bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamical theory of topological defects II: universal aspects of defect motion
Authors: Romano Jacopo , Mahault Benoît , Golestanian Ramin
Published: March 2024

We study the dynamics of topological defects in continuum theories governed by a free energy minimization principle, building on our recently developed framework (Romano et al 2023 J. Stat. Mech. 083211). We show how the equation of motion of point defects, domain walls, disclination lines and any other singularity can be understood with one unifying mathematical framework. For disclination lines, this also allows us to study the interplay between the internal line tension and the interaction with other lines. This interplay is non-trivial, allowing defect loops to expand, instead of contracting, due to external interaction. We also use this framework to obtain an analytical description of two long-lasting problems in point defect motion, namely the scale dependence of the defect mobility and the role of elastic anisotropy in the motion of defects in liquid crystals. For the former, we show that the effective defect mobility is strongly problem-dependent, but it can be computed with high accuracy for a pair of annihilating defects. For the latter, we show that at the first order in perturbation theory, anisotropy causes a non-radial force, making the trajectory of annihilating defects deviate from a straight line. At higher orders, it also induces a correction in the mobility, which becomes non-isotropic for the

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defect. We argue that, due to its generality, our method can help to shed light on the motion of singularities in many different systems, including driven and active non-equilibrium theories.
Generative adversarial network based resource optimization for UAV jamming assisted cognitive covert communication
Authors: Liao Xiaomin , Lin Chushan , Nie Shaotao , Wang Haipeng , Zhao Chuanyin
Published: March 2024

This paper discusses a resource optimization problem for unmanned aerial vehicle (UAV) jamming assisted cognitive covert communication. Specially, the secondary users adopt underlay strategy for spectrum access and the UAV transmits the noise signal to confuse the underlay detection of eavesdropper. According to the dynamic game characteristics in the covert communication process, a new generative adversarial network-based covert communication resource optimization algorithm (GAN-RO) is proposed for the joint optimization of UAV’s trajectory and power in cognitive covert communication assisted by UAV’s interference. The generator simulates the legitimate user to generate the resource allocation scheme, while the discriminator imitates the eavesdropper to detect covert communication. The dynamic game process between the generator and discriminator can obtain covert communication schemes by achieving Nash equilibrium. Simulation results indicate that the proposed GAN-RO algorithm can obtain a near-optimal resource optimization scheme with a rapid converge speed for non-ideal UAV jamming assisted cognitive covert communication system.
Optimization of Fuel Injection Process and Structural Analysis
Authors: Li Shuai , Zhang You Jun , Hao Jun , Gu Wen Yu , Lei Yu Qi
Published: March 2024

In order to solve the problem of precise and controllable ignition fuel injection point in the process of UCG, this paper proposes a process method of presetting the ignition agent. The method achieves the purpose of improving the ignition success rate by increasing the downhole ambient temperature and reducing the ignition threshold. By simulating and analyzing the fluid properties of the fuel in the pipeline, the velocity and dynamic pressure at the outlet of the pipeline under different initial velocities are obtained. The results show that the outlet velocity, dynamic pressure and initial velocity have an irregular curvature relationship. As the initial velocity increases, the outlet velocity and dynamic pressure continue to increase. After calculation, the relationship between the exit speed (Y) and the initial speed (X) is Y=-0.5069X2+2.0909X+5.0624. Therefore, long-distance injection is not conducive to the successful ignition of the fuel downhole.
Application study of radiant floor compo site air-conditioning system for heating and cooling
Authors: Gu Xiaosong , Yuan Yongzhe
Published: March 2024

Radiant floor air-conditioning systems are characterized by energy efficiency and comfort. However, at higher sensible heat loads and higher humidity conditions, problems such as condensation, poor comfort, slow thermal response, and difficulty in zoning control may occur. To mitigate these limitations, this study presents a composite air-conditioning system for radiant flooring that includes an air source heat pump., an underfloor coil, a fan coil and a dehumidifier for fresh outdoor air. The composite system was experimentally tested and analyzed for indoor thermal comfort under various operation modes in summer and winter in a specific thermal zone. On the basis of the experiments, the composite system comprises multiple energy supply points, and varying combinations between these functional endpoints can fulfill the comfort needs of the human body even in year-round working conditions. The radiant floor temperature varies from the dew point air temperature by roughly 7°C. Following the test day, summer radiant systems take approximately 30 minutes to reach the set indoor temperature and humidity level.. An hour after the indoor air has reached the desired temperature and humidity, the winter radiation system is activated.
Combustion efficiency control method of circulating fluidized bed boiler based on adaptive genetic algorithm
Authors: Ren Lijun
Published: March 2024

In order to improve the traditional boiler combustion efficiency control method, which has the problem of low efficiency after control, a new combustion efficiency control method of circulating fluidized bed boiler based on adaptive genetic algorithm is proposed in this paper. Firstly, the iterative principle of adaptive genetic algorithm is analyzed; Secondly, the combustion process model of circulating fluidized bed boiler is constructed by BP neural network method; Finally, based on the above model, the optimal control objective function of adaptive genetic algorithm is constructed, and the objective function is solved according to the iterative principle of adaptive genetic algorithm to complete the control of combustion efficiency of circulating fluidized bed boiler. The experimental results show that compared with the traditional control method, the combustion efficiency of the boiler controlled by this method is always more than 98%.
Simulation Study on the Influence of Grain Operation Conditions on the Dynamic Characteristics of Vehicle Body based on RecurDyn
Authors: Jiang Chunying , Guan Xu , Ye Changlong , Zhou Huan , Tang Zuomin
Published: March 2024

At present, the grain storage depot has introduced the warehouse closing vehicle to replace the manual grain surface leveling operation. Aiming at the problems of subsidence, vibration and slipping when the warehouse car walks on the grain surface, the multi-body dynamics simulation is carried out for the four complex working conditions and load conditions of the car body in the grain depot environment, including straight running, turning, tilting and obstacle crossing, and its driving dynamic characteristics are analyzed. It can be seen from the simulation results that in the turning condition, the required driving force is the largest, the sliding condition is the most serious, the sinking degree is the deepest, and the stability is the worst. The driving dynamics of the clearance car will change suddenly when entering and leaving the pit under the obstacle crossing condition. Through the dynamic simulation results, the change law of the driving dynamic characteristics of the clearance car is summarized, and the vibration damping performance, adhesion performance and Through performance and work efficiency, it provides a theoretical basis for vehicle body design and optimization.
Research on User Data Protection for Electric-driven Bicycle
Authors: Duan KunLun , Han WenBao , Ou Wei
Published: March 2024

Under the fast growth of new industries such as the Internet of Things, cloud computing, and artificial intelligence, the shared electric-driven bicycle has proved its great market competitiveness as a product of the era of mobile internet and sharing economy. However, the frequent interaction of large-scale data and the cross-fertilization of massively stored information have exposed a series of problems such as user privacy leakage, data island, imperfect credit systems, etc. For this objective, a data security protection model for shared electric-driven bicycles has been developed. To replace the centralized update mechanism and Blockchain technology, the model uses SM2 and Blockchain identity authentication protocols, decentralized cryptographic storage and multi-factor authentication, asynchronous federated learning mechanism, and distributed end-to-end parameter update mechanism. The experimental results show that the adoption of this data protection model can effectively resist replay attacks and prevent attackers from decrypting user identity information offline. It can also mitigate the risk of parameter leakage caused by centralized servers and establish a secure and trustworthy distributed data sharing mechanism for users of the shared electric-driven bicycle network.
K3 surface entropy and automorphism groups
Authors: Yu Xun
Published: March 2024

We derive a characterization of the complex projective K3 surfaces which have automorphisms of positive entropy in terms of their Néron–Severi lattices. Along the way, we classify the projective K3 surfaces of zero entropy with infinite automorphism groups and we determine the projective K3 surfaces of Picard number at least five with almost abelian automorphism groups, which gives an answer to a long standing question of Nikulin.
Women and Employment in Public Policy
Authors: Milner Susan
Published: March 2024

The book analyses the development of public policy on women and employment in the New Labour years (1997–2010) and tracks the development of policy since 2010, to assess the degree of continuity and divergence. It covers five areas examined by the Women and Work Commission, which sat in 2004–6 and in 2009: equal pay, part-time work, work–family policy, education and training, and the public sector. It argues that policy is characterized by a ‘stalled revolution’ whereby policy has failed to keep pace with societal change and to maintain momentum after a period of innovation in the Labour years. It shows that a combination of late policy and party modernization, uneven commitment to the equality and women’s policy machineries, and competing leadership priorities explains the stalling of policy, despite sustained efforts by campaigners, parliamentarians, and ministers. It makes a case for the continued relevance of policy on women and employment, even in the rapidly changing labour market of today.
The Women’s Policy Machinery
Authors: Milner Susan
Published: March 2024

This chapter charts the development of the women’s policy machinery after 1997, focusing on the Labour years of government. Alongside the post of minister for women (later for women and equality) and the Women’s Unit (WU) within the civil service, the chapter briefly considers the role of women’s organizations and the Women’s National Commission (WNC), which was strengthened during the Labour years but dismantled in 2010. The Labour years were a period of women’s activism within and outside government, and the minister for women served as a focal point for agenda-setting. However, the women’s policy machinery was weak, owing to frequent changes of location and personnel. Leading Labour women, in particular Patricia Hewitt and Harriet Harman, were critical actors in shaping policy on women, because of their status and access to party leaders, but had to frame demands within dominant policy preferences.
The Part-Time Working Penalty and the Undervaluing of Women’s Work
Authors: Milner Susan
Published: March 2024

The part-time working gap remains a structural feature of the British labour market, although it has narrowed slightly in recent years. It contributes significantly to the aggregate gender pay gap, because part-time working is disproportionately associated with low-paid, low-status work. Women lose out financially over the life course by periods spent working part-time; for some women, it becomes impossible to find well-paid full-time employment after working part-time. The anti-discrimination approach, aimed at equalizing conditions for part-time and full-time workers, addresses this disparity only partially, because it does not challenge the labour-market structures and practices that result in gender segregation. The Women and Work Commission (WWC) in 2006 recommended employer actions to improve the quality of part-time work and funding for a pilot project with this aim. However, the pilot project was underfunded and did not generate sufficient engagement from the private sector. Since then, no policy initiatives have addressed the quality of part-time employment, although (as discussed in Chapter 11) the right to request flexible working aims at normalizing adaptation of working hours to suit family and other employee commitments.
Training and Skills
Authors: Milner Susan
Published: March 2024

There is wide consensus on the need to address labour-market disadvantage, as well as the productivity of the economy, through investment in skills training. Equality campaigners have long highlighted the consequences of educational choices for women’s pay and career development and identified the obstacles to women’s full access to education and training opportunities. Poor training opportunities are a factor of occupational segregation. Yet, despite several decades of sectoral initiatives, progress in desegregating jobs through more gender-balanced routes such as apprenticeships is slow, and blockages are evident in some (well-paid) sectors such as engineering, technology, and construction. This chapter examines reasons for this policy failure, focusing on a lack of strategic investment in training policy more widely, and a lack of attention in policy formulation and delivery to the specific problems faced by women and other groups of workers experiencing labour-market disadvantage.
Setting the Standard?
Authors: Milner Susan
Published: March 2024

The public sector is an important employer of women and an important site of innovation in policy aimed at equalizing pay and conditions for men and women at work. During the Labour years, the public sector was the focus of major policy initiatives, first on job evaluation in health and local government, building on negotiations between employers and trade unions; and second on new forms of active duties on employers to promote equality at work, and in service delivery. This chapter critically discusses those initiatives and identifies gaps in implementation that weaken their impact, despite the potential for transformative change. The chapter also shows the importance of policy design in creating effective duties, with reference to the opportunities created by the devolution of decision-making in Scotland and Wales in particular, but also their limits.
Conclusion
Authors: Milner Susan
Published: March 2024

The conclusion presents an overview of the five areas of policy on women and employment, tracking its development and assessing the degree of continuity and divergence since 2010. It argues that path dependency continues to shape policy, but it is mediated by ideology. It goes on to review the questions about women’s representation and the regulatory space outlined in Chapters 1–3 in the light of the policy overview.
The Role of Exercise in the Prevention and Treatment of Hypertension
Authors: Siegel William C. , Blumenthal James A.
Published: March 2024

In recent years, interest in the use of exercise to lower elevated blood pressure or prevent the development of hypertension has burgeoned. A large body of literature supports the notion that increasing aerobic fitness will decrease blood pressure both in normotensive and in hypertensive subjects. Numerous observational and interventional studies have reported moderate, clinically significant decreases in both systolic and diastolic blood pressure. The mechanism for these changes is unclear, though much effort has focused on the sympathetic nervous system because of the decrease in sympathetic activity that occurs with increased fitness. However, even in the best-studied population, White middle-aged men with mild hypertension, the evidence is inconsistent and the existing studies are flawed. Much more work is needed to help clarify the effect of aerobic training on blood pressure, as well as the effects of medications, co-existing medical conditions, and demographic factors on the fitness/blood pressure relationship.
Evaluating the Efficacy of Physical Activity for Influencing Quality-of-Life Outcomes in Older Adults
Authors: Stewart Anita L. , King Abby C.
Published: March 2024

Exercise and other forms of physical activity are known to have a variety of physiologic and fitness benefits for older adults. Less is known, however, about whether physical activity can improve quality-of-life in older adults. Quality-of-life is defined in terms of multiple concepts pertaining to day-to-day functioning and well-being. This article presents a conceptual framework of quality-of-life concepts that are appropriate for evaluating the efficacy of physical activity in older adults. The available studies of the relationship of exercise or physical activity to each concept are reviewed. The concepts are organized into seven categories: physical functioning, cognitive functioning, activities (self-maintenance, role, social, recreation/hobbies), bodily well-being, emotional well-being, self-concept, and global perceptions, including health perceptions and life satisfaction. Methodological and measurement issues are noted that are of special relevance for quality-of-life and exercise studies. Very few exercise studies were found that evaluated intervention efficacy in terms of quality-of-life in older adults. Those that were available focused on a limited number of components of quality-of-life. Because the few studies available generally found beneficial effects, the study of exercise- related quality-of-life outcomes is a promising area for future study.
Physical Activity, Glucose Tolerance, and Diabetes in Older Adults
Authors: Laws Ami , Reaven Gerald M.
Published: March 2024

Non-insulin-dependent diabetes and other disorders of carbohydrate metabolism are common health problems among older American adults resulting in substantial morbidity and mortality. A number of cross-sectional and interventional studies suggest that physical activity can be of benefit in both prevention and treatment of these disorders. However, because the improvements achieved by exercise in these disorders are transient, exercise must be performed regularly to be of benefit. It is most likely that the greatest benefit would be derived if individuals were to remain physically fit throughout their lifetimes.
The Regulation of Body Weight: Evidence and Clinical Implications
Authors: Stallone Daryth D. , Stunkard Albert J.
Published: March 2024

We review the concept of the regulation of body weight and discuss its clinical significance. Evidence that body weight is regulated in animals of normal weight and in some obese animals suggests that some types of obesity manifest regulation of body weight at an elevated level We show that the concept of regulation applies not only to maintenance of a stable body weight, but also to variations of body weight. Endogenous factors related to hibernation, migration, and the ovulatory cycle, and experimental interventions, such as brain lesions and “appetite suppressant” medication, can alter the level at which body weight is regulated. Evidence is presented that body weight regulation may also occur in both normal weight and obese humans. We conclude with a discussion of a new role for “appetite suppressant” medication in the treatment of obesity.
Twin Studies of Cardiovascular Response to Psychological Challenge: A Review and Suggested Future Directions
Authors: Turner J. Rick , Hewitt John K.
Published: March 2024

This review examines studies which have explored the origins of individual differences in cardiovascular response to psychological challenge by employing the classical twin study methodology. The studies discussed focus on heart rate and/or blood pressure responses. While the widely ranging analytical techniques, relatively small sample sizes, varying health status of subjects, and the use of mainly male samples make more definitive conclusions difficult to draw, the evidence suggests that reactivity to psychological stress is indeed moderately heritable. Further, it appears unlikely that non-genetic influences shared by siblings play any substantial or lasting role in determining individual differences in responsivity. Suggested future directions for research include the incorporation of a wider range of physiological parameters, adoption of some of the new generation of behavioral medicine tasks focusing on psychosocial or social situations, racial and gender group comparisons, and investigation of genetic influences on ambulatory cardiovascular parameters. Finally, the most recent advances in appropriate behavioral genetic analytical approaches are discussed, and path analysis is suggested as the technique of choice for research in this area. By combining the most recent advances in cardiovascular psychophysiology, behavioral medicine, and behavioral genetics, future studies adopting integrative research strategies should further our understanding of genetic influences on cardiovascular reactivity.
Determinants of Body Fat Localization and its Implications for Health
Authors: Rodin Judith
Published: March 2024

Recent epidemiologic evidence suggests that a pattern of abdominally-localized fat significantly increases risk for cardiovascular disease, diabetes, hypertension, and some cancers. Four major cases of factors that regulate the distribution of body fat to different regions of the body have recently been suggested. These are: genetics, the aging process, gender, and environmental/lifestyle variables. The present review briefly discusses the current status of evidence for each of these variables, with a more extended discussion of the role of stress and stress-related lifestyle variables, such as weight cycling and cigarette smoking. It is proposed that these lifestyle factors may be of considerable significance since they may promote fat deposition selectively to the visceral intra-abdominal depots, which have recently been implicated in impaired insulin metabolism and elevated plasma lipid and lipoprotein levels.
Fibromyalgia: Clinical Signs, Research Findings, Treatment Implications, and Future Directions
Authors: Baumstark Karen E. , Buckelew Susan P.
Published: March 2024

Fibromyalgia syndrome (FS), a chronic painful condition, affects approximately six million Americans. Criteria for the diagnosis of fibromyalgia include widespread pain and the presence of reproducible and characteristic tender points. Despite the physical impairment and distress associated with FS, there are few objective findings. Therefore, psychological factors have been proposed as important in the maintenance and exacerbation of the condition. There has been a proliferation of research findings on FS in the last ten years. This article reviews the clinical signs; research findings, including the role of physical and psychological factors; treatment implications; and future directions.
Statistical Analysis of Temporal Data With Many Observations: Issues For Behavioral Medicine Data
Authors: Jaccard James , Wan Choi K.
Published: March 2024

Approaches to the analysis of behavioral medicine data with few individuals but many repeated observations are discussed. Difficulties with common analytic strategies are noted and applications from econometrics using cross-sectional pooled time series designs are recommended. Additional complications due to outliers, missing data, measurement error, and aggregation bias are discussed.
Coronary Heart Disease in Women: Influences on Diagnosis and Treatment
Authors: Frank Erica , Taylor C. Barr
Published: March 2024

Coronary heart disease (CHD) is the leading cause of mortality in the United States in both sexes. Recent advances in diagnostic and treatment techniques can lessen mortality. However, for uncertain reasons, U.S. women receive less aggressive diagnosis and treatment of CHD than do U.S. men. This article explores this gender-linked differential, examines some potential medical and psychosocial reasons for why it exists, and presents some ramifications for health professionals.
Benefits of Psychological Preparation for Surgery: a Meta-Analysis
Authors: Johnston Marie , Vögele Claus
Published: March 2024

There is now substantial agreement that psychological preparation for surgery is beneficial to patients. It is important, however, to establish which benefits can be achieved by psychological preparation and if all forms of preparation are equally effective. The results of randomized controlled trials of psychological methods of preparing adult patients for surgery were analyzed in terms of eight outputs (negative affect, pain, pain medication, length of stay, behavioral and clinical indices of recovery, physiological indices, and satisfaction). In order to reduce publication bias, published as well as unpublished studies were included in the meta-analysis. It was concluded that significant benefits can be obtained on all of the major outcome variables that have been explored. Procedural information and behavioral instructions show the most ubiquitous effects in improving measures of postoperative recovery. The results have implications for the improvement of patient care in surgical units.
Issues in the Prevention of Weight Gain after Smoking Cessation
Authors: Perkins Kenneth A.
Published: March 2024

Although commonly accepted, there is essentially no direct support for the assumption that preventing weight gain after smoking cessation will improve the likelihood of remaining abstinent from smoking. First, developing interventions to prevent this weight gain has proven to be extremely difficult. To date, no adjunct behavioral treatment has been shown to be successful in attenuating cessation-induced weight gain in healthy ex-smokers. Reasons for this failure may stem from inadequate intensity of interventions, poor compliance due to the complexity of interventions aimed at both eliminating smoking and controlling weight, or to biological pressures for weight to increase after removal of the weight suppressing effects of smoking (i.e. altered energy regulation). Pharmacological interventions, despite being successful during brief periods of active use, have not been studied beyond several months' duration of treatment. Second and more importantly, prospective studies have not reported that weight gain after cessation directly predicts relapse, and results of a recent intervention indicate that adjunct weight control treatment may be associated with greater smoking relapse. Although contrary to common belief these findings are very consistent with a large body of basic animal research showing that food or weight restriction increases drug intake. In light of these observations, a more prudent and fruitful approach for basic and clinical research may be to re-examine the fundamental relationships among smoking, eating, body weight, and perhaps weight-related attitudes, rather than developing intensive strategies for combating weight gain after smoking cessation. If further study continues to find no positive relationship between this weight gain and risk of subsequent smoking relapse, it may be necessary to consider developing treatments designed to help ex-smokers accept, rather than fight, weight gain after cessation.
Social Support and Marital Coping with Chronic Illness
Authors: Revenson Tracey A.
Published: March 2024

This article reviews a number of issues related to married couples' coping with and adjustment to chronic physical illness. Spouses occupy a dual role in the coping process, as primary provider of support to the ill partner and as a family member who needs support in coping with the illness-related stresses he or she is experiencing. Studies on the impact of illness on the healthy spouse and the marital relationship are reviewed, with a focus on social support transactions between partners. In addition, sources of support for the healthy spouse are described. Two theoretical models of couples' coping are presented and suggested for future research in the area: one focuses on relationship-focused coping efforts and the other focuses on the congruence or fit between husbands' and wives' coping efforts. An integrative framework is presented, and a call is sounded for research on couples' coping with chronic stress that addresses the multiple influences of gender.
Treatments for Childhood and Adolescent Obesity
Authors: Haddck C. Keith , Shadish William R. , Klesges Robert C. , Stein Risa J.
Published: March 2024

The current review provides the first comprehensive metaanalysis of the childhood and adolescent obesity treatment literature. A total of 41 controlled, treatment outcome studies were included in the analyses. Results indicated that treatments for childhood and adolescent obesity produce significantly better outcomes than control conditions both at posttest and follow-up. Three variables were most consistently related to treatment outcome. First, comprehensive behavioral treatments—those using a combination of behavioral modification procedures, a special diet, and an exercise program—emerged as the treatment of choice for childhood and adolescent obesity. Second, treatments which included behavioral modification techniques produced better treatment results than weight loss programs not using behavioral modification. Third, studies using heavier children as subjects produced larger absolute weight losses. Suggestions for future research are discussed in relation to the limitations of the current childhood obesity treatment literature.
Mammography Use in the U.S.: Trends and the Impact of Interventions
Authors: Rimer Barbara K.
Published: March 2024

Mammography use has increased dramatically over the last five years. In 1990, 63% of U.S. women over age 40 reported ever having had a mammogram. The most important barriers to mammography have remained stable—lack of a physician recommendation and not knowing that mammograms are needed in the absence of symptoms. A range of interventions have been employed to increase mammography use. These include media campaigns, patient-directed interventions, system-directed or physician-directed interventions, access-enhancing interventions, policy-level interventions, social network interventions, and multi-strategy interventions. Six studies were reviewed in which single-intervention strategies were evaluated. Two of the six studies showed main effects; the others evidenced interventions. Fourteen studies included multi-strategy approaches to intervention: 11 of 14 had main effects. The others showed interactions. Thus, 33% of the single-intervention trials resulted in significant main effects compared to 85% of the multi-intervention studies. In the future, there should be more attention to standardization of measures and to the refinement of interventions for women over age 50 who are not currently getting regular mammograms.
III—Doing Our ‘Best’? Utilitarianism, Rationality and the Altruist’s Dilemma
Authors: Hayward Max Khan
Published: March 2024

Utilitarians think that what matters in ethics is making the world a better place. In that case, it might seem that we each rationally ought to do our best—perform the actions, out of those open to each of us, with the best expected outcomes. In other words, we should follow act-utilitarian reasons. But often the result of many altruistic agents following such individualistic reasons is worse than the result of them following collectivist ‘team-reasons’. So utilitarians should reject act utilitarianism, and accept a dualist view according to which both individualistic and team reasons are fundamental. In order to align these distinct kinds of reason, utilitarians must focus centrally on questions of political and social reform—as did their historical forebears.
Ophthalmate is a new regulator of motor functions via CaSR: implications for movement disorders
Authors: Alhassen Sammy , Hogenkamp Derk , Nguyen Hung Anh , Al Masri Saeed , Abbott Geoffrey W , Civelli Olivier , Alachkar Amal
Published: March 2024

Dopamine’s role as the principal neurotransmitter in motor functions has long been accepted. We broaden this conventional perspective by demonstrating the involvement of non-dopaminergic mechanisms. In mouse models of Parkinson’s disease, we observed that L-DOPA elicited a substantial motor response even when its conversion to dopamine was blocked by inhibiting the enzyme aromatic amino acid decarboxylase (AADC). Remarkably, the motor activity response to L-DOPA in the presence of an AADC inhibitor (NSD1015) showed a delayed onset, yet greater intensity and longer duration, peaking at 7 h, compared to when L-DOPA was administered alone. This suggests an alternative pathway or mechanism, independent of dopamine signalling, mediating the motor functions. We sought to determine the metabolites associated with the pronounced hyperactivity observed, using comprehensive metabolomics analysis.

Our results revealed that the peak in motor activity induced by NSD1015/L-DOPA in Parkinson’s disease mice is associated with a surge (20-fold) in brain levels of the tripeptide ophthalmic acid (also known as ophthalmate in its anionic form). Interestingly, we found that administering ophthalmate directly to the brain rescued motor deficits in Parkinson’s disease mice in a dose-dependent manner. We investigated the molecular mechanisms underlying ophthalmate’s action and discovered, through radioligand binding and cAMP-luminescence assays, that ophthalmate binds to and activates the calcium-sensing receptor (CaSR).

Additionally, our findings demonstrated that a CaSR antagonist inhibits the motor-enhancing effects of ophthalmate, further solidifying the evidence that ophthalmate modulates motor functions through the activation of the CaSR. The discovery of ophthalmate as a novel regulator of motor function presents significant potential to transform our understanding of brain mechanisms of movement control and the therapeutic management of related disorders.
BioKC: a collaborative platform for curation and annotation of molecular interactions
Authors: Vega Carlos , Ostaszewski Marek , Grouès Valentin , Schneider Reinhard , Satagopam Venkata
Published: March 2024

Curation of biomedical knowledge into systems biology diagrammatic or computational models is essential for studying complex biological processes. However, systems-level curation is a laborious manual process, especially when facing ever-increasing growth of domain literature. New findings demonstrating elaborate relationships between multiple molecules, pathways and cells have to be represented in a format suitable for systems biology applications. Importantly, curation should capture the complexity of molecular interactions in such a format together with annotations of the involved elements and support stable identifiers and versioning. This challenge calls for novel collaborative tools and platforms allowing to improve the quality and the output of the curation process. In particular, community-based curation, an important source of curated knowledge, requires support in role management, reviewing features and versioning. Here, we present Biological Knowledge Curation (BioKC), a web-based collaborative platform for the curation and annotation of biomedical knowledge following the standard data model from Systems Biology Markup Language (SBML). BioKC offers a graphical user interface for curation of complex molecular interactions and their annotation with stable identifiers and supporting sentences. With the support of collaborative curation and review, it allows to construct building blocks for systems biology diagrams and computational models. These building blocks can be published under stable identifiers and versioned and used as annotations, supporting knowledge building for modelling activities.
Evolution and characteristics of studies estimating attributable mortality to second-hand smoke: a systematic review
Authors: López-Medina Diana C , Candal-Pedreira Cristina , Rey-Brandariz Julia , Guerra-Tort Carla , García Guadalupe , Martín-Gisbert Lucia , Casal-Acción Beatriz , Ruano-Ravina Alberto , Varela-Lema Leonor , Pérez-Ríos Mónica
Published: March 2024

Background

Several studies have estimated the impact of second-hand smoke (SHS) exposure on mortality in the population of different countries. This study aimed to identify and describe studies that have estimated the attributable mortality (AM) associated with SHS exposure in the adult population.

Methods

A literature search was conducted in MEDLINE, EMBASE, Cochrane Library and CINAHL databases up to January 2023. Studies that estimated the AM associated with SHS exposure in the adult population and used a prevalence-dependent method were included. The main characteristics of the studies and their results were described.

Results

Fifty-three studies were included. Most of them were conducted in North America (n = 13), Europe (n = 14) and China (n = 6) and included lung cancer (n = 46) or ischaemic heart disease (n = 22) as causes of death. There was considerable variety in the population under study regarding the relationship with tobacco: non-smokers (n = 30); never-smokers (n = 9); both non and never-smokers (n = 2); the whole population (n = 1) and not known (n = 11). The age at which AM was estimated also varied between studies, ranging from 15  to 40 years and older.

Conclusions

Studies estimating AM associated with SHS exposure are heterogeneous in terms of the causes of death studied, the age at which mortality is attributed, or the population to which mortality referred: consensus should be reached. Despite their importance, studies assessing AM to SHS are infrequent in low- and middle-income countries.
Emergence of phenotypic plasticity through epigenetic mechanisms
Authors: Romero-Mujalli Daniel , Fuchs Laura I R , Haase Martin , Hildebrandt Jan-Peter , Weissing Franz J , Revilla Tomás A
Published: March 2024

Plasticity is found in all domains of life and is particularly relevant when populations experience variable environmental conditions. Traditionally, evolutionary models of plasticity are non-mechanistic: they typically view reactions norms as the target of selection, without considering the underlying genetics explicitly. Consequently, there have been difficulties in understanding the emergence of plasticity, and in explaining its limits and costs. In this paper, we offer a novel mechanistic approximation for the emergence and evolution of plasticity. We simulate random “epigenetic mutations” in the genotype–phenotype mapping, of the kind enabled by DNA-methylations/demethylations. The frequency of epigenetic mutations at loci affecting the phenotype is sensitive to organism stress (trait–environment mismatch), but is also genetically determined and evolvable. Thus, the “random motion” of epigenetic markers enables developmental learning-like behaviors that can improve adaptation within the limits imposed by the genotypes. However, with random motion being “goal-less,” this mechanism is also vulnerable to developmental noise leading to maladaptation. Our individual-based simulations show that epigenetic mutations can hide alleles that are temporarily unfavorable, thus enabling cryptic genetic variation. These alleles can be advantageous at later times, under regimes of environmental change, in spite of the accumulation of genetic loads. Simulations also demonstrate that plasticity is favored by natural selection in constant environments, but more under periodic environmental change. Plasticity also evolves under directional environmental change as long as the pace of change is not too fast and costs are low.
Embargoes, Weapons, and Violence: The Conditional Effects of Arms Embargoes on Civilian Targeting
Authors: Jadoon Amira , Early Bryan R
Published: March 2024

A primary goal of arms embargoes is to mitigate the humanitarian effects of conflict within target states by restricting access to foreign weaponry. Within this study, we investigate how embargoed governments adapt their violent strategies in response to restrictions on arms imports. We theorize that arms embargoes that undermine governments’ military strength may inadvertently increase their reliance on civilian repression as an alternative approach to countering domestic threats. However, we expect that targeted governments’ ability to acquire weapons from non-participating or non-compliant suppliers will have a mitigating effect. A global examination of the effects of arms embargoes between 1989 and 2004 supports our argument and also suggests that both the levels of arms received and who supplies them matter. Our findings suggest that policymakers who employ arms embargoes should consider increased violence against civilians as a potential unintended consequence and closely monitor target governments’ use of repression.
Advance Care Planning in the Context of Dementia: Defining Concordance
Authors: Clayton Jordana L , Supiano Katherine P , Aruscavage Nancy , Bybee Sara G , Utz Rebecca L , Iacob Eli , Dassel Kara B
Published: March 2024

Background and Objectives

Individuals with dementia may require a surrogate decision maker as their disease progresses. To prepare for this potential role, dementia care partners need to develop a thorough understanding of their care recipient’s end-of-life values and preferences, or care dyad advance care planning (ACP) concordance. As part of our pilot study implementing the LEAD intervention with dementia care dyads, we conducted a multimethod investigation to define care dyad ACP concordance.

Research Design and Methods

We conducted a scoping review of peer-reviewed studies published after 1991 in English focusing on care dyad ACP concordance in dementia care and included 34 articles. Concurrently, we used descriptive qualitative analysis to analyze 7 dyadic ACP conversations from a pilot study about dyadic dementia ACP.

Results

The scoping review demonstrated (a) no definition of care dyad ACP concordance was reported; (b) surrogate accuracy in end-of-life decisions varies widely; and (c) best practices for ACP in dementia may aid in achieving ACP concordance, but do not prioritize it as an outcome. Qualitative analysis identified 7 elements for achieving concordance: Respect/Regard; use of Clarifying Processes; Conveying Health Care Scenarios; Affirmation of Understanding; Recognizing Uncertainty; Expression of Positive Emotions; and Trust.

Discussion and Implications

Care dyad ACP concordance occurs when care recipients and care partners both understand a care recipient’s end-of-life values, understand the end-of-life preferences informed by those values, and the care partner expresses a willingness to accomplish the care recipient’s wishes to the best of their ability. ACP concordance can be further operationalized for research and clinical care.
Crohn’s Disease Phenotypes and Associations With Comorbidities, Surgery Risk, Medications and Nonmedication Approaches: The MAGIC in IMAGINE Study
Authors: Bernstein Charles N , Panaccione Remo , Nugent Zoann , Marshall Deborah A , Kaplan Gilaad G , Vanner Stephen , Dieleman Levinus A , Graff Lesley A , Otley Anthony , Jones Jennifer , Buresi Michelle , Murthy Sanjay , Borgaonkar Mark , Bressler Brian , Bitton Alain , Croitoru Kenneth , Sidani Sacha , Fernandes Aida , Moayyedi Paul
Published: March 2024

Background

We aimed to establish a cohort of persons with Crohn’s disease (CD) enrolled from 14 Canadian centers to describe the contemporary presentation of CD in Canada.

Methods

All enrollees were at least 18 years old and underwent chart review for phenotype documentation by Montreal Classification at time of enrollment, comorbidities, inflammatory bowel disease (IBD) and other surgeries, and use IBD and other therapies.

Results

Of 2112 adults, 59% were female, and the mean age was 44.1 (+/-14.9SD) years. The phenotype distribution was B1 = 50.4%, B2 = 22.4%, B3 = 17.3%, and missing information = 9.9%. Perineal disease was present in 14.2%. Pertaining to disease location, 35.2% of patients had disease in L1, 16.8% in L2, 48% in L3, and 0.4% in L4. There was no difference in phenotype by gender, anxiety score, depression score. Disease duration was significantly different depending on disease behavior type (B1 = 12.2 ± 10.1; B2 = 19.4 ± 12.9; B3 = 18.9 ± 11.8, P < .0001). Isolated colonic disease was much less likely to be fibrostenotic or penetrating than inflammatory disease. Penetrating disease was more likely to be associated with ileocolonic location than other locations. Perineal disease was most commonly seen in persons with B3 disease behavior (24%) than other behaviors (11% B1; 20% B2 disease, P < .0001) and more likely to be seen in ileocolonic disease (L3;19%) vs L2 (17%) and L1 (11%; P < .0001). Surgery related to IBD occurred across each behavior types at the following rates: B1 = 23%, B2 = 64%, and B3 = 74%. Inflammatory bowel disease–related surgery rates by location of disease were L1 = 48%, L2 = 21%, and L3 = 51%.

Conclusions

In exploring this large contemporary CD cohort we have determined that inflammatory disease is the main CD phenotype in Canada and that CD-related surgery remains very common.
Accurate, Robust, and Scalable Machine Abstraction of Mayo Endoscopic Subscores From Colonoscopy Reports
Authors: Silverman Anna L , Bhasuran Balu , Mosenia Arman , Yasini Fatema , Ramasamy Gokul , Banerjee Imon , Gupta Saransh , Mardirossian Taline , Narain Rohan , Sewell Justin , Butte Atul J , Rudrapatna Vivek A
Published: March 2024

Background

The Mayo endoscopic subscore (MES) is an important quantitative measure of disease activity in ulcerative colitis. Colonoscopy reports in routine clinical care usually characterize ulcerative colitis disease activity using free text description, limiting their utility for clinical research and quality improvement. We sought to develop algorithms to classify colonoscopy reports according to their MES.

Methods

We annotated 500 colonoscopy reports from 2 health systems. We trained and evaluated 4 classes of algorithms. Our primary outcome was accuracy in identifying scorable reports (binary) and assigning an MES (ordinal). Secondary outcomes included learning efficiency, generalizability, and fairness.

Results

Automated machine learning models achieved 98% and 97% accuracy on the binary and ordinal prediction tasks, outperforming other models. Binary models trained on the University of California, San Francisco data alone maintained accuracy (96%) on validation data from Zuckerberg San Francisco General. When using 80% of the training data, models remained accurate for the binary task (97% [n = 320]) but lost accuracy on the ordinal task (67% [n = 194]). We found no evidence of bias by gender (P = .65) or area deprivation index (P = .80).

Conclusions

We derived a highly accurate pair of models capable of classifying reports by their MES and recognizing when to abstain from prediction. Our models were generalizable on outside institution validation. There was no evidence of algorithmic bias. Our methods have the potential to enable retrospective studies of treatment effectiveness, prospective identification of patients meeting study criteria, and quality improvement efforts in inflammatory bowel diseases.