@article{GruschwitzHartungErguenetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Erg{\"u}n, S{\"u}leyman and Peter, Dominik and Lichthardt, Sven and Huflage, Henner and Hendel, Robin and Pannenbecker, Pauline and Augustin, Anne Marie and Kunz, Andreas Steven and Feldle, Philipp and Bley, Thorsten Alexander and Grunz, Jan-Peter},
  title     = {Comparison of ultrahigh and standard resolution photon-counting CT angiography of the femoral arteries in a continuously perfused in vitro model},
  series = {European Radiology Experimental},
  volume    = {7},
  journal   = {European Radiology Experimental},
  doi       = {10.1186/s41747-023-00398-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357905},
  year      = {2023},
  abstract  = {Background With the emergence of photon-counting CT, ultrahigh-resolution (UHR) imaging can be performed without dose penalty. This study aims to directly compare the image quality of UHR and standard resolution (SR) scan mode in femoral artery angiographies. Methods After establishing continuous extracorporeal perfusion in four fresh-frozen cadaveric specimens, photon-counting CT angiographies were performed with a radiation dose of 5 mGy and tube voltage of 120 kV in both SR and UHR mode. Images were reconstructed with dedicated convolution kernels (soft: Body-vascular (Bv)48; sharp: Bv60; ultrasharp: Bv76). Six radiologists evaluated the image quality by means of a pairwise forced-choice comparison tool. Kendall's concordance coefficient (W) was calculated to quantify interrater agreement. Image quality was further assessed by measuring intraluminal attenuation and image noise as well as by calculating signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR). Results UHR yielded lower noise than SR for identical reconstructions with kernels ≥ Bv60 (p < 0.001). UHR scans exhibited lower intraluminal attenuation compared to SR (Bv60: 406.4 ± 25.1 versus 418.1 ± 30.1 HU; p < 0.001). Irrespective of scan mode, SNR and CNR decreased while noise increased with sharper kernels but UHR scans were objectively superior to SR nonetheless (Bv60: SNR 25.9 ± 6.4 versus 20.9 ± 5.3; CNR 22.7 ± 5.8 versus 18.4 ± 4.8; p < 0.001). Notably, UHR scans were preferred in subjective assessment when images were reconstructed with the ultrasharp Bv76 kernel, whereas SR was rated superior for Bv60. Interrater agreement was high (W = 0.935). Conclusions Combinations of UHR scan mode and ultrasharp convolution kernel are able to exploit the full image quality potential in photon-counting CT angiography of the femoral arteries. Relevance statement The UHR scan mode offers improved image quality and may increase diagnostic accuracy in CT angiography of the peripheral arterial runoff when optimized reconstruction parameters are chosen. Key points • UHR photon-counting CT improves image quality in combination with ultrasharp convolution kernels. • UHR datasets display lower image noise compared with identically reconstructed standard resolution scans. • Scans in UHR mode show decreased intraluminal attenuation compared with standard resolution imaging.},
  language  = {en}
}
@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Peter, Dominik and Lichthardt, Sven and Huflage, Henner and Grunz, Jan-Peter and Augustin, Anne Marie and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Petritsch, Bernhard},
  title     = {Continuous extracorporeal femoral perfusion model for intravascular ultrasound, computed tomography and digital subtraction angiography},
  series = {PLoS One},
  volume    = {18},
  journal   = {PLoS One},
  number    = {5},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0285810},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350136},
  year      = {2023},
  abstract  = {Objectives We developed a novel human cadaveric perfusion model with continuous extracorporeal femoral perfusion suitable for performing intra-individual comparison studies, training of interventional procedures and preclinical testing of endovascular devices. Objective of this study was to introduce the techniques and evaluate the feasibility for realistic computed tomography angiography (CTA), digital subtraction angiography (DSA) including vascular interventions, and intravascular ultrasound (IVUS). Methods The establishment of the extracorporeal perfusion was attempted using one formalin-fixed and five fresh-frozen human cadavers. In all specimens, the common femoral and popliteal arteries were prepared, introducer sheaths inserted, and perfusion established by a peristaltic pump. Subsequently, we performed CTA and bilateral DSA in five cadavers and IVUS on both legs of four donors. Examination time without unintentional interruption was measured both with and without non-contrast planning CT. Percutaneous transluminal angioplasty and stenting was performed by two interventional radiologists on nine extremities (five donors) using a broad spectrum of different intravascular devices. Results The perfusion of the upper leg arteries was successfully established in all fresh-frozen but not in the formalin-fixed cadaver. The experimental setup generated a stable circulation in each procedure (ten upper legs) for a period of more than six hours. Images acquired with CT, DSA and IVUS offered a realistic impression and enabled the sufficient visualization of all examined vessel segments. Arterial cannulating, percutaneous transluminal angioplasty as well as stent deployment were feasible in a way that is comparable to a vascular intervention in vivo. The perfusion model allowed for introduction and testing of previously not used devices. Conclusions The continuous femoral perfusion model can be established with moderate effort, works stable, and is utilizable for medical imaging of the peripheral arterial system using CTA, DSA and IVUS. Therefore, it appears suitable for research studies, developing skills in interventional procedures and testing of new or unfamiliar vascular devices.},
  language  = {en}
}
@article{GoetzRueckschlossBalketal.2023,
  author    = {G{\"o}tz, Lisa and Rueckschloss, Uwe and Balk, G{\"o}zde and Pfeiffer, Verena and Erg{\"u}n, S{\"u}leyman and Kleefeldt, Florian},
  title     = {The role of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer},
  series = {Frontiers in Immunology},
  volume    = {14},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2023.1295232},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357250},
  year      = {2023},
  abstract  = {The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. CEACAM1 was shown to be a prognostic marker in patients suffering from cancer. In this review, we summarize pre-clinical and clinical evidence linking CEACAM1 to tumorigenicity and cancer progression. Furthermore, we discuss potential CEACAM1-based mechanisms that may affect cancer biology.},
  language  = {en}
}
@article{LuetkensGrunzKunzetal.2023,
  author    = {Luetkens, Karsten Sebastian and Grunz, Jan-Peter and Kunz, Andreas Steven and Huflage, Henner and Weißenberger, Manuel and Hartung, Viktor and Patzer, Theresa Sophie and Gruschwitz, Philipp and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Feldle, Philipp},
  title     = {Ultra-high-resolution photon-counting detector CT arthrography of the ankle: a feasibility study},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {13},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13132201},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362622},
  year      = {2023},
  abstract  = {This study was designed to investigate the image quality of ultra-high-resolution ankle arthrography employing a photon-counting detector CT. Bilateral arthrograms were acquired in four cadaveric specimens with full-dose (10 mGy) and low-dose (3 mGy) scan protocols. Three convolution kernels with different spatial frequencies were utilized for image reconstruction (ρ\(_{50}\); Br98: 39.0, Br84: 22.6, Br76: 16.5 lp/cm). Seven radiologists subjectively assessed the image quality regarding the depiction of bone, hyaline cartilage, and ligaments. An additional quantitative assessment comprised the measurement of noise and the computation of contrast-to-noise ratios (CNR). While an optimal depiction of bone tissue was achieved with the ultra-sharp Br98 kernel (S ≤ 0.043), the visualization of cartilage improved with lower modulation transfer functions at each dose level (p ≤ 0.014). The interrater reliability ranged from good to excellent for all assessed tissues (intraclass correlation coefficient ≥ 0.805). The noise levels in subcutaneous fat decreased with reduced spatial frequency (p \&lt; 0.001). Notably, the low-dose Br76 matched the CNR of the full-dose Br84 (p 0.999) and superseded Br98 (p \&lt; 0.001) in all tissues. Based on the reported results, a photon-counting detector CT arthrography of the ankle with an ultra-high-resolution collimation offers stellar image quality and tissue assessability, improving the evaluation of miniscule anatomical structures. While bone depiction was superior in combination with an ultra-sharp convolution kernel, soft tissue evaluation benefited from employing a lower spatial frequency.},
  language  = {en}
}
@article{ElsnerKunzWagneretal.2023,
  author    = {Elsner, Clara and Kunz, Andreas Steven and Wagner, Nicole and Huflage, Henner and H{\"u}bner, Stefan and Luetkens, Karsten Sebastian and Bley, Thorsten Alexander and Schmitt, Rainer and Erg{\"u}n, S{\"u}leyman and Grunz, Jan-Peter},
  title     = {MRI-based evaluation of the flexor digitorum superficialis anatomy: investigating the prevalence and morphometry of the "chiasma antebrachii"},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {14},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13142406},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362631},
  year      = {2023},
  abstract  = {Recent dissection studies resulted in the introduction of the term "chiasma antebrachii", which represents an intersection of the flexor digitorum superficialis (FDS) tendons for digits 2 and 3 in the distal third of the forearm. This retrospective investigation aimed to provide an MRI-based morphologic analysis of the chiasma antebrachii. In 89 patients (41 women, 39.3 ± 21.3 years), MRI examinations of the forearm (2010-2021) were reviewed by two radiologists, who evaluated all studies for the presence and length of the chiasma as well as its distance from the distal radioulnar and elbow joint. The chiasma antebrachii was identified in the distal third of the forearm in 88 patients (98.9\%), while one intersection was located more proximally in the middle part. The chiasma had a median length of 28 mm (interquartile range: 24-35 mm). Its distances to the distal radioulnar and elbow joint were 16 mm (8-25 mm) and 215 mm (187-227 mm), respectively. T1-weighted post-contrast sequences were found to be superior to T2- or proton-density-weighted sequences in 71 cases (79.8\%). To conclude, the chiasma antebrachii is part of the standard FDS anatomy. Knowledge of its morphology is important, e.g., in targeted injections of therapeutics or reconstructive surgery.},
  language  = {en}
}
@phdthesis{Hoehn2023,
  author    = {H{\"o}hn, Marie},
  title     = {Ver{\"a}nderung der Tumorimmunumgebung muriner Mamma-Karzinome durch Inhibierung der Kollagensynthese},
  doi       = {10.25972/OPUS-28492},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284929},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Das Mamma-Karzinom geh{\"o}rt zu den sogenannten desmoplastischen Tumorarten. Hierbei handelt es sich um Tumoren mit erh{\"o}hter Ansammlung von Bindegewebszellen und einer Akkumulation von Extrazellul{\"a}rer Matrix (EZM). Diese verdichtete EZM wirkt sowohl auf mechanischer als auch auf Signalweg-vermittelter Ebene als eine Barriere, welche die therapeutische Wirksamkeit erheblich vermindert. Einer der Hauptbestandteile der EZM ist Kollagen. Durch Anwendung von Pr{\"a}paraten, welche die Kollagensynthese und -reifung inhibieren, kann die rigide Struktur aufgelockert werden. Daraus ergibt sich eine verbesserte Versorgung mit N{\"a}hrstoffen und eine verbesserte Infiltrationsm{\"o}glichkeit f{\"u}r Immunzellen. Dies ist f{\"u}r die Effizienz der Immuntherapie, welche sich in den letzten Jahren als vielversprechende Alternative zu den Grunds{\"a}ulen der Krebstherapie entwickelt hat, unabdinglich. In der vorliegenden Arbeit wurden murine Mamma-Karzinome der 4T1-Linie nach Behandlung mit EZM-destabilisierenden Kollageninhibitoren auf ihre Immunumgebung hin untersucht. Verwendet wurden drei Wirkstoffe, welche an unterschiedlichen Punkten in die Kollagensynthese und -reifung eingreifen: βAPN als LOX(L)-Inhibitor, 1,4-DPCA als P4HA-Inhibitor und Minoxidil als LH-Inhibitor. Die Behandlung f{\"u}hrte zu einem deutlichen Anstieg aller untersuchten Immunzellen und deutet somit auf eine verbesserte Infiltrationsm{\"o}glichkeit hin. Zudem wurde die Expression maligner Signalwege, wie die der Angiogenese, Hypoxie, Metastasierungsneigung, Invasivit{\"a}t und Immunsuppression, verringert und tumorsuppressive Immunantworten verst{\"a}rkt. Die Kollageninhibition hatte zus{\"a}tzlich ein verringertes Tumorwachstum und eine Reduktion der Blutgef{\"a}ßdichte zufolge. Als Fazit gilt es festzuhalten, dass die Verwendung von Kollageninhibitoren in der Immuntherapie eine vielversprechende Option zur Verbesserung der Effizienz dieser Therapeutika darstellt. Diese Erkenntnis gilt es im Rahmen k{\"u}nftiger wissenschaftlicher Untersuchungen weiterzuentwickeln.},
  subject      = {Brustkrebs},
  language  = {de}
}
@article{DrenckhahnGottschlichZonneveld2023,
  author    = {Drenckhahn, Detlev and Gottschlich, G{\"u}nter and Zonneveld, Ben},
  title     = {Neubeschreibungen und 2C-Werte von Pilosella macranthela subsp. silvae-pici (Spessart-Mausohrhabichtskraut) und Pilosella ottonis (Otto-Mausohrhabichtskraut) mit einer {\"U}bersicht {\"u}ber das Vorkommen von P. macranthela-Taxa in Bayern.},
  series = {Forum Geobotanicum},
  volume    = {11},
  journal   = {Forum Geobotanicum},
  issn      = {1867-9315},
  doi       = {10.3264/FG.2023.1114},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-344797},
  pages     = {21-34},
  year      = {2023},
  abstract  = {A pentaploid taxon from the Pilosella macranthela group was discovered in Lower Franconia/Bavaria which is newly described here as P. macranthela subsp. sylvae-pici. It grows mainly in the Bavarian Bunter Spessart and occurs with three small, isolated stands also in the limestone area of the Main valley and Tauber area. Its habit of growth is intermediate between the furcata and laxicephala types of Pilosellae with epigeal and partly hypogeal stolons and a tendency to form clusters. The upper and lower surfaces of the rosette leaves have stellate hairs. The peduncles and the phyllaries are densely covered with dark glandular hairs with yellowish glandular heads. The lateral teeth of the ligules often are separated by incisions. A tetra- und pentaploid transitional taxon between P. macranthela subsp. sylvae-pici and P. officinarum is described as P. ottonis. P. ottonis is tetra- and pentaploid with up to 7 capitula. It is densely covered with dark stalk glands on phyllaries and resembles forms of P. acutifolia in habit. The phyllaries of P. ottonis are covered with numerous epidermal papillae with a diameter of about 10-20 μm and in this aspect resemble P. macranthela subsp. sylvae-pici and P. glomerata. However, in P. officinarum epidermal papillae are absent. Plants of genetically heterogeneous tetra- and heptaploid P. macranthela have been found outside the Spessart as spontaneous hybrids between P. glomerata and P. officinarum and also occur sporadically without P. glomerata in the vicinity.},
  subject      = {Habichtskraut},
  language  = {de}
}
@article{WatermannMeyerWagneretal.2023,
  author    = {Watermann, Christoph and Meyer, Malin Tordis and Wagner, Steffen and Wittekindt, Claus and Klussmann, Jens Peter and Erguen, Sueleyman and Baumgart-Vogt, Eveline and Karnati, Srikanth},
  title     = {Peroxisomes are highly abundant and heterogeneous in human parotid glands},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {5},
  issn      = {1422-0067},
  doi       = {10.3390/ijms24054783},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311079},
  year      = {2023},
  abstract  = {The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland's striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue.},
  language  = {en}
}
@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Erg{\"u}n, S{\"u}leyman and Lichthardt, Sven and Huflage, Henner and Hendel, Robin and Kunz, Andreas Steven and Pannenbecker, Pauline and Kuhl, Philipp Josef and Augustin, Anne Marie and Bley, Thorsten Alexander and Petritsch, Bernhard and Grunz, Jan-Peter},
  title     = {Standardized assessment of vascular reconstruction kernels in photon-counting CT angiographies of the leg using a continuous extracorporeal perfusion model},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-39063-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357912},
  year      = {2023},
  abstract  = {This study evaluated the influence of different vascular reconstruction kernels on the image quality of CT angiographies of the lower extremity runoff using a 1st-generation photon-counting-detector CT (PCD-CT) compared with dose-matched examinations on a 3rd-generation energy-integrating-detector CT (EID-CT). Inducing continuous extracorporeal perfusion in a human cadaveric model, we performed CT angiographies of eight upper leg arterial runoffs with radiation dose-equivalent 120 kVp acquisition protocols (CTDIvol 5 mGy). Reconstructions were executed with different vascular kernels, matching the individual modulation transfer functions between scanners. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were computed to assess objective image quality. Six radiologists evaluated image quality subjectively using a forced-choice pairwise comparison tool. Interrater agreement was determined by calculating Kendall's concordance coefficient (W). The intraluminal attenuation of PCD-CT images was significantly higher than of EID-CT (414.7 ± 27.3 HU vs. 329.3 ± 24.5 HU; p < 0.001). Using comparable kernels, image noise with PCD-CT was significantly lower than with EID-CT (p ≤ 0.044). Correspondingly, SNR and CNR were approximately twofold higher for PCD-CT (p < 0.001). Increasing the spatial frequency for PCD-CT reconstructions by one level resulted in similar metrics compared to EID-CT (CNRfat; EID-CT Bv49: 21.7 ± 3.7 versus PCD-CT Bv60: 21.4 ± 3.5). Overall image quality of PCD-CTA achieved ratings superior to EID-CTA irrespective of the used reconstruction kernels (best: PCD-CT Bv60; worst: EID-CT Bv40; p < 0.001). Interrater agreement was good (W = 0.78). Concluding, PCD-CT offers superior intraluminal attenuation, SNR, and CNR compared to EID-CT in angiographies of the upper leg arterial runoff. Combined with improved subjective image quality, PCD-CT facilitates the use of sharper convolution kernels and ultimately bears the potential of improved vascular structure assessability.},
  language  = {en}
}
@article{PatzerKunzHuflageetal.2023,
  author    = {Patzer, Theresa Sophie and Kunz, Andreas Steven and Huflage, Henner and Conrads, Nora and Luetkens, Karsten Sebastian and Pannenbecker, Pauline and Paul, Mila Marie and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Grunz, Jan-Peter},
  title     = {Ultrahigh-resolution photon-counting CT in cadaveric fracture models: spatial frequency is not everything},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {10},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13101677},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319281},
  year      = {2023},
  abstract  = {In this study, the impact of reconstruction sharpness on the visualization of the appendicular skeleton in ultrahigh-resolution (UHR) photon-counting detector (PCD) CT was investigated. Sixteen cadaveric extremities (eight fractured) were examined with a standardized 120 kVp scan protocol (CTDI\(_{vol}\) 10 mGy). Images were reconstructed with the sharpest non-UHR kernel (Br76) and all available UHR kernels (Br80 to Br96). Seven radiologists evaluated image quality and fracture assessability. Interrater agreement was assessed with the intraclass correlation coefficient. For quantitative comparisons, signal-to-noise-ratios (SNRs) were calculated. Subjective image quality was best for Br84 (median 1, interquartile range 1-3; p ≤ 0.003). Regarding fracture assessability, no significant difference was ascertained between Br76, Br80 and Br84 (p > 0.999), with inferior ratings for all sharper kernels (p < 0.001). Interrater agreement for image quality (0.795, 0.732-0.848; p < 0.001) and fracture assessability (0.880; 0.842-0.911; p < 0.001) was good. SNR was highest for Br76 (3.4, 3.0-3.9) with no significant difference to Br80 and Br84 (p > 0.999). Br76 and Br80 produced higher SNRs than all kernels sharper than Br84 (p ≤ 0.026). In conclusion, PCD-CT reconstructions with a moderate UHR kernel offer superior image quality for visualizing the appendicular skeleton. Fracture assessability benefits from sharp non-UHR and moderate UHR kernels, while ultra-sharp reconstructions incur augmented image noise.},
  language  = {en}
}
@article{HuflageGrunzPatzeretal.2023,
  author    = {Huflage, Henner and Grunz, Jan-Peter and Patzer, Theresa Sophie and Pannenbecker, Pauline and Feldle, Philipp and Sauer, Stephanie Tina and Petritsch, Bernhard and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Kunz, Andreas Steven},
  title     = {Potential of unenhanced ultra-low-dose abdominal photon-counting CT with tin filtration: a cadaveric study},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {4},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13040603},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304122},
  year      = {2023},
  abstract  = {Objectives: This study investigated the feasibility and image quality of ultra-low-dose unenhanced abdominal CT using photon-counting detector technology and tin prefiltration. Materials and Methods: Employing a first-generation photon-counting CT scanner, eight cadaveric specimens were examined both with tin prefiltration (Sn 100 kVp) and polychromatic (120 kVp) scan protocols matched for radiation dose at three different levels: standard-dose (3 mGy), low-dose (1 mGy) and ultra-low-dose (0.5 mGy). Image quality was evaluated quantitatively by means of contrast-to-noise-ratios (CNR) with regions of interest placed in the renal cortex and subcutaneous fat. Additionally, three independent radiologists performed subjective evaluation of image quality. The intraclass correlation coefficient was calculated as a measure of interrater reliability. Results: Irrespective of scan mode, CNR in the renal cortex decreased with lower radiation dose. Despite similar mean energy of the applied x-ray spectrum, CNR was superior for Sn 100 kVp over 120 kVp at standard-dose (17.75 ± 3.51 vs. 14.13 ± 4.02), low-dose (13.99 ± 2.6 vs. 10.68 ± 2.17) and ultra-low-dose levels (8.88 ± 2.01 vs. 11.06 ± 1.74) (all p ≤ 0.05). Subjective image quality was highest for both standard-dose protocols (score 5; interquartile range 5-5). While no difference was ascertained between Sn 100 kVp and 120 kVp examinations at standard and low-dose levels, the subjective image quality of tin-filtered scans was superior to 120 kVp with ultra-low radiation dose (p < 0.05). An intraclass correlation coefficient of 0.844 (95\% confidence interval 0.763-0.906; p < 0.001) indicated good interrater reliability. Conclusions: Photon-counting detector CT permits excellent image quality in unenhanced abdominal CT with very low radiation dose. Employment of tin prefiltration at 100 kVp instead of polychromatic imaging at 120 kVp increases the image quality even further in the ultra-low-dose range of 0.5 mGy.},
  language  = {en}
}
@article{PatzerKunzHuflageetal.2023,
  author    = {Patzer, Theresa Sophie and Kunz, Andreas Steven and Huflage, Henner and Luetkens, Karsten Sebastian and Conrads, Nora and Gruschwitz, Philipp and Pannenbecker, Pauline and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Grunz, Jan-Peter},
  title     = {Quantitative and qualitative image quality assessment in shoulder examinations with a first-generation photon-counting detector CT},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-35367-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357925},
  year      = {2023},
  abstract  = {Photon-counting detector (PCD) CT allows for ultra-high-resolution (UHR) examinations of the shoulder without requiring an additional post-patient comb filter to narrow the detector aperture. This study was designed to compare the PCD performance with a high-end energy-integrating detector (EID) CT. Sixteen cadaveric shoulders were examined with both scanners using dose-matched 120 kVp acquisition protocols (low-dose/full-dose: CTDI\(_{vol}\) = 5.0/10.0 mGy). Specimens were scanned in UHR mode with the PCD-CT, whereas EID-CT examinations were conducted in accordance with the clinical standard as "non-UHR". Reconstruction of EID data employed the sharpest kernel available for standard-resolution scans (ρ\(_{50}\) = 12.3 lp/cm), while PCD data were reconstructed with both a comparable kernel (11.8 lp/cm) and a sharper dedicated bone kernel (16.5 lp/cm). Six radiologists with 2-9 years of experience in musculoskeletal imaging rated image quality subjectively. Interrater agreement was analyzed by calculation of the intraclass correlation coefficient in a two-way random effects model. Quantitative analyses comprised noise recording and calculating signal-to-noise ratios based on attenuation measurements in bone and soft tissue. Subjective image quality was higher in UHR-PCD-CT than in EID-CT and non-UHR-PCD-CT datasets (all p < 0.001). While low-dose UHR-PCD-CT was considered superior to full-dose non-UHR studies on either scanner (all p < 0.001), ratings of low-dose non-UHR-PCD-CT and full-dose EID-CT examinations did not differ (p > 0.99). Interrater reliability was moderate, indicated by a single measures intraclass correlation coefficient of 0.66 (95\% confidence interval: 0.58-0.73; p < 0.001). Image noise was lowest and signal-to-noise ratios were highest in non-UHR-PCD-CT reconstructions at either dose level (p < 0.001). This investigation demonstrates that superior depiction of trabecular microstructure and considerable denoising can be realized without additional radiation dose by employing a PCD for shoulder CT imaging. Allowing for UHR scans without dose penalty, PCD-CT appears as a promising alternative to EID-CT for shoulder trauma assessment in clinical routine.},
  language  = {en}
}
@article{SchreiberLohrBaltesetal.2023,
  author    = {Schreiber, Laura M. and Lohr, David and Baltes, Steffen and Vogel, Ulrich and Elabyad, Ibrahim A. and Bille, Maya and Reiter, Theresa and Kosmala, Aleksander and Gassenmaier, Tobias and Stefanescu, Maria R. and Kollmann, Alena and Aures, Julia and Schnitter, Florian and Pali, Mihaela and Ueda, Yuichiro and Williams, Tatiana and Christa, Martin and Hofmann, Ulrich and Bauer, Wolfgang and Gerull, Brenda and Zernecke, Alma and Erg{\"u}n, S{\"u}leyman and Terekhov, Maxim},
  title     = {Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {10},
  journal   = {Frontiers in Cardiovascular Medicine},
  issn      = {2297-055X},
  doi       = {10.3389/fcvm.2023.1068390},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317398},
  year      = {2023},
  abstract  = {A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.},
  language  = {en}
}
@article{PozziBolzoniBiellaetal.2023,
  author    = {Pozzi, Nicol{\´o} Gabriele and Bolzoni, Francesco and Biella, Gabriele Eliseo Mario and Pezzoli, Gianni and Ip, Chi Wang and Volkmann, Jens and Cavallari, Paolo and Asan, Esther and Isaias, Ioannis Ugo},
  title     = {Brain noradrenergic innervation supports the development of Parkinson's tremor: a study in a reserpinized rat model},
  series = {Cells},
  volume    = {12},
  journal   = {Cells},
  number    = {21},
  issn      = {2073-4409},
  doi       = {10.3390/cells12212529},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357721},
  year      = {2023},
  abstract  = {The pathophysiology of tremor in Parkinson's disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um\(^2\), p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (\% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic-rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients.},
  language  = {en}
}
@article{Haveman2023,
  author    = {Haveman, Rense},
  title     = {Phytosociological notes on hedges in South Ayrshire, Scotland},
  series = {Forum Geobotanicum},
  volume    = {11},
  journal   = {Forum Geobotanicum},
  issn      = {1867-9315},
  doi       = {10.3264/FG.2023.0420},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312634},
  pages     = {1-7},
  year      = {2023},
  abstract  = {On the basis of four relev{\´e}es of hedges around Straiton en Dailly in South Ayrshire, Scotland, some features of hedges are discussed. On the basis of the brambles, the vegetation of these hedges can be assigned to the Pruno-Rubion sprengelii, which comprises the bramble scrubs of circumneutral and nutrient rich soils in West Europe (Haveman et al. 2017, Haveman \& de Ronde 2019). Until now, this alliance was thought to be restricted to the northwestern edge of the European continent, but based on these relev{\´e}es and the known distribution area of Rubus nemoralis and Rubus polyanthemus, both characteristic for the Pruno-Rubion sprengelii, large parts of North England and Scotland have to be included in the distribution area of the alliance. The Pruno-Rubion sprengelii is optimally developed in rather narrow structures, like hedges, which are pruned every year. Here, brambles and herbs alike can grow with and under the shrubs, facilitated by the light that reaches large parts of the ground. Where the economic base of hedges perishes, they are not longer maintained, and the shrubs can grow out to their natural proportions. This changes the amount of light reaching the surface in the inner parts of the thicket, changing the competition between the species. The brambles as well as the herbs are displaced to the outer edges of the scrub, and the vegetation "dissociates" in a high-growing scrub, a fore-mantle ("cuff") with brambles, and a fringe with perennial herbs. These elements can hardly ever be assigned to the Pruno-Rubion anymore. The Pruno-Rubion sprengelii in optima forma is a scrub in which the three elements (shrubs, brambles, and herbs) grow closely intertwined. This is rarely found in natural landscapes, and thus the alliance is a typical element of the old farmer landscape. What is more: the typical species of the alliance, like Rubus nemoralis and R. polyanthemus, could only evolve after the landscape was opened by farmers in the last six millennia (Matzke-Hajek 1997), giving way to Rubus ulmifolius to expand its distribution area. This caused an explosion of hybrids which stabilised through apomixis into the wealth of Rubus species inhibiting the West European landscape nowadays (Sochor et al. 2015). Many of these species have their original home in a man-made landscape. Therefore, the Pruno-Rubion sprengelii can be characterised as a "farmers alliance" pur sang.},
  subject      = {Brombeere},
  language  = {en}
}
@article{Gottschlich2023,
  author    = {Gottschlich, G{\"u}nter},
  title     = {Hieracium rotundatum subsp. silvae-bavaricae, eine neue Hieracium-Sippe aus dem Bayerischen Wald (Deutschland)},
  series = {Forum Geobotanicum},
  volume    = {11},
  journal   = {Forum Geobotanicum},
  issn      = {1867-9315},
  doi       = {10.3264/FG.2023.0912},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327145},
  pages     = {8-14},
  year      = {2023},
  abstract  = {Hieracium rotundatum subsp. silvae-bavaricae is described as new for science and illustrated. The new subspecies belongs to a group of species (H. rotundatum, H. transylvanicum) whose main distribution is in the Balkans. The changeful nomenclatural history of the species name is described. Diagnostic features to distinguish the growth habit-similar species H. murorum, H. rotundatum and H. transylvanicum are discussed. Particular attention is drawn to the importance of the development of the basic leaf cycle. Contrary to previous knowledge, the northwestern distribution limit of H.rotundatum extends now to southeastern Bavaria. During the search for H. rotundatum a morphologically conspicuous subspecies of H. rotundatum could be detected, which is described here as new.},
  subject      = {Habichtskraut},
  language  = {de}
}
@article{JanzWalzCirnuetal.2024,
  author    = {Janz, Anna and Walz, Katharina and Cirnu, Alexandra and Surjanto, Jessica and Urlaub, Daniela and Leskien, Miriam and Kohlhaas, Michael and Nickel, Alexander and Brand, Theresa and Nose, Naoko and W{\"o}rsd{\"o}rfer, Philipp and Wagner, Nicole and Higuchi, Takahiro and Maack, Christoph and Dudek, Jan and Lorenz, Kristina and Klopocki, Eva and Erg{\"u}n, S{\"u}leyman and Duff, Henry J. and Gerull, Brenda},
  title     = {Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes},
  series = {Molecular Metabolism},
  volume    = {79},
  journal   = {Molecular Metabolism},
  issn      = {2212-8778},
  doi       = {10.1016/j.molmet.2023.101859},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350393},
  year      = {2024},
  abstract  = {Highlights • Loss of DNAJC19's DnaJ domain disrupts cardiac mitochondrial structure, leading to abnormal cristae formation in iPSC-CMs. • Impaired mitochondrial structures lead to an increased mitochondrial respiration, ROS and an elevated membrane potential. • Mutant iPSC-CMs show sarcomere dysfunction and a trend to more arrhythmias, resembling DCMA-associated cardiomyopathy. Background Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from truncating mutations in DNAJC19, which encodes an inner mitochondrial membrane protein. Clinical features include an early onset, often life-threatening, cardiomyopathy associated with other metabolic features. Here, we aim to understand the metabolic and pathophysiological mechanisms of mutant DNAJC19 for the development of cardiomyopathy. Methods We generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two affected siblings with DCMA and a gene-edited truncation variant (tv) of DNAJC19 which all lack the conserved DnaJ interaction domain. The mutant iPSC-CMs and their respective control cells were subjected to various analyses, including assessments of morphology, metabolic function, and physiological consequences such as Ca\(^{2+}\) kinetics, contractility, and arrhythmic potential. Validation of respiration analysis was done in a gene-edited HeLa cell line (DNAJC19tv\(_{HeLa}\)). Results Structural analyses revealed mitochondrial fragmentation and abnormal cristae formation associated with an overall reduced mitochondrial protein expression in mutant iPSC-CMs. Morphological alterations were associated with higher oxygen consumption rates (OCRs) in all three mutant iPSC-CMs, indicating higher electron transport chain activity to meet cellular ATP demands. Additionally, increased extracellular acidification rates suggested an increase in overall metabolic flux, while radioactive tracer uptake studies revealed decreased fatty acid uptake and utilization of glucose. Mutant iPSC-CMs also showed increased reactive oxygen species (ROS) and an elevated mitochondrial membrane potential. Increased mitochondrial respiration with pyruvate and malate as substrates was observed in mutant DNAJC19tv HeLa cells in addition to an upregulation of respiratory chain complexes, while cellular ATP-levels remain the same. Moreover, mitochondrial alterations were associated with increased beating frequencies, elevated diastolic Ca\(^{2+}\) concentrations, reduced sarcomere shortening and an increased beat-to-beat rate variability in mutant cell lines in response to β-adrenergic stimulation. Conclusions Loss of the DnaJ domain disturbs cardiac mitochondrial structure with abnormal cristae formation and leads to mitochondrial dysfunction, suggesting that DNAJC19 plays an essential role in mitochondrial morphogenesis and biogenesis. Moreover, increased mitochondrial respiration, altered substrate utilization, increased ROS production and abnormal Ca\(^{2+}\) kinetics provide insights into the pathogenesis of DCMA-related cardiomyopathy.},
  language  = {en}
}
@phdthesis{Rainer2024,
  author    = {Rainer, Johannes},
  title     = {Vaskulartoxische Wirkung von Taxanen bei fortgeschrittenen Tumorerkrankungen},
  doi       = {10.25972/OPUS-35072},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350722},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Taxane (wie Paclitaxel oder Cabazitaxel) sind bew{\"a}hrte Arzneimittel in den systemischen Therapieschemata vieler b{\"o}sartiger Erkrankungen, einschließlich Brust- und Eierstockkrebs. Sie f{\"o}rdern die Stabilisierung der Mikrotubuli, was zu einem Stillstand des Zellzyklus w{\"a}hrend der Mitose f{\"u}hrt, auf den die Apoptose folgt. Neben dieser antimitotischen Wirkung von Taxanen ist seit einiger Zeit auch eine gef{\"a}ßver{\"a}ndernde Wirkung von Taxanen bekannt. K{\"u}rzlich wurde gezeigt, dass Taxane tats{\"a}chlich St{\"o}rungen in der Gef{\"a}ßarchitektur verursachen, indem sie den Kalziumeinstrom {\"u}ber TRPC6, einen unselektiven Kationenkanal, ausl{\"o}sen. Der erh{\"o}hte intrazellul{\"a}re Ca2+-Spiegel bewirkt eine Rundung der Endothelzellen, was zu einer St{\"o}rung des endothelialen Monolayers, Serumausfluss und Gef{\"a}ßkollaps f{\"u}hrt. In dieser Arbeit konzentrierten wir uns auf die Gef{\"a}ßbetten von peripheren Organen wie dem Herzen oder der Niere in Abh{\"a}ngigkeit vom Tumorstadium und der Taxol-Behandlung. Die Organe wurden mit immunhistochemischen Techniken angef{\"a}rbt, um Ver{\"a}nderungen in der Architektur und Morphologie der Blutgef{\"a}ße zu untersuchen. Wir fanden Ver{\"a}nderungen in der Morphologie der Kapillaren des Herzens und dar{\"u}ber hinaus Ver{\"a}nderungen in der Expression endothelialer Antigene in Abh{\"a}ngigkeit vom Tumorstadium, insbesondere eine zunehmende endotheliale Expression von TRPC6 in Abh{\"a}ngigkeit vom Tumorstadium. Diese Ergebnisse liefern neue Erkenntnisse f{\"u}r das Verst{\"a}ndnis der systemischen Auswirkungen maligner Erkrankungen und tragen dazu bei, Folgeerkrankungen bei Patienten mit fortgeschrittenem Krebs zu verhindern.},
  subject      = {Taxane},
  language  = {de}
}
@phdthesis{Funke2024,
  author    = {Funke, Caroline},
  title     = {Untersuchung des Tumorgef{\"a}ßbildes an murinen Tumormodellen unter antiangiogener Therapie mit Axitinib und mG6-31},
  doi       = {10.25972/OPUS-36982},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369820},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die Tumorangiogenese ist ein Prozess, der zur Ausbildung eines tumoreigenen Gef{\"a}ßnetzwerks f{\"u}hrt und kritisch ist f{\"u}r die Progression des Tumorwachstums, sowie f{\"u}r dessen Malignisierung und Metastasierung. Zytokine wie VEGF und PDGF steuern angiogene Prozesse. Die resultierende Tumorvaskulatur ist jedoch dysfunktional und unterscheidet sich in Struktur und Funktion stark von normalen Gef{\"a}ßen. Die antiangiogene Therapie richtet sich gegen die Tumorvaskulatur indem Angiogenese-induzierende Signalwege inhibiert werden. Es existieren zahlreiche therapeutische Ans{\"a}tze, zu denen u.a. Anti-VEGF- Antik{\"o}rper und Rezeptortyrosinkinaseinhibitoren z{\"a}hlen. Ziel der antiangiogenen Therapie ist es, die Ausbildung neuer Blutgef{\"a}ße im Tumor zu stoppen sowie existierende unreife Blutgef{\"a}ße zu zerst{\"o}ren. Das Konzept der Gef{\"a}ßnormalisierung beschreibt im Rahmen der antiangiogenen Therapie Prozesse, die zu einer transienten Verbesserung dieser defekten Tumorvaskulatur und zu ihrer tendenziellen Angleichung an Struktur und Funktion von normalen Gef{\"a}ßen f{\"u}hren sollen. In dieser Studie wurden Ver{\"a}nderungen von Gef{\"a}ßparametern in murinen AT3- Mammakarzinomen und murinen Lewis-lung-Karzinomen miteinander verglichen, die entweder (a) mit mG6-31, einem monoklonalen Anti-VEGF- Antik{\"o}rper, (b) mit Axitinib, einem niedermolekularen VEGF-R-/PDGF-R- Tyrosinkinaseinhibitor antiangiogen behandelt oder (c) nicht behandelt wurden. Ziel war es dabei, Aussagen {\"u}ber die antiangiogene Wirksamkeit sowie die Gef{\"a}ß- normalisierende Effektivit{\"a}t der o.g. Antiangiogenetika zu treffen. In einer bereits abgeschlossenen Forschungsarbeit von Ascheid (vgl. Absatz 7.2) wurden mit dem gleichen Experimentalaufbau wie zuvor beschrieben ebenfalls murine Tumoren hinsichtlich makroskopischer Gef{\"a}ßstruktur und -organisation untersucht. Dabei wurde aufgezeigt, dass Gef{\"a}ß-normalisierende Prozesse durch o.g. Angiogenetika in geringem Umfang stattfanden. Die durchgef{\"u}hrte Studie zielte darauf ab, die bereits erfassten Resultate zu komplettieren und somit eine abschließende Aussage {\"u}ber das Auftreten von Gef{\"a}ßnormalisierung zu erm{\"o}glichen. 88 In den mG6-31-/Axitinib-/unbehandelten AT3-/LLC-Tumorschnitten wurden die Parameter Gef{\"a}ßdichte, Apoptoserate, Proliferationsrate, Perizytenbesatz, Intaktheit der vaskul{\"a}ren Basalmembran und endotheliale Expression von TRPC6-Kan{\"a}len immunhistochemisch bzw. mittels Immunfluoreszenz detektiert, mikroskopisch aufgenommen und quantifiziert. Diese Arbeit zeigt, dass Axitinib deutliche antiangiogene Effekte in der Tumorvaskulatur hervorruft, mG6-31 hingegen wirkt schw{\"a}cher antiangiogen. Im Unterschied zu den Ergebnissen aus Ascheids Arbeit (Ascheid, 2018) konnten- Effekte auf der Ebene der individuellen Blutgef{\"a}ße nachgewiesen werden, die in der Literatur als Anzeichen f{\"u}r eine Gef{\"a}ßnormalisierung beschrieben werden. Wiederum waren diese Effekte unter Axitinib st{\"a}rker ausgepr{\"a}gt als unter mG6- 31-Behandlung. Die Resultate beider Forschungsarbeiten zusammengefasst betrachtet, kann man feststellen, dass die Zusammenfassung der gef{\"a}ßver{\"a}ndernden Effekte, die antiangiogene Wirkstoffe hervorrufen, unter dem Begriff „Normalisierung" in Frage gestellt werden sollte.},
  subject      = {Antiangiogenese},
  language  = {de}
}
@phdthesis{Schuhmair2024,
  author    = {Schuhmair, Leah Sophia},
  title     = {Etablierung eines in-situ-Immunfluoreszenzf{\"a}rbeverfahrens zur dreidimensionalen Darstellung und Quantifizierung der Immunzellinfiltration in experimentellen Tumoren},
  doi       = {10.25972/OPUS-37094},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370945},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Brustkrebs ist die h{\"a}ufigste diagnostizierte Krebserkrankung weltweit. Trotz der vielf{\"a}ltigen Behandlungsm{\"o}glichkeiten endet die Diagnose Brustkrebs in vielen F{\"a}llen noch immer t{\"o}dlich. Aus diesem Grund ist die Entwicklung neuer Therapieans{\"a}tze wichtig. Ein Therapieansatz, der in den letzten zehn Jahren immer mehr an Bedeutung gewonnen hat, ist die Immuntherapie. Allerdings konnte sie bei Brustkrebs noch keine großen Erfolge erzielen. Ursache hierf{\"u}r ist die geringe Immunzellinfiltration in Brusttumoren. Um Brustkrebs f{\"u}r Immuntherapie empf{\"a}nglicher zu machen, m{\"u}ssten Immuntherapeutika in Kombination mit Medikamenten angewendet werden, die die Immunzellinfiltration steigern. Um die Wirksamkeit solcher Medikamente in pr{\"a}klinischen Studien zu testen, braucht es eine Methode, mit der man die T-Zellverteilung innerhalb des Tumors darstellen kann. F{\"u}r umfassendes Verst{\"a}ndnis ist dreidimensionale Darstellung der Zellen im Tumor notwendig, da es einen großen Unterschied macht, ob sich die T-Zellen im Tumorstroma oder in unmittelbarer N{\"a}he zu den Tumorzellen befinden. Die starke Fibrotisierung der Extrazellul{\"a}ren Matrix, die typisch f{\"u}r Brusttumoren ist, erschwert nicht nur die Immunzellinfiltration, sondern auch die Diffusion der fluoreszierenden Antik{\"o}rper ins Gewebe. Im Zuge dieser Arbeit wurde eine Methode entwickelt, um im dreidimensionalen CD4 und CD8-positive T-Zellen in Brusttumoren darzustellen. Dies gelang mittels Immunfluoreszenzf{\"a}rbung und anschließender dreidimensionaler Aufnahme mithilfe optischer Sektionierung am Lichtblattmikroskop. Erreicht wurde dies durch deutliche Erh{\"o}hung der Inkubationszeiten, aggressive Permeabilisierung des Gewebes, Testen unterschiedlicher Antik{\"o}rper bzw. Antik{\"o}rperkombinationen und Entf{\"a}rbung sowie Kl{\"a}rung des Tumorgewebes. Dar{\"u}ber hinaus konnten erste Schritte in der nachtr{\"a}glichen Bearbeitung der Aufnahmen inklusive Rekonstruktion der Zellen gemacht werden. F{\"u}r die Anwendung des Verfahrens in Studien zur Medikamentenwirksamkeit ist noch weitere Optimierung notwendig.},
  subject      = {Immunfluoreszenz},
  language  = {de}
}