Available computational methods for tumor phylogeny inference via single-cell sequencing (SCS) data typically aim to identify the most likely perfect phylogeny tree satisfying the infinite sites assumption (ISA). However, the limitations of SCS technologies including frequent allele dropout and variable sequence coverage may prohibit a perfect phylogeny. In addition, ISA violations are commonly observed in tumor phylogenies due to the loss of heterozygosity, deletions, and convergent evolution. In order to address such limitations, we introduce the optimal subperfect phylogeny problem which asks to integrate SCS data with matching bulk sequencing data by minimizing a linear combination of potential false negatives (due to allele dropout or variance in sequence coverage), false positives (due to read errors) among mutation calls, and the number of mutations that violate ISA (real or because of incorrect copy number estimation). We then describe a combinatorial formulation to solve this problem which ensures that several lineage constraints imposed by the use of variant allele frequencies (VAFs, derived from bulk sequence data) are satisfied. We express our formulation both in the form of an integer linear program (ILP) and—as a first in tumor phylogeny reconstruction—a Boolean constraint satisfaction problem (CSP) and solve them by leveraging state-of-the-art ILP/CSP solvers. The resulting method, which we name PhISCS, is the first to integrate SCS and bulk sequencing data while accounting for ISA violating mutations. In contrast to the alternative methods, typically based on probabilistic approaches, PhISCS provides a guarantee of optimality in reported solutions. Using simulated and real data sets, we demonstrate that PhISCS is more general and accurate than all available approaches.

At university, you are continually engaged with other people’s ideas: You read them in texts, hear them in lectures and seminars, discuss them in class, and incorporate them into your own writing. Not least, you build on other people’s ideas in developing your own ideas. As a consequence, it is very important that you give credit where it is due. If you do not do that, you plagiarize. Plagiarism is using others’ ideas and words without clearly acknowledging these sources.

Feohromocitom je neuroendokrini tumor, čija je glavna karakteristika sekrecijakateholamina sa posljedičnom hipertenzijom. Vrlo je rijedak u pedijatrijskoj populaciji,uobičajeno se javlja u bolesnika srednje životne dobi. Klinička slika podrazumijevaparoksizmalne napade glavobolje, bljedila, palpitacije i znojenja. Cilj rada je prikazslučaja feohromocitoma kod desetogodišnjeg dječaka, kao rijetkog tumora u pedijatrijskojpopulaciji.

Rapid population growth and urbanisation has entailed a strong motivation to develop more sustainable construction solutions in line with the 7th basic requirement for construction works sustainable use of natural resources. One of the strategies is to use materials available in abundant quantities as partial replacement for cement, or to create alternative binders for concrete. The aim of the paper is to provide an overview of the current state of the art in the field of alternative binders for concrete, and to point to the opportunities and challenges for their more systematic application in engineering practice. The state of the art review is connected to scientific projects currently undertaken at the Department of Materials, Faculty of Civil Engineering University of Zagreb, Croatia.

In this paper, the room temperature mechanical properties, as well as the microstructure of HK 30 Nb steel, were tested in the initial as-cast and solution annealed condition. Results show that tensile properties after the solution annealing have a slightly lower value than as-cast samples. Microstructural analysis of samples after solution annealing showed dissolution of primary carbides present in the initial as-cast condition. The morphology and composition of carbides were changed during a solution annealing. Analysis of microstructure was done by optical microscopy (OM) and scanning electron microscope (SEM), whereas hardness and tensile tests were performed for characterization of mechanical properties.

In an open letter more than five years ago, a group of scientists called for adopting Registered Reports in all journals of the life sciences. This letter and subsequent efforts have yielded some notable success. At time of writing, 207 journals support the Registered Reports format, with many more currently considering its implementation. However, these numbers are still small in comparison to the many journals that rely exclusively on the traditional way of evaluating scientific quality. We, a group of over 250 scientists, want to emphatically reiterate the importance of accepting studies before the results are in. We call for all empirical journals in the social and life sciences to offer Registered Reports, alongside the traditional publication formats.

Continuous progress in the nursing profession has a significant impact on the quality in the process of clinical care, which brings about new challenges and tasks for nurses to invest in new knowledge and skills. The healthcare process requires a systematic team approach in the design of evidence-based tasks, good clinical practice and clinical guidelines, documented standardized phenomena and evaluated measurements and tests. Measurement instruments and statistical tests of treatment effectiveness are used to assess the quality of health care provided. For a successful measurement and analysis of the quality of clinical care, it is necessary to have standardized healthcare documentation that allows treatment and outcomes monitoring. Qualitative and safety indicators are used to assess the quality of clinical health care, which represent a means of measurement, screening or warning. Monitoring Quality and Safety Indicators in Health Care Services is used as a guide to monitoring, evaluating and improving the quality of health care, and supporting services and organizational functions. In the field of health care, we measure the total treatment, outcome of the healthcare process, patient satisfaction, unwanted events,quality of life, etc.

Abstract Vancomycin is a tricyclic glycopeptide antibiotic, mostly used in the treatment of severe staphylococcal and enterococcal infections, especially in orthopedic surgery. The purpose of this analysis was to develop a population pharmacokinetic (PPK) model of vancomycine in hospitalized patients with bone fractures and identify important factors which influence its clearance (CL). A total of ninety-nine measurements of vancomycin serum concentrations were used in our population modeling. A two-compartment model was applied to describe the pharmacokinetics of vancomycin using subroutines ADVAN3 and TRANS4. The study population included patients of both sexes, with the mean age of 62.12±14.69 years and body weight of 80.32±12.44kg. Vancomycin was administered as intravenous infusion with average daily dose of 1772.73±521.34mg. Out of twenty different factors evaluated in the study (including demographic, clinical and laboratory data), only daily dose of vancomycin (DD) and co-medication with piperacillin/tazobactam (PT) showed significant effect on clearance of vancomycin. The final model was described by the following equation: CL (l/h) = 0.03 + 0.000468 x DD + 0.675 x PT. Bootstrapping was used for validation of the final model. In conclusion, the main causes of variability in the clearance of vancomycin among adult patients with bone fractures are daily dose of vancomycin and co-medication with piperacillin/tazobactam.

The paper reviews the current role of information and communication technologies in veterinary medicine, management of animal health, animal production and food safety worldwide and discusses the shift from recognising the digital revolution as a novelty to accepting it as a norm. Due to the diversity in veterinary medicine, it is unlikely that information and communication technologies will fully substitute the need for field veterinarians in direct contact with animals, farms, diseases, food production and food products. However, information and communication technology has a growing role in our work and provides opportunities to exploit new technologies for professional and societal affirmation. Consumers, trade and regulations drive demands on veterinary medicine, reflected in our increased focus on prevention and early recognition of animal diseases and food safety issues through output-based and integrated monitoring systems and shared responsibility between public and private sectors. Simultaneously, information and communication technology has been incorporated within these demands and so now has roles in: veterinary clinical practice, heard health management, animal health databases, traceability of animals and their products, trade and veterinary certification, animal disease data analysis, tools for veterinary education and animal health diagnostics. The symbiosis of bio- and information technologies has opened a new era in health and food production, providing a novel chance for veterinarians to make a significant leap in their professional development, achievable only through strategic and active participation as leaders and collaborators.

Mastitis is frequent and costly disease in dairy farming, while antimicrobial resistance is an important public health threat. Increasing resistance among zoonotic pathogens led to more investigation among animal pathogens. Study, conducted on dairy farms in Canton Sarajevo, aimed to establish mastitis prevalence in dairy cows, causative bacteria and investigate antimicrobial resistance. Lactating animals (n=1214) were tested using the California Mastitis Test during November 2017. Milk from positive animals was microbiologically cultivated. The overall prevalence of mastitis was 9.9 %, while 19 out of 180 dairy farms had at least one mastitis case. In 49.2% of samples, we identified S. aureus, 2.5% contained E. coli, 0.8% contained Enterobacteriaceae, 13.3 % had mixed infection and 34.2% samples had no growth. Using disk diffusion test highest resistances were observed to bacitracin (E. coli), trimethoprim/sulfamethoxazole (Enterobacteriaceae) and penicillin (S. aureus). Since oversight on antimicrobial use in farm animals is sporadic in the country, additional investigations of antimicrobial usage and trends in antimicrobial resistance causing agents are needed. Reducing mastitis rates on farms requires compliance with preventive measures alongside early detection, isolation of cases, culling of repeated cases, microbiological monitoring and testing for antimicrobial resistance before treatment.

Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized by HER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant‐7 (AR‐V7) in some SDC cases could result in resistance to anti‐androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next‐generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations were found in all but 1 case and affected TP53 (n = 19), HRAS (n = 7), PIK3CA, ERBB2 (HER2), and NF1 (n = 5 each); KMT2C (MLL3) and PTEN (n = 3 each); BRAF (p.V600E), KDM5C and NOTCH1 (n = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR‐V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was expressed in 11 of 28 cases. The majority of SDC cases had no biomarkers predictive of immunotherapy response: 5 cases exhibited low (1%‐8%) programmed death ligand 1 (PD‐L1) expression in tumor cells, 2 cases exhibited elevated TMB, and no samples exhibited microsatellite instability. Notably, the pre‐treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti‐androgen therapy, showed AR expression and no AR splice variants. We conclude that comprehensive molecular profiling of SDCs can guide the selection of patients for targeted therapies involving AR, HER2, PD‐L1, mitogen‐activated protein kinase, and PIK3CA pathways.

Objective Recent data suggest that increased levels of the HOTAIR long non-coding RNA (lncRNA) are involved in the development of various types of malignancy, including breast cancer. The aim of present study was to investigate HOTAIR lncRNA expression profile in breast cancer (BC) patients and cell lines. Materials and Methods In this experimental study, expression level of HOTAIR lncRNA was evaluated in BC and normal tissues of 15 patients as well as MDA-MB-231, MCF-7 and MCF-10A cell lines, using quantitative reverse- transcription polymerase chain reaction (qRT-PCR). HOTAIR lncRNA expression levels were estimated using 2-ΔΔCt method. Further, receiver operating characteristic (ROC) curve analysis was done to evaluate the selected lncRNA diagnostic potential. The Cox’s proportional hazards regression model was performed to evaluate the predictive value of this lncRNA level in BC patients. Results The results of present study demonstrated no significant difference in the expression of HOTAIR lncRNA in MCF7 and MDA-MB-231 cancer cell lines compared to MCF-10A as normal cell line (P>0.05). However, we observed a significantly increase in the expression of HOTAIR in BC patients compared to normal tissues (P<0.001). Significant associations were found between gene expression and tumour size and margin. We found 91.1% sensitivity and 95.7% specificity of circulating HOTAIR with an area under the ROC curve of 0.969. The Kaplan-Meier analysis indicated significant correlation between HOTAIR expression and overall survival. Conclusion This study demonstrated that expression of HOTAIR is increased in BC and might be associated with its progression. According to these findings, HOTAIR expression could be proposed as biomarkers for BC early diagnosis and prognosis.