Regulatory Guidelines Research Articles

An exploratory study on the issues in weightages-based profit distribution mechanism in Islamic banking institutions: the case of Pakistan

Purpose This study aims to explore and analyze the issues in weightages-based profit distribution mechanism in Islamic banks from Shari’ah, practical and regulatory perspectives. Design/methodology/approach A qualitative research approach was used in this study based on primary data collected through semi-structured interviews from Shari’ah practitioners and senior industry experts in the field of pool management in the Islamic Financial Services Industry of Pakistan. Findings The current study found that the weightages-based mechanism conforms to the rules of Mudarabah and; therefore, permissible. However, the elements of exploitation, transparency and fairness require further research, as these elements seem to exist in this mechanism. It was also found that there are many loopholes in the regulatory guidelines for pool management in Islamic banking institutions (IBIs) in Pakistan resulting in practical issues. Practical implications The findings of this study may help improve pool management in IBIs, which in turn may cater the objections raised by academicians, customers and industry experts. Moreover, the alternative solution based on the findings of this study can be transformed into a proposal for regulators to take necessary actions against unfair profit distribution and issue further improved guidelines for IBIs in Pakistan. Originality/value To the best of the authors’ knowledge, very limited studies have been conducted on pool management particularly with issues from different perspectives and alternative solutions have been suggested that may act as a proposal for IBIs as well as regulatory authorities.

Néphrectomie pour don de rein : quel système utiliser pour la ligature de l’artère rénale ? Aspects réglementaires et résultats de l’enquête nationale du CTAFU

Polymer Locking Clips (Weck* Hem-o-lok*, Teleflex Medical) are widely used for the vascular control during laparoscopic nephrectomy. However, those clips are contraindicated for use in ligating the renal artery during laparoscopic nephrectomies in living donor patients since 2005. We reviewed regulatory aspects, meta-analysis and guidelines published on the means used to ligate the renal artery during laparoscopic living donor nephrectomy. We although investigated among 31 French kidney transplant centers about their technic to occlude the renal artery. This survey was compared to those previously published in North America and in Europe.

Validation of a New Patient-Reported Outcome Measure of the Functional Impact of Essential Tremor on Activities of Daily Living.

The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines. Develop and validate a TETRAS PRO subscale. Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for 67 adults with ET or ET plus. Test-retest reliability was computed at intervals of 1 and 30 days. The influence of mood (Hospital Anxiety and Depression Scale, HADS) and coping behaviors (Essen Coping Questionnaire, ECQ) was examined with multiple linear regression. TETRAS PRO was strongly correlated (r > 0.7) with TETRAS ADL, TETRAS-P, and QUEST and exhibited good to excellent reliability (Cronbach alpha 95%CI = 0.853-0.926; 30-day test-retest intraclass correlation 95%CI = 0.814-0.921). The 30-day estimate of minimum detectable change (MDC) was 6.6 (95%CI 5.2-8.0). TETRAS-P (rsemipartial = 0.607), HADS depression (rsemipartial = 0.384), and the coping strategy of information seeking and exchange of experiences (rsemipartial = 0.176) contributed statistically to TETRAS PRO in a multiple linear regression (R2 = 0.67). TETRAS PRO is a valid and reliable scale that is influenced strongly by tremor severity, moderately by mood (depression), and minimally by coping skills. The MDC for TETRAS PRO is probably sufficient to detect clinically important change.

Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a Delphi approach.

Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome,and in selected cases with other RS types. Noninvasive ventilationshould be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriateand tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomyin patients at increased risk of ab ingestis pneumonia. This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

Ethical Considerations in the Development of AI-Powered Healthcare Assistants

Advances in the field of artificial intelligence (AI) have led to the development of increasingly sophisticated health assistants that can provide support in diagnosis, treatment and general health management. However, as with the use of new technologies in the healthcare context, ethical considerations play an important role in the design, development, and implementation of AI-based health assistants. In this paper, we investigate various ethical considerations associated with the development of AI-based healthcare assistants. We explore issues such as the privacy and security of patient data, transparency and accountability in decision making, and the social and psychological impact of reliance on technology in the healthcare context. We also discuss efforts that can be taken to address these ethical challenges, including the development of appropriate regulatory guidelines, ongoing monitoring of system performance, and education and training for health professionals and end users. By seriously considering ethical aspects in the development of AI-based healthcare assistants, we hope to ensure that this technology can provide maximum benefit to patients while maintaining the ethical and moral values that underlie good healthcare practices.

Radon Exposure Assessment in Occupational and Environmental Settings: An Overview of Instruments and Methods.

Radon is a naturally occurring noble radioactive gas that poses significant health risks, particularly lung cancer, due to its colorless, odorless, and tasteless nature, which makes detection challenging without formal testing. It is found in soil, rock, and water, and it infiltrates indoor environments, necessitating regulatory standards and guidelines from organizations such as the Environmental Protection Agency, the World Health Organization, and the Occupational Health and Safety Agency to mitigate exposure. In this paper, we present various methods and instruments for radon assessment in occupational and environmental settings. Discussion on long- and short-term monitoring, including grab sampling, radon dosimetry, and continuous real-time monitoring, is provided. The comparative analysis of detection techniques-active versus passive-is highlighted from real-time data and long-term exposure assessment, including advances in sensor technology, data processing, and public awareness, to improve radon exposure evaluation techniques.

Ensuring Sustainable Hospitality: A Case Study on Occupational Health and Safety Governance at Ros-In Hotel

Workplace accidents often stem from worker negligence, human error, and insufficient management, including substandard occupational health and safety measures. Case studies, a common qualitative research method, utilize interviews and observations for primary data collection. In a specific case study at Hotel Ros-In, Yogyakarta, the Human Resources Manager was the key informant, participating in a 60-minute interview with three sub-themes: Covid-19 Post-Pandemic Regulation, Occupational Health and Safety, and Environmental Health. During the interview, Ros-In Hotel exhibited a robust commitment to complying with Ministry of Tourism and Creative Economy guidelines on hygiene, health, safety, and environmental sustainability. In the industrial sector, effective health and safety governance is crucial for maintaining consumer confidence and ensuring facilities meet stringent standards, protecting both consumers and workers. Strong safety protocols actively reduce workplace accidents and occupational diseases, fostering a safer work environment. This commitment not only benefits employees' well-being but enhances the company's overall reputation. Companies like Ros-In Hotel, through adherence to regulatory guidelines and robust safety measures, play a vital role in establishing a secure working atmosphere, instilling confidence in consumers and the broader community.

Estimation of potential health risks on metals and metalloids contaminants in black goby (Gobius niger) consumption in selected niger delta coast, nigeria

IntroductionThe Niger Delta in Nigeria is subject to anthropogenic influences, impacting the quality of its water bodies, including the Sombrero River. This study aims to investigate the concentrations of metals and metalloids in Gobius niger from the Sombrero River, as these contaminants can pose risks to human health through seafood consumption. Specifically, zinc (Zn), iron (Fe), copper (Cu), lead (Pb), arsenic (As), and cadmium (Cd) were analyzed using atomic absorption spectroscopy (AAS). Materials and MethodsSamples were collected from three different stations along the Sombrero River. The concentrations of Zn, Fe, Cu, Pb, As, and Cd were determined using AAS. Hazard Quotients (HQ), Chronic Daily Intake (CDI), Hazard Index (HI), and Individual Lifetime Cancer Risk (ILCR) values were calculated to assess the potential health risks associated with consuming fish contaminated with these metals and metalloids. ResultsStation 1 had the highest Zn concentration, followed by Fe, Cu, Pb, Cd, and As, with Zn reaching 104.8 ± 1.37 mg kg−1. Station 2 exhibited a similar trend, while Station 3 had Zn as the predominant metal and metalloid. Notably, Pb, As, and Cd levels were consistently low at all stations. While Pb was within permissible limits set by FAO/WHO for contaminants in the fish samples, Zn exceeded regulatory guidelines, suggesting a potential source of contamination. Hazard Quotients (HQ) highlighted a significant risk associated with zinc, especially for children. Chronic Daily Intake values showed metals in fish consumed by adults and children were generally within safe limits, except for Zn, which exceeded Maximum Tolerable Daily Intake (MTDI). Hazard Index values pointed to a substantial long-term health risk, particularly for children due to high zinc levels. However, Individual Lifetime Cancer Risk (ILCR) values were generally below 1, indicating relatively low cancer risks from G. niger consumption for both age groups. ConclusionThis study emphasizes the need for monitoring and managing metals and metalloid pollution in the Niger Delta region to ensure safe seafood consumption and community well-being. While certain metals pose minimal health risks, it highlights the necessity of specific interventions to reduce excessive zinc exposure and safeguard long-term health in the region.

Assessment of the Developmental Neurotoxicity of Environmental Chemicals: Investigating the Mechanisms & Identifying Potential Biomarkers

Background: Developmental neurotoxicity resulting from exposure to environmental chemicals is a significant public health concern. Understanding the mechanisms underlying such neurotoxicity and identifying potential biomarkers are essential for early detection and effective risk assessment. Objective: This study aimed to assess the developmental neurotoxicity of selected environmental chemicals and investigate the underlying mechanisms. Additionally, the study sought to identify potential biomarkers for early detection and monitoring of developmental neurotoxicity. Methods: In vitro neurodevelopmental models were established, including neuronal cell cultures and organoid systems, to evaluate the neurotoxic effects of environmental chemicals. Key endpoints, such as neuronal viability, morphology, neurite outgrowth, synaptogenesis, and synaptic activity, were assessed using appropriate assays and imaging techniques. Mechanistic investigations involved exploring oxidative stress, inflammation, disruption of neurotransmitter systems, and interference with neurodevelopmental processes through gene expression analysis, protein profiling, and signaling pathway investigations. Results: Exposure of the in vitro models to selected environmental chemicals resulted in significant neurotoxic effects, including impaired neuronal viability, disrupted morphological development, and altered synaptic activity. Mechanistic investigations revealed the involvement of oxidative stress and disruption of neurotransmitter systems in the observed neurotoxicity. Furthermore, several potential biomarkers, including gene expression changes and epigenetic modifications, showed significant correlations with developmental neurotoxicity. Conclusion: This study demonstrates the developmental neurotoxicity of environmental chemicals in in vitro neurodevelopmental models. The findings highlight the role of oxidative stress and neurotransmitter disruption as key mechanisms underlying neurotoxic effects. Moreover, the identification of potential biomarkers provides promising avenues for early detection and monitoring of developmental neurotoxicity. These results contribute to a better understanding of the risks associated with environmental chemical exposure during neurodevelopment and have implications for risk assessment and regulatory guidelines.

Evaluation of Novel Food Additives on Product Acceptability in France

Purpose: The aim of the study was to analyze the evaluation of novel food additives on product acceptability in France. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: This study evaluating novel food additives on product acceptability in France, it was found that natural and organic additives significantly enhanced consumer acceptance. The additives were primarily valued for their perceived health benefits and minimal processing. Taste testing revealed that products with natural flavors and colors were preferred over those with synthetic counterparts. However, there was resistance among certain demographics, particularly older consumers, who showed a preference for traditional flavors. Overall, the study suggests that while novel additives can increase acceptability, consumer education and transparent labeling are crucial for widespread adoption. Unique Contribution to Theory, Practice and Policy: Theory of planned behavior (TPB), diffusion of innovations theory & expectancy-value theory may be used to anchor future studies on analyze the evaluation of novel food additives on product acceptability in France. Implement educational programs that inform consumers about the benefits and safety of novel food additives. Advocate for the development of clearer, more consistent regulatory guidelines for novel food additives to ensure safety and quality across markets.

A Review of Laser Threat and Safety Measures in Dental Practices

Laser technology has become increasingly prevalent in modern dental practice, offering numerous benefits such as precise tissue ablation, hemostasis, and reduced patient discomfort. However, with the integration of lasers into routine dental procedures comes the imperative of ensuring safety for both patients and dental professionals. This review critically examines the potential hazards associated with the use of lasers in dental practice and elucidates strategies and protocols aimed at mitigating these risks. Topics covered include the types of dental lasers commonly utilized, the inherent risks of laser therapy, regulatory guidelines governing laser use in dentistry, and best practices for ensuring safe and effective laser applications. By comprehensively addressing the "laser menace" and providing evidence-based safety strategies, this review aims to equip dental practitioners with the knowledge and resources necessary to harness the full potential of laser technology while safeguarding the well-being of all stakeholders involved in dental care.

SARS-CoV-2 spike protein expression as an identification in quality control testing for Adenovector based COVID-19 vaccine

AimQuality control testing of the vaccine for lot release is of paramount importance in public health. A recent pandemic caused by the SARS-CoV-2 virus brought together all spheres of vaccine to combat the virus. The scientific advancement in the development of vaccines facilitated the scientists to develop the vaccine against SARS-CoV-2 in a record time. Thus, these vaccines should be stringently monitored for their safety and efficacy as per the latest WHO and national regulatory guidelines, and quality control evaluation of the product should be done at national control laboratories before releasing the product into the market as it assures the quality and safety of the vaccine. MethodsThe SARS-CoV-2 exploited the ACE2 (Angiotensin Converting Enzyme 2) receptor, a surface protein on mammalian cells to gain entry into the host cells. The viral surface protein that interacted with the ACE2 receptor is the Spike protein of SARS-CoV-2. Thus, in the development of the vaccine and assessing its quality, the Spike protein of SARS-CoV-2 became an attractive immunodominant antigen. In National Institute of Biologicals, an apex body in the testing of biologicals in India, received the Adenovector (Adenovirus + vector) based COVID-19 vaccine, a finished product for quality evaluation. Due to the lack of a pharmacopeial monograph, the testing of the vaccine was done as per the manufacturer's specifications and methods. The routine assays of identification employed by the manufacturer do not reflect the expression of Spike protein which is required for the immune system to get activated. In this report, we showed the determination of Spike protein expression by immunoblotting and immunofluorescence for identification parameters in the quality testing of the COVID-19 vaccine. We determined the translation of the SARS-CoV-2 Spike gene cloned into an Adenovector. ResultsThe results from these experiments indicated the expression of Spike protein upon infection of mammalian cells with viral particles suggested that the expression of immunodominant Spike protein of SARS-CoV-2 may be employed by quality control laboratories as a parameter for identification. ConclusionThe study suggested that the determination of the expression of Spike protein is pertinent to identifying the Adenovector based vaccines against COVID-19.

Survey of Pharmaceutical Industry's Best Practices around In Vitro Transporter Assessment and Implications for Drug Development: Considerations from the International Consortium for Innovation and Quality for Pharmaceutical Development Transporter Working Group.

The International Consortium for Innovation and Quality in Pharmaceutical Development Transporter Working Group had a rare opportunity to analyze a crosspharma collation of in vitro data and assay methods for the evaluation of drug transporter substrate and inhibitor potential. Experiments were generally performed in accordance with regulatory guidelines. Discrepancies, such as not considering the impact of preincubation for inhibition and free or measured in vitro drug concentrations, may be due to the retrospective nature of the dataset and analysis. Lipophilicity was a frequent indicator of crosstransport inhibition (P-gp, BCRP, OATP1B, and OCT1), with high molecular weight (MW ≥500 Da) also common for OATP1B and BCRP inhibitors. A high level of overlap in in vitro inhibition across transporters was identified for BCRP, OATP1B1, and MATE1, suggesting that prediction of DDIs for these transporters will be common. In contrast, inhibition of OAT1 did not coincide with inhibition of any other transporter. Neutrals, bases, and compounds with intermediate-high lipophilicity tended to be P-gp and/or BCRP substrates, whereas compounds with MW <500 Da tended to be OAT3 substrates. Interestingly, the majority of in vitro inhibitors were not reported to be followed up with a clinical study by the submitting company, whereas those compounds identified as substrates generally were. Approaches to metabolite testing were generally found to be similar to parent testing, with metabolites generally being equally or less potent than parent compounds. However, examples where metabolites inhibited transporters in vitro were identified, supporting the regulatory requirement for in vitro testing of metabolites to enable integrated clinical DDI risk assessment. SIGNIFICANCE STATEMENT: A diverse dataset showed that transporter inhibition often correlated with lipophilicity and molecular weight (>500 Da). Overlapping transporter inhibition was identified, particularly that inhibition of BCRP, OATP1B1, and MATE1 was frequent if the compound inhibited other transporters. In contrast, inhibition of OAT1 did not correlate with the other drug transporters tested.

Radiation Dose Optimization in Radiology: A Comprehensive Review of Safeguarding Patients and Preserving Image Fidelity.

Radiation dose optimization in radiology is a critical aspect of modern healthcare, aimed at balancing the necessity of diagnostic imaging with the imperative of patient safety. This comprehensive review explores the fundamental principles, techniques, and considerations in optimizing radiation dose to safeguard patients while preserving image fidelity. Beginning with acknowledging the inherent risks associated with medical radiation exposure, the review highlights strategies such as the As Low as Reasonably Achievable (ALARA) principle, technological advancements, and quality assurance measures to minimize radiation dose without compromising diagnostic accuracy. Regulatory guidelines and the importance of patient education and informed consent are also discussed. Through a synthesis of current knowledge and emerging trends, the review underscores the pivotal role of radiation dose optimization in radiology practice. Furthermore, it emphasizes the need for ongoing research and collaboration to advance dose reduction strategies, establish standards for radiation safety, and explore personalized dose optimization approaches. By prioritizing radiation dose optimization, healthcare providers can ensure the highest standards of patient care while minimizing potential risks associated with medical radiation exposure.

Insights on molecular modeling and supramolecular arrangement of bilastine polymorphs.

The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms.This study provides a significant contribution to understanding bilastine's polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products. The molecular conformation of two bilastine forms was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311 + + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

Adult and pediatric relapsing multiple sclerosis phase II and phase III trial design and their primary end points: Asystematic review.

No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and primary end points (PEs) of phase II and III trials intended to modify the natural course of the disease in patients with RMS. The purpose of the study is to explore trends/topics and discussion points in clinical trial design and PE, comparing them to regulatory guidelines and expert recommendations. Three trial registration systems, ClinicalTrials.gov, the EU Clinical Trials Register, and the Japan Registry of Clinical Trials, were used and 60 trials were evaluated. The dominant clinical trial design was a randomized controlled parallel-arms trial and other details were as follows: in adult phase III confirmatory trials (n = 32), active-controlled double-blind trial (DBT) (53%) and active-controlled open-label assessor-masking trial (16%); in adult phase II dose-finding trials (n = 9), placebo- and active-controlled DBT (44%), placebo-controlled DBT (22%), and placebo-controlled add-on DBT (22%); and in pediatric phase III confirmatory trials (n = 8), active-controlled DBT (38%) and active-controlled open-label non-masking trial (25%). The most common PEs were as follows: in adult confirmatory trials, annual relapse rate (ARR) (56%) and no evidence of disease activity-3 (NEDA-3) (13%); in adult dose-finding trials, the cumulative number of T1 gadolinium-enhancing lesions (56%), combined unique active lesions (22%), and overall disability response score (22%); and in pediatric confirmatory trials, ARR (38%) and time to first relapse (25%). It was suggested that some parts of the regulatory guidelines and expert recommendations need to be revised.

Physicochemical Properties and Functionalities of Food Emulsifiers

Purpose: This study sought to analyze the physiochemical properties and functionalities of food emulsifiers. Methodology: The study adopted a desktop research methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library. Findings: The findings reveal that there exists a contextual and methodological gap relating to the physiochemical properties and functionalities of food emulsifiers. Preliminary empirical review revealed that the importance of considering emulsifier properties in food product development. The findings underscored the significance of optimizing emulsifier selection and formulation to meet consumer demands for healthier, more sustainable, and better-performing food products. Continued research in this area promises to drive further innovation and advancements in food technology. Unique Contribution to Theory, Practice and Policy: The Interfacial Tension theory, HLB (Hydrophilic- Lipophilic Balance) theory and Emulsion Phase Inversion theory may be used to anchor future studies on the physiochemical properties and functionalities of food emulsifiers. The study made significant contributions to theoretical understanding, practical application, and policy considerations in the field of food science and technology. It advanced theoretical knowledge by exploring molecular mechanisms and integrating principles from colloid and interface science. In practice, the study recommended systematic approaches for emulsifier selection and process optimization to enhance product quality and consistency. From a policy perspective, it emphasized the importance of regulatory guidelines and transparency in emulsifier usage. Additionally, the study advocated for sustainability, innovation, and consumer-centric approaches to promote environmental responsibility, drive technological advancements, and prioritize consumer well-being in emulsifier research and application.

Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network

Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated invitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of invitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112). Following 2020 PRISMA guidelines, original research articles focusing on DILI which used invitro human models and performed at least one hepatotoxicity assay with positive and negative control compounds, were included. Bias of the studies was assessed by a modified 'Toxicological Data Reliability Assessment Tool'. A total of 51 studies (out of 2,936) met the inclusion criteria, with 30 categorized as reliable without restrictions. Although there was a broad consensus on positive compounds, the selection of negative compounds lacked clarity. 2D monoculture, short exposure times and cytotoxicity endpoints were the most tested, although there was no consensus on drug concentrations. Extensive analysis highlighted the lack of agreement on control compounds for invitro DILI assessment. Following comprehensive invitro and clinical data analysis together with input from the expert committee, an evidence-based consensus-driven list of 10 positive and negative control drugs for validation of invitro models of DILI is proposed. Prediction of human toxicity early in the drug development process remains a major challenge, necessitating the development of more physiologically relevant liver models and careful selection of drug-induced liver injury (DILI)-positive and -negative control drugs to better predict the risk of DILI associated with new drug candidates. Thus, this systematic study has crucial implications for standardizing the validation of new invitro models of DILI. By establishing a consensus-driven list of positive and negative control drugs, the study provides a scientifically justified framework for enhancing the consistency of preclinical testing, thereby addressing a significant challenge in early hepatotoxicity identification. Practically, these findings can guide researchers in evaluating safety profiles of new drugs, refining invitro models, and informing regulatory agencies on potential improvements to regulatory guidelines, ensuring a more systematic and efficient approach to drug safety assessment.

Understanding the configurational causes of traveler's moral ambiguity in the sharing economy: Evidence from PLS‐fsQCA

AbstractAlthough the sharing economy in tourism has garnered much positive attention, perennial ethical gray areas have been ignored. Drawing upon the ecological systems theory, we investigate the influence of different systemic factors, classified as individual differences and environmental context, on the ethical behavior of travelers (i.e., reporting malfunctions in a bike‐sharing context and saving water/electricity in a peer‐to‐peer accommodation context). PLS‐SEM and fsQCA are applied to analyze and examine proposed hypotheses. The results complement the factor configuration differences between the two behaviors. Moreover, this study provides new insights into the regulatory guidelines for shared service operators in the tourism industry.

Adaptive Study Design Methodology vs. Standard Randomized Clinical Trial in Different Therapeutic Area: A Review

Adaptive Study Design Methodology vs. Standard Randomized Clinical Trial in Different Therapeutic Area: A Review