bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a membrane-based Gi-CASE biosensor assay for profiling compounds at cannabinoid receptors
Authors: Scott-Dennis Morgan , Rafani Fikri A. , Yi Yicheng , Perera Themiya , Harwood Clare R. , Guba Wolfgang , Rufer Arne C. , Grether Uwe , Veprintsev Dmitry B. , Sykes David A. 
Published: August 2023

Introduction: The cannabinoid receptor (CBR) subtypes 1 (CB1R) and 2 (CB2R) are key components of the endocannabinoid system (ECS), playing a central role in the control of peripheral pain, inflammation and the immune response, with further roles in the endocrine regulation of food intake and energy balance. So far, few medicines targeting these receptors have reached the clinic, suggesting that a better understanding of the receptor signalling properties of existing tool compounds and clinical candidates may open the door to the development of more effective and safer treatments. Both CB1R and CB2R are Gαi protein-coupled receptors but detecting Gαi protein signalling activity reliably and reproducibly is challenging. This is due to the inherent variability in live cell-based assays and restrictions around the use of radioactive [35S]-GTPγS, a favoured technology for developing higher-throughput membrane-based Gαi protein activity assays.Methods: Here, we describe the development of a membrane-based Gαi signalling system, produced from membrane preparations of HEK293TR cells, stably overexpressing CB1R or CB2R, and components of the Gαi-CASE biosensor. This BRET-based system allows direct detection of Gαi signalling in both cells and membranes by monitoring bioluminescence resonance energy transfer (BRET) between the α and the βγ subunits. Cells and membranes were subject to increasing concentrations of reference cannabinoid compounds, with 10 μM furimazine added to generate RET signals, which were detected on a PHERAstar FSX plate reader, then processed using MARS software and analysed in GraphPad PRISM 9.2.Results: In membranes expressing the Gi-CASE biosensor, the cannabinoid ligands profiled were found to show agonist and inverse agonist activity. Agonist activity elicited a decrease in the BRET signal, indicative of receptor activation and G protein dissociation. Inverse agonist activity caused an increase in BRET signal, indicative of receptor inactivation, and the accumulation of inactive G protein. Our membrane-based Gi-CASE NanoBRET system successfully characterised the potency (pEC50) and efficacy (Emax) of CBR agonists and inverse agonists in a 384-well screening format. Values obtained were in-line with whole-cell Gi-CASE assays and consistent with literature values obtained in the GTPγS screening format.Discussion: This novel, membrane-based Gαi protein activation assay is applicable to other Gαi-coupled GPCRs, including orphan receptors, allowing real-time higher-throughput measurements of receptor activation.
MBC and ECBL libraries: outstanding tools for drug discovery
Authors: Ginex Tiziana , Madruga Enrique , Martinez Ana , Gil Carmen 
Published: August 2023

Chemical libraries have become of utmost importance to boost drug discovery processes. It is widely accepted that the quality of a chemical library depends, among others, on its availability and chemical diversity which help in rising the chances of finding good hits. In this regard, our group has developed a source for useful chemicals named Medicinal and Biological Chemistry (MBC) library. It originates from more than 30 years of experience in drug design and discovery of our research group and has successfully provided effective hits for neurological, neurodegenerative and infectious diseases. Moreover, in the last years, the European research infrastructure for chemical biology EU-OPENSCREEN has generated the European Chemical Biology library (ECBL) to be used as a source of hits for drug discovery. Here we present and discuss the updated version of the MBC library (MBC v.2022), enriched with new scaffolds and containing more than 2,500 compounds together with ECBL that collects about 100,000 small molecules. To properly address the improved potentialities of the new version of our MBC library in drug discovery, up to 44 among physicochemical and pharmaceutical properties have been calculated and compared with those of other well-known publicly available libraries. For comparison, we have used ZINC20, DrugBank, ChEMBL library, ECBL and NuBBE along with an approved drug library. Final results allowed to confirm the competitive chemical space covered by MBC v.2022 and ECBL together with suitable drug-like properties. In all, we can affirm that these two libraries represent an interesting source of new hits for drug discovery.
A common self-advantage across the implicit and explicit levels for self-body recognition
Authors: Xiang Sijia , Zhao Minghui , Yu Lunhao , Liu Ning 
Published: August 2023

IntroductionAlthough self-bias has been extensively studied and confirmed in various self-related stimuli, it remains controversial whether self-body can induce recognition advantage at the explicit level. After careful examination of previous experiments related to self-body processing, we proposed that participant strategies may influence explicit task outcomes.MethodsTo test our hypothesis, we designed a novel explicit task. For comparison, we also conducted classic explicit and implicit tasks.ResultsWith the newly designed explicit task, we found clear and robust evidence of self-hand recognition advantage at the explicit level. Moreover, we found that there was a strong link between self-advantage found in the classic implicit task and the newly designed explicit task, indicating that the self-advantage processing by these two pathways may be linked.DiscussionThese findings provide new insights into the long-standing inconsistencies in previous studies and open a new avenue for studying self-bias using self-body stimuli.
Introverted and yet effective? A faceted approach to the relationship between leadership and extraversion
Authors: Liegl Simon , Furtner Marco R. 
Published: August 2023

IntroductionExtraversion and its facets of assertiveness and sociability were identified as stable predictors for leader emergence and effectiveness. However, recent research suggested that extraversion may lie in the eyes of the beholder; it might not be the leader’s possession but their followers’ attribution of the trait that shapes these criteria of leader success.MethodsIn our study, we reverse-engineered this relationship and assessed the effects of effective leadership behaviors on personality perceptions. More specifically, we created scenarios of a leader responding to coordination challenges with passive-avoidant, transactional, or transformational leadership behaviors. We presented 204 participants with these scenarios and assessed how extraverted, assertive, and sociable they perceived the leader to be.ResultsInterestingly, and not fully meeting our expectations, ascriptions of extraversion and its facets of assertiveness and sociability did not directly relate to the effectiveness of the behaviors, as the moderately effective transactional leadership style garnered the highest ascriptions of extraversion and its facets. Further, ascriptions of extraversion to the transformational behavior of intellectual stimulation were remarkably low, matched only by the laissez-faire dimension of the passive-avoidant leadership style.DiscussionWe integrate and contrast these unexpected but explainable findings with current research, discuss potential associations between introversion and empowering leadership practices and provide suggestions for future discourse, illustrating the potential of investigating the presence of an introverted leadership advantage in the workplace of tomorrow.
The program for introduction of basic mathematical knowledge: the effects in six years old Mexican children
Authors: Solovieva Yulia , Zavaleta José Rodríguez , Carrillo Andrea Celeste Rosete , Quintanar Luis , Plotnikova Valeriya 
Published: August 2023

IntroductionThe process of teaching and learning mathematics in primary school represents an obstacle for both teachers and pupils. According to the historical-cultural conception of development and education, the way how intellectual concepts are initially introduced may radically affect a student’s success in learning. The historical-cultural conception of development, together with activity theory, may serve as the basis for creating a novel methodology for pedagogical work on mathematical concepts with pre-school and school children.MethodsThe goal of the present study was to show the effects of work with an original program for the initial introduction of mathematical concepts to young school children. The program included reflexive symbolic and logical actions on the materialized and perceptual level, which were introduced and performed collectively by six-year-old children under the guidance and assistance of a teacher. The pupils were tested before and after their work with the program.ResultsThe results showed important qualitative and quantitative progress by the children in solving the tasks of the assessment, together with an increment of reflection on their intellectual actions.DiscussionThe study points to the necessity for more intensive and extensive research, involving specialists in psychology and pedagogy trained in cultural-historical methodology.
Public stigma toward fatigue—do social characteristics of affected persons matter? Results from the SOMA.SOC study
Authors: von dem Knesebeck Olaf , Barbek Rieke 
Published: August 2023

ObjectivesAlthough public stigma imposes a great burden on those affected with manifold negative consequence there is not much known about public stigma related to fatigue. Therefore, this study addresses the following research questions: (1) What is the magnitude of public stigma toward individuals with fatigue? (2) Are there differences in public stigma depending on the social characteristics of the affected person (sex, occupation, and migration)?MethodsAnalyses are based on a national telephone survey in Germany (N = 1,209). A vignette describing a person with symptoms of fatigue was presented to the respondents. Vignettes were varied according to sex, occupational status, and migration status. Stigma toward the person presented in the vignette was measured by stereotypes and negative emotional reactions (anger).ResultsOf the stereotypes under study, “hypersensitive” was most frequently endorsed by the respondents (35.7%), followed by “weak will” (27.2%). About 15–20% of the respondents agreed that they react with anger, annoyance or incomprehension. There were considerable differences in fatigue stigma according to the social characteristics of the affected person. In two social groups public stigma was particularly pronounced: (1) male persons with a low occupational status and a migration background; (2) female persons with a high occupational status and without a migration status. In contrast, women with a low occupational status and a migration background were less stigmatized.ConclusionIndividuals suffering from fatigue symptoms are confronted with stereotypes and negative emotional reactions by the public. Magnitude of public stigma considerably varies according to social characteristics of the afflicted person. Future studies should consider applying an intersectional approach to identify groups that are at risk of multiple stigma.
The worse we feel, the more intensively we need to stick together: a qualitative study of couples’ emotional co-regulation of the challenge of multimorbidity
Authors: Horn Andrea B. , Zimmerli Lukas , Maercker Andreas , Holzer Barbara M. 
Published: August 2023

IntroductionBeing faced with multimorbidity (i.e., being diagnosed with at least two chronic conditions), is not only demanding in terms of following complicated medical regimes and changing health behaviors. The changes and threats involved also provoke emotional responses in the patients but also in their romantic partners. This study aims at exploring the ways of emotional co-regulation that couples facing multimorbidity express when interviewed together.MethodN = 15 opposite sex couples with one multimorbid patient after an acute health crisis that led to hospitalization were asked in a semi-structured interview about how they found ways to deal with the health situation, what they would recommend to other couples in a similar situation, and how they regulated their emotional responses. Interviews were analyzed qualitatively following open, axial, and selective coding, as in the grounded theory framework.ResultsEmerging categories from the romantic partners’ and the patients’ utterances revealed three main categories: First,overlapping cognitive appraisals about the situation(from fighting spirit to fatalism)and we-ness(construing the couple self as a unit) emerged as higher order factor from the utterances. Second,relationship-related strategiesincluding strategies aimed at maintaining high relationship quality in spite of the asymmetric situation like strengthening the common ground and balancing autonomy and equity in the couple were often mentioned. Third, some couples mentioned how they benefit fromindividual strategiesthat involve fostering individual resources of the partners outside the couple relationship (such as cultivating relationships with grandchildren or going outdoors to nature).DiscussionResults underline the importance of a dyadic perspective not only on coping with disease but also on regulating the emotional responses to this shared challenging situation. The utterances of the couples were in line with earlier conceptualizations of interpersonal emotion regulation and dyadic perspectives on we-disease. They broaden the view by integrating the interplay between individual and interpersonal regulation strategies and underline the importance of balancing individual and relational resources when supporting couples faced with chronic diseases.
Racial and ethnic disparities in COVID-19 booster vaccination among U.S. older adults differ by geographic region and Medicare enrollment
Authors: Hayes Kaleen N. , Harris Daniel A. , Zullo Andrew R. , Chachlani Preeti , Wen Katherine J. , Smith-Ray Renae L. , Djibo Djeneba Audrey , McCarthy Ellen P. , Pralea Alexander , Singh Tanya G. , McMahill-Walraven Cheryl , Taitel Michael S. , Deng Yalin , Gravenstein Stefan , Mor Vincent 
Published: August 2023

IntroductionCOVID-19 booster vaccines are highly effective at reducing severe illness and death from COVID-19. Research is needed to identify whether racial and ethnic disparities observed for the primary series of the COVID-19 vaccines persist for booster vaccinations and how those disparities may vary by other characteristics. We aimed to measure racial and ethnic differences in booster vaccine receipt among U.S. Medicare beneficiaries and characterize potential variation by demographic characteristics.MethodsWe conducted a cohort study using CVS Health and Walgreens pharmacy data linked to Medicare claims. We included community-dwelling Medicare beneficiaries aged ≥66 years who received two mRNA vaccine doses (BNT162b2 and mRNA-1273) as of 8/1/2021. We followed beneficiaries from 8/1/2021 until booster vaccine receipt, death, Medicare disenrollment, or end of follow-up (12/31/2021). Adjusted Poisson regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) comparing vaccine uptake between groups.ResultsWe identified 11,339,103 eligible beneficiaries (mean age 76 years, 60% female, 78% White). Overall, 67% received a booster vaccine (White = 68.5%; Asian = 67.0%; Black = 57.0%; Hispanic = 53.3%). Compared to White individuals, Black (RR = 0.78 [95%CI = 0.78–0.78]) and Hispanic individuals (RR = 0.72 [95% = CI 0.72–0.72]) had lower rates of booster vaccination. Disparities varied by geographic region, urbanicity, and Medicare plan/Medicaid eligibility. The relative magnitude of disparities was lesser in areas where vaccine uptake was lower in White individuals.DiscussionRacial and ethnic disparities in COVID-19 vaccination have persisted for booster vaccines. These findings highlight that interventions to improve vaccine uptake should be designed at the intersection of race and ethnicity and geographic location.
Characterization of antimicrobial and antioxidant performance of dihydroeugenol and its glycoside incorporated into whey protein isolate films
Authors: Resende Déborah Braga , Simões Luara Aparecida , Teixeira Fernandes Natalia de Andrade , Luvizaro Lucas Baldo , Dias Marali Vilela , Carvalho Diogo Teixeira , Piccoli Roberta Hilsdorf , Schwan Rosane Freitas , Dias Disney Ribeiro 
Published: August 2023

Bio-based plastics are gaining attention as environmentally friendly alternatives to traditional petroleum-based plastics in food packaging. Biodegradable films made from biocompatible macromolecules like polysaccharides and proteins offer promising solutions. This study investigated the effects of incorporating dihydroeugenol and glycoside into whey protein isolate (WPI) films to enhance their antimicrobial and antioxidant properties for food packaging. The findings showed that the glycoside film surpassed the dihydroeugenol film in inhibiting bacterial growth, forming larger inhibition halos against Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Salmonella Enteritidis (inhibition halos ≥15 mm). The glycoside film exhibited superior effectiveness against Gram-positive bacteria, indicating enhanced penetration through their cell membranes. Additionally, the synthesized compounds significantly boosted the antioxidant activity of the films compared to the control film without dihydroeugenol and glycoside. With a relatively low solubility (23% ± 2.87% and 24% ± 3.92% for dihydroeugenol and glycoside, respectively), these films are suitable for packaging and safeguarding food products with medium to high humidity. This study concluded that incorporating dihydroeugenol and its glycoside into WPI films holds great promise for developing active packaging solutions in the food industry. These films offer both antibacterial and antioxidant properties, particularly advantageous for food products with medium to high humidity.
What interventions should we implement in England's mental health services? The mental health implementation network (MHIN) mixed-methods approach to rapid prioritisation
Authors: Ahuja Shalini , Phillips Lawrence , Smartt Caroline , Khalid Sundus , Coldham Tina , Fischer Laura , Rae Sarah , Sevdalis Nick , Boaz Annette , Robinson Sarah , Gaughran Fiona , Lelliott Zoe , Jones Peter , Thornicroft Graham , Munshi Jayati-Das , Drummond Colin , Perez Jesus , Littlejohns Peter 
Published: August 2023

IntroductionSetting mental health priorities helps researchers, policy makers, and service funders improve mental health services. In the context of a national mental health implementation programme in England, this study aims to identify implementable evidence-based interventions in key priority areas to improve mental health service delivery.MethodsA mixed-methods research design was used for a three step prioritisation approach involving systematic scoping reviews (additional manuscript under development), expert consultations and data triangulation. Groups with diverse expertise, including experts by experience, worked together to improve decision-making quality by promoting more inclusive and comprehensive discussions. A multi-criteria decision analysis (MCDA) model was used to combine participants' varied opinions, data and judgments about the data's relevance to the issues at hand during a decision conferencing workshop where the priorities were finalised.ResultsThe study identified mental health interventions in three mental health priority areas: mental health inequalities, child and adolescent mental health, comorbidities with a focus on integration of mental and physical health services and mental health and substance misuse problems. Key interventions in all the priority areas are outlined. The programme is putting some of these evidence-based interventions into action nationwide in each of these three priority mental health priority areas.ConclusionWe report an inclusive attempt to ensure that the list of mental health service priorities agrees with perceived needs on the ground and focuses on evidence-based interventions. Other fields of healthcare may also benefit from this methodological approach if they need to make rapid health-prioritisation decisions.
The Impact of Weir Construction in Korea’s Nakdong River on the Population Genetic Variability of the Endangered Fish Species, Rapid Small Gudgeon (Microphysogobio rapidus)
Authors: Hong Yang-Ki , Kim Kang-Rae , Kim Keun-Sik , Bang In-Chul 
Published: August 2023

Microphysogobio rapidus, an endemic cyprinid fish species found exclusively in Korea, has been identified in only two tributaries of the Nakdong River. The species predominantly occupies the near-gravel bottom waters within shallow sections of the middle and lower reaches of the river, characterized by swift currents. M. rapidus is currently recognized as a critically endangered species due to its distinct habitat preference, as well as the negative impacts of stream dam development and water environment pollution. In this study, we used 10 microsatellite markers to examine the genetic diversity of M. rapidus in the upper Nam (UN), lower Nam (LN), and Deokcheon Rivers (DC) in Korea, with a specific focus on assessment of the impact of dam development. Fish sampled from the UN and LN showed a greater average number of alleles and allelic richness (A = 18.3–18.4, AR = 13.8) compared to those from DC (A = 11.8, AR = 11.5). The observed heterozygosity among the fish examined ranged from HO = 0.748 (LN) to 0.766 (DC). All three fish groups exhibited a significant departure from Hardy–Weinberg equilibrium (HWE) (p < 0.05). Despite having the largest effective population size (Ne = 175 and 157, respectively), the fish sampled from UN and LN showed the highest inbreeding coefficients (FIS = 0.056–0.053, respectively), which were highly significant (p < 0.01). In contrast, the fish sampled from DC exhibited the smallest effective population size (Ne = 61) and showed an inbreeding coefficient close to zero (p > 0.05). BOTTLENECK analysis and estimated M-ratio values (0.341–0.372) revealed indications of past population size reduction in all fish groups examined. No significant genetic differentiation (FST < 0.05) was detected using the DAPC, STRUCTURE, and AMOVA among the fish studied. However, pairwise comparisons of FST between fish sampled from the Nam and Deokcheon Rivers revealed significant values (p < 0.001) ranging from 0.013 to 0.014. In addition, the closest genetic distance (0.026) was observed between UN and LN, while the greatest distance (0.087) was found between UN and DC. Analysis of gene flow rates among the fish examined indicated asymmetrical gene exchange within the Nam River, which was 31.51% in the downstream direction (from UN to LN), with a minimal gene flow rate (0.41%) in the upstream (from LN to UN) direction. The opposite trend was recorded between DC and LN, with a higher gene flow rate (29.74%) in the upstream direction compared to the downstream direction (0.12%). Our study highlighted the importance of implementing long-term conservation efforts focused on maintaining river integrity by removing water barriers such as weirs that impede fish migration and implementing active protection measures, such as aquaculture breeding and reasonable stocking practices, to preserve M. rapidus in the study area.