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Marlena R. Fraune, S. Šabanović, T. Kanda

As robots become more prevalent in public spaces, such as museums, malls, and schools, they are coming into increasing contact with groups of people, rather than just individuals. Groups, compared to individuals, can differ in robot acceptance based on the mere presence of a group, group characteristics such as entitativity (i.e., cohesiveness), and group social norms; however, group dynamics are seldom studied in relation to robots in naturalistic settings. To examine how these factors affect human-robot interaction, we observed 2,714 people in a Japanese mall receiving directions from the humanoid robot Robovie. Video and survey responses evaluating the interaction indicate that groups, especially entitative groups, interacted more often, for longer, and more positively with the robot than individuals. Participants also followed the social norms of the groups they were part of; participants who would not be expected to interact with the robot based on their individual characteristics were more likely to interact with it if other members of their group did. These results illustrate the importance of taking into account the presence of a group, group characteristics, and group norms when designing robots for successful interactions in naturalistic settings.

Hong‐Mei Liu, Libor Ekrt, P. Koutecký, J. Pellicer, O. Hidalgo, J. Marquardt, F. Pustahija, A. Ebihara et al.

Recent studies investigating the evolution of genome size diversity in ferns have shown that they have a distinctive genome profile compared with other land plants. Ferns are typically characterized by possessing medium‐sized genomes, although a few lineages have evolved very large genomes. Ferns are different from other vascular plant lineages as they are the only group to show evidence for a correlation between genome size and chromosome number. In this study, we aim to explore whether the evolution of fern genome sizes is not only shaped by chromosome number changes arising from polyploidy but also by constraints on the average amount of DNA per chromosome. We selected the genus Asplenium L. as a model genus to study the question because of the unique combination of a highly conserved base chromosome number and a high frequency of polyploidy. New genome size data for Asplenium taxa were combined with existing data and analyzed within a phylogenetic framework. Genome size varied substantially between diploid species, resulting in overlapping genome sizes among diploid and tetraploid spleenworts. The observed additive pattern indicates the absence of genome downsizing following polyploidy. The genome size of diploids varied non‐randomly and we found evidence for clade‐specific trends towards larger or smaller genomes. The 578‐fold range of fern genome sizes have arisen not only from repeated cycles of polyploidy but also through clade‐specific constraints governing accumulation and/or elimination of DNA.

Brigitte Fuchs, H. Tahirović

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.

M. Gojić, Ivana Ivanić, T. Grgurić, S. Kožuh, O. Beganović, D. Ćubela

Taxus baccata L., yew, is dioecious, small to medium-sized evergreen tree, native to Europe, Africa and Asia, but it is cultivated worldwide because of its ornamental features. It is long known that all parts of yew (except for aril) are toxic, due to the alkaloid taxine. Nevertheless, some parts of yew tree can be used to treat cancer and as antimicrobial agents. Unlike its antibacterial properties, antifungal activity of T. baccata is poorly investigated. In this research, antifungal activity of yew methanolic and aqueous extracts was tested against Candida albicans ATCC 10231, Aspergillus brasiliensis ATCC 16404, and Ascosphaera apis MUCL 30769, through the agar well diffusion method. Leaves, bark and reproductive structures extracts were prepared separately for male and female plants. Unlike the aqueous, methanolic extracts caused variable degree of fungal growth inhibition. The strongest inhibition was observed in the activity of the aril extract against A. brasiliensis and C. albicans, with the activity of the male bark extract against A. apis following close. Considering the emerging multidrug resistance in C. albicans, an interesting finding is the inhibition of this species by all tested methanolic extracts, which is significantly stronger in comparison to the inhibition by standard antimycotic solution. According to the available data, male reproductive structures of this species were not tested earlier for their antifungal activity, and our study showed high level of antifungal activity of methanolic microstrobili extract.           

Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are detrimental, there is a lack of information on the toxicity of mixtures. In this study, two common heavy metals, lead and cadmium, were introduced individually and as mixtures to HL-60 and JURKAT cell lines for 24 hours. The study established that exposures to these two heavy metals induced cytotoxic and genotoxic effects on both cell lines. Also, cadmium exhibited a higher cytotoxic and genotoxic potential than lead. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the effect additivity method. Metal mixtures showed synergistic effect in HL-60 cells and antagonistic effect in JURKAT cells, compared to individual metals. The combined effects should be considered in the risk assessment of heavy metal co-exposure and potency.

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.

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

A. Ahmić, R. Hadziselimovic, Elma Silajdžić, Irma Mujkić, N. Pojskić

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.

Harsha Trivedi, Heather M. Kling, T. Treece, W. Audeh, G. Srkalović

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.

W. Audeh, L. Blumencranz, Heather M. Kling, Harsha Trivedi, G. Srkalović

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.

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