Control Charting Genomic Data.

Background: Control charting is routine in the quality assurance of traditional clinical laboratory testing. Genomic tests are not typically managed by control charting. We examined control charting to monitor the performance of a clinical next-generation sequencing (NGS) assay.

Long-term exposure of human endothelial cells to metformin modulates miRNAs and isomiRs.

Increasing evidence suggest that the glucose-lowering drug metformin exerts a valuable anti-senescence role. The ability of metformin to affect the biogenesis of selected microRNAs (miRNAs) was recently suggested. MicroRNA isoforms (isomiRs) are distinct variations of miRNA sequences, harboring addition or deletion of one or more nucleotides at the 5' and/or 3' ends of the canonical miRNA sequence.

Gene selection for optimal prediction of cell position in tissues from single-cell transcriptomics data.

Single-cell RNA-sequencing (scRNAseq) technologies are rapidly evolving. Although very informative, in standard scRNAseq experiments, the spatial organization of the cells in the tissue of origin is lost. Conversely, spatial RNA-seq technologies designed to maintain cell localization have limited throughput and gene coverage.

On the expanding roles of tRNA fragments in modulating cell behavior.

The fragments that derive from transfer RNAs (tRNAs) are an emerging category of regulatory RNAs. Known as tRFs, these fragments were reported for the first time only a decade ago, making them a relatively recent addition to the ever-expanding pantheon of non-coding RNAs. tRFs are short, 16-35 nucleotides (nts) in length, and produced through cleavage of mature and precursor tRNAs at various positions.

Complete chemical structures of human mitochondrial tRNAs.

Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes.

Controlled anti-cancer drug release through advanced nano-drug delivery systems: Static and dynamic targeting strategies.

Advances in nanomedicine, including early cancer detection, targeted drug delivery, and personalized approaches to cancer treatment are on the rise. For example, targeted drug delivery systems can improve intracellular delivery because of their multifunctionality. Novel endogenous-based and exogenous-based stimulus-responsive drug delivery systems have been proposed to prevent the cancer progression with proper drug delivery.

Numerical study of microwave induced thermoacoustic imaging for initial detection of cancer of breast on anatomically realistic breast phantom.

Background And Objective: Microwave-induced thermoacoustic imaging (MITAI) represents an innovative imaging approach for detection of breast cancer at initial phases by integrating the benefits provided by procedures of microwave and ultrasound imaging. The present investigation examines an innovative three-dimensional numerical modeling of MITAI as a problem with multi-physics nature.

Methods: Simulations are performed by the use of COMSOL software.

Use of microwave ablation for thermal treatment of solid tumors with different shapes and sizes-A computational approach.

Microwave Ablation (MWA) is one of the most recent developments in the field of thermal therapy. This approach is an effective method for thermal tumor ablation by increasing the temperature above the normal physiological threshold to kill cancer cells with minimum side effects to surrounding organs due to rapid heat dispersive tissues. In the present study, the effects of the shape and size of the tumor on MWA are investigated.

Drug delivery to solid tumors with heterogeneous microvascular networks: Novel insights from image-based numerical modeling.

The present study examines chemotherapy by incorporating multi-scale mathematical modeling to predict drug delivery and its effects. This approach leads to a more-realistic physiological tumor model than is possible with previous approaches, as it obtains the capillary network geometry from an image, and also considers the tumor's necrotic core, drug binding, and cellular uptake. Modeling of the fluid flow and drug transport is then performed in the extracellular matrix.

Oxidative stress enhances the expression of 2',3'-cyclic phosphate-containing RNAs.

Eukaryotic cells equip robust systems to respond to stress conditions. In stressed mammalian cells, angiogenin endoribonuclease cleaves anticodon-loops of tRNAs to generate tRNA halves termed tRNA-derived stress-induced RNAs (tiRNAs), which promote stress granule formation and regulate translation. The 5'-tiRNAs (5'-tRNA halves) contain a 2',3'-cyclic phosphate (cP) and thus belong to cP-containing RNAs (cP-RNAs).

A new computational method of modeling and evaluation of dissolving microneedle for drug delivery applications: Extension to theoretical modeling of a novel design of microneedle (array in array) for efficient drug delivery.

Today, dissolving microneedles have grabbed much attention due to their fascinating features. As the first step, recognition of their behavior under different circumstances is needed. By gathering such information, modifications with the aim of eliminating the defects of the last models would be possible.

Reinforcement learning for optimal scheduling of Glioblastoma treatment with Temozolomide.

Background: Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults and Temozolomide (TMZ) is an effective chemotherapeutic agent for its treatment. In Silico models of GBM growth provide an appropriate foundation for analysis and comparison of different regimens. We propose a mathematical frame for patient specific design of optimal chemotherapy regimens for GBM patients.

Ribosomal RNA fragmentation into short RNAs (rRFs) is modulated in a sex- and population of origin-specific manner.

Background: The advent of next generation sequencing (NGS) has allowed the discovery of short and long non-coding RNAs (ncRNAs) in an unbiased manner using reverse genetics approaches, enabling the discovery of multiple categories of ncRNAs and characterization of the way their expression is regulated. We previously showed that the identities and abundances of microRNA isoforms (isomiRs) and transfer RNA-derived fragments (tRFs) are tightly regulated, and that they depend on a person's sex and population origin, as well as on tissue type, tissue state, and disease type. Here, we characterize the regulation and distribution of fragments derived from ribosomal RNAs (rRNAs).

Cyclin D1 promotes secretion of pro-oncogenic immuno-miRNAs and piRNAs.

The molecular mechanisms governing the secretion of the non-coding genome are poorly understood. We show herein that cyclin D1, the regulatory subunit of the cyclin-dependent kinase that drives cell-cycle progression, governs the secretion and relative proportion of secreted non-coding RNA subtypes (miRNA, rRNA, tRNA, CDBox, scRNA, HAcaBox. scaRNA, piRNA) in human breast cancer.

AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria.

Antibiotic-resistant superbug bacteria represent a global health problem with no imminent solutions. Here we demonstrate that the combination (termed AB569) of acidified nitrite (A-NO) and Na-EDTA (disodium ethylenediaminetetraacetic acid) inhibited all Gram-negative and Gram-positive bacteria tested. AB569 was also efficacious at killing the model organism in biofilms and in a murine chronic lung infection model.

Expression of Tryptophan 2,3-Dioxygenase in Metastatic Uveal Melanoma.

Uveal melanoma (UM) is the most common primary eye malignancy in adults and up to 50% of patients subsequently develop systemic metastasis. Metastatic uveal melanoma (MUM) is highly resistant to immunotherapy. One of the mechanisms for resistance would be the immune-suppressive tumor microenvironment.

Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer.

Objective: To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target.

Design: FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA.

A novel in silico platform for a fully automatic personalized brain tumor growth.

Glioblastoma Multiforme is the most common and most aggressive type of brain tumors. Although accurate prediction of Glioblastoma borders and shape is absolutely essential for neurosurgeons, there are not many in silico platforms that can make such predictions. In the current study, an automatic patient-specific simulation of Glioblastoma growth would be described.

Estimation of drug and tumor properties using novel hybrid meta-heuristic methods.

One of the major drawbacks in mathematical modeling of the drug delivery in living species is application of a common value for a specific property such as diffusion coefficient of drug in tissue, while this property is unique for each person or species. Therefore, knowledge on the species-specific values of these properties can improve the process of drug delivery and treatment. Inverse problem methods can achieve these unique properties for each specimen.

Genome-wide identification of short 2',3'-cyclic phosphate-containing RNAs and their regulation in aging.

RNA molecules generated by ribonuclease cleavage sometimes harbor a 2',3'-cyclic phosphate (cP) at their 3'-ends. Those cP-containing RNAs (cP-RNAs) form a hidden layer of transcriptome because standard RNA-seq cannot capture them as a result of cP's prevention of an adapter ligation reaction. Here we provide genome-wide analyses of short cP-RNA transcriptome across multiple mouse tissues.

Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health.

Maintenance of glycolytic metabolism is postulated to be required for health of the spinal column. In the hypoxic tissues of the intervertebral disc and glycolytic cells of vertebral bone, glucose is metabolized into pyruvate for ATP generation and reduced to lactate to sustain redox balance. The rise in intracellular H /lactate concentrations are balanced by plasma-membrane monocarboxylate transporters (MCTs).

Validation of a Miniaturized Permeability Assay Compatible with CRISPR-Mediated Genome-Wide Screen.

The impermeability of the luminal endothelial cell monolayer is crucial for the normal performance of the vascular and lymphatic systems. A key to this function is the integrity of the monolayer's intercellular junctions. The known repertoire of junction-regulating genes is incomplete.

Numerical modeling of high-intensity focused ultrasound-mediated intraperitoneal delivery of thermosensitive liposomal doxorubicin for cancer chemotherapy.

Although intraperitoneal chemotherapy (IPC) has been suggested as a promising method for the management of peritoneal dissemination (PD) of ovarian or colorectal cancers, the actual clinical use of this method has been restricted due to such problems as poor drug penetration into the tumor and high side effects. It is, therefore, necessary to develop new strategies to improve the efficacy of this approach. In the present work, a new strategy is proposed based on intraperitoneal (IP) injection of thermosensitive liposomal doxorubicin (TSL-Dox) with triggered release by mild hyperthermia induced by high intensity focused ultrasound (HIFU).

Exploration of CCA-added RNAs revealed the expression of mitochondrial non-coding RNAs regulated by CCA-adding enzyme.

Post-transcriptional non-template additions of nucleotides to 3'-ends of RNAs play important roles in the stability and function of RNA molecules. Although tRNA nucleotidyltransferase (CCA-adding enzyme) is known to add CCA trinucleotides to 3'-ends of tRNAs, whether other RNA species can be endogenous substrates of CCA-adding enzyme has not been widely explored yet. Herein, we used YAMAT-seq to identify non-tRNA substrates of CCA-adding enzyme.

Unification of miRNA and isomiR research: the mirGFF3 format and the mirtop API.

Motivation: MicroRNAs (miRNAs) are small RNA molecules (∼22 nucleotide long) involved in post-transcriptional gene regulation. Advances in high-throughput sequencing technologies led to the discovery of isomiRs, which are miRNA sequence variants. While many miRNA-seq analysis tools exist, the diversity of output formats hinders accurate comparisons between tools and precludes data sharing and the development of common downstream analysis methods.