Robustness of differential gene expression analysis of RNA-seq.

RNA-sequencing (RNA-seq) is a relatively new technology that lacks standardisation. RNA-seq can be used for Differential Gene Expression (DGE) analysis, however, no consensus exists as to which methodology ensures robust and reproducible results. Indeed, it is broadly acknowledged that DGE methods provide disparate results. Despite obstacles, RNA-seq assays are in advanced development for clinical use but further optimisation will be needed. Herein, five DGE models (DESeq2, voom + limma, edgeR, EBSeq, NOISeq) for gene-level detection were investigated for robustness to sequencing alterations using a controlled analysis of fixed count matrices. Two breast cancer datasets were analysed with full and reduced sample sizes. DGE model robustness was compared between filtering regimes and for different expression levels (high, low) using unbiased metrics. Test sensitivity estimated as relative False Discovery Rate (FDR), concordance between model outputs and comparisons of a 'population' of slopes of relative FDRs across different library sizes, generated using linear regressions, were examined. Patterns of relative DGE model robustness proved dataset-agnostic and reliable for drawing conclusions when sample sizes were sufficiently large. Overall, the non-parametric method NOISeq was the most robust followed by edgeR, voom, EBSeq and DESeq2. Our rigorous appraisal provides information for method selection for molecular diagnostics. Metrics may prove useful towards improving the standardisation of RNA-seq for precision medicine.

[Diagnostic criteria for the transition from occlusal splints to non-removable orthopedic appliances in patients with TMJ dysfunction with disc disorders]. / Kriterii perekhoda ot okkliuzionnoi shiny k vremennym nes''emnym ortopedicheskim konstruktsiiam pri lechenii patsientov s sindromom bolevoi disfunktsii visochno-nizhnecheliustnogo sustava s diskovymi narusheniiami.

The aim of the study was to elaborate Diagnostic criteria for the transition from occlusal splints to non-removable orthopedic appliances in patients with TMJ dysfunction with disc disorders. The study involved 95 patients with the clinics of TMJ dysfunction. An examination included electrovibrography and computerized electromyography in order to assess diagnostic value of the methods. Electrovibrography is a method based on arthrophonography, which makes it possible to obtain data on intraarticular noise in the TMJ. Computerized electromyography provides an objective assessment of the bioelectrical activity of the masticatory muscles in occlusive disorders, changes in the height of the lower facial area, and their relationship with the development of musculo-articular dysfunction of the TMJ and allows monitoring the effectiveness of orthopedic treatment. Within the normal function of the jaws the graphic trajectories of mandibular movements are within the limits of norm, and in the case of a violation of the TMP function, the graphic and linear indices are significantly different from the normal values.

Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches.

Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, the median survival is 12-15 months. Patients with matched recurrent glioblastomas were investigated to try to find actionable mutations. Tumours were profiled using a validated DNA-based gene panel. Copy number variations (CNVs) and single nucleotide variants (SNVs) were examined, and potentially pathogenic variants and clinically actionable mutations were identified. The results revealed that glioblastomas were IDH-wildtype (IDH WT; n = 38) and IDH-mutant (IDH MUT; n = 3). SNVs in TSC2, MSH6, TP53, CREBBP, and IDH1 were variants of unknown significance (VUS) that were predicted to be pathogenic in both subtypes. IDH WT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, and G-protein pathways. Many tumours had BRCA1/2 (18%) variants, including confirmed somatic mutations in haemangioblastoma. IDH WT recurrent tumours had fewer pathways impacted (RTK/Ras/PI(3)K, p53, WNT, and G-protein) and CNV gains (BRCA2, GNAS, and EGFR) and losses (TERT and SMARCA4). IDH MUT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, and WNT pathways. VUS in KLK1 was possibly pathogenic in IDH MUT. Recurrent tumours also had fewer pathways (p53, WNT, and G-protein) impacted by genetic alterations. Public datasets (TCGA and GDC) confirmed the clinical significance of findings in both subtypes. Overall in this cohort, potentially actionable variation was most often identified in EGFR, PTEN, BRCA1/2, and ATM. This study underlines the need for detailed molecular profiling to identify individual GBM patients who may be eligible for novel treatment approaches. This information is also crucial for patient recruitment to clinical trials.

[Use of functional packages of medical stuff by military level of medical service of the Armed Forces].

Authors submitted results of recent developments made by The Kirov Military-Medical Academy and OOO "Special medical equipment" in accordance with State defence order in the area of modernization of the system of organizational equipment of military level of medical service of the Armed Forces of the Russian Federation. Along with other samples of organizational equipment, new functional equipment of medical stuff was developed and approved as supply. New equipment of medical stuff meets modern requirements and is highly valuated by medical services of foreign countries. Authors came to conclusion that functional equipment which is approved as supply and included into the Supply rate provides operational flexibility of set-up/tear-down stages of medical evacuation under the conditions of battlefield, allows to deliver medical aid on the basis of innovative medical technologies.

[Use of modern first-aid kits in the Armed Forces of the Russian Federation].

Taken to supply of the Armed Forces of the Russian Federation, individual and group first aid kits include a range of innovative pharmaceuticals and medical devices, which ensures effective implementation of measures of first aid to servicemen injured and wounded in the performance of combat training missions, the conduct of hostilities with conventional weapons and weapons of mass destruction, as well as the occurrence of natural and man-made disasters (catastrophes).

[Development of the rationing of medical equipment for troops in the modern world].

Specification of new legal document of medical service of Armed Forces of Russian Federation is presented. It is the calculate norms of medical equipment for delivery of health care and treatment for the wounded. This document was developed for the purpose of development the rationing of medical equipment in the design of measures of the military medical arrangement instead of identical norm of the 1995 edition. The document is adapted to the modern economic conditions; its implementation guarantees the stiffening of medical service readiness for the accomplishment of mission.

[Organization of support and quality control of medicaments in Russian Federation Armed Forces medical service].

The article presents the chronological analysis of formation of the system for providing the medicament quality control in the medical service of Russian Federation Armed Forces. The role of Centers of medicament quality control and certification in the State system for providing medicament quality is demonstrated. The aims of these Centers are to prevent the getting of poor and falsified medicaments into the troops. The practical work of the Centers during 4 years was analyzed. As the result 35 types of falsified and 97 types of poor medicaments were revealed. The proposals for improving medicament quality control in the medical service of RF Armed Forces are given.