Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues.

This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.

Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines.

Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.

Analyzing the impact of fintech industry and green financing on energy poverty in the European countries.

In the fourth industrial revolution, the fintech has significantly expanded during the last several years, and this has caused scholars to worry about how much electricity is being used. Because energy poverty is one of the most critical social policy concerns facing the majority of nations in the world in the modern era. This study adds to what has already been written by looking at how the fintech industry affects the environment and energy in European countries. The current study investigates how the growing awareness of the need to preserve energy and the environment has an effect on society, and analyzes the role of the fintech industry, green finance, energy efficiency, and research and development on energy poverty across European nations from 2013 to 2020. To estimate long- and short-term impacts, DOLS and FMOLS are used along with diagnostic tests. The outcomes found that there is a tight relationship between energy poverty and all the factors taken into consideration (fintech, green finance, energy efficiency, and R&D). EU governments should employ "green finance" to encourage and enable the fintech industry since fintech plays a vital role in enhancing environmental effectiveness. The financing of environmentally friendly projects is very beneficial and might help alleviate energy poverty. The findings also indicate that more financing, ecological subsidies, and social assistance programs are necessary in order to satisfy the needs for energy and put an end to energy poverty in Europe. Policymakers in the tech world may be especially interested in the results.

Linkages between environmental sustainability, disaggregated emission, renewable energy, and energy efficiency: An evidence from BRI countries.

This paper examines the long-term and short-run causative relationship among environmental sustainability, energy efficiency, renewable energy and carbon emissions from all over sources (coal, oil and fossil fuels) and sector wise division (heat and power, transportation, residential, manufacturing and other sectors. The empirical evidence presented in this study is derived from a balanced panel dataset spanning the annual periods from 2000 to 2021. The dataset specifically focuses on a selection of BRI Countries. The Kao test demonstrates the presence of cointegration across variables such as carbon dioxide emissions, environmental suitability, energy efficiency and renewable energy. The Panel Pooled Mean Group-Autoregressive Distributed Lag (PMG-ARDL) model indicates a statistically significant positive association between the environmental sustainability and disaggregated CO2 emissions over a long-term period. The study found a positive relationship between disaggregated CO2 emissions and environmental sustainability and energy efficiency, with renewable energy sources reducing emissions. It suggests a need for a structural transition from an energy-intensive economy to a decarbonized one, with sectors like heat and power positively impacting sustainability. Implementing measures to reduce emissions is crucial for tackling climate change.

How institutional quality, and energy production sources, affect the environmental sustainability of bri countries: A comparison of different income groups.

Institutions and energy production sources shape environmental policies and practices. Institutions establish frameworks for renewable energy and enforce environmental protection measures. Conventional energy sources cause pollution and climate change, while green energy sources have lower environmental impacts. In this study we analyzed how quality institutions, along with different types of energy production sources affect the quality of environment in 101 countries that are part of the BRI, a global development project. We used a statistical method called panel quantile regression to analyze data from 2000 to 2020. We found that producing energy from renewable sources, such as wind and solar, reduces CO2 emissions by 0.003% in BRI countries. However, producing energy from non-renewable sources, such as gas and coal, harms the environment more in high-income and middle-income countries. We also found that having better institutional quality reduces CO2 emissions by 3.421%, 2.710%, and 0.006% in different groups of BRI countries. This means that having stronger and fairer institutions can help protect the environment by limiting the use of non-renewable energy sources and encouraging the use of renewable ones. Our study suggests that improving institutional quality is a key factor for achieving green energy and environmental sustainability in BRI countries.

How environmental protection activities and industrial revolution contributes in the nexus of energy security and environmental sustainability?

The booming fintech industry seeks to revolutionize traditional financial practices, introducing new business models and innovative applications to enhance financial services. However, the widespread adoption of fintech may lead to increased energy consumption, posing environmental challenges. Comprehensive research is essential to understand the impact of fintech on economies, financial culture, and the environment, facilitating informed decision-making to foster sustainable growth in the sector. Therefore, the present research will explore how the fintech industry, green finance, and energy efficiency play their role in energy security and the achievement of a sustainable environment. The current study used data from 2000 to 2020 by employing Fourier autoregressive distributed lag (ARDL), fully modified least squares (FMOLS), and dynamic ordinary least squares (DOLS) econometric techniques to explore how the industrial revolution, environmental protection activities, and energy efficiency affect energy security and the environment across European countries. According to the findings, the fintech sector encourages the use of eco-friendly and energy-efficient technology, which assists in lowering carbon emissions and boosting energy security and efficiency. The outcomes of energy efficiency show a negative relationship with carbon emissions but a considerably positive relationship with energy security. This research shows that green financing has a favorable influence on energy security, and in European nations, green financing drives the majority of investments made for environmental conservation.

Environmental sustainability and green technologies across BRICS countries: the role of institutional quality.

In recent years, a growing body of research has focused on the environment and economic growth nexus. However, there has not been much research done on how environmentally friendly technologies and institutional quality affect pollution levels. It is found that in developed countries, the rate of environmental deterioration has slowed thanks to more sustainable environmental regulations, advances in technology, and improvements in the quality of institutions. In contrast, limited modern technology in developing nations has resulted in havens of high carbon emissions. Therefore, the current research tried to analyze the environmental quality by using green technologies (GT), institutional quality (IQ), and energy efficiency (EE) as independent variables. In this study, we utilized data from 1995 to 2019 from BRICS countries to estimate long-term and short-term relationships. Used second-generation econometric techniques indicated that IQ, GT, and EE repair reduced environmental damage. The EKC does not exist, which means pollution in selected countries will improve with an expansion in economic activities. In the long term, a reform in institutions and more spending are required on green technologies to secure a sustainable future in BRICS countries. Results hold up when it comes to policy implications.

An empirical analysis of the nexus between digital financial inclusion, industrial structure distortion, and China's energy intensity.

Stimulating the shift to low-carbon energy and decreasing energy intensity are crucial strategies for green growth. Reducing energy intensity is an important measure to achieve the goal of "double carbon" and building a beautiful new China. Based on the provincial panel data of China from 2011 to 2020, this paper empirically tests the relationship among digital financial inclusion, industrial structure distortion, and energy intensity by using the spatial Durbin model and the intermediary effect method. The results show that the development of digital financial inclusion can promote the decline of energy intensity, and industrial structure distortion has a partial intermediary effect in the relationship between digital financial inclusion and energy intensity. Because of this, it is important to speed up the development of digital financial inclusion, increase the innovation of digital financial inclusion products and services, strengthen the supervision of digital financial inclusion, and reduce the distortion of the industrial structure so that digital finance can play its full role in reducing energy intensity.

Unveiling the nexus between marine energy consumption, seaborne trade, and greenhouse gases emissions from international shipping.

As a result of the globalization of production processes and the expansion of international trade, both water-based trade and the use of marine energy are expanding quickly. Marine energy consumption is rapidly increasing as a result of globalization. Despite being ignored for many decades, reducing marine emissions is today a top priority among European nations. Thus, the present study contributes to the existing literature by investigating the nexus between marine energy consumption, seaborne trade, and GHG emissions by employing time series data for eight Northern European nations from 2005 to 2017. The extended EKC model and three proxy variables for seaborne trade (i.e., container throughput, liner shipping connectivity index, and trade openness) are used to investigate the nexus between these variables. FMOLS and DOLS methods have been employed to control the problems of endogeneity and serial correlation. Only in Denmark, Norway, and Sweden did the data corroborate an inverted U-shaped relationship (the EKC curve) between maritime GHG emissions and economic development. The increase in energy utilization across all nations directly increased marine GHG emissions; however, the adverse effect of energy consumption on the environment is severe in Denmark, Norway, and Sweden. Container throughput, linear shipping connectivity index, and trade openness exhibit a positive impact on marine GHG emissions. The impact of seaborne proxy variables is severe in Denmark and Sweden. In order to have a robust assessment and to confirm the validity and uniformity of the results, Driscoll-Kraay standard errors (DKSE) and robust standard error (RSE) regression techniques are being employed.

Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis.

Obesity is increasing worldwide and leads to a multitude of metabolic diseases, including cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis (NASH). Cysteine-rich angiogenic inducer 61 (CYR61) is associated with the progression of NASH, but it has been described to have anti- and proinflammatory properties. We sought to examine the role of liver CYR61 in NASH progression. CYR61 liver-specific knockout mice on a NASH diet showed improved glucose tolerance, decreased liver inflammation, and reduced fibrosis. CYR61 polarized infiltrating monocytes promoting a proinflammatory/profibrotic phenotype through an IRAK4/SYK/NF-κB signaling cascade. In vitro, CYR61 activated a profibrotic program, including PDGFa/PDGFb expression in macrophages, in an IRAK4/SYK/NF-κB-dependent manner. Furthermore, targeted-antibody blockade reduced CYR61-driven signaling in macrophages in vitro and in vivo, reducing fibrotic development. This study demonstrates that CYR61 is a key driver of liver inflammation and fibrosis in NASH.

Nexus between disaggregated energy sources, institutional quality, and environmental degradation in BRI countries: a penal quantile regression analysis.

The present study aims to contribute to the existing literature by examining the role of institutional quality in the nexus of disaggregated energy sources and environmental degradation for belt and road initiative countries. To empirically support the theoretically presented propositions, a series of analytical techniques are used, such as LLC, IPS for unit root, Johansen-Fisher panel co-integration to check the long-run association between the considered variables from 2000 to 2020. Further, a panel quantile regression and panel fixed effect model is used in the study to explore the nexus. The study found a long-run association between institutional quality (IQ), energy production from oil (EPOil), natural gas (EPGas), coal (EPCoal), renewables (EPRenew), and CO2 emission in BRI countries. According to panel unit-root tests, all variables are integrated of order I(1), and the panel co-integration test showed a log-run association among variables. The results of panel quantile regression and panel fixed effect model showed a positive association between IQ and CO2 emission. Similarly, an association of CO2 emission with EPGas, EPOil, and EPCoal is also significantly positive. The extraction and use of fossil fuels (natural gas, oil, and coal) pollute the air, while, on the other hand, there is a negative relationship found between CO2 emission and EPRenew. When developing environmental protection measures, governments should choose to concentrate on the quality of institutions. The effectiveness of institutions in BRI countries will provide appropriate rules, regulations, property rights, and methods to fight corruption, which, if followed systematically, would decrease CO2 emissions and enhance the quality of the environment in BRI countries.

Striving towards sustainable development: how environmental degradation and energy efficiency interact with health expenditures in SAARC countries.

The previous studies focused on environmental issues, identifying their root causes, urging prompt action to reduce environmental degradation. In this context, the current article extends the literature by incorporating the ecological impacts on the health sector and the role of sustainable development. The present study adds to the body of knowledge by examining the relationship between CO2 emissions, sustainable development, energy efficiency, energy intensity, and health expenditures for SAARC countries from 2000 to 2020. Fully modified OLS (FMOLS) and dynamic OLS (DOLS) are used and diagnostic tests to check the association between the variables. The empirical analysis validated the long-run impact of the examined factors on health expenditures. The results show that energy efficiency and sustainable development have a statistically significant negative effect on health expenditures, vice-versa for CO2 emission. Energy efficiency, energy intensity, and CO2 emissions have been shown to have a one-way causative relationship with health expenditures, but sustainable development and economic growth have a two-way causation relationship. The better health status of the SAARC economies necessitates the establishment of long-term development strategies, environmental sustainability, and an examination of the energy sector. This work's conceptual and empirical advances have significant policy ramifications for this part of the globe and its efforts to improve sustainability.

The nexus of sectoral-based CO2 emissions and fiscal policy instruments in the light of Belt and Road Initiative.

Climate change due to global warming is becoming a major global issue over the past few decades. The emission of carbon dioxide (CO2) and other greenhouse gasses cause global warming. Most carbon emissions come from energy sectors, whereas transportation, industrial, and residential sectors are among the chief contributors. The present study investigates the effect of fiscal policy instruments, economic development, and foreign direct investment (FDI) on the sectoral emissions in Belt and Road Initiative (BRI) countries. The data used in this study is taken from the World Development Indicators (WDI) for the period between 2000 and 2018. Dynamic ordinary least squares (DOLS) and fully modified ordinary least squares (FMOLS) have been used to analyze the long-run impact of fiscal policy instruments, economic development, and FDI on CO2 emissions from transportation, energy, and industrial sectors. Furthermore, the pairwise Dumitrescu and Hurlin panel causality test was used to authorize the causal relationship among the variables under consideration. The results reveal that fiscal policy instruments, per capita gross domestic product, FDI, and CO2 emissions show a strong correlation in the industrial, electrical, and transportation sectors. Furthermore, it is shown that public spending is a more reliable tool to reduce CO2 emissions in the transportation and industrial sectors in the BRI region. This study provides useful information for policy-makers on taking preventive and corrective measures to reduce CO2 emissions in different sectors and promote sustainable development.

A Stemness and EMT Based Gene Expression Signature Identifies Phenotypic Plasticity and is A Predictive but Not Prognostic Biomarker for Breast Cancer.

Aims: Molecular heterogeneity of breast cancer results in variation in morphology, metastatic potential and response to therapy. We previously showed that breast cancer cell line sub-groups obtained by a clustering approach using highly variable genes overlapped almost completely with sub-groups generated by a drug cytotoxicity-profile based approach. Two distinct cell populations thus identified were CSC(cancer stem cell)-like and non-CSC-like. In this study we asked whether an mRNA based gene signature identifying these two cell types would explain variation in stemness, EMT, drug sensitivity, and prognosis in silico and in vitro. Main methods: In silico analyses were performed using publicly available cell line and patient tumor datasets. In vitro analyses of phenotypic plasticity and drug responsiveness were obtained using human breast cancer cell lines. Key findings: We find a novel gene list (CNCL) that can generate both categorical and continuous variables corresponding to the stemness/EMT (epithelial to mesenchymal transition) state of tumors. We are presenting a novel robust gene signature that unites previous observations related either to EMT or stemness in breast cancer. We show in silico, that this signature perfectly predicts behavior of tumor cells tested in vitro, and can reflect tumor plasticity. We thus demonstrate for the first time, that breast cancer subtypes are sensitive to either Lapatinib or Midostaurin. The same gene list is not capable of predicting prognosis in most cohorts, except for one that includes patients receiving neo-adjuvant taxene therapy. Significance: CNCL is a robust gene list that can identify both stemness and the EMT state of cell lines and tumors. It can be used to trace tumor cells during the course of phenotypic changes they undergo, that result in altered responses to therapeutic agents. The fact that such a list cannot be used to identify prognosis in most patient cohorts suggests that presence of factors other than stemness and EMT affect mortality.

A novel 20-gene prognostic score in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. In order to better prognosticate patients with PDAC, we identified 20 genes by utilizing publically available high-throughput transcriptomic data from GEO, TCGA and ICGC which are associated with overall survival and event-free survival. A score generated based on the expression matrix of these genes was validated in two independent cohorts. We find that this "Pancreatic cancer prognostic score 20 -PPS20" is independent of the confounding factors in multivariate analyses, is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological sub-groups but can predict response to targeted therapy as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.

Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide.

Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML.

The nexus of fiscal policy instruments and environmental degradation in China.

As one of the world's largest economies, Chinese economy is maintaining the rapid economic development along with the cost of environmental degradation. The role of fiscal policy instruments is still unknown in the Chinese pollution equation. To do this, the present study is an effort to quantify the nexus of fiscal policy instruments and environmental degradation for Chinese economy over 1980 to 2016. The results reveal that fiscal policy instruments significantly increase the environmental degradation in the long run. The GDP and energy consumption of Chinese economy also enhance the environmental degradation respectively. The innovative accounting approach and diagnostics tests also applied to confirm the empirical estimates of study are reliable and valid for policy implications. The outcomes of study reveal that expansionary fiscal policy will lead to environmental degradation. Therefore, the Chinese authorities may consider the usage of advance and eco-friendly production methods to sustain the fast-growing economic growth along with the healthier environment.

Simultaneous miRNA and mRNA transcriptome profiling of glioblastoma samples reveals a novel set of OncomiR candidates and their target genes.

Although glioblastomas are common, there remains a need to elucidate the underlying mechanisms behind their initiation and progression and identify molecular pathways for improving treatment. In this study, sixteen fresh-frozen glioblastoma samples and seven samples of healthy brain tissues were analyzed with miRNA and whole transcriptome microarray chips. Candidate miRNAs and mRNAs were selected to validate expression in fifty patient samples in total with the criteria of abundance, relevance and prediction scores. miRNA and target mRNA relationships were assessed by inhibiting selected miRNAs in glioblastoma cells. Functional tests have been conducted in order to see the effects of miRNAs on invasion, migration and apoptosis of GBM cells. Analyses were carried out to determine correlations between selected molecules and clinicopathological features. 1332 genes and 319 miRNAs were found to be dysregulated by the microarrays. The results were combined and analyzed with Transcriptome Analysis Console 3 software and the DAVID online database. Primary differential pathways included Ras, HIF-1, MAPK signaling and cell adhesion. OncomiR candidates 21-5p, 92b-3p, 182-5p and 339-5p for glioblastoma negatively correlated with notable mRNA targets both in tissues and in in vitro experiments. miR-21-5p and miR-339-5p significantly affected migration, invasion and apoptosis of GBM cells in vitro. Significant correlations with overall survival, tumor volume, recurrence and age at diagnosis were discovered. In this article we present valuable integrated microarray analysis of glioblastoma samples regarding miRNA and gene-expression levels. Notable biomarkers and miRNA-mRNA interactions have been identified, some of which correlated with clinicopathological features in our cohort.

Seroprevalence and risk factors associated with bovine brucellosis in the Potohar Plateau, Pakistan.

BACKGROUND: The seroprevalence and risk factors of bovine brucellosis were studied at animal and herd level using a combination of culture, serological and molecular methods. The study was conducted in 253 randomly selected cattle herds of the Potohar plateau, Pakistan from which a total of 2709 serum (1462 cattle and 1247 buffaloes) and 2330 milk (1168 cattle and 1162 buffaloes) samples were collected. Data on risk factors associated with seroprevalence of brucellosis were collected through interviews using questionnaires. Univariable and multivariable random effects logistic regression models were used for identifying important risk factors at animal and herd levels. RESULTS: One hundred and seventy (6.3%) samples and 47 (18.6%) herds were seropositive for brucellosis by Rose Bengal Plate test. Variations in seroprevalence were observed across the different sampling sites. At animal level, sex, species and stock replacement were found to be potential risk factors for brucellosis. At herd level, herd size (≥9 animals) and insemination method used were important risk factors. The presence of Brucella DNA was confirmed with a real-time polymerase chain reaction assay (qRT-PCR) in 52.4% out of 170 serological positive samples. In total, 156 (6.7%) milk samples were positive by milk ring test. B. abortus biovar 1 was cultured from 5 positive milk samples. CONCLUSION: This study shows that the seroprevalence of bovine brucellosis is high in some regions in Pakistan. Prevalence was associated with herd size, abortion history, insemination methods used, age, sex and stock replacement methods. The infected animal may act as source of infection for other animals and for humans. The development of control strategies for bovine brucellosis through implementation of continuous surveillance and education programs in Pakistan is warranted.