Waterfowl as the main reservoir of avian influenza A (H5N6) virus in wet markets

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Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2)

Introduction: Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor approved for treatment-naive and crizotinib-refractory advanced ALK-positive (ALK+) NSCLC. We evaluated brigatinib after other next-generation ALK tyrosine kinase inhibitors. Methods: In this single-arm, phase 2, ALK in Lung Cancer Trial of brigAtinib-2 (NCT03535740), patients with advanced ALK+ NSCLC whose disease progressed on alec-tinib or ceritinib received brigatinib 180 mg once daily (after 7-d 90-mg lead-in). Primary end point was indepen-dent review committee (IRC)-assessed overall response rate (ORR). Circulating tumor DNA (ctDNA) was analyzed. Results: Among 103 patients (data cutoff: September 30, 2020; median follow-up [range]: 10.8 [0.5-17.7] mo), confirmed IRC-ORR was 26.2% (95% confidence interval [CI]: 18.0-35.8), median duration of response, 6.3 months (95% CI: 5.6-not reached), and median progression-free survival (mPFS), 3.8 months (95% CI: 3.5-5.8). mPFS was 1.9 months (95% CI: 1.8-3.7) in patients with ctDNA-detectable baseline ALK fusion (n = 64). Among 86 pa-tients who progressed on alectinib, IRC-ORR was 29.1% (95% CI: 19.8-39.9); mPFS was 3.8 months (95% CI: 1.9- 5.4). Resistance mutations were present in 33.3% (26 of 78) of baseline ctDNA; 54% (14 of 26) of mutations were G1202R; 52% (33 of 64) of patients with detectable ALK fusion had EML4-ALK variant 3. Most common all-grade treatment-related adverse events were increased creatine phosphokinase (32%) and diarrhea (27%). The mean dose intensity of brigatinib (180 mg once daily) was 85.9%. Conclusions: In ALK in Lung Cancer Trial of brigAtinib-2, brigatinib was found to have a limited activity in patients with ALK+ NSCLC post-ceritinib or post-alectinib therapy. mPFS was longer with brigatinib in patients without base-line detectable plasma ALK fusion. (c) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).Y

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field