Accumulation of somatic mutations in genomic DNA is nearly exclusive to cancer cells. During proliferation, a fraction of cancer cells die and release genomic DNA fragments. These released genomic DNA fragments, termed circulating tumor DNA (ctDNA), can be found in blood. ctDNA has potential uses in cancer diagnostics, particularly since the emergence of “massively parallel” next generation sequencing (NGS). However, the detection limit of NGSs was recently shown to be far higher than the actual concentration of ctDNA. To quantify ctDNA as a tumor marker, digital PCR (dPCR) is required to detect very low (i.e., <1%) concentrations of somatic mutations. We have designed a dPCR primer/probe library specific for cancer mutations that were selected from public databases containing 12.5 million entries. Our newly developed system using this library, the Off-The-Shelf (OTS)-Assay, can measure as little as 0.01% of ctDNA, which allows highly sensitive post-treatment cancer surveillance for cancer patients. The high sensitivity of the OTS-Assay may change approaches for measurement of residual cancer during and after treatment.

View full abstract

Recent studies on adult spinal deformity report complications including anterior longitudinal ligament (ALL) rupture, which may cause instrumentation failure. This study aimed to evaluate the effect of ALL rupture on instrumentation failure. We used a three-dimensional finite element method (3D-FEM) to study the rupture of the ALL. A 3D-FEM model of the lumbar spine was generated using computed tomography images. A posterior instrument was then adapted to the L1-S1 vertebrae as a fixed model. Simulations of ALL rupture were performed at L3/4 in 25% increments and virtual excision of the intervertebral disc (IVD) was performed for each model. Thus, we prepared standard models and L1-S1 fixed models with and without disc excision under ALL rupture conditions. We evaluated displacement (mm) during extension and the von Mises stress (MPa) on the IVD, vertebral body around the screws, and posterior instrument. In the standard models, with and without disc excision, displacement during extension and the stress on IVDs increased as the degree of ALL rupture increased. In L1-S1 fixed models, the displacement similarly increased. The stress on IVDs, vertebral bodies around the screws, and posterior instruments also increased. ALL rupture may pose a potential risk of vertebral instability, leading to instrumentation failure.

View full abstract

　We evaluated whether magnetic resonance diffusion kurtosis imaging (DKI) could reveal brain microstructural changes in childhood epilepsies with motor coordination problems (MCP) and whether DKI findings are correlated with neuropsychological assessments. Sixteen patients with childhood epilepsies were included; eight of these had lower scores on the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ-J) than the cutoff value, and these patients were categorized as the MCP group. Regions of interest analyses of the cortex were performed to compare the mean kurtosis (MK), fractional anisotropy, and mean diffusivity between the MCP and non-MCP groups. The MK value of the right precentral gyrus (PrCG) was significantly lower in the MCP group than in the non-MCP group (p = .021). Significant correlations between diffusion kurtosis metrics and the DCDQ-J scores were observed, particularly in the paracentral lobules. The receiver operating characteristic analysis for all patients indicated that the area under the curve for MK values of the right PrCG was 0.844, and the cutoff MK value to distinguish whether MCP was present was 0.587 (sensitivity, 100%; specificity, 75%). Our results indicate that the DKI findings of the right precentral cortex may be substantially useful as a biomarker for MCP associated with childhood epilepsy.

View full abstract