Clinical potential of SKP2 as diagnostic marker and therapeutic target in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The overall survival has not improved significantly over the last decades because no major therapeutic breakthroughs have been achieved for over 15 years. METHODS: We analyzed a genome-wide loss-of-function screening database to identify vulnerabilities in SCLC for the development of urgently needed novel therapies. RESULTS: We identified SKP2 (encoding S-phase kinase-associated protein 2) and CKS1B (encoding CDC28 protein kinase regulatory subunit 1B) as the two most essential genes in that order in SCLC. Notably, SKP2 and CKS1B comprise the p27 binding pocket of the E3 ubiquitin ligase SCFSKP2 complex. Immunohistochemistry on tissue microarrays revealed that SKP2 was expressed in >95% of samples at substantially higher levels than that observed for commonly used neuroendocrine markers. As expected, SCLC cell lines were sensitive to SKP2 inhibition. Furthermore, SKP2 or CKS1B knockdown induced apoptosis in RB1 mutant cells, whereas it induced senescence in RB1 wild-type cells. CONCLUSION: Although the mechanism underlying SKP2 knockdown-induced growth inhibition differs between RB1-wild-type and -mutant SCLC, SKP2 can be considered a novel therapeutic target for patients with SCLC regardless of the RB1 mutation status. Our findings indicate that SKP2 is a potential novel clinical diagnostic marker and therapeutic target in SCLC.

Willingness to Pay (WTP) for COVID-19 Vaccine Booster Dose and Its Determinants in Indonesia.

Willingness to pay (WTP) for booster doses of coronavirus disease 2019 (COVID-19) vaccines is an under studied research topic. Therefore, the current study aimed to investigate the WTP for the booster doses of COVID-19 vaccines and its predictors in Indonesia using an online survey distributed all over the provinces of this low-middle-income country. The WTP was evaluated using a basic dichotomous contingent valuation approach, and its associated determinants were evaluated using a linear regression model. Out of 2935 responders, 66.2% (1942/2935) were willing to pay for a booster dose of the COVID-19 vaccine. The majority of respondents (63.5%) were willing to pay within a price range of 100,000-500,000 Indonesian rupiah (IDR), i.e., USD 6.71-33.57. Being older than 40 years, having a higher educational level, having a higher income, knowing and understanding that booster doses were important, and having a vaccine status that is certified halal (permissible in Islamic law), were all associated with a higher WTP for the booster dose of COVID-19 vaccines. The study findings imply that the WTP for a booster dose of COVID-19 vaccination in Indonesia is lower compared to acceptance of vaccines provided free of charge. This WTP data can be utilized to develop a pricing scheme for the booster doses of COVID-19 vaccination in the country with potential benefits in other low-income countries. The government may be required to provide subsidies for the herd immunity vaccination process to proceed as anticipated. Furthermore, the public community must be educated on the importance of vaccination as well as the fact that the COVID-19 epidemic is far from being over.

Drivers of and Barriers to COVID-19 Vaccine Booster Dose Acceptance in Indonesia.

Obtaining a booster dose of coronavirus disease 2019 (COVID-19) vaccine is required to maintain the protective level of neutralizing antibodies and therefore herd immunity in the community, and the success of booster dose programs depends on public acceptance. The aim of this study was to determine the acceptance of a booster dose of COVID-19 vaccine and its drivers and barriers in Indonesia. A cross-sectional survey was conducted in the provinces of Indonesia between 1 and 15 August 2022. Individuals who completed the primary series of the COVID-19 vaccine were asked about their acceptance of a booster dose. Those who refused the booster dose were questioned about their reasons. A logistic regression was used to determine the determinants associated with rejection of a booster dose of COVID-19 vaccine. A total of 2935 respondents were included in the final analysis. With no information on the efficacy and safety of the COVID-19 vaccine, 95% of respondents agreed to receive a booster dose if it were provided for free by the government. This acceptance was reduced to only 50.3% if the vaccine had a 75% efficacy with a 20% chance of side effects. The adjusted logistic regression analysis indicated that there were eight factors associated with the rejection of the booster dose: age, marital status, religion, occupation, type of the first two vaccines received, knowledge regarding the importance of the booster dose, belief that natural immunity is sufficient to prevent COVID-19 and disbelief in the effectiveness of the booster dose. In conclusion, the hesitancy toward booster doses in Indonesia is influenced by some intrinsic factors such as lack of knowledge on the benefits of the booster dose, worries regarding the unexpected side effects and concerns about the halal status of the provided vaccines and extrinsic determinants such as the effectiveness and safety of the vaccine. These findings suggest the need for more campaigns and promotions regarding the booster dose benefits to increase its acceptance.

Knowledge and Attitudes of Indonesian General Practitioners Towards the Isoniazid Preventive Therapy Program in Indonesia.

OBJECTIVES: The Indonesian Ministry of Health launched isoniazid preventive therapy (IPT) in 2016, with general practitioners (GPs) at the frontline of this program. However, the extent to which GPs have internalized this program remains uncertain. The aim of this study was to identify the knowledge and attitudes of GPs towards the IPT program in Indonesia. METHODS: This study used an online, self-administered questionnaire distributed via e-mail and social messaging services. A logistic regression model was employed to identify the explanatory variables influencing the level of knowledge and attitudes toward IPT among GPs in Indonesia. An empirical analysis was conducted separately for each response variable (knowledge and attitudes). RESULTS: Of the 418 respondents, 128 (30.6%) had a good knowledge of IPT. Working at a public hospital was the only variable associated with good knowledge, with an adjusted odds ratio (aOR) of 1.69 (95% confidence interval [CI], 1.02 to 2.81). Furthermore, 279 respondents (66.7%) had favorable attitudes toward IPT. In the adjusted logistic regression analysis, good knowledge (aOR, 0.55; 95% CI, 0.34 to 0.89), 1-5 years of work experience (aOR, 2.09; 95% CI, 1.21 to 3.60), and having experienced IPT training (aOR, 0.48; 95% CI, 0.25 to 0.93), were significantly associated with favorable attitudes. CONCLUSIONS: In general, GPs in Indonesia had favorable attitudes toward IPT. However, their knowledge of IPT was limited. GPs are an essential element of the IPT program in the country, and therefore, adequate information dissemination to improve their understanding is critical for the long-term viability and quality of the IPT program in Indonesia.