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Abstract Background Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. Results We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Conclusion Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

Background: Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. Results: We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Conclusion: Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases. [ABSTRACT FROM AUTHOR]

Background: According to data from the USA, the incidence of incidentally discovered pulmonary nodules is 5.8 per 1000 person-years for women and 5.2 per 1000 person-years for men. Their management as recommended in the pertinent guidelines can substantially improve clinical outcomes. More than 95% of all pulmonary nodules revealed by computed tomography (CT) are benign, but many cases are not managed in conformity with the guidelines. In this article, we summarize the appropriate clinical approach and provide an overview of the pertinent diagnostic studies and when they should be performed., Methods: This review is based on relevant publications retrieved by a selective search in PubMed. The authors examined English-language recommendations issued since 2010 for the management of pulmonary nodules, supplemented by comments from the German lung cancer guideline., Results: In general, the risk that an incidentally discovered pulmonary nodule is malignant is low but rises markedly with increasing size and the presence of risk factors. When such a nodule is detected, the further recommendation, depending on size, is either for follow-up examinations with chest CT or else for an extended evaluation with positron emission tomography-CT and biopsy for histology. The diagnostic evaluation should include consideration of any earlier imaging studies that may be available as an indication of possible growth over time. Single nodules measuring less than 6 mm, in patients with few or no risk factors, do not require any follow-up. Lung cancer is diagnosed in just under 10% of patients with a nodule measuring more than 8 mm., Conclusion: The recommendations of the guidelines for the management of incidentally discovered pulmonary nodules are intended to prevent both over- and undertreatment. If a tumor is suspected, further care should be provided by an interdisciplinary team.

PET using 68 Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, 18 F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently 18 F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic 68 Ga-FAPI-46 PET in the 18 F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Methods: Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic 68 Ga-FAPI-46 PET in addition to 18 F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUV max , SUV mean , and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters ( 68 Ga-FAPI-46 in relation to 18 F-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, k 1 , k 2 , k 3 , and k 4 ) were extracted from dynamic 68 Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. Results: FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated 68 Ga-FAPI-46 uptake, higher TBRs, and higher 68 Ga-FAPI-46-to- 18 F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative 68 Ga-FAPI-46-to- 18 F-FDG ratios regarding SUV max and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Conclusion: 68 Ga-FAPI-46 PET is a powerful new tool for the assessment of single 18 F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)