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.

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.

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.

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.

In this paper, the authors referred to criminal autonomy and certain specificities of the crime of international trafficking in human beings, as well as the differentiation of the said criminal offense in relation to other related criminal offenses. This criminal offense is often unnecessarily identified with other related criminal offenses, although by its criminal law it constitutes an autonomous or autonomous criminal offense with clearly prescribed objectively-subjective characteristics. International human trafficking is a complex social legal phenomenon that is not a novelty in society, but its phenomenological manifestations have changed and adapted to certain conditions and circumstances in the phenomenological sense in different periods of history. Also, this paper articulates the complexity of discovering, investigating and proving this criminal offense, taking into account the restrictive legal requirements of the criminal and material nature that determine the actions of the law enforcement entities. It is not disputed that at the international level there is a clear commitment to the efficient and energetic struggle against this criminal offense, and in that sense, numerous international legal documents that form the platform or basis for the creation of national regulations in Bosnia and Herzegovina have been drafted and adopted, appreciating the complex constitutional the structure and existence of different levels of government. However, despite all the efforts at the international and national level, it is evident that international human trafficking is nevertheless a social and legal reality that is present even in economically developed and democratically regulated states, and as such presents a challenge to the present in terms of its criminal-law suppression.

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.

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.

The aim of the study was to develop a population pharmacokinetic (PK) model for clearance of 2-oxo-clopidogrel in patients with acute coronary syndrome (ACS). Population pharmacokinetic analysis was performed by using 72 plasma concentrations from the same number of patients (mean age of 60.82±10.76 years; total body weight (TBW) of 73.63±9.67 kg) with ACS using non-linear mixed-effect modeling (NONMEM). Validation of the final PPK model was carried out through the bootstrap analysis with 200 runs and it was used to estimate the predictive performance of the pharmacokinetic model. The typical mean value for 2-oxo-clopidogrel clearance (CL), estimated by the base model (without covariates), in our population was 39.2 l h−1.The value of aspartate transaminase and co-medication with digoxin were determinants of a derived population model. The final regression model for the clearance of 2-oxo-clopidogrel was the following: CL (lh-1) = 1.7 + 1.31*AST + 115*DIGOXIN. The derived PK model describes the clearance of 2-oxo-clopidogrel in patients with ACS, showing that the value of aspartate transaminase and co-medication with digoxin are the most important covariate. This finding will provide the basis for future PK studies.

Motivation Gene and species tree reconciliation methods can be used to root gene trees and correct uncertainties that are due to scarcity of signal in multiple sequence alignments. So far, reconciliation tools have not been integrated in standard phylogenetic software and they either lack of performance on certain functions, or usability for biologists. Results We present Treerecs, a phylogenetic software based on duplication-loss reconciliation. Treerecs is simple to install and to use, fast, versatile, with a graphic output, and can be used along with methods for phylogenetic inference on multiple alignments like PLL and Seaview. Availability Treerecs is open-source. Its source code (C++, AGPLv3) and manuals are available from https://project.inria.fr/treerecs/ Contact eric.tannier@inria.fr or david.parsons@inria.fr online.

The increasing number of stray dogs and the lack of sufficient data on the prevalence of leptospirosis among dogs were the main reasons for conducting this research in different populations of dogs on the territory of Bosnia and Herzegovina. A total of 300 serum samples were tested from three different categories of dogs of various breeds from 12 cities. Twelve leptospiral serovars were used in the microscopic agglutination test (MAT). The presence of specific antibodies was confirmed for eight serovars. The proportion of seropositive dogs was 22.3% (67/300). The highest seropositivity (n = 38; 42.7%) was found for the serovar Pomona. The seropositivity rates found for the other serovars tested were as follow: Canicola (14.6%), Icterohaemorrhagiae (13.5%), Sejroe (12.4%), Autumnalis (12.4%), Grippotyphosa (2.2%), Bratislava (1.1%), and Australis (1.1%). The highest number of positive responses was obtained at the serum dilution of 1:100 (39.3%, n = 35). The highest number of positive reactions was identified in the category of ‘house dogs’ (29.3%, 29/99) followed by ‘stray dogs’ (21.6%, 24/111), while the lowest number of positive tests was recorded in the category of ‘guard/ hunting dogs’ (15.6%, 14/90). Vaccination with tetravalent vaccines, including the serovars Icterohaemorrhagiae, Canicola, Pomona and Grippotyphosa could be an effective measure for the prevention of canine leptospirosis.