony-forming ability. Xenograft tumors harboring the fusion gene demonstrated significantly elevated tumor growth. Ectopic expression of the fusion gene stimulated the phosphorylation of KIF5B-MET as well as downstream STAT3, AKT, and ERK1/2 signaling pathways. The MET inhibitors significantly repressed cell proliferation; phosphorylation of downstream STAT3, AKT, and ERK1/2; and xenograft tumorigenicity. In conclusion, the KIF5B-MET variant was demonstrated to have an oncogenic function in cancer cells. These findings have immediate clinical implications for the targeted therapy of subgroups of non-small cell lung cancer patients.

Thanks to the advanced technology in astronomical observations, astronomers have collected massive data sets. One of the research tasks is to discover asteroids based on observational data. However, with the fast-growing volume of astronomical data sets, this task becomes enormously relied on computing power. Therefore, the cloud-enable distributed computation and super powerful computation power can offer a good solution to this field. We adopt the Hough transform to link the sequential DETECTIONs of asteroids, and also design a distributed algorithm to process this task on distributed cloud environment for flexible and efficient calculation. Our designs are developed on MapReduce and Spark frameworks. We also utilizes HDFS and HBase in order to reduce disk I/O overhead and increase reliability and scalability. The system architecture is built on the OpenStack which allocates hardware resources flexibly. Our experiment results show significant improvements of calculation time. We believe this will help astronomers to interactively access and analyze data to discover asteroids. The system can also incrementally update DETECTIONs linking with new observed data. It also provides the visual interface to inspect the linked DETECTIONs of asteroids.

Patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer show a dramatic response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired drug resistance eventually develops. This study explored the novel mechanisms related to TKI resistance. To identify the genes associated with TKI resistance, an integrative approach was used to analyze public datasets. Molecular manipulations were performed to investigate the roles of insulin-like growth factor binding protein 7 (IGFBP7) in lung adenocarcinoma. Clinical specimens were collected to validate the impact of IGFBP7 on the efficacy of EGFR TKI treatment. IGFBP7 mRNA expression in cancer cells isolated from malignant pleural effusions after acquired resistance to EGFR-TKI was significantly higher than in cancer cells from treatment-na&iuml, ve effusions. IGFBP7 expression was markedly increased in cells with long-term TKI-induced resistance compared to in TKI-sensitive parental cells. Reduced IGFBP7 in TKI-resistant cells reversed the resistance to EGFR-TKIs and increased EGFR-TKI-induced apoptosis by up-regulating B-cell lymphoma 2 interacting mediator of cell death (BIM) and activating caspases. Suppression of IGFBP7 attenuated the phosphorylation of insulin-like growth factor 1 receptor (IGF-IR) and downstream protein kinase B (AKT) in TKI-resistant cells. Clinically, higher serum IGFBP7 levels and tumors with positive IGFBP7-immunohistochemical staining were associated with poor TKI-treatment outcomes. IGFBP7 confers resistance to EGFR-TKIs and is a potential therapeutic target for treating EGFR-TKI-resistant cancers.

The intra-night trajectories of asteroids can be approximated by straight lines, and so are their intra-night detections. Therefore, the Hough transform, a line detecting algorithm, can be used to connect the line-up detections to find asteroids. We applied this algorithm to a high-cadence Pan-STARRS 1 (PS1) observation, which was originally designed to collect asteroid light curves for rotation period measurements (Chang et al., 2019). The algorithm recovered most of the known asteroids in the observing fields and, moreover, discovered 3574 new asteroids with magnitude mainly of 21.5 < w_p1 < 22.5 mag. This magnitude range is equivalent to sub-kilometer main-belt asteroids (MBAs), which usually lack of rotation period measurements due to their faintness. Using the light curves of the 3574 new asteroids, we obtained 122 reliable rotation periods, of which 13 are super-fast rotators (SRFs; i.e., rotation period of < 2 hr). The required cohesion to survive these SFRs range from tens to thousands of Pa, a value consistent with the known SFRs and the regolith on the Moon and Mars. The higher chance of discovering SFRs here suggests that sub-kilometer MBAs probably harbor more SFRs., Submitted to AJ, at 1st revise

N-myc down-regulated gene 1 (NDRG1) is a member of the NDRG family which belongs to α/β hydrolase superfamily, but without presenting a hydrolytic catalytic site. NDRG1 gene has been proposed that involved in cellular stress response pathways, including the heavy metal response, hypoxia response, DNA damage response, cellular differentiation, and proliferation. An oncogenic and tumor-promoting role of NDRG1 has been suggested in lung cancer and various malignant cancers. However, the biological functions and downstream molecular mechanisms of NDRG1 gene in lung cancer are still unclear. In this study, we detected the expression of NDRG1 in various lung adenocarcinoma cell lines using quantitative RT-PCR and Western blotting methods. The constitutive NDRG1-expression, and NDRG1-knockdown stable transfectants were established. Over-expression of NDRG1 in lung cancer cells exhibited markedly promoting in the proliferation and anchorage independent growth, whereas reduced of NDRG1 was found to suppress lung cancer cell progression. We also indicated that NDRG1 play an important role in the epithelial-mesenchymal transition (EMT) features, including a morphological change, increased migratory and invasive ability, reduction the epithelial marker expression and up-regulated EMT regulators. In addition, microarray assays were performed to further explore the potential molecular mechanisms of NDRG1 in lung cancer. The candidate NDRG1-regulated genes, including IL11, SOX7, TCF4, IGF2, SLUG and SLIT2, were verified by quantitative RT- PCR. Finally, we demonstrated that NDRG1 induces EMT and invasion process in lung cancer cell through up-regulation SLUG expression. These results will provide information and help us to understand the roles of NDRG1 in lung cancer cells. Citation Format: En-Chu Liu, Hui-Chia Liu, Jeremy J. M. Chen, Meng-Feng Tsai. NDRG1 promotes epithelial-mesenchymal transition in lung cancer cells by upregulation of SLUG expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1539.