Tissue sampling of biliary tract carcinomas (BTCs) for molecular characterization is challenging. The aim of this study was to investigate the possibility of identifying individual actionable mutations derived from bile cell-free DNA (cfDNA) using targeted deep sequencing. Ten BTC patients, four with gallbladder carcinomas and six with cholangiocarcinomas, were enrolled in the present study. Using targeted deep sequencing with a panel of 150 tumor-related genes, paired bile cfDNA and tumor DNA were analyzed for mutational variants individually and then compared. The present study, to the best of our knowledge, is the first to reveal that bile cfDNA is predominantly comprised of long DNA fragments, which is not the case for plasma cfDNA. Herein, paired bile cfDNA and tumors from ten BTC patients were examined using targeted deep sequencing. When comparing bile cfDNA and tumor DNA for single nucleotide variation (SNV)/insertion and deletion (Indel), the results using targeted deep sequencing revealed high sensitivity (94.7%) and specificity (99.9%). Additionally, the sensitivity of detecting a copy number variation (CNV) was 75.0%, with a specificity of 98.9%. When comparing two bile extraction methods, including percutaneous transhepatic cholangial drainage and operation, no significant difference in SNV/Indel or CNV detection sensitivity was noted. Moreover, when examining the tumor stage and incidence site, AJCC stage II and the distal bile duct both had significantly decreased CNV detection sensitivities. The present study revealed that targeted deep sequencing can reliably detect mutational variants within bile cfDNA obtained from BTC patients. These preliminary results may shed light on bile cfDNA as a promising liquid biopsy for BTC patients.
This study was approved by the Washington University Human Protection Office (#201810227).Purpose: Left ventricular assist devices (LVAD) are an alternative treatment for patients with heart failure. The purposes of this study were to describe patients immediately post-LVAD surgery, determine differences between functional outcome measures and discharge location, and the potential for initial Functional Status Score of the Intensive Care Unit (FSS-ICU) to assist in discharge recommendations. Methods: A retrospective study (n 5 100) was conducted with the following data obtained: general demographics, FSS-ICU, ICU Mobility Scale (IMS), maximal ambulation distance, and discharge location. Patients were divided into 2 groups based on discharge location (home vs facility). Results: The mean age was 52.8 years, with 64% male. A significant improvement in all functional outcomes was observed from evaluation to discharge. Patients discharged home (76%) exhibited significantly higher FSS-ICU and IMS scores and tolerated out-of-bed activity and ambulation earlier. A score of 14 or higher on the initial FSS-ICU was predictive for discharge to home recommendation. Conclusion: Patients post-LVAD implantation exhibited low levels of functional mobility initially, yet were able to tolerate early activity. Patients discharged home had higher functional scores during the initial evaluation. Using the results of the FSS-ICU may assist in discharge recommendations; further research is needed.
A knowledge of the adsorption and desorption behavior of sorbates on surface adsorptive site (SAS) is the key to optimizing the chemical reactivity of catalysts. However, direct identification of the chemical reactivity of SASs is still a challenge due to the limitations of characterization techniques. Here, we present a new pathway to determine the kinetics of adsorption/desorption on SASs of graphene oxide (GO) based on total internal reflectance fluorescence microscopy. The switching on and off of the fluorescent signal of SAS lit by carbon dots (CDs) was used to trace the adsorption process and desorption process. We find that sodium pyrophosphate (PPi) could increase the adsorption equilibrium of CDs thermodynamically and promote the substrate-assisted desorption pathway kinetically. At the single turnover level, it was disclosed that the species that can promote desorption may also be an adsorption promoter. Such discovery provides significant guidance for improving the chemical reactivity of the heterogeneous catalyst.
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