bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Potential Drug Targets for Varicose Veins through Integration of GWAS and eQTL Summary Data
Authors: Cui Yu , Hu Mengting , Zhou He , Guo Jiarui , Wang Qijia , Xu Zaihua , Chen Liyun , Zhang Wancong , Tang Shijie 
Published: January 2024

AbstractBackgroundVaricose veins (VV) is a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic burden on the healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, to identify potential pathogenic genes and drug targets for VV treatment.MethodsThis study conducted summary-data-based Mendelian randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies (GWASs) and cis-expression quantitative trait loci (cis-eQTL) databases. Only genes with PP. H4 > 0.7 were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies (TWAS) analysis and The Drug-Gene Interaction Database (DGIdb,https://dgidb.org)data to identify and screen the remaining genes and identified four drug targets for the treatment of VV.ResultsWe identified four genes significantly associated with VV, namelyKRTAP5-AS1(OR = 1.08, 95% CI: 1.05−1.11, p = 1.42e−10) andPLEKHA5(OR = 1.13, 95% CI: 1.06-1.20, p = 6.90e−5),CBWD1(OR = 1.05, 95% CI: 1.01-1.11, p = 1.42e−2) andCRIM1(OR = 0.87, 95% CI: 0.81-0.95, p = 3.67e−3). Increased expression of three genes, namelyKRTAP5-AS1,PLEKHA5, andCBWD1, was associated with increased risk of the disease, and increased expression ofCRIM1was associated with decreased risk of the disease. These four genes could be targeted for VV therapy.ConclusionThis study identified four drug targets for potential treatment of VV, and the results may contribute to improving the quality of life of VV patients.
Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction
Authors: Fournier Luke A. , Phadke Rhushikesh A. , Salgado Maria , Brack Alison , Nocon Jian Carlo , Bolshakova Sonia , Grant Jaylyn R. , Luna Nicole M. Padró , Sen Kamal , Cruz-Martín Alberto 
Published: January 2024

SUMMARYFast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity, and their dysfunction is consistently observed in myriad brain diseases. To understand how immune complement dysregulation – a prevalent locus of brain disease etiology – in PV cells may drive disease pathogenesis, we have developed a transgenic mouse line that permits cell-type specific overexpression of the schizophrenia-associated complement component 4 (C4) gene. We found that overexpression of mouseC4(mC4) in PV cells causes sex-specific behavioral alterations and concomitant deficits in synaptic connectivity and excitability of PV cells of the prefrontal cortex. Using a computational network, we demonstrated that these microcircuit deficits led to hyperactivity and disrupted neural communication. Finally, pan-neuronal overexpression ofmC4failed to evoke the same deficits in behavior as PV-specificmC4overexpression, suggesting thatC4perturbations in fast-spiking neurons are more harmful to brain function than pan-neuronal alterations. Together, these results provide a causative link betweenC4and the vulnerability of PV cells in brain disease.
A Conserved Mechanism of Cardiac Hypertrophy Regression through FoxO1
Authors: Martin Thomas G. , Hunt Dakota R. , Langer Stephen J. , Tan Yuxiao , Ebmeier Christopher C. , Crocini Claudia , Chung Eunhee , Leinwand Leslie A. 
Published: January 2024

SUMMARYThe heart is a highly plastic organ that responds to diverse stimuli to modify form and function. The molecular mechanisms of adaptive physiological cardiac hypertrophy are well-established; however, the regulation of hypertrophy regression is poorly understood. To identify molecular features of regression, we studied Burmese pythons which experience reversible cardiac hypertrophy following large, infrequent meals. Using multi-omics screens followed by targeted analyses, we found forkhead box protein O1 (FoxO1) transcription factor signaling, and downstream autophagy activity, were downregulated during hypertrophy, but re-activated with regression. To determine whether these events were mechanistically related to regression, we established anin vitroplatform of cardiomyocyte hypertrophy and regression from treatment with fed python plasma. FoxO1 inhibition prevented regression in this system, while FoxO1 activation reversed fed python plasma-induced hypertrophy in an autophagy-dependent manner. We next examined whether FoxO1 was implicated in mammalian models of reversible hypertrophy from exercise and pregnancy and found that in both cases FoxO1 was activated during regression. In these models, as in pythons, activation of FoxO1 was associated with increased expression FoxO1 target genes involved in autophagy. Taken together, our findings suggest FoxO1-dependent autophagy is a conserved mechanism for regression of physiological cardiac hypertrophy across species.HIGHLIGHTSPost-prandial cardiac remodeling in Burmese pythons is associated with dynamic regulation of FoxO1 and autophagy.Regression of fed python plasma-induced hypertrophy in mammalian cardiomyocytes is FoxO1-dependent.Activation of FoxO1-dependent autophagy is a conserved feature of physiological hypertrophy regression in mammalian models.
RANDOMIZED CONTROLLED TRIAL OF INTERMITTENT CALORIE RESTRICTION IN PEOPLE WITH MULTIPLE SCLEROSIS
Authors: Ghezzi Laura , Tosti Valeria , Shi Lisa , Cantoni Claudia , Mikesell Robert , Lancia Samantha , Zhou Yanjiao , Obert Kathleen , Sen Monokesh K. , Ge Anjie , Tolentino Miguel , Bollman Bryan , Don Anthony S. , Matarese Giuseppe , Colamatteo Alessandra , Rocca Claudia La , Lepore Maria Teresa , Wu Gregory F. , Cross Anne H. , Naismith Robert T. , Fontana Luigi , Salter Amber , Piccio Laura 
Published: January 2024

ABSTRACTBackgroundCalorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) through reduction of inflammation. The aim of this trial was to study the effects of 12-week iCR on metabolic, immunological and clinical outcomes in people with MS (pwMS).MethodsParticipants with relapsing-remitting MS were randomly assigned to intermittent CR (iCR) or a control group for 12 weeks. Primary outcome was change in leptin levels; secondary outcomes included changes in anthropometric and body composition measures, peripheral blood metabolic and immunologic profiling, and clinical measures. Mixed effects linear regression models were used to evaluate differences.ResultsForty-two pwMS were randomized, 34 completed the study (17 iCR and 17 control). Leptin levels decreased in the iCR group and were significantly lower in the iCR than the control group at 6 (mean difference 11.49 mg/dL, 95% CI 32.54, 9.54;P=0.01) and 12 weeks (6.97 mg/dL, 95% CI 28.02, 14.06;P=0.03). We observed a significant reduction of weight, body mass index and body adiposity measures over the 6 and 12-weeks in the iCR group. Immune profiling showed a significant increase in CD45RO+regulatory T cell numbers after 6 weeks of iCR. Lysophosphatidylcholine, lysophophatidylethanolamine and phosphatidylinositol lipid species were significantly increased after 12 weeks in the iCR group compared to baseline, and all three were higher at 12 weeks compared to controls. Exploratory cognitive testing demonstrated improvement in the symbol digit modality test score in the iCR group.ConclusionsShort term iCR is safe, feasible and can benefit metabolic and immunologic profiles in pwMS.ClinicalTrial.gov number:NCT03539094(first patient screened on 11/14/17; first patient recruited on 1/29/2018; last patient recruited on 11/24/2021).
Complex interactions in the life cycle of a simple parasite shape the evolution of virulence
Authors: Silva Luís M. , Koella Jacob C. 
Published: January 2024

AbstractEvolutionary expectations about the virulence of parasites (i.e., the parasite-induced mortality rate of the host) often focus solely on the within-host transmission stage, overlooking the time spent between hosts and variations in transmission cycles. Moreover, parasite growth rate within the host is closely linked to virulence. We here suggest that a simplified view of transmission and parasite evolution makes it difficult to predict how virulence will evolve. We illustrate our ideas with a parasite with a simple life cycle, the microsporidianVavraia culicis, which infects the mosquitoAnopheles gambiae. We selected the parasite over six host generations for early or late host transmission, corresponding to shorter or longer time within the host. Selecting for late transmission increased their exploitation of the host, resulting in higher virulence and a shorter life cycle with rapid infective spore production, comparatively to selection for early transmission. In response, hosts infected with late-selected spores shortened their life cycle and shifted to earlier reproduction. Notably, higher virulence was negatively correlated with the endurance of infective spores outside the host, demonstrated in a parallel study using these parasite lines. These findings emphasize the importance of considering the entire transmission cycle in studies of parasite evolution and raise concerns about how host density and social settings might influence virulence evolution.Significance statementClassical expectations on parasite evolution assume a trade-off between transmission rate and harm to the host (virulence), favoring parasites with intermediate virulence. However, recent studies challenge this idea, suggesting it is too simplistic. Here, by selecting the parasiteVavraia culicisfor early or late transmission (or shorter and longer time within the host) in the hostAnopheles gambiaewe demonstrate that understanding virulence evolution requires considering the entirety and the type of transmission cycle and not merely the within-host stage. These findings highlight the importance of including all transmission stages in parasite evolution studies and demonstrate how certain social conditions might unintentionally select more virulent parasites.
Long-term mouse spinal cord organotypic slice culture as a platform for validating cell transplantation in spinal cord injury
Authors: Merighi Francesca , De Vincentiis Sara , Onorati Marco , Raffa Vittoria 
Published: January 2024

ABSTRACTSpinal cord injury (SCI) is an extremely invalidating condition with a severe physical and psychological impact. Resolutive cures are still lacking, due to its complex pathophysiology. One of the most promising regenerative approaches is based on stem cell transplantation to replace lost tissue and promote functional recovery. This approach should be explored betterin vitroandex vivofor safety and efficacy before proceeding with more expensive and time-consuming animal testing. In this work, we show the establishment of a long-term platform based on mouse spinal cord (SC) organotypic slices transplanted with human neural stem cells to test cellular replacement therapies for SCI. Standard SC organotypic cultures are maintained for up to 2 or 3 weeksin vitro. Here, we describe an optimized protocol for long-term maintenance for up to three months (90 days). The medium used for long-term culturing of SC slices was also optimized for transplanting neural stem cells into the organotypic model. Human SC-derived neuroepithelial stem (h-SC-NES) cells carrying a GFP reporter were transplanted into mouse SC-slices. 30 days after the transplant, cells still show GFP expression, and a low apoptotic rate, suggesting that the optimized environment sustained their survival and integration inside the tissue. This protocol represents a robust reference for efficiently testing cell replacement therapies in the SC tissue. This platform will allow researchers to perform an ex vivopre-screening of different cell transplantation therapies, helping them to choose the most appropriate strategy before proceeding within vivoexperiments.SUMMARYIn this paper, we provide a reproducible method to generate and maintain long–term spinal cord organotypic slices transplanted with neural stem cells as anex vivomodel for testing cellular replacement therapies.
Local glycolysis supports injury-induced axonal regeneration
Authors: Masin Luca , Bergmans Steven , Van Dyck Annelies , De Groef Lies , Farrow Karl , Moons Lieve 
Published: January 2024

SUMMARYSuccessful axonal regeneration following injury requires the effective allocation of energy. Mitochondria play a pivotal role, accumulating at the tips of growing axons to fuel regeneration. However, how axons withstand the initial disruption in mitochondrial energy production caused by the injury, and subsequently initiate regrowth is poorly understood. Using retinal cultures in a multicompartment microfluidic device, we observed increased regrowth and enhanced mitochondrial trafficking in the axons of retinal ganglion cells with the deletion of bothPtenandSocs3. While wild-type axons relied on mitochondrial metabolism, after injury, in the absence ofPtenandSocs3, energy production was demonstrated to be supported by local glycolysis. Slowing down glycolysis in these axons impaired both regrowth and energy production. Together, these observations reveal that glycolytic ATP, combined with sustained mitochondrial transport, is essential for injury-induced axonal regrowth, providing new insights into the metabolic underpinnings of axonal regeneration.
Prestimulus alpha phase modulates visual temporal integration
Authors: Johannknecht Michelle , Schnitzler Alfons , Lange Joachim 
Published: January 2024

AbstractWhen presented shortly after another, discrete pictures are naturally perceived as continuous. The neuronal mechanism underlying such continuous or discrete perception are not well understood. While continuous alpha oscillations are a candidate for orchestrating such neuronal mechanisms, recent evidence is mixed. In this study, we investigated the influence of prestimulus alpha oscillation on visual temporal perception. Specifically, we were interested whether prestimulus alpha phase modulates neuronal and perceptual processes underlying discrete or continuous perception. Participant had to report the location of a missing object in a visual temporal integration task, while simultaneously MEG data was recorded. Using source reconstruction, we evaluated local phase effects by contrasting phase angle values between correctly and incorrectly integrated trials. Our results show a phase opposition cluster between - 0.8 to - 0.5 s (relative to stimulus presentation) and between 6 - 20 Hz. These momentary phase angle values were correlated with behavioural performance and event related potential amplitude. There was no evidence that frequency defined a window of temporal integration.Significance StatementIn light with the current debate if our visual perception is a rhythmic or discrete process, we give new insight to this debate. We investigated potential underling mechanism defining potential rhythmic perception and highlight the complexity of this process. This will help us further understand how our brain operates and processes incoming unimodal visual stimuli. In a visual temporal integration task, we were able to show that the incoming information were processed in rhythmic fashion. Our data supports the idea that the phase of prestimulus alpha oscillation modulates poststimulus visual processing by defining good and less good phases for early visual processes. We were not able to show that prestimulus alpha oscillation defines windows were two visual stimuli are integrated into one single event.
Support farmers: sustainability claims that influence moral satisfaction and purchase intention
Authors: Arboleda Ana M. , Pilar Acosta 
Published: January 2024

PurposeThis paper evaluates consumers' responses to claims regarding fruit sustainability. The authors compared the effects of this factor on consumers' moral satisfaction and purchase intention with respect to 12 sustainability claims.Design/methodology/approachA mixed-model experiment was conducted with seven fruits (i.e. guava, pineapple, red apple, green apple, red grape, green grape and avocado) to evaluate the effects of the 12 sustainability claims on purchase intention through moral satisfaction, relative to a control condition.FindingsThe results show that claims of supporting local farmers are those that move consumers the most. Claims regarding local farmers' production positively affect moral satisfaction and purchase intention.Practical implicationsThis paper takes a consumer behavior approach to sustainability, enabling organizations to consider consumer behavior outcomes that could affect their strategic investments and commitment to social responsibility.Originality/valueFood-related studies have not produced consistent results with respect to the relevance that sustainability claims have for consumers. This study differs from previous studies, as it focuses on fruit, a product that is important for social and environmental sustainability issues. This study demonstrates that, in the case of fruit, sustainability arguments are meaningful to young consumers through the mediating effect of moral satisfaction. Thus, the effect of claims is predicted by the meaning these arguments have for the consumer.
Industrial relations, the New Right and the praxis of mismanagement
Authors: Dobbins Tony , Dundon Tony 
Published: January 2024

PurposeThe purpose of the article is to outline the insights provided by Alan Fox in Man Mismanagement in relation to the rise of the New Right political economy and the spread of unitarist managerialism. The article assesses the contemporary work and employment relations implications of mismanagement arising from a “second wave” of the New Right ideology from 2010 in the UK.Design/methodology/approachResponding to the Special Issue on Alan Fox, the article focuses on Alan Fox's book Man Mismanagement, considering industrial relations developments arising between the 1st (1974b) and 2nd (1985) editions relating to the political rise of the New Right. It reviews various literature that illustrates the contemporary IR relevance of the book and Fox's insights.FindingsThe New Right’s ideology has further fragmented work, disjointed labour rights and undermined collective industrial relations institutions, and macho mismanagement praxis is even more commonplace, compared to when Fox wrote Man Mismanagement. The stripping away of the institutional architecture of IR renders the renewal of pluralist praxis, like collective bargaining and other forms of joint regulation of work, a formidable task.Originality/valueThe value of the article relates to the identification of dramatic historical industrial relations events and change in the UK in Alan Fox's book Man Mismanagement, most notably relating to the rise to power of the Thatcherite New Right in 1979. Originality is evidenced by the authors’ drawing on Fox's ideas and assessing the implications of the “second wave” of the New Right in the contemporary industrial relations (IR) context of the 2020s under the conceptual themes of fragmented work, disjointed labour rights and undermined collectivism.
Gender-modulated relationships among depression, light household tasks and physical activity: population-based moderation analysis
Authors: de-Pedro-Jiménez Domingo , Foncubierta-Sierra Esther , Domínguez-Romero Esther , Vega-Escaño Juan , Hernández Martín Marta , Gavira Fernández Cristina 
Published: January 2024

Purpose
This paper aims to study the influence of leisure-time physical activity on depression crises and the difficulty in performing light household tasks.

Design/methodology/approach
A population-based cross-sectional study was conducted using data from the 2020 European Health Survey in Spain. A total of 1,076 individuals diagnosed with depression were selected. ANOVA, chi-square, Fisher’s exact test and Mann–Whitney U test were applied, and a simple moderation analysis was conducted using the SPSS PROCESS 4.0 macro.

Findings
Women had higher percentages of some or much difficulty in performing domestic activities (p = 0.007). Differences were found between experiencing a crisis in the past 12 months versus not having one (p < 0.001): less physical activity was performed, perceived health was worse and difficulty in performing domestic activities increased. The moderation analysis confirmed the moderating effect of physical activity on the relationship between experiencing a crisis and having difficulty with domestic activities (p = 0.017).

Research limitations/implications
The usual limitation of descriptive cross-sectional studies, which cannot establish causal relationships, must be added to low sample sizes in some categories.

Practical implications
The analysis with gender differentiation, promoting gender-specific adapted practices, considering age and personal circumstances of the patient, appropriate exercise prescription, as well as its evaluation and follow-up, are areas where specialist nurses need to delve deeper to enhance the quality of care.

Originality/value
Leisure-time physical activity moderates the relationship between experiencing a crisis and having difficulty with light household tasks: those who engage in occasional physical activity have less difficulty compared to those who do not engage in it.
Study motivations of Bhutanese students in hospitality and tourism courses
Authors: Strickland Paul Christopher , Ratten Vanessa 
Published: January 2024

PurposeThe main purpose of this article is to understand the motivations for Bhutanese students to study hospitality and tourism courses. The second objective is to analyse what countries are the preferred destinations for study abroad and visitation for students. This includes focussing on new course topic areas such as sustainability for business in hospitality and tourism courses.Design/methodology/approachA quantitative methodology approach was undertaken with two surveys administered to the first and second student intakes into the Bhutan Middle Management Hotel Program. Motivational and reasoned action theory form the basis of the theoretical framework to understand behavioural intentions regarding educational choices in hospitality and tourism courses.FindingsThe results of the surveys indicate that the main motivations to study hospitality and tourism are for attraction, career opportunities, status, broader benefits and aptitude. In addition, it was found that students studying hospitality and tourism in Bhutan are likely to stay in the sector for a long period of time thereby contributing to the economic and social development of Bhutan. Moreover, it was found that the United Nations Sustainable Development goals are increasingly being integrated into the tourism and hospitality sector, which is influencing students to study these topic areas.Research limitations/implicationsThe results of this study will help government and hospitality providers support educational training programs by focussing on new education topic areas. This study is limited to Bhutan.Practical implicationsThe results of this study will help government and hospitality providers support educational training programs by focussing on new education topic areas such as sustainability for business management. This will enable hospitality and tourism providers in Bhutan to update their curriculum and to focus on emerging industry needs.Originality/valueThis is amongst the first studies on Bhutanese students motivations for studying hospitality and tourism. It will provide practical and policy advise about how to train workers in order to become less reliant on foreign training providers and the importance of integrating sustainability topics in course design.