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Abstract Background Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. Methods Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. Results Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%. Conclusions Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.

The paper focuses on the acid-free hydrothermal process for the synthesis of bioactive glass. The new method avoids the use of harmful acid catalysts, which are usually used in the sol-gel process. On the other hand, the processing time was reduced compared with the sol-gel method. A well-known ternary bioactive glass 58SiO2-33CaO-9P2O5 (wt%), which has been widely synthesized through the sol-gel method, was selected to apply to this new process. Thermal behavior, textural property, phase composition, morphology, and ionic exchange were investigated by thermal analysis, N2 adsorption/desorption, XRD, FTIR, SEM, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. The bioactivity and biocompatibility of synthetic bioactive glass were evaluated by in vitro experiments with a simulated body fluid (SBF) solution and cell culture medium. The obtained results confirmed that the acid-free hydrothermal process is one of the ideal methods for preparing ternary bioactive glass. [ABSTRACT FROM AUTHOR]

Background: Therapy with sofosbuvir-ledipasvir (SOF-LDV) has been very effective in chronic HCV genotype-1 in clinical trials and several real-world cohorts. However, the safety and efficacy data of SOF-LDV for HCV genotype-6 is quite limited., Methods: This open-label, clinical experience evaluated the safety and efficacy of SOF-LDV with or without ribavirin (RBV) for 12-24 weeks in patients with HCV genotype-1 (n=356) and genotype-6 (n=175) in Vietnam between September 2015 and May 2017., Results: Among 539 patients evaluated for therapy, 531 patients completed treatment with either SOF-LDV for 12 weeks (n=284); SOF-LDV + RBV for 12 weeks (n=109); SOF-LDV for 24 weeks (n=36); or SOF-LDV + RBV for 24 weeks (n=102). 45% were male with a mean age of 56.3 (range 20-87) years. The mean HCV RNA was 4,370,000 IU/ml and 72.7% had high viral load of >800,000 IU/ml. 17.3% failed prior interferon-based therapy and 52.5% had advanced fibrosis (F3-4) as noted by transient elastography. The overall sustained virological response (SVR12) rate was 99.6% (529/531). Virological relapses occurred in two patients with genotype-1 in the SOF-LDV for 12 weeks and SOF-LDV + RBV for 24 weeks treatment groups. There was no significant difference in demographic data and treatment outcomes between patients with genotype-1 versus 6. Adverse events were mild with all SOF-LDV regimens, but appeared to be more common with 24-week treatment groups., Conclusions: SOF-LDV with or without RBV was highly effective and safe in Vietnamese patients with HCV genotype-1 and 6.