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ABSTRACT Traditional therapeutic approaches in the treatment of cancer have many side effects and are often ineffective and non-specific, leading to the development of therapy-resistant tumour cells. Recently, numerous discoveries about stem cells have given a new outlook on their application in oncology. Stem cells are unique because of their biological attributes, including self-renewal, differentiation in different types of specialized cells and synthesis of molecules that interplay with tumour niche. They are already used as an effective therapeutic option for haematological malignancies, such as multiple myeloma and leukaemia. The main goal of this study is to investigate the possible applications of different types of stem cells in cancer treatment and to summarize novel advances, as well as the limitations of their application in cancer treatment. Research and clinical trials that are underway revealed and confirmed the enormous potential of regenerative medicine in the treatment of cancer, especially when combined with different nanomaterials. Nanoengineering of stem cells has been the focus of novel studies in the area of regenerative medicine, such as the production of nanoshells and nanocarriers that enhance the transport and uptake of stem cells in their targeted tumour niche and enable the effective monitoring of stem cell effects on tumour cells. Although nanotechnology has a lot of limitations, it provides new opportunities for the development of effective and innovative stem cell therapies.

M. Račić, Marcos I Roche-Miranda, Gina Fatahi

Abstract Racism has implicit and explicit manifestations that perpetuate disparities and negatively influence patient-centered health outcomes. Subsequently, a list of action items was provided to assist medical schools in becoming anti-racist institutions. A deep subject matter knowledge, beliefs, and reflections were a driving force for the management of medical schools or faculty members involved in undergraduate and postgraduate medical education to move forward toward inclusion of anti-racism in traditional medical curriculum or adapting existing training modules on diversity, equity, and inclusion. This paper proposes twelve practical and specific tips for implementing and teaching anti-racism in medical education. These twelve tips elaborate on the proposed actions for leaders in undergraduate and postgraduate medical education, valuable for designing future curricula and educational activities.

Danielle Cristina Ferrarezi Barboza, Bianca Pereira dos Santos, C. Costa, Giovana Rodrigues Leite, Caroline Lourenço de Almeida

Rialda Spahic, M. Lundteigen, V. Hepsø

This research examines the factors contributing to the exterior material degradation of subsea oil and gas pipelines monitored with autonomous underwater systems (AUS). The AUS have a role of gathering image data that is further analyzed with artificial intelligence data analysis methods. Corrosion and potential ruptures on pipeline surfaces are complex processes involving several competing elements, such as the geographical properties, composition of soil, atmosphere, and marine life, whose eflt in substantial environmental damage and financial loss. Despite extensive research, corrosion monitoring and prediction remain a persistent challenge in the industry. There is a lack of knowledge map that can enable image ausing an AUS to recognize ongoing degradation processes and potentially prevent substantial damage. The main contribution of this research is the knowledge map for increased context and risk awareness to improve the reliability of image-based monitoring and inspection by autonomous underwater systems in detecting hazards and early signs of material degradation on subsea pipeline surfaces.

Yasaman Yazdanpanah, Mohamad Taghi Toghraee, Aidin Salamzadeh, J. Scott, R. Palalić

PurposeThis paper explores how entrepreneurial culture (EC) and organizational learning (OL) determine the entrepreneurial orientation (EO) of new technology-based firms (NTBFs). These NTBFs are located in Isfahan Science and Technology Town (ISTT), Iran. These entities face substantial challenges in a highly-sanctioned economy, which makes adopting, acquiring or transferring new technologies daunting.Design/methodology/approachThis paper analyzes a sample of 200 NTBFs. The participants were trained chief executive officers and observed by applying pre-test and post-test designs. As a final step, empirical data were collected using questionnaires and analyzed accordingly. The structural equation modeling (SEM) with the partial least squares (PLS) approach was used by the SmartPLS2 software.Findings OL was found to mediate the relationship between EC and EO in the studied NTBFs. Additionally, the indirect effect of EC on EO and the direct impact of OL on EO were significant (=1.96). Therefore, this study focuses on selected NTBFs within Iran's particular and distinctive context.Research limitations/implicationsThis study has several limitations. These were the time consuming nature, the lack of cooperation by managers and the COVID-19 pandemic-related challenges. Nonetheless, the findings offer several important implications for practitioners, scholars and policymakers.Originality/valueThe paper sought to explore how EC and OL determine EO in Iranian NTBFs. It, thus, investigates the case of a highly-sanctioned context during the coronavirus pandemic, which imposed several basic and technological limitations on their practices.

M. Lačković, V. Samardzic, B. Joksimović, M. Sinik, M. Tomasovic, E. Isenovic, Z. Gluvić

I. Salimović-Bešić, Semir Hrvo, Edin Zahirović, El-Jesah Đulić, R. Baljić, A. Dedeić-Ljubović

Introduction. Bosnia and Herzegovina (B and H) has been recognized for decades as a country with a high risk of diseases caused by hantaviruses.Gap statement. The severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) pandemic has diverted attention from many pathogens, including hantavirus.Aim. To provide a socio-demographic, temporal, geographical and clinical laboratory overview of the expansion of hantavirus infection cases during the SARS-CoV-2 pandemic in B and H in 2021.Methodology. The RecomLine HantaPlus IgG, IgM immuno-line assay (Mikrogen, Germany) was used to detect IgG and IgM antibodies to hantavirus serotypes in human sera from clinically suspected cases.Results. In 2021 (January-October), the number of confirmed cases of hantavirus infection and tested persons (92/140; 65,71 %) was higher than in the previous 2 years, 2020 (2/20; 10.00 %) and 2019 (10/61; 16.39 %). Most of the infected persons were men (84/92; 91.30 %). Hantavirus infections were recorded from January to October 2021, and the peak was reached in July (25/92; 27.17 %). Six out of 10 cantons in the Federation of Bosnia and Herzegovina (FB and H) were affected, namely Sarajevo Canton, Central Bosnia Canton, Neretva Canton, Zenica-Doboj Canton, Posavina Canton and Bosnian-Podrinje Canton Goražde, in descending order. Of the 38/92 (41.30 %) infected patients with characteristic clinical manifestations of haemorrhagic fever, including renal (mainly) or pulmonary syndrome, 32/92 (34.78 %) were hospitalized in the Clinical Center of the University of Sarajevo. Two cases were detected with dual infection, hantavirus (Puumala) with Leptospira in one and SARS-CoV-2 in another case. The largest number of infections was related to Puumala (PUUV) (83/92; 90.22 %), while the rest of the infections were caused by the hantavirus Dobrava serotype (DOBV).Conclusion. The reported infections were probably caused by exposure of individuals to at-risk areas inhabited by contaminated rodents as natural reservoirs of hantavirus. As a highly endemic area, B and H requires continuous monitoring and increased awareness of this problem.

G. Zakharova, Alexander Modestov, Polina Pugacheva, Rijalda Mekic, Ekaterina A. Savina, A. Guryanova, Anastasia Rachkova, S. Yakushov et al.

The evolution of protein-coding genes has both structural and regulatory components. The first can be assessed by measuring the ratio of non-synonymous to synonymous nucleotide substitutions. The second component can be measured as the normalized proportion of transposable elements that are used as regulatory elements. For the first time, we characterized in parallel the regulatory and structural evolutionary profiles for 10,890 human genes and 2972 molecular pathways. We observed a ~0.1 correlation between the structural and regulatory metrics at the gene level, which appeared much higher (~0.4) at the pathway level. We deposited the data in the publicly available database RetroSpect. We also analyzed the evolutionary dynamics of six cancer pathways of two major axes: Notch/WNT/Hedgehog and AKT/mTOR/EGFR. The Hedgehog pathway had both components slower, whereas the Akt pathway had clearly accelerated structural evolution. In particular, the major hub nodes Akt and beta-catenin showed both components strongly decreased, whereas two major regulators of Akt TCL1 and CTMP had outstandingly high evolutionary rates. We also noticed structural conservation of serine/threonine kinases and the genes related to guanosine metabolism in cancer signaling: GPCRs, G proteins, and small regulatory GTPases (Src, Rac, Ras); however, this was compensated by the accelerated regulatory evolution.

Minghao Si, Yunjia Wang, H. Šiljak, C. Seow, Hongchao Yang

Implementing line-of-sight (LOS) and none-line-of-sight (NLOS) identification in ultra-wideband (UWB) systems is crucial. Convolutional neural network (CNN) based identification methods can extract higher-level features automatically, but they are based on channel impulse response (CIR)-turned image ingested features that impose calculation complexity and do not make use of manual features due to the data inundation risk. In this letter, we propose a novel multilayer perceptron (MLP)-based LOS/NLOS identification algorithm that can utilize both manually extracted features and feature from CNN based on raw CIR inputs with only 7.39% calculation complexity as compared to the traditional image-based CNN. Three experiments, at a teaching building, an office, and an underground mine, were conducted to verify the proposed method’s performance. Our proposed features are conducive to LOS/NLOS identification, especially the proposed raw CIR-based feature from the CNN, achieving 26.9% improvement over existing manual features. Furthermore, the proposed method outperformed the traditional image-based CNN with an improvement of 44.16%.

Roberto Stabile, Mario Román Cabezas, Mathijs P. Verhagen, F. Tucci, T. V. D. van den Bosch, M. D. De Herdt, Berdine van der Steen, A. Nigg et al.

Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1; also known as deleted in oral cancer or DOC1) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the DOC1 acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as much CDK2AP1 mRNA as proficient cell lines. Here, by combining in silico and in vitro approaches, and by taking advantage of patient-derived data and tumor material in the analysis of loss of CDK2AP1 expression, we identified a set of microRNAs, namely miR-21-5p, miR-23b-3p, miR-26b-5p, miR-93-5p, and miR-155-5p, which inhibit its translation in both cell lines and patient-derived OSCCs. Of note, no synergistic effects were observed of the different miRs on the CDK2AP1–3-UTR common target. We also developed a novel approach to the combined ISH/IF tissue microarray analysis to study the expression patterns of miRs and their target genes in the context of tumor architecture. Last, we show that CDK2AP1 loss, as the result of miRNA expression, correlates with overall survival, thus highlighting the clinical relevance of these processes for carcinomas of the oral cavity.

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