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Funnell, Jessica L.; Fougere, Jasper; Zahn, Diana; Dutz, Silvio; Gilbert, Ryan J.
Delivery of TGFβ3 from magnetically responsive coaxial fibers reduces spinal cord astrocyte reactivity in vitro. - In: Advanced biology, ISSN 2701-0198, Bd. 0 (2024), 0, 2300531, S. 1-14

A spinal cord injury (SCI) compresses the spinal cord, killing neurons and glia at the injury site and resulting in prolonged inflammation and scarring that prevents regeneration. Astrocytes, the main glia in the spinal cord, become reactive following SCI and contribute to adverse outcomes. The anti-inflammatory cytokine transforming growth factor beta 3 (TGFβ3) has been shown to mitigate astrocyte reactivity; however, the effects of prolonged TGFβ3 exposure on reactive astrocyte phenotype have not yet been explored. This study investigates whether magnetic core-shell electrospun fibers can be used to alter the release rate of TGFβ3 using externally applied magnetic fields, with the eventual application of tailored drug delivery based on SCI severity. Magnetic core-shell fibers are fabricated by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the shell and TGFβ3 into the core solution for coaxial electrospinning. Magnetic field stimulation increased the release rate of TGFβ3 from the fibers by 25% over 7 days and released TGFβ3 reduced gene expression of key astrocyte reactivity markers by at least twofold. This is the first study to magnetically deliver bioactive proteins from magnetic fibers and to assess the effect of sustained release of TGFβ3 on reactive astrocyte phenotype.



https://doi.org/10.1002/adbi.202300531
Zahn, Diana; Diegel, Marco; Valitova, Alina; Dellith, Jan; Dutz, Silvio
Magnetic barium hexaferrite nanoparticles with tunable coercivity as potential magnetic heating agents. - In: Nanomaterials, ISSN 2079-4991, Bd. 14 (2024), 12, 992, S. 1-20

Using magnetic nanoparticles (MNPs) for extracorporeal heating applications results in higher field strength and, therefore, particles of higher coercivity can be used, compared to intracorporeal applications. In this study, we report the synthesis and characterization of barium hexa-ferrite (BaFe12O19) nanoparticles as potential particles for magnetic heating. Using a precipitation method followed by high-temperature calcination, we first studied the influence of varied synthesis parameters on the particles’ properties. Second, the iron-to-barium ratio (Fe/Ba = r) was varied between 2 and 12. Vibrating sample magnetometry, scanning electron microscopy and X-ray diffraction were used for characterization. A considerable influence of the calcination temperature (Tcal) was found on the resulting magnetic properties, with a decrease in coercivity (HC) from values above 370 kA/m for Tcal = 800-1000 ˚C to HC = 45-70 kA/m for Tcal = 1200 ˚C. We attribute this drop in HC mainly to the formation of entirely multi-domain particles at high Tcal. For the varying Fe/Ba ratios, increasing amounts of BaFe2O4 as an additional phase were detected by XRD in the small r (barium surplus) samples, lowering the particles’ magnetization. A decrease in HC was found in the increased r samples. Crystal size ranged from 47 nm to 240 nm and large agglomerates were seen in SEM images. The reported particles, due to their controllable coercivity, can be a candidate for extracorporeal heating applications in the biomedical or biotechnological field.



https://doi.org/10.3390/nano14120992
Petkoviâc, Bojana; Ziolkowski, Marek; Töpfer, Hannes; Haueisen, Jens
A new stress tensor approach for application to the conductor surface. - In: Compel, ISSN 2054-5606, Bd. 0 (2024), 0

Purpose: The purpose of this paper is to derive a new stress tensor for calculating the Lorentz force acting on an arbitrarily shaped nonmagnetic conductive specimen moving in the field of a permanent magnet. The stress tensor allows for a transition from a volume to a surface integral for force calculation. Design/methodology/approach: This paper derives a new stress tensor which consists of two parts: the first part corresponds to the scaled Poynting vector and the second part corresponds to the velocity term. This paper converts the triple integral over the volume of the conductor to a double integral over its surface, where the subintegral functions are continuous through the different compartments of the model. Numerical results and comparison to the standard volume discretization using the finite element method are given. Findings: This paper evaluated the performance of the new stress tensor computation on a thick and thin cuboid, a thin disk, a sphere and a thin cuboid containing a surface defect. The integrals are valid for any geometry of the specimen and the position and orientation of the magnet. The normalized root mean square errors are below 0.26% with respect to a reference finite element solution applying volume integration. Originality/value: Tensor elements are continuous throughout the model, allowing integration directly over the conductor surface.



https://doi.org/10.1108/COMPEL-10-2023-0543
Fischer, Gerald; Haueisen, Jens; Baumgarten, Daniel; Kofler, Markus
Spectral separation of evoked and spontaneous cortical activity, Part 2: Somatosensory high frequency oscillations. - In: Biomedical signal processing and control, ISSN 1746-8108, Volume 95, part A (2024), article 106456, S. 1-8

N-Interval Fourier Analysis (N-FTA) allows for simultaneous spectral assessment of evoked and spontaneous activity in the frequency domain. We applied this method to signals following peripheral electrical nerve stimulation and performed analysis of cortical somatosensory evoked potentials within the 400 to 750 Hz band. For median nerve stimulation, data from eleven volunteers were analyzed. For tibial nerve stimulation, three subjects were investigated. For both stimulation sites, evoked high frequency oscillations (HFOs) components were identified. Furthermore, two kinds of background HFO activity were detected in sham stimulation trials. Spectral component models were applied for quantifying signal properties. Evoked spectral components reflected HFOs being time-locked to the stimulus. The detected spectral components were distributed over the entire investigated spectral band. Their spectral amplitude was close to the limit of the resolution of N-FTA. The experimentally observed spectral amplitude were in quantitative agreement with a model using a Morlet morphology. Within the HFO band, a flat noise floor was observed. Spontaneous physiological background activity contributes significantly to the spectral amplitude. This random activity is the dominant source of interference when extracting evoked HFOs. Within the HFO band, narrow spectral peaks in background activity were detected – both for real and sham stimulation. In the data sampled at 9.6 kHz, such peaks were observed in all recordings. For the 5.0 kHz sampling rate, these peaks were visible in about half of the recordings, and their amplitude was reduced. Based on a mathematical model, these peaks may be generated by organized spontaneous HFO activity producing a stable background wave.



https://doi.org/10.1016/j.bspc.2024.106456
Sendecki, Adam; Ledwoân, Daniel; Nycz, Julia; W&hlink;asowska, Anna; Boguszewska-Chachulska, Anna; Mitas, Andrzej W.; Wyl&hlink;egała, Edward; Teper, Sławomir
A deep learning approach to explore the association of age-related macular degeneration polygenic risk score with retinal optical coherence tomography: a preliminary study. - In: Acta ophthalmologica, ISSN 1755-3768, Bd. 0 (2024), 0, S. 1-11

Purpose: Age-related macular degeneration (AMD) is a complex eye disorder affecting millions worldwide. This article uses deep learning techniques to investigate the relationship between AMD, genetics and optical coherence tomography (OCT) scans. Methods: The cohort consisted of 332 patients, of which 235 were diagnosed with AMD and 97 were controls with no signs of AMD. The genome-wide association studies summary statistics utilized to establish the polygenic risk score (PRS) in relation to AMD were derived from the GERA European study. A PRS estimation based on OCT volumes for both eyes was performed using a proprietary convolutional neural network (CNN) model supported by machine learning models. The method's performance was assessed using numerical evaluation metrics, and the Grad-CAM technique was used to evaluate the results by visualizing the features learned by the model. Results: The best results were obtained with the CNN and the Extra Tree regressor (MAE = 0.55, MSE = 0.49, RMSE = 0.70, R2 = 0.34). Extending the feature vector with additional information on AMD diagnosis, age and smoking history improved the results slightly, with mainly AMD diagnosis used by the model (MAE = 0.54, MSE = 0.44, RMSE = 0.66, R2 = 0.42). Grad-CAM heatmap evaluation showed that the model decisions rely on retinal morphology factors relevant to AMD diagnosis. Conclusion: The developed method allows an efficient PRS estimation from OCT images. A new technique for analysing the association of OCT images with PRS of AMD, using a deep learning approach, may provide an opportunity to discover new associations between genotype-based AMD risk and retinal morphology.



https://doi.org/10.1111/aos.16710
Sendecki, Adam; Ledwoân, Daniel; Tuszy, Aleksandra; Nycz, Julia; W&hlink;asowska, Anna; Boguszewska-Chachulska, Anna; Wyl&hlink;egała, Adam; Mitas, Andrzej W.; Wyl&hlink;egała, Edward; Teper, Sławomir
Association of genetic risk for age-related macular degeneration with morphological features of the retinal microvascular network. - In: Diagnostics, ISSN 2075-4418, Bd. 14 (2024), 7, 770, S. 1-13

Background: Age-related macular degeneration (AMD) is a multifactorial disease encompassing a complex interaction between aging, environmental risk factors, and genetic susceptibility. The study aimed to determine whether there is a relationship between the polygenic risk score (PRS) in patients with AMD and the characteristics of the retinal vascular network visualized by optical coherence tomography angiography (OCTA). Methods: 235 patients with AMD and 97 healthy controls were included. We used data from a previous AMD PRS study with the same group. The vascular features from different retina layers were compared between the control group and the patients with AMD. The association between features and PRS was then analyzed using univariate and multivariate approaches. Results: Significant differences between the control group and AMD patients were found in the vessel diameter distribution (variance: p = 0.0193, skewness: p = 0.0457) and fractal dimension distribution (mean: p = 0.0024, variance: p = 0.0123). Both univariate and multivariate analyses showed no direct and significant association between the characteristics of the vascular network and AMD PRS. Conclusions: The vascular features of the retina do not constitute a biomarker of the risk of AMD. We have not identified a genotype-phenotype relationship, and the expression of AMD-related genes is perhaps not associated with the characteristics of the retinal vascular network.



https://doi.org/10.3390/diagnostics14070770
Fischer, Gerald; Haueisen, Jens; Baumgarten, Daniel; Kofler, Markus
Spectral separation of evoked and spontaneous cortical activity, Part 1: Delta to high gamma band. - In: Biomedical signal processing and control, ISSN 1746-8108, Bd. 92 (2024), 106094, S. 1-11

Spectral analysis of repeatedly evoked potentials (EPs) is challenging since recordings contain a superposition of evoked signals and spontaneous activity. We developed a novel approach, N-interval Fourier Transform Analysis (N-FTA), which allows for reliable separation and simultaneous assessment of triggered and background spectral components. Median nerve stimulation data from a total of eleven volunteers recorded in two labs with different experimental settings were investigated. Consistently, short latency spectral components were mainly contained in the gamma and high gamma bands. In contrast, spontaneous activity displayed a 1/f spectral profile with distinct alpha and beta peaks. Spontaneous power spectral densities (PSDs) obtained for real and sham stimulation were highly comparable. The low frequency background PSD was more than two orders of magnitude above the spectral short latency peaks. Within the 30Hz to 90Hz band, the evoked peaks were -17dB to -4dB below the background suggesting that target band filtered short latency deflection might be extracted using less than 100 trials. SEPs following tibial nerve stimulation (3 subjects) displayed a narrower spectral band at about half the bandwidth as compared to median nerve stimulation. Evoked peaks were between 30Hz and 37Hz at PSD levels being -10dB to -4dB below the background activity. These spectral peaks were related to the short latency response of typical W-morphology. Cortical short latency responses are contained in distinct spectral target bands which are much narrower than the standard bandwidth recommendations for routine recordings. In particular, the high pass corner frequency may be selected about one order of magnitude above the current standard. This might render SEP recordings more robust since it eases the suppression of spontaneous activity and movement artifacts such as eye-blinks. Real-time zero-phase filters are required for translating these findings into improved recording systems.



https://doi.org/10.1016/j.bspc.2024.106094
Oppermann, Hannes; Thelen, Antonia; Haueisen, Jens
Single-trial EEG analysis reveals burst structure during photic driving. - In: Clinical neurophysiology, ISSN 1872-8952, Bd. 159 (2024), S. 66-74

Objective: Photic driving in the human visual cortex evoked by intermittent photic stimulation is usually characterized in averaged data by an ongoing oscillation showing frequency entrainment and resonance phenomena during the course of stimulation. We challenge this view of an ongoing oscillation by analyzing unaveraged data. Methods: 64-channel EEGs were recorded during visual stimulation with light flashes at eight stimulation frequencies between 7.8 and 23 Hz for fourteen healthy volunteers. Time-frequency analyses were performed in averaged and unaveraged data. Results: While we find ongoing oscillations in the averaged data during intermittent photic stimulation, we find transient events (bursts) of activity in the unaveraged data. Both resonance and entrainment occur for the ongoing oscillations in the averaged data and the bursts in the unaveraged data. Conclusions: We argue that the continuous oscillations in the averaged signal may be composed of brief, transient bursts in single trials. Our results can also explain previously observed amplitude fluctuations in averaged photic driving data. Significance: Single-trial analyses might consequently improve our understanding of resonance and entrainment phenomena in the brain.



https://doi.org/10.1016/j.clinph.2024.01.005
Schuler, Ramona; Langer, Andreas; Marquardt, Christoph; Kalev, Georgi; Meisinger, Maximilian; Bandura, Julia; Schiedeck, Thomas; Goos, Matthias; Vette, Albert; Konschake, Marko
Automatic muscle impedance and nerve analyzer (AMINA) as a novel approach for classifying bioimpedance signals in intraoperative pelvic neuromonitoring. - In: Scientific reports, ISSN 2045-2322, Bd. 14 (2024), 654, S. 1-15

Frequent complications arising from low anterior resections include urinary and fecal incontinence, as well as sexual disorders, which are commonly associated with damage to the pelvic autonomic nerves during surgery. To assist the surgeon in preserving pelvic autonomic nerves, a novel approach for intraoperative pelvic neuromonitoring was investigated that is based on impedance measurements of the innervated organs. The objective of this work was to develop an algorithm called AMINA to classify the bioimpedance signals, with the goal of facilitating signal interpretation for the surgeon. Thirty patients included in a clinical investigation underwent nerve-preserving robotic rectal surgery using intraoperative pelvic neuromonitoring. Contraction of the urinary bladder and/or rectum, triggered by direct stimulation of the innervating nerves, resulted in a change in tissue impedance signal, allowing the nerves to be identified and preserved. Impedance signal characteristics in the time domain and the time-frequency domain were calculated and classified to develop the AMINA. Stimulation-induced positive impedance changes were statistically significantly different from negative stimulation responses by the percent amplitude of impedance change Amax in the time domain. Positive impedance changes and artifacts were distinguished by classifying wavelet scales resulting from peak detection in the continuous wavelet transform scalogram, which allowed implementation of a decision tree underlying the AMINA. The sensitivity of the software-based signal evaluation by the AMINA was 96.3%, whereas its specificity was 91.2%. This approach streamlines and automates the interpretation of impedance signals during intraoperative pelvic neuromonitoring.



https://doi.org/10.1038/s41598-023-50504-7
Machts, René; Hunold, Alexander; Drebenstedt, Christian; Rock, Michael; Leu, Carsten; Haueisen, Jens
Rain may improve survival from direct lightning strikes to the human head. - In: Scientific reports, ISSN 2045-2322, Bd. 14 (2024), 1695, S. 1-9

There is evidence that humans can survive a direct lightning strike to the head. Our question is: could water (rain) on the skin contribute to an increase in the survival rate? We measure the influence of rain during high-energy direct lightning strikes on a realistic three-compartment human head phantom. We find a lower number of perforations and eroded areas near the lightning strike impact points on the head phantom when rain was applied compared to no rain. Current amplitudes in the brain were lower with rain compared to no rain before a fully formed flashover. We conclude that rain on the scalp potentially contributes to the survival rate of 70-90% due to: (1) lower current exposition in the brain before a fully formed flashover, and (2) reduced mechanical and thermal damage.



https://doi.org/10.1038/s41598-023-50563-w