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Ersilia Vallefuoco, C. Bravaccio, G. Gison, L. Pecchia, A. Pepino

The majority of people with Autism Spectrum Disorder (ASD) exhibit difficulties in social communication and behavior, which hinder their learning capability, amid others. Among technological solutions for people with ASD, serious games are frequently used to enhance learning of specific skills and instructional contents. However, because of heterogeneity in applications and game design, few studies have investigated their use in training daily activities. This paper presents a 3D personalized serious game we developed and validated to help ASD patients practice with shopping activities. Personalized training is paramount in people with ASD, thus several elements of this game were personalized to improve engagement and therefore the effectiveness of the virtual training. In order to assess the validity of the game, ten subjects (age $\text{11.9} \pm \text{2.7}$, 20% female) with ASD played ten sessions of the serious game, once per week. The participants underwent a real-life experience pre- and post-training in a real-life supermarket. Changes in daily living skills among participants were evaluated through specific tools: a form based on the International Classification of Functioning, Disability and Health for Children and Youth; and the Vineland Adaptive Behavior Scale II. Significant improvements (p$< $0.05) were detected in the main skills trained with the serious game, especially in learning the shopping procedure, directing attention, and problem-solving skills. These findings suggest that personalized serious games can represent a prominent tool to enhance daily living skills, but future work should clinically validate their efficacy.

Stina Börchers, Jean-Philippe Krieger, Mohammed H. Asker, Ivana Marić, K. Skibicka

M. Cotte, V. Gonzalez, F. Vanmeert, Letizia Monico, C. Dejoie, M. Burghammer, L. Huder, W. de Nolf et al.

The European Synchrotron Radiation Facility (ESRF) has recently commissioned the new Extremely Brilliant Source (EBS). The gain in brightness as well as the continuous development of beamline instruments boosts the beamline performances, in particular in terms of accelerated data acquisition. This has motivated the development of new access modes as an alternative to standard proposals for access to beamtime, in particular via the “block allocation group” (BAG) mode. Here, we present the recently implemented “historical materials BAG”: a community proposal giving to 10 European institutes the opportunity for guaranteed beamtime at two X-ray powder diffraction (XRPD) beamlines—ID13, for 2D high lateral resolution XRPD mapping, and ID22 for high angular resolution XRPD bulk analyses—with a particular focus on applications to cultural heritage. The capabilities offered by these instruments, the specific hardware and software developments to facilitate and speed-up data acquisition and data processing are detailed, and the first results from this new access are illustrated with recent applications to pigments, paintings, ceramics and wood.

Mersid Poturak, Inda Mulaahmetović

The aim of the study is to investigate consumer attitudes towards specific Customer Social Responsibility Activities in Bosnia and Herzegovina. In order to support this research, a case study method, combined with qualitative and quantitative research methods (referenced survey) was used. To get an insight into the companies’ perspective, when it comes to an engagement in the employment practices, as an integral part of Corporate Social Responsibility, data regarding “The Most Desirable Employer” project- “Najpoželjniji poslodavac”, organized by Kolektiv d.o.o.-MojPosao.ba, for years 2020, 2019 and 2018 will be analyzed. The study should illustrate the exact scenario of customer loyalty in Bosnia and Herzegovina to the companies included in CSR activities and contribute to an advancement of overall knowledge in the field of CSR in Bosnia and Herzegovina. The directing outcome uncovers those corporate capacities have a critical part in fortifying the relationship between corporate social responsibility drives and customer trust in Bosnia and Herzegovina, in light of the fact that high corporate capacities with professional corporate social responsibility actions lead to high faithfulness of customers. The examination features the meaning of the corporate social responsibility activities, which are obligatory for authoritative achievement and guides the policymakers of companies, supervisors, and researchers.

M. D. De Herdt, Berdine van der Steen, R. J. Baatenburg de Jong, L. Looijenga, S. Koljenović, J. Hardillo

Simple Summary Head and neck cancer is the sixth most common cancer type worldwide, comprising tumors of the upper aero/digestive tract. Approximately 50% of these cancers originate in the oral cavity. Depending on disease stage, oral cancer patients are treated with single-modality surgery, or in combination with radiotherapy with or without chemotherapy. Despite advances in these modalities, the 5-year survival rate is merely 50%. Therefore, implementation of targeted therapies, directed against signaling molecules, has gained attention. One potential target is the MET protein, which can be present on the surface of cancer cells, orchestrating aggressive behavior. As cancer cells can shed the extracellular part of MET from their surface, it is important to identify for MET positive patients whether they possess the entire and/or only the intracellular part of the receptor to assess whether targeted therapies directed against the extracellular, intracellular, or both parts of MET need to be implemented. Abstract The receptor tyrosine kinase MET has gained attention as a therapeutic target. Although MET immunoreactivity is associated with progressive disease, use of targeted therapies has not yet led to major survival benefits. A possible explanation is the lack of companion diagnostics (CDx) that account for proteolytic processing. During presenilin-regulated intramembrane proteolysis, MET’s ectodomain is shed into the extracellular space, which is followed by γ-secretase-mediated cleavage of the residual membranous C-terminal fragment. The resulting intracellular fragment is degraded by the proteasome, leading to downregulation of MET signaling. Conversely, a membrane-bound MET fragment lacking the ectodomain (MET-EC-) can confer malignant potential. Use of C- and N-terminal MET monoclonal antibodies (moAbs) has illustrated that MET-EC- occurs in transmembranous C-terminal MET-positive oral squamous cell carcinoma (OSCC). Here, we propose that ectodomain shedding, resulting from G-protein-coupled receptor transactivation of epidermal growth factor receptor signaling, and/or overexpression of ADAM10/17 and/or MET, stabilizes and possibly activates MET-EC- in OSCC. As MET-EC- is associated with poor prognosis in OSCC, it potentially has impact on the use of targeted therapies. Therefore, MET-EC- should be incorporated in the design of CDx to improve patient stratification and ultimately prolong survival. Hence, MET-EC- requires further investigation seen its oncogenic and predictive properties.

G. Yamey, A. Arya, Z. Bhutta, S. Causevic, Carolyn Chisadza, Sara Fewer, P. Friberg, Siri Gloppen et al.

Faris Kadić, E. Begić, Mirza Pašić, Ali Gavrankapetanović, A. Mujaković, Aida Pidro, Ada Djozic

Background: Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). The exact mechanism by which arterial hypertension (particularly regulated) could affect the presentation and outcome of Coronavirus disease-19 (COVID-19) has not been fully elucidated. Objective: The aim of this study was to analyze the parameters of patients with verified COVID-19 and existing arterial hypertension at the time of hospital admission and to develop neural network model. Methods: The research had a cross-sectional descriptive and analytical character, and included patients (n=634) who were hospitalized in the General Hospital “Prim. dr. Abdulah Nakas” in Sarajevo, Bosnia and Herzegovina, in the period from 01 Sep 2020 to 01 May 2021. From the hospital information system, which is used in everyday clinical work, laboratory parameters at admission were verified, along with demographic data, the comorbidities, while the outcome (recovery, death) was recorded thirty days after the admission. Results: Out of the total number, in 314 patients (200 males), arterial hypertension was verified, out of which, 56 (17.83%) patients died. Patients were divided into two groups, according to outcome, i.e., whether they survived COVID-19 infection or not. A significant difference in age (p = 0.00), erythrocyte count (p = 0.03), haemoglobin (p = 0.05), hematocrit (p = 0.03), platelets count (p = 0.00), leukocytes (p = 0.01), neutrophils (p = 0.00), lymphocytes (p = 0.00), monocytes (p = 0.00), basophils (p = 0.00), eosinophils (p = 0.00), C-reactive protein (p = 0.00) and D-dimer (p = 0.01) was noted. When patients who died and had hypertension were compared with those who died and did not have hypertension (n = 15), out of alll the analyzed parameters, the only significant difference was established in the patient’s age (p = 0.00). In case when patients with hypertension who died were compared to patients with hypertension and diabetes mellitus who died no significant differences were found between features. Conclusion: Patients with hypertension and COVID-19 who died were older, had higher values of erythrocytes, hemoglobin, hematocrit, leukocytes, neutrophils, CRP and D-dimer, and lower values of platelets, lymphocytes, monocytes, basophils and eosinophils count at admission. Compared to deaths without hypertension, the only difference that was established was that patients with hypertension were older.

C. Caldas, M. Rescigno, S. Turajlic, A. Madabhushi, Zemin Zhang, P. Lito, Christine E. Brown, K. Pantel et al.

M. Jusufbegović, A. Pandžić, A. Šehić, R. Jašić, F. Julardžija, S. Vegar-Zubović, A. Beganović

INTRODUCTION Additive production refers to the process of prototyping, which allows the production of highly complex medical devices and products. Interpretation of additive manufacturing (AM) material in Computed Tomography (CT) has not been widely investigated. The aim of this study was to determine the CT number values of commercially available fused deposition modelling (FDM) and stereolithography (SLA) AM materials. METHODS Total of 15 AM materials, 7 FMD and 8 SLA, were selected and scanned on CT to determine the HU value and appearance on the images. All test object were designed as rectangular blocks and after their production physical description were calculated. AM materials were scanned on CT operating at 80, 100, 120 and 135 kV. RESULTS All materials correspond to a certain human tissue and they have uniformity when printed with 100% infill. CT number ranged from a minimum of -188.0 HU to a maximum of 189.1 HU, for FDM materials, and from -15.8 HU to 167.3 HU, for SLA materials. CONCLUSION Knowing the CT number of an AM materials can allow the design of medical or rehabilitation products with a specific appearance on CT images. Analysed and collected data can find application in the design and manufacture of immobilization devices that can be easily distinguished from other materials or human tissue. IMPLICATIONS FOR PRACTICE This study provides information that can be used in the design and fabrication of anthropomorphic diagnostic and therapeutic phantoms. There is significant potential for the use of AM material for sophisticated test objects when used in medical image modality testing. Knowing actual CT numbers of frequently used AM materials allows manufacturing anthropomorphic phantoms to investigate radiation doses in diagnostic radiology and radiotherapy.

Emina Smajić, D. Avdić, Aleksandra Pašić, Alden Prcić, Maja Stancic

Background: Scientific research is usually classified as quantitative or qualitative. However, methodologists are increasingly emphasizing the integration of qualitative and quantitative data as the center of mixed methods (mix methodologies). Mixed research method implies the use of different research methods, ie. quantitative and qualitative methods in one study. Objective: The aim of this review paper is to present the purpose of using a mixed methodology in health research. Methods: The relevant articles were searched from online data sources including PubMed and Google Scholar. Results: This approach to the use of mixed methods creates opportunities for a deeper study of various problems. The purpose of using mixed research methods is to obtain valid answers to research questions, however the researcher may still have different reasons or purposes for which he wants to strengthen the research study and its conclusions by applying mixed methods. The use of mixed scientific methodology is widely used in the field of health outcomes and should not be limited to a closed list of possible methodological options. Conclusion: Recently, there has been an increase in the number of scientific studies in healthcare that use mixed research methods. The advantage of applying this scientific method is that through the triangulation of data obtained by different (quantitative / qualitative) approaches, we get a deeper and more complete picture of the phenomenon in health care that we observe.

The goal of this part of the study was to optimize the sequencing procedure for 16 human genes and their regulatory regions that might be associated with differential immunological response to COVID-19. The study was performed on 60 COVID-19 patients from the General Hospital of Tešanj, Bosnia and Herzegovina, categorized into three groups of mild, moderate, and severe clinical manifestation, based on the diagnosis by the residential physician. Target coding sequences and their regulatory regions were amplified for the following genes: HLA-A, HLA-B, HLA-C, ACE2, IL-6, IL-4, TMPRSS2, IFITM3, IL-12, RIG-I/DDX58, IRF-7, IRF-9, IL-1B, IL-1A, CD55, and TNF-α. DNA was isolated from the whole blood samples stored at -20°C for six months using QIAamp® DNA Mini Kit according to manufacturer’s instructions. Since NGS analysis of target genomic regions was performed on the Ion Torrent GeneStudio™ S5 platforms, libraries were prepared using Ion AmpliSeq™ Library Kit Plus according to manufacturer’s instructions in a protocol optimized for low-quality DNA. Due to dissatisfactory sequencing results, further protocol optimization steps were employed through separating two primer pools, increasing the number of PCR cycles, and decreasing the annealing temperature for the primer pool which showed poorer amplification results. In the end, 36 samples produced optimal results, while the remaining 24 samples will be re-sequenced following repeated sample collection and DNA isolation, accompanied by additional protocol modifications.

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