Background Immune checkpoint inhibitors (ICIs) have significantly improved the outcome in metastatic cutaneous melanoma (CM). However, therapy response is limited to subgroups of patients and clinically useful predictive biomarkers are lacking. Methods To discover treatment-related systemic changes in plasma and potential biomarkers associated with treatment outcome, we analyzed serial plasma samples from 24 patients with metastatic CM, collected before and during ICI treatment, with mass-spectrometry-based global proteomics (high-resolution isoelectric focusing liquid chromatography–mass spectrometry (HiRIEF LC-MS/MS)) and targeted proteomics with proximity extension assays (PEAs). In addition, we analyzed plasma proteomes of 24 patients with metastatic CM treated with mitogen-activated protein kinase inhibitors (MAPKis), to pinpoint changes in protein plasma levels specific to the ICI treatment. To detect plasma proteins associated with treatment response, we performed stratified analyses in anti-programmed cell death protein 1 (anti-PD-1) responders and non-responders. In addition, we analyzed the association between protein plasma levels and progression-free survival (PFS) by Cox proportional hazards models. Results Unbiased HiRIEF LC-MS/MS-based proteomics showed plasma levels’ alterations related to anti-PD-1 treatment in 80 out of 1160 quantified proteins. Circulating PD-1 had the highest increase during anti-PD-1 treatment (log2-FC=2.03, p=0.0008) and in anti-PD-1 responders (log2-FC=2.09, p=0.005), but did not change in the MAPKis cohort. Targeted, antibody-based proteomics by PEA confirmed this observation. Anti-PD-1 responders had an increase in plasma proteins involved in T-cell response, neutrophil degranulation, inflammation, cell adhesion, and immune suppression. Furthermore, we discovered new associations between plasma proteins (eg, interleukin 6, interleukin 10, proline-rich acidic protein 1, desmocollin 3, C-C motif chemokine ligands 2, 3 and 4, vascular endothelial growth factor A) and PFS, which may serve as predictive biomarkers. Conclusions We detected an increase in circulating PD-1 during anti-PD-1 treatment, as well as diverse immune plasma proteomic signatures in anti-PD-1 responders. This study demonstrates the potential of plasma proteomics as a liquid biopsy method and in discovery of putative predictive biomarkers for anti-PD-1 treatment in metastatic CM.

The reliability of the operations of the high-voltage circuit breaker is the key to the stable power system, so it’s fault diagnosis and condition assessment it is of great significance. Considering that high-voltage circuit breaker vibration fingerprints contain valuable information about its mechanical integrity and that the vibration measurements are non-invasive, this paper presents the algorithm for the analysis of residual life of a high-voltage circuit breaker. The algorithm is based on the variational mode decomposition (VMD) and Shannon information entropy mean (EM) in order to obtain indices that are used as an indicator of the circuit breaker structural deterioration.

Abstract Introduction. Bladder cancer is the most common malignancy involving the urinary system. Recent research tends to emphasize the role of oxidative stress products in the carcinogenesis of bladder cancer. The level of oxidative stress can be measured by assessing the MDA levels. This study aimed to evaluate serum MDA levels in patients with bladder cancer, as well as to determine its potential role as a biomarker in the diagnosis of the disease and progression risk considerations. Methods. The study was designed as a cross-sectional study and included 90 patients, divided into three groups with 30 patients each: Ta, T1and T2–T4 group, based on histopathological findings after transurethral resection of the tumor. The control group included 30 healthy volunteers. MDA level was determined using the spectrophotometric method. Results. Serum MDA level in patients with bladder cancer [0.86 (0.78–1.05) μmol/L] was significantly higher than the serum MDA level in control group [0.70 (0.69–0.72) μmol/L] (p < 0.001). Serum MDA level in Ta group [0.73 (0.70–1.05) μmol/L], T1 group [0.85 (0.80–1.12) μmol/L] and in T2–T4 group [0.91 (0.84–1.04) μmol/L] was significantly higher than the serum MDA level in control group [0.70 (0.69–0.72) μmol/L] (p < 0.01). MDA level in T1 and T2–T4 group was significantly higher than the MDA level in Ta group (p < 0.01). No significant difference was observed in MDA level between T1 and T2–T4 group (p = NS). A statistically significant positive correlation was found between tumor size and serum MDA level in patients with bladder cancer (rho = 0.254 p < 0.01). Conclusions. The results of the present study suggest that MDA serum level might play a significant role as a biomarker in the diagnosis of bladder cancer, as well as in the monitoring of its progression.

Under the AKP government, Turkey’s foreign policy towards the Western Balkans, and Bosnia and Herzegovina in particular, has led many analysts to suspect it of possessing neo-imperial, or so-called neo-Ottoman, objectives. These suspicions have been compounded by the repeated declarations of former Prime Minister Davutoğlu and current President Erdoğan that the history and religious identity shared by Turks and Western Balkan Muslims forms the basis of both Turkish-Balkan relations and a common future. Critical examination of official Ankara’s attitudes toward the Western Balkans in general, and especially Bosnia and Herzegovina, identifies four distinct phases in which cultural, historical, and religious appeals morphed into the set of distinctive foreign policies. These policies have also been shaped by pragmatic pursuits of regional influence, the effects of internal (Turkish) transformations, and more recently, the ad hoc policies of President Erdoğan. This article will reconstruct the development of Turkish foreign policy since 1990, from multilateral and soft power efforts to religious and economic objectives, and will analyse the limits of this policy.

Machine learning, particularly in the form of deep learning (DL), has driven most of the recent fundamental developments in artificial intelligence (AI). DL is based on computational models that are, to a certain extent, bio‐inspired, as they rely on networks of connected simple computing units operating in parallel. The success of DL is supported by three factors: availability of vast amounts of data, continuous growth in computing power, and algorithmic innovations. The approaching demise of Moore's law, and the consequent expected modest improvements in computing power that can be achieved by scaling, raises the question of whether the progress will be slowed or halted due to hardware limitations. This article reviews the case for a novel beyond‐complementary metal–oxide–semiconductor (CMOS) technology—memristors—as a potential solution for the implementation of power‐efficient in‐memory computing, DL accelerators, and spiking neural networks. Central themes are the reliance on non‐von‐Neumann computing architectures and the need for developing tailored learning and inference algorithms. To argue that lessons from biology can be useful in providing directions for further progress in AI, an example‐based reservoir computing is briefly discussed. At the end, speculation is given on the “big picture” view of future neuromorphic and brain‐inspired computing systems.

Mechanisation used in forest utilisation has an impact on the occurrence of damage in stand and on forest land. The research in this work had the objective of determining damage on fir trees and other tree species during felling and processing of trees and their skidding using the forest cable-skidder. The research wasconducted in mixed beech and fir forests in the area of FMA “Glamočko”, M.U. “Hrbinje-Kujača”. The following data were gathered on damaged trees: tree type, breast height diameter, economic importance of the tree, amount of damage, location of damage, cause of damage, types of damage. Damage was recorded on a total of 305 trees, 133 trees of silver fir (Abies alba), 130 trees of European beech (Fagus sylvatica), 33 trees of European spruce (Picea abies), 8 trees of rowan/mountain-ash (Sorbusaucuparia) and one tree of sycamore (Acer pseudoplatanus). The overall damage intensity was 18.7%, but together with the old damages, the overall number of ‘wounds’ is 496. According to this, when the old damage isalso considered, then the intensity of damage amounts to 30.6%. The largest amount of damage is in the diameter sub-class ranging from 10 to 14.99 cm. According to the cause of damage, the largest amount of damage occurred during the wood extraction phase (217 trees), while during the felling phase, 88 trees or 29% were damaged. Since the wood extraction phase is divided into the winching and skidding phases, the total number of damaged trees during the winching phase amounted to 157 or 52%, while during the skidding phase, the number of damaged trees was 60 or 19%. To reduce damage to the trees during following operations in forest utilisation, it is necessary to perform more frequent training of all employees working on forest utilisation, to increase controls in execution of operations during forest utilisation, modernise machines used during forest exploitation, and in quality manner open compartments with forest road infrastructure.

This paper presents a framework capable of accurately forecasting future sales in the retail industry and classifying the product portfolio according to the expected level of forecasting reliability. The proposed framework, that would be of great use for any company operating in the retail industry, is based on Facebook's Prophet algorithm and backtesting strategy. Real-world sales forecasting benchmark data obtained experimentally in a production environment in one of the biggest retail companies in Bosnia and Herzegovina is used to evaluate the framework and demonstrate its capabilities in a real-world use case scenario.

Derived from mesenchymal stem cells (MSCs) under the influence of various local factors and growth hormones, osteoblasts are one of the leading components of the bone tissue. 1,25-dihydroxyvitamin D3 (calcitriol), an active form of vitamin D, plays an important role in retaining calcium and phosphate homeostasis within the body. Since vitamin D is also known to have effects on cell proliferation, our study aimed to investigate the effects of different concentrations of calcitriol on the proliferation of in vitro cultured osteoblast-like cells from the bone marrow of 90-95 days old young adult rats of both sexes. Calcitriol was applied at six (6) different concentrations (nM): 0.1, 1, 10, 20, 40 i 60. Each concentration was tested four times, counting the cells after 24 and 48 hours. After 24 and 48 hours treatment, the most effective dose of calcitriol for cell proliferation was 0.1 nM for both males and females. The greatest reduction in the frequency of OB-like cells from both sexes after treatment of 24 and 48 hours, was a 60 nM calcitriol concentration. Higher proliferative values of osteoblast-like cells were obtained in males compared to those obtained in females. Thus, the results of the current study reveal that calcitriol treatment induces the proliferation of osteoblast-like cells in a dose-dependent manner and this effect shows difference in cells from different genders.

Purpose: Determining the state of the student and his situational-motor skills, and their comparison, enables the teacher to control his work in an immediate manner, and he programmes and implements well planned and additional contents in order to realize the set goals. In order to achieve these functions, it is necessary to determine the current state of the students, as well as the state after the implemented specific contents and programs. The aim of the research was to determine the partial changes (differences) of situationalmotor abilities that were created under the influence of a four-month program of basketball, volleyball and handball in the pupils of the fifth grades of elementary school. Material: The study included N = 106 class V students, aged 10 to 11 years. The sample of respondents was divided into two subgroups, an experimental group (53 students), who conducted physical and health education classes according to the modified plan and program of sports games (basketball, volleyball and handball) for a half-year and control group (53 students) who attended regular classes from physical and health culture according to the current curriculum. 9 variables were used to assess situational-motor abilities. Descriptive statistics and discriminatory analysis were used to determine the changes (differences) in situational-motor skills. Results: The results of the research at the descriptive level showed certain differences between the groups in the final versus the initial measurements on the individual variables of situational motors. Based on the results of the discriminatory analysis, the relative contribution of each of the variables of the situational motor in the final measurement is seen. The SMKVLS (Running the ball with your hand in the slalom) and SMRBLZ (Throwing the ball against the wall for 30 seconds) variables are the biggest contributors, and the smallest SMOGCPM (Aiming the goal over the net from the basic stand) and SMOSD (Lower frontal serve). Conclusions: Physical and health culture in schools has the primary task of influencing positive transformation processes in all dimensions of students by applying appropriate content.

Background Universally, negative or misinformed stuttering attitudes abound, which often lead to inaccurate stereotyping and/or stigmatization of people who stutter [1]. Attitudes toward any phenomenon are partly formed by what a person believes to be true, as well as how they feel and react toward that phenomenon [2]. In stuttering, attitudinal research has been particularly critical in global efforts to reduce marginalization of people who stutter. St. Louis [3] developed a standard and translatable stuttering attitude instrument, the Public Opinion Survey on Human Attributes-Stuttering (POSHA-S), which provides an impression about respondents’ overall beliefs about stuttering and Purpose: A growing body of research has addressed children’s stuttering attitudes between preschool and upper elementary school. Attitudes among preschoolers and kindergarteners have been reported to be much lower that fifth graders’ attitudes, at which time children’s attitudes seemingly converge with their parents’ attitudes. It has been suggested these observed changes align with children’s social and cognitive development and are resistant to the influence of other variables, such as their culture. The purposes of this study were (a) to extend cultural examinations of children’s stuttering attitudes in a sample of kindergarteners through sixth graders in Bosnia & Herzegovina (B&H), and (b) to compare their attitudes with their parents’ attitudes.