bluuebunny/crossref_metadata_2025 huggingface dataset:
Gambling Operators’ Use of Advertising Strategies on Social Media and Their Effects: A Systematic Review
Authors: Singer Johannes , Wöhr Andrea , Otterbach Steffen
Published: March 2024

Purpose of Review

Social media offer gambling operators an attractive channel for connecting with gamblers and promoting their products. The aim of the present study is to review the recent literature to summarise the latest findings on marketing strategies of gambling operators, and their effects, with particular focus on social media.

Recent Findings

A systematic review on gambling advertising in social media has been conducted, taking into account English-language journal articles from 2021 onwards, which include primary data collection. Searching three data bases, a total number of 12 studies from peer-reviewed journals were identified. Gambling advertising has an enormous reach, including esports sponsorship and a surge in popularity on streaming platforms, which raises concerns about the protection of gamblers in general and of vulnerable groups in particular. The studies identify individual advertising strategies and investigate the influence of incentives and tips on gambling behaviour. Gaps in the current literature include evidence from certain regions or countries, research into communication strategies on individual social media platforms, and questions about the effectiveness of regulatory measures regarding gambling advertising.

Gambling operators flexibly adapt their advertising strategies to the surrounding conditions. This appears to be problematic, as the intensity and complexity of gambling advertising increases at the same time as the boundaries between advertising and seemingly neutral content blur. Vulnerable groups, especially children and adolescents, are at special risk, because advertising on social media is particularly attractive for them, while protection mechanisms such as age limits are often missing or being ignored.
Temporal trends in the clinical presentation of Graves’ orbitopathy: a single–center retrospective study
Authors: Le Moli R. , Naselli A. , Giudice F. Lo , Costanzo G. , Frasca F. , Belfiore A.
Published: March 2024

Purpose

Graves’ ophthalmopathy (GO) is an autoimmune disease that affects orbital soft tissues and represents the most common extrathyroidal manifestation of Graves’ disease (GD). The European Group of Graves’ Ophthalmopathy (EUGOGO) has attempted to shed light on the European epidemiological picture of GO, suggesting that GO in newly diagnosed patients in recent years has a trend towards a less severe clinical presentation. There are no studies that focus this issue on the population of our area; we aimed to evaluate the trend of GO clinical presentation in our outpatient clinic through an observation period of 10 years.

Methods

We compared 55 consecutive patients, 11 males (F) and 44 females (M), who came to our observation from January 2005 to December 2006 [Group 1 (G1)], with 56 patients, 15 males, and 41 females, who were referred to us from 2015 to 2016 [Group 2 (G2)]. We studied the following putative predictors of GO presentation and severity: thyroid function, smoking, diabetes, hypercholesterolemia, time from GO diagnosis to referral to our thyroid centre (TGOD), sex and age.

Results

GO severity was significantly reduced in G2 vs. G1 (p = 0.04). TGOD ≥ 3 months was related to clinical characteristics of GO (severity and Clinical Activity Score ≥ 4) and was an independent predictor of GO severity (p = 0.01). The other variables evaluated had no independent effects.

Conclusions

We found that GO severity at presentation was significantly reduced over a ten-year observation period (2005–2006 vs. 2015–2016) in GO patients referred to our tertiary thyroid centre. TGOD ≥ 3 months was an independent predictor of GO severity.
Comprehensive kinetic study on ammonia/ethylene counter-flow diffusion flames: influences of diluents
Authors: Shu Zhimei , Xu Tingting , Xiao Jiayi , Deng Qige , Zhao Xuan , Li Tianjiao , Ying Yaoyao , Liu Dong
Published: March 2024

This study aimed to investigate the effects of ammonia addition on ethylene counter-flow diffusion flames with different diluents on the fuel or oxidizer side, using kinetic analyses. A special emphasis was put on assessing the coupled chemical effects of NH3 and CO2 on C2H4 combustion chemistry. The chemical effects could be evaluated by comparing fictitious inert NH3 or CO2 with normal active NH3 or CO2. The results revealed that the addition of NH3 decreased the mole fractions and production rates of key soot precursors, such as acetylene, propynyl, and benzene. When CO2 was used as the dilution gas, the coupled chemical effects of NH3 and CO2 were affected by the chemical effects of CO2 to varying degrees. With the oxidizer-side CO2 addition, the coupled chemical effects of NH3 and CO2 reduced the mole fractions of H, O, OH radicals, acetylene, propynyl, and benzene, while the effects differed from the fuel-side CO2 addition. The coupled chemical effects of NH3 and CO2 also promoted the formation of aldehyde contaminants, such as acetaldehyde, to some extent, particularly with CO2 addition on the oxidizer side.
Systematic Radio Telescope Alignment Using Portable Fringe Projection Profilometry
Authors: Berkson Joel , Hyatt Justin , Julicher Nathan , Jeong Byeongjoon , Pimienta Isaac , Ball Rachel , Ellis Wyatt , Voris Jason , Torres-Barajas Diego , Kim Daewook
Published: March 2024

In 2019, the Event Horizon Telescope (EHT) released the first-ever image of a black hole event horizon. Astronomers are now aiming for higher angular resolutions of distant targets, like black holes, to understand more about the fundamental laws of gravity that govern our universe. To achieve this higher resolution and increased sensitivity, larger radio telescopes are needed to operate at higher frequencies and in larger quantities. Projects like the next-generation Very Large Array (ngVLA) and the Square-Kilometer Array (SKA) require building hundreds of telescopes with diameters greater than 10 ms over the next decade. This has a twofold effect. Radio telescope surfaces need to be more accurate to operate at higher frequencies, and the logistics involved in maintaining a radio telescope need to be simplified to support them properly in large quantities. Both of these problems can be solved with improved methods for surface metrology that are faster and more accurate with a higher resolution. This leads to faster and more accurate panel alignment and, therefore, a more productive observatory. In this paper, we present the use of binocular fringe projection profilometry as a solution to this problem and demonstrate it by aligning two panels on a 3-m radio telescope dish. The measurement takes only 10 min and directly delivers feedback on the tip, tilt, and piston of each panel to create the ideal reflector shape.
Integrated Bus Timetabling and Scheduling with a Mutation-Based Evolutionary Scheme Maximizing Headway Quality and Connections
Authors: Mertens Lucas , Amberg Bastian , Kliewer Natalia
Published: March 2024

Public transport planning is a multi-level process that includes various complex tasks. These tasks are traditionally executed sequentially, and the result of each task serves as input for consecutive tasks. A simultaneous integrated consideration of multiple tasks may lead to an overall improved solution, but further increase the complexity of already hard-to-solve planning problems. This work focuses on timetabling and vehicle scheduling and evaluates synergies from the integrated optimization. We investigate an exact sequential, exact integrated, and heuristic approach to solve the combined problem for large public transport networks considering the interlining of vehicles, multiple vehicle types, or multiple depots while additionally aiming to maximize regular “clock-faced’’ headways and transfer connections. Compared to sequential optimization, an integrated approach significantly reduces nominal and operational costs while maintaining high service quality. However, an exact integrated approach is only able to compute solutions for problems of limited size in a reasonable time. We propose an adaptive modular evolutionary extendable scheme that effectively balances computational efficiency and solution quality. By utilizing various problem-specific mutation operators and adaptively applying them based on their impact, the heuristic can compute high-quality solutions for large real-world-inspired public transport networks in a reasonable time while considering short connecting times between lines and regular clock-faced headways.
Liquid chromatography–tandem mass spectrometry method for mycophenolic acid and its glucuronide determination in saliva samples from children with nephrotic syndrome
Authors: Sobiak Joanna , Resztak Matylda , Sikora Weronika , Zachwieja Jacek , Ostalska-Nowicka Danuta
Published: March 2024

Background

Saliva sampling is one of the methods of therapeutic drug monitoring for mycophenolic acid (MPA) and its metabolite, mycophenolic acid glucuronide (MPAG). The study describes the liquid chromatography tandem mass spectrometry (LC–MS/MS) method developed for saliva MPA and MPAG determination in children with nephrotic syndrome.

Methods

The mobile phase consisted of methanol and water at gradient flow, both with 0.1% formic acid. Firstly, 100 µL of saliva was evaporated at 45 °C for 2 h to dryness, secondly, it was reconstituted in the mobile phase, and finally 10 µL was injected into the LC–MS/MS system. Saliva from ten children with nephrotic syndrome treated with mycophenolate mofetil was collected with Salivette®.

Results

For MPA and MPAG, within the 2–500 ng/mL range, the method was selective, specific, accurate and precise within-run and between-run. No carry-over and matrix effects were observed. Stability tests showed that MPA and MPAG were stable in saliva samples if stored for 2 h at room temperature, 18 h at 4 °C, and at least 5 months at − 80 °C as well as after three freeze–thaw cycles, in a dry extract for 16 h at 4 °C, and for 8 h at 15 °C in the autosampler. The analytes were not adsorbed onto Salivette® cotton swabs. For concentrations above 500 ng/mL, the samples may be diluted twofold. In children, saliva MPA and MPAG were within the ranges of 4.6–531.8 ng/mL and 10.7–183.7 ng/mL, respectively.

Conclusions

The evaluated LC–MS/MS method has met the validation requirements for saliva MPA and MPAG determination in children with nephrotic syndrome. Further studies are needed to explore plasma–saliva correlations and assess their potential contribution to MPA monitoring.

Graphical abstract
Leveraging an Open-Access Digital Design Notebook for Graduate Biomedical Engineering Education in Nigeria
Authors: Casserly Padraic , Dare Ademola , Onuh Joy , Baah Williams , Taylor Ashley
Published: March 2024

Amidst the dual challenges of an eight-month university closure from nationwide public university strikes in Nigeria and the lingering impacts of the Covid-19 pandemic, we needed to innovate the delivery of BME graduate curriculum to ensure graduate students continued to progress in their studies. To ensure BME graduate students were engaging in team-based, clinician-identified engineering design challenges, we developed a digital design notebook (DDN) using Google Sites as an open-access, collaborative tool for scaffolding and documenting the engineering design process. Student design teams remotely uploaded digital content documenting their project work onto scaffolded DDNs created by program instructors. DDNs were purposefully designed to shepherd students through the design process such that each phase of the design process corresponded to an editable “page” of the DDN. Video lectures, learning resources, assignments, and other program information were embedded into the DDN for students to access throughout their design challenge. Project mentors and program instructors remotely monitored and assessed students’ work using the DDN. At the end of the design challenge, students effectively created an e-portfolio which showcased the work they conducted to build a biomedical prototype. Designing and implementing the DDN builds on previous research which demonstrates that “structured” design notebooks can be used as effective tools in engineering design and design thinking education. Our work also leverages educational frameworks for infusing engineering design into existing graduate biomedical engineering curriculum in Nigeria.
Concrete narrative and media ranking effect on consumer satisfaction of DiDi services in China
Authors: Malik Tariq H.
Published: March 2024

Narratives drive consumer satisfaction on the one hand and the reputation of the reporting media on the other hand, but current research addresses either alone. This article integrates the narrative of the consumer and the ranking of the reporting media to understand the consumer satisfaction in response to the direct effects and interaction effects. Construal Level Theory (CLT) explains the net and interaction effects whether and how concrete vs. abstract narrative of the user in a high technology service provider reflect on the consumer’s assessment of the service, and if so, how does the media ranking moderate this concrete-abstract narrative on the consumer satisfaction so that we can explain why it matters? We used multilevel mixed effects methods for direct and indirect results based on a large dataset on DiDi company in China, comprising 12,747 entries made by consumers on digital media platforms. Our analysis shows that, independently, concrete narrative and media ranking positively predict consumer satisfaction. However, interactively, concrete narrative becomes negative and the interaction coefficient is positive and stronger than either alone coefficient alone through direct effects. Moreover, the net effect of either the concrete narrative or media ranking becomes insignificant, suggesting a strong moderation effect of the media ranking between narratives and satisfaction. We also discovered a surprising factor in the data analysis, regarding the driver of the hailing service versus the company. The narrative referring to the company (DiDi) creates a positive assessment; the narrative referring to the driver creates a negative assessment. This study suggests the need for education, social skills and behavioural training for the drivers of DiDi can indirectly influence the company.
The Mexican Economy
Authors: Cárdenas Enrique
Published: March 2024

Mexico is the sixteenth largest economy in the world and Latin America's biggest exporter and importer. Despite the country's relative macroeconomic stability, there are two Mexicos: one more prosperous, advanced and modern, the other poor, isolated and disadvantaged, and this polarization characterizes much of the country's recent economic development.

Enrique Cárdenas provides a concise survey of Mexico's recent economic history and examines its attempts to address the economic challenges thrown up by regional disparities, low productivity and an export-fuelled economy overwhelmingly dependent on demand from its largest neighbour. The book investigates the relative robustness of the macroeconomic fundamentals alongside specific industry-level economic trends, especially those sectors dependent on free trade agreements. Demographic trends, in particular migration to the north, urbanization, poor labour relations, organized crime and entrenched corruption are all shown to have impacted the economic path Mexico has taken.

The book offers an up-to-date analysis of Mexico's economic development, social reform programmes and political economy suitable for a range of courses in Latin American studies and development studies.
Disease
Authors: Darlington-Pollock Frances
Published: March 2024

In 1942 life expectancy at birth was 66 for women and 60 for men. Death was usually due to degenerative and infectious diseases. The greatest postwar success in the fight against disease was the establishment of the NHS and care that was free at the point of delivery. Life expectancy rose dramatically, but since 2011 incremental improvements have stalled and even, in some regions, begun to reverse. Infant mortality rates have crept up and the postcode lottery of health provision underscores the level of social inequality in the UK.

Good health is not simply the absence of disease. It is the collective of physical, social and mental well-being. It is the product of nutrition and genetics, of healthy lifestyles and preventative health interventions. It is the interaction between the conditions in which we live, work, play and age. Yet access to many of the things that make and keep us healthy are not evenly distributed in the population. Achieving good health is then deeply entwined with all aspects of society and cannot simply be solved by policies in one area alone.

In our rediscovery of Beveridge, the shadow of the pandemic looms large. It has never been more urgent to address the underlying causes of disease. And it has never been clearer that these determinants are not only social or physiological, but also political.
Want
Authors: Barnard Helen
Published: March 2024

Poverty in modern-day Britain looks different to the form it took in Beveridge's day but it has not disappeared. For 14 million people across the UK the lack of access to the goods and services necessary to live a decent life and to participate fully in society remains a grim reality. Despite rising standards of living, social and economic structures continue to trap those at the bottom in constant job insecurity, ill-health, overcrowded housing and educational disadvantage. Helen Barnard considers what it might take to finally slay the giant of poverty in Britain. She examines how we might build a fairer, more equal society, and what a modern welfare state should aim to achieve, including an honest appraisal of the trade-offs and choices involved in creating it.
A Troubled Constitutional Future
Authors: Murphy Mary C. , Evershed Jonathan
Published: March 2024

The UK's decision to leave the EU has opened up huge existential questions for Northern Ireland as it marks its centenary. Constitutional conflict in Northern Ireland had been regarded as largely resolved and settled, but Brexit has altered the wider constitutional framework within which the 1998 Good Friday Agreement is situated. With the question of Irish unity gaining renewed and sustained traction, and with trade, relationships and politics across 'these islands' in a state of flux, Northern Ireland approaches a constitutional moment.

Murphy and Evershed examine the factors, actors and dynamics that are most likely to be influential, and potentially transformative, in determining Northern Ireland's constitutional future. This book offers an assessment of how Brexit and its fallout may lead to constitutional upheaval, and a cautionary warning about the need to prepare for it.
Political Racism
Authors: Shaw Martin
Published: March 2024

Political Racism conceptualizes a distinctive form of racism - intentional, organized hostility mobilized by political actors - and examines its role in the Brexit conflict and in the rise of a new nationalist politics in the UK.

In a compelling analysis the book argues that Powellite anti-immigrant racism, reinterpreted in numerical terms, was combined with anti-East European and anti-Muslim hostility to inform the Vote Leave victory. This type of racism, which has a special significance in societies where racism has been delegitimized, is shown to have further shaped the form of EU withdrawal and also the government's post-Brexit policies.
Terrorist Financing
Authors: Vlcek William
Published: March 2024

This clear and rigorous examination of the international efforts to combat the financing of terrorism is suitable for a range of courses in international relations, politics and global political economy. It provides a comprehensive examination of the post-9/11 efforts to counter financial support for terrorist actors, including the more recent challenges of non-cash payment technologies as well as how to combat the financing of terrorism in regimes where territories and populations are controlled, as in the case of Islamic State.
Divided They Fell
Authors: McDaniel Sean
Published: March 2024

Why has Europe's centre-left failed to respond to the crisis of neoliberalism in Europe? Rather than opening up a moment in political time for the centre-left to puncture the dominance of neoliberalism, the multitude of crises in Europe since 2008 have consolidated its difficulties and contributed to the rise of radical and populist alternatives.

Divided They Fell examines the failures of mainstream politics, and in particular the inability of the centre-left to respond to the global financial crisis more effectively. By exploring the cases of the UK Labour Party and France's Parti Socialiste, the book investigates the role of, and interplay between, institutional intra-party dynamics, the parties' ideational landscapes and the wider political economy in shaping their responses to the crisis.

Important reputational, ideational and strategic path dependencies in both parties, it is shown, constrained the flow of fresh ideas and entrenched their internal organizational divisions, leaving them unable to offer an effective post-neoliberal economic alternative. Ultimately, this fractured the parties and sparked a crisis of centre-left identity that opened the door to emergent alternative parties and movements in both cases.

Divided They Fell helps to diagnose what has gone wrong for the centre-left in Europe and forces us to consider whether such parties are, in the context of new and emerging crises, still fit for purpose.
A representation-learning approach for insurance pricing with images
Authors: Blier-Wong Christopher , Lamontagne Luc , Marceau Etienne
Published: March 2024

Unstructured data are a promising new source of information that insurance companies may use to understand their risk portfolio better and improve the customer experience. However, these novel data sources are difficult to incorporate into existing ratemaking frameworks due to the size and format of the unstructured data. This paper proposes a framework to use street view imagery within a generalized linear model. To do so, we use representation learning to extract an embedding vector containing useful information from the image. This embedding is dense and low dimensional, making it appropriate to use within existing ratemaking models. We find that there is useful information included in street view imagery to predict the frequency of claims for certain types of perils. This model can be used as in a ratemaking framework but also opens the door to future empirical research on attempting to extract which characteristics within the image leads to increased or decreased predicted claim frequencies. Throughout, we discuss the practical difficulties (technical and social) of using this type of data for insurance pricing.
An explainable multi-agent recommendation system for energy-efficient decision support in smart homes
Authors: Zharova Alona , Boer Annika , Knoblauch Julia , Schewina Kai Ingo , Vihs Jana
Published: March 2024

Transparent, understandable, and persuasive recommendations support the electricity consumers’ behavioral change to tackle the energy efficiency problem. This paper proposes an explainable multi-agent recommendation system for load shifting for household appliances. First, we extend a novel multi-agent approach by designing and implementing an Explainability Agent that provides explainable recommendations for optimal appliance scheduling in a textual and visual manner. Second, we enhance the predictive capacity of other agents by including weather data and applying state-of-the-art models (i.e., k-nearest-neighbors, extreme gradient boosting, adaptive boosting, Random Forest, logistic regression, and explainable boosting machines). Since we want to help the user understand a single recommendation, we focus on local explainability approaches. In particular, we apply post-model approaches local, interpretable, model-agnostic explanation and SHapley Additive exPlanations as model-agnostic tools that can explain the predictions of the chosen classifiers. We further provide an overview of the predictive and explainability performance. Our results show a substantial improvement in the performance of the multi-agent system while at the same time opening up the “black box” of recommendations.
Modulations of turbulent/non-turbulent interfaces by particles in turbulent boundary layers
Authors: Wei Qingqing , Wang Ping , Zheng Xiaojing
Published: March 2024

A spatially developing flat-plate boundary layer free from and two-way coupled with inertial solid particles is simulated to investigate the interaction between particles and the turbulent/non-turbulent interface. Particle Stokes numbers based on the outer scale are

$St=2$

(low), 11 (moderate) and 53 (high). The Eulerian–Lagrangian point-particle approach is deployed for the simulation of particle-laden flow. The outer edge of the turbulent/non-turbulent interface layer is detected as an iso-surface of vorticity magnitude. Results show that the particles tend to accumulate below the interface due to the centrifugal effect of large-scale vortices in the outer region of wall turbulence and the combined barrier effect of potential flow. Consequently, the conditionally averaged fluid velocity and vorticity vary more significantly across the interface through momentum exchange and the feedback of force in the enstrophy transport. The large-scale structures in the outer layer of turbulence become smoother and less inclined in particle-laden flow due to the modulation of turbulence by the inertial particles. As a result, the geometric features of the interface layer are changed, namely, the spatial undulation increases, the fractal dimension decreases and the thickness becomes thinner in particle-laden flow as compared with unladen case. These effects become more pronounced as particle inertia increases.
A CHARACTERISATION OF SOLUBLE
${PST}$
-GROUPS
Authors: WANG ZHIGANG , LIU A-MING , SAFONOV VASILY G. , SKIBA ALEXANDER N.
Published: March 2024

Let G be a finite group. A subgroup A of G is said to be S-permutable in G if A permutes with every Sylow subgroup P of G, that is,
$AP=PA$
. Let
$A_{sG}$
be the subgroup of A generated by all S-permutable subgroups of G contained in A and
$A^{sG}$
be the intersection of all S-permutable subgroups of G containing A. We prove that if G is a soluble group, then S-permutability is a transitive relation in G if and only if the nilpotent residual
$G^{\mathfrak {N}}$
of G avoids the pair
$(A^{s G}, A_{sG})$
, that is,
$G^{\mathfrak {N}}\cap A^{sG}= G^{\mathfrak {N}}\cap A_{sG}$
for every subnormal subgroup A of G.
Inquiry, Questions, and Actions
Authors: Guilielmo Benoit
Published: March 2024

This article aims to contribute to the elucidation of the nature of inquiry. I start with some common desiderata for any theory of inquiry. I then categorize inquiry as a structured process. By focusing on its essential components, I advance a new characterization of inquiry as a combination of questioning attitudes guiding actions. Finally, I turn to the recent objection that questioning attitudes are not necessary for inquiry. I argue that inquiry is a structured process essentially constituted by questioning attitudes having two precise functional roles, initiating and guiding the deployment of cognitive capacities towards an epistemic goal.
Wireless vision-based digital media fixed-point DSP processor depending robots for natural calamities
Authors: Mary Joans S. , Gomathi N. , Ponsudha P.
Published: March 2024

Natural calamities are affecting many parts of the world. Natural disasters, terrorist attacks, earthquakes, wildfires, floods and all unpredicted phenomena. Disasters cause emergency conditions, so imperative to coordinate the prompt delivery of essential services to the sufferers. Often, disasters lead many people to perish by becoming trapped inside, but many more also perish as a result of individuals receiving rescue either too late or not at all. The implementation and design of a Receiver module utilizing Davinci code processor DVM6437, Wireless camera receiver, Zigbee Transceiver and Global Positioning System (GPS) is proposed in this manuscript for Wireless Vision-based Semi-Autonomous rescue robots that are employed in rough terrain. The receiver side’s Zigbee transceiver module eliminates the limitations of tele-operating rescue robots by enabling the control station to receive GPS data signals and aids in robot management by sending control signals wirelessly. Half and full-duplex communication are supported by the Davinci processor DVM6437, a digital media fixed-point DSP processor that relies on Very Long Instruction Words. It includes an extensive instruction set that is ideal for real-time salvage operations. DVM processor is coded utilizing MATLAB Simulink. MATLAB codes and Simulink blocks are employed under Embedded IDE link.
Career Mobility and Performance Evaluation of China's SOE Managerial Elites
Authors: Zhang Linlin , Liu Feng , Yuan Xin
Published: March 2024

This paper examines the career mobility and performance evaluation of the leaders of China's state-owned enterprises (SOEs) at the central, provincial and prefectural levels. Using data on executive turnover within publicly listed SOEs, we find that central and local SOE leaders have a similar career flow pattern. Specifically, vertical mobility within the same business group is common and more than 60 per cent of SOE leaders leave their office within three years. Only a minority of SOE leaders achieve political promotion. We also find that performance evaluation criteria are different across central and local SOEs. The leaders who provide better economic outcomes for central SOEs obtain a higher evaluation score, while close political connections boost the promotion prospects of local SOE leaders. Overall, our findings provide granular evidence on the personnel management of China's SOEs from a comparative perspective.
A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans
Authors: Kings Emilia , Ioannidis Konstantinos , Grant Jon E. , Chamberlain Samuel R.
Published: March 2024

Objective

The catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomized controlled studies.

Methods

The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria.

Results

Of the 22 full-text papers identified, 13 randomized control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory; however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val–Val participants). There were insufficient nature and number of studies for meta-analysis.

Conclusion

The cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, the results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore the effects of different dosing regimens (different doses; and single versus repeated administration).
Election integrity across Europe: who thinks elections are held fairly and why?
Authors: Goldberg Andreas C. , Plescia Carolina
Published: March 2024

If elections are to perform their legitimizing role, they should not only be objectively free, fair and non-fraudulent, but should also be perceived by the public as such. This paper investigates who perceives elections to be fair and why by contrasting two main logics: one based on the idea that perceptions of election integrity arise from external cues voters get from their environment and a second logic claiming that perceptions are internally created based on attitudes and beliefs. We use original survey data collected in ten countries around the European Elections 2019. We find that perceptions of election fairness are unrelated to country levels of integrity but mainly relate to voters’ status as winners/losers of the elections, attachment to the institutions they elect and populist attitudes. We also find beliefs on fake news influence to weakly mediate the relation between populist attitudes and perceptions of election fairness.
Self-Harm Among 17-Year-Old Adolescents With/Without Disabilities in the United Kingdom
Authors: Emerson Eric , Aitken Zoe , Arciuli Joanne , King Tania , Llewellyn Gwynnyth , Kavanagh Anne
Published: March 2024

Abstract: Background: Self-harm is a critical public health issue for adolescents/young adults. Aims: To estimate the prevalence of self-harm among adolescents with/without disabilities in the United Kingdom. Method: Secondary analysis of data collected at age 17 in the UK’s Millennium Cohort Study. Results: Prevalence of self-harm was significantly greater among adolescents with disabilities for suicide attempts and six forms of self-harming behaviors. The lifetime prevalence of suicide attempts was 5.3% (4.5–6.3) among adolescents without disabilities, 21.9% (18.2–26.2) among adolescents with less limiting disabilities, and 25.5% (17.2–35.9) among adolescents with more limiting disabilities. Adjusted prevalence rate ratios ranged from 5.13 (3.58–7.36) for those with mental health limitations to 1.48 (0.65–3.35) for those with mobility limitations. Similar patterns were observed for the 12-month prevalence of six self-harming behaviors. Limitations: Further studies are needed to identify potential mediators of the association between disability and self-harm that are potentially modifiable. Conclusion: Adolescents with disabilities are at markedly greater probability of suicide attempts and self-harming behaviors than their peers.
The Processometric Consensus Rorschach Test (pCRT-II) – An	Improved Evaluation System
Authors: Tóth-Vajna Rita , Bagdy Emőke , Lakatos Csilla , Szatmári Zsolt , Martos Tamás
Published: March 2024

Abstract: The processometric Consensus Rorschach Test is a method for analyzing the dynamics of couple communication in negotiation-based interactions. We present the development and first psychometric evaluation of the processometric Consensus Rorschach Test II (pCRT-II), which introduces several innovations to previous coding systems. Using the pCRT-II, couple communication can be assessed on dimensions of dominance, constructiveness, and emotional closeness. Intercoder reliability was demonstrated using intraclass correlations in three coders’ 15 pCRT-II protocols. Results showed that trained coders can code the three pCRT-II dimensions reliably. Moreover, we assessed the interactions of 155 heterosexual couples using the pCRT-II. Internal consistency tests of the scores of the three dimensions of the pCRT-II on the 10 Rorschach cards separately aggregated by gender indicated that the reliability of the scales is adequate. We also administered the Dyadic Coping Inventory (DCI) and the Relationship Assessment Scale (RAS) to a subsample of 134 couples and tested the associations of the scales with the pCRT-II dimensions using the actor–partner interdependence model (APIM). Results demonstrated that pCRT-II has adequate concurrent validity. Based on the findings, the coding system is promising in that it can be used to gain new insights into the functioning of couples by examining their communication processes in detail.
NFKBIE mutations are selected by the tumor microenvironment and contribute to immune escape in chronic lymphocytic leukemia
Authors: Bonato Alice , Chakraborty Supriya , Bomben Riccardo , Canarutto Giulia , Felician Giulia , Martines Claudio , Zucchetto Antonella , Pozzo Federico , Vujovikj Marija , Polesel Jerry , Chiarenza Annalisa , Del Principe Maria Ilaria , Del Poeta Giovanni , D’Arena Giovanni , Marasca Roberto , Tafuri Agostino , Laurenti Luca , Piazza Silvano , Dimovski Aleksandar J. , Gattei Valter , Efremov Dimitar G.
Published: March 2024

Loss-of-function mutations in NFKBIE, which encodes for the NF-κB inhibitor IκBε, are frequent in chronic lymphocytic leukemia (CLL) and certain other B-cell malignancies and have been associated with accelerated disease progression and inferior responses to chemotherapy. Using in vitro and in vivo murine models and primary patient samples, we now show that NFKBIE-mutated CLL cells are selected by microenvironmental signals that activate the NF-κB pathway and induce alterations within the tumor microenvironment that can allow for immune escape, including expansion of CD8+ T-cells with an exhausted phenotype and increased PD-L1 expression on the malignant B-cells. Consistent with the latter observations, we find increased expression of exhaustion markers on T-cells from patients with NFKBIE-mutated CLL. In addition, we show that NFKBIE-mutated murine CLL cells display selective resistance to ibrutinib and report inferior outcomes to ibrutinib treatment in NFKBIE-mutated CLL patients. These findings suggest that NFKBIE mutations can contribute to CLL progression through multiple mechanisms, including a bidirectional crosstalk with the microenvironment and reduced sensitivity to BTK inhibitor treatment.
Rhesus infant nervous temperament predicts peri-adolescent central amygdala metabolism & behavioral inhibition measured by a machine-learning approach
Authors: Holley D. , Campos L. J. , Drzewiecki C. M. , Zhang Y. , Capitanio J. P. , Fox A. S.
Published: March 2024

Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys (Macaca mulatta) predict anxiety-like behavior later in life. In recent years, clinical and basic researchers have implicated the central extended amygdala (EAc)—a neuroanatomical concept that includes the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST)—as a key neural substrate for the expression of anxious and inhibited behavior. An improved understanding of how early-life behavioral inhibition relates to an increased lifetime risk of anxiety disorders—and how this relationship is mediated by alterations in the EAc—could lead to improved treatments and preventive strategies. In this study, we explored the relationships between infant behavioral inhibition and peri-adolescent defensive behavior and brain metabolism in 18 female rhesus monkeys. We coupled a mildly threatening behavioral assay with concurrent multimodal neuroimaging, and related those findings to various measures of infant temperament. To score the behavioral assay, we developed and validated UC-Freeze, a semi-automated machine-learning (ML) tool that uses unsupervised clustering to quantify freezing. Consistent with previous work, we found that heightened Ce metabolism predicted elevated defensive behavior (i.e., more freezing) in the presence of an unfamiliar human intruder. Although we found no link between infant-inhibited temperament and peri-adolescent EAc metabolism or defensive behavior, we did identify infant nervous temperament as a significant predictor of peri-adolescent defensive behavior. Our findings suggest a connection between infant nervous temperament and the eventual development of anxiety and depressive disorders. Moreover, our approach highlights the potential for ML tools to augment existing behavioral neuroscience methods.
BARD1 deletion in a patient with suspected hereditary colorectal cancer
Authors: Takaiso Nobue , Imoto Issei , Yoshimura Akiyo , Ouchi Akira , Komori Koji , Iwata Hiroji , Shimizu Yasuhiro
Published: March 2024

Deleterious germline variants in the BRCA1-associated ring domain (BARD1) gene moderately elevate breast cancer risk; however, their potential association with other neoplasms remains unclear. Here, we present the case of a 43-year-old female patient diagnosed with sigmoid colon adenocarcinoma whose maternal family members met the Amsterdam Criteria II for Lynch syndrome. Comprehensive multigene panel testing revealed a heterozygous BARD1 exon 3 deletion.
Near-field detection of gate-tunable anisotropic plasmon polaritons in black phosphorus at terahertz frequencies
Authors: Pogna Eva A. A. , Pistore Valentino , Viti Leonardo , Li Lianhe , Davies A. Giles , Linfield Edmund H. , Vitiello Miriam S.
Published: March 2024

Polaritons in two-dimensional layered crystals offer an effective solution to confine, enhance and manipulate terahertz (THz) frequency electromagnetic waves at the nanoscale. Recently, strong THz field confinement has been achieved in a graphene-insulator-metal structure, exploiting THz plasmon polaritons (PPs) with strongly reduced wavelength (λp ≈ λ0/66) compared to the photon wavelength λ0. However, graphene PPs propagate isotropically, complicating the directional control of the THz field, which, on the contrary, can be achieved exploiting anisotropic layered crystals, such as orthorhombic black-phosphorus. Here, we detect PPs, at THz frequencies, in hBN-encapsulated black phosphorus field effect transistors through THz near-field photocurrent nanoscopy. The real-space mapping of the thermoelectrical near-field photocurrents reveals deeply sub-wavelength THz PPs (λp ≈ λ0/76), with dispersion tunable by electrostatic control of the carrier density. The in-plane anisotropy of the dielectric response results into anisotropic polariton propagation along the armchair and zigzag crystallographic axes of black-phosphorus. The achieved directional subwavelength light confinement makes this material system a versatile platform for sensing and quantum technology based on nonlinear optics.
Proinflammatory polarization of engineered heat-inducible macrophages reprogram the tumor immune microenvironment during cancer immunotherapy
Authors: Xue Yanan , Yan Xiaojie , Li Da , Dong Shurong , Ping Yuan
Published: March 2024

The success of macrophage-based adoptive cell therapy is largely constrained by poor polarization from alternatively activated (M2-like) to classically activated (M1-like) phenotype in the immunosuppressive tumor microenvironment (TME). Here, we show that the engineered macrophage (eMac) with a heat-inducible genetic switch can induce both self-polarization of adoptively transferred eMac and re-polarization of tumour-associated macrophages in response to mild temperature elevation in a mouse model. The locoregional production of proinflammatory cytokines by eMac in the TME dose not only induces the strong polarization of macrophages into a classically activated phenotype, but also ensures that the side effects typical for systemically administrate proinflammatory cytokines are avoided. We also present a wearable warming device which is adaptable for human patients and can be remotely controlled by a smartphone. In summary, our work represents a safe and efficient adoptive transfer immunotherapy method with potential for human translation.
N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution
Authors: Li Jiayan , Dong Ziyang , Chen Yang , Yang Zhanhui , Yan Xinen , Wang Meng , Li Chenyang , Zhao Changgui
Published: March 2024

Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of planar-chiral cyclophanes. This transformation occurs through a dynamic kinetic resolution (DKR) process to convert racemic substrates into planar-chiral macrocycle scaffolds in good to high yields with high to excellent enantioselectivities. The ansa chain length and aromatic ring substituent size is crucial to achieve the DKR approach. Controlled experiments and DFT calculations were performed to clarify the DKR process.
Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides
Authors: Ferreira Humberto J. , Stevenson Brian J. , Pak HuiSong , Yu Fengchao , Almeida Oliveira Jessica , Huber Florian , Taillandier-Coindard Marie , Michaux Justine , Ricart-Altimiras Emma , Kraemer Anne I. , Kandalaft Lana E. , Speiser Daniel E. , Nesvizhskii Alexey I. , Müller Markus , Bassani-Sternberg Michal
Published: March 2024

Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5’ cap and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed circRNAs in human cancers could be an unexplored source of tumor-specific antigens, potentially mediating anti-tumor T cell responses. This study presents an immunopeptidomics workflow with a specific focus on generating a circRNA-specific protein fasta reference. The main goal of this workflow is to streamline the process of identifying and validating human leukocyte antigen (HLA) bound peptides potentially originating from circRNAs. We increase the analytical stringency of our workflow by retaining peptides identified independently by two mass spectrometry search engines and/or by applying a group-specific FDR for canonical-derived and circRNA-derived peptides. A subset of circRNA-derived peptides specifically encoded by the region spanning the back-splice junction (BSJ) are validated with targeted MS, and with direct Sanger sequencing of the respective source transcripts. Our workflow identifies 54 unique BSJ-spanning circRNA-derived peptides in the immunopeptidome of melanoma and lung cancer samples. Our approach enlarges the catalog of source proteins that can be explored for immunotherapy.
Complexes of tubulin oligomers and tau form a viscoelastic intervening network cross-bridging microtubules into bundles
Authors: Kohl Phillip A. , Song Chaeyeon , Fletcher Bretton J. , Best Rebecca L. , Tchounwou Christine , Garcia Arceo Ximena , Chung Peter J. , Miller Herbert P. , Wilson Leslie , Choi Myung Chul , Li Youli , Feinstein Stuart C. , Safinya Cyrus R.
Published: March 2024

The axon-initial-segment (AIS) of mature neurons contains microtubule (MT) fascicles (linear bundles) implicated as retrograde diffusion barriers in the retention of MT-associated protein (MAP) tau inside axons. Tau dysfunction and leakage outside of the axon is associated with neurodegeneration. We report on the structure of steady-state MT bundles in varying concentrations of Mg2+ or Ca2+ divalent cations in mixtures containing αβ-tubulin, full-length tau, and GTP at 37 °C in a physiological buffer. A concentration-time kinetic phase diagram generated by synchrotron SAXS reveals a wide-spacing MT bundle phase (Bws), a transient intermediate MT bundle phase (Bint), and a tubulin ring phase. SAXS with TEM of plastic-embedded samples provides evidence of a viscoelastic intervening network (IN) of complexes of tubulin oligomers and tau stabilizing MT bundles. In this model, αβ-tubulin oligomers in the IN are crosslinked by tau’s MT binding repeats, which also link αβ-tubulin oligomers to αβ-tubulin within the MT lattice. The model challenges whether the cross-bridging of MTs is attributed entirely to MAPs. Tubulin-tau complexes in the IN or bound to isolated MTs are potential sites for enzymatic modification of tau, promoting nucleation and growth of tau fibrils in tauopathies.