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JLUpub ist das institutionelle Repositorium der Justus-Liebig-Universität.
JLUpub bietet Mitgliedern und Angehörigen der Universität die Möglichkeit neben wissenschaftlichen Dokumenten auch Forschungsdaten elektronisch zu veröffentlichen und dauerhaft zugänglich zu machen. Alle Veröffentlichungen erhalten einen Digital Object Identifier (DOI) und werden über nationale und internationale Bibliothekskataloge sowie Suchmaschinen nachgewiesen und auffindbar.
Neue Veröffentlichungen:
Prognostic value of metabolic tumor volume on [18F]FDG PET/CT in addition to the TNM classification system of locally advanced non-small cell lung cancer
(2024) Brose, Alexander; Miederer, Isabelle; König, Jochem; Gkika, Eleni; Sahlmann, Jörg; Schimek-Jasch, Tanja; Schreckenberger, Mathias; Nestle, Ursula; Kappes, Jutta; Miederer, Matthias
Purpose: Staging of non-small cell lung cancer (NSCLC) is commonly based on [18F]FDG PET/CT, in particular to exclude distant metastases and guide local therapy approaches like resection and radiotherapy. Although it is hoped that PET/CT will increase the value of primary staging compared to conventional imaging, it is generally limited to the characterization of TNM. The first aim of this study was to evaluate the PET parameter metabolic tumor volume (MTV) above liver background uptake as a prognostic marker in lung cancer. The second aim was to investigate the possibility of incorporating MTV into the TNM classification system for disease prognosis in locally advanced NSCLC treated with chemoradiotherapy.
Methods: Retrospective evaluation of 235 patients with histologically proven, locally advanced NSCLC from the multi-centre randomized clinical PETPLAN trial and a clinical cohort from a hospital registry. The PET parameters SUVmax, SULpeak, MTV and TLG above liver background uptake were determined. Kaplan-Meier curves and stratified Cox proportional hazard regression models were used to investigate the prognostic value of PET parameters and TNM along with clinical variables. Subgroup analyses were performed to compare hazard ratios according to TNM, MTV, and the two variables combined.
Results: In the multivariable Cox regression analysis, MTV was associated with significantly worse overall survival independent of stage and other prognostic variables. In locally advanced disease stages treated with chemoradiotherapy, higher MTV was significantly associated with worse survival (median 17 vs. 32 months). Using simple cut-off values (45 ml for stage IIIa, 48 ml for stage IIIb, and 105 ml for stage IIIc), MTV was able to further predict differences in survival for stages IIIa-c. The combination of TNM and MTV staging system showed better discrimination for overall survival in locally advanced disease stages, compared to TNM alone.
Conclusion: Higher metabolic tumor volume is significantly associated with worse overall survival and combined with TNM staging, it provides more precise information about the disease prognosis in locally advanced NSCLC treated with chemoradiotherapy compared to TNM alone. As a PET parameter with volumetric information, MTV represents a useful addition to TNM.
Protocol and research program of the European registry and biobank for interstitial lung diseases (eurILDreg)
(2024) Krauss, Ekaterina; Tello, Silke; Naumann, Jennifer; Wobisch, Sandra; Ruppert, Clemens; Kuhn, Stefan; Mahavadi, Poornima; Majeed, Raphael W.; Bonniaud, Philippe; Molina-Molina, Maria; Wells, Athol; Hirani, Nik; Vancheri, Carlo; Walsh, Simon; Griese, Matthias; Crestani, Bruno; Guenther, Andreas; Borie, Raphael; Kannengiesser, Caroline; Poletti, Venerino; Behr, Juergen; Drakopanagiotakis, Fotios; Bastos, Helder; Ravaglia, Claudia; Hurley, Killian; Eils, Roland; Gut, Ivo; Haick, Hossam; Broza, Yoav Y.
Background and Aims: Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis.
Methods: The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen.
Discussion: The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices.
Physiological phenotyping of transpiration response to vapour pressure deficit in wheat
(2024) Moritz, Anna; Eckert, Andreas; Vukasovic, Stjepan; Snowdon, Rod; Stahl, Andreas
Background: Precision phenotyping of short-term transpiration response to environmental conditions and transpiration patterns throughout wheat development enables a better understanding of specific trait compositions that lead to improved transpiration efficiency. Transpiration and related traits were evaluated in a set of 79 winter wheat lines using the custom-built “DroughtSpotter XXL” facility. The 120 l plant growth containers implemented in this phenotyping platform enable gravimetric quantification of water use in real-time under semi-controlled, yet field-like conditions across the entire crop life cycle.
Results: The resulting high-resolution data enabled identification of significant developmental stage-specific variation for genotype rankings in transpiration efficiency. In addition, for all examined genotypes we identified the genotype-specific breakpoint in transpiration in response to increasing vapour pressure deficit, with breakpoints ranging between 2.75 and 4.1 kPa.
Conclusion: Continuous monitoring of transpiration efficiency and diurnal transpiration patterns enables identification of hidden, heritable genotypic variation for transpiration traits relevant for wheat under drought stress. Since the unique experimental setup mimics field-like growth conditions, the results of this study have good transferability to field conditions.
Assessing the potential of nature-based solutions as sustainable land and water management strategies in the high tropical Andean páramo ecosystem
(2024) Fonseca, Kalina; Acero Triana, Juan S.; Ramírez, Miguel; Martínez, William; Ilbay, Mercy; Espitia-Sarmiento, Edgar; Breuer, Lutz
Nature-based solutions (NbS) are gaining attention as viable strategies for restoring water-rich ecosystems such as the páramo. However, the lack of evidence on their effectiveness, coupled with a limited understanding of their political, economic, social, technological, environmental, and legal (PESTEL) context, hinders their widespread adoption. To address this gap, we propose a multi-method framework that (i) captures PESTEL factors influencing the implementation of passive ecological restoration in páramo ecosystems as a measure of NbS and (ii) assesses its associated environmental impacts. Our approach integrates a scoping review with remote sensing techniques, water quality assessment, and correlation analyses. Focusing on the Upper Pita and Upper Cutuchi River Basins-key water sources for Andean communities in Ecuador, we reveal that the deterioration of their páramo ecosystems in the 20th century was mainly due to camelid grazing and pine timber production. In response to these threats, bottom-up management efforts starting in 1999, guided by various PESTEL factors, promoted policies, regulations, social agreements, and financial support for achieving passive ecological restoration between 2010 and 2017 in the Upper Pita River Basin. As a result, the conservation of 73.4% of natural páramo with excellent water quality in 2022. By contrast, top-down management in the Upper Cutuchi River Basin was ineffective because national strategies failed to tackle the local environmental challenges posed by the PESTEL factors. Hence, only 31.6% of the natural páramo remained with poor water quality by 2022. Our study is the first to demonstrate that passive ecological restoration benefits these ecosystems, while its absence results in significant changes that require additional restoration strategies.
Relevance of charged and polar amino acids for functionality of membrane toxin TisB
(2024) Leinberger, Florian H.; Berghoff, Bork A.
Bacterial dormancy is marked by reduced cellular activity and the suspension of growth. It represents a valuable strategy to survive stressful conditions, as exemplified by the long-term tolerance towards antibiotics that is attributable to a fraction of dormant cells, so-called persisters. Here, we investigate the membrane toxin TisB (29 amino acids) from the chromosomal toxin-antitoxin system tisB/istR-1 in Escherichia coli. TisB depolarizes the inner membrane in response to DNA damage, which eventually promotes a stress-tolerant state of dormancy within a small fraction of the population. Using a plasmid-based system for moderate tisB expression and single amino acid substitutions, we dissect the importance of charged and polar amino acids. We observe that the central amino acids lysine 12 and glutamine 19 are of major importance for TisB functionality, which is further validated for lysine 12 in the native context upon treatment with the DNA-damaging antibiotic ciprofloxacin. Finally, we apply a library-based approach to test additional TisB variants in higher throughput, revealing that at least one positive charge at the C-terminus (either lysine 26 or 29) is mandatory for TisB-mediated dormancy. Our study provides insights into the molecular basis for TisB functionality and extends our understanding of bacterial membrane toxins.