Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/β-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.

Numerous studies have explored the impact of family planning policies on income distribution, but the impact of policy relaxation remains largely unexplored. To address this gap, we investigate the effects of China's selective two-child policy, which was implemented in 2013, using provincial panel data from 2011 to 2016. Specifically, we employ a generalized difference-in-differences model to empirically analyze the impact and mechanism of the policy relaxation on residents' income distribution. Our findings are as follows. Firstly, the selective two-child policy has narrowed the income distribution gap. Secondly, male labor force participation, the urban-rural income gap, and disposable income serve as mechanisms through which the selective two-child policy affects income distribution. Thirdly, the robustness test confirms the robustness of our conclusions. Finally, we observe regional heterogeneity in the impact of the selective two-child policy on residents' income distribution. Specifically, the policy has had significant effects in the western and northeastern regions, but not in other regions. Overall, our results shed light on the impact of childbearing policies on income distribution, providing important insights for optimizing China's childbearing policies and promoting common prosperity.

This paper analyses a model of private value auctions with symmetric risk-neutral bidders, where bidders' private values of an indivisible good are fuzzy. The auction is studied as a game with incomplete information. Fuzzy random variables, their quantile functions, and expressions for expectations through quantile functions are used. An explicit expression for the solution is found. Also, expected bidders' payments are studied.

Using an international dataset, this letter finds that high stock returns are associated with increased death rates from drug use disorders. Although the out-of-pocket expenditure on healthcare also rises following a stock market surge, the net effect on life expectancy is significantly negative.

In this paper, a portfolio analysis is carried out using the Sharpe ratio to identify the optimal market portfolio. The measure of investment performance with a Sharpe ratio is compared to results obtained with bootstrapped resamples of the Sharpe ratio. The results indicate that the choice of the market portfolio is highly affected by the uncertainty regarding the estimation of the expected returns and the variance-covariance matrix between the returns, that is, the estimation risk associated with these parameters.

In the statistical standard of population aging adopted by the United Nations in 1956, the UN only focused on age, which is no longer a good statistical indicator in the context of deepening global population aging. To some extent, population aging is also the embodiment of social progress. This paper suggests improving the existing statistical standards of population aging to better adapt to the reality of social development.

This research letter investigates hedonic and utilitarian orientations to Online shopping. The data highlight a positive correlation of hedonism with both the length and the frequency of connection to the Internet. It considers two products, jeans and personal computers, that previous literature had identified as being characterized by utilitarian and hedonic features. The results show that consumers prefer to buy products and brands on the Web if they have already seen and experienced them Offline.

This paper estimates panel vector autoregressions to analyze the endogenous connection between COVID-19 and non-communicable diseases (NCDs). Using weekly, US state-level data, the study finds evidence of a significant positive effect of NCD-related mortality on deaths due to COVID-19. I find this effect to be higher for males than females. Results are robust to several sensitivity checks, so large deviations are unexpected.

We examine the impact of environmental provisions in regional trade agreements (RTAs) on the environmentally harmful exports. Results show that environmental clauses in RTAs help reduce “dirty” exports, whereas RTA depth promotes exports. The exporting country may divert its polluting exports to its trading partner if it faces more environmental provisions with other countries.

In this paper, we review the research on the substitution between social security wealth and private wealth. Our review includes over 100 theoretical and empirical contributions. Nearly 70% of the literature identifies the statistically significant impact of social security wealth on different forms of private savings. A strong majority of authors, who obtain statistically significant results find the negative impact of social security on private savings. We discuss the main limitations of the literature.

Part of the present inflation is caused by the breakdown of globalization, in particular supply chains, part is caused by the Corona Pandemic, in particular lockdowns, part is caused by the Ukrainian War, part is caused by European sanctions, and part – and not the smallest one – is caused by the European Central Bank’s printing money by hook or by crook in the past and in the presence. This paper attributes inflation decisively to the overwhelming money creation by the European Central Bank.

Achieving food security through improved agricultural technology is one of the greatest challenges of our time. Indeed, it is one of the elements explicitly mentioned in the Sustainable Development Goals (SDGs). One factor that can lead to improved production and distribution systems is the availability of data of all kinds on the sector. In this paper we study what is happening in this respect in two Mediterranean olive oil producing countries, and show how available data can facilitate the coordination and communication of technical developments and improve the competitiveness of producers.

The study analyses the long growth rate period contribution to human development in West African Economic and Monetary Union (WAEMU) from 1996 to 2019 introducing time and institutional indicators effects analyses. Time and institutional effects both greatly improve model's diagnostics statistics. Time effects reduce growth variable coefficient and its significance, but not institutional effects. Combined effects inhibit growth contribution to human development. It appears essential to increase the resiliency of growth and the efficiency of government institutions.

Major economic and financial contractions usually go hand-in-hand with muted inflation. This has been true for the Great Depression, the Global Financial Crisis, as well as the Covid-19 crisis. In this paper, we theoretically highlight and discuss the evolution of instruments and approaches monetary-policy decision makers at the Federal Reserve have in lifting inflation to desired levels in times of the zero-lower bound, paying particular focus on more rigorous developments like asymmetric average inflation and temporary price-level targeting.

Bank deposit is closely related to systemic risks. In addition, considering that resident deposits in China have significant seasonal characteristics, this paper focuses on which component of deposits drives the systemic risk volatility, that is, it can supplement the existing forecast information. We use X-13ARIMA-SEATS to decompose deposit into three subsequences. The research findings show that the forecast effect of subsequence models is better than that of benchmark series. Most importantly, the model with trend component has the best forecast performance.

This paper deals with the gender gap in accessing and using financial services provided by mobile money and financial institutions. Using data from ECOWAS member countries, we applied the Fairlie decomposition method to estimate and decompose the gender gap. The results show that mobile money contributes to improving of the use of services compared to financial institutions. However, it also increases the gender gap in women's disadvantages in accessing and using these services. The difference in the level of education and income between males and females is the main factor explaining the gender gap.

This research evaluates the efficacy of survival models in forecasting startup failures and investigates their economic implications. Several machine learning survival models, including Kernel SVM, DeepSurv, Survival Random Forest, and MTLR, are assessed using the concordance index (C-index) as a measure of prediction accuracy. The findings reveal that more sophisticated models, such as Multi-Task Logical Regression (MTLR) and Random Forest, outperform the standard Cox and Kaplan Meier (K-M) models in terms of predicted accuracy.

Calculating the amount of regulatory capital to cover unexpected losses due to operational events in the upcoming year has caused problems because of difficulties in fitting probability distributions to data. It is consequently difficult to judge an appropriate level of capital that reflects the risk profile of a financial institution. We provide theoretical and empirical analyses to link the calculated capital to the sum of losses using appropriate statistical approximations. We conclude that, in order to reasonably reflect the associated risk, the capital should be approximately half the sum of losses, with a wide bound for the ratio of capital to sum.

This paper examines whether sell-side analyst-affiliated investors trade stocks before their analysts release material information. Using class action lawsuits, I explore the pre-lawsuit periods and investigate how potentially informed analysts trade their covered firms. The event study finds that analyst-affiliated investors reduce their stockholdings of firms prior to their own analyst downgrades. The findings are more pronounced among investors employed by investment banks. The post-trading performance of analyst-affiliated investors suggests that they have superior information and front-run to maximize benefits.

How does democracy relate to the initial economic policy responses to Covid-19? Using a cross country analysis, we find that countries with a higher degree of democracy have stronger economic policy responses than their peers. However, when we separate monetary and financial policies from fiscal policy, democracy is not associated with the latter when we control for the income level of a country. Finally, for countries with lower levels of labor participation, high levels of income inequality are associated with weaker policy responses.