Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA ...remains challenging, partially because of the undefined biological background of cf-DNA.
We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 × 10−7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA.
Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely ‘passenger mutations’ of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors.
Hematopoietic clone-derived mutations, including ‘driver mutations’ and ‘passenger mutations’, are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.
While adult idiom comprehension has been addressed fairly extensively in experimental research across languages, developmental studies have emerged more recently and have primarily addressed English ...and few other languages. In this study we tested for the first time idiomatic knowledge in younger children (preschoolers), and older children (third-graders) with Bulgarian as L1, compared to adults. Our main hypothesis was that around age ten children's knowledge of idioms starts approximating adult-like knowledge (Kempler et al, 1999). We hypothesise that the ability to work with figurative language (including idioms) correlates with age and years of schooling and is linked to other linguistic abilities, e.g., meta-linguistic awareness, and the ability to infer from context (Benneli et al., 2006; Levorato & Cacciari, 2002). Our hypotheses were confirmed. While idiom comprehension is scarce among the younger group, the older children display advanced linguistic skills in the comprehension and interpretation of idioms. Our study also provides independent evidence of usage-based theories of language acquisition (Tomasello 1992, 2003), and embodied perspectives on language (Barsalou et al. 2003). Adapted from the source document
Both natural and recombinant interferons (IFNs) exert antitumor effects in man. Much work has to be done to construct optimal use of the IFN system. Its physiological role is not fully understood. ...Various IFN effects are described, all of which probably play a role for clinical effectiveness. Doses and schedules are discussed and pharmacokinetics and side-effects described. IFN therapy of benign and malignant tumor disease is pursued as clinical trials. Efficacy on various diseases is reported in the present article. Combination therapy is suggested for the future.
PDF
