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Causal Inference Approaches Reveal Associations Between LDL Oxidation, NO Metabolism, Telomere Length and DNA Integrity Within the MARK-AGE Study
No full textGenomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35–75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values.publishe
Gap Junctional Communication Required for the Establishment of Long-Term Robust Ca2<sup>+</sup> Oscillations Across Human Neuronal Spheroids and Extended 2D Cultures
No full textSynchronized oscillatory fluctuations in intracellular calcium concentration across extended neuronal networks represent a functional indicator of connectivity and signal coordination. In this study, a model of human immature neurons (differentiated from LUHMES precursors) has been used to establish a robust protocol for generating reproducible intracellular Ca2+ oscillations in both two-dimensional monolayers and three-dimensional spheroids. Oscillatory activity was induced by defined ionic conditions in combination with potassium channel blockade. It was characterized by stable frequencies of approximately 0.2 Hz and high synchronization indices across millimeter-scale cultures. These properties were consistently reproduced in independent experiments and across laboratories. Single-cell imaging confirmed that oscillations were coordinated throughout large cell populations. Pharmacological interventions demonstrated that neither excitatory nor inhibitory chemical synaptic transmission influenced oscillatory dynamics. Gap junction blockers completely disrupted synchronization, while leaving individual cell activity unaffected. Functional dye-transfer assays provided additional evidence for electrical coupling. This was further supported by connexin-43 expression profiles and immunostaining. Collectively, these findings indicate that synchronized Ca2+ oscillations in LUHMES cultures are mediated by gap junctional communication rather than by conventional synaptic mechanisms. This system offers a practical platform for studying fundamental principles of network coordination and for evaluating pharmacological or toxicological modulators of intercellular coupling. Moreover, it may provide a relevant human-based model to explore aspects of neuronal maturation and to assess compounds with potential neurodevelopmental toxicity.publishe
Exploring the energy spectrum of a four-terminal Josephson junction : Towards topological Andreev band structures
No full textHybrid multiterminal Josephson junctions (JJs) are expected to harbor a novel class of Andreev bound states (ABSs), including topologically nontrivial states in four-terminal devices. In these systems, topological phases emerge when ABSs depend on at least three superconducting phase differences, resulting in a three-dimensional (3D) energy spectrum characterized by Weyl nodes at zero energy. Here, we realize a four-terminal JJ in a hybrid Al/InAs heterostructure, where ABSs form a synthetic 3D band structure. We probe the energy spectrum using tunneling spectroscopy and identify spectral features associated with the formation of a tri-Andreev molecule, a bound state whose energy depends on three superconducting phases and, therefore, is able to host topological ABSs. The experimental observations are well described by a numerical model. The calculations predict the appearance of four Weyl nodes at zero energy within a gap smaller than the experimental resolution. These topological states are theoretically predicted to remain stable within an extended region of the parameter space, well accessible by our device. These findings establish an experimental foundation to study high-dimensional synthetic band structures in multiterminal JJs and to realize topological Andreev bands.publishe
Effectiveness of HAPA-based oral hygiene instruction in patients over 65 years of age : a randomized controlled trial
No full textObjective: The aim of the study was to provide oral hygiene instructions tailored to behavioral stages based on the Health Action Process Approach (HAPA) and to assess their impact on oral health compared with standardized instructions in patients aged 65 and older.
Methods: A total of 67 university clinic patients were randomly assigned to an intervention (n = 33) and a control group (n = 34) and 62 patients, aged 65 to 87 years (M = 71.3, SD = 5.3), participated in both the baseline and the follow-up visit. To assess oral hygiene, the parameters Gingival Bleeding Index (GBI) and Plaque Control Record (PCR) were recorded at baseline and 12 weeks after instruction. In the intervention group, a questionnaire was used at the beginning of both visits to survey oral hygiene behavior and motivation to change behavior. For both groups, the first visit included a survey on oral hygiene parameters followed by either HAPA-based or standard instruction with demonstration of oral hygiene aids.
Results: Analyses of covariance with baseline control revealed no difference in GBI between the intervention and control group at the 12-week follow-up. Both the intervention group, t(29) = 3.91, p <.001, d = 0.71, as well as the control group, t(31) = 3.67, p <.001, d = 0.65, demonstrated significant improvement in GBI. In contrast, only the intervention group showed a significant improvement in PCR at reevaluation, t(29) = 2.29, p =.03, d = 0.42. Additionally, the intervention group reported a significant increase in motivation and the frequency of interdental care, t(29), 6.67, p <.001, d = 1.22.
Conclusion: This study provides first evidence on the HAPA model being effectively applicable in the context of dental prophylaxis among university clinic patients older than the age of 65. A positive effect on patients’ behavior and oral hygiene could be demonstrated. While general instruction proved effective in reducing gingival bleeding, the theory-based HAPA intervention offered specific advantages in motivation, interdental care, and plaque buildup.
Trial registration: German Study Register of Clinical Studies (DRKS, ID DRKS00030040, German Clinical Trials Register, Date of registration 22.03.2023).publishe
Equal rights to move? : Public attitudes towards the free movement of patients, students and workers in the EU
No full textWhile the free movement of people is one of the cornerstones of the European integration project, a pressing question remains whether public support depends on who is moving. Against the backdrop of increasing debates on the development of a European Health Union, this study focuses on the case of patient mobility and compares support levels to those of student and worker mobility rights. To this end, the study draws on an original survey conducted among 6000 respondents in Germany. The results reveal that patients are less supported than students and workers, both for incoming and outgoing mobility. We also find evidence of differentiated drivers of free movement attitudes, as a higher socio-economic status increases support for student and worker mobility but not for patient mobility.publishe
Conscientiousness of representatives and agreement with their party positions
No full textParty unity is an important feature in contemporary democracies. Ideologicalloyalty, disciplinary measures implemented by party leaders and homogeneityof preferences among elected representatives lead them to act in unison. Thisstudy focuses on the last mechanism and assesses under which conditionsparty representatives agree on policy positions. It argues that the personalitytrait of conscientiousness is linked to how a representative agrees with herparty’s position and that this relationship is moderated by her knowledge ofdissent between party voters and representatives. This study use data from acomparative survey conducted among 866 representatives in Belgium,Canada, Germany and Switzerland, and among the party constituencies in thefour countries. Results show that conscientious representatives are more likelyto differ significantly from the position of their party peers if they spend moretime on constituency work and if their voters’preferences are not congruentwith those of their fellow representatives.publishe
Understanding the Mechanisms that Drive Relational Events Dynamics and Structure in Corruption Networks
No full textObjectives
Relational hyperevent data, i.e., time-stamped events comprising two or more actors, provide the most granular picture of network dynamics. Using hyperevent data on communication related to corruption, we answer two research questions related to corruption network structure and dynamics. First, we test core-periphery structure fit and measure temporal escalation. Second, we test the relational micro-mechanisms that bring about these structures and dynamics. We include attribute-related mechanisms (selection, heterophily), hyperevent-specific endogenous mechanisms (repeated interaction, repeated co-participation, subordination), and general endogenous mechanisms (triadic closure, reciprocity, tie accumulation)
Methods
Utilising publicly available data on three dynamic corporate corruption networks from Deferred Prosecution Agreements in the UK, we first measure each network’s core-periphery structure and temporal escalation. Then, we test the mechanisms that drive their evolution by modelling the sequence of relational hyperevents with relational hyper-event model (RHEM) recently developed to model such data. In RHEM, events are modelled as hyperedges in a hypergraph allowing to connect multiple nodes simultaneously.
Results
Two networks display strong signs of both core-periphery structures and temporal escalation, whereas the last one displays temporal escalation but a rather weak signs of a core-periphery structure. Using RHEM, we find evidence for the effects of repeated interaction and repeated co-participation in all the networks together with various forms hierarchical tendencies, yet little evidence for triadic closure.
Conclusions
We highlight the usefulness of RHEM for vast array of criminal network data that is frequently recorded as hyperevents (e.g., co-offending). We also discuss potential practical implications for prevention and disruption of corruption networks using descriptive and model-based evidence.publishe
Neural Image abstraction using long smoothing B-splines
No full textWe integrate smoothing B-splines into a standard differentiable vector graphics (DiffVG) pipeline through linear mapping, and show how this can be used to generate smooth and arbitrarily long paths within image-based deep learning systems. We take advantage of derivative-based smoothing costs for parametric control of fidelity vs. simplicity tradeoffs, while also enabling stylization control in geometric and image spaces. The proposed pipeline is compatible with recent vector graphics generation and vectorization methods. We demonstrate the versatility of our approach with four applications aimed at the generation of stylized vector graphics: stylized space-filling path generation, stroke-based image abstraction, closed-area image abstraction, and stylized text generation.publishe
Symbiodiniaceae shifts over the last decade on the hottest coral reefs on Earth
No full textCorals in the Persian/Arabian Gulf (PAG) are resilient to various stressors, whose levels exceed those of coral reefs globally. These corals thereby offer insight into mechanisms underlying thermal resilience, e.g., regarding the role of endosymbiotic microalgae in the family Symbiodiniaceae. Previous studies have identified the thermotolerant species Cladocopium thermophilum as broadly associated with corals in the southern PAG. However, algal-host specificity at the within-species level and the temporal stability of these associations are not well understood. Here we sampled two dominant stony corals ( Porites harrisoni , n = 119 and Platygyra daedalea , n = 79) at three sites in the southern PAG and the neighboring Gulf of Oman (GO) to explore algal symbiont assemblage and specificity, whereby a prior dataset provided the opportunity to assess symbiont community stability in P. daedalea across a decadal time frame. Using high-throughput ITS2 marker gene sequencing and the SymPortal framework, we identified distinct, largely non-overlapping ITS2 type profiles of C. thermophilum as the dominant symbiotic partners in P. harrisoni and P. daedalea in the southern PAG, highlighting high host fidelity at the subspecies level. Despite this, we observed notable changes in C. thermophilum genotype diversity and an overall decrease over the course of a decade. By comparison, algal symbiont diversity in the neighboring GO corals increased, with formerly prevalent ITS2 type profiles being replaced by novel genotypes. Decadal data on P. daedalea suggest a shift in algal symbiont assemblage signified by the decline of formerly dominant algal type profiles and the emergence of novel genotypes. It is currently unknown whether the respective coral colonies associated with novel algae or became rare or extinct themselves. Understanding long-term algal population dynamics is critical to forecast how algal lineage loss or, alternatively, an increase in algal diversity will impact coral resilience and survival.publishe