Scientific publications of the Saarland University
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Laminar Flow Alters EV Composition in HUVECs: A Study of Culture Medium Optimization and Molecular Profiling of Vesicle Cargo
Get PDFEndothelial cells (ECs) experience shear stress associated with blood flow. Such shear stress regulates endothelial function by altering cell physiology. Since most cell culture protocols and media compositions are designed for static cultures and experiments with ECs are predominantly conducted under these non-physiological conditions, a model for culturing ECs under flow conditions is developed, which more closely mimics their physiological environment. This approach also enables the isolation of EVs while minimizing FCS-derived contaminants. In this study, a comprehensive assessment of how physiologically relevant cultivation conditions influence the vesicle composition and function of ECs is provided. A detailed investigation is conducted for the effect of different cell culture media on morphology and marker expression of human umbilical cord endothelial cells (HUVECs) and EVs, and optimize the conditions to culture ECs under flow, tailoring them specifically to facilitate the efficient isolation of EVs using a hollow-fiber system model. These EVs are then characterized and compared to those isolated from traditional static culture conditions. Overall, this study presents a model on isolating EC-derived EVs under conditions that closely mimic physiological environments, and characterization at their proteome, gene expression, and microRNA profile
Staphylococcus aureus Adhesion on Hydrophobin Coatings: Adhesion Forces and the Influence of Surface Charge
Get PDFStaphylococcus aureus (S. aureus) is one of the
bacterial species capable of forming multilayered biofilms on
implants. Such biofilms formed on implanted medical devices often
require the removal of the implant in order to avoid sepsis or, in the
worst case, even the death of the patient. To address the problem of
unwanted S. aureus biofilm formation, its first step, i.e., adhesion,
must be understood and prevented. Thus, the development of
adhesion-reducing surface coatings for implant materials is of
utmost importance. In this work, we used single-cell force
spectroscopy to analyze the adhesion of the biofilm-forming S.
aureus strain SA113 on naive and protein-coated silicon surfaces
(SiO2). In addition to the wild type, we used the SA113 ΔdltA
knockout mutant to further investigate the effect of D-alanylation of
lipoteichoic acids of the cell wall. In order to examine how the surface charge affects adhesion, we coated silanized SiO2 surfaces with
amphiphilic class II hydrophobins. The naturally occurring hydrophobin HFBI was used as well as the HFBI variant D40Q/D43N,
which is less negatively charged at physiological pH due to the exchange of two acidic aspartate residues. These two types of
hydrophobin-coated surfaces resemble each other in roughness and wettability but differ only in charge. By measurement of the
forces with which each S. aureus strain binds to hydrophobin-coated surfaces, we show that the adhesion of S. aureus at surfaces can
be influenced by the charges exposed by the target surfaces. Therefore, in addition to hydrogen bonding, electrostatic interactions
between the cell and the hydrophilic surface govern adhesion on these surfaces. Moreover, we found that for both HFBI coatings, the
adhesion strength of S. aureus is reduced by nearly a factor of 30 compared to silanized SiO2 surfaces. Therefore, hydrophobin
coatings are of great interest for further use in the field of biomedical surface coating
Seeding of Dermal Substitutes with Glucose-Pretreated Nanofat Accelerates In Vivo Vascularization and Tissue Integration
Get PDFThe exposure of endothelial cells to high glucose concentrations promotes angiogene sis. The present study investigated whether this pro-angiogenic effect of glucose is suit able to improve the capability of nanofat to vascularize implanted dermal substitutes.
Nanofat was processed from white adipose tissue originating from green fluorescent pro tein (GFP)+ C57BL/6J donor mice and incubated for 1 h in Hank’s Balanced Salt Solution
with or without (control) a high level of glucose (30 mM). The pretreated nanofat was
seeded onto dermal substitutes, which were analyzed by intravital fluorescence microscopy,
histology and immunohistochemistry in dorsal skinfold chambers of GFP− C57BL/6J
mice to assess their vivo performance over a period of 14 days. A high level of glucose pretreated nanofat did not induce a stronger immune response when compared to the
control. However, it improved the vascularization of the implants, as shown by a sig nificantly higher density of blood-perfused microvessels in the border zones (~3.6-fold
increase) and more CD31+/GFP+ microvessels (~3-fold increase) inside the implants. Ac cordingly, high glucose-pretreated nanofat levels also enhanced the tissue integration of
the dermal substitutes, as indicated by the deposition of more type I collagen (~2.9-fold
increase). These findings suggest that the short-term exposure of nanofat to a high level of
glucose represents a promising and clinically feasible strategy to enhance its regenerative
properties when seeded onto dermal substitutes
Vergleich der Komplikationsrate und Verschlussrate nach Versorgung intrakranieller nicht-rupturierter Aneurysmen aus den Jahren 2010- 2012 und 2020-2022: Ist ein Fortschritt in der Aneurysmatherapie über einen Zeitraum von 10 Jahren zu verzeichnen?
Get PDFHintergrund: In Deutschland liegt die Prävalenz für ein nicht-rupturiertes intrakranielle Aneurysmas
bei 2-3%[101]. Die Inzidenzen für eine möglicherweise aus diesen Aneurysmen folgenden aneurysmabedingte SAB ist zwischen 1960 bis 2017 weltweit um 1,7% jährlich (95% CI: 0,6-2,8) gesunken. Sie ist
jedoch aufgrund der hohen Morbidität und Mortalität weiterhin sowohl von individueller als auch von
gesellschaftlicher und sozioökonomischer Wichtigkeit [18]. Um dieser Vorzubeugen können die Aneurysmen elektiv endovaskulär versorgt werden. In der Literatur wird die Morbidität bei durchgeführter
endovaskulärer Versorgung zwischen 3,7% und 9,5 angegeben [12,34,40,92,97]. Derzeit ist eine neure
Leitlinie zur Therapie von nicht-rupturierten Aneurysmen in Arbeit. Diesen Umstand nimmt sich die folgende Arbeit zu Grunde, um zurückzublicken und die Komplikationen bzw. Erfolge der im Zeitraum
zwischen 2010-2012 und 2020-2022 in der Neuroradiologie des UKS Homburg endovaskuläre versorgten
UIA zu vergleichen.
Methoden: Die vorliegende retrospektive Single-Center Studie stellt den Vergleich zwischen den am
UKS Homburg in den Jahren 2010-2012 (Gruppe 1) und den Jahren 2020-2022 (Gruppe 2) endovaskulär
versorgten intrakraniellen nicht-rupturierten Aneurysmen mit Blick auf die 30-Tage Komplikationsrate
der wichtigsten Komplikationen und der Verschlussrate, sowie der daraus möglicherweise nötigen Reeingriffsrate. Zum primären Endpunkt gehören das klinische Outcome, sowie das Vorliegen eines ischämischen Infarkts, einer transistorisch ischämische Attacke und die Ruptur des Aneurysmas bzw. eine auftretende intrakranielle Blutung. Der sekundäre Endpunkt beschäftigt sich mit der Verschlussrate der
Aneurysmen durch die Intervention.
Ergebnis: Die Studie verglich 148 endovaskuläre Interventionen in den Jahre 2010-2012 mit 130 in den
Jahren 2020-2022. Innerhalb des primären Endpunktes konnte eine signifikante Reduktion (p = 0,005)
zwischen den beiden Gruppen erfasst werden (14,86% zu 4,61%). Dies ist vor Allem auf die Reduktion
der ischämischen Schlaganfälle (p = 0,018) zurückzuführen. Diese sank von 10,81% (16) in den Jahren
2010-2012 auf 3,08% (4) in den Jahren 2020-2022. Bei 12 der 20 von einem ischämischen Schlaganfall
betroffenen Patienten waren die Symptome in Nachbeobachtungszeitraum vollständig rückläufig, sodass
lediglich 2,52% aller Patienten ein dauerhaftes neurologisches Defizit erlitten. Auch die Morbidität sank
über die Zeit hinweg signifikant (p = 0,011) von 14,86% auf 5,38%. Bei ähnlichen primären Verschlussraten der Klasse I nach MRRC von 83,1% und 80,1%, Klasse II 11,5% und 16,9%, Klasse IIIa 2,7% und
1,5% und Klasse IIIb 2,7% und 0,8% senkte sich jedoch die Reeingriffsrate signifikant von 10,8% in der
ersten Gruppe auf 2,3% in der zweiten Gruppe. Für die Variablen Alter, Geschlecht, Durchleuchtungszeit,
Art der Ersttherapie, präinterventionellem CRP, familiäre Vorbelastung, Seite und Lokalisation konnte
kein Zusammenhang mit dem primären Endpunkt dargestellt werden. Die Größe der zu behandelnden
Aneurysmen und die Anzahl der periinterventionell verwendeten Coils hingegen stehen im positiven Zusammenhang mit der Komplikationsrate. Während ein Größenunterschied des Aneurysmas von 1mm
zu einer Risikozunahme von 18,6% führt, erhöht ein zusätzlich verwendeter Coil das Risiko um 17%.
Die Mortalität und die Herzinfarktrate lag dabei, über die gesamte Datenerhebung hinweg bei 0%.
Fazit: Im Vergleich der beiden Patientenkollektive des UKS Homburg in den Jahren 2010-2012 und
2020-2022 konnte eine signifikante Reduktion der Komplikationsrate erfasst werden. Die Okklusionsraten konnte dabei nicht deutlich gesteigert werden, liegt jedoch mit insgesamt 82% vollständiger Verschlüsse bereits in einem hohen Bereich. Dies zeigt, dass die endovaskuläre Versorgung weiterhin eine
sichere und zuverlässige Methode zum Verschluss von intrakraniellen nicht rupturierten Aneurysmen darstellt. Bei der Indikationsstellung zur Versorgung sollte jedoch weiterhin auf die Größe des Aneurysmas
und die Anzahl der verwendeten Coils geachtet werden.Comparison of the complication rate and occlusion rate after treatment of intracranial nonruptured
aneurysms from 2010 - 2012 and 2020 - 2022: Is there progress in aneurysm therapy
over a period of 10 years?
Background: In Germany, the prevalence of non-ruptured intracranial aneurysms is 2-3% [92]. The
incidence of aneurysm-related SAH possibly resulting from these aneurysms decreased worldwide by
1.7% annually (95% CI: 0.6-2.8) between 1960 and 2017. However, due to the high morbidity and mortality,
it is still of individual as well as societal and socioeconomic importance [18]. To prevent this,
aneurysms can be treated electively by endovascular means. In the literature, the morbidity rate for endovascular
treatment is between 3.7% and 9.5 [11,34,40,84,88]. A new guideline on the treatment of nonruptured
aneurysms is currently in preparation. The following paper takes this circumstance as a basis to
look back and compare the complications and successes of UIAs treated endovascularly in the neuroradiology
department of the UKS Homburg between 2010-2012 and 2020-2022.
Methods: This retrospective single-center study compares intracranial non-ruptured aneurysms treated
endovascularly at the UKS Homburg in the years 2010-2012 (group 1) and 2020-2022 (group 2) about
the 30-day complication rate of the most important complications and the occlusion rate, as well as the
potentially necessary reintervention rate. The primary endpoint includes the clinical outcome, as well as
the presence of an ischemic infarction, a transient ischemic attack and the rupture of the aneurysm or the
occurrence of intracranial hemorrhage. The secondary endpoint deals with the occlusion rate of the aneurysms
because of the intervention.
Result: The study compared 148 endovascular interventions in the years 2010-2012 with 130 in the years
2020-2022. Within the primary endpoint, a significant reduction (p = 0.005) was recorded between the
two groups (14.86% to 4.61%). This is mainly due to the reduction in ischemic strokes (p = 0.018). This
fell from 10.81% (16) in the years 2010-2012 to 3.08% (4) in the years 2020-2022. Morbidity also fell
significantly over time (p = 0.011) from 14.86% to 5.38%. However, with similar primary closure rates
of class I according to MRRC of 83.1% and 80.1%, class II 11.5% and 16.9%, class IIIa 2.7% and 1.5%
and class IIIb 2.7% and 0.8%, the reintervention rate decreased significantly from 10.8% in the first group
to 2.3% in the second group. For the variables age, gender, fluoroscopy time, type of initial therapy, preinterventional
CRP, family history, side and localization, no correlation with the primary endpoint could
be shown. The size of the aneurysms to be treated and the number of coils used periinterventionally, on
the other hand, are positively correlated with the complication rate. While a difference in aneurysm size
of 1 mm leads to an increase in risk of 18.6%, an additional coil used increases the risk by 17%. The
mortality and heart attack rate was 0% over the entire data collection period.
Conclusion: A significant reduction in the complication rate was recorded in a comparison of the two
patient collectives at the UKS Homburg in the years 2010-2012 and 2020-2022. The occlusion rates could not be significantly increased but are already in a high range with a total of 82% complete occlusions.
This shows that endovascular treatment continues to be a safe and reliable method for the occlusion of
intracranial non-ruptured aneurysms. However, the size of the aneurysm and the number of coils used
should still be taken into account when determining the indication for treatment
Support on four paws-does the integration of a therapy dog reduce anxiety and increase positive affect in spider phobics during in vivo exposure therapy?: study protocol for a parallel randomised controlled trial of two groups to compare one-session in vivo exposure treatment of spider phobia with and without a therapy dog
Get PDFIntroduction Exposure is a central component in the
treatment of a range of mental disorders. However, despite
high efficacy and efficiency, dissemination of exposure based treatments is limited. Important factors that
contribute to this limited dissemination are negative beliefs
about exposure on the part of the public, the therapists,
and the patients. While patients perceive exposure therapy
as burdensome, therapists are concerned about putting
too much strain on their patients during exposure, leading
to suboptimal delivery of exposure. In a previous study,
in which healthy participants underwent a differential
fear conditioning paradigm, we found initial evidence that
the integration of a therapy dog into exposure reduces
participants’ anxiety and increases participants’ positive
affect without causing poor treatment outcome. Thus,
the integration of a therapy dog into exposure might be a
promising approach to address patients’ and therapists’
concerns and, thus, to (1) foster dissemination of exposure
that is (2) delivered in an optimal manner. To scrutinise
our findings in a clinical sample, we designed the present
study. We test the following hypotheses: (H1) participants
in the dog group report significantly less anxiety during
the course of the treatment than participants in the
control group. (H2) Participants in the dog group report
significantly more positive affect during the course of
the treatment than participants in the control group. (H3)
Participants in the dog group report significantly higher
therapy motivation than participants in the control group.
(H4) Participants in the dog group report significantly lower
anticipatory anxiety than participants in the control group.
(H5) The treatment in the dog group is not inferior to the
treatment in the control group
Modeling of lung-liver interaction during infection in a human fluidic organ-on-a-chip
Get PDFRespiratory infections, including pneumonia and COVID-19, are major causes of global mortality and morbidity. Recent advancements in organ-on-a-chip (OOC) technologies have paved the way for human-based disease models, offering new tools for studying disease mechanisms and accelerating drug development. The aim of this study was to establish a lung-liver fluidic system to study the interaction of both organ modules during infection. A two organ (lung-liver) fluidic system was established using primary human bronchial (HBECs) or alveolar type epithelial cells (AT) for the lung module and Huh-7 cells for the liver module. Inactivated non-typeable Haemophilus influenzae (NTHi) and Pseudomonas aeruginosa PAO1 (PAO1) were applied to the lung module. Secreted mediators were screened by dot-blot analysis and quantified. The impact of bacteria-exposed epithelial cells on the liver cell transcriptome was analyzed via mRNA sequencing. Lung and liver cells established stable cultures in a circulatory fluidic system. Activation of HBECs or ATCs with NTHi or PAO1 resulted in the secretion of multiple inflammatory mediators into the microfluidic medium including tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1-α (MIP-1α). Addition of lung cells and application of bacterial onto the HBEC module led to significant transcriptomic alterations in the liver cell module. Gene ontology enrichment analysis showed the induction of various pathways involved in host defense, metabolism, repair, and acute phase response. In conclusion, a two-organ lung-liver fluidic system was established to study the interaction of the organ modules during infection. Mediators like cytokines are released from epithelial culture modules into the fluidic circulation after exposure to bacterial pathogens that significantly modify the gene expression patterns of liver cells
Threat Modeling and Attacks on Digital Twins of Vehicles: A Systematic Literature Review
Get PDFThis systematic literature review pioneers the synthesis of cybersecurity challenges for automotive digital twins (DTs), a critical yet underexplored frontier in connected vehicle security. The notion of digital twins, which act as simulated counterparts to real-world systems, is revolutionizing secure system design within the automotive sector. As contemporary vehicles become more dependent on interconnected electronic systems, the likelihood of cyber threats is escalating. This comprehensive literature review seeks to analyze existing research on threat modeling and security testing in automotive digital twins, aiming to pinpoint emerging patterns, evaluate current approaches, and identify future research avenues. Guided by the PRISMA framework, we rigorously analyze 23 studies from 882 publications to address three research questions: (1) How are threats to automotive DTs identified and assessed? (2) What methodologies drive threat modeling? Lastly, (3) what techniques validate threat models and simulate attacks? The novelty of this study lies in its structured classification of digital twin types (physics based, data driven, hybrid), its inclusion of a groundbreaking threat taxonomy across architectural layers (e.g., ECU tampering, CAN-Bus spoofing), the integration of the 5C taxonomy with layered architectures for DT security testing, and its analysis of domain-specific tools such as VehicleLang and embedded intrusion detection systems. The findings expose significant deficiencies in the strength and validation of threat models, highlighting the necessity for more adaptable and comprehensive testing methods. By exposing gaps in scalability, trust, and safety, and proposing actionable solutions aligned with UNECE R155, this SLR delivers a robust framework to advance secure DT development, empowering researchers and industry to fortify vehicle resilience against evolving cyber threats
Development and content validation of an instrument to assess the prevalence of psychiatric medication use among dental students at Brazilian universities
Get PDFObjective To develop and validate a measurement instrument aimed at assessing the prevalence of psychiatric
medication use among final-year dental students enrolled in Brazilian universities. Methods: The process emphasized
both the construction of the questionnaire and the collection of evidence for its content validity. A mixed-methods
approach was employed, integrating quantitative and qualitative methodologies. The initial stages involved defining
the main research problem, establishing the instrument’s objectives, determining its conceptual domains, identifying
the target population, and constructing the items, scoring system, and response scales. Based on a comprehensive
literature review, a preliminary questionnaire consisting of 23 open- and closed-ended items was created. This
version was submitted to a panel of eight expert judges—academics and/or researchers specializing in Psychology,
Psychiatry, Pedagogy, and Dentistry/Instrument Development—tasked with evaluating each item’s clarity. Results:
Content analysis was conducted using consensus thresholds. Quantitatively, the agreement rate among judges was
calculated as the proportion of experts endorsing each item. Items with less than 90% agreement were revised;
items with 90% or greater agreement were considered acceptable. In the first round of evaluation, 14 items were
rejected. After modification based on judge feedback, all items were approved in the second round. The high level
of agreement among experts was deemed sufficient to provide evidence of content validity. Following expert
validation, a pre-test was conducted with dental students’ representative of the target population. Based on both
qualitative and quantitative feedback, two questions were adjusted, leading to the development of the final version of
the instrument. Conclusions: These initial findings and methodological steps form the foundation for the instrument’s
definitive application in future research assessing psychiatric medication use among undergraduate dental students
Impact of knowledge-sharing platforms on software security and academic research
Get PDFStack Overflow is a widely used platform among software developers and researchers. Developers frequently rely on it as a source of functional, copy-ready code snippets, while researchers study its content to analyze trends, behaviors, and the implications of code reuse—particularly concerning security. However, code on Stack Overflow is not static; the community revises posted code snippets, sometimes addressing bugs and vulnerabilities, much like code in version-controlled repositories. This ongoing evolution raises important questions about its effect on software security and research methodology. In this dissertation, we study the evolving nature of Stack Overflow code snippets and its impact on software security and research results. Developers often reuse snippets without tracking updates, leading to outdated and potentially vulnerable code in open-source projects. Our analysis of over 11,000 GitHub projects revealed thousands of such outdated snippets, including missed critical security fixes. This suggests the need to support developers with tools to help constantly monitor Stack Overflow for security warnings or code fixes. Additionally, the evolving nature of Stack Overflow code snippets and its surrounding context impacts the replicability of cross-sectional research findings, with six studies that we replicated yielding significantly different results on a newer dataset version. Accordingly, we recommend that researchers treat Stack Overflow data as a time series data source to provide better context for interpreting cross-sectional research findings.Stack Overflow ist eine beliebte Plattform bei Softwareentwicklern und -forschern. Entwickler nutzen sie häufig als Quelle für funktionale, kopierfertige Code-Snippets, während Forscher ihre Inhalte analysieren, um Trends, Verhaltensweisen und die Auswirkungen von Code-Wiederverwendung zu analysieren – insbesondere im Hinblick auf Sicherheit. Der Code auf Stack Overflow ist jedoch nicht statisch; die Community überarbeitet Code-Snippets und behebt dabei manchmal Fehler und Schwachstellen, ähnlich wie bei Code in versionskontrollierten Repositories. Diese fortlaufende Weiterentwicklung von Code-Snippets wirft wichtige Fragen zu ihren Auswirkungen auf die Softwaresicherheit und die Forschungsmethodik auf. In dieser Dissertation untersuchen wir die Weiterentwicklung der Stack Overflow-Code-Snippets und ihre Auswirkungen auf die Softwaresicherheit und Forschungsergebnisse. Entwickler verwenden Snippets häufig wieder, ohne deren Updates zu verfolgen, was zu veraltetem und potenziell anfälligem Code in Open-Source-Projekten führt. Unsere Analyse von über 11.000 GitHub-Projekten fand Tausende solcher veralteten Snippets, darunter auch verpasste kritische Sicherheitsfixes. Dies legt die Notwendigkeit nahe, Entwickler mit Tools zu unterstützen, die Stack Overflow kontinuierlich auf Sicherheitswarnungen oder Code-Fixes überwachen. Darüber hinaus beeinflusst die Weiterentwicklung der Stack Overflow-Code-Snippets und ihres Kontextes die Reproduzierbarkeit von Forschungsergebnissen. Sechs von uns replizierte Studien lieferten auf einer neueren Datensatzversion deutlich unterschiedliche Ergebnisse. Deshalb empfehlen wir Forschern, Stack Overflow-Daten als Zeitreihendaten zu betrachten, um einen besseren Kontext für die Interpretation der Ergebnisse zu schaffen
Trade-off analysis and identification of optimization potentials between lightweight design and design for circularity
Get PDFThe pressing need for resource conservation and environmental impact reduction in sustainable development emphasizes the importance of lightweight design and design for circularity in product development. However, the complexity and multidisciplinary nature of decision-making in these areas pose a major challenge.
In the present work, a novel approach for trade-off analyses is proposed to meticulously analyze the relationships between both design disciplines, facilitating decision-making and the identification of optimization potentials throughout design. Illustrated by material selection and a case study on the development of a semi-mobile handling system, two fundamental design approaches for decision-making in view of different and shared development objectives between lightweight design and design for circularity are identified. This enables the prioritization of development objectives in early phases and enhances eco-effectivity with regard to resource conservation and environmental impact reduction in the context of complex design considerations