Scientific publications of the Saarland University
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Ki-67 as a Prognostic Marker in Squamous Cell Carcinomas of the Vulva: A Systematic Review
Get PDFBackground/Objectives: To evaluate the prognostic impact of immunohistochemical ki-67 staining analysis regarding lymph node involvement and survival data
(overall/progression-free survival) in squamous cell carcinoma of the vulva. Methods:
A systematic literature search of English and German articles was conducted (PubMed,
Embase, Scopus, Web of Science) from 1980 to December 2023, including the search terms
“vulvar Neoplasms”, “vulvar cancer”, “vulvar carcinoma”, “vulvar tumor”, ”vulvar tumour”, “vulvar malignancy”, “vulvar malignant”, “ki-67”, “MIB-1”, “MIB1”, “proliferative
index”, “proliferative activity”, “mitotic index”, and “mitotic count”. Study quality was
assessed using a two-step “mixed-criteria” approach; to synthesize study results, a narrative summary is provided. Results: In total, 13 studies were included in this systematic
literature review. In general, two distinct methods of staining interpretation could be
retrieved: A “pattern-based” method, as well as a cell count-based method. Ten of the
included studies examined the relationship between ki-67 and lymph node involvement,
nine studies included survival data as a parameter of interest; and only five studies defined both groin lymph node metastasis and survival data as outcome variables. While
nine out of ten studies found no statistically significant association between ki-67 staining
and lymph node metastasis, five out of nine studies determined an association between
ki-67 status and overall survival, especially when employing a “pattern-based” method
of staining interpretation. Conclusions: The prognostic value of ki-67 staining in terms
of survival data has been reported ambivalently and should be subject to future studies.
Furthermore, we did not find convincing evidence of an association between ki-67 and
lymph node involvement
The cellular response of lipopolysaccharide-induced inflammation in keratoconus human corneal fibroblasts to RB-PDT: Insights into cytokines, chemokines and related signaling pathways
Get PDFPurpose
Rose Bengal Photodynamic Therapy (RB-PDT) offers dual therapeutic benefits by enhancing corneal stiffness and providing antibacterial activity, presenting significant potential for
patients with keratoconus complicated by keratitis. Our purpose was to assess the effect of
rose bengal photodynamic therapy (RB-PDT) on the expression of pro-inflammatory cytokines and chemokines, as well as on extracellular matrix (ECM)-related molecules, in lipopolysaccharide (LPS)-induced inflammation of keratoconus human corneal fibroblasts (KCHCFs). Additionally, the involvement of the mitogen-activated protein kinase (MAPK) and
nuclear factor kappa B (NF-κB) signaling pathways which are downstream of the Toll-like
receptor 4 (TLR4) pathway were examined.
Methods
KC-HCFs were stimulated with varying concentrations of LPS (0–10 μg/ml), which was followed by RB-PDT. The expression levels of interleukin-1β (IL-1β), IL-6, IL-8, interferon
alpha 2 (IFNA2), IFNB1, intercellular adhesion molecule 1 (ICAM-1), chemokine (C-C motif)
ligand 4 (CCL-4), collagen I, collagen V, lysyl oxidase (LOX), transforming growth factor β 1
(TGF-β1) were measured using qPCR, ELISA, or western blot. The activation of the NF-κB
and MAPK pathways was assessed using qPCR and western blot.
Results
In LPS-induced inflammation of KC-HCFs, the expression of IL-6 was further amplified by
the treatment with RB-PDT (p = 0.001). However, the activation of the MAPK and NF-κB pathways did not increase following RB-PDT. Additionally, RB-PDT reduced the transcription of collagen I and collagen V (p�0.03), while the transcription of LOX and TGF-β1 secretion remained unchanged in KC-HCFs exposed to LPS.
Conclusion
In LPS-induced inflammation of KC-HCFs treated with RB-PDT, despite the increased
expression of pro-inflammatory cytokines, the activation of the TLR4 signaling pathways is
lacking. RB-PDT may have no adverse effects on corneal scar formation of keratoconus
corneas in the short term
Is ultralow friction on graphite sustainable in contaminated environments?
Get PDFStructural lubricity typically occurs in incommensurate, dry contacts where short-range elastic instability is
minimized. Under ambient conditions, however, airborne molecules can adsorb onto solid surfaces, forming a
viscous medium that alters interfacial properties. We hypothesize that despite the presence of physisorbed
contaminants, structural lubricity on graphite can persist due to molecular ordering. Molecular dynamics
simulations were performed with a newly parameterized interfacial potential to study -hexadecane as a
model contaminant on graphite surfaces. We investigated the effects of -hexadecane coverage on shear
stress, comparing behavior on graphite and gold (111). Results reveal that a monolayer of -hexadecane
molecules adheres strongly to graphite, replicating its lattice and maintaining solid-like behavior, which leads
to orientation-dependent shear stresses. This behavior is absent on gold. As the contaminant film thickens,
the orientation effect diminishes, and the shear stress-velocity relationship transitions from Coulomb to quasiStokesian and back to quasi-Coulomb as coverage increases. Despite a substantial increase in shear stress under
ambient conditions, ultralow friction, or superlubricity, remains on graphite
Growth of nonmotile stress-responsive bacteria in 3D colonies under confining pressure
Get PDFWe numerically study three-dimensional colonies of nonmotile stress-responsive bacteria growing under
confining isotropic pressure in a nutrient-rich environment. We develop a novel simulation method to demonstrate how imposing
an external pressure leads to a denser aggregate and strengthens the mechanical interactions between bacteria. Unlike rigid
confinements that prevent bacterial growth, confining pressure acts as a soft constraint and allows colony expansion with a
nearly linear long-term population growth and colony size. Enhancing the mechanosensitivity reduces instantaneous bacterial
growth rates and the overall colony size, though its impact is modest compared to pressure for our studied set of biologically
relevant parameter values. The doubling time grows exponentially at low mechanosensitivity or pressure in our bacterial growth
model. We provide an analytical estimate of the doubling time and develop a population dynamics model consistent with our
simulations. Our findings align with previous experimental results for E. coli colonies under pressure. Understanding the growth
dynamics of stress-responsive bacteria under mechanical stresses provides insight into their adaptive response to varying environmental conditions
[18F]FDG PET/CT of Langerhans Cell Histiocytosis with Vertebra Plana
Get PDFWe present an 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) scan of a 27 y/o patient with long-standing
significant B symptoms, diffuse bone pain, increased inflammation parameters, and polydipsia revealing multiple FDG-avid osteolytic lesions of the axial skeleton including a
vertebra plana of T7 and paraosseous soft tissue lesions. A CT-guided biopsy confirmed
the diagnosis of Langerhans cell histiocytosis (LCH). This case highlights the importance
of considering LCH in young patients with vertebral collapse and underscores the role of
PET/CT imaging in establishing an accurate diagnosis
Syntheses of Marine Natural Products via Matteson Homologations and Related Processes
Get PDFMatteson homologation, a successive extension of chiral boronic esters, is perfectly suited for the synthesis of complex molecular structures containing several stereogenic centers. The “classical version” allows the introduction of various functional groups
in a 1,2-anti-configuration. The absolute configuration is determined by the choice of the
chiral auxiliary, which can be used to introduce several stereogenic centers. In contrast, in
Aggarwal’s lithiation-borylation strategy, new chiral auxiliary reagents must be used in
each reaction step, which on the other hand allows the individual insertion of the desired
stereogenic centers. Both methods have their individual advantages and disadvantages
and are well suited for the synthesis of marine natural products
Computer-supported assistive systems for In-Situ movement guidance in sports
No full textSports have evolved from a means of preparing for hunting or battle to an established component of modern physical fitness and recreation. Regardless of the level of professionalism, correct movement techniques are essential to enhance performance and to reduce the risk of injuries. Traditional autodidactic training methods to learn those techniques, such as books or videos, rely on the trainees understanding of the principles conveyed and their ability to implement them independently. Personal trainers bridge this gap by delivering tailored guidance. However, their accessibility is limited. To address these challenges, computer-supported assistive systems have emerged as a promising addition, providing context-dependent feedback during movement execution. This thesis contributes to future design, implementation, and invesitgation of those systems by presenting several artifacts and accompanying studies, specifically for real-time feedback in rock-climbing and slacklining. Firstly, we implement and study a computer-supported slackling training assistant that teaches novices to walk on a slackline by means of automatic instructions and real-time feedback during the exercise. We show that the system can serve as an effective method for autonomously learning the basics of slackline training. Next, we investigate the perception of different notification channels during a rock climbing ascent. We show that audible and vibro-tactile feedback prove effective for delivering real-time notifications during climbing while visual notifications emerging from the wrist are unsuitable. Following this, we investigate different visualization approaches for real-time expert modelling in rock climbing. We find that none of the visualization techniques excell in every aspect of guiding through a movement by itself. Instead, we propose a hybrid approach that combines the strengths of each technique while minimizing their weaknesses. Finally, we introduce two systems designed to enable future research in computer-supported assistive systems for sports. The first is a toolkit for rapid prototyping of smart insoles, using low-cost pressure sensors and microcontrollers to support the development of sensing applications for foot-related feedback. This is followed by a platform for creating mixed reality climbing experiences on physical rock climbing walls and climbing treadmills. We argue that these technologies allow for the design of flexible, controlled research environments where technology induced constraints or physical limitations in real-world setups can be mitigated.Sport hat sich im Laufe der Zeit von einem Mittel zur Vorbereitung auf die Jagd oder den Kampf zu einem festen Bestandteil der modernen körperlichen Fitness und Freizeitgestaltung entwickelt. Unabhängig von dem Niveau, auf dem der Sport betrieben wird, sind korrekte Bewegungstechniken für die Verbesserung der Leistung und die Verringerung des Verletzungsrisikos unerlässlich. Klassische autodidaktische Trainingsmethoden zum Erlernen dieser Techniken, wie Bücher oder Videos, setzen voraus, dass die Trainierenden die vermittelten Prinzipien vollständig verstehen und selbstständig umsetzen können. Persönliche Trainer schließen diese Lücke, indem sie maßgeschneidertes Feedback geben, sind jedoch nicht immer verfügbar. Um diese Herausforderungen zu adressieren, haben sich computergestützte Assistenzsysteme als vielversprechende Ergänzung herauskristallisiert, die ein an den Sportkontext angepasstes Feedback während der Bewegungen liefern. Die vorliegende Arbeit leistet einen Beitrag zur Gestaltung, Implementierung und Erprobung solcher Systeme, indem sie mehrere Systeme und begleitende Studien im Kontext Echtzeit-Feedback beim Klettern und Slacklinen vorstellt. Zunächst implementieren und untersuchen wir einen computergestützten Slackline-Trainingsassistenten, der Anfängern das Gehen auf einer Slackline mittels Echtzeit-Feedback während der Übung beibringt. Eine begleitende Nutzerstudie zeigt, dass das System eine effektive Methode zum autonomen Erlernen der Grundlagen des Slackline-Trainings darstellt. Darauf folgend untersuchen wir die Wahrnehmung verschiedener Modalitäten für Notifikationen während des Kletterns. Es zeigt sich, dass akustisches und vibrotaktiles Feedback eine geeignete Modalität ist, während sich visuelle Benachrichtigungen am Handgelenk als ungeeignet erwiesen haben. Anschließend untersuchen wir verschiedene Visualisierungsansätze, in denen Trainierende die Bewegungen von virtuellen Experten nachahmen sollen. Aus den Ergebnissen leiten wir ab, dass keine der Visualisierungstechniken für sich genommen in allen Aspekten der Bewegungsführung überlegen ist. Alternativ schlagen wir einen hybriden Ansatz vor, der die Stärken der einzelnen Techniken kombiniert und ihre Schwächen minimiert. Abschließend stellen wir zwei Systeme vor, die zukünftige Forschung im Bereich computergestützter Assistenzsysteme für den Sport ermöglichen sollen. Das erste System ist ein Toolkit für das Entwerfen schneller Prototypen-Designs von intelligenten Einlegesohlen, das kostengünstige Drucksensoren und Mikrocontroller verwendet, um die Entwicklung von Sensoranwendungen für Feedback zur Fußtechnik zu unterstützen. Das zweite System stellt eine Plattform für die Entwicklung von Mixed-Reality-Klettererlebnissen an physischen Kletterwänden und Kletterlaufbändern dar. Durch dieses System wird die Gestaltung flexibler, kontrollierter Forschungsumgebungen ermöglicht, in denen technologiebedingte Einschränkungen oder physische Beschränkungen in realen Umgebungen aufgehoben werden können
Comment on Akil et al. Nonintubated versus Intubated Lung Volume Reduction Surgery in Patients with End-Stage Lung Emphysema and Hypercapnia. J. Clin. Med. 2023, 12, 3750
Get PDFWe read with interest the study by Akil et al [...
Dynamics of T cell subpopulations and plasma cytokines during the first year of antineoplastic therapy in patients with breast cancer: the BEGYN-1 study
Get PDFBackground The role of T cell immunity during antineoplastic therapy is poorly understood. In the BEGYN-1 study,
patients with breast cancer underwent quarterly assessments prior to and during antineoplastic therapy over a period
of 12 months.
Methods We used flow cytometry and multiplex immunoassays to quantify 25 T cell subpopulations and seven
T cell associated plasma cytokines in peripheral blood from 92 non-metastatic breast cancer patients, respectively.
In addition, the association between T cell dynamics and the outcome of patients undergoing neoadjuvant
chemotherapy was investigated.
Results In patients undergoing chemotherapy, a significant reduction in T helper (Th) cells, particularly naïve
central and effector cells and thymus positive Th cells, was observed over time. Interestingly, Th1 immune responseassociated cytokines (IL-12, TNF, IFN-γ) declined while Th2 cells and cytotoxic T cells increased over time.
Conclusions We conclude that in breast cancer patients, chemotherapy is associated with a transition from a Th1
immune response towards Th2 and an increase in cytotoxic T cells, whereas in patients without chemotherapy, these
alterations were less pronounced. Future studies should clarify whether patterns of T cell subsets or plasma cytokines
can be used as biomarkers to monitor or even improve therapeutic interventions
Exploration of CYP4B1 Substrate Promiscuity Across Three Species
Get PDFEnzymes of the cytochrome P450 monooxygenase family 4 (CYP4) in mammals are generally involved either in endobiotic metabolism (e.g., acting on fatty acids
or eicosanoids), or the modification of xenobiotics including therapeutic drugs. CYP4B1
is special, as it is an enigmatic enzyme acting at the interface between xenobiotic and
endobiotic metabolism. However, a systematic analysis of CYP4B1’s substrate scope has
not yet been reported. Herein, a three-step approach to identify novel substrates for
three CYP4B1 orthologs (namely from rabbits, green monkeys, and mouse lemurs) is described. First, screening of a library containing 502 natural products revealed potential
novel substrate groups for CYP4B1. Second, based on these results, a systematic library
was defined consisting of 63 compounds representing 10 compound groups. Third, in vitro
conversion of these compounds by CYP4B1 and identification of conversion products were
conducted, supported by in silico docking, allowing the prediction of binding probabilities
and potential oxidation sites. We report five new substrate groups (acyclic, monocyclic
and bicyclic terpenoids, stilbenoids, and vanilloids), twenty-eight new substrates (inter
alia capsaicin, gingerol, genistein, stilbene, myristicin, thioanisole), and two new reaction
types for CYP4B1 (S-oxidation, O-demethylation). Consequently, CYP4B1 is a far more
promiscuous enzyme than previously thought