Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials

Background and objectives: Targeted therapy is widely used in the era of precision medicine. Whether the sequence in which targeted therapy and chemotherapy are performed matters, is however not known. We examined the impact of the sequential treatment of targeted therapy and chemotherapy among advanced anaplastic lymphoma kinase (ALK), non-small cell lung cancer (NSCLC) patients. Materials and Methods: Randomized controlled trials comparing the use of ALK inhibitors with chemotherapy were included in this meta-analysis. We estimated the hazard ratios (HRs) and 95% confidence intervals (CI), for progression-free survival (PFS) and overall survival (OS) from a random effects model. Two-sided statistical tests were used to determine the significance of these estimates. Results: In five eligible studies (1404 patients), ALK targeted therapy, in comparison with chemotherapy, had a significantly higher PFS (HR = 0.48; 95% CI, 0.42(-)0.55), but not significantly higher OS (HR = 0.88; 95% CI, 0.72(-)1.07). Crossover from chemotherapy to ALK inhibitors was allowed after progression in all trials. The sensitivity analysis of the use of ALK inhibitors as either the first- or second-line treatment, showed improvements in PFS but not in OS. Conclusions: Our results indicate that using targeted therapy first improved PFS, but that the sequence in which the treatments were performed did not cause a significant difference in overall survival

The Identification Of Squillid Mantis Shrimp And Preliminary Study On Reproduction And Larviculture Of Oratosquillina Interrupta Found In Penang Waters

Stomatopods or mantis shrimps were historically sold as cheap by-catches. Presently, with increased economic importance in various countries and it is commercially captured for its unique taste and texture. Mantis shrimp has a potential for local aquaculture practices. This study focuses on assessing optimal breeding protocol and determination of larval developmental stages, particularly for the mantis shrimp Oratosquillina interrupt

Functional characterization of RGA downstream targets in the GA signaling pathway

Ph.DDOCTOR OF PHILOSOPH

A Holographic Theory for the Phase Transitions Between Fermionic Symmetry-protected Topological States

In an earlier work we developed a holographic theory for the phase transition between bosonic symmetry-protected topological (SPT) states. This paper is a continuation of it. Here we present the holographic theory for fermionic SPT phase transitions. We show that in any dimension $d$, the critical states of fermionic SPT phase transitions has an emergent $Z_2^T$ symmetry and can be realized on the boundary of a $d+1$-dimensional bulk SPT with an extra $Z_2^T$ symmetry.Comment: 35 pages, 10 figure

Insertion of sequences at the original provirus integration site of mouse ROSA26 locus using the CRISPR/Cas9 system.

Targeted transgenic mouse models, where an exogenous gene is inserted into a specified genomic locus to achieve its stable and reliable expression, have been widely used in biomedical research. However, the available methodologies for targeted insertion of sequences require many laborious steps that involve the use of embryonic stem (ES) cells. We recently developed Pronuclear Injection-based Targeted Transgenesis (PITT), a method that uses a recombinase-mediated cassette exchange (RMCE) to enable insertion of sequences at a predetermined genomic locus, such as ROSA26. The PITT technique uses fertilized eggs (instead of ES cells) collected from \u27seed mice\u27 that contain the RMCE landing pad. The PITT method can rapidly generate reliable targeted transgenic mice; it requires a seed mouse, which in our previous study was generated using ES cell targeting approaches. Here, we demonstrate that seed mice containing the RMCE landing pad can be developed rapidly by using the CRISPR/Cas9 system. One of the CRISPR targets tested in this study enabled the insertion of sequences precisely at the original ROSA26 provirus integration site. We anticipate that using a similar approach, PITT landing pad sequences can be rapidly and precisely inserted at other genomic loci to develop an array of PITT tools. This two-step strategy combines the best features of the two newer technologies-rapid creation of PITT landing pads using the CRISPR/Cas9 system and efficient and precise insertion of larger cassettes at the landing pads using PITT. This study also revealed that anomalous and mosaic sequence insertions can occur with the CRISPR/Cas9 system

Girdling improved berry coloration in summer but suppressed return growth in the following spring in 'Kyoho' grapevines cultivated in the subtropical double cropping system

Improving berry skin coloration is one of the major challenges in the tropical and subtropical viticulture. In this paper we aimed to document the effects of girdling at veraison on berry coloration and quality in grapevines on different rootstocks and we assessed the seasonal variations of girdling effects in the subtropical double cropping system. In the first experiment, gird-ling at veraison was tested in 'Kyoho' on 5C rootstocks. In the second experiment, own-rooted 'Kyoho', 5C or 1202C rootstocks were compared. Vines were trained to a horizontal overhead trellis with a single trunk and two short arms. One arm of each vine was girdled at veraison and the other arm served as the control. Girdling at veraison significantly improved skin color of berries from own-rooted vines or 5C rootstocks in the summer cropping cycle but was less effective in the winter cropping cycle. Girdling improved total soluble solids in own-rooted vines in the summer cropping cycle and in vines on 1202C in the winter cropping cycle. Girdling made in the winter cropping cycle did not completely heal until post-bloom in the following spring and reduced length of the fruiting shoot, number of leaves per shoot, and length of inflorescences of the next summer cropping cycle. We concluded that girdling at veraison is a good practice to improve berry color and quality for the summer cropping cycle but is not recommended for the winter cropping cycle