Quantitative MRI (qMRI) probes the microstructural properties of the central nervous system (CNS) by providing biophysical measures of tissue characteristics. In this work, we aimed to (i) identify qMRI measures that distinguish histological lesion types in postmortem multiple sclerosis (MS) brains, especially the remyelinated ones; and to (ii) investigate the relationship between those measures and quantitative histological markers of myelin, axons, and astrocytes in the same experimental setting. Three fixed MS whole brains were imaged with qMRI at 3T to obtain magnetization transfer ratio (MTR), myelin water fraction (MWF), quantitative T1 (qT1), quantitative susceptibility mapping (QSM), fractional anisotropy (FA) and radial diffusivity (RD) maps. The identification of lesion types (active, inactive, chronic active, or remyelinated) and quantification of tissue components were performed using histological staining methods as well as immunohistochemistry and immunofluorescence. Pairwise logistic and LASSO regression models were used to identify the best qMRI discriminators of lesion types. The association between qMRI and quantitative histological measures was performed using Spearman's correlations and linear mixed‐effect models. We identified a total of 65 lesions. MTR and MWF best predicted the chance of a lesion to be remyelinated, whereas RD and QSM were useful in the discrimination of active lesions. The measurement of microstructural properties through qMRI did not show any difference between chronic active and inactive lesions. MWF and RD were associated with myelin content in both lesions and normal‐appearing white matter (NAWM), FA was the measure most associated with axon content in both locations, while MWF was associated with astrocyte immunoreactivity only in lesions. Moreover, we provided evidence of extensive astrogliosis in remyelinated lesions. Our study provides new information on the discriminative power of qMRI in differentiating MS lesions ‐especially remyelinated ones‐ as well as on the relative association between multiple qMRI measures and myelin, axon and astrocytes.

Introduction Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. Methods In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Results and discussion Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

In recent decades, many researchers and practitioners have believed that reaching a high level of business excellence leads to the continuous realization of a set of business goals. In the literature, a vast number of models for business excellence evaluation that contain different criteria depending on the cultural, technological, organizational, and socio-economic factors can be found. The aims of the proposed fuzzy two-stage model are to address some of the main shortcomings of the EFQM2020 model and to adapt it to the needs of process manufacturing. The relative importance of quality criteria and their values are presented by pre-defined linguistic expressions modeled by the triangular fuzzy numbers. The determination of the weight vector of criteria is stated as a fuzzy group decision-making problem and determined by using the fuzzy best-worst method. The proposed fuzzy multi-objective optimization by ratio analysis is implemented for determining the rank of enterprises. The management initiatives that should lead to the improvement of business excellence should be based on the business practices of enterprises that are highly placed in the rank. Testing and verification of the proposed model are performed on real data originating from enterprises operating in the same economic sector.

Cause-effect graphs are often used as a method for deriving test case suites for black-box testing different types of systems. This paper represents a survey focusing entirely on the cause-effect graphing technique. A comparison of different available algorithms for converting cause-effect graph specifications to test case suites and problems which may arise when using different approaches are explained. Different types of graphical notation for describing nodes, logical relations and constraints used when creating cause-effect graph specifications are also discussed. An overview of available tools for creating cause-effect graph specifications and deriving test case suites is given. The systematic approach in this paper is meant to offer aid to domain experts and end users in choosing the most appropriate algorithm and, optionally, available software tools, for deriving test case suites in accordance to specific system priorities. A presentation of proposed graphical notation types should help in gaining a better level of understanding of the notation used for specifying cause-effect graphs. In this way, the most common mistakes in the usage of graphical notation while creating cause-effect graph specifications can be avoided.

Order-picking process management is one of the most demanding tasks within the operations of a warehouse system. It is especially evident in companies that have a high intensity of product flows, so the question of increasing the productivity of order picking arises. In this paper, a novel integrated fuzzy MCDM (Multicriteria Decision-Making) model was developed for the evaluation and selection of information technologies for order picking in a warehouse system, which is one of the most important novelties and contributions of the paper. Barcode, pick-to-light, pick-to-voice, and pick-to-vision technologies were evaluated based on IMF SWARA (improved fuzzy stepwise weight assessment ratio analysis) and fuzzy EDAS (evaluation based on distance from average solution) based on Z numbers. IMF SWARA-Z was applied to determine the importance of four criteria while the information technologies for order picking were evaluated with the fuzzy EDAS-Z method. The averaging of the estimates of the critera and alternatives was performed using the fuzzy Dombi aggregator. The results show that in this particular case under these research conditions, pick-to-vision is the best order-picking technology. Subsequently, validation tests were carried out, and they included the simulation of criteria weights and the impact of the reverse rank matrix.

BACKGROUND: Defibrillators are medical devices (MDs) used in the most critical situations, hence their performance must be ensured at all times. This requires defibrillators to be subjected to regular performance assessments after they have been placed on the market. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel evidence-based method for conformity assessment testing of defibrillators. METHOD: The proposed method is developed in accordance with the International Organisation of Legal Metrology (OIML) guidelines and is intended to be used for conformity assessment testing of defibrillators for post-market surveillance purposes. RESULTS: The developed method was validated from 2018 to 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of defibrillators as a method used during PMS contributes to significant improvement in devices’ accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of defibrillators during PMS, besides increasing reliability of the devices, is the first step in the digital transformation of the management of these devices in healthcare institutions opening possibility for use of artificial intelligence.

Introduction: Pleural complications in coronavirus disease 2019 (COVID-19) are relatively uncommon findings. Pleural involvement in these patients may directly correlate to disease severity and overall prognosis. We aimed to review clinical features and treatment approaches for pleural complications (accumulation of fluid/air inside the pleural cavity) in 45 patients with COVID-19, who were treated at our institution between April 2020 and October 2021. Methods: Our study was designed as single-center, observational, cross-sectional study of 45 patients with COVID-19 and at least one radiologically verified pleural complication. Demographic data, radiological findings, as well as type and number of thoracosurgical intervention(s) were recorded for every patient. We included patients of both genders and various age groups, with positive RT-PCR assay for COVID-19 and radiologic features of pleural complications, which required single or multiple thoracosurgical interventions. Results: Unilateral pleural complications were more common, right-sided pleural complications were found in 44.4% of patients. Right-sided pneumothorax was reported in 26.7% of patients. Almost one-fourth of our patients required invasive mechanical ventilation. Tube thoracostomy was performed in 84.4% of patients with unilateral pleural complications. A fatal outcome was most common in patients over 60 years old. More than half of patients with bilateral pleural complications died in our study. Conclusions: Pleural complications are a rare finding in patients with COVID-19. Tube thoracostomy is the mainstay of treatment for most symptomatic patients with pleural complications. Future research should be directed toward investigation of long-term pulmonary consequences in patients with COVID-19.

Ljudi i mjesta su povezani u više slučajeva, mjesta i gradovi su glavno sjećanje našeg života i podsjećaju nas na naše zajedničko naslijeđe. Kao svjetionici u našem sjećanju, oni se odnose na nas, rodni grad ili mjesta koja smo posjetili ili kroz koja samo prolazimo kada smo na odmoru, mjesta ostaju u našoj viziji zauvijek. Živimo, posjećujemo i radimo na ovim mjestima i smatramo ih svojima. Ovo je dodatna vrijednost kada se razmišlja o događaju u zajednici, brendiranju ili mjestu marketinške prakse razvoju destinacije. Bez obzira da li se radi o stanovniku ili posjetiocu, mi imamo posebnu vezu sa mjestom ili događajem, ovaj događaj je alat za dobru praksu „samo mjesto na kojem vrijedi živjeti, je mjesto koje vrijedi posjetiti“. Vizija i vrijednosti mjesta su slike njihovih stanovnika. Ova mjesta žele da povećaju svoju ekonomiju i status kroz turizam i razvoj treba da dođu do glavnih tema o tome:  Želimo da budemo poznati po...?  Najbolji smo u?  Kada izgovore ime našeg mjesta o čemu razmišljaju?  Imamo ovo i ovo, kako to možemo iskoristiti?

ABSTRAKT Akutna bubrežna insuficijencija nakon kontrastnih procedura ili contrast indukovana nefropatija (CIN-Contrast-induced nephropaty) se definiše kao povečanje vrijednosti serum kreatinina najmanje 0,5 % mg/dl ili 25% do 50 % u odnosu na predproceduralne vrijednosti u toku 48 do 72 sata nakon apliciranja kontrasta, u odsustvu drugih objašnjenja za nastanak oštećenja bubrežne funkcije. Ona je odgovorna za pojavu akutne bubrežne insuficijencije u 11 do 14,5 % slućajeva. CILJ STUDIJE: Cilj ove studije je određivanje rizićnih grupa pacijenata i faktora kao I profilaktičkih mjera za kontrastnu nefropatiju nakon koronarografije. U studiju je ukljućeno 200 pacijenata (dijabetičari i nedijabetičari) koji su uradili koronarografiju zbog indikacije na koronarnu bolest. ZAKLJUČAK: Rizićni faktori za nastanak kontrastne nefropatije kod ovih pacijenata su, šećerna bolest, starija životna dob, aplicirana veća kolićina kontrasta, prethodne bolesti bubrega i srćana slabost.

Essential role in replication and transcription of coronavirus makes the main protease of SARS-CoV-2 a great traget for drug design. The aim of this study was to predict structural interactions of compounds isolated from the Bosnian-Herzegovinian endemic plant Knautia sarajevensis (G. Beck) Szabó against the 3CLpro of SARS-CoV-2 virus. The three-dimensional crystal structure of SARS-CoV-2 main protease was retrieved from the RCSB Protein Data Bank and the three-dimensional structures of isolated compounds were obtained from the PubChem database. Active site was predicted using PrankWeb, while the preparation of protease and compounds was performed using AutoDock Tools and OpenBabel. Molecular docking was carried out using AutoDock Vina. Structural interactions are visualised and analyzed using PyMOL, LigPlus and UCSF Chimera. Apigenin, kaempferol, myricetin and quercetin showed the highest binding affinity for SARS-CoV-2 main protease and formed significant hydrogen bonds with the given protein. Results obtained in this study are in accordance with previous studies and showed that these compounds could potentially have antiviral effects against SARS-CoV-2. These findings indicate that K. sarajevensis could be potentially utilized as an adjuvant in the treatment of coronavirus disease 2019, but further pharmacological studies are required in order to prove the potential medicinal use of the plant.

We present a new algorithm called policy iteration plus (PI+) for the optimal control of nonlinear deterministic discrete-time plants with general cost functions. PI+ builds upon classical policy iteration and has the distinctive feature to enforce recursive feasibility under mild conditions, in the sense that the minimization problems solved at each iteration are guaranteed to admit a solution. While recursive feasibility is a desired property, it appears that existing results on the policy iteration algorithm fail to ensure it in general, contrary to PI+. We also establish the recursive stability of PI+: the policies generated at each iteration ensure a stability property for the closed-loop system. We prove our results under more general conditions than those currently available for policy iteration, by notably covering set stability. Finally, we present characterizations of near-optimality bounds for PI+ and prove the uniform convergence of the value functions generated by PI+ to the optimal value function. We believe that these results would benefit the burgeoning literature on approximate dynamic programming and reinforcement learning, where recursive feasibility is typically assumed without a clear method for verifying it and where recursive stability is essential for safe operation of the system.

ABSTRACT Uvod: Karcinom glave i vrata čini 3-5 % svih malignih oboljenja, koji je većinom zastupljen kod muškaraca. Napretkom radioterapije omogućen je optimalniji pristup u liječenju karcinoma glave i vrata, sa poboljšanim ishodom liječenja. Primjena savremenih imidžing tehnika u verifikaciji preciznosti tretmana znatno je promijenila tok radioterapije u liječenju malignih bolesti u smislu eskalacije doze na ciljni volumen uz veću poštedu zdravih struktura. Svrha rada je dokazati značaj i ulogu slikovne verifikacije CBCT imidžing metodom u preciznosti liječenja i kontroli tumora tokom tretmana. Materijal i metode: Istraživanje je provedeno prospektivno u trajanju od 6 mjeseci, na Klinici za onkologiju, Kliničkog centra Univerziteta u Sarajevu. U studiju je uključeno 30 pacijenata sa karcinomom glave i vrata, kod kojih je primjenom slikovne verifikacije CBCT-om uočen gubitak tjelesne težine ili promjena ciljnog volumena. Pacijenti su zračeni VMAT tehnikom na linearnom akceleratoru TrueBeam. Rezultati: Rezultati istraživanja su pokazali da je većina pacijenata bila muškog spola (19), starije životne dobi, sa karcinom larinksa koji je bio prisutan u čak 11 ispitanika. Jači nusefekti bili su prisutni samo kod 3,33% pacijenata, a najzastupljenije neželjene reakcije bile su blaga promuklost, suhoća usta, zamor, otežano gutanje. Od ukupnog broja pacijenata, kod 16 pacijenata uočeno je smanjenje volumena targeta koji je inicijalno prosječno iznosio 80,16 cm3, dok je nakon prosječno 18 frakcija zračenja iznosio 77,58 cm3, što je sigifikanto statistički dokazano (p= 0,007). Utvrđeno je smanjenje volumena lijeve parotidne žlijezde nakon reskeniranja u odnosu na inicijalnu vrijednost (17.37±7.55/16.93±7.06 cm3). Kod svih pacijenata na CBCT volumetrijskim slikama uočen je gubitak tjelesne težine. Zaključak: Radioterapija karcinoma glave i vrata jedan je od učinkovitih modaliteta liječenja, koji moće biti praćen određenim neželjenim reakcijama. Primjena IGRT-a na osnovu kompjuterizirane tomografije konusnog snopa (CBCT), uveliko doprinosi peciznoj isporuci propisane doze zračenja, uz smanjenu toksičnost tretmana. Volumetrijski prikaz anatomskih struktura CBCT metodom, omogućio je da se promijeni tok kursa radioterapije u smislu prilagođavanja PTV margina u toku tretmana, odnosno primjenu adaptivne radioterapije.  

This note gives an overview of the tools for the precision matching of ultraviolet theories to the Standard Model effective field theory (SMEFT) at the tree level and one loop. Several semi- and fully automated codes are presented, as well as some supplementary codes for the basis conversion and the subsequent running and matching at low energies. A suggestion to collect information for cross-validations of current and future codes is made.

Data from past earthquakes is an important tool to reveal the impact of future earthquakes on engineering structures, especially in earthquake-prone regions. These data are important indicators for revealing the seismic loading effects that structures will be exposed to in future earthquakes. Five different earthquakes from six countries with high seismic risk were selected and were within the scope of this study. The measured peak ground acceleration (PGA) for each earthquake was compared with the suggested PGA for the respective region. Structural analyzes were performed for a reinforced-concrete (RC) building model with four different variables, including the number of storeys, local soil types, building importance class and concrete class. Target displacements specified in the Eurocode-8 were obtained for both the suggested and measured PGA values for each earthquake. The main goal of this study is to reveal whether the proposed and measured PGA values are adequately represented in different countries. We tried to reveal whether the seismic risk was taken into account at a sufficient level. In addition, target displacements have been obtained separately in order to demonstrate whether the measured and suggested PGA values for these countries are adequately represented in structural analysis and evaluations. It was concluded that both seismic risk and target displacements were adequately represented for some earthquakes, while not adequately represented for others. Comments were made about the existing building stock of the countries considering the obtained results.

Background and Study Aim. Musculoskeletal disorders (MSD) are incredibly common and are often related to work load. For any occupational or public health intervention, injury prevention is preferred to injury treatment. Occupational health and injury prevention research has the potential to help mitigate MSD in the workplace. The aim of this study was to determine how the work demands of ski instructors may affect the health of their musculoskeletal system. Material and Methods. A cross-sectional study involved the participation of 87 ski instructors (age = 34.61 ±10.67) in Bosnia and Herzegovina (ATUS in Bosnia and Herzegovina). Observed variables were the prevalence of MSD measured using a modified Nordic questionnaire about injuries during the previous ski season (neck, shoulders, elbows, wrist, upper back, lower back, one or both hips, one or both knees, and ankle). Means and standard deviations for each of the variables were calculated, and differences between genders were examined using an independent sample t-test. Results. Prevalence of MSDs in ski instructors was most common in neck (13.8%), shoulders (12.6%), elbows (4.6%), wrist (9.2%), upper back (10.3%), lower back (46.0%), one or both hips (9.2%), one or both knees (29.9%), and ankle (9.2%). The results showed statistically significant differences in MSD between genders in the neck (p=.034); shoulders (p=.017); upper back (p=.027); one or both knees (p=.003) and in the ankle joint (p=.011). Conclusions. MSD’s are common in ski instructors, especially in the low back and knees of female employees. Future research or injury prevention programs would benefit these populations.