This research paper examines changes in patient care management in acute care hospitals between 2001 and 2011. During this time, there were two opposing factors at play: the competition effect of the reform and the policymaker’s decision to reduce public hospitals across France. By studying the trends, it is evident that there has been a significant overall shift in patient care management during this period. This change could be attributed to the global competition effect and the concentration of in-patients in specific public facilities. Through the difference-in-difference method, the study analyzed time variations in the intensity of local competition. It was found that local competition had a negligible impact on patient care management. Additionally, the study revealed that there was a significant positive competition effect on high-technical procedures for the private sector, which is in line with the market segment where private sector hospitals have a leadership position and the pro-competitive reform intensified this position. The study also uncovered a negative competition effect on the length of stay for public hospitals. Prior to the implementation of the DRG-based payment reform, public sector hospitals were paid a global budget. However, after the reform was implemented, they had to shorten the length of stay to increase the number of stays. For-profit hospitals have always been paid based on the number of stays. The results are robust and consistent when alternative measures of local competition are used.

Gravity Energy Storage (GES) systems are recently being considered as a viable solution for storing intermittent renewable energy power, specifically in high curtailment zones. While a few studies have analyzed the material costs of GES systems, there is a paucity of literature on analyzing the socioeconomic costs of GES systems. This study analyzes the location-dependent costs of GES plants using a multi-factor spatial parameterization model for evaluating the existence of a point of minimum cost in a suburban mountainous geography. A case study of 500x500 points in a 50x50km2 area in the suburban area of Fukuoka city in Japan is performed. It is found that the cost of material transportation and transmission is more dominant in determining the position of an optimal cost location than factors of excavation and land costs. The position of the minima is also related to the principal urban area in that the line connecting the Center Business District (CBD) and suburban flat areas (line 1) is where the potential minima lie. The intersection point of an orthogonal to the line connecting the CBD with a substation nearest to the flat area with line 1, is the potential zone of minima location. The findings of this study are critical for urban energy planners and reveals how socioeconomic cost factors can aid in geolocation a suitable GES installation site.

The study investigates the impact of COVID-19 on African exchange rates, employing a panel dataset over the period 2016-2022 from 13 African economies and employing pooled OLS estimator. The findings reveal a noteworthy positive correlation between COVID-19 levels and exchange rates within the region. However, this association necessitates deeper exploration due to its multifaceted implications, including economic disruptions, government interventions, global market interconnections, regional stability perceptions, and investor behavior. Economic indicators, such as GDP, inflation rate, real interest rate, and unemployment rate, significantly influence exchange rates. While GDP positively impacts exchange rates through economic growth, investor confidence, and trade strength, controlled inflation fosters investor confidence and export competitiveness, positively affecting exchange rates. Moreover, a pronounced positive impact of the real interest rate indicates economic stability, attracting investment and contributing to currency appreciation. Conversely, high unemployment negatively affects exchange rates, signaling economic weaknesses and eroding investor confidence. These findings emphasize nuanced policy responses for managing health crisis-induced economic disruptions and suggest future research directions focusing on specific country-level analyses and multifaceted factors influencing currency valuations within African economies.

Although docetaxel treatment yields a high survival rate for prostate cancer (PCa), resistance eventually develops in many patients. Understanding the underlying mechanisms of docetaxel resistance is essential for improving treatment strategies. Cytokines, which play a role in cell signaling and immune responses, have been implicated in drug resistance mechanisms. The study revealed that interleukin-8 (IL-8) was consistently overexpressed in both docetaxel-resistant PCa cell lines. Thus, the expression levels of cytokines released from docetaxel-sensitive (PC-3- and DU-145) and resistant (PC-3/R-DU-145/R) PCa cells were compared. IL-8 was found to be commonly expressed in resistant cell lines. This finding led to the hypothesis that IL-8 could play a key role in mediating PCa cell resistance to docetaxel. IL-8 siRNA treatment increased docetaxel sensitivity in both resistant cells. To demonstrate the mechanism of IL-8-related resistance, MDR1 expression was evaluated. After IL-8 siRNA treatment MDR1 expression was reduced in both resistant cells suggesting that IL-8 regulates the docetaxel resistance of PCa cells via modulation of multidrug resistance 1 (MDR1). By expanding the knowledge of the cytokines and their effect mechanisms, novel approaches can be developed for the treatment of docetaxel-resistant prostate cancer. Further investigations into the role of IL-8 in docetaxel resistance could offer valuable insights into the development of effective treatment strategies for PCa patients.

It's critical for environmental governance to understand the effectiveness of policy interventions as well as their working mechanisms. This paper focuses on the vehicle license plate-based management, a sort of policy intervention understudied in environmental governance literature. Specifically, we study the automobile purchase restriction (APR), a major method of license management to address urban air pollution and traffic congestion recently launched by the authorities of China. However, limited studies have quantified the environmental impact of such purchase restriction. Based on the panel data of PM2.5 concentration in 330 cities in China during 1998-2016, this study aims to explore the causal impact of Beijing automobile purchase restriction on air quality, using the regression control method and high-dimensional data regression of machine learning. The average PM2.5 concentration did not decrease but increased because of the purchase restriction. Over time, the deterioration effect on urban air quality will not alleviate. Besides, the restriction cannot enhance urban air quality by decreasing the increase of PM2.5. Despite excluding the impact of driving restriction, the purchase restriction markedly aggravate urban air quality. This paper has some policy implications for policymakers on the impact of urban vehicle license management with caution. Hence, it is essential to promote urban economy, production, and lifestyle to attain the win-win goal of air pollution control and urban development.

Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.

Since the Industrial Revolution, the emission of carbon dioxide and other greenhouse gases by human production activities has increased year by year, and the greenhouse effect has also increased. A series of problems, such as global warming, melting of the Antarctic continent, sea level rise and frequent occurrence of extreme climate, have attracted the attention of countries all over the world. As a developing country with the fastest economic growth rate, China's rapid economic growth is inseparable from the contribution of manufacturing industry. As an important engine of China's economic development, manufacturing industry inevitably brings environmental problems and a large number of greenhouse gas emissions while promoting rapid economic development. Therefore, manufacturing has become a major area for China to achieve its carbon emission reduction targets. With the "Made in China" to the world, the export trade of manufacturing industry plays a decisive role in China's total export trade and even the global trade. But whether the huge export demands will affect carbon emissions. Through the empirical study on carbon emissions of China's manufacturing export trade, the paper found that the increase of export demand of manufacturing industry will indeed bring a significant increase in carbon emissions, but also affected by some other factors. Finally, it provides reference for the high-quality development and export of China's manufacturing industry under the background of the target of “dual-carbon”.

The latent transforming growth factor-beta (TGF-β) binding protein 1 (LTBP1) has been implicated in various cellular processes, but its role in triple-negative breast cancer (TNBC) remains unclear. In this study, we investigated the impact of LTBP1 on TNBC progression and its underlying mechanisms. Analysis of online datasets revealed elevated LTBP1 mRNA expression in breast cancer tissues compared to normal adjacent tissues. Kaplan-Meier Plotter analysis indicated that high LTBP1 expression was negatively correlated with relapse-free survival (RFS), distant-metastasis free survival (DMFS), and overall survival (OS) of breast cancer patients. Additionally, LTBP1 mRNA levels were associated with chemotherapy resistance. Functional assays in TNBC cells demonstrated that LTBP1 knockdown suppressed cell proliferation, induced apoptosis, and attenuated migration and invasion. In vivo studies confirmed that LTBP1 knockdown inhibited tumor growth in a xenograft mouse model. Mechanistically, LTBP1 positively correlated with genes involved in signaling regulation and organelle organization, with significant associations to GTPase binding and the RhoA/ROCK pathway. LTBP1 knockdown reduced RhoA activity and phosphorylation of Myosin Light Chain 2 (MLC2), suggesting inhibition of the RhoA/ROCK signaling pathway. Moreover, activation of the RhoA/ROCK pathway partially rescued the effects of LTBP1 knockdown on TNBC cell proliferation, apoptosis, migration, and invasion. In conclusion, our findings suggest that LTBP1 promotes TNBC progression through activation of the RhoA/ROCK signaling pathway, highlighting its potential as a therapeutic target for TNBC.

The paramount prerequisite for effective anti-cancer drugs is their ability to eradicate malignant cells while sparing non-cancer cells. The divergence in properties between malignant and non-cancer cells establishes a "therapeutic window," a critical consideration for achieving desirable treatment outcomes. Central to this is the imperative of a cancer drug's "selectivity and specificity." Taxanes, a pivotal class of successful anti-cancer drugs, continue to serve as the linchpin of cancer treatment due to their efficacy across a spectrum of cancer types. Operating as broad-spectrum chemotherapeutic agents, taxanes exert cytotoxic effects on proliferative cancer cells by binding to and stabilizing microtubules, disrupting mitosis, inducing mitotic catastrophe, and resulting in cell death. The distinct proliferative nature of cancer cells, as opposed to less proliferative non-cancer cells, affords taxanes a measure of specificity and selectivity. Nevertheless, sporadic yet recurring evidence suggests that taxanes also operate through non-mitotic mechanisms. Taxanes' binding and stabilization of microtubules lead to micronucleation and subsequent cell death, impacting both mitotic and non-mitotic cells. Recent discoveries indicate that the flexible and weakened nuclear envelope of malignant cells renders them sensitive to taxane-mediated micronucleation and cell death during various phases of the cell cycle. Conversely, non-cancerous cells typically exhibit a more robust and sturdy nuclear envelope, rendering them more tolerant to taxane-induced nuclear envelope fragmentation and subsequent micronucleation and cell death. The expression levels of nuclear envelope structural proteins, particularly Lamin A/C, emerge as indicators of taxane sensitivity. This evolving understanding underscores that nuclear envelope malleability, in conjunction with a high proliferation rate, is a pivotal determinant of taxane specificity and selectivity against malignant cells. These insights necessitate reconsidering oncological strategies to augment taxane efficacy, overcome resistance, and mitigate side effects.