48 research outputs found
Minimalno invazivni diagnostični pristopi pri primarnih možganskih tumorjih z uporabo prosto cirkulirajočih nukleinskih kislin
Overstaged Rectal Cancer by MRI due to Fibrosis Induced by Tattoo Marker
Endoscopic colorectal tattooing with carbon-based dyes is commonly employed in order to assist with later localization of the lesion. Although carbon is thought to be nontoxic, there usually is some inflammatory reaction with fibrosis and granuloma formation after tissue injection. The aim of this report is to alert to a possible underestimated, late consequence of colorectal carbon-based marker tattooing, namely pronounced fibrosis at the site of the injection that could lead to a blurring and misinterpretation of changes evaluated by radiological techniques. We describe a case of cT stage overestimation due to fibrosis of the rectal wall and perirectal fat, induced by carbon-based dye injection in a 66-year-old patient. In our case it was an overestimation of MR evaluation in the case of early invasive carcinoma. Although there have been some studies on tissue effect of carbon-based dyes, the possible scenario consequence of cancer stage overestimation due to fibrosis has not yet been described. Such a mistake could lead to inappropriate overtreatment. Clinicians must be aware of the possible consequences of dye injection and resultant overestimation of T stage of colorectal cancer. More histological studies concerning histological changes after carbon-based marker tattooing are needed to establish the extent of its significance
Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
Graphical Abstract Highlights d Derivation of human neocortical and spinal cord neuroepithelial stem (NES) cells d Zika virus (ZIKV) infects NES cells and radial glia, impairing mitosis and survival d ZIKV induces mitochondrial sequestration of centrosomal phospho-TBK1 d Nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death In Brief Onorati et al. establish neuroepithelial stem (NES) cells as a model for studying human neurodevelopment and ZIKV-induced microcephaly. Together with analyses in human brain slices and microcephalic human fetal tissue, they find that ZIKV predominantly infects NES and radial glial cells, reveal a pivotal role for pTBK1, and find that nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death
AUTHENTICATION SYSTEMS FOR PERSONAL USE
Diplomsko delo predstavlja pregled glavnih overitvenih pristopov za osebno uporabo. Najprej smo opisali osnovne koncepte overjanja ter obravnavali tri glavne načine overjanja: kaj nekdo ve, kaj nekdo je in kaj nekdo ima. Predstavili smo tudi prednosti in slabosti teh metod in raziskali, katera je najbolj primerna za osebno rabo. Posebej smo se osredotočili na prepoznavanje obrazov, kjer smo tudi opisali različne vrste algoritmov, ki jih sistemi uporabljajo. Na koncu pa smo implementirali metodo prepoznavanja obrazov s pomočjo algoritma Eigenobraz.The thesis presents an overview of the main authentication systems for personal use. At first, we have intruduced the basic concepts of authentication and adressed that there are three main methods of authentication: what one knows, what one is and what one has. We have identified the advantages and disadvantages of these methods and researched which one would be the most suitable for personal use. In particular, we had focused on facial recognition, where we also described the various types of algorithms used by the systems. At the end, we have implemented method for face recognition with the help of algorithm Eigenface
Handball Player Localisation in Handball Using Deep Pre-trained Models
Umetna inteligenca ter računalniški vid sta v športu zelo koristna in kakovostna pripomočka, saj nam skrajšata čas iskanja, zbiranja ter analiziranja podatkov. Ker pa umetna inteligenca še ni dovolj napredna za nekoliko kompleksnejše programe ter ideje, je človeško znanje trenutno še v veliki prednosti. Če si predstavljamo program, ki bi potreboval samo posnetek rokometne tekme in v hipu vrnil segmentirane podatke vseh posameznikov ter njihovih strelov, se mogoče zasnova za tak program ne zdi tako kompleksna.
Ob podrobni poglobitvi v zasnovo se zavemo, da je za nastanek takšne aplikacije potrebno mnogo različnih pristopov ter vloženega dela. Ena izmed največjih osnov za takšno aplikacijo bi bila lokalizacija igralcev z globoko naučenimi algoritmi. Takšna lokalizacija je precej odvisna od človeške pomoči, saj je potrebno algoritme zaganjati fizično. Vendar je nekje potrebno začeti, saj lahko samo tako pridemo do želenih ciljev. S pomočjo različnih vnaprej pripravljenih algoritmov ter lastnega znanja lahko iz amaterskih posnetkov rokometne tekme pridobimo lokacijo igralcev na tlorisu rokometnega igrišča oziroma iz tridimenzionalnega v dvodimenzionalni prostor.
Rezultati, ki jih vrne lokalizacija, so zadovoljivi za pogoje, v katerih so bili podatki zajeti. Zaradi amaterskih posnetkov, uporabe ene samcate kamere ter slabe postavitve pri preslikavah igralcev prihaja do odstopanj. V popolnih delovnih pogojih, kjer bi bilo več kamer, ki bi bile postavljene na boljših položajih, bi bili rezultati nekoliko točnejši, vendar nikoli dovolj precizni, zaradi nepopolne transformacije iz tridimenzionalnega v dvodimenzionalni prostor.Artificial intelligence and computer vision are very useful and high-quality tools in sport, as they reduce the time needed to search, collect and analyse data. However, as artificial intelligence is not yet advanced enough for slightly advanced programs and ideas, human knowledge is currently still at a great advantage. If we imagine a program that only needed to take a snapshot of a handball match and instantly return segmented data of all the individuals and their shots, perhaps the design for such a program does not seem so complex.
When we look into the design in more detail, we realise that many different approaches and work are needed to create such an application. One of the biggest basics for such an application would be the localization of players with deeply learned algorithms. Such localization relies heavily on human assistance, as the algorithms need to be physically launched. But we have to start somewhere, because that is the only way to get to the desired goals. With the help of various pre-prepared algorithms and our own knowledge, we can extract the location of players on the layout of a handball court from amateur footage of a handball match, or from three-dimensional to two-dimensional space.
The results returned by the localisation are acceptable for the conditions in which the data were captured. Due to amateur shots, the use of a single camera and poor placement, there are deviations in the mapping of the players. In perfect working conditions, where there would be several cameras placed in better positions, the results would be slightly more accurate, but never precise enough, due to the incomplete transformation from three-dimensional to two-dimensional space
Bioinformatic and clinical experimental assay uncovers resistance and susceptibility mechanisms of human glioblastomas to temozolomide and identifies new combined and individual survival biomarkers outperforming MGMT promoter methylation
Background: Glioblastoma (GBM) is the most aggressive and lethal central nervous system (CNS) tumor. The treatment strategy is mainly surgery and/or radiation therapy, both combined with adjuvant temozolomide (TMZ) chemotherapy. Historically, methylation of MGMT gene promoter is used as the major biomarker predicting individual tumor response to TMZ. Objectives: This research aimed to analyze genes and molecular pathways of DNA repair as biomarkers for sensitivity to TMZ treatment in GBM using updated The Cancer Genome Atlas (TCGA) data and validate the results on experimental datasets.
Methods: Survival analysis of GBM patients under TMZ therapy and hazard ratio (HR) calculation were used to assess all putative biomarkers on World Health Organization CNS5 reclassified TCGA project collection of molecular profiles and experimental multicenter GBM patient cohort. Pathway activation levels were calculated for 38 DNA repair pathways. TMZ sensitivity pathway was reconstructed using a human interactome model built using pairwise interactions extracted from 51,672 human molecular pathways. Results: We found that expression/activation levels of seven and six emerging gene/pathway biomarkers served as high-quality positive (HR 1.63), respectively, patient survival biomarkers performing better than MGMT methylation. Positive survival biomarkers were enriched in the processes of ATM-dependent checkpoint activation and cell cycle arrest whereas negative-in excision DNA repair. We also built and characterized gene pathways which were informative for GBM patient survival following TMZ administration (HR 0.18-0.44, p < 0.0009area under the curve 0.68-0.9).
Conclusion: In this study, a comprehensive analysis of the expression of 361 DNA repair genes and activation levels of 38 DNA repair pathways revealed 13 potential survival biomarkers with increased prognostic potential compared to MGMT methylation. We algorithmically reconstructed the TMZ sensitivity pathway with strong predictive capacity in GBM
Metabolic brain changes can predict the underlying pathology in neurodegenerative brain disorders
The co-occurrence of multiple proteinopathies is being increasingly recognized in neurodegenerative disorders and poses a challenge in differential diagnosis and patient selection for clinical trials. Changes in brain metabolism captured by positron emission tomography (PET) with F-fluorodeoxyglucose (FDG) allow us to differentiate between different neurodegenerative disorders either by visual exploration or by studying disease-specific metabolic networks in individual patients. However, the impact of multiple proteinopathies on brain metabolism and metabolic networks remains unknown due to the absence of pathological studies. In this case study, we present a 67-year-old patient with rapidly progressing dementia clinically diagnosed with probable sporadic Creutzfeldt–Jakob disease (sCJD). However, in addition to the expected pronounced cortical and subcortical hypometabolism characteristic of sCJD, the brain FDG PET revealed an intriguing finding of unexpected relative hypermetabolism in the bilateral putamina, raising suspicions of coexisting Parkinson’s disease (PD). Additional investigation of disease-specific metabolic brain networks revealed elevated expression of both CJD-related pattern (CJDRP) and PD-related pattern (PDRP) networks. The patient eventually developed akinetic mutism and passed away seven weeks after symptom onset. Neuropathological examination confirmed neuropathological changes consistent with sCJD and the presence of Lewy bodies confirming PD pathology. Additionally, hyperphosphorylated tau and TDP-43 pathology were observed, a combination of four proteinopathies that had not been previously reported. Overall, this case provides valuable insights into the complex interplay of neurodegenerative pathologies and their impact on metabolic brain changes, emphasizing the role of metabolic brain imaging in evaluating potential presence of multiple proteinopathies
Anti-vimentin, anti-TUFM, anti-NAP1L1 and anti-DPYSL2 nanobodies display cytotoxic effect and reduce glioblastoma cell migration
Background: Glioblastoma is a particularly common and very aggressive primary brain tumour. One of the main causes of therapy failure is the presence of glioblastoma stem cells that are resistant to chemotherapy and radiotherapy, and that have the potential to form new tumours. This study focuses on validation of eight novel antigens, TRIM28, nucleolin, vimentin, nucleosome assembly protein 1-like 1 (NAP1L1), mitochondrial translation elongation factor (EF-TU) (TUFM), dihydropyrimidinase-related protein 2 (DPYSL2), collapsin response mediator protein 1 (CRMP1) and Aly/REF export factor (ALYREF), as putative glioblastoma targets, using nanobodies.
Methods: Expression of these eight antigens was analysed at the cellular level by qPCR, ELISA and immunocytochemistry, and in tissues by immunohistochemistry. The cytotoxic effects of the nanobodies were determined using AlamarBlue and water-soluble tetrazolium tests. Annexin V/propidium iodide tests were used to determine apoptotsis/necrosis of the cells in the presence of the nanobodies. Cell migration assays were performed to determine the effects of the nanobodies on cell migration.
Results: NAP1L1 and CRMP1 were significantly overexpressed in glioblastoma stem cells in comparison with astrocytes and glioblastoma cell lines at the mRNA and protein levels. Vimentin, DPYSL2 and ALYREF were overexpressed in glioblastoma cell lines only at the protein level. The functional part of the study examined the cytotoxic effects of the nanobodies on glioblastoma cell lines. Four of the nanobodies were selected in terms of their specificity towards glioblastoma cells and protein overexpression: anti-vimentin (Nb79), anti-NAP1L1 (Nb179), anti-TUFM (Nb225) and anti-DPYSL2 (Nb314). In further experiments to optimise the nanobody treatment schemes, to increase their effects, and to determine their impact on migration of glioblastoma cells, the anti-TUFM nanobody showed large cytotoxic effects on glioblastoma stem cells, while the anti-vimentin, anti-NAP1L1 and anti-DPYSL2 nanobodies were indicated as agents to target mature glioblastoma cells. The anti-vimentin nanobody also had significant effects on migration of mature glioblastoma cells.
Conclusion: Nb79 (anti-vimentin), Nb179 (anti-NAP1L1), Nb225 (anti-TUFM) and Nb314 (anti-DPYSL2) nanobodies are indicated for further examination for cell targeting. The anti-TUFM nanobody, Nb225, is particularly potent for inhibition of cell growth after long-term exposure of glioblastoma stem cells, with minor effects seen for astrocytes. The anti-vimentin nanobody represents an agent for inhibition of cell migration
