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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Bioengineering and Biotechnology Vol. 8 ( 2020-12-3)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 8 ( 2020-12-3)
    Abstract: Cell-derived extracellular matrices (CD-ECMs) captured increasing attention since the first studies in the 1980s. The biological resemblance of CD-ECMs to their in vivo counterparts and natural complexity provide them with a prevailing bioactivity. CD-ECMs offer the opportunity to produce microenvironments with costumizable biological and biophysical properties in a controlled setting. As a result, CD-ECMs can improve cellular functions such as stemness or be employed as a platform to study cellular niches in health and disease. Either on their own or integrated with other materials, CD-ECMs can also be utilized as biomaterials to engineer tissues de novo or facilitate endogenous healing and regeneration. This review provides a brief overview over the methodologies used to facilitate CD-ECM deposition and manufacturing. It explores the versatile uses of CD-ECM in fundamental research and therapeutic approaches, while highlighting innovative strategies. Furthermore, current challenges are identified and it is accentuated that advancements in methodologies, as well as innovative interdisciplinary approaches are needed to take CD-ECM-based research to the next level.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2719493-0
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Neurology Vol. 14 ( 2023-3-2)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-3-2)
    Abstract: The endothelin receptor antagonist (ERA) clazosentan is being investigated for the medical prevention of cerebral vasospasm and associated complications, such as delayed cerebral ischemia (DCI), after aneurysmal subarachnoid hemorrhage (aSAH). This study quantified how clinicians weigh the benefits and risks of ERAs for DCI prevention to better understand their treatment needs and expectations. Methods An online choice experiment was conducted to elicit preferences of neurologists, intensivists, and neurosurgeons treating aSAH in the US and UK for the use of ERAs. The design of the choice experiment was informed by a feasibility assessment ( N = 100), one-on-one interviews with clinicians ( N = 10), a qualitative pilot ( N = 13), and a quantitative pilot ( N = 50). Selected treatment attributes included in the choice experiment were: one benefit (likelihood of DCI); and three risks (lung complications, hypotension, and anemia). In the choice experiment, clinicians repeatedly chose best and worst treatment options based on a scenario of a patient being treated in the ICU after aneurism repair. A correlated mixed logit model determined the relative attribute importance (RAI) and associated highest density interval (HDI) as well as acceptable benefit-risk trade-offs. Results The final choice experiment was completed by 350 clinicians (116 neurologists, 129 intensivists/intensive care clinicians, and 105 neurosurgeons; mean age, 47.4 years). Reducing the likelihood of DCI (RAI = 56.5% [HDI, 53.6–59.5%]) had the largest impact on clinicians' treatment choices, followed by avoiding the risks of lung complications (RAI = 29.6% [HDI, 27.1–32.3%] ), hypotension (RAI = 9.2% [HDI, 7.5–10.8%]), and anemia (RAI = 4.7% [HDI, 3.7–5.8%] ). Clinicians expected the likelihood of DCI to decrease by ≥8.1% for a 20% increase in the risk of lung complications, ≥2.4% for a 20% increase in the risk of hypotension, and ≥1.2% for a 20% increase in the risk of anemia. Conclusions Clinicians were willing to accept certain increased risks of adverse events for a reduced risk of DCI after aSAH. The likelihood of DCI occurring after aSAH can therefore be considered a clinically relevant endpoint in aSAH treatment development. Thus, evaluations of ERAs might focus on whether improvements (i.e., reductions) in the likelihood of DCI justify the risks of adverse events.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2016
    In:  Frontiers in Plant Science Vol. 7 ( 2016-06-07)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 7 ( 2016-06-07)
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2016
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 4
    In: Frontiers in Physics, Frontiers Media SA, Vol. 12 ( 2024-4-4)
    Abstract: Aim: High-sensitivity hybrid positron emission tomography (PET) imaging using advanced whole-body (WB) or total-body PET/computed tomography (CT) systems permits reducing injected tracer activity while preserving diagnostic quality. Such approaches are promising for healthy control studies or exploring inter-organ communication in systemic diseases. This study assessed test/retest variations in the fluoro-2-deoxy-D-glucose (FDG) uptake in key organs from low-dose (LD) and standard-dose (STD) [18F]FDG-PET/CT imaging protocols in healthy controls and lung cancer patients. Methods: A total of 19 healthy controls (19–62 years, 46–104 kg, 10 M/9 F) and 7 lung cancer patients (47–77 years, 50–88 kg, 4 M/3 F) underwent [18F]FDG-PET/CT imaging. All subjects were first injected (“test,” LD) with 28 ± 2 MBq FDG and underwent a dynamic (0–67 min post-injection) WB imaging protocol with LD-CT. Then, 90 min post-LD injection, the subjects were repositioned and injected with 275 ± 16 MBq FDG (“retest,” STD). Second LD-CT and STD-CT scans were acquired for healthy controls and patients, respectively. Static images (55–67 min post-injection) were considered for subsequent analysis. The CT images were used to automatically segment the target volumes of interest. Standardized uptake values normalized to the body weight (SUV BW ) were extracted for each volume of interest. The mean SUV BW were compared for both LD/STD conditions with paired t-tests. In patients, FDG-avid lesions were manually delineated on LD and STD static images. Effective dose levels were estimated from both the CT and PET acquisitions. Results: Organ-based mean SUV BW were similar between the LD and STD (mean %difference ≤5%) in both healthy controls and cancer patients, except in the heart. Intra-control test/retest variability was significant in the brain, heart, and skeletal muscle ( p & lt; 0.05). While 17 lesions were delineated on the STD images of the patients, only 10/17 lesions were identified on the LD images due to increased image noise. Lesion-based mean SUV BW were similar between LD and STD acquisitions ( p = 0.49, %difference = 10%). In patients, the effective doses were (1.9 ± 0.2) mSv (LD-CT), (16.6 ± 5.4) mSv (STD-CT), (0.5 ± 0.1) mSv (LD-PET), and (4.6 ± 0.3) mSv (STD-PET). Conclusion: LD and STD [18F]FDG injections in healthy controls and lung cancer patients yielded comparable mean SUV BW , except in the heart. Dose levels may be reduced for [18F]FDG-PET imaging without a loss in mean SUV BW accuracy, promoting LD-PET/CT protocols for studying multi-organ metabolic patterns. In oncology patients, this approach may be hindered by a lower diagnostic quality in the presence of significant noise.
    Type of Medium: Online Resource
    ISSN: 2296-424X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2721033-9
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  • 5
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-7-18)
    Abstract: Recent improvements in microbiology and molecular epidemiology were largely stimulated by whole- genome sequencing (WGS), which provides an unprecedented resolution in discriminating highly related genetic backgrounds. WGS is becoming the method of choice in epidemiology of fungal diseases, but its application is still in a pioneer stage, mainly due to the limited number of available genomes. Fungal pathogens often belong to complexes composed of numerous cryptic species. Detecting cryptic diversity is fundamental to understand the dynamics and the evolutionary relationships underlying disease outbreaks. In this study, we explore the value of whole-genome SNP analyses in identification of the pandemic pathogen Fusarium graminearum sensu stricto ( F.g .). This species is responsible for cereal diseases and negatively impacts grain production worldwide. The fungus belongs to the monophyletic fungal complex referred to as F. graminearum species complex including at least sixteen cryptic species, a few among them may be involved in cereal diseases in certain agricultural areas. We analyzed WGS data from a collection of 99 F.g. strains and 33 strains representing all known cryptic species belonging to the FGSC complex. As a first step, we performed a phylogenomic analysis to reveal species-specific clustering. A RAxML maximum likelihood tree grouped all analyzed strains of F.g. into a single clade, supporting the clustering-based identification approach. Although, phylogenetic reconstructions are essential in detecting cryptic species, a phylogenomic tree does not fulfill the criteria for rapid and cost-effective approach for identification of fungi, due to the time-consuming nature of the analysis. As an alternative, analysis of WGS information by mapping sequence data from individual strains against reference genomes may provide useful markers for the rapid identification of fungi. We provide a robust framework for typing F.g. through the web-based PhaME workflow available at EDGE bioinformatics. The method was validated through multiple comparisons of assembly genomes to F.g. reference strain PH-1. We showed that the difference between intra- and interspecies variability was at least two times higher than intraspecific variation facilitating successful typing of F.g . This is the first study which employs WGS data for typing plant pathogenic fusaria.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 6
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 11 ( 2020-5-25)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587354-4
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  • 7
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2023-1-5)
    Abstract: The main management strategy of heart failure with preserved ejection fraction (HFpEF) is prevention since HFpEF is associated with many cardiovascular (CV) risk factors, especially since HFpEF is linked to a high risk for both mortality and recurrent heart failure (HF) hospitalizations. Therefore, there is a need for new tools to identify patients with a high risk profile early. Regional strain assessment by CMR seems to be superior in describing deformation impairment in HF. The MyoHealth score is a promising tool to identify cardiac changes early. Methods and results Heart failure patients irrespective of LVEF and asymptomatic controls were recruited, and CMR based measures were obtained. For this analysis the asymptomatic control group ( n = 19) was divided into asymptomatic subjects without CV co-morbidities or evidence of cardiac abnormalities and ( n = 12) and asymptomatic subjects with CV co-morbidities or evidence of cardiac abnormalities ( n = 7) as well as patients with HFpEF ( n = 19). We performed CMR scans at rest and during a stress test using isometric handgrip exercise (HG). Assessing the MyoHealth score at rest revealed preserved regional strain in 85 ± 9% of LV segments in controls, 73 ± 11% in at Risk subjects and 73 ± 8% in HFpEF patients. During stress the MyoHealth score was 84 ± 7% in controls, 83 ± 7 in at risk subjects and 74 ± 11 in HFpEF patients. Conclusion In summary, we show for the first time that asymptomatic subjects with increased CV risk present with HFpEF like impaired myocardial deformation at rest, while they show results like controls under HG stress. The potential of preventive treatment in this group of patients merits further investigation in future. Clinical trial registration [ https://drks.de/search/de/trial/DRKS00015615 ], identifier [DRKS00015615] .
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Cardiovascular Medicine Vol. 10 ( 2023-2-9)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 10 ( 2023-2-9)
    Abstract: Heart failure (HF) does not only reduce the life expectancy in patients, but their life is also often limited by HF symptoms leading to a reduced quality of life (QoL) and a diminished exercise capacity. Novel parameters in cardiac imaging, including both global and regional myocardial strain imaging, promise to contribute to better patient characterization and ultimately to better patient management. However, many of these methods are not part of clinical routine yet, their associations with clinical parameters have been poorly studied. An imaging parameters that also indicate the clinical symptom burden of HF patients would make cardiac imaging more robust toward incomplete clinical information and support the clinical decision process. Methods and results This prospective study conducted at two centers in Germany between 2017 and 2018 enrolled stable outpatient subjects with HF [ n = 56, including HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] and a control cohort ( n = 19). Parameters assessed included measures for external myocardial function, for example, cardiac index and myocardial deformation measurements by cardiovascular magnetic resonance imaging, left ventricular global longitudinal strain (GLS), the global circumferential strain (GCS), and the regional distribution of segment deformation within the LV myocardium, as well as basic phenotypical characteristics including the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the 6-minute walk test (6MWT). If less than 80% of the LV segments are preserved in their deformation capacity the functional capacity by 6MWT (6 minutes walking distance: MyoHealth ≥ 80%: 579.8 ± 177.6 m; MyoHealth 60– & lt;80%: 401.3 ± 121.7 m; MyoHealth 40– & lt;60%: 456.4 ± 68.9 m; MyoHealth & lt; 40%: 397.6 ± 125.9 m, overall p -value: 0.03) as well as the symptom burden are significantly impaired (NYHA class: MyoHealth ≥ 80%: 0.6 ± 1.1 m; MyoHealth 60– & lt;80%: 1.7 ± 1.2 m; MyoHealth 40– & lt;60%: 1.8 ± 0.7 m; MyoHealth & lt; 40%: 2.4 ± 0.5 m; overall p -value & lt; 0.01). Differences were also observed in the perceived exertion assessed by on the Borg scale (MyoHealth ≥ 80%: 8.2 ± 2.3 m; MyoHealth 60– & lt;80%: 10.4 ± 3.2 m; MyoHealth 40– & lt;60%: 9.8 ± 2.1 m; MyoHealth & lt; 40%: 11.0 ± 2.9 m; overall p -value: 0.20) as well as quality of life measures (MLHFQ; MyoHealth ≥ 80%: 7.5 ± 12.4 m; MyoHealth 60– & lt;80%: 23.4 ± 23.4 m; MyoHealth 40– & lt;60%: 20.5 ± 21.2 m; MyoHealth & lt; 40%: 27.4 ± 24.4 m; overall p -value: 0.15)–while these differences were not significant. Conclusion The share of LV segments with preserved myocardial contraction promises to discriminate between symptomatic and asymptomatic subjects based on the imaging findings, even when the LV ejection fraction is preserved. This finding is promising to make imaging studies more robust toward incomplete clinical information.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 9
    In: Frontiers in Physics, Frontiers Media SA, Vol. 10 ( 2022-10-28)
    Abstract: Aim/Introduction: Patient head motion poses a significant challenge when performing dynamic PET brain studies. In response, we developed a fast, robust, easily implementable and tracer-independent brain motion correction technique that facilitates accurate alignment of dynamic PET images. Materials and methods: Correction of head motion was performed using motion vectors derived by the application of Gaussian scale-space theory. A multiscale pyramid consisting of three different resolution levels (1/4x: coarse, 1/2x: medium, and 1x: fine) was applied to all image frames (37 frames, framing of 12 × 10s, 15 × 30s, 10 × 300s) of the dynamic PET sequence. Frame image alignment was initially performed at the coarse scale, which was subsequently used to initialise coregistration at the next finer scale, a process repeated until the finest possible scale, that is, the original resolution was reached. In addition, as tracer distribution changes during the dynamic frame sequence, a mutual information (MI) score was used to identify the starting frame for motion correction that is characterised by a sufficiently similar tracer distribution with the reference (last) frame. Validation of the approach was performed based on a simulated F18-fluoro-deoxy-glucose (FDG) dynamic sequence synthesised from the digital Zubal phantom. Inter-frame motion was added to each dynamic frame (except the reference frame). Total brain voxel displacement based on the added motion was constrained to 25 mm, which included both translation (0–15 mm in x, y and z) and rotation (0–0.3 rad for each Euler angle). Twenty repetitions were performed for each dataset with arbitrarily simulated motion, resulting in 20 synthetic datasets, each consisting of 36 dynamic frames (frame 37 was the reference frame). Assessment of motion correction accuracy across the dynamic sequence was performed based on the uncorrected/residual displacement remaining after the application of our algorithm. To investigate the clinical utility of the developed algorithm, three clinically cases that underwent list-mode PET imaging utilising different tracers ([18F] -fluoro-deoxy-glucose [18F]FDG [18F] -fluoroethyl- l -tyrosine [18F]FET [11C] -alpha-methyl-tryptophan [11C]AMT), each characterised by a different temporal tracer distribution were included in this study. Improvements in the Dice score coefficient (DSC) following frame alignment were evaluated as the correlation significance between the identified displacement for each frame of the clinical FDG, FET and AMT dynamic sequences. Results: Sub-millimetre accuracy (0.4 ± 0.2 mm) was achieved in the Zubal phantom for all frames after 5 min p. i., with early frames (30 s–180 s) displaying a higher residual displacement of ∼3 mm (3.2 ± 0.6 mm) due to differences in tracer distribution relative to the reference frame. The effect of these differences was also seen in MI scores; the MI plateau phase was reached at 35s p. i., 2.0 and 2.5 min p. i. At the coarse, medium and fine resolution levels, respectively. For the clinical images, a significant correlation between the identified (and corrected) displacement and the improvement in DSC score was seen in all dynamic studies (FET: R = 0.49, p & lt; 0.001; FDG: R = 0.82, p & lt; 0.001; AMT: R = 0.92, p & lt; 0.001). Conclusion: The developed motion correction method is insensitive to any specific tracer distribution pattern, thus enabling improved correction of motion artefacts in a variety of clinical applications of extended PET imaging of the brain without the need for fiducial markers.
    Type of Medium: Online Resource
    ISSN: 2296-424X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2721033-9
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  • 10
    In: Frontiers in Physics, Frontiers Media SA, Vol. 7 ( 2019-9-24)
    Type of Medium: Online Resource
    ISSN: 2296-424X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2721033-9
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