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Objective: To compare the prescribing practice and pharmacotherapy outpatient cost of hypertension and its common complications between two neighboring countries, Bulgaria and Serbia. The study questions focus on consistency of the prescribing practice with the treatment guidelines; comparability of the treatment patterns among both countries, and burden of hypertension cost to the population and third party payer in the countries under consideration.Methods: Retrospective study, one year time horizon is for outpatient therapy.Results: Patients with arterial hypertension in Bulgaria are most often on monotherapy (61% vs 6% in Serbia), as well as those with complications (66% vs 0% Serbia). In both countries the first choice of therapy are the ACE inhibitors (37.01% in Serbia and 41% in Bulgaria) and then follows the calcium antagonists, beta-blockers, and diuretics. The weighed monthly cost of hypertension and complicated hypertension is almost doubled in Serbia (12.56 vs 8.23 EUR for hypertension, and 13.39 vs 8.23 EUR) and prevailing part is reimbursed (88% vs 44% in Bulgaria).Conclusion: Our study confirms that hypertension and its complications therapy consumes a huge amount of financial resources. In both countries under consideration the therapy is corresponding with the European treatment guidelines. The international cost comparisons are possible but they depend on many external factors as the regulatory measures, prescribing habits and reimbursement policy and should be analysed within this framework.

This paper introduces a new Python API called text2graphAPI. It is an easy-to-use library for transforming text documents into different graph representations, such as Word-Cooccurrence, Heterogeneous, and Integrated Syntactic Graphs. In addition, it contains a text pre-processing module that supports input text in different languages: English, Spanish, and French. These generated graph structures can be used to solve tasks in various areas, such as Authorship Analysis, Information Retrieval, and Topic Classification, to name a few.

We contribute to the fields of mineral economics, environmental and economic history in two respects: first, we construct a novel time series data set for the levels of aggregates extraction in Serbia between 1973 and 2015; the second, we estimate a change point ordinary least squares regression to model the dynamics of aggregates extraction in the aforementioned period. Our cliometric estimates are in great accordance with the major business cycle facts of the Serbian economy in the last 40 years. The most important policy implication of our results pertains to the potential slowdown of aggregates extraction from the onset of the Great Recession.

A study of decorated Neolithic pottery samples from excavation site Pločnik, Serbia, was performed using X-ray powder diffraction (XRPD), Fourier transform infrared (FTIR) and X-ray fluorescence (XRF) spectroscopy. Investigated samples belong to the era of the Vinča culture which existed at the central Balkan region from mid VI until the first half of V millennium BCE. The mineralogical composition of pottery samples and comparison of investigated pottery with thermally treated local clay indicated firing temperature in the range from 600 to 800°C. Two different types of white pigments have been identified in white incrusted decorations: calcium carbonate and Bone White (composed of crushed bones). This is the first evidence of use of bones for decorations in Vinča culture pottery from excavation site Pločnik. In addition to this, it was revealed that the potters used the iron reduction technique for obtaining the black decorations. [Projekat Ministartsva nauke Republike Srbije, br. 177021 I br. 177012]

Two mechanical extraction techniques were used for the extraction of environmentaly interesting elements from coal fly ash: shaking, in which the extraction process lasted from 6 to 24 hours, and ultrasonic sonication during 15 to 60 minutes, with water as extractant. The concentration of anions in fly ash extracts were determined by ion chromatography, while atomic absorption spectrometry was used for determination of: As, Pb, Cd, Ni, Cr, Zn, Cu, Fe, Mn and Al. The ultrasonic sonication yielded slightly higher amounts of extracted anions and Pb, Al, Mn and Fe, while shaking-assisted extraction was more efficient for the Cr, As, Zn and Ni ions. The changes in pH value, particle size distribution in colloid, zeta potential and conductivity during ultrasound-assisted extraction were measured in order to explain changes on the surface of fly ash particles in contact with water and different processes (adsorption, ion exchange, flocculation) that occur in environmental conditions. Principal Component Analysis were used for assessing the effect of observed process parameters. Essential from a practical point of view is a quantitative evaluation of these elements leachable from coal fly ash to surface waters in environmental conditions and contamination of the environment. [Projekat Ministarstva nauke Republike Srbije, br. 172030, br. III45012 i br. III43009]

Introduction. Adherence to proposed lifestyle changes and prescribed medication in patients with stable coronary artery disease (SCAD) is poor. Objective. We sought to investigate the influence of adjusting guideline proposed medications on relief of angina in a large group of patients with SCAD in Serbia. Methods. The study included a total of 3,490 patients from 15 cardiology clinics with symptoms of stable angina and at least one of the following criteria: abnormal electrocardiogram (ECG), history of myocardial infarction (MI), positive stress test, significant coronary artery disease on coronary angiogram or previous revascularization. All the patients underwent comprehensive evaluation at initial visit and after two months. The relief of angina was study end-point defined as any reduction in Canadian Cardiology Society (CCS) class, number of angina attacks per week and/or number of tablets of short-acting nitrates per week. Results. Most patients were included based on abnormal ECG (48.4%). At Visit 1, the average number of prescribed classes of medications to a single patient increased from 4.16 ± 1.29 to 4.63 ± 1.57 (p < 0.001). At the follow-up, the patients had significantly lower blood pressure (141 ± 19 / 85 ± 11 vs. 130 ± 12 / 80 ± 8 mmHg; p < 0.001) and most of them reported CCS class I (63.3%). The average weekly number of angina attacks was reduced from 2.82 ± 2.50 at Visit 1 to 1.72 0 ± 1.66 at Visit 2, as well as average weekly use of short-acting nitrates to treat these attacks (2.69 ± 2.53 to 1.74 ± 1.47 tablets; p < 0.001 for all). Conclusion. Adjustment of prescribed medications to guideline recommendations in a large Serbian patient population with prevalent risk factors led to significant relief of angina.

We have analyzed the behaviour of primary fiscal balance and public debt in Serbia before and in the aftermath of the global financial crisis. The results of our analysis are: i) public debt to GDP ratioexhibits (near) unit root behaviour with an overall upward time trend; ii) the response of primary fiscal balance to public debt has been insufficient to mean revert the upward trend in government debt; iii) the efforts of the Serbian government to repay the debt principal after the fiscal rule breach have not been persistent, providing empirical support to the fiscal fatigue hypothesis; iv) the government budget constraint has deteriorated since the beginning of the global financial crisis; v) the response of primary fiscal balance to public debt from the onset of the global financial crisis has dropped more severely in comparison to other European economies.

We focus on the response of primary fiscal balance to interest payments and borrowing costs on Serbian public debt before, during and in the aftermath of the global financial crisis. Our analysis reveals: i) policy makers financed up to 50% of each percentage point increase in interest payments to GDP ratio with new public debt issuance; ii) the government has responded to rising interest payments and borrowing costs by reducing primary fiscal balance from the onset of the global financial crisis; iii) the response of primary fiscal balance to interest payments mimics the response of primary fiscal balance to the costs of borrowing; iv) fiscal austerity measures adopted after the breach of fiscal rule for public debt have been insufficient to stabilize fiscal policy stance in Serbia.

Multianalytical study of two Serbian icons, “The Virgin and Child” and “St. Petka”, painted on canvas by unknown authors was performed in order to identify materials used as pigments, binders and ground layer. Investigated icons belong to the Museum of the Serbian Orthodox Church in Belgrade. Samples, collected from different parts of the icons, were analysed by: optical microscopy (OM), energy dispersive X-Ray fluorescence (EDXRF), Fourier transform infrared (FTIR) and micro-Raman spectroscopy. Obtained results reveal presence of the following pigments: Prussian blue, ultramarine, green earth, iron oxides, lead white and zinc white. Linseed oil was used as a binder. Materials used for ground layers were gypsum, calcite, baryte and lead white. Gilded surface of the icon “The Virgin and Child” was made of gold. Gilded surface on the frame of this icon was made of imitation of gold i.e. Schlagmetal, since EDXRF spectroscopy showed presence of copper and zinc, while gold was not detected. Based on style and art historian consideration as well as on obtained results for corresponding pigments and binder both icons were the most probably made at the end of 19th or beginning of the 20th century. [Projekat Ministarstva nauke Republike Srbije, br. 177021]

The paper presents DTA/TG results of polymetallic sulphide copper concentrate from the mine 'Veliki Krivelj' (Serbia) at 25-1000 °C. The reaction mechanism at elevated temperatures was proposed. As confirmation to the proposed mechanism, the results of EDXRF and, XRD analysis of the initial sample and the oxidation products at 550 and 950 °C, and the results of SEM/EDS analysis of the initial sample and the oxidation products at 675 ° C were presented. It can be concluded that the oxidation process goes through sulfide oxidation with characteristic exothermic effects, followed by sulfates and oxy- sulfates formation and their. Kinetic analysis of the oxidation process concentrates the test was performed according to the methods of Kissinger and Ozawa in non-isothermal conditions. The results of kinetic studies have shown that the oxidation process in the whole investigated temperature range is located in the kinetic field.

Contemporary agriculture production is based on use of mineral fertilizers, which however can have high activity of natural radionuclides and so cause the appearance of technologically elevated radioactivity. In order to determine the influence of mineral fertilizers application in arable land, there was used gamma spectrometric method for defining the activity of natural radionuclides (40 K, 238U, 226Ra) in imported mineral fertilizers as well as in arable and fallow land in the area of suburban municipalities of Belgrade. The obtained results have shown that in the tested mineral fertilizers the measured activity of 40K ranged from 70 to 4590 Bq/kg, 238U from 18 to 1400 Bq/kg and 226Ra from 15 to 999Bq/kg. Average activities of natural radionuclides in arable land are: 626 Bq/kg for 40K, 54 Bq/kg for 238U, 55 Bq/kg for 226Ra and 55Bq/kg for 232Th, and in fallow land 596 Bq/kg for 40K, 54 Bq/kg for 238U, 54 Bq/kg for 226Ra and 53 Bq/kg for 232Th. Average values of radium radioactivity equivalent (175 Bq/kg) and index of radiation risk (0,48), point out that in the tested areas there is no significant radiation risk for inhabitants due to terrestrial exposure. This investigation has also shown that current use of mineral fertilizers has not caused the increase of natural radioactivity in the tested arable land. [Projekat Ministarstva nauke Republike Srbije, br. TR 31003]

The main aim of this study was to investigate the impact of the coal mine in Lazarevac, and the coal-fired power stations in Obrenovac, on the activity concentrations of radionuclides 40K, 238U, 232Th, and 137Cs in some parts of human food chain of people living in the surrounding area. The obtained results showed that natural environment around the examined coal mine and the coal-fired power stations are not significantly affected by the emission of primordial radionuclides. The activity concentrations of 238U in the soil around the open coal mine and the coal processing installations (66.4-76.0 Bq/kg) and in the soil around the coal-fired power stations (55.5-61.2 Bq/kg) were not significantly higher than the average values in Serbia. The significant increase in the activity concentrations of natural radioisotopes in the samples of soil, vegetation, and animal products, was not confirmed. Food of animal origin used in human consumption is safe, i. e. not contaminated by radiation. [Projekat Ministarstva nauke Republike Srbije, br. TR 31003 i br. TR34013]

The radiological risk due to the presence of natural and man-made radionuclides in beach sands from several renowned seaside and riverbank public beaches was estimated in this study. The exposure levels to terrestrial radiation of the beaches were determined, as well as hazards due to human use of the analyzed sands in industry and in building constructions. Specific radionuclides concentrations in the sand samples were determined by standard gamma-spectrometry. The corresponding radiation hazards arising due to the use of sand as a building material were estimated by three different radiological hazard indices. The total absorbed gamma dose rate in the air was determined and the corresponding annual effective dose outdoors was estimated. The obtained data are relevant both from human health and environmental monitoring aspects.

Background/Aim. Eustachian tube is a connection between throat and the middle ear. Inflammatory processes and malformations of nasal cavity could lead to dysfunction of the whole upper respiratory tract, this emphasizing the evaluation of the Eustachian tube function both in surgery and in medicine in general. The aim of this study was to evaluate the Eustachian tube passage and function by tympanometry in different types of nasal resistance. Methods. Eustachian tube passage and function was tested in 102 patients with different types of nasal pathology and nasal resistance and compared to the results of 41 healthy persons with normal values of nasal resistance included in the control group. The patients with nasal pathology were divided into three subgroups: with mechanical, inflammatory and mixed alterations. Nasal resistance was carried out with constant body plethysmography (Jaeger). The test of Eustachian tube passage and function was performed using tympanometric Toynbee-deglutition/Valsalva-deglutition test. The results of measurements were compared with those in the healthy control group and analyzed by means of parametric and nonparametric statistic tests, Pearson χ2 test, Fisher test of exact probability and variance analysis. Results. The subgroup with inflammatory alterations had significantly higher values of pathological tympanograms than other subgroups and the control group (p < 0,05). The dysfunction of the Eustachian tube was significantly more present in all subgroups than in the control group (p < 0,05). Conclusion. Pathological form of tympanograms is more often present in purely inflammatory changes of nasal cavities with higher nasal resistance than in mechanical nasal obstruction. All forms of higher nasal resistance are more often accompanied with Eustachian tube dysfunction. There was no significant differences in Eustachian tube passage between the subgroups and the control group.

Abstract Background Portable energy dispersive X-ray fluorescence (pEDXRF) spectrometry analysis was applied for the characterisation of archaeological ceramic findings from three Neolithic sites in Serbia. Two dimension reduction techniques, principal component analysis (PCA) and scattering matrices-based dimension reduction were used to examine the possible classification of those findings, and to extract the most discriminant features. Results A decision-making procedure is proposed, whose goal is to classify unknown ceramic findings based on their elemental compositions derived by pEDXRF spectrometry. As a major part of decision-making procedure, the possibilities of two dimension reduction methods were tested. Scattering matrices-based dimension reduction was found to be the more efficient method for the purpose. Linear classifiers designed based on the desired output allowed for 7 of 8 unknown samples from the test set to be correctly classified. Conclusions Based on the results, the conclusion is that despite the constraints typical of the applied analytical technique, the elemental composition can be considered as viable information in provenience studies. With a fully-developed procedure, ceramic artefacts can be classified based on their elemental composition and well-known provenance.

The most common scientific analysis of archaeological ceramics aims to determine the raw material source and/or production technology. Scientists and archaeologists widely use XRF-based techniques as a tool in a provenance study. After conducting XRF analysis, the results are often analyzed using multivariate analysis in addition to interpretation and conclusions. Various multivariate techniques have already been applied in archaeological ceramics provenance studies to reveal different raw material sources, identify imported pieces, or determine different production recipes. This study aims to evaluate the results of multivariate analysis in the provenance study of ceramics that belong to three cultures that settled in the same area during various prehistoric periods. Portable energy-dispersive X-ray fluorescence spectrometry (pEDXRF) was used to determine the elemental composition of the ceramic material. The ceramic material was prepared in two different ways. The ceramic body material was ground into powder, homogenized, and then pressed into tablets. After that, the same fragments are polished in suitable places. Quantitative and qualitative analyses were performed on the tablets and polished pieces. The results were subjected to both unsupervised and supervised multivariate analysis. Based on the results, it was concluded that qualitative analysis of the well-prepared shards' surface using EDXRF spectrometry could be utilized in provenance studies, even when the ceramic assemblages were made of similar raw materials.

With people living with HIV (PLWH) reaching the senium, the importance of aging-related comorbidities such as metabolic syndrome (MS) becomes increasingly important. This study aimed to determine the additive effect of MS on brain atrophy in PLWH. This prospective study included 43 PLWH, average age of 43.02 ± 10.93 years, and 24 healthy controls, average age of 36.87 ± 8.89 years. PLWH were divided into two subgroups: without MS and with MS, according to NCEP ATP III criteria. All patients underwent brain magnetic resonance imaging (MRI) on a 3T clinical scanner with MR volumetry, used for defining volumes of cerebrospinal fluid (CSF) spaces and white and grey matter structures, including basal ganglia. A Student's t -test was used to determine differences in brain volumes between subject subgroups. The binary classification was performed to determine the sensitivity and specificity of volumetry findings and cut-off values. Statistical significance was set at p < 0.05. PLWH presented with significantly lower volumes of gray matter, putamen, thalamus, globus pallidus, and nc. accumbens compared to healthy controls; cut-off values were: for gray matter 738.130 cm 3 , putamen 8.535 cm 3 , thalamus 11.895 cm 3 , globus pallidus 2.252 cm 3 , and nc. accumbens 0.715 cm 3 . The volumes of CSF and left lateral ventricles were found to be higher in PLWH with MS compared to those without MS, where, with a specificity of 0.310 and sensitivity of 0.714, it can be assumed that PLWH with a CSF volume exceeding 212.83 cm 3 are likely to also have MS. This suggests that PLWH with metabolic syndrome may exhibit increased CSF volume above 212.83 cm 3 as a consequence of brain atrophy. There seems to be an important connection between MS and brain volume reduction in PLWH with MS, which may add to the accurate identification of persons at risk of developing HIV-associated cognitive impairment., Competing Interests: The authors declare no conflicts of interest.

EDXRF spectrometry is a well-established and often-used analytical technique in examining materials from which cultural heritage objects are made. The analytical results are traditionally subjected to additional multivariate analysis for archaeometry studies to reduce the initial data's dimensionality based on informative features. Nowadays, artificial intelligence (AI) techniques are used more for this purpose. Different soft computing techniques are used to improve speed and accuracy. Choosing the most suitable AI method can increase the sustainability of the analytical process and postprocessing activities. An autoencoder neural network has been designed and used as a dimension reduction tool of initial [Formula: see text] data collected in the raw EDXRF spectra, containing information about the selected points' elemental composition on the canvas paintings' surface. The autoencoder network design enables the best possible reconstruction of the original EDXRF spectrum and the most informative feature extraction, which has been used for dimension reduction. Such configuration allows for efficient classification algorithms and their performances. The autoencoder neural network approach is more sustainable, especially in processing time consumption and experts' manual work., (© 2024. The Author(s).)

LncRNAs represent an abundant group of noncoding transcripts, some of which carry out important regulatory functions. To survey the biological and molecular roles of lncRNAs, reliable strategies for their genetic inactivation are required. Several lncRNA features make them challenging to target by genome editing. First, lncRNA loci often span large genomic distances. As such, full or partial deletion alleles are not always easy to generate and interpret as they might affect DNA regulatory elements. Second, in contrast to proteins, lncRNA transcripts are usually resistant to the minimally invasive approach of point substitutions. Third, lncRNA sequences exhibit rapid evolutionary turnover, impeding prediction and targeting of the specific functional sequence elements. Nonetheless, advances in genome editing and comparative genomics have expanded the repertoire of genetic strategies to dissect lncRNA functions in model organisms and cell lines. In this review, we discuss several approaches that have been used to generate lncRNA mutant alleles, focusing on vertebrate lncRNAs. We also briefly highlight comparative genomics approaches to identify conserved lncRNA sequence motifs, which represent attractive target sequences to abrogate lncRNA functions and to pinpoint functional contributions of these elements., (© 2022 The Authors. IUBMB Life published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant disorder that predisposes individuals to developing tumors in many organs. There is significant phenotypic variability and genetic variants encountered within this syndrome, posing a considerable challenge to patient care. The lack of VHL variant data sharing paired with the absence of aggregated genotype-phenotype information results in an arduous process, when characterizing genetic variants and predicting patient prognosis. To address these gaps in knowledge, the Clinical Genome Resource (ClinGen) VHL Variant Curation Expert Panel (VCEP) has been resolving a list of variants of uncertain significance within the VHL gene. Through community curation, we crowdsourced the laborious task of variant annotation by modifying the ClinGen Community Curation (C3)-developed Baseline Annotation protocol and annotating all published VHL cases with the reported genotype-phenotype information in Hypothes.is, an open-access web annotation tool. This process, incorporated into the ClinGen VCEP's workflow, will aid in their curation efforts. To facilitate the curation at all levels of genetics expertise, our team developed a 4-day biocuration training protocol and resource guide. To date, 91.3% of annotations have been completed by undergraduate and high-school students without formal academic genetics specialization. Here, we present our VHL-specific annotation protocol utilizing Hypothes.is, which offers a standardized method to present case-resolution data, and our biocuration training protocol, which can be adapted for other rare disease platforms. By facilitating training for community curation of VHL disease, we increased student engagement with clinical genetics while enhancing knowledge translation in the field of hereditary cancer. Database URL: https://hypothes.is/groups/dKymJJpZ/vhl-hypothesis-annotation., (© The Author(s) 2023. Published by Oxford University Press.)

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome where individuals are predisposed to tumor development in the brain, adrenal gland, kidney, and other organs. It is caused by pathogenic variants in the VHL tumor suppressor gene. Standardized disease information has been difficult to collect due to the rarity and diversity of VHL patients. Over 4100 unique articles published until October 2019 were screened for germline genotype-phenotype data. Patient data were translated into standardized descriptions using Human Genome Variation Society gene variant nomenclature and Human Phenotype Ontology terms and has been manually curated into an open-access knowledgebase called Clinical Interpretation of Variants in Cancer. In total, 634 unique VHL variants, 2882 patients, and 1991 families from 427 papers were captured. We identified relationship trends between phenotype and genotype data using classic statistical methods and spectral clustering unsupervised learning. Our analyses reveal earlier onset of pheochromocytoma/paraganglioma and retinal angiomas, phenotype co-occurrences and genotype-phenotype correlations including hotspots. It confirms existing VHL associations and can be used to identify new patterns and associations in VHL disease. Our database serves as an aggregate knowledge translation tool to facilitate sharing information about the pathogenicity of VHL variants., (© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)