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Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are the standard treatment for patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. This study aimed to evaluate the efficacy of EGFR‐TKIs and prognostic factors for patients with NSCLC harboring uncommon EGFR mutations, which account for 10% of EGFR mutations. Methods A total of 230 treatment‐naive patients with NSCLC harboring uncommon EGFR mutations treated with first‐line EGFR‐TKIs between 2011 and 2018 at four hospitals (belonging to four institutions, Linkou, Kaohsiung, Keelung, and Chiayi, of the Chang Gung Memorial Hospital) in Taiwan were retrospectively reviewed. Their clinicopathological characteristics, adverse events (AEs), objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS) were collected. Univariate and multivariate analyses were performed to identify potential prognostic factors for PFS. Results Overall, patients who received afatinib (n = 62) had better PFS (median: 6.4 vs. 5.9 months, p = 0.022) and OS (median: 13.4 vs. 13.0 months, p = 0.008) than those who received gefitinib/erlotinib (n = 124), although no significant differences were observed for ORR (46.8% vs. 35.5%, p = 0.137) or DCR (59.7% vs. 58.9%, p = 0.916). Patients who received afatinib showed significantly higher ORR (58.3% vs. 31.3%, p = 0.027) but not DCR compared with gefitinib/erlotinib for major uncommon mutations. Afatinib trended toward better PFS and OS for major uncommon mutations and compound mutations. No EGFR‐TKIs were effective for most NSCLC patients with exon 20 insertions. Performance status, metastasis of the liver and pleura, and dose reduction were independent prognostic factors for PFS. Conclusion Afatinib demonstrated better survival outcomes than gefitinib/erlotinib for NSCLC patients harboring major EGFR uncommon mutations and compound mutations. Performance status and metastatic sites may be useful for predicting PFS for major uncommon mutations and compound mutations.

Abstract Background This study aimed to evaluate possible treatment strategies for patients with de novo T790M mutation‐positive (T790M+) non‐small‐cell lung cancer (NSCLC). Methods Patients diagnosed with de novo T790M+ NSCLC and treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) between 2011 and 2018 at a regional hospital in Taiwan were retrospectively reviewed. Their clinicopathological characteristics and subsequent treatment information were collected, and potential prognostic factors were identified using univariate and multivariate analyses. Results All tumors with T790M mutations coexisted with sensitizing mutations. Through the last follow‐up in May 2021, afatinib and osimertinib demonstrated better progression‐free survival (PFS, p

Abstract Comparison of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy or with bevacizumab in real-world non-small cell lung cancer (NSCLC) patients was lacking. 310 patients of advanced NSCLC with common EGFR mutation receiving first-generation EGFR-TKI monotherapy or with bevacizumab were included and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutation were analysed. Patients receiving EGFR-TKI and bevacizumab were significantly younger, had better performance status and with high incidence of brain metastasis (55.8%). In the propensity-score matched cohort, PFS (13.5 vs. 13.7 months; log-rank p = 0.700) was similar between the two groups. The OS (61.3 vs. 34.2 months; log-rank p = 0.010) and risk reduction of death (HR 0.42 [95% CI 0.20–0.85]; p = 0.017) were significantly improved in EGFR-TKI plus bevacizumab group. Analysis of treatment by brain metastasis status demonstrated EGFR-TKI plus bevacizumab in patients with brain metastasis was associated with significant OS benefit compared to other groups (log-rank p = 0.030) and these patients had lower early-CNS and early-systemic progressions. The secondary T790M did not significantly differ between EGFR-TKI plus bevacizumab and EGFR-TKI monotherapy groups (66.7% vs. 75.0%, p = 0.460). Forty-one (31.1%) and 31 (23.5%) patients received subsequent osimertinib and chemotherapy, respectively. The post-progression OS of osimertinib and chemotherapy were 22.1 and 44.9 months in EGFR-TKI plus bevacizumab group and were 10.0 and 14.1 months in EGFR-TKI monotherpay group, respectively. First-generation EGFR-TKI with bevacizumab improved treatment efficacy in real-world patients of NSCLC with EGFR mutation. Patients with brain metastasis received additional OS benefit from this treatment.

Coronary artery ectasia (CAE) is a rare vascular phenotype characterized by abnormal dilation of blood vessels and disruption of coronary artery blood flow, which may promote thrombosis and an inflammatory response. We performed a cross-sectional study to investigate the association of white blood cells to mean platelet volume ratio (WMR) with CAE. Consecutive eligible patients (n = 492) were divided into two groups: including 238 patients with CAE and 254 patients in the normal coronary artery (NCA) group. WMR, the systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR) were found to be significantly associated with CAE in both univariate and multivariate logistic regression analyses. In multivariate analysis, the presence of WMR was associated with CAE (the odds ratios (OR) = 1.002, 95% CI: 1.001–1.003, P <.001). In the ROC analysis, the statistics (Z-values) of WMR vs SII and WMR vs NLR were 2.427 and 2.670 and were statistically significant (P =.015 and P =.008), indicating that WMR was superior to SII and NLR in distinguishing WMR. The optimal cut-off value was calculated from the point of maximal sensitivity and specificity by using Youden's index, which was determined to be 635.50. WMR has the potential to be a cost-effective tool to monitor CAE. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Pd‐mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules, precise regulation of protein function, and cellular engineering. However, the availability of cleavable "caging" groups is quite limited, and their application in nucleic acid modification has seldom been reported. Herein, we introduce a method based on Pd‐catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules. We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function, followed by the release of biological activity through Pd‐catalyzed NaBH4 reduction amination reaction. This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes, prodrugs, and to regulate the biological function of RNA, including reverse transcription extension, binding to ligands, and cleavage activity of the CRISPR‐Cas system. All results confirm that this strategy provides an efficient and controllable "OFF to ON" biological switch, capable of achieving significant regulatory effects substoichiometrically, and is expected to be extended to other biological applications. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Pd‐mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules, precise regulation of protein function, and cellular engineering. However, the availability of cleavable "caging" groups is quite limited, and their application in nucleic acid modification has seldom been reported. Herein, we introduce a method based on Pd‐catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules. We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function, followed by the release of biological activity through Pd‐catalyzed NaBH4 reduction amination reaction. This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes, prodrugs, and to regulate the biological function of RNA, including reverse transcription extension, binding to ligands, and cleavage activity of the CRISPR‐Cas system. All results confirm that this strategy provides an efficient and controllable "OFF to ON" biological switch, capable of achieving significant regulatory effects substoichiometrically, and is expected to be extended to other biological applications. [ABSTRACT FROM AUTHOR]

This paper presents two modifications for Loidreau's cryptosystem, a rank metric-based cryptosystem constructed by using Gabidulin codes in the McEliece setting. Recently a polynomial-time key recovery attack was proposed to break this cryptosystem in some cases. To prevent this attack, we propose the use of subcodes to disguise the secret codes in Modification I. In Modification II, we choose a random matrix of low column rank to mix with the secret matrix. Our analysis shows that these two modifications can both resist the existing structural attacks. Furthermore, these modifications have a much more compact representation of public keys compared to Classic McEliece, which has been selected into the fourth round of the NIST-PQC project. [ABSTRACT FROM AUTHOR]