Search Results (163)

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metastatic. In this context, drug repurposing has emerged as a promising strategy to improve treatment options due to the limited number of effective treatments and the heterogeneity of the disease. Indeed, a large number of non-oncology drugs have the potential to address more than one target that could be therapeutic for cancer patients. Although many repurposed drugs are used off-label, efficacy for the new use must be demonstrated in clinical trials. Within regulatory frameworks, both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have procedures to reduce the need for extensive new studies and to expedite the review of drugs for serious conditions when preliminary evidence indicates substantial clinical improvement over available therapy. In spite of several advantages, including reduced development time, lower costs, known safety profiles, and faster regulatory approval, difficulty in obtaining new patents for old drugs with limited protection for intellectual property may reduce commercial returns and disincentivize investments. This review aims to provide comprehensive information on some marketed drugs currently under investigation to be repurposed or used in clinical practice for NETs and to discuss the major clinical challenges. Although drug repurposing is a useful strategy for early access to medicines, the monitoring of the clinical benefit of oncologic drugs during the post-marketing authorization is crucial to support the safety and effectiveness of treatments. Full article

In this study, we utilize a unique quarterly dataset of non-GAAP earnings to re-examine the “informational” role of non-GAAP earnings from the perspective of value relevance and earnings predictability in the post-Reg G period. We find that non-GAAP earnings are more value relevant and can better predict future operating earnings of a firm compared to equivalent GAAP earnings. Additionally, we also find empirical evidence suggesting that the difference in the value relevance and earnings predictability between non-GAAP and equivalent GAAP earnings can vary across but cannot be completely mitigated by firm-level characteristics, such as the market value of equity, accruals quality, analyst coverage, and managerial ability of a firm. Moreover, our supplementary analysis reveals that the superior value relevance and predictive power of non-GAAP earnings persist even after the SEC’s release of the Compliance and Disclosure Interpretations (C&DI) in 2010. Overall, our empirical evidence suggests a superior “informational” role of non-GAAP earnings to equivalent GAAP earnings in terms of valuation and predictability on future operating performance in the post-Reg G period. Full article

This study defines evidence-based minimum internal floor areas required to support long-term residential use across different household types. It addresses the following question: what is the smallest viable floor area that supports sustained occupancy without persistent stress, conflict, or turnover? An integrative review method was employed, drawing from behavioural studies in environmental psychology, international regulatory standards, and real-world market data. The analysis focuses on essential domestic functions including sleep, hygiene, food preparation, storage, social interaction, and work. Quantitative findings from tenancy surveys, post-occupancy research, and market performance data indicate that residential units below 30 square metres for single occupants and 45 square metres for couples are consistently associated with reduced satisfaction and shorter tenancies. Regulatory minimums across diverse jurisdictions tend to converge near these same thresholds. The study proposes technical minimums of 30, 45, and 60 square metres for one-, two-, and three-person households, respectively. These values reflect functional lower bounds rather than ideal or aspirational sizes and are intended to inform performance-based housing standards. Full article

Background: Neisseria meningitidis B is one of the main causative pathogens of meningitis and other forms of severe meningococcal disease. In the past decade, meningococcal B vaccines have been developed to address this infection and its sequelae. Objective: This article aims to present an example of how the EU regulatory framework allowed the early authorisation of two life-saving vaccines initially based on immunogenicity surrogates of clinical evidence. This was subsequently followed by post-marketing surveillance providing real-world evidence to support their safety profile and impact on the paediatric population in the EU. Methods: We review the evidence supporting the initial regulatory approval of the vaccines, the confirmatory data demonstrating vaccine effectiveness post-authorisation, and the real-world impact of these vaccines on the paediatric population. Results: Two vaccines were approved in the EU for active immunisation to prevent IMD caused by MenB (4CMenB in 2013 and MenB-fHBP in 2017). Both marketing authorisations were based on immunogenicity data (efficacy studies were not feasible due to the rarity of the disease) and safety data generated from pre-authorisation studies. Additional pharmacovigilance activities to further investigate the safety profile and effectiveness studies were requested to be conducted after approval. Both the effectiveness and safety profile of the vaccines were confirmed by these data. Conclusions: This paper illustrates that the EU medicines regulatory framework and safety monitoring system are robust. By supplementing the initial evidence with post-authorisation studies, further effectiveness and safety data enabled regulators to confirm the positive benefit–risk of the vaccines without delaying their access to the people who need them. Full article

In today’s competitive environment of online service industries, particularly e-commerce, meeting consumer expectations is essential for service providers to ensure service quality. However, service failures are unavoidable, leading to unfavorable consequences for businesses. Understanding the mechanisms for customer recovery after negative service experiences is crucial. Using cognitive–emotional personality systems theory and benign violation theory, this study constructed a theoretical model. A total of 351 samples were collected through a situational simulation experiment for a linear regression analysis. A self-mocking response strategy positively influenced brand trust through perceived brand authenticity regarding the dimensions of credibility, integrity, and symbolism. Simultaneously, brand trust was identified as a key driver of post-recovery satisfaction. This study proposes a chain mediation model, which incorporates perceived authenticity and brand trust, to fully comprehend the mechanisms underlying consumers’ satisfaction after service recovery. Our findings provide empirical evidence for the effects of self-mockery on post-recovery satisfaction, as well as suggestions for marketers seeking efficient means to meet consumers’ emotional and cognitive demands during service recovery situations. Full article

In the context of macroeconomic recovery and accelerating digital transformation in the post-pandemic era, the hotel industry in China is undergoing profound structural changes. This research investigates the core competencies required for hotel managers to navigate these challenges. Data was collected via a quantitative survey involving a structured questionnaire, was conducted among hotel managers in Shanghai, China, resulting in 404 valid responses. Employing exploratory factor analysis using SPSS, this study identifies seven key competency dimensions encompassing 36 ranked items, including interpersonal communication, leadership, operational knowledge, human resource management, financial analysis, technology, and administrative management. The results show that economic recovery has brought new opportunities but also challenges to the hotel industry, and that managers must possess a diverse set of core competencies to adapt to the demanding new market changes. The novelty of this research lies in its empirical grounding and its focus on the intersection of digitalization and economic recovery within China’s hotel industry. It pioneers a dynamic strategic competency framework tailored to the evolving demands of the hotel industry during a period of economic volatility, providing empirical evidence and advice for optimizing the industry’s talent training systems. Simultaneously, it brings a new perspective for dealing with the recovery path for the hotel enterprises in other urban and travel destinations, aiming to promote industry sustainability and competitive advantages. Future research could extend the proposed framework by exploring its applicability across different cultural and economic contexts. Full article

Purpose: The acquirer’s corporate environmental performance (CEP) in mergers and acquisitions has been a subject of debate, yielding mixed results. This paper uses the US firm-level data of 1437 M&A deals from 2002–2019 to examine the impact of overall CEP, resource use, emissions, and innovation on the acquirers’ post-merger market value. Design/methodology/approach: This study employs multi-level fixed effects panel regression using Ordinary Least Squares (OLS) and the instrumental variable (IV) 2SLS method to estimate the models and compare the results with those from robust estimation. Absorbing the multiple levels of fixed effects (i.e., firm, industry, and year) offers a novel and robust algorithm for efficiently accounting for unobserved heterogeneity. The results from IV (2SLS) are more convincing, as the method overcomes the problem of endogeneity due to reverse causality and sample selection bias. Findings: The authors find that CEP has a significant impact on market value, particularly in the long term. While both resource use and emissions performance have positive effects, emissions performance has a stronger impact, presumably because external stakeholders and market participants are more concerned about emissions reduction. The performance of environmental innovation is relatively weak compared to other pillars. Descriptive analysis shows low average scores in environmental innovation compared to the resource use and emissions performance of the acquirers. However, large deals yield significant returns from investing in environmental innovation in both the short and long term compared to small deals. Practical implications: This paper offers several practical implications. First, environmental performance can help improve the acquirer’s long-term market value. Second, managers can focus on the strategic side of environmental performance, based on its pillars, and benchmark their relative position against peers. Third, environmental innovation can be considered a new potential, as the market as a whole in this area is still lagging. Given the growing pressure to improve environmental technology and innovation, prospective acquirers should confidently prioritise actions on green revenue, product innovation, and capital expenditure now rather than ticking these boxes later. Originality value: The key contribution is offering valuable insights into the impact of acquirers’ environmental performance on long-term value creation in mergers and acquisitions (M&A). These results fill the gap in the literature focusing mainly on the effect of environmental pillar and sub-pillar scores on acquirer’s firm value. The authors claim that analysing sub-pillar-level granularity is crucial for accurately measuring the effects on firm-level performance. Full article

Background/Objectives: Due to limited current evidence, this post-marketing database surveillance study aimed to investigate the occurrence of hospitalization due to community-acquired pneumonia (CAP) among patients with chronic obstructive pulmonary disease in Japan who received single-inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) or multiple-inhaler triple therapy (MITT). Methods: This retrospective cohort study used health insurance claims data from the Medical Data Vision Co., Ltd. database (November 2017–April 2023) to identify overall and incident users of FF/UMEC/VI or MITT. Index date was the start of FF/UMEC/VI or MITT. Hazard ratios (HRs) for CAP hospitalization were assessed using inverse probability of treatment weighting based on propensity scores (PS). Incidence rates and time to occurrence of CAP hospitalization were also assessed. Adjustments were made to the PS model to address missing body mass index data. Results: In total, 8790 and 10,881 patients were included in the overall FF/UMEC/VI and MITT cohorts, and 3939 and 4017 patients were included in the incident FF/UMEC/VI and MITT cohorts, respectively. HR for CAP hospitalization among incident users ranged from 1.05 to 1.15 across all PS adjustments. Similar incidence rates of CAP hospitalization were reported among both cohorts and across all PS adjustments. The cumulative adjusted incidence rates of first CAP hospitalization at 360 days post-index among incident users was 0.060 and 0.054 in the FF/UMEC/VI and MITT cohorts, respectively. Conclusions: There was no difference in the risk of CAP between patients treated with FF/UMEC/VI and MITT. This safety information may help healthcare providers select appropriate treatments. Full article

This study explores the drivers and evolution of the shadow economy in Bosnia and Herzegovina—a transitional, post-conflict country facing persistent institutional fragility. Using the Multiple Indicators and Multiple Causes (MIMIC) model, an extension of Structural Equation Modeling, the paper estimates the size and dynamics of the shadow economy from 1996 to 2022. The model integrates macroeconomic indicators (employment rate, GDP per capita, tax revenues) and institutional variables (rule of law, control of corruption), with data primarily sourced from the World Bank. The results show that institutional quality, tax burden, and labor market conditions are significant determinants of the informal sector. The model demonstrates strong statistical validity (CFI = 0.986, RMSEA = 0.05), supported by robustness checks including unit root tests, structural break analysis, and the exclusion of controversial benchmarking methods. The shadow economy responds markedly to major shocks such as the 2008 global financial crisis and the 2014 floods. Findings provide valuable policy insights: strengthening institutions, simplifying tax systems, and encouraging formal labor market participation can significantly reduce informality. The study supports evidence-based reforms to enhance transparency, resilience, and sustainable development in Bosnia and Herzegovina. Full article

Background/Objectives: We reviewed Post-Marketing Requirements (PMRs) under the Pediatric Research Equity Act (PREA) for antibiotics approved in adults from 2009 to 2024 to better understand factors associated with PMR study completion. Methods: Initial PMRs, including study design and completion timelines were extracted from Food and Drug Administration (FDA) approval letters. Studies were cross-referenced at clinicaltrials.gov, with follow-up from adult approval to study completion or through 31 December 2024. Results: Eighteen antibiotics were approved in adults from 2009 to 2024, with 53 associated PREA PMRs. A total of nine PMRs were excluded from analysis (six exclusions for projected study completion dates on or after 12/31/2024, one exclusion due to lack of information, and two exclusions because the study type was not categorizable as Phase 1 or Phase 2). Of the 44 remaining PMRs in the analysis set, the median pediatric study follow-up time from adult approval was 5.3 years (range 0.94 to 11.5 years), with a study completion rate of 54.5% (N = 24). Small- and medium-sized companies had a study completion rate of 10% (N = 2/20) over a median of 6.44 years of follow-up, with no pediatric approvals. Large pharmaceutical corporations had a significantly higher study completion rate of 91.6% (N = 22/24; adjusted hazard ratio 20.3 95%CI, 5.02 to 82.4) over a median follow-up time of 4.7 years and achieved pediatric approval with labelling updates for 75% of antibiotics (N = 6/8). Conclusions: Compared to larger organizations, smaller pharmaceutical companies have experienced difficulty in PREA PMR antibiotic study completion, which may be related to financial difficulties in the challenging market for antibiotics. To improve PMR study completion, smaller companies require continued financial support and innovation in study design. For pediatric antibiotic development, the FDA accepts the extrapolation of efficacy from well-conducted randomized adult trials (i.e., pharmacokinetics (PK) and the safety approach). Therefore, sponsors should consider the use of single-arm, non-comparative PK and safety study designs to reduce the size and scope of trials. Sponsors should also assess whether the evaluation of an antibiotic is necessary in adolescents, or if data in a surrogate population of adults (e.g., low-weight adults) may serve as adequate evidence for adolescent approval. Full article

Background: Protein supplements are among the most popular, available and growing complementary products. Fraud related to the mislabeling, inaccurate analysis or declaration of ingredient quantities, and health claims not aligned with those approved by EFSA is high. This study aims to analyze the claims related to protein supplements in commercial messages. Methods: An observational cross-sectional study was conducted to analyze the content and the degree to which health claims stated on the labeling or technical data sheets of protein supplements comply with those authorized by current European legislation and supported by existing scientific evidence. The products were searched for using Amazon and Google Shopping. Results: Of the 209 health claims evaluated, 60 claims fully complied with the recommendations, representing 28.7% of the total (n = 209). In contrast, 12 claims in which the stated text did not conform to the health claims established by EFSA were identified, representing 5.7% of the total (n = 209). The most widely used unauthorized health claims on the market are those referring to “Post-workout recovery” (11.1%), followed by “Promotes muscle recovery (casein)” (9.5% each), referring to whey protein and casein, respectively. Of all the products analyzed in the study, 43.8% (n = 46) of the products made health claims not authorized by the EFSA. Conclusions: These findings suggest that the high-quality advertising of protein supplements should engage consumers, industry stakeholders, scientific research, and the European Food Safety Authority to ensure compliance with European regulations, provide accurate guidance for manufacturers, and protect consumer rights under current legislation. Full article

In wine production, technology influences its chemical composition, which in turn affects its organoleptic properties. As a result, innovative production techniques play a crucial role on the competitive wine market. Underwater wine aging has gained increasing popularity in recent years as an innovative method that can expand the variety of products available and bring engaging story telling. Some companies now offer this service to wine producers, although there is still limited knowledge about its effects on different wine types. This preliminary study investigated the impact of underwater aging by examining a well-structured red wine that was submerged for several months in spring water, comparing them to the same wine aged in a cellar for the same period. The chemical properties of the wines were analyzed after both the first (12 months of underwater and cellar aging), second (another 12 months), and third aging periods (further 12 months), to determine if there were any significant differences between them. The results revealed that underwater aging had a significant impact on the wines’ chemical composition. The dissolved oxygen level and total anthocyanin content were most notably affected by the different aging methods, while the phenolic profile and color compounds showed less influence from the treatments. The sensory test indicated that the wines aged under water and in the cellar were perceived differently, depending on the aging method and the time of evaluation (after 12, 24 or 36 months). The results of the organoleptic tests underline how the effect of the conservation environment on the sensory properties is of greater impact in the early stages of post-bottling refinement, while the differences tend to disappear when the post-bottling refinement is extended up to 36 months. The first results of a second experimental campaign seem to confirm the trends detected in the first one, although with less evidence. Further investigation is required to gain a comprehensive understanding of the complexities of underwater aging and its wider impact on wine production. Full article

The rapid adoption of smart technologies is increasingly evident in both personal and business contexts. The ‘post-pandemic’ economic recovery of 2022 and 2023 coincided with a global energy supply shortage driven by heightened energy demand and supply chain disruptions stemming from the ongoing Russian-Ukrainian conflict. The implementation of smart metering systems is a central component of European policies aimed at enhancing the competitiveness and environmental sustainability of energy markets. However, limited research exists on the acceptance of Smart Meter Technology (SMT) in general, specifically in Norway, as compared to other nations. SMT devices offer the potential for real-time energy consumption monitoring, enabling users to track and modify their usage patterns for optimized consumption. This study employs a mixed-methods research design to gather insights from both SMT consumers and vendors. Findings underscore the pivotal roles of familiarity, cost, social influence, and perceived usefulness in shaping consumer adoption of SMT. This article provides critical insights and implications for researchers, network operators, electricity companies, and government agencies. Full article

The inherent uncertainty and information asymmetry in financial markets create significant challenges for accurate price forecasting. Although investor sentiment analysis has gained traction in recent research, the temporal dimension of sentiment dynamics remains underexplored. This study develops a novel framework that enhances stock price prediction by integrating time-partitioned investor sentiment, while improving model interpretability via Shapley additive explanations (SHAP) analysis. Employing the ERNIE (enhanced representation through knowledge integration) 3.0 model for sentiment extraction from China’s Eastmoney Guba stock forum, we quantitatively distinguish intraday and post-market investor sentiment then integrate these temporal components with technical indicators through neural network architecture. Our results indicate that temporal sentiment partitioning effectively reduces uncertainty. Empirical evidence demonstrates that our long short-term memory (LSTM) model integrating intraday and post-market sentiment indicators achieves better prediction accuracy, and SHAP analysis reveals the importance of intraday and post-market investor sentiment to stock price prediction models. Implementing quantitative trading strategies based on these insights generates significantly more annualized returns for representative stocks with controlled risk, outperforming sentiment-agnostic and non-temporal sentiment models. This research provides methodological innovations for processing temporal unstructured data in finance, while the SHAP framework offers regulators and investors actionable insights into sentiment-driven market dynamics. Full article

Complex interventions are often poorly described, making it difficult to understand their development, implementation, and evaluation (i.e., context), which can aid in replicating and translating evidence into practice and policy. Therefore, we examined the development and implementation of an approach to scaling-out (increasing the numbers of) a psychosocial intervention for people affected by dementia across a rural county in England during 2019–2024. We used an adapted version of the TIDieR checklist to consider key items essential for replicating complex interventions at scale. We triangulated document analysis with interview data, and key programme stakeholders ratified the results of this study. We identified three programme components and sub-components, including how planned components were delivered, by whom, and under what conditions. Implementation outcomes related to the inner (e.g., top-down structure) and outer contexts (e.g., market failures) led to modifications that increased programme complexity. This study highlights the importance of programme leaders who can convene and drive systems and culture change to address implementation challenges, as well as the need for scaling science during programme development, for example, to determine optimal scale. Further research should include testing implementation outcomes to understand if the intervention is a scalable solution to the gap in post-diagnostic support in the UK. Full article