Medizin

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    2-LED-μspectrophotometer for rapid on-site detection of pathogens using noble-metal nanoparticle-based colorimetric assays
    (Basel : MDPI, 2020) Reuter, Cornelia; Urban, Matthias; Arnold, Manuel; Stranik, Ondrej; Csáki, Andrea; Fritzsche, Wolfgang
    Novel point-of-care compatible methods such as colorimetric assays have become increasingly important in the field of early pathogen detection. A simple and hand-held prototype device for carrying out DNA-amplification assay based on plasmonic nanoparticles in the colorimetric detection is presented. The low-cost device with two channels (sample and reference) consists of two spectrally different light emitting diodes (LEDs) for detection of the plasmon shift. The color change of the gold-nanoparticle-DNA conjugates caused by a salt-induced aggregation test is examined in particular. A specific and sensitive detection of the waterborne human pathogen Legionella pneumophila is demonstrated. This colorimetric assay, with a simple assay design and simple readout device requirements, can be monitored in real-time on-site. © 2020 by the authors.
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    3D Printing of Piezoelectric Barium Titanate-Hydroxyapatite Scaffolds with Interconnected Porosity for Bone Tissue Engineering
    (Basel : MDPI, 2020) Polley, Christian; Distler, Thomas; Detsch, Rainer; Lund, Henrik; Springer, Armin; Boccaccini, Aldo R.; Seitz, Hermann
    The prevalence of large bone defects is still a major problem in surgical clinics. It is, thus, not a surprise that bone-related research, especially in the field of bone tissue engineering, is a major issue in medical research. Researchers worldwide are searching for the missing link in engineering bone graft materials that mimic bones, and foster osteogenesis and bone remodeling. One approach is the combination of additive manufacturing technology with smart and additionally electrically active biomaterials. In this study, we performed a three-dimensional (3D) printing process to fabricate piezoelectric, porous barium titanate (BaTiO3) and hydroxyapatite (HA) composite scaffolds. The printed scaffolds indicate good cytocompatibility and cell attachment as well as bone mimicking piezoelectric properties with a piezoelectric constant of 3 pC/N. This work represents a promising first approach to creating an implant material with improved bone regenerating potential, in combination with an interconnected porous network and a microporosity, known to enhance bone growth and vascularization.
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    3D Quantification of Vascular-Like Structures in z Stack Confocal Images
    (Amsterdam : Elsevier, 2020) Bonda, Ulrich; Jaeschke, Anna; Lighterness, Anthony; Baldwin, Jeremy; Werner, Carsten; De-Juan-Pardo, Elena M.; Bray, Laura J.
    Optical slice microscopy is commonly used to characterize the morphometric features of 3D cellular cultures, such as in vitro vascularization. However, the quantitative analysis of those structures is often performed on a single 2D maximum intensity projection image, limiting the accuracy of data obtained from 3D cultures. Here, we present a protocol for the quantitative analysis of z stack images, utilizing Fiji, Amira, and WinFiber3D. This protocol facilitates the in-depth examination of vascular-like structures within 3D cell culture models.
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    3D-Printing of Structure-Controlled Antigen Nanoparticles for Vaccine Delivery
    (Columbus, Ohio : American Chemical Soc., 2020) Nishiguchi, Akihiro; Shima, Fumiaki; Singh, Smriti; Akashi, Mitsuru; Moeller, Martin
    Targeted delivery of antigens to immune cells using micro/nanocarriers may serve as a therapeutic application for vaccination. However, synthetic carriers have potential drawbacks including cytotoxicity, low encapsulation efficiency of antigen, and lack of a morphological design, which limit the translation of the delivery system to clinical use. Here, we report a carrier-free and three-dimensional (3D)-shape-designed antigen nanoparticle by multiphoton lithography-based 3D-printing. This simple, versatile 3D-printing approach provides freedom for the precise design of particle shapes with a nanoscale resolution. Importantly, shape-designed antigen nanoparticles with distinct aspect ratios show shape-dependent immune responses. The 3D-printing approach for the rational design of nanomaterials with increasing safety, complexity, and efficacy offers an emerging platform to develop vaccine delivery systems and mechanistic understanding.
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    A 50 ps resolution monolithic active pixel sensor without internal gain in SiGe BiCMOS technology
    (London : Inst. of Physics, 2019) Iacobucci, G.; Cardarelli, R.; Débieux, S.; Di Bello, F.A.; Favre, Y.; Hayakawa, D.; Kaynak, M.; Nessi, M.; Paolozzi, L.; Rücker, H.; Sultan, D.M.S.; Valerio, P.
    A monolithic pixelated silicon detector designed for high time resolution has been produced in the SG13G2 130 nm SiGe BiCMOS technology of IHP. This proof-of-concept chip contains hexagonal pixels of 65 µm and 130 µm side. The SiGe front-end electronics implemented provides an equivalent noise charge of 90 and 160 e- for a pixel capacitance of 70 and 220 fF, respectively, and a total time walk of less than 1 ns. Lab measurements with a 90Sr source show a time resolution of the order of 50 ps. This result is competitive with silicon technologies that integrate an avalanche gain mechanism. © 2019 CERN.
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    A Rotating Spiral Micromotor for Noninvasive Zygote Transfer
    (Hoboke, NJ : Wiley, 2020) Schwarz, Lukas; Karnaushenko, Dmitriy D.; Hebenstreit, Franziska; Naumann, Ronald; Schmidt, Oliver G.; Medina-Sánchez, Mariana
    Embryo transfer (ET) is a decisive step in the in vitro fertilization process. In most cases, the embryo is transferred to the uterus after several days of in vitro culture. Although studies have identified the beneficial effects of ET on proper embryo development in the earlier stages, this strategy is compromised by the necessity to transfer early embryos (zygotes) back to the fallopian tube instead of the uterus, which requires a more invasive, laparoscopic procedure, termed zygote intrafallopian transfer (ZIFT). Magnetic micromotors offer the possibility to mitigate such surgical interventions, as they have the potential to transport and deliver cellular cargo such as zygotes through the uterus and fallopian tube noninvasively, actuated by an externally applied rotating magnetic field. This study presents the capture, transport, and release of bovine and murine zygotes using two types of magnetic micropropellers, helix and spiral. Although helices represent an established micromotor architecture, spirals surpass them in terms of motion performance and with their ability to reliably capture and secure the cargo during both motion and transfer between different environments. Herein, this is demonstrated with murine oocytes/zygotes as the cargo; this is the first step toward the application of noninvasive, magnetic micromotor‐assisted ZIFT.
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    Abschlussbericht zum Verbundprojekt Campus PlasmaMed, Teilvorhaben Campus PlasmaMed 6
    (Hannover : Technische Informationsbibliothek (TIB), 2011) Weltmann, Klaus-Dieter
    [no abstract available]
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    Accurate in vivo tumor detection using plasmonic-enhanced shifted-excitation Raman difference spectroscopy (SERDS)
    (Wyoming, NSW : Ivyspring, 2021) Strobbia, Pietro; Cupil-Garcia, Vanessa; Crawford, Bridget M.; Fales, Andrew M.; Pfefer, T. Joshua; Liu, Yang; Maiwald, Martin; Sumpf, Bernd; Vo-Dinh, Tuan
    For the majority of cancer patients, surgery is the primary method of treatment. In these cases, accurately removing the entire tumor without harming surrounding tissue is critical; however, due to the lack of intraoperative imaging techniques, surgeons rely on visual and physical inspection to identify tumors. Surface-enhanced Raman scattering (SERS) is emerging as a non-invasive optical alternative for intraoperative tumor identification, with high accuracy and stability. However, Raman detection requires dark rooms to work, which is not consistent with surgical settings. Methods: Herein, we used SERS nanoprobes combined with shifted-excitation Raman difference spectroscopy (SERDS) detection, to accurately detect tumors in xenograft murine model. Results: We demonstrate for the first time the use of SERDS for in vivo tumor detection in a murine model under ambient light conditions. We compare traditional Raman detection with SERDS, showing that our method can improve sensitivity and accuracy for this task. Conclusion: Our results show that this method can be used to improve the accuracy and robustness of in vivo Raman/SERS biomedical application, aiding the process of clinical translation of these technologies. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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    Acquired cancer tyrosine kinase inhibitor resistance: ROS as critical determinants
    (London : Macmillan Publishers, part of Springer Nature, 2021) Bekeschus, Sander
    [No abstract available]
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    Activation of murine immune cells upon co-culture with plasma-treated B16F10 melanoma cells
    (Basel : MDPI, 2019) Rödder, Katrin; Moritz, Juliane; Miller, Vandana; Weltmann, Klaus-Dieter; Metelmann, Hans-Robert; Gandhirajan, Rajesh; Bekeschus, Sander
    Recent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells. Moreover, an immune-stimulatory role of plasma treatment, as well as plasma-killed tumor cells, was recently proposed, but studies using primary immune cells are scarce. To this end, we investigated the role of plasma-treated murine B16F10 melanoma cells in modulating murine immune cells' activation and marker profile. Melanoma cells exposed to plasma showed reduced metabolic and migratory activity, and an increased release of danger signals (ATP, CXCL1). This led to an altered cytokine profile with interleukin-1β (IL-1β) and CCL4 being significantly increased in plasma-treated mono- and co-cultures with immune cells. In T cells, plasma-treated melanoma cells induced extracellular signal-regulated Kinase (ERK) phosphorylation and increased CD28 expression, suggesting their activation. In monocytes, CD115 expression was elevated as a marker for activation. In summary, here we provide proof of concept that plasma-killed tumor cells are recognized immunologically, and that plasma exerts stimulating effects on immune cells alone. © 2019 by the authors.
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    Active Matrix Flexible Sensory Systems: Materials, Design, Fabrication, and Integration
    (Weinheim : Wiley-VCH Verlag GmbH & Co. KGaA, 2022) Bao, Bin; Karnaushenko, Dmitriy D.; Schmidt, Oliver G.; Song, Yanlin; Karnaushenko, Daniil
    A variety of modern applications including soft robotics, prosthetics, and health monitoring devices that cover electronic skins (e-skins), wearables as well as implants have been developed within the last two decades to bridge the gap between artificial and biological systems. During this development, high-density integration of various sensing modalities into flexible electronic devices becomes vitally important to improve the perception and interaction of the human bodies and robotic appliances with external environment. As a key component in flexible electronics, the flexible thin-film transistors (TFTs) have seen significant advances, allowing for building flexible active matrices. The flexible active matrices have been integrated with distributed arrays of sensing elements, enabling the detection of signals over a large area. The integration of sensors within pixels of flexible active matrices has brought the application scenarios to a higher level of sophistication with many advanced functionalities. Herein, recent progress in the active matrix flexible sensory systems is reviewed. The materials used to construct the semiconductor channels, the dielectric layers, and the flexible substrates for the active matrices are summarized. The pixel designs and fabrication strategies for the active matrix flexible sensory systems are briefly discussed. The applications of the flexible sensory systems are exemplified by reviewing pressure sensors, temperature sensors, photodetectors, magnetic sensors, and biosignal sensors. At the end, the recent development is summarized and the vision on the further advances of flexible active matrix sensory systems is provided.
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    Adamant: a JSON schema-based metadata editor for research data management workflows [version 1; peer review: 2 approved]
    (London : F1000 Research Ltd, 2022) Chaerony Siffa, Ihda; Schäfer, Jan; Becker, Markus M.
    The web tool Adamant has been developed to systematically collect research metadata as early as the conception of the experiment. Adamant enables a continuous, consistent, and transparent research data management (RDM) process, which is a key element of good scientific practice ensuring the path to Findable, Accessible, Interoperable, Reusable (FAIR) research data. It simplifies the creation of on-demand metadata schemas and the collection of metadata according to established or new standards. The approach is based on JavaScript Object Notation (JSON) schema, where any valid schema can be presented as an interactive web-form. Furthermore, Adamant eases the integration of numerous available RDM methods and software tools into the everyday research activities of especially small independent laboratories. A programming interface allows programmatic integration with other software tools such as electronic lab books or repositories. The user interface (UI) of Adamant is designed to be as user friendly as possible. Each UI element is self-explanatory and intuitive to use, which makes it accessible for users that have little to no experience with JSON format and programming in general. Several examples of research data management workflows that can be implemented using Adamant are introduced. Adamant (client-only version) is available from: https://plasma-mds.github.io/adamant.
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    Advanced Signal Processing and Adaptive Learning Methods
    (New York, NY [u.a.] : Hindawi Publ. Corp., 2019) Delić, Vlado; Stamenković, Zoran; Pokrajac, David
    [No abstract available]
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    The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury
    ([London] : Nature Publishing Group UK, 2022) Bretheau, Floriane; Castellanos-Molina, Adrian; Bélanger, Dominic; Kusik, Maxime; Mailhot, Benoit; Boisvert, Ana; Vallières, Nicolas; Lessard, Martine; Gunzer, Matthias; Liu, Xiaoyu; Boilard, Éric; Quan, Ning; Lacroix, Steve
    Spinal cord injury (SCI) triggers neuroinflammation, and subsequently secondary degeneration and oligodendrocyte (OL) death. We report that the alarmin interleukin (IL)−1α is produced by damaged microglia after SCI. Intra-cisterna magna injection of IL-1α in mice rapidly induces neutrophil infiltration and OL death throughout the spinal cord, mimicking the injury cascade seen in SCI sites. These effects are abolished through co-treatment with the IL-1R1 antagonist anakinra, as well as in IL-1R1-knockout mice which demonstrate enhanced locomotor recovery after SCI. Conditional restoration of IL-1R1 expression in astrocytes or endothelial cells (ECs), but not in OLs or microglia, restores IL-1α-induced effects, while astrocyte- or EC-specific Il1r1 deletion reduces OL loss. Conditioned medium derived from IL-1α-stimulated astrocytes results in toxicity for OLs; further, IL-1α-stimulated astrocytes generate reactive oxygen species (ROS), and blocking ROS production in IL-1α-treated or SCI mice prevented OL loss. Thus, after SCI, microglia release IL-1α, inducing astrocyte- and EC-mediated OL degeneration.
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    Alterations in Event Related Potentials (ERP) associated with tinnitus distress and attention
    (Dordrecht [u.a.] : Springer Science + Business Media B.V, 2008) Delb, W.; Strauss, D.J.; Low, Y.F.; Seidler, H.; Rheinschmitt, A.; Wobrock, T.; D'Amelio, R.
    Tinnitus related distress corresponds to different degrees of attention paid to the tinnitus. Shifting attention to a signal other than the tinnitus is therefore particularly difficult for patients with high tinnitus related distress. As attention effects on Event Related Potentials (ERP) have been shown this should be reflected in ERP measurements (N100, phase locking). In order to prove this hypothesis single sweep ERP recordings were obtained in 41 tinnitus patients as well as 10 control subjects during a period of time when attention was shifted to a tone (attended) and during a second phase (unattended) when they did not focus attention to the tone. Whereas tinnitus patients with low distress showed a significant reduction in both N100 amplitude and phase locking when comparing the attended and unattended measurement condition a group of patients with high tinnitus related distress did not show such ERP alterations. Using single sweep ERP measurements the results of our study show, that attention in high tinnitus related distress patients is captured by their tinnitus significantly more than in low distress patients. Furthermore our results provide the basis for future neurofeedback based tinnitus therapies aiming at maximizing the ability to shift attention away from the tinnitus. © 2008 The Author(s).
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    Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities
    (Amsterdam : Elsevier, 2021) Chen, Kai; Breitner, Susanne; Wolf, Kathrin; Stafoggia, Massimo; Sera, Francesco; Vicedo-Cabrera, Ana M.; Guo, Yuming; Tong, Shilu; Lavigne, Eric; Matus, Patricia; Valdés, Nicolás; Kan, Haidong; Jaakkola, Jouni J. K.; Ryti, Niilo R. I.; Huber, Veronika; Scortichini, Matteo; Hashizume, Masahiro; Honda, Yasushi; Nunes, Baltazar; Madureira, Joana; Holobâcă, Iulian Horia; Fratianni, Simona; Kim, Ho; Lee, Whanhee; Tobias, Aurelio; Íñiguez, Carmen; Forsberg, Bertil; Åström, Christofer; Ragettli, Martina S.; Guo, Yue-Liang Leon; Chen, Bing-Yu; Li, Shanshan; Milojevic, Ai; Zanobetti, Antonella; Schwartz, Joel; Bell, Michelle L.; Gasparrini, Antonio; Schneider, Alexandra
    Background Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants.
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    The amino acid metabolism is essential for evading physical plasma-induced tumour cell death
    (Edinburgh : Nature Publ. Group, 2021) Gandhirajan, Rajesh Kumar; Meyer, Dorothee; Sagwal, Sanjeev Kumar; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Bekeschus, Sander
    Background: Recent studies have emphasised the important role of amino acids in cancer metabolism. Cold physical plasma is an evolving technology employed to target tumour cells by introducing reactive oxygen species (ROS). However, limited understanding is available on the role of metabolic reprogramming in tumour cells fostering or reducing plasma-induced cancer cell death. Methods: The utilisation and impact of major metabolic substrates of fatty acid, amino acid and TCA pathways were investigated in several tumour cell lines following plasma exposure by qPCR, immunoblotting and cell death analysis. Results: Metabolic substrates were utilised in Panc-1 and HeLa but not in OVCAR3 and SK-MEL-28 cells following plasma treatment. Among the key genes governing these pathways, ASCT2 and SLC3A2 were consistently upregulated in Panc-1, Miapaca2GR, HeLa and MeWo cells. siRNA-mediated knockdown of ASCT2, glutamine depletion and pharmacological inhibition with V9302 sensitised HeLa cells to the plasma-induced cell death. Exogenous supplementation of glutamine, valine or tyrosine led to improved metabolism and viability of tumour cells following plasma treatment. Conclusion: These data suggest the amino acid influx driving metabolic reprogramming in tumour cells exposed to physical plasma, governing the extent of cell death. This pathway could be targeted in combination with existing anti-tumour agents. © 2021, The Author(s).
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    AMPA-15N - Synthesis and application as standard compound in traceable degradation studies of glyphosate
    (Amsterdam : Elsevier, 2021) Wirth, Marisa A.; Longwitz, Lars; Kanwischer, Marion; Gros, Peter; Leinweber, Peter; Werner, Thomas
    Stable isotope labeling of pollutants is a valuable tool to investigate their environmental transport and degradation. For the globally most frequently used herbicide glyphosate, such studies have, so far, been hampered by the absence of an analytical standard for its labeled metabolite AMPA-15N, which is formed during the degradation of all commercially available glyphosate isotopologues. Without such a standard, detection and quantitation of AMPA-15N, e.g. with LC-MS/MS, is not possible. Therefore, a synthetic pathway to AMPA-15N from benzamide-15N via the hemiaminal was developed. AMPA-15N was obtained in sufficient yield and purity to be used as a standard compound for LC-MS/MS analysis. Suitable MS-detection settings as well as a calibration using the internal standard (IS) approach were established for Fmoc-derivatized AMPA-15N. The use of different AMPA isotopologues as IS was complicated by the parallel formation of [M+H]+ and [M]+• AMPA-Fmoc precursor ions in ESI-positive mode, causing signal interferences between analyte and IS. We recommend the use of either AMPA-13C-15N, AMPA-13C-15N-D2 or a glyphosate isotopologue as IS, as they do not affect the linearity of the calibration curve. As a proof of concept, the developed analysis procedure for AMPA-15N was used to refine the results from a field lysimeter experiment investigating leaching and degradation of glyphosate-2-13C-15N. The newly enabled quantitation of AMPA-15N in soil extracts showed that similar amounts (0.05 - 0.22 mg·kg-1) of the parent herbicide glyphosate and its primary metabolite AMPA persisted in the topsoil over the study period of one year, while vertical transport through the soil column did not occur for either of the compounds. The herein developed analysis concepts will facilitate future design and execution of experiments on the environmental fate of the herbicide glyphosate.
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    Analysing Interlinked Frequency Dynamics of the Urban Acoustic Environment
    (Basel : MDPI AG, 2022) Haselhoff, Timo; Braun, Tobias; Hornberg, Jonas; Lawrence, Bryce T.; Ahmed, Salman; Gruehn, Dietwald; Moebus, Susanne
    As sustainable metropolitan regions require more densely built-up areas, a comprehensive understanding of the urban acoustic environment (AE) is needed. However, comprehensive datasets of the urban AE and well-established research methods for the AE are scarce. Datasets of audio recordings tend to be large and require a lot of storage space as well as computationally expensive analyses. Thus, knowledge about the long-term urban AE is limited. In recent years, however, these limitations have been steadily overcome, allowing a more comprehensive analysis of the urban AE. In this respect, the objective of this work is to contribute to a better understanding of the time-frequency domain of the urban AE, analysing automatic audio recordings from nine urban settings over ten months. We compute median power spectra as well as normalised spectrograms for all settings. Additionally, we demonstrate the use of frequency correlation matrices (FCMs) as a novel approach to access large audio datasets. Our results show site-dependent patterns in frequency dynamics. Normalised spectrograms reveal that frequency bins with low power hold relevant information and that the AE changes considerably over a year. We demonstrate that this information can be captured by using FCMs, which also unravel communities of interlinked frequency dynamics for all settings.