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Through the use of SPPs, we were able to offer combination therapy targeting <i>MET</i>-amplified resistance identified on the first-in-human study of selpercatinib. These data suggest that MET dependence is a recurring and potentially targetable mechanism of resistance to selective RET inhibition in advanced NSCLC.

We examine performance impact on management by investigating whether information on past organizational performance (‘performance feedback’) influences future managerial quality. We employ a regression discontinuity design to analyse the performance and managerial quality of Korean metropolitan governments’ utility services. We find that (1) providing performance feedback improves managerial quality, but this impact is observed only among low-performing organizations, and (2) the impact of perfo

Assembly of RAS molecules into complexes at the cell membrane is critical for RAS signaling. We previously showed that oncogenic KRAS codon 61 mutations increase its affinity for RAF, raising the possibility that KRAS^Q61H, the most common KRAS mutation at codon 61, upregulates RAS signaling through mechanisms at the level of RAS assemblies. We show here that KRAS^Q61H exhibits preferential binding to RAF relative to PI3K in cells, leading to enhanced MAPK signaling in <i>in

While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 t

Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa) development. Oestradiol (E₂ ) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin (K14) promoter. E₂ mainly functions through oestrogen receptor α (ERα). However, the role of ERα in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERα-co

Data mining is a process of discovering useful patterns or information from large amount of data. Decision tree is one of the data mining algorithms that can be used for both classification and prediction and has been widely used for various applications because of its flexibility and interpretability. Decision trees for classification generally generate a number of rules that belong to one of the predefined category and some rules may belong to the same category. In this case, it is necessary t

This study examines the relationship between pronunciation assessment (PRN) and speaking performance (SPK) among Korean learners of Spanish, based on the “Korean Learners’ Spanish Speech Corpus” provided by AI Hub in Korea. The research aims to investigate how automatically generated pronunciation scores relate to actual speaking indicators, and whether this relationship varies depending on learners’ language proficiency. To this end, the study addresses the following research questions: (1) Do

&lt;div&gt;Abstract&lt;p&gt;In-frame insertions in exon 20 of HER2 are the most common &lt;i&gt;HER2&lt;/i&gt; mutations in patients with non–small cell lung cancer (NSCLC), a disease in which approved EGFR/HER2 tyrosine kinase inhibitors (TKI) display poor efficiency and undesirable side effects due to their strong inhibition of wild-type (WT) EGFR. Here, we report a HER2-selective covalent TKI, JBJ-08–178–01, that targets multiple &lt;i&gt;HER2&lt;/i&gt; activating mutations, including exon 20

Abstract Estradiol (E2) and human papillomavirus (HPV) cooperate to cause cervical cancer. The role of estrogen receptor α (ERα) in cervical cancer has been underappreciated. Chronic treatment with E2 promotes the development of cervical cancer in K14E7 transgenic mice expressing HPV16 E7 oncoprotein. In the present study, we bred K14E7 to mice with conditional ablation of Esr1 (ERα-coding gene) in the cervical epithelial cells (Wnt7aCre/Esr1f/f; Esr1ed/ed). We found that E2 promoted the develop

Supplementary Data from A Novel HER2-Selective Kinase Inhibitor Is Effective in HER2 Mutant and Amplified Non–Small Cell Lung Cancer

&lt;div&gt;Abstract&lt;p&gt;In-frame insertions in exon 20 of HER2 are the most common &lt;i&gt;HER2&lt;/i&gt; mutations in patients with non–small cell lung cancer (NSCLC), a disease in which approved EGFR/HER2 tyrosine kinase inhibitors (TKI) display poor efficiency and undesirable side effects due to their strong inhibition of wild-type (WT) EGFR. Here, we report a HER2-selective covalent TKI, JBJ-08–178–01, that targets multiple &lt;i&gt;HER2&lt;/i&gt; activating mutations, including exon 20

Supplementary Data from A Novel HER2-Selective Kinase Inhibitor Is Effective in HER2 Mutant and Amplified Non–Small Cell Lung Cancer