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Introduction: Several vaccine candidates are being clinically tested in response to the 2019 coronavirus disease (COVID-19) pandemic. This study was conducted to assess the acceptance of a 50 or 95% effective COVID-19 vaccine, when it becomes available in southeast Asia, among the general population in Indonesia. Methods: A cross-sectional online survey was conducted between March 25 and April 6, 2020. Participants were asked if they would accept a free vaccine which was 95 or 50% effective. Using a logistic regression model, we assessed the associations between sociodemographic characteristics, exposure to COVID-19 information, or perceived risk of infection with acceptance of a hypothetical COVID-19 vaccine. Results: Among 1,359 respondents, 93.3% of respondents (1,268/1,359) would like to be vaccinated for a 95% effective vaccine, but this acceptance decreased to 67.0% (911/1,359) for a vaccine with 50% effectiveness. For a 95% effective vaccine, being a healthcare worker and having a higher perceived risk of COVID-19 infection were associated with higher acceptance, adjusted odds ratio (aOR): 2.01; 95%CI: 1.01, 4.00 and aOR: 2.21; 95%CI: 1.07, 4.59, respectively; compared to civil servants, being retired was associated with less acceptance (aOR: 0.15; 95%CI: 0.04, 0.63). For a 50% effective vaccine, being a healthcare worker was also associated with greater acceptance, aOR: 1.57; 95%CI: 1.12, 2.20. Conclusion: Acceptance of a COVID-19 vaccine was highly influenced by the baseline effectiveness of the vaccine. Preparing the general population to accept a vaccine with relatively low effectiveness may be difficult.

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The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

BackgroundOsimertinib (AZD9291) is a third‐generation EGFR‐tyrosine kinase inhibitor (TKI) that selectively inhibits the activating EGFR mutation and T790M mutation, and is currently used globally to treat EGFR‐mutant non‐small cell lung cancer (NSCLC). However, acquired resistance to osimertinib is inevitable.MethodsWe established osimertinib‐resistant cells (PC9/T790M/AZDR and H1975/AZDR) derived from EGFR‐mutant NSCLC cells harboring T790M mutation, and investigated the mechanism of acquired resistance to osimertinib by whole‐exome sequencing and multiple phospho‐receptor tyrosine kinase (RTK) array. A tumor specimen from an EGFR‐mutant NSCLC patient with acquired resistance to osimertinib was also subjected to immunohistochemical analysis.ResultsWhole‐exome sequencing analysis demonstrated that genetic alterations, such as acquisition of EGFR C797S, loss of T790M mutation, MET amplification, or mutated KRAS, MEK, BRAF, PIK3CA, were not detected. Analysis of phospho‐RTK array revealed that insulin‐like growth factor‐1 receptor (IGF1R) was activated in PC9/T790M/AZDR and H1975/AZDR cells. Knockdown of IGF1R by siRNA as well as inhibition of IGF1R activation by linstinib (IGF1R inhibitor) significantly restored the sensitivity to osimertinib. Immunohistochemical analysis revealed that the expression level of phosphorylated IGF1R was higher in the tumor specimen from the EGFR‐mutant NSCLC patient with acquired resistance to osimertinib than in the specimen collected prior to the treatment.ConclusionsIGF1R activation could occur following treatment with osimertinib in EGFR‐mutant NSCLC with T790M mutation, and might be one of the mechanisms underlying osimertinib resistance. Combined treatment of osimertinib and IGF1R inhibitor might be effective in overcoming the acquired resistance to osimertinib induced by IGF1R activation.Key points Significant findings of the study: Using osimertinib‐resistant cells, we found that IGF1R activation induced by osimertinib treatment in EGFR‐mutant NSCLC with T790M mutation is involved in resistance. Increased phosphorylation of IGF1R was observed in the tumor specimen from an EGFR‐mutant NSCLC patient with acquired osimertinib resistance. What this study adds: IGF1R activation might be one of the mechanisms of osimertinib resistance. A combination therapy with osimertinib and an IGF1R inhibitor might be an optimal approach for overcoming the acquired resistance to osimertinib induced by IGF1R activation.