Scientific publications of the Saarland University
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Evaluation of Tumor Budding and Poorly Defined Clusters as Histological Biomarkers in Squamous Cell Carcinomas of the Vulva
Full text linkBackground/Objectives: Several histopathological risk factors have been examined in vulvar cancer (VC) so far. However, the prognostic relevance of morphological
biomarkers such as tumor budding (TB) and poorly defined clusters (PDCs) remains to
be determined. Material and Methods: We histologically analyzed the formation of peritumoral and intratumoral TB and PDCs in a cohort of 157 patients with VC. We assessed
their association with clinico-pathological features and evaluated their prognostic impact
in terms of the risk of local recurrence and occurrence of metastasis (Fisher’s exact test)
as well as overall survival (Log-rank test). Results: We determined a distinct prognostic
relevance of peritumoral TB with regard to occurrence of metastasis (Fisher’s exact test;
p = 0.0415) as well as a significant reduced risk of local recurrence in the group with absent
intratumoral TB (Fisher’s exact test; p = 0.0004). Furthermore, we showed that patients
without peritumoral budding formation had a significant superior prognosis in terms
of overall survival (p = 0.0366, x2 = 4.370). Conclusions: This study shows that several
new histomorphological biomarkers may serve useful in predicting the clinical course
of patients with VC, identifying patients at a lower risk of developing metastases/local
recurrence as well as improved overall survival
Ungleich willkommen: Unterschiede in den Einstellungen von Österreicher*innen gegenüber arabischen/afghanischen und ukrainischen Flüchtigen. Der Einfluss von Wertvorstellungen und Bedrohungswahrnehmungen
Full text linkThis article examines whether Austrians hold different attitudes towards
Ukrainian refugees compared to Arab/Afghan refugees and explores key mechanisms driving these attitudinal differences. Using data from the third wave of the
Austrian Values in Crisis Panel (N= 1357), the study confirms that Austrians exhibit
more favorable views towards Ukrainian refugees. Negative attitudes towards Arab/
Afghan refugees are associated with feelings of realistic threat (particularly crime),
while both Arabs/Afghans and Ukrainians are associated with symbolic threat. Basic value orientations further impact attitudes towards refugees. Self-Transcendence
values correlate with favorable attitudes towards refugees overall, Self-Enhancement
values only correlate with more favorable attitudes towards Ukrainians. Conservation
values indirectly impact attitudes towards Arab/Afghan refugees by intensifying the
influence of perceived threat. These results suggest that differences in attitudes stem
from concerns about realistic threats and the differing impact of value orientations.Dieser Artikel untersucht die Einstellungen in der österreichischen Bevölkerung gegenüber ukrainischen und arabischen/afghanischen Flüchtlingen. Die Daten der dritten Welle der österreichischen Version des Values in Crisis Panels (N= 1357) zeigen, dass Österreicher*innen positivere Einstellungen gegenüber
ukrainischen Flüchtlingen aufweisen als gegenüber arabischen/afghanischen Flüchtlingen. Der Artikel beleuchtet auch wichtige Ursachen für diese Unterschiede. Negative Einstellungen gegenüber arabischen/afghanischen Flüchtlinge korrelieren mit
Bedrohungsgefühlen (insb. in Bezug auf Kriminalität), während beide Flüchtlingsgruppen mit symbolischer Bedrohung assoziiert werden. Wertvorstellungen nehmen
zusätzlich Einfluss auf diese Einstellungen. Selbsttranszendenzwerte korrelieren mit
positiveren Einstellungen zu beiden Flüchtlingsgruppen, Selbstverbesserungswerte
korrelieren nur mit positiven Einstellungen zu Ukrainer*innen. Konservative Werte
wirken sich indirekt auf Einstellungen gegenüber Flüchtlingen aus, da sie Bedrohungsgefühle verstärken. Diese Ergebnisse implizieren, dass Bedrohungsgefühle und
Wertüberzeugungen Unterschiede in Einstellungen über Flüchtlinge erzeugen
Heart failure guideline implementation in developing countries: A testimony from Syria
Full text linkComparative Analysis of Two Elastic Types of Surface‐Crosslinked Gelatin Nanoparticles as Suitable Systems for Macromolecular Drug Delivery
Full text linkWith a steadily rising number of novel biopharmaceuticals in development,
the demand for applicable delivery systems for macromolecular drugs
persists. Polymeric nanoparticles, consisting of the natural product gelatin,
present beneficial attributes for this application. To stabilize those
nanoparticles without interfering with encapsulated macromolecules,
surface-crosslinked gelatin particles are developed and thoroughly
characterized for their physicochemical and mechanical properties. With only
limited data available for the latter, investigating the elastic properties can
offer a more comprehensive understanding of the crosslinking processes
involved and of the gelatin particles’ potential applications. In this study,
protocols for surface-crosslinked gelatin particles type A (GNP-A) and B
(GNP-B) are described. Significant differences between the two types of
gelatin are reported regarding their physicochemical and mechanical
properties. GNP-A consists of a lower crosslinking degree, leading to
pronounced swelling in aqueous environments and softer nanoparticles. They
possess contrary properties compared to the more extensively crosslinked
and stiffer GNP-B. However, this doesn’t affect encapsulation efficiency,
allowing to develop nanoparticulate systems suitable for various applications
by adjusting the particle properties while maintaining the same drug load.
These findings provide a deeper understanding of polymeric gelatin particles
and reveal the importance of investigating the mechanical properties of drug
delivery systems during pharmaceutical development
The Chalcogen Exchange: The Replacement of Oxygen with Sulfur and Selenium to Boost the Activity of Natural Products
Full text linkAntioxidants, such as stilbenes, anthocyanidins, coumarins, tannins and
flavonoids, are often based on oxygen-containing redox systems and tend to feature several
hydroxyl groups in their chemical structures. From a synthetic perspective, oxygen atoms
are prone to bioisosteric replacement with sulfur and, notably, selenium. The main objective
of this narrative literature review is to explore if and how bioisosteric substitution of oxygen
with sulfur or selenium can enhance the biological activity of natural products. This re placement boosts the biological activity of the resulting molecules considerably as they now
combine the redox and antioxidant properties of the original flavonoids and other natural
products with the specific redox behavior of sulfur and selenium. Besides sequestering
free radicals and peroxides, they may, for instance, also catalyze the removal of oxidative
stressors, capture free metal ions and even provide scope for selenium supplementation.
Since these molecules resemble their natural counterparts, they also exhibit considerable
selectivity inside the body and a good pharmacokinetic profile. Still, the synthesis of
such hybrid molecules integrating sulfur and selenium into flavonoids and other natural
products is a challenge and requires innovative synthetic strategies and approaches
The Role of Nanoparticle Elasticity on Biological Hydrogel Penetration
Full text linkThe latest advancements in nanomedicine have led to increased therapeutic
efficacy and reduced complications. However, nanoparticle penetration is significantly
influenced by biological hydrogels, such as mucus, the extracellular matrix, biofilms, and
nucleoporins. Solely modifying well-studied physicochemical properties like size, charge,
and surface chemistry is insufficient to fully elucidate or overcome these barriers. Recent
studies have investigated the impact of particle elasticity, a relatively unexplored yet crucial
physicochemical property influencing many biological processes. Hence, it is important to
explore the impact of particle elasticity on penetrating biological hydrogels. This review
examines biological hydrogels’ structural and functional features as diffusion barriers, pro vides an overview of particle elasticity, key elasticity measurement techniques, and explores
strategies for elasticity modulation in nanoparticles, such as composition, crosslinking den sity, and structural design. Furthermore, nanoparticle penetration mechanisms, influenced
by particle deformability, hydrogel mesh size, and adhesive interactions, are investigated
by integrating theoretical and experimental findings. The evaluation of experimental data
reveals the commonly observed particle elasticity trends in mucus penetration, extracellular
matrix permeation, and corneal penetration of nanoparticles. Overall, this review offers
valuable insights into designing next-generation nanomedicines capable of overcoming
biological barriers
Tailored Lignin Fractions via Ionic Liquid Pretreatment for Sustainable Polymer Systems
Full text linkThe valorization of advanced biorefinery lignins remains a significant challenge,
owing to the presence of residual carbohydrates. These lignin-associated carbohydrates
hinder lignin purification, reduce its homogeneity, and complicate chemical modifications,
ultimately limiting the efficient conversion of lignin into high-value products such as
chemicals and materials. This study presents a protic ionic liquid-based lignin fractiona tion process developed using softwood biomass. Triethylammonium methane sulfonate
([N222H][OMS]) was used to fractionate Pinus sylvestris, yielding two distinct fractions:
a low-molecular-weight lignin fraction (LF) and a high-molecular-weight lignin fraction
(HF). The extracted fractions were comprehensively characterized using nuclear magnetic
resonance (NMR) to quantify changes in interunit linkages (β-O-4, β-5, and β-β) and hy droxyl group distribution, whereas methanolysis gas chromatography/mass spectrometry
(GC/MS) was used to quantify residual carbohydrates. The fractionation process achieved
LF and HF yields of approximately 70.32% and 17.58%, respectively. Further analysis
revealed that the HF contained 59.92 ± 2.12 mg/g carbohydrates, whereas the LF contained
only 27.37 ± 1.13 mg/g. These findings underscore the effectiveness of the protic ionic liq uid fractionation process in reducing carbohydrate impurities and enhancing lignin purity,
paving the way for the more efficient utilization of lignin in value-added applications
Deep High Dynamic Range Imaging: Reconstruction, Generation and Display
No full textHigh Dynamic Range (HDR) images offer significant advantages over Low Dynamic Range (LDR) images, including greater bit depth, a wider color gamut, and a higher dynamic range. These features not only provide users with an enhanced visual experience but also facilitate post-production processes in photography and filmmaking. Despite the considerable advancements in HDR technology over the years, significant challenges persist in the acquisition and display of HDR content. This thesis systematically explores the potential of leveraging deep learning techniques combined with physical prior knowledge to address these challenges. First, it investigates how implicit neural representations can be utilized to reconstruct all-in-focus HDR images from sparse, defocused LDR inputs, enabling flexible refocusing and re-exposure. Additionally, it extends the scope to the 3D domain by employing 3D Gaussian Splatting to reconstruct HDR all-in-focus fields from multi-view LDR defocused images, supporting novel view synthesis with refocusing and re-exposure capabilities. Expanding further, the thesis investigates strategies for generating HDR content from the in-the-wild LDR data or limited HDR datasets, and subsequently utilizes the resulting HDR generative models as priors to enable the transformation of LDR images into HDR. Finally, it proposes a feature contrast masking loss inspired by visual masking theory, enabling a self-supervised learning tone mapper to display the HDR content on LDR devices.High Dynamic Range (HDR)-Bilder bieten im Vergleich zu Low Dynamic Range (LDR)-Bildern erhebliche Vorteile, darunter eine höhere Bittiefe, ein breiteres Farbspektrum und einen größeren Dynamikbereich. Diese Eigenschaften bieten den Nutzern nicht nur eine verbesserte visuelle Erfahrung, sondern erleichtern auch die Nachbearbeitungsprozesse in der Fotografie und Filmproduktion. Trotz der erheblichen Fortschritte in der HDR-Technologie in den letzten Jahren bestehen weiterhin große Herausforderungen bei der Erfassung und Darstellung von HDRInhalten. Diese Dissertation untersucht systematisch das Potenzial des Einsatzes von Deep-Learning-Techniken in Kombination mit physikalischem Vorwissen, um diese Herausforderungen zu bewältigen. Zunächst wird der Einsatz impliziter neuronaler Netzwerke untersucht, um HDR-Bilder mit vollständigem Fokus aus spärlichen LDRBildern mit Defokus zu rekonstruieren und dabei flexible Nachfokussierungs- und Belichtungsanpassungen zu ermöglichen. Darüber hinaus wird der Anwendungsbereich auf den 3D-Bereich erweitert, indem 3D-Gaussian Splatting verwendet wird, um HDR-Felder mit vollständigem Fokus aus Multi-View-LDR-Bildern mit Defokus zu rekonstruieren, wodurch die Synthese neuer Ansichten mit Nachfokussierungsund Belichtungsanpassungsfunktionen unterstützt wird. Weiterführend untersucht die Dissertation Strategien zur Generierung von HDR-Inhalten aus unstrukturierten LDR-Daten oder begrenzten HDR-Datensätzen und nutzt die resultierenden HDR-Generativmodelle als Prior, um die Umwandlung von LDR- in HDR-Bilder zu ermöglichen. Schließlich wird ein Feature Contrast Masking Loss vorgeschlagen, der von der Theorie der visuellen Maskierung inspiriert ist und einen selbstüberwachten Tone-Mapping-Ansatz ermöglicht, um HDR-Inhalte auf LDR-Geräten darzustellen
Transcatheter Embolization of Systemic-to-Pulmonary Collaterals: A New Approach Using Concerto™ Helix Nylon-Fibered Microcoils
Full text linkBackground: Systemic-to-pulmonary collaterals (SPCs) are common in congenital
heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation,
SPC can both complicate the postoperative course and lead to clinical deterioration in
the long term. The treatment of SPC is controversial. The aim of our study was (1) to
retrospectively analyse patients who underwent SPC embolization using Concerto™ Helix
nylon-fibred microcoils (CHMs) and (2) to describe the interventional technique. Methods:
In this single-centre retrospective observational cohort study, we analysed clinical and
imaging data of all patients who underwent transcatheter embolization of SPCs using
CHMs from January 2016 to December 2023. Results: In 38 consecutive patients (65.8%
male, median age 41 months, range 2–490), a total number of 141 CHMs had been implanted
into 64 SPCs in 49 procedures. The majority were arterial SPCs (n = 59/64) originating
from the thoracic aorta or its branches; 5/64 were veno-venous SPCs. Primary closure
succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm
being the most commonly used diameter. The mean coil/SPC ratio was 2.6 (range 1.3–5.3).
CHM implantation was performed via four French sheaths. Both detachment and stable
positioning were simple and safe. Neither non-target embolization nor coil migration
occurred. One complication was a vascular injury with resulting extravasation of contrast
medium. In 18/49 procedures (36.7%), coils other than CHMs or vascular plugs were
additionally inserted into separate SPCs. Conclusions: CHMs are appropriate for SPC
embolization in all age groups, including infants, with a low complication rate. The coils are
particularly suitable for the closure of collaterals with a small diameter or tortuous course.
They can be used in combination with other embolization devices to achieve comprehensive
collateral closure
Methodology for the Automatic Generation of Optimization Models of Systems of Flexible Energy Resources
Full text linkThe integration of increasing shares of intermittent renewable energy necessitates
flexibility in both energy generation and consumption. Typically, the operation of flexible
energy resources is orchestrated through optimization models. However, the manual
creation of these models is a complex and error-prone task, often requiring the expertise
of domain specialists. This work introduces a methodology for the automatic generation
of optimization models for systems of flexible energy resources to simplify the modeling
process and increase the use of energy flexibility. This methodology utilizes a modular,
generic model structure designed to depict systems of flexible energy resources. It incorporates algorithms for model parameter derivation from operational data and an information
model that represents the system’s structure and dependencies of resources. The efficacy
of this methodology is demonstrated in two case studies, highlighting its relevance and
ability to significantly streamline the optimization modeling process by minimizing the
need for manual intervention