MammaPrint was the first genomic assay in breast cancer to be validated with a prospective randomized trial, the MINDACT trial. The 70 gene MammaPrint assay was developed to determine the risk of distant metastasis in early stage breast cancer through gene expression analysis and was the first FDA cleared genomic assay for breast cancer. The assay identifies primary breast cancers likely to metastasize within the first five years of diagnosis and has clinical utility for helping to determine the expected benefit from adjuvant chemotherapy. The MINDACT Trial was the first trial of a genomic assay in breast cancer to provide prospective, randomized evidence of clinical utility for this important clinical question, identifying a significant proportion of patients who could safely forgo chemotherapy within a cohort of patients with high risk clinical characteristics. Nearly half of all patients (46%) who would have been advised chemotherapy according to clinical guidelines were identified genomically by MammaPrint as being low risk and found to have equivalent rates of freedom from metastasis at 5 years with or without chemotherapy. Based upon the MINDACT trial, the ASCO Biomarker Guidelines now approve the use of MammaPrint to inform decisions regarding chemotherapy for women with clinically high-risk ER+ breast cancer, and as the only approved assay for use in women with 1-3 involved lymph nodes. Recent studies suggest information obtained from the 70-gene assay may also help inform decisions regarding endocrine therapy, as well as chemotherapy, targeted therapy and immunotherapy. CONCLUSION: The power of gene expression analysis in breast cancer, effectively illustrated with MammaPrint in the MINDACT trial, is now being explored through examination of the full transcriptome in breast cancer.

OBJECTIVE This paper describes our experience and outcomes from 54 cases presented to the (Molecular tumor board) MTB. METHODS 54 Cases presented between July 2017 and April 2018 were included in this analysis. These patients had different types of cancers that had either failed standard therapy or were expected to fail and physicians were looking for future options for anticipated progression. Patients who had obvious mutations and were candidates for Targeted Agent and Profiling Utilization Registry or Molecular Analysis for Treatment Choice clinical trials were not included. Oncologists presented the cases virtually and Foundation Medicine scientific and clinical team discussed the molecular pathways to find targeted options or trials. Tumor board attendees included oncologists, nurses, pharmacists, mid-level providers, residents and staff of the Cancer Center. RESULTS Amongst the 54 cases presented 81% had one or more potentially actionable alteration. 12 (22%) patients received genomically matched therapy as per MTB recommendations. Additional 13 (24%) patients have options available when they progress. Out of 12 patients who got treatment six are alive at the time of this analysis. Genomically matched therapy or Clinical Trials option were offered to the 46% of patients based on the MTB discussion. CONCLUSION More widespread use of molecular diagnostics, better physician education and multidisciplinary collaboration between the staff involved in diagnosis and treatment, as well as third party payers are necessary for consensus on treatment and care of oncology patients.

The current paper discusses the use of genomics in the context of the changing landscape of clinical practice and modern medicine. Medical practice has shifted considerably over the past few decades, from empirical to evidence-based to personalized medicine, and the transition from reliance on observation to measureable parameters. Scientific innovation is required to collect an ever-increasing number and variety of data points and sophisticated analyses capable of distilling vast datasets into meaningful information. The next phase of innovation seeks to personalize disease management, in particular through genomics in oncology. With expanding use of genomics in medicine, and several initiatives collecting genomic data at the population level, education of patients and physicians is critical for data utility. By combining genomic and clinical data, bioinformatics approaches can be applied to developing individualized or targeted therapies. Breast cancer provides an example through which to understand the evolution of genomic data from pure science to clinical utility. From intrinsic subtype classification to development of multigene panels estimating recurrence risk, new studies, such as the FLEX trial, will expand to evaluate the whole transcriptome of tumours. This approach will enable discovery of novel gene signatures and ultimately pave the way toward a personalized approach to breast cancer management. CONCLUSION: Despite the potential for genomics to personalize treatments, a number of challenges remain to fully integrate these types of large datasets in a manner that provides clinicians and patients with meaningful, actionable information. However, if challenges are addressed, precision medicine has the capacity to transform patient care.

No abstract available.

This biographical note details Anna Bayerová's (1853-1924) activities as the first female Austro-Hungarian health officer in 1878 to1918 occupied Bosnia and Herzegovina (BH). Anna Bayerová is known as a heroine of Czech feminism and the 'first Czech female physician', though she only practised in the Czech lands from 1913 to 1916. In 1891, Bayerová was enrolled as the first Austro-Hungarian female health officer and assigned to treat Muslim women in the district of Tuzla, Bosnia. She pursued this mission for the first three months of 1892, had herself transferred to Sarajevo in the summer, and soon thereafter quitted the service. Her biographers point to a series of political and personal motivations to abandon her mission in Bosnia, which, from the viewpoint of Czech feminists, included fulfilling her professional duties in an exemplary way. She spent most of her professional life as a physician in Switzerland and did not request Austrian recognition of her medical degree until 1913. Bayerová died in Prague in 1924. Conclusion. Bayerová, partly for political reasons and partly due to her panic-fuelled fear of catching tuberculosis, quitted her role as the first Austro-Hungarian female health officer in BH soon after her arrival in 1892.

Apoptosis, as a well-studied process of a programmed cell death, is essential for the maintenance of cell homeostasis and integrity of organisms. This process occurs normally during development and aging and it is a balance of the sustainability of the tissue cell population. In addition, apoptosis also occurs as a defensive mechanism such as an immune response or after cell damage as a consequence of a pathological condition or the action of harmful agents. Apoptotic activation tends to be less responsive with aging, causing accumulation of non-functional cells and pathological changes such are degenerative diseases or tumor transformation. This overview aims to provide summarized facts about different approaches of apoptosis research, targeting and regulation in tumors especially in leukemic cells as a way of pharmacological manipulation with a potential therapeutic benefit.

Next Generation Sequencing (NGS) has become powerful tool in molecular oncology. It allows multiparallel targeted sequencing that enables comprehensive assessment of tumor heterogeneity. Detection of mutations in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) defines patients diagnosis, therapy and prognosis. Multiple genes, their somatic mutations to be precise, carry different degrees of importance for any of these stages. Ion AmpliSeq™ Colon and Lung Cancer Research Panel v2, which was used in this study, allows detection of hotspot mutations on 22 genes in a single reaction. Droplet digital PCR (ddPCR) has a unique advantage in low frequency mutation detection and it has been used as a validation method for mutations that were detected with NGS. It has high sensitivity and enables accurate detection of mutant allele in a background of abundant wild type alleles. For this study 35 samples of CRC and NSCLC were sequenced and same samples were analysed on ddPCR for KRAS, NRAS, EGFR and BRAF genes. All processed samples were successfully sequenced and had average base coverage >500X. NGS sequencing proved itself to be cost effective, has shorter turnaround time and is highly sensitive. Out of 35 samples, 25 had genetic alterations, while 10 samples are reported as wild type but were still tested on ddPCR as controls. In three samples low frequency somatic mutations were detected by NGS and verified using ddPCR, which leads us to conclusion that ddPCR is a good tool for verification of somatic mutations in CRC and NSCLC.

This study was designed on the analysis of the mtDNA polymorphisms in three ethnic populations of Tuzla Canton of Bosnia and Herzegovina (Bosniaks, Croats and Serbs). The main aim of this study was to analyze the influences of the maternal gene flow on the genetic profile of the analyzed populations. The analysis of mtDNA variation based on relevant restriction fragment length polymorphisms (RFLP) in combination with HVSI variations of the control region (for detection of subhaplogroups of the haplogroup U) enabled the identification of the typical of the Western-Eurasian haplogroups (H, I, J, T, W, U, HV, HVO, K, V, and X), African/Near East lineages N1a and Asian haplogroup M. Our results suggest that mitochondrial gene pool of the three main ethnic groups of Tuzla region was shaped by influences of early and late migration routes which marked the settlement process of the Balkans. The effects of different migration directions are illustrated by the distribution of important indicators of the Late Glacial expansion (U5a), postglacial re-colonisation of Europe from glacial refuges of southwestern European (H, V, U5b1), central-eastern European Plain (U4), Italian Peninsula (U5b3) and neolithic expansion (U3, N1a, J and T). Our data can indicate a common genetic history, origin, as well as a similar contribution of the parental and maternal gene flow on genetic structure of the three main ethnic populations of modern Bosnia and Herzegovina.

It is widely accepted that understanding the heterogeneity of a population is important in assessment of the vulnerability of a conservation unit (Frankham et al., 2002). Standard measures such as estimation of heterozygosity, deviations from Hardy–Weinberg equilibrium, effective population size, inbreeding coefficients are widely used. Minor, but very important elements of these measures are allelic diversity, effective number of alleles and allelic richness which characterize the extent of genetic diversity. Allelic diversity (An) represents an average number of alleles per locus determined by direct count. When more than one locus is considered, it is calculated as a number of alleles averaged over loci expressed as k/l where k is the total number of alleles determined at all the observed loci and l is the number of loci (Frankham et al., 2002). The effective number of alleles (Ae) is a measure that shows the number of alleles required to ensure the same level of heterozygosity under the assumption of balanced allele frequency and low influence of rare alleles. It is expressed as 1/Σpi 2

This work follows the recent discovery of a zinc-bearing Egyptian blue (EB) pigment widely used for the production of the early medieval mural paintings cycle in Santa Maria foris portas Church at Castelseprio (Lombardy Region, Italy). The inclusion of zinc in the synthesis of EB has been studied for the first time trying to evaluate whether its addition could be casual or deliberate. Historical reconstructions of the pigment have been carried out with a special focus on the use of zinc besides copper, using the different production methods. The influence of zinc on the pigment’s NIR photoluminescence and VIS-NIR reflectance has been characterized using FORS spectroscopy, X-ray diffraction, optical microscopy, and scanning electron microscopy-energy dispersive X-ray spectroscopy. A comparison of the production methods including salt-flux, solid-state, and Zn-rich syntheses showed that the solid-state synthesis results in particularly efficient NIR photoluminescence and VIS-NIR reflectance. Modern replicas were compared with an ancient sample in order to understand the zinc environment inside the structure of the Zn-enriched EB. Zn was found to be concentrated in a glass-based matrix surrounding cuprorivaite crystals, the main mineral associated with the EB pigment, and not included in a hypothetical Zn-doped cuprorivaite with formula CaCu1−xZnxSi4O10. The Zn-rich synthesis opens up the possibility of producing EB from brass and demonstrates that EB used in Castelseprio’s mural paintings could have been produced in this way. The relationship between the microstructure and the NIR photoluminescence of cuprorivaite-like pigments is of interest also for applications in modern and future technologies.

The purpose of this study was to compare unenhanced MR angiography with contrast-enhanced MR angiography and visualisation of renal arteries with its segment branches using both techniques. We performed renal MRA on 22 patients using a 1.5T MRI unit. For renal MRA, a three dimensional balanced type steady-state free precession (SSFP) sequence (Time-SLIP, Canon) was used with respiratory gating and conventional CE-MRA sequnce (upisati tačan naziv). For analysis, two radiologists independently evaluated the visual quality of the axial images and axial maximum intensity projection images (MIP) of Time SLIP and CE MRA. Visualisation of aorta and main stem of the renal arteries were satisfactory on both techniques, and there was no statistically significant difference. The score of segmental renal artery appeared superior with Time-SLIP and showed a statistically significant difference (P<0.05). Visualisation of segmental renal arteries, interlobar renal arteries and kidneys parenchyma was significantly superiorwith Time-SLIP technique. We compared visualisation of renal arteries and its branches using unenhanced MRA, Time-SLIP, in comparison with contrast-enhanced MRA. Although it is slightly time-consuming and its clinical utility is necessary to further investigate, unenhanced MRA provides superior visualization of peripheral branches even in this study. Further improvement of the technique would make it even more sensitive in detecting small vessel abnormalities and it is promising for clinical use.

INTRODUCTION: Diseases of the locomotor system or musculoskeletal disease are on the rise, mainly due to the ageing of the population but also due to lifestyle changes. Those are the main cause of chronic pain and disability in the modern world. Thanks to the achievements of modern medicine, in patients with advanced osteoarthritis of the hip or knee it is possible to replace the diseased joint with an endoprosthesis, with very good long-term results related to pain reduction and function improvement. The aim of this study is to examine are there any differences in the quality of people's life before and after implantation of total knee endoprosthesis. RESPONDENTS AND RESEARCH METHODS: There were 30 subjects of both genders with knee joint disease enrolled in the study, who were treated with the surgical course at the Orthopedics clinic and the traumatology of the UKCS by implanting a total endoprosthesis, from the beginning of April until the end of October 2018. As an instruments of this research are used standardized SF-36 questionnaire for assessing the quality of life and overall health status and a modified questionnaire on the socio-demographic characteristics of the respondents. RESULTS: Patients after implantation of total knee endoprosthesis have a better quality of life, i.e. statistical significance at physical function level (P = 0.0001), role limits due to physical problems (P = 0.0001), social functions (p = 0.0001), energy or vitality (P = 0.0001), pain (p = 0.0001), limitations of the role due to emotional problems (P = 0.0001), and emotional prosperity (P = 0.0001) and general health (P = 0.004). CONCLUSIONS: The quality of life of patients was worse before the period after the total knee endoprosthesis, where statistically significant improvement was demonstrated.

Currently, blockchain technology has been widely used due to its support of transaction trust and security in next generation society. Using Internet of Things (IoT) to mine makes blockchain more ubiquitous and decentralized, which has become a main development trend of blockchain. However, the limited resources of existing IoT cannot satisfy the high requirements of on-demand energy consumption in the mining process through a decentralized way. To address this, we propose a decentralized on-demand energy supply approach based on microgrids to provide decentralized on-demand energy for mining in IoT devices. First, energy supply architecture is proposed to satisfy different energy demands of miners in response to different consensus protocols. Then, we formulate the energy allocation as a Stackelberg game and adapt backward induction to achieve an optimal profit strategy for both microgrids and miners in IoT. The simulation results show the fairness and incentive of the proposed approach.