Restricted Action Research Articles

Titanium dioxide (TiO2) in herbal and health products registered by Saudi Food and Drug Authority (SFDA): A descriptive study

BackgroundTitanium dioxide (TiO2) is a brightening compound used as an additive in food and pharmaceuticals. TiO2 safety has been debated since evidence of carcinogenicity and genotoxicity emerged. While TiO2 is provisionally used as food additive by North America, it is banned by European Union (EU) countries and Saudi Arabia. There are no international regulations regarding TiO2 as an additive in medicinal, herbal or health products. In this study, the primary objective is to identify the percentage of herbal and health products containing TiO2 among all Saudi Food and Drugs Authority (SFDA) newly registered products during the period from 2018 to 2022. A secondary objective is to describe products containing TiO2 according to product type, pharmaceutical form, registration year and manufacturing country. MethodsThis study is a retrospective secondary data analysis using data derived from SFDA electronic products registration records (EURS) and drug management system (DMS). Descriptive analysis is conducted to describe the percentage of herbal and health products containing TiO2 among all SFDA- newly registered products during the period from 1st, Jan 2018 to 31st, Dec 2022. ResultsOne third [N:115, (31%)] of herbal and health products contain TiO2. Most TiO2-containing products were found in capsule pharmaceutical form [97 out of 115 (84%)], with significant statistical correlation (P=0.02). TiO2-containing products registration has peaked in 2020, then declined afterwards. Most products are provided by USA manufacturing companies, Spain and local companies, collectively. ConclusionTitanium dioxide is used as an additive in food and pharmaceutical products including health and herbal products. It has been banned in food products by countries and provisionally used by other countries. Concerning pharmaceutical products, regulatory authorities and policy makers are in need of insights for any potential TiO2 restriction in these products. One third of newly registered herbal and health products contain TiO2, of which market availability may be affected in case of restrictive regulatory actions. USA and local manufacturing companies are leading contributors to TiO2-containing herbal and health products registered by SFDA. Exploring alternatives for TiO2 and TiO2-free products is needed.

Smart pain relief: Harnessing conservative Q learning for personalized and dynamic pain management

Pain represents a multifaceted sensory and emotional experience often linked to tissue damage, bearing substantial healthcare costs and profound effects on patient well-being. Within intensive care units, effective pain management is paramount. However, determining suitable dosages of primary pain management drugs like morphine remains challenging due to their reliance on diverse patient-specific factors, including cardiovascular responses and pain intensity. To date, only a singular effort has explored personalized pain treatment recommendations through reinforcement learning. Regrettably, this pioneering study faced limitations stemming from incomplete patient state observations, a restricted action space, and the use of Deep Q-Networks, known for their sample inefficiency and lack of clinical interpretability. In our work, we introduced a Conservative Q-learning-based system for pain recommendation, enriching it with expanded state and action spaces. Additionally, we developed a comprehensive pipeline for both qualitative and quantitative evaluations, focusing on assessing the trained model’s performance. Our findings indicate a slight performance improvement over the clinician’s policy, offering a more clinically sensible and understandable approach compared to the current state-of-the-art methodologies.

Microbial fuel cell-assisted composting shows stronger capacity to immobilize phosphorus: Emphasized on bacterial structures and functional enzymes

Limited scientific evidence exists on phosphorus immobilization under autogenetic electrochemical reactions in composting systems. This study exploited a composting procedure using microbial fuel cell (MFC) to ascertain phosphorus redistribution during composting process. Compared to the control without MFC equipment, MFC-assisted treatment yielded a 13 % decrease in phosphorus availability due to the transformation of exchangeable fraction (Ex-P) to aluminum-bound (Al-P) and calcium-bound (Ca-P) fractions. During the composting process, organic humification primarily controlled phosphorus redistribution and immobilization. Biotic factors, including bacterial communities (i.e., Firmicutes, Proteobacteria, Bacteroidota, and Gemmatimonadota) and functional enzymes (i.e., acid phosphatase, alkaline phosphatase, phytase, and C-P lyase), significantly influenced phosphorus availability in the composting systems. Temperature-dependent composting phases restricted microbial actions on phosphorus transformation. These findings highlight the mechanisms underlying phosphorus transformation in composting systems, and provide valuable insights for advancing composting technology and protecting agricultural ecosystems.

Structural knowledge and subjective knowledge, not factual knowledge, promotes corrective and restrictive actions towards healthy eating misinformation in China: a multigroup comparison of extended cognitive mediation model based on altruism

Structural knowledge and subjective knowledge, not factual knowledge, promotes corrective and restrictive actions towards healthy eating misinformation in China: a multigroup comparison of extended cognitive mediation model based on altruism

A Highly Potent, Orally Bioavailable Pyrazole-Derived Cannabinoid CB2 Receptor- Selective Full Agonist for In Vivo Studies.

The cannabinoid CB2 receptor (CB2R) is a potential therapeutic target for distinct forms of tissue injury and inflammatory diseases. To thoroughly investigate the role of CB2R in pathophysiological conditions and for target validation in vivo, optimal pharmacological tool compounds are essential. Despite the sizable progress in the generation of potent and selective CB2R ligands, pharmacokinetic parameters are often neglected for in vivo studies. Here, we report the generation and characterization of a tetra-substituted pyrazole CB2R full agonist named RNB-61 with high potency (K i 0.13-1.81 nM, depending on species) and a peripherally restricted action due to P-glycoprotein-mediated efflux from the brain. 3H and 14C labeled RNB-61 showed apparent K d values of <4 nM toward human CB2R in both cell and tissue experiments. The 6,800-fold selectivity over CB1 receptors and negligible off-targets in vitro, combined with high oral bioavailability and suitable systemic pharmacokinetic (PK) properties, prompted the assessment of RNB-61 in a mouse ischemia-reperfusion model of acute kidney injury (AKI) and in a rat model of chronic kidney injury/inflammation and fibrosis (CKI) induced by unilateral ureteral obstruction. RNB-61 exerted dose-dependent nephroprotective and/or antifibrotic effects in the AKI/CKI models. Thus, RNB-61 is an optimal CB2R tool compound for preclinical in vivo studies with superior biophysical and PK properties over generally used CB2R ligands.

Examining the impact of digital information environments, information processing, and presumed influence on behavioral responses to COVID-19 misinformation in Asia

This study examines exposure to, perception of, and behavioral responses to misinformation about COVID-19 on social media from the influence of presumed influence (IPI) framework. To understand how the digital information environment of a society shapes the spread and responses to pandemic misinformation, four culturally similar Asian cities—Beijing, Hong Kong, Singapore, and Taipei—were selected, generating a sample of 4094 respondents. Our findings suggest a paradox—the more information respondents in the four cities have access to, the less likely they are to view misinformation on COVID-19 and accept it as true without elaboration. Moreover, the study extends IPI theory by demonstrating negative emotions as a mechanism that mediates the relationship between perceived social impact and behavioral intentions. That is, the more respondents perceived misinformation to be harmful, the more negatively they felt about misinformation, which led to greater likelihood of taking restrictive, promotional, and corrective actions.

Does a perceptual gap lead to actions against digital misinformation? A third-person effect study among medical students

BackgroundWe are making progress in the fight against health-related misinformation, but mass participation and active engagement are far from adequate. Focusing on pre-professional medical students with above-average medical knowledge, our study examined whether and how third-person perceptions (TPP), which hypothesize that people tend to perceive media messages as having a greater effect on others than on themselves, would motivate their actions against misinformation.MethodsWe collected the cross-sectional data through a self-administered paper-and-pencil survey of 1,500 medical students in China during April 2022.ResultsStructural equation modeling (SEM) analysis, showed that TPP was negatively associated with medical students’ actions against digital misinformation, including rebuttal of misinformation and promotion of corrective information. However, self-efficacy and collectivism served as positive predictors of both actions. Additionally, we found professional identification failed to play a significant role in influencing TPP, while digital misinformation self-efficacy was found to broaden the third-person perceptual gap and collectivism tended to reduce the perceptual bias significantly.ConclusionsOur study contributes both to theory and practice. It extends the third-person effect theory by moving beyond the examination of restrictive actions and toward the exploration of corrective and promotional actions in the context of misinformation., It also lends a new perspective to the current efforts to counter digital misinformation; involving pre-professionals (in this case, medical students) in the fight.

Multicentral Agent-Based Model of Six Epidemic Waves of COVID-19 in the Nizhny Novgorod Region of Russian Federation

Relevance. To investigate the characteristics of the COVID-19 pandemic and introduce timely and effective measures, there is a need for models that can predict the impact of various restrictive actions or characteristics of disease itself on COVID-19 spread dynamics. Employing agent-based models can be attractive because they take into consideration different population characteristics (e.g., age distribution and social activity) and restrictive measures, laboratory testing, etc., as well as random factors that are usually omitted in traditional modifications of the SIR-like dynamic models. Aim. Improvement of the previously proposed agent-based model [23,24] for modeling the spread of COVID-19 in various regions of the Russian Federation. At this stage, six waves of the spread of COVID-19 have been modeled in the Nizhny Novgorod region as a whole region, as well as in its individual cities, taking into account restrictive measures and vaccination of the population. Materials and Methods. In this paper we extend a recently proposed agent-based model for Monte Carlo-based numerical simulation of the spread of COVID-19 with consideration of testing and vaccination strategies. Analysis is performed in MATLAB/ GNU Octave. Results. Developed multicentral model allows for more accurate simulation of the epidemic dynamics within one region, when a patient zero usually arrives at a regional center, after which the distribution chains capture the periphery of the region due to pendulum migration. Furthermore, we demonstrate the application of the developed model to analyze the epidemic spread in the Nizhny Novgorod region of Russian Federation. The simulated dynamics of the daily newly detected cases and COVID-19-related deaths was in good agreement with the official statistical data both for the region as whole and different periphery cities. Conclusions. The results obtained with developed model suggest that the actual number of COVID-19 cases might be 1.5–3.0 times higher than the number of reported cases. The developed model also took into account the effect of vaccination. It is shown that with the same modeling parameters, but without vaccination, the third and fourth waves of the epidemic would be united into one characterized by a huge rise in the morbidity rates and the occurrence of natural individual immunity with the absence of further pandemic waves. Nonetheless, the number of deaths would exceed the real one by about 9–10 times.

A highly potent, orally bioavailable pyrazole-derived cannabinoid CB2 receptor-selective full agonist for in vivo studies.

The cannabinoid CB2 receptor (CB2R) is a potential therapeutic target for distinct forms of tissue injury and inflammatory diseases. To thoroughly investigate the role of CB2R in pathophysiological conditions and for target validation in vivo, optimal pharmacological tool compounds are essential. Despite the sizable progress in the generation of potent and selective CB2R ligands, pharmacokinetic parameters are often neglected for in vivo studies. Here, we report the generation and characterization of a tetra-substituted pyrazole CB2R full agonist named RNB-61 with high potency (K i 0.13-1.81 nM, depending on species) and a peripherally restricted action due to P-glycoprotein mediated efflux from the brain. 3H and 14C labelled RNB-61 showed apparent K d values < 4 nM towards human CB2R in both cell and tissue experiments. The >6000-fold selectivity over CB1 receptors and negligible off-targets in vitro, combined with high oral bioavailability and suitable systemic pharmacokinetic (PK) properties, prompted the assessment of RNB-61 in a mouse ischemia-reperfusion model of acute kidney injury (AKI) and in a rat model of chronic kidney injury/inflammation and fibrosis (CKI) induced by unilateral ureteral obstruction. RNB-61 exerted dose-dependent nephroprotective and/or antifibrotic effects in the AKI/CKI models. Thus, RNB-61 is an optimal CB2R tool compound for preclinical in vivo studies with superior biophysical and PK properties over generally used CB2R ligands.

Оговорки в международных коммерческих договорах с участием российских предпринимателей

Currently, Russian entrepreneurs are faced with great difficulties in concluding and executing international commercial contracts. The difficulties of Russian entrepreneurs are caused by the restrictive actions, which are imposed by unfriendly States (the USA, Great Britain, Australia, the European Union and others). In this regard, it is necessary for Russian entrepreneurs not only to take into account these restrictions, but also to take actions reducing the negative consequences of these restrictions. For this reason, the author of this work has made an attempt to analyze some clauses advisable to include in international commercial contracts with the participation of Russian persons.

Copyright Content Moderation in the European Union: State of the Art, Ways Forward and Policy Recommendations

This Opinion describes and summarises the results of the interdisciplinary research carried out by the authors during the course of a three-year project on intermediaries’ practices regarding copyright content moderation. This research includes the mapping of the EU legal framework and intermediaries’ practices regarding copyright content moderation, the evaluation and measuring of the impact of moderation practices and technologies on access and diversity, and a set of policy recommendations. Our recommendations touch on the following topics: the definition of “online content-sharing service provider”; the recognition and operationalisation of user rights; the complementary nature of complaint and redress safeguards; the scope of permissible preventive filtering; the clarification of the relationship between Art. 17 of the new Copyright Directive and the Digital Services Act; monetisation and restrictive content moderation actions; recommender systems and copyright content moderation; transparency and data access for researchers; trade secret protection and transparency of content moderation systems; the relationship between the copyright acquis, the Digital Services Act and the upcoming Artificial Intelligence Act; and human competences in copyright content moderation.

Cadmium exposure exacerbates immunological abnormalities in a BTBR T+ Itpr3tf/J autistic mouse model by upregulating inflammatory mediators in CD45R-expressing cells

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by behavior, learning, communication, and social interaction abnormalities in various situations. Individuals with impairments usually exhibit restricted and repetitive actions. The actual cause of ASD is yet unknown. It is believed, however, that a mix of genetic and environmental factors may play a role in its development. Certain metals have been linked to the development of neurological diseases, and the prevalence of ASD has shown a positive association with industrialization. Cadmium chloride (Cd) is a neurotoxic chemical linked to cognitive impairment, tremors, and neurodegenerative diseases. The BTBR T+ Itpr3tf/J (BTBR) inbred mice are generally used as a model for ASD and display a range of autistic phenotypes. We looked at how Cd exposure affected the signaling of inflammatory mediators in CD45R-expressing cells in the BTBR mouse model of ASD. In this study, we looked at how Cd affected the expression of numerous markers in the spleen, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. Furthermore, we investigated the effect of Cd exposure on the expression levels of numerous mRNA molecules in brain tissue, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. The RT-PCR technique was used for this analysis. Cd exposure increased the number of CD45R+IFN-γ+, CD45R+IL-6+, CD45R+NF-κB p65+, CD45R+GM-CSF+, CD45R+GM-CSF+, CD45R+iNOS+, and CD45R+Notch1+ cells in the spleen of BTBR mice. Cd treatment also enhanced mRNA expression in brain tissue for IFN-γ, IL-6, NF-κB, GM-CSF, iNOS, MCP-1, and Notch1. In general, Cd increases the signaling of inflammatory mediators in BTBR mice. This study is the first to show that Cd exposure causes immune function dysregulation in the BTBR ASD mouse model. As a result, our study supports the role of Cd exposure in the development of ASD.

Field investigation on a pilot energy piled retaining wall

This study presents the thermal and thermo-mechanical responses of a pilot energy wall located in Melbourne, Australia, which is believed to be one of the first instrumented energy soldier piled walls in the world. The full-scale field thermal and thermo-mechanical conditions of the wall were monitored during the period of a full-cycle thermal response test (TRT) conducted on a single soldier pile over 2 months. The monitored pile and ground temperature responses reveal the significance of the thermal condition in the excavated space on the thermal performance of such energy geostructures, which increases complexities in design and analysis. Furthermore, this study reports the profiles of axial strains and induced thermal stresses in the tested soldier pile, demonstrating how the applied thermal load from the TRT influenced the mechanical performance of the pile and wall and how the restrictive action of the support elements controlled the induced conditions. Here, we show that soldier pile responds differently from energy piles or borehole heat exchangers; however, residual axial strains were minimal and similar to those reported in energy piles foundations due to a thermo-elastic response to the imposed thermal loads and wall rigidity. Finally, the unique experimental dataset is made available for further studies.

Permanence of deaf students at the Federal University of Acre: remote education and pandemic

This article aims to list the difficulties and challenges of deaf students, college professor and translators and interpreters of Libras during the COVID-19 pandemic. The research was applied at the Federal University of Acre - Campus Sede, in Rio Branco, and the Campus Floresta, in Cruzeiro do Sul in the State of Acre in 2021. The methodology is qualitative and the study comprises field research of an exploratory and descriptive nature, whose production of empirical data was based on individual and collective interviews and a questionnaire focused on the thematic axes of bilingual education for the deaf, permanence and pandemic. We can indicate numerous limitations imposed on deaf college professor and students in relation to the reality they experience, always permeated by fear, uncertainty and severe exhaustion, by the insufficient and restricted actions proposed by the analyzed institution.

What's in the black box? How algorithmic knowledge promotes corrective and restrictive actions to counter misinformation in the USA, the UK, South Korea and Mexico

PurposeWhile there has been a growing call for insights on algorithms given their impact on what people encounter on social media, it remains unknown how enhanced algorithmic knowledge serves as a countermeasure to problematic information flow. To fill this gap, this study aims to investigate how algorithmic knowledge predicts people's attitudes and behaviors regarding misinformation through the lens of the third-person effect.Design/methodology/approachFour national surveys in the USA (N = 1,415), the UK (N = 1,435), South Korea (N = 1,798) and Mexico (N = 784) were conducted between April and September 2021. The survey questionnaire measured algorithmic knowledge, perceived influence of misinformation on self and others, intention to take corrective actions, support for government regulation and content moderation. Collected data were analyzed using multigroup SEM.FindingsResults indicate that algorithmic knowledge was associated with presumed influence of misinformation on self and others to different degrees. Presumed media influence on self was a strong predictor of intention to take actions to correct misinformation, while presumed media influence on others was a strong predictor of support for government-led platform regulation and platform-led content moderation. There were nuanced but noteworthy differences in the link between presumed media influence and behavioral responses across the four countries studied.Originality/valueThese findings are relevant for grasping the role of algorithmic knowledge in countering rampant misinformation on social media, as well as for expanding US-centered extant literature by elucidating the distinctive views regarding social media algorithms and misinformation in four countries.

Forecasting and what-if analysis of new positive COVID-19 cases during the first three waves in Italy

The joint exploitation of data related to epidemiological, mobility, and restriction aspects of COVID-19 with machine learning algorithms can support the development of predictive models that can be used to forecast new positive cases and study the impact of more or less severe restrictions. In this work, we integrate heterogeneous data from several sources and solve a multivariate time series forecasting task, specifically targeting the Italian case at both national and regional levels, during the first three waves of the pandemic. The goal is to build a robust predictive model to predict the number of new cases over a given time horizon so that any restrictive actions can be better planned. In addition, we perform a what-if analysis based on the best-identified predictive models to evaluate the impact of specific restrictions on the trend of positive cases. Our focus on the first three waves is motivated by the fact that it represents a typical emergency scenario (when no stable cure or vaccine is available) that may occur when a new pandemic spreads. Our experimental results prove that exploiting the considered heterogeneous data leads to accurate predictive models, reaching a WAPE of 5.75% at the national level. Furthermore, in the subsequent what-if analysis, we observed that strong all-in-one initiatives, such as total lockdowns, may not be adequate, while more specific and targeted solutions should be adopted. The developed models can help policy and decision-makers better plan intervention strategies and retrospectively analyze the effects of the decisions made at different scales.Graphical abstractJoint exploitation of data on epidemiological, mobility, and restriction aspects of COVID-19 with machine learning algorithms to learn predictive models to forecast new positive cases.

Dynamic role discovery and assignment in multi-agent task decomposition

Effective multi-agent teamwork can be facilitated by using personas to decompose goals into lower-level team subtasks through a shared understanding of multi-agent tasks. However, traditional methods for role discovery and assignment are not scalable and fail to adapt to dynamic changes in the environment. To solve this problem, we propose a new framework for learning dynamic role discovery and assignment. We first introduce an action encoder to construct a vector representation for each action based on its characteristics, and define and classify roles from a more comprehensive perspective based on both action differences and action contributions. To rationally assign roles to agents, we propose a representation-based role selection policy based on consideration of role differences and reward horizons, which enables agents to play roles dynamically by dynamically assigning agents with similar abilities to play the same role. Agents playing the same role share their learning of the role, and different roles correspond to different action spaces. We also introduce regularizers to increase the differences between roles and stabilize training by preventing agents from changing roles frequently. Role selection and role policy integrate action representations and role differences in a restricted action space, improving learning efficiency. We conducted experiments in the SMAC benchmark and showed that our method enables effective role discovery and assignment, outperforming the baseline on four of the six scenarios, with an average improvement in win rate of 20%, and is effective in hard and super hard maps. We also conduct ablation experiments to demonstrate the importance of each component in our approach.

Complexities of men’s engagement in early childhood care and development in Africa

ABSTRACT Men as equitable non-violent caregivers in early childhood care and development (ECCD) are important for the well-being of children and women. Africa, with its strong traditional and cultural practices, forms an ideal context to explore men’s engagement in ECCD. This article illuminates the entanglements of men’s engagement through a focus on barriers and attempts to effect change. The framing of caring masculinities is used to identify the fault lines and possibilities for men to rework their identities in more affirming ways for ECCD. The data for the study was produced through a literature review and two online workshops with participants from Anglophone and Francophone Africa. The findings show that barriers to men’s engagement include restrictive cultural practices, gatekeeping, and limited state action. Attempts to effect change are influenced by the overall under-development of ECCD as public service and resistant traditional cultures that naturally gravitate towards care as women’s work. Both these dimensions have implications for policy and practice.

Advance drug delivery and combinational drug approaches for hepatoprotective action of berberine: A progressive overview with underlying mechanism

Abstract Objectives Berberine has attracted prominent interest recently due to its wide pharmacological actions in management and treatments of several disease including liver. However, restricted bioavailability and permeability makes this drug as better choice to develop several value added products for improvement of both safety and efficacy. Many of research already conducted in this direction using several approaches to fix this issue. Therefore, current article was designed to summarize all approaches taking together to enhance hepatoprotection by berberine including molecular mechanism. Methods Online scientific databases from PubMed was assessed for collecting information on berberine. All the collected informations were classified and incorporated into different sections such as recent progress of research on advance drug delivery systems and combinational approaches addressing above issue for improvement of hepatoprotective action of berberine. Key finding The electronically PubMed database search yielded 7454 articles from different countries in several languages. Out of them two seventy articles published between 1932 and 2022 were included, corresponding to all detailed overview on berberine including research pertaining on toxicity and safety, biodistribution, pharmacokinetics, biopharmaceutics classification system (BCS), hepatoprotection against various hepatotoxicant agent, advance drug delivery system, combinational drug approaches, clinical Trial for hepatoprotection and patents. The review of the literature reveals that berberine exhibits a potent hepatoprotective action with several molecular action mechanisms. Additionally, current trends of formulation technology for enhancement of hepatoprotective action of berberine in terms of safety and efficacy are well co-related with present work. Conclusion It was well established and concluded from present work that both advance drug delivery system and combinational drug approaches may serve for enhancement of restricted hepatoprotective action of berberine due to poor bioavailability, solubility and permeability. Additionally, berberine based advance delivery system including in combination with bioavailability and permeability enhancer may provide an added advantage in near future to meet the objectives.

The Concept of Financial Stability in Theory and Law

State intervention in the functioning of the economy is necessarily based on some public interests, which may serve as a reason for restrictive state action against the individual, or their freedoms and rights. In legislation, financial stability can be identified as a form of public interest, whereby the need to define the substance of the concept is expressed as an expectation towards the legislator, all the more so because it forms the basis of significant administrative intervention of the public authority type. The study analyses how the concept of financial stability appears in the literature, in legislation and in legal enforcement. Although the concept of financial stability is strongly reflected in the theoretical literature and even in legislation and legal enforcement, its substance is difficult to capture and has evolved constantly. In view of the above, the author offers a definition for the general legal concept of financial stability.