Scientific publications of the Saarland University
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From Injury to Full Recovery: Monitoring Patient Progress Through Advanced Sensor and Motion Capture Technology
Get PDFBackground: Advanced sensor insoles and motion capture technology can significantly
enhance the monitoring of rehabilitation progress for patients with distal tibial fractures.
This study leverages the potential of these innovative tools to provide a more compre hensive assessment of a patient’s gait and weight-bearing capacity following surgical
intervention, thereby offering the possibility of improved patient outcomes. Methods: A
patient who underwent distal medial tibial plating surgery in August 2023 and subse quently required revision surgery due to implant failure, involving plate removal and the
insertion of an intramedullary nail in December 2023, was meticulously monitored over
a 12-week period. Initial assessments in November 2023 revealed pain upon full weight bearing without crutches. Following the revision, precise weekly measurements were
taken, starting two days after surgery, which instilled confidence in accurately tracking
the patient’s progress from initial crutch-assisted walking to full recovery. The monitoring
tools included insoles, hand pads for force absorption of the crutches, and a motion capture
system. The patient was accompanied throughout all steps of his daily life. Objectives: The
study aimed to evaluate the hypothesis that the approximation and formation of a healthy
gait curve are decisive tools for monitoring healing. Specifically, it investigated whether
cadence, imbalance factors, and ground reaction forces could be significant indicators of
healing status and potential disorders. Results: The gait parameters, cadence, factor of
imbalance ground reaction forces, and the temporal progression of kinematic parameters
significantly correlate with the patient’s recovery trajectory. These metrics enable the early
identification of deviations from expected healing patterns, facilitating timely interven tions and underscoring the transformative potential of these technologies in patient care.
Conclusions: Integrating sensor insoles and motion capture technology offers a promising
approach for monitoring the recovery process in patients with distal tibial fractures. This
method provides valuable insights into the patient’s healing status, potentially predicting
and addressing healing disorders more effectively. Future studies are recommended to
validate these findings in a larger cohort and explore the potential integration of these
technologies into clinical practice
IFNγ Expression Correlates with Enhanced Cytotoxicity in CD8+ T Cells
Get PDFCD8+ T lymphocytes (CTLs) act as serial killers of infected or malignant cells by releasing
large amounts of interferon-gamma (IFNγ) and granzymes. Although IFNγ is a pleiotropic
cytokine with diverse immunomodulatory functions, its precise spatiotemporal regulation
and role in CTL-mediated cytotoxicity remain incompletely understood. Using wild-type
and granzyme B-mTFP knock-in mice, we employed a combination of in vitro approaches,
including T cell isolation and culture, plate-bound anti-CD3e stimulation, degranulation
assays, flow cytometry, immunofluorescence, and structured illumination microscopy, to
investigate IFNγ dynamics in CTLs. IFNγ expression in CTLs was rapid, transient, and
strictly dependent on T cell receptor (TCR) activation. We identified two functionally
distinct IFNγ-producing subsets: IFNγ
high (IFNγ
hi) and IFNγ
low (IFNγ
lo) CTLs. IFNγ
hi
CTLs exhibited an effector/effector memory phenotype, significantly elevated CD107a
surface expression (a marker of lytic granule exocytosis), and higher colocalization with
cis-Golgi and granzyme B compared to IFNγ
lo CTLs. Furthermore, CRTAM, an early
activation marker, correlated with IFNγ expression in naive CTLs. Our findings establish
a link between elevated IFNγ production and enhanced CTL cytotoxicity, implicating
CRTAM as a potential regulator of early CTL activation and IFNγ induction. These insights
provide a foundation for optimizing T cell-based immunotherapies against infections
and cancers
Highly adaptable deep-learning platform for automated detection and analysis of vesicle exocytosis
Get PDFActivity recognition in live-cell imaging is labor-intensive and requires significant human effort. Existing automated analysis tools are largely limited in versatility. We present the Intelligent Vesicle Exocytosis Analysis (IVEA) platform, an ImageJ plugin for automated, reliable analysis of fluorescence-labeled vesicle fusion events and other burst-like activity. IVEA includes three specialized modules for detecting: (1) synaptic transmission in neurons, (2) single-vesicle exocytosis in any cell type, and (3) nano-sensor-detected exocytosis. Each module uses distinct techniques, including deep learning, allowing the detection of rare events often missed by humans at a speed estimated to be approximately 60 times faster than manual analysis. IVEA’s versatility can be expanded by refining or training new models via an integrated interface. With its impressive speed and remarkable accuracy, IVEA represents a seminal advancement in exocytosis image analysis and other burst-like fluorescence fluctuations applicable to a wide range of microscope types and fluorescent dyes
Swiftly identifying strongly unique k-mers
Get PDFMotivation Short DNA sequences of length k that appear in a single location (e.g., at a single genomic position,
in a single species from a larger set of species, etc.) are called unique k-mers. They are useful for placing sequenced
DNA fragments at the correct location without computing alignments and without ambiguity. However, they are
not necessarily robust: A single basepair change may turn a unique k-mer into a diferent one that may in fact be
present at one or more diferent locations, which may give confusing or contradictory information when attempting
to place a read by its k-mer content. A more robust concept are strongly unique k-mers, i.e., unique k-mers for which
no Hamming-distance-1 neighbor with conficting information exists in all of the considered sequences. Given a set
of k-mers, it is therefore of interest to have an efcient method that can distinguish k-mers with a Hamming-dis tance-1 neighbor in the collection from those that do not.
Results We present engineered algorithms to identify and mark within a set K of (canonical) k-mers all elements
that have a Hamming-distance-1 neighbor in the same set. One algorithm is based on recursively running a 4-way
comparison on sub-intervals of the sorted set. The other algorithm is based on bucketing and running a pairwise
bit-parallel Hamming distance test on small buckets of the sorted set. Both methods consider canonical k-mers (i.e.,
taking reverse complements into account) and allow for efcient parallelization. The methods have been imple mented and applied in practice to sets consisting of several billions of k-mers. An optimized combined approach run ning with 16 threads on a 16-core workstation yields wall times below 20 seconds on the 2.5 billion distinct 31-mers
of the human telomere-to-telomere reference genome.
Availability An implementation can be found at https://gitlab.com/rahmannlab/strong-k-mers
A new preclinical sheep model of medial meniscus anterior root repair: Part 1-Quantitative morphology and relationships to adjacent structures
Get PDFPurpose
To analyse the quantitative morphology of the menisci, their roots and relations with a focus on the medial meniscus anterior root (MAR) as a basis for a preclinical model.
Methods
Data was obtained from 24 tibial plateaus of skeletally mature, female Merino ewes. The MAR attachment (MARA) was scanned with micro-computed tomography and stained with hematoxylin and eosin. Data of relevant anatomical structures was subjected to principal component analysis (PCA) and Spearman correlations.
Results
The osteo-ligamentous junction of the MARA represents a classical enthesis with a type-I insertion into the cortical bone. The medial tibial plateau was of a significantly smaller area than lateral. Its sagittal length was significantly longer than lateral. The widths of the MAR and lateral meniscus anterior root (LAR) were approximately half of both anterior horn widths. The MAR was significantly wider than the LAR. The medial meniscus body, posterior horn and medial posterior root were significantly thinner than lateral. PCA and cluster analysis revealed a striking, significant distinction between the structures of the medial and lateral tibial plateau. The sagittal length of the articular cartilage of both tibial plateaus correlated with the primary axis length of both menisci. The maximum width of the articular cartilage of both plateaus correlated with the area of both menisci. Significant correlations also existed between the length of the MAR and the total width of the tibia plateau and between the size of the MARA and the coronal distance to the medial tibial eminence (MTE), to the tibial tuberosity and the sagittal distance to the MTE.
Conclusion
The ovine MAR may be appropriate for repair approaches because of its morphological similarities to the human situation. The substantial differences between the medial and lateral tibial plateau have to be respected.
Level of Evidence
Not applicable
Synthesis and Self-Assembly of Pore-Forming Three-Arm Amphiphilic Block Copolymers
Get PDFThe synthesis of an amphiphilic three-arm block copolymer (AB)3-BCP, which
consists of poly(methyl methacrylate) (PMMA) and poly(butyl methacrylate)
(PBMA) in the hydrophobic inner block, is reported. The hydrophilic block
segment is based on poly(2-hydroxyethyl methacrylate) (PHEMA) originating
from 2-(trimethylsiloxyl)ethyl methacrylate (HEMA-TMS). The preparation is
carried out in two steps using a core-first approach. Using atom transfer
radical polymerization (ATRP) as a controlled polymerization technique, three
(AB)3-BPCs with HEMA contents of 15 to 38 mol−1 % are prepared, applying
different reaction conditions. Porous structures are generated from these
BCPs by applying a self-assembly and nonsolvent-induced phase separation
(SNIPS) protocol. Complex surface structures are observed using scanning
electron microscopy (SEM). Bulk morphologies are investigated for a better
understanding of the underlying self-assembly. For PHEMA-rich (AB)3-BCPs,
non-regular lamellar microphases are observed in transmission electron
microscopy (TEM) and confirmed by small-angle X-ray scattering (SAXS). The
porous structures and their expected swelling characteristics are analyzed
using atomic force microscopy (AFM) in air and water. Time-resolved
measurements in water indicate a rapid swelling after immersion into the
water bath. The present study paves the way for exciting porous materials
based on the herein synthesized amphiphilic three-arm block copolymers
useful for applications as absorber materials and coatings
Impact of Geometry on Chemical Analysis Exemplified for Photoelectron Spectroscopy of Black Silicon
Get PDFFor smooth surfaces, chemical composition can be readily analyzed using
various spectroscopic techniques, a prominent example is X-ray
photoelectron spectroscopy (XPS), where the relative proportions of the
elements are mainly determined by the intensity ratio of the element-specific
photoelectrons. However, this analysis becomes more complex for nanorough
surfaces like black silicon (b-Si) due to the geometry’s steep slopes, which
mimic local variations in emission angles. In this study, this effect is explicitly
quantified through an integral geometric analysis using Minkowski tensors,
correlating XPS chemical data with topographical information from Atomic
Force Microscopy (AFM). This approach yields reliable estimates of layer
thicknesses for nanorough surfaces. For b-Si, it is found that the oxide layer is
≈50%–80% thicker than the native oxide layer on a standard Si wafer. This
study underscores the significant impact of nanoscale geometries on
chemical property analysis
The Wisdom of Electronic Employee Crowds—Employee Reviews as a Data Source in Finance, Accounting, Economics, and Management Research: A Systematic Literature Review
Get PDFThis study explores the wealth of information inherent in online employee reviews as an emerging resource in academic research. The focus is on the fields of finance, accounting, economics, and management, with an emphasis on how employee reviews contribute to our understanding of these areas. A systematic literature review (SLR) of 70 high-quality articles highlights the insights gleaned from employee reviews. Their data points, such as employee satisfaction, employee outlook, evaluation of culture, management, and colleagues, and text comments are mainly used in (1) explaining and predicting firm performance, (2) predicting and understanding performance and satisfaction of specific job groups, and (3) CSR- and ESG-related research. This SLR is important because the three main topics mentioned in which employee reviews are mainly used are spread across the fields of finance, accounting, economics, and management. This SLR therefore provides researchers with an important and necessary overview of the research already addressed across these fields. Furthermore, the SLR provides an overview of employer rating platforms utilized for academic research and methods used to harness employee reviews for research purposes. Here, a significant finding of this SLR is the predominant use of Glassdoor as a data source and the focus on US markets. The SLR concludes by proposing five potential avenues for future research, paving the way for a deeper understanding of the interplay between employee reviews (information) and organizational dynamics
Der Einfluss von Sildenafil und Cilostazol auf die Frakturheilung in der alten Maus
Get PDFDer demografische Wandel unserer Gesellschaft bedingt, dass die Medizin der Zukunft noch stärker von älteren Patienten geprägt sein wird, als dies schon in der Gegenwart der Fall ist. Da im Alter eine geringere Heilungskapazität besteht und Frakturen mit einer höheren Mortalität assoziiert sind, ist es von besonderem Interesse, diese fachgerecht behandeln zu können. Viele Faktoren können zur Verschlechterung der Knochenregeneration im Alter beitragen, darunter eine verringerte Angiogenese, eine beeinträchtigte Entzündungsregulierung sowie weitere negative Auswirkungen des Alters auf eine Vielzahl molekularer und zellulärer Prozesse. In der vorliegenden Studie werden zum ersten Mal die Auswirkungen von Sildenafil und Cilostazol auf die Frakturheilung bei älteren Mäusen unter Verwendung eines Modells für geschlossene Femurfrakturen untersucht. Sildenafil hemmt die Phosphodiesterase-5 und wird sehr häufig bei erektiler Dysfunktion eingesetzt. Zudem ist es auch zur Therapie der pulmonalarteriellen Hypertonie zugelassen. Darüber hinaus konnte in vorherigen Studien gezeigt werden, dass Sildenafil die Angiogenese und die Knochenneubildung fördert. Cilostazol ist ein Hemmstoff der Phosphodiesterase-3 und für die Therapie der pAVK im Stadium II zugelassen. Der Wirkstoff besitzt unter anderem thrombozytenaggregationshemmende Eigenschaften und hat, ähnlich wie Sildenafil, in präklinischen Studien proangiogene und proosteogene Wirkungen gezeigt. Für die Studie wurde bei alten CD-1-Mäusen (Alter: 16-18 Monate) in Narkose mithilfe einer Guillotine eine geschlossene Fraktur des Femurs verursacht und diese durch Einbringen der Mouse ScrewTM osteosynthetisch versorgt. Für den ersten Studienabschnitt wurde eine Sildenafilgruppe (n=21) und eine Kontrollgruppe (n=21) gebildet. Die Tiere erhielten postoperativ täglich in der Sildenafilgruppe 5 mg/kg KG Sildenafil und in der Kontrollgruppe 0,9%ige NaCl-Lösung über eine Magensonde oral verabreicht.
Für den zweiten Studienabschnitt wurde eine Cilostazolgruppe (n=21) und eine Kontrollgruppe (n=21) gebildet. Die Tiere erhielten postoperativ täglich in der Cilostazolgruppe 30 mg/kg KG Cilostazol und in der Kontrollgruppe 0,9%ige NaCl-Lösung über eine Magensonde oral verabreicht. Nach 2 und 5 Wochen Versuchszeit wurden die Tiere getötet und ihre Femora für röntgenologische, biomechanische, mikrocomputertomographische, histologische und immunhistochemische Untersuchungen verwendet. Zudem wurden nach 2 Wochen proteinbiochemische Analysen mittels Western Blot durchgeführt. Die durchgeführten Analysen zeigen, dass bei den mit Sildenafil behandelten Mäusen das Knochenvolumen und das Verhältnis von Kallus zu Durchmesser des Femurs 5 Wochen nach der Fraktur im Vergleich zu Kontrolltieren signifikant zunahmen. Dies ging mit einer verringerten Anzahl von Osteoklasten sowie einer erhöhten Expression von Osteoprotegerin (OPG) und einer verringerten Expression des Nuclear factor erythroid 2-related factor 2 (Nrf2) einher. Diese Ergebnisse deuten darauf hin, dass Sildenafil die Frakturheilung im Alter nicht verbessert, sondern den Prozess des Knochenumbaus verzögert, was höchstwahrscheinlich auf eine geringere Anzahl und Aktivität von Osteoklasten im Kallusgewebe zurückzuführen ist. Bei den mit Cilostazol behandelten Tieren zeigen die Ergebnisse im Vergleich zu den Kontrolltieren eine signifikant erhöhte Biegesteifigkeit nach 2 Wochen und eine verstärkte Knochenbildung nach 5 Wochen. Dies ging mit einer höheren Anzahl neu gebildeter CD31-positiver Mikrogefäße sowie einer erhöhten Expression von Phosphoinositid-3-Kinase (PI3K) und Runt-related transcription factor 2 (RUNX2) im Kallusgewebe einher. Die Ergebnisse deuten darauf hin, dass Cilostazol die Frakturheilung bei alten Mäusen beschleunigt, indem es die Angiogenese und die Expression von PI3K und RUNX2 stimuliert. Daher könnte Cilostazol ein vielversprechender Wirkstoff zur Förderung der Knochenheilung nach Frakturen im Alter sein.The demographic changes in our society lead to a steadily increasing number of geriatric patients. Lower
bone healing capacity and fractures in aged are associated with higher mortality when compared to
young adults. Therefore, geriatric patients represent a major challenge for our health care system. Many
factors may contribute to the deterioration of bone regeneration in the elderly, including reduced
angiogenesis, impaired inflammatory regulation and other negative effects of age on a variety of
molecular and cellular processes. In our study, we investigated the effects of sildenafil and cilostazol on
fracture healing in old mice using a model of closed femur fractures.
Sildenafil is a phosphodiesterase-5 inhibitor. It is commonly used for treating erectile dysfunction and
is also approved for the treatment of pulmonary arterial hypertension. In addition, previous experimental
studies have shown that sildenafil promotes angiogenesis and bone formation.
Cilostazol is a phosphodieesterase-3 inhibitor and is approved for the treatment of stage II peripheral
artery disease. Moreover, the drug has antiplatelet properties and demonstrates pro-angiogenic and proosteogenic
effects in preclinical studies.
For the present study, a fracture of the femur was induced in aged CD-1 mice (age: 16-18 months) under
anesthesia using a 3-point bending device. The fracture was stabilized by inserting a MouseScrewTMImplant.
In the first part of the study, the sildenafil group (n=21) was compared with a control group (n=21).
After fracture, the animals received 5 mg/kg body weight sildenafil in the sildenafil group and 0.9%
NaCl solution in the control group orally by gavage daily.
In the second part of the study, the cilostazol group (n=21) was compared with a control group (n=21)
respectively. After fracture, the animals received 30 mg/kg bodyweight cilostazol in the cilostazol group
and 0.9% NaCl solution in the control group orally by gavage daily.
At 2 and 5 weeks after surgery, the animals were sacrificed and the femora were used for radiological,
biomechanical, microcomputertomographic, histologic and immunohistochemical examinations. In
addition, proteinbiochemical analyses were performed at 2 weeks after surgery by Western blotting.
The analysis of the first part of the study revealed a significantly increased bone volume and higher ratio
of callus to femora bone diameter at 5 weeks after fracture in sildenafil-treated mice when compared to
controls. This was associated with a reduced number of osteoclasts as well as an elevated expression of osteoprotegerin (OPG) and a reduced expression of nuclear factor erythroid 2-related factor 2 (Nrf2).
These findings indicate that sildenafil does not improve fracture healing in the elderly but delays the
process of bone remodeling, most likely due to a reduced number and activity of osteoclasts within the
callus tissue.
The analysis of the second part of the study showed a significantly increased bending stiffness at 2
weeks and an increased bone formation at 5 weeks after surgery in cilostazol-treated animals compared
with controls. This was associated with a higher number of newly formed CD31-positive microvessels
and an increased expression of phosphoinositide 3-kinase (PI3K) and runt-related transcription factor 2
(RUNX2) within the callus tissue. These results suggest that cilostazol accelerates fracture healing in
aged mice by stimulating angiogenesis and the expression of PI3K and RUNX2. Therefore, cilostazol
may be a promising agent to promote bone healing after fractures in the elderly