Small Molecule Therapeutics in the Pipeline Targeting for Triple-Negative Breast Cancer: Origin, Challenges, Opportunities, and Mechanisms of Action.

Triple-negative breast cancer (TNBC) cells are devoid of estrogen receptors (ERs), progesterone receptor (PRs), and human epidermal growth factor receptor 2 (HER2), and it (TNBC) counts for about 10-15% of all breast cancers. TNBC is highly invasive, having a faster growth rate and a higher risk of metastasis and recurrence. Still, chemotherapy is one of the widely used options for treating TNBC. This study reviewed the histological and molecular characterization of TNBC subtypes, signaling pathways that are aberrantly expressed, and small molecules targeting these pathways, as either single agents or in combination with other therapeutic agents like chemotherapeutics, immunotherapeutics, and antibody-drug conjugates; their mechanisms of action, challenges, and future perspectives were also reviewed. A detailed analytical review was carried out using the literature collected from the SciFinder, PubMed, ScienceDirect, Google Scholar, ACS, Springer, and Wiley databases. Several small molecule inhibitors were found to be therapeutics for treating TNBC. The mechanism of action and the different signaling pathways through which the small molecules exert their effects were studied, including clinical trials, if reported. These small molecule inhibitors include buparlisib, everolimus, vandetanib, apatinib, olaparib, salidroside, etc. Some of the signaling pathways involved in TNBC, including the VEGF, PARP, STAT3, MAPK, EGFR, P13K, and SRC pathways, were discussed. Due to the absence of these biomarkers, drug development for treating TNBC is challenging, with chemotherapy being the main therapeutic agent. However, chemotherapy is associated with chemoresistance and a high toxicity to healthy cells as side effects. Hence, there is a continuous demand for small-molecule inhibitors that specifically target several signaling pathways that are abnormally expressed in TNBC. We attempted to include all the recent developments in this field. Any omission is truly unintentional.

Iron-Imine Cocktail in Drug Development: A Contemporary Update.

Organometallic drug development is still in its early stage, but recent studies show that organometallics having iron as the central atom have the possibility of becoming good drug candidates because iron is an important micro-nutrient, and it is compatible with many biological systems, including the human body. Being an eco-friendly Lewis acid, iron can accept the lone pair of electrons from imino(sp2)-nitrogen, and the resultant iron-imine complexes with iron as a central atom have the possibility of interacting with several proteins and enzymes in humans. Iron-imine complexes have demonstrated significant potential with anticancer, bactericidal, fungicidal, and other medicinal activities in recent years. This article systematically discusses major synthetic methods and pharmacological potentials of iron-imine complexes having in vitro activity to significant clinical performance from 2016 to date. In a nutshell, this manuscript offers a simplistic view of iron complexes in medicinal inorganic chemistry: for instance, iron is presented as an "eco-friendly non-toxic" metal (as opposed to platinum) that will lead to non-toxic pharmaceuticals. The abundant literature on iron chelators shows that many iron complexes, particularly if redox-active in cells, can be quite cytotoxic, which can be beneficial for future targeted therapies. While we made every effort to include all the related papers, any omission is purely unintentional.

Exploring the optimal threshold of FDI inflows for carbon-neutral growth in Africa.

This study investigates the relationship between foreign direct investment (FDI) and CO2 emissions in Africa, primarily emphasizing carbon-neutral growth. Employing advanced econometric methods like the Generalized Method of Moments (GMM), fixed effect, and Two-Stage Least Squares (2SLS), we identify critical threshold values for key variables, including economic growth, trade openness, human capital, financial development, inflation, and population growth. Our findings indicate that GDP significantly influences the FDI-CO2 emissions relationship as economies expand, shifting from negative to positive, potentially leading to increased carbon emissions. Higher trade-to-GDP ratios are associated with reduced CO2 emissions due to cleaner technologies and greener production practices. Additionally, financial development plays a pivotal role, enabling investment in sustainable technologies. Nations with a more skilled workforce are more likely to adopt sustainable practices. The influence of population growth on CO2 emissions is complex, balancing increased demand with investments in clean technologies. The study recommends that African policymakers prioritize FDI aligned with carbon-neutral growth by promoting sustainability, investing in human capital, and carefully balancing population growth with sustainability.

Rethinking frontline health workers' safety performance in times of pandemic: the role of spiritual leadership.

This study examined the impact of spiritual leadership style on frontline health workers' safety performance through the mediating role of safety climate. Also, leader-member exchange (LMX) was examined as a moderator of the safety climate and safety performance relationship. Survey data from 582 frontline health workers in Ghana's Greater Accra and Ashanti regions were analyzed using AMOS version 23. Findings showed that spiritual leadership dimensions significantly influenced health workers' safety performance. Altruistic love and vision also significantly influenced safety climate. However, hope did not influenced safety climate. Moreover, safety climate had an impact onsafety performance dimensions. Furthermore, safety climate mediated the relationship between altruistic love, vision, and safety performance. However, safety climate did not mediate the relationship between hope and safety performance. Lastly, LMX moderated the positive effect of safety climate on safety compliance but not on safety participation. This study offers valuable insights for improving frontline health workers' safety performance during pandemics.

Green financial development efficiency: a catalyst for driving China's green transformation agenda towards sustainable development.

The pursuit of a green transformation agenda in China is an important aspect of achieving sustainable development. The role played by green financial development efficiency (GFDE) in this pursuit cannot be overlooked. This paper explored the impact of GFDE on China's green transformation agenda and its contributions toward sustainable development. The study adopts a systematic approach to examine the relationship between GFDE and green transformation, utilizing relevant data and literature. The study aligns with previous research in the field that highlights the importance of green finance in reducing carbon emissions and promoting sustainable development in China. It also adds to the existing literature by specifically focusing on the role of green financial development efficiency in the pursuit of a green transformation agenda in China. The study found a significant improvement in GFDE over the period of 2010 to 2020 in promoting green transformation in China. Both systems generalized method of moments and fixed-effect models revealed that trade openness, foreign investments, technological innovation, and government budget positively influenced GFDE while energy consumption and economic policy uncertainty had a significant adverse effect on GFDE. The results of this study inform policymakers and stakeholders of the importance of green finance in promoting sustainable development. The study intimated that the financial sector should provide support for green technologies and businesses by offering range of green products such as green bonds, funds, and loans.

A cross-sectional study of barriers to cervical cancer screening uptake in Ghana: An application of the health belief model.

BACKGROUND: The high incidence (32.9, age-standardized per 100,000) and mortality (23.0, age-standardized per 100,000) of cervical cancer (CC) in Ghana have been largely attributed to low screening uptake (0.8%). Although the low cost (Visual inspection with acetic acid) screening services available at various local health facilities screening uptake is meager. OBJECTIVE: The purpose of the study is to determine the barriers influencing CC screening among women in the Ashanti Region of Ghana using the health belief model. METHODS: A analytical cross-sectional study design was conducted between January and March 2019 at Kenyase, the Ashanti Region of Ghana. The study employed self-administered questionnaires were used to collect data from 200 women. Descriptive statistics were used to examine the differences in interest and non-interest in participating in CC screening on barriers affecting CC screening. Multivariable logistic regression was used to determine factors affecting CC screening at a significance level of p<0.05. RESULTS: Unemployed women were less likely to have an interest in CC screening than those who were employed (adjustes odds ratio (aOR) = 0.005, 95%CI:0.001-0.041, p = 0.005). Women who were highly educated were 122 times very likely to be interested in CC screening than those with no or low formal education (aOR = 121.915 95%CI: 14.096-1054.469, p<0.001) and those who were unmarried were less likely to be interested in CC screening than those with those who were married (aOR = 0.124, 95%CI: 0.024-0.647, p = 0.013). Also, perceived threat, perceived benefits, perceived barriers and cues for action showed significant differences with interest in participating in screening with a P-values <0.003. The association was different for long waiting time, prioritizing early morning and late evening screening which showed no significant difference (P-value > 0.003). CONCLUSIONS: Married women, unemployed and those with no formal education are less likely to participate in CC screening. The study details significant barriers to cervical cancer screening uptake in Ghana. It is recommended that the Ghana health services should develop appropriate, culturally tailored educational materials to inform individuals with no formal education through health campaigns in schools, churches and communities to enhance CC screening uptake.