Plasma Cell-Free Tumor Methylome as a Biomarker in Solid Tumors: Biology and Applications.

DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation is strongly implicated in cancer development. Cancers possess an extensively hypomethylated genome with focal regions of hypermethylation at CPG islands. Due to the highly conserved nature of cancer-specific methylation, its detection in cell-free DNA in plasma using liquid biopsies constitutes an area of interest in biomarker research. The advent of next-generation sequencing and newer computational technologies have allowed for the development of diagnostic and prognostic biomarkers that utilize methylation profiling to diagnose disease and stratify risk. Methylome-based predictive biomarkers can determine the response to anti-cancer therapy. An additional emerging application of these biomarkers is in minimal residual disease monitoring. Several key challenges need to be addressed before cfDNA-based methylation biomarkers become fully integrated into practice. The first relates to the biology and stability of cfDNA. The second concerns the clinical validity and generalizability of methylation-based assays, many of which are cancer type-specific. The third involves their practicability, which is a stumbling block for translating technologies from bench to clinic. Future work on developing pan-cancer assays with their respective validities confirmed using well-designed, prospective clinical trials is crucial in pushing for the greater use of these tools in oncology.

Heat transfer analysis in a non-Newtonian hybrid nanofluid over an exponentially oscillating plate using fractional Caputo-Fabrizio derivative.

In this paper, we have been study a hybrid nanofluid over an exponentially oscillating vertical flat plate. Therefore the fractional derivatives definition of Caputo-Fabrizio approach is applied to transform the classical model for this hybrid nanofluid to fractional model. Together with an oscillating boundary motion, therefore the heat transfer is cause as a result of the buoyancy force produce due temperature differences between the plate and the fluid. The dimensionless classical model is generalized by transforming it to the time fractional model using Caputo-Fabrizio time fractional derivative. Exact analytical solutions are obtained by using Laplace transform method to the set of dimensionless fractional governing equations, containing the momentum and energy equations subjected to the boundary and initial conditions. Numerical computations and graphical illustrations are used to checked the results of the Caputo-Fabrizio time-fractional parameter, the second-grade parameter, the magnetic parameter and the Grashof numbers on the velocity field. An assessment for time spin-off is shown graphically of integer order versus fractional-order for these non-Newtonian hybrid nanofluid through Mathcad software. The fluid velocity increases for increasing the value of the fractional parameter, second-grade parameter and Grashof number. Also for increasing the values of the MHD parameter the fluid velocity decreases.

Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction.

Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq. Peripheral blood leukocyte methylation (PRIME) subtraction to improve tumor specificity. SCLC cfDNA methylation is distinct from non-cancer but correlates with CDX tumor methylation. PRIME and k-means consensus identified two methylome clusters with prognostic associations that related to axon guidance, neuroactive ligand-receptor interaction, pluripotency of stem cells, and differentially methylated at long noncoding RNA and other repeats features. We comprehensively profiled the SCLC methylome in a large patient cohort and identified methylome clusters with prognostic associations. Our work demonstrates the potential of liquid biopsies in examining SCLC biology encoded in the methylome.

Free convection flow of second grade dusty fluid between two parallel plates using Fick's and Fourier's laws: a fractional model.

The paper aims to investigate the channel flow of second grade visco-elastic fluid generated due to an oscillating wall. The effect of heat and mass transfer has been taken into account. The phenomenon has been modelled in terms of PDEs. The constitutive equations are fractionalized by using the definition of the Caputo fractional operator with Fick's and Fourier's Laws. The system of fractional PDEs is non-dimensionalized by using appropriate dimensionless variables. The closed-form solutions of thermal and concentration boundary layers are obtained by using the Laplace and finite Fourier-Sine transforms, while the momentum equation is solved by a numerical approach by Zakian using [Formula: see text]. Furthermore, the parametric influence of various embedded physical parameters on momentum, temperature, and concentration distributions is depicted through various graphs. It is observed that the fractional approach is more convenient and realistic as compared to the classical approach. It is worth noting that the increasing values of [Formula: see text], [Formula: see text] and [Formula: see text] retard the boundary layer profile. For instance, this behaviour of [Formula: see text] is significant where boundary control is necessary. That is, in the case of resonance, the physical solution may be obtained by adding the effect of MHD. The Reynolds number is useful in characterising the transport properties of a fluid or a particle travelling through a fluid. The Reynolds number is one of the main controlling parameters in all viscous flow. It determines whether the fluid flow is laminar or turbulent. The evolution of the rate of heat, mass transfer, and skin friction on the left plate with various physical parameters are presented in tables. These quantities are of high interest for engineers. Keeping in mind the effect of various parameters on these engineering quantities, they make their feasibility reports.