Articles

<b>Background: </b>While the link between depression and smoking is known, less is known about<b> </b>the relationship between hopelessness and smoking in large national community-based sample of Black people.<b> </b><b>Aims: </b>This study investigates the association between hopelessness and smoking status, using data from the National Survey of American Life (NSAL), which is the only ethnically diverse nationally representative sample of Black adults.<b> </b><b>Methods: </b>Data from the NSAL were analyzed. Hopelessness and smoking status were assessed using structured interviews. Logistic regression was employed to assess the link between hopelessness and smoking status, controlling for potential confounders such as demographic factors and socioeconomic indicators as well as depression.<b> </b><b>Results: </b>4,939 participants entered our analysis. Hopelessness was significantly associated with higher odds of smoking status. This association remained robust after adjusting for confounders such as demographic factors, socioeconomic status, and depression.<b> </b><b>Conclusions: </b>Hopelessness<b> </b>may be a critical risk factor for smoking in Black adults. Promoting hope as a component of targeted tobacco cessation programs may help reduce tobacco use of Black populations.

<b>Background: </b>Emotional problems have been associated with substance use, yet longitudinal research examining this relationship during childhood and adolescence in large, diverse, community-based samples remains limited.<b> </b><b>Aims: </b>This study investigates the prospective associations between three emotional problems—hopelessness, depression, and suicide attempts—before ages 9–10 and the subsequent initiation of tobacco and marijuana use before ages 14–15, using data from the Adolescent Brain Cognitive Development (ABCD) study.<b> </b><b>Methods: </b>Data from the ABCD study were analyzed. Baseline emotional problems, including hopelessness, depression, and suicide attempts, were assessed at ages 9–10 through structured parent interviews. Substance use outcomes (tobacco and marijuana initiation) were tracked from baseline to follow-up at ages 14–15 using structured self-report measures. Structural Equation Modeling (SEM) was employed to assess the predictive roles of these early-life emotional problems, controlling for potential confounders such as demographic factors and family and neighborhood socioeconomic status.<b> </b><b>Results: </b>Baseline hopelessness, depression, and suicide attempts at ages 9–10 were significant predictors of tobacco and marijuana use initiation at ages 14–15. These associations remained robust after adjusting for confounders, indicating the independent effects of early emotional problems on adolescent substance use initiation.<b> </b><b>Conclusions: </b>Emotional problems in early childhood, including hopelessness, depression, and suicidal behavior, are critical predictors of substance use initiation during adolescence. These findings underscore the importance of early identification and targeted mental health interventions to reduce the risk of substance use among vulnerable youth.

Pharmaceutical supply chains are critical to ensuring the availability of safe and effective medications, yet they face numerous challenges that can jeopardize public health. This article provides a comprehensive analysis of the key issues impacting pharmaceutical supply chains, including regulatory compliance, demand forecasting, supply chain visibility, quality assurance, and geopolitical risks. Regulatory compliance remains a significant concern due to the stringent guidelines imposed by authorities such as the FDA and EMA, which can lead to increased operational costs and time delays. Additionally, traditional demand forecasting methods often fail to accurately predict fluctuations in drug demand, resulting in stockouts or excess inventory. Limited supply chain visibility further complicates these challenges, hindering timely decision-making and operational efficiency. Quality assurance is paramount, as maintaining the integrity of pharmaceutical products throughout the supply chain is crucial to preventing costly recalls and ensuring patient safety. Moreover, the globalization of supply chains introduces vulnerabilities to geopolitical risks, trade disputes, and natural disasters. In response to these issues, this article outlines strategic recommendations for optimizing pharmaceutical supply chains. These include leveraging advanced analytics and IoT technologies to enhance demand forecasting and visibility, strengthening compliance through automated systems and training, fostering collaboration among stakeholders, implementing robust risk management frameworks, and investing in quality management systems. By adopting these strategies, pharmaceutical companies can enhance the efficiency and resilience of their supply chains, ultimately ensuring the continuous availability of essential medications for patients worldwide. This analysis serves as a critical resource for industry professionals seeking to navigate the complexities of pharmaceutical supply chains in an increasingly dynamic global environment.

Active Pharmaceutical Ingredients (APIs) serve as the cornerstone of pharmaceutical development, driving therapeutic efficacy and safety in drug formulations. This article provides a comprehensive overview of the lifecycle of APIs, starting from their discovery and development, through to manufacturing processes and regulatory oversight. The development of APIs begins with intensive research and discovery efforts, where medicinal chemists and pharmacologists identify and optimize potential compounds through computational modelling, high-throughput screening, and structure-activity relationship studies. Promising candidates undergo rigorous preclinical testing to assess pharmacological properties, safety profiles, and potential adverse effects in animal models. Upon successful preclinical outcomes, APIs progress to clinical trials, involving phases of testing in human subjects to evaluate efficacy, dosage regimens, and safety profiles under controlled conditions. Clinical trial data are meticulously analyzed to support regulatory submissions, demonstrating the API's therapeutic benefits and safety for eventual patient use. Manufacturing APIs involves complex chemical synthesis or biotechnological methods, ensuring precise control over reaction conditions, purity, and yield. The scale-up from laboratory synthesis to industrial production demands adherence to Good Manufacturing Practices (GMP), where stringent quality control measures verify consistency, potency, and stability throughout production batches. Regulatory oversight by authorities such as the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) in Europe ensures that APIs meet stringent standards of safety, efficacy, and quality before market approval. Manufacturers must submit comprehensive Chemistry, Manufacturing, and Controls (CMC) data, detailing manufacturing processes, analytical methods, and stability studies to support regulatory filings.

The pharmaceutical industry relies extensively on Active Pharmaceutical Ingredients (APIs) as essential components in the production of drugs. The supply chain supporting these APIs is complex, encompassing multiple stages from raw material sourcing to distribution to pharmaceutical manufacturers worldwide. This manuscript explores the intricate challenges encountered within the pharmaceutical API supply chain, focusing on regulatory compliance, quality control, supply chain disruptions, and global dependencies. Regulatory compliance poses a significant hurdle, with varying standards across regions necessitating meticulous adherence to ensure market access and product safety. Quality control and assurance are paramount to maintaining consistency and purity in APIs, yet they present ongoing challenges such as batch variability and contamination risks. Supply chain disruptions, ranging from natural disasters to geopolitical tensions, highlight vulnerabilities in global sourcing strategies, underscoring the need for resilient supply chain management practices. Global dependencies on a limited number of suppliers or regions expose the industry to supply shortages and pricing pressures, exacerbated by geopolitical events and trade policies. These dependencies necessitate strategic diversification and risk mitigation efforts to ensure continuity in API availability and affordability. By addressing these challenges collaboratively, stakeholders can enhance the resilience and reliability of the pharmaceutical API supply chain, thereby ensuring uninterrupted access to essential medications and improving global healthcare outcomes.

The global pharmaceutical supply chain plays a crucial role in ensuring the timely and safe delivery of medicines to patients worldwide. However, the increasing presence of counterfeit drugs within this supply chain poses a significant and growing risk to public health, patient safety, and the integrity of the pharmaceutical industry. Counterfeit drugs—medications that are fraudulently manufactured, mislabeled, or contain incorrect or harmful ingredients—are a major concern as they can lead to ineffective treatments, adverse health effects, and even death. Despite stringent regulatory frameworks and advanced technological solutions, counterfeit drugs continue to infiltrate legitimate supply chains due to factors such as the complexity of the distribution system, global trade practices, and inadequate enforcement in certain regions. This manuscript explores the primary causes behind the proliferation of counterfeit drugs in pharmaceutical distribution, the associated risks, and the multifaceted approaches required to address this growing threat. It discusses the importance of regulatory measures, including international cooperation and stronger compliance frameworks, as well as the role of emerging technologies like serialization, blockchain, and RFID in ensuring traceability and product authenticity. By focusing on the integration of these technologies, the paper also highlights the potential of innovative solutions to enhance transparency, reduce vulnerabilities, and protect the integrity of pharmaceutical supply chains. Additionally, it emphasizes the importance of public awareness campaigns and collaboration between key stakeholders, including pharmaceutical manufacturers, distributors, regulators, and healthcare providers, in creating a more secure and trustworthy pharmaceutical distribution ecosystem. Through a comprehensive exploration of these strategies, this manuscript aims to provide a roadmap for mitigating the risks posed by counterfeit drugs and ensuring the safety and efficacy of medicines for consumers worldwide.

Alpha emitters in internal contamination are the main cause of homosexuality. There is a pattern that can be identified and described precisely as a hormone cloning process, after initial loss from alpha emitters of testosterone, and development of a painkilling effect through steroid accumulation with sodomy feeding development of steroidogenic cells. This altogether explains how homosexuality becomes a self-refeeding bubble. A treatment method is proposed at the end to break the cycle and help the subject return into heterosexuality.

The equipment used in the construction industry is usually associated with a high impact on the environment. Although sustainable design has shown to be a main player among the initiatives focused on reducing environmental impact, it has been driven by the workers and processes, leaving the equipment endeavors in more restrictive and later stages. The equipment industry has been a constant target of environmental standards and economic pressure, but the increasing technological development allows it to respond to sustainability and safety expectations while enhancing its performance. However, there are still several limitations that lead this sector to be one of the last to reach upgrading levels in terms of development. A study identified some gaps in the equipment design that require a greater effort to effectively support the workers and companies towards sustainable construction. This chapter is based on a study aiming to understand the consolidated knowledge of technologically sustainable equipment design and to identify the challenges left for its full development. The findings support the development of innovative eco-friendly equipment, taking into consideration sustainable materials and product guidelines, as well as green economy initiatives. It also supports complex system approaches and safety by design specificities to establish a corporate knowledge of sustainable equipment and align it with the new regulations of the construction industry. The chapter introduces the context of construction equipment in terms of new challenges when faced with the need to provide construction work with a greater capacity for safety, from an environmental and energy efficiency perspective, and within the paradigm of sustainability. Then, it presents the concept of sustainable equipment considering its principles, followed by a characterization of the agents involved in its life cycle.

Triple negative breast carcinoma (TNBC) is a rapid progressive tumor and has a poor overall survival. Therefore, it is crucial to find out effective molecular targets and develop optimal therapeutic strategies for TNBC. In this study, immunohistochemical staining was used to detect expressions of programmed death-ligand 1 (PD-L1) and phosphatase and tensin homolog (PTEN) in 136 breast carcinomas including 50 TNBC. The effect of PTEN on regulation of PD-L1 expression was assessed in vitro in the PTEN knockdown TNBC cells. We found that PD-L1(SP142) positive rate in TNBC (48.0%) was significantly higher than non-TNBC (23.3%). PTEN negative rate was 42% in TNBC. The inverse correlation between PTEN and PD-L1(SP142) expression in TNBC was statistically significant (<i>P</i><0.05). After PTEN knockdown, PD-L1 expression in TNBC cells increased significantly, and the expression level of AKT increased simultaneously. PTEN knockdown promoted cell proliferation, viability and G1/S switch of TNBC cells. These results suggested that PTEN may involve in regulation of PD-L1 expression, because PTEN loss can upregulate PD-L1 expression in TNBC. Antitumor immunity of PD-L1 could be enhanced in TNBC when targeting PTEN at the same time.

Environmental regulation is one of the most important subsets of social regulation. Regulation is a framework for implementing the rules adopted in society, and legal standards guarantee this framework. Thus, if the legislation prohibits the dumping of waste on public waterways and imposes a penalty for its violation, this prohibition can be interpreted as an expression of society's public commitment to environmental protection and public condemnation of polluting behaviors. On the other hand, it can be said that the destruction of the environment is morally wrong, and therefore the legal prohibition of these behaviors can be interpreted as an expression of this moral claim. This research is based on library studies and descriptive-analytical methods and has an innovative approach. The purpose of this study is to explain the role of law as a facilitator of the executive structure of environmental regulation inappropriate conditions in line with social interaction. It also seeks to explain the importance of regulation and regulation. Regulation is one of the most important social standards and guarantees the strong implementation of legal obligations in society. This fundamental standard has been established in public law and seems to be an important approach to protecting the environment and citizens' adherence to environmental obligations.

This paper shows how Big Data Analytics (BDA) and Artificial Intelligence (AI) automation facilitate regulatory compliance in Finance. Regulatory compliance is essential in helping institutions to mitigate reputational, litigation, and financial risk. Existing literature reveals several preconditions for compliance. However, much of the literature has adopted an internal view of compliance without considering external regulatory frameworks. This research draws on the cognitive model of regulation that looks at regulatory compliance as a social construct. It uses a triangulation research method comprising literature review, interview of trade compliance experts, and questionnaire survey of compliance practitioners to understand how regulation affects compliance and what role ICTs play in implementing compliance. The findings of this study present a regulatory compliance framework comprising four cognitive stages and a conceptual regulatory compliance system that presents how BDA and AI automation are applied to mitigate regulatory complexity and enhance regulatory compliance. The conceptual regulatory compliance system shows how BDA and AI enable institutions to dynamically assess regulatory risk, automatically monitor compliance, and intelligently predict risk violations mitigating regulatory complexity and preventing producing unnecessary documents. It provides theoretical contributions to understanding regulatory evolution and compliance and practical implications for understanding how regulation evolves to be more complicated and elements of a regulatory compliance system mitigate proliferating regulations. Additionally, it provides avenues for future research into the relationship between competing regulatory mandates and how institutions cope with that. Regulations are important for ensuring compliance and governance in finance and to curb systemic risk. Complying with regulations is difficult due to their growing volume, complexity, and fragmentation. Institutions use large-scale Information and Communication Technologies (ICTs), such as Big Data Analytics (BDA) and Artificial Intelligence (AI) automation, to monitor compliance and mitigate regulatory complexity. However, less is known about how firms comply with regulation. Most literature does not thoroughly investigate regulatory elements nor explicitly relate them to compliance.

The multitude of services and resources available in multi-cloud environments has increased the importance of analytics applications in cloud brokering. These applications can orchestrate services and resources that reside in different domains and require inputs that a single cloud provider could not easily acquire. Yet, despite their distinct characteristics, multi-cloud analytics users have no voice in the ranking of the services in brokerage marketplaces. In this chapter, we introduce the concept and propose the implementation of explainable analytics to increase transparency and user satisfaction in multi-cloud environments. The criteria that we have identified and measured in order to summarize them in explainable results allow cloud users to acquire an understanding of the ranking rules, a crucial requirement in trustful decision-making. Our proposal accounts for a set of regulations for intelligent systems and targets their specific adaptation and use in multi-cloud environments.