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“Investigating lattice strain in Au nanodecahedrons”. Goris B, De Beenhouwer J, de Backer A, Zanaga D, Batenburg J, Sanchez-Iglesias A, Liz-Marzan L, Van Aert S, Sijbers J, Van Tendeloo G, Bals S, , 11 (2016). http://doi.org/10.1002/9783527808465.EMC2016.5519
Keywords: P1 Proceeding; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1002/9783527808465.EMC2016.5519
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De Backer J (2023) The versatile nature of cytoglobin, the Swiss army knife among globins, with a preference for oxidative stress. XVIII, 232 p
Abstract: Since its discovery 20 years ago, many studies have been performed to gain insight into the functional role of cytoglobin (Cygb). However, Cygb has been proven to be a promiscuous protein. Yet, there is a consensus that Cygb is a cytoprotective protein involved in redox homeostasis. CYGB is a ubiquitously expressed hexacoordinated globin that is highly expressed in melanocytes and is often found to be downregulated during melanocyte-to-melanoma transition. In Chapter III, we investigated the molecular mechanism through which CYGB could be involved in redox regulation. Here, we showed that CYGB contains two redox-sensitive cysteine residues and that the formation of an intramolecular disulfide bridge resulted in the heme group becoming more accessible to external ligands. This supports the hypothesis that Cys38 and Cys83 serve as sensitive redox sensors. In Chapter IV we showed that CYGB mRNA and protein levels were elevated upon exposure to hypoxia. Interestingly, this upregulation was most likely HIF-2α-dependent. We propose that in melanoma, HIF-2α, rather than HIF-1α, positively regulates CYGB under hypoxic conditions in a cell type specific way. In Chapter V, the cytotoxic effect of indirect NTP treatment in two melanoma cell lines with divergent endogenous CYGB expression levels was investigated. We confirmed that NTP endows cytotoxicity that induces cell death through apoptosis and that this was mediated through the production of ROS. Moreover, we showed that CYGB protects melanoma cells from ROS-induced apoptosis by the scavenging of ROS. Interestingly, CYGB expression influenced the expression of NRF2 and HO-1. We identified the lncRNA MEG3 as a possible mechanism through which NRF2 expression and its downstream target HO-1 can be regulated by CYGB. In chapter VI, increased basal ROS levels and higher degree of lipid peroxidation upon RSL3 treatment contributed to the increased sensitivity of CYGB knockdown G361 cells to ferroptosis. Furthermore, transcriptome analysis demonstrates the enrichment of multiple cancer malignancy pathways upon CYGB knockdown, supporting a tumor-suppressive role for CYGB. Remarkably, CYGB expression regulation was identified as a critical determinant of the ferroptosis–pyroptosis therapy response. This suggests that CYGB is involved in the regulation of multiple modes of programmed cell death. FInally, we sought to delineate the RONS that are responsible for plasma-induced ICD. Our results highlight the importance of the short-lived species. Furthermore, we are first to demonstrate that NTP-created vaccine is safely prepared and offers complete protection. Moreover, we provide conclusive evidence that direct application of NTP induces ICD in melanoma.
Keywords: Doctoral thesis; Pharmacology. Therapy; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Proteinscience, proteomics and epigenetic signaling (PPES)
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“Clinical applications of image-based airway computational fluid dynamics: assessment of inhalation medication and endobronchial devices”. de Backer JW, Vos WG, Germonpré, P, Salgado R, Parizel PM, de Backer W, Proceedings of the Society of Photo-optical Instrumentation Engineers 7262, 72621p (2009). http://doi.org/10.1117/12.811476
Abstract: Computational fluid dynamics (CFD) is a technique that is used increasingly in the biomedical field. Solving the flow equations numerically provides a convenient way to assess the efficiency of therapies and devices, ranging from cardiovascular stents and heart valves to hemodialysis workflows. Also in the respiratory field CFD has gained increasing interest, especially through the combination of three dimensional image reconstruction which results in highend patient-specific models. This paper provides an overview of clinical applications of CFD through image based modeling, resulting from recent studies performed in our center. We focused on two applications: assessment of the efficiency of inhalation medication and analysis of endobronchial valve placement. In the first application we assessed the mode of action of a novel bronchodilator in 10 treated patients and 4 controls. We assessed the local volume increase and resistance change based on the combination of imaging and CFD. We found a good correlation between the changes in volume and resistance coming from the CFD results and the clinical tests. In the second application we assessed the placement and effect of one way endobronchial valves on respiratory function in 6 patients. We found a strong patientspecific result of the therapy where in some patients the therapy resulted in complete atelectasis of the target lobe while in others the lobe remained inflated. We concluded from these applications that CFD can provide a better insight into clinically relevant therapies.
Keywords: A3 Journal article; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP)
DOI: 10.1117/12.811476
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“Functional imaging to predict treatment success of mandibular advancement devices in sleep-disordered breathing”. de Backer J, Vanderveken O, Vos W, Devolder A, Verhulst S, Verbraecken J Antwerpen, page 141 (2008).
Keywords: H3 Book chapter; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP); Translational Neurosciences (TNW)
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“Klinische semiologie en radiologie”. Parizel PM, Corthouts B, Snoeckx A, de Backer J, de Backer W Acco, Leuven, page 133 (2007).
Keywords: H3 Book chapter; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP)
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de Backer A (2015) Quantitative atomic resolution electron microscopy using advanced statistical techniques. Antwerpen
Keywords: Doctoral thesis; Electron microscopy for materials research (EMAT)
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“Quantitative annular dark field scanning transmission electron microscopy for nanoparticle atom-counting: What are the limits?”.De Backer A, De Wael A, Gonnissen J, Martinez GT, Béché, A, MacArthur KE, Jones L, Nellist PD, Van Aert S, Journal of physics : conference series 644Electron Microscopy and Analysis Group Conference (EMAG), JUN 02-JUL 02, 2015, Manchester, ENGLAND, 012034 (2015). http://doi.org/10.1088/1742-6596/644/1/012034
Abstract: Quantitative atomic resolution annular dark field scanning transmission electron microscopy (ADF STEM) has become a powerful technique for nanoparticle atom-counting. However, a lot of nanoparticles provide a severe characterisation challenge because of their limited size and beam sensitivity. Therefore, quantitative ADF STEM may greatly benefit from statistical detection theory in order to optimise the instrumental microscope settings such that the incoming electron dose can be kept as low as possible whilst still retaining single-atom precision. The principles of detection theory are used to quantify the probability of error for atom-counting. This enables us to decide between different image performance measures and to optimise the experimental detector settings for atom-counting in ADF STEM in an objective manner. To demonstrate this, ADF STEM imaging of an industrial catalyst has been conducted using the near-optimal detector settings. For this experiment, we discussed the limits for atom-counting diagnosed by combining a thorough statistical method and detailed image simulations.
Keywords: P1 Proceeding; Electron microscopy for materials research (EMAT)
DOI: 10.1088/1742-6596/644/1/012034
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“Quantitative annular dark field scanning transmission electron microscopy for nanoparticle atom-counting : what are the limits?”.de Backer A, De wael A, Gonnissen J, Martinez GT, Béché, A, MacArthur KE, Jones L, Nellist PD, Van Aert S, Journal of physics : conference series 644, 012034 (2015). http://doi.org/10.1088/1742-6596/644/012034
Abstract: Quantitative atomic resolution annular dark field scanning transmission electron microscopy (ADF STEM) has become a powerful technique for nanoparticle atom-counting. However, a lot of nanoparticles provide a severe characterisation challenge because of their limited size and beam sensitivity. Therefore, quantitative ADF STEM may greatly benefit from statistical detection theory in order to optimise the instrumental microscope settings such that the incoming electron dose can be kept as low as possible whilst still retaining single-atom precision. The principles of detection theory are used to quantify the probability of error for atom-counting. This enables us to decide between different image performance measures and to optimise the experimental detector settings for atom-counting in ADF STEM in an objective manner. To demonstrate this, ADF STEM imaging of an industrial catalyst has been conducted using the near-optimal detector settings. For this experiment, we discussed the limits for atomcounting diagnosed by combining a thorough statistical method and detailed image simulations.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT)
DOI: 10.1088/1742-6596/644/012034
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“Atom column detection”. Fatermans J, de Backer A, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 177 (2021).
Abstract: By combining statistical parameter estimation and model-order selection using a Bayesian framework, the maximum a posteriori (MAP) probability rule is proposed in this chapter as an objective and quantitative method to detect atom columns from high-resolution scanning transmission electron microscopy (HRSTEM) images. The validity and usefulness of this approach is demonstrated to both simulated and experimental annular dark-field (ADF) STEM images, but also to simultaneously acquired annular bright-field (ABF) and ADF STEM image data.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.006
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“Atom counting”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 91 (2021).
Abstract: In this chapter, a statistical model-based method to count the number of atoms of monotype crystalline nanostructures from high-resolution annular dark-field (ADF) scanning transmission electron microscopy (STEM) images is discussed in detail together with a thorough study on the possibilities and inherent limitations. We show that this method can be applied to nanocrystals of arbitrary shape, size, and atom type. The validity of the atom-counting results is confirmed by means of detailed image simulations and it is shown that the high sensitivity of our method enables us to count atoms with single atom sensitivity.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.004
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“Efficient fitting algorithm”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 73 (2021).
Abstract: An efficient model-based estimation algorithm is introduced to quantify the atomic column positions and intensities from atomic-resolution (scanning) transmission electron microscopy ((S)TEM) images. This algorithm uses the least squares estimator on image segments containing individual columns fully accounting for overlap between neighboring columns, enabling the analysis of a large field of view. To provide end-users with this well-established quantification method, a user friendly program, StatSTEM, is developed which is freely available under a GNU public license. In this chapter, this efficient algorithm is applied to three different nanostructures for which the analysis of a large field of view is required.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT)
DOI: 10.1016/BS.AIEP.2021.01.003
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“General conclusions and future perspectives”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 243 (2021).
Abstract: This chapter provides an overview of statistical and quantitative methodologies that have pushed (scanning) transmission electron microscopy ((S)TEM) toward accurate and precise measurements of unknown structure parameters for understanding the relation between the structure of a material and its properties. Hereby, statistical parameter estimation theory has extensively been used which enabled not only measuring atomic column positions, but also quantifying the number of atoms, and detecting atomic columns as accurately and precisely as possible from experimental images. As a general conclusion, it can be stated that advanced statistical techniques are ideal tools to perform quantitative electron microscopy at the atomic scale. In the future, statistical methods will continue to be developed and novel quantification procedures will open up new possibilities for studying material structures at the atomic scale.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.008
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“Image-quality evaluation and model selection with maximum a posteriori probability”. Fatermans J, de Backer A, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 215 (2021).
Abstract: The maximum a posteriori (MAP) probability rule for atom column detection can also be used as a tool to evaluate the relation between scanning transmission electron microscopy (STEM) image quality and atom detectability. In this chapter, a new image-quality measure is proposed that correlates well with atom detectability, namely the integrated contrast-to-noise ratio (ICNR). Furthermore, the working principle of the MAP probability rule is described in detail showing a close relation to the principles of model-selection methods.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.007
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“Introduction”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 1 (2021).
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT)
DOI: 10.1016/BS.AIEP.2021.01.001
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“Optimal experiment design for nanoparticle atom counting from ADF STEM images”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 145 (2021).
Abstract: In this chapter, the principles of detection theory are used to quantify the probability of error for atom counting from high-resolution scanning transmission electron microscopy (HRSTEM) images. Binary and multiple hypothesis testing have been investigated in order to determine the limits to the precision with which the number of atoms in a projected atomic column can be estimated. The probability of error has been calculated when using STEM images, scattering cross-sections or peak intensities as a criterion to count atoms. Based on this analysis, we conclude that scattering cross-sections perform almost equally well as images and perform better than peak intensities. Furthermore, the optimal STEM detector design can be derived for atom counting using the expression of the probability of error. We show that for very thin objects the low-angle annular dark-field (LAADF) regime is optimal and that for thicker objects the optimal inner detector angle increases.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.005
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“Statistical parameter estimation theory : principles and simulation studies”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 29 (2021).
Abstract: In this chapter, the principles of statistical parameter estimation theory for a quantitative analysis of atomic-resolution electron microscopy images are introduced. Within this framework, electron microscopy images are described by a parametric statistical model. Here, parametric models are introduced for different types of electron microscopy images: reconstructed exit waves, annular dark-field (ADF) scanning transmission electron microscopy (STEM) images, and simultaneously acquired ADF and annular bright-field (ABF) STEM images. Furthermore, the Cramér-Rao lower bound (CRLB) is introduced, i.e. a theoretical lower bound on the variance of any unbiased estimator. This CRLB is used to quantify the precision of the structure parameters of interest, such as the atomic column positions and the integrated atomic column intensities.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.002
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“A decade of atom-counting in STEM: From the first results toward reliable 3D atomic models from a single projection”. De Backer A, Bals S, Van Aert S, Ultramicroscopy , 113702 (2023). http://doi.org/10.1016/j.ultramic.2023.113702
Abstract: Quantitative structure determination is needed in order to study and understand nanomaterials at the atomic scale. Materials characterisation resulting in precise structural information is a crucial point to understand the structure–property relation of materials. Counting the number of atoms and retrieving the 3D atomic structure of nanoparticles plays an important role here. In this paper, an overview will be given of the atom-counting methodology and its applications over the past decade. The procedure to count the number of atoms will be discussed in detail and it will be shown how the performance of the method can be further improved. Furthermore, advances toward mixed element nanostructures, 3D atomic modelling based on the atom-counting results, and quantifying the nanoparticle dynamics will be highlighted.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT)
Impact Factor: 2.2
Times cited: 3
DOI: 10.1016/j.ultramic.2023.113702
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“Acquired non-thermal plasma resistance mediates a shift towards aerobic glycolysis and ferroptotic cell death in melanoma”. Lin A, Sahun M, Biscop E, Verswyvel H, De Waele J, De Backer J, Theys C, Cuypers B, Laukens K, Berghe WV, Smits E, Bogaerts A, Drug resistance updates 67, 100914 (2023). http://doi.org/10.1016/j.drup.2022.100914
Abstract: To gain insights into the underlying mechanisms of NTP therapy sensitivity and resistance, using the firstever
NTP-resistant cell line derived from sensitive melanoma cells (A375).
Methods: Melanoma cells were exposed to NTP and re-cultured for 12 consecutive weeks before evaluation
against the parental control cells. Whole transcriptome sequencing analysis was performed to identify differentially
expressed genes and enriched molecular pathways. Glucose uptake, extracellular lactate, media acidification,
and mitochondrial respiration was analyzed to determine metabolic changes. Cell death inhibitors were
used to assess the NTP-induced cell death mechanisms, and apoptosis and ferroptosis was further validated via
Annexin V, Caspase 3/7, and lipid peroxidation analysis.
Results: Cells continuously exposed to NTP became 10 times more resistant to NTP compared to the parental cell
line of the same passage, based on their half-maximal inhibitory concentration (IC50). Sequencing and metabolic
analysis indicated that NTP-resistant cells had a preference towards aerobic glycolysis, while cell death analysis
revealed that NTP-resistant cells exhibited less apoptosis but were more vulnerable to lipid peroxidation and
ferroptosis.
Conclusions: A preference towards aerobic glycolysis and ferroptotic cell death are key physiological changes in
NTP-resistance cells, which opens new avenues for further, in-depth research into other cancer types.
Keywords: A1 Journal article; Pharmacology. Therapy; ADReM Data Lab (ADReM); Center for Oncological Research (CORE); Proteinscience, proteomics and epigenetic signaling (PPES); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Impact Factor: 24.3
DOI: 10.1016/j.drup.2022.100914
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“Fast generation of calculated ADF-EDX scattering cross-sections under channelling conditions”. Zhang Z, Lobato I, De Backer A, Van Aert S, Nellist P, Ultramicroscopy 246, 113671 (2023). http://doi.org/10.1016/j.ultramic.2022.113671
Abstract: Advanced materials often consist of multiple elements which are arranged in a complicated structure. Quantitative scanning transmission electron microscopy is useful to determine the composition and thickness of nanostructures at the atomic scale. However, significant difficulties remain to quantify mixed columns by comparing the resulting atomic resolution images and spectroscopy data with multislice simulations where dynamic scattering needs to be taken into account. The combination of the computationally intensive nature of these simulations and the enormous amount of possible mixed column configurations for a given composition indeed severely hamper the quantification process. To overcome these challenges, we here report the development of an incoherent non-linear method for the fast prediction of ADF-EDX scattering cross-sections of mixed columns under channelling conditions. We first explain the origin of the ADF and EDX incoherence from scattering physics suggesting a linear dependence between those two signals in the case of a high-angle ADF detector. Taking EDX as a perfect incoherent reference mode, we quantitatively examine the ADF longitudinal incoherence under different microscope conditions using multislice simulations. Based on incoherent imaging, the atomic lensing model previously developed for ADF is now expanded to EDX, which yields ADF-EDX scattering cross-section predictions in good agreement with multislice simulations for mixed columns in a core–shell nanoparticle and a high entropy alloy. The fast and accurate prediction of ADF-EDX scattering cross-sections opens up new opportunities to explore the wide range of ordering possibilities of heterogeneous materials with multiple elements.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT)
Impact Factor: 2.2
DOI: 10.1016/j.ultramic.2022.113671
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“Detailed nitrogen and phosphorus flow analysis, nutrient use efficiency and circularity in the agri-food system of a livestock-intensive region”. Vingerhoets R, Spiller M, De Backer J, Adriaens A, Vlaeminck SE, Meers E, Journal of cleaner production 410, 137278 (2023). http://doi.org/10.1016/J.JCLEPRO.2023.137278
Abstract: The agri-food value chain is a major cause of nitrogen (N) and phosphorus (P) emissions and associated environmental and health impacts. The EU's farm-to-fork strategy (F2F) demands an agri-food value chain approach to reduce nutrient emissions by 50% and fertilizer use by 20%. Substance flow analysis (SFA) is a method that can be applied to study complex systems such as the agri-food chain. A review of 60 SFA studies shows that they often lack detail by not sufficiently distinguishing between nodes, products and types of emissions. The present study aims to assess the added value of detail in SFAs and to illustrate that valuable indicators can be derived from detailed assessments. This aim will be attained by presenting a highly-detailed SFA for the livestock-intensive region of Flanders, Belgium. The SFA distinguishes 40 nodes and 1827 flows that are classified into eight different categories (e.g. by-products, point source emissions) following life cycle methods. Eight novel indicators were calculated, including indicators that assess the N and P recovery potential. Flanders has a low overall nutrient use efficiency (11% N, 18% P). About 55% of the N and 56% of the P embedded in recoverable streams are reused providing 35% and 37% of the total N and P input. Optimized nutrient recycling could replace 45% of N and 48% of P of the external nutrient input, exceeding the target set by the F2F strategy. Detailed accounting for N and P flows and nodes leads to the identification of more recoverable streams and larger N and P flows. More detailed flow accounting is a prerequisite for the quantification of technological intervention options. Future research should focus on including concentration and quality as a parameter in SFAs.
Keywords: A1 Journal article; Engineering sciences. Technology; Sustainable Energy, Air and Water Technology (DuEL)
Impact Factor: 11.1
DOI: 10.1016/J.JCLEPRO.2023.137278
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“Quantifying Strain and Dislocation Density at Nanocube Interfaces after Assembly and Epitaxy”. Agrawal H, Patra BK, Altantzis T, De Backer A, Garnett EC, Acs Applied Materials &, Interfaces 12, 8788 (2020). http://doi.org/10.1021/acsami.9b17779
Abstract: Nanoparticle self-assembly and epitaxy are utilized extensively to make 1D and 2D structures with complex shapes. High-resolution transmission electron microscopy (HRTEM) has shown that single-crystalline interfaces can form, but little is known about the strain and dislocations at these interfaces. Such information is critically important for applications: drastically reducing
dislocation density was the key breakthrough enabling widespread implementation of light-emitting diodes, while strain engineering has been fundamental to modern high-performance transistors, solar cells, and thermoelectrics. In this work, the interfacial defect and strain formation after selfassembly and room temperature epitaxy of 7 nm Pd nanocubes capped with polyvinylpyrrolidone (PVP) is examined. It is observed that, during ligand removal, the cubes move over large distances on the substrate, leading to both spontaneous self-assembly and epitaxy to form single crystals. Subsequently, atomically resolved images are used to quantify the strain and dislocation density at the epitaxial interfaces between cubes with different lateral and angular misorientations. It is shown that dislocation- and strain-free interfaces form when the nanocubes align parallel to each other. Angular misalignment between adjacent cubes does not necessarily lead to grain boundaries but does cause dislocations, with higher densities associated with larger rotations.
Keywords: A1 Journal article; Engineering sciences. Technology; Electron microscopy for materials research (EMAT); Applied Electrochemistry & Catalysis (ELCAT)
Impact Factor: 9.5
DOI: 10.1021/acsami.9b17779
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“Non‐Thermal Plasma as a Unique Delivery System of Short‐Lived Reactive Oxygen and Nitrogen Species for Immunogenic Cell Death in Melanoma Cells”. Lin A, Gorbanev Y, De Backer J, Van Loenhout J, Van Boxem W, Lemière F, Cos P, Dewilde S, Smits E, Bogaerts A, Advanced Science 6, 1802062 (2019). http://doi.org/10.1002/advs.201802062
Keywords: A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Impact Factor: 9.034
Times cited: 39
DOI: 10.1002/advs.201802062
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“Recent breakthroughs in scanning transmission electron microscopy of small species”. van den Bos KHW, Altantzis T, De Backer A, Van Aert S, Bals S, Advances in Physics: X 3, 1480420 (2018). http://doi.org/10.1080/23746149.2018.1480420
Abstract: Over the last decade, scanning transmission electron microscopy has become one of the most powerful tools to characterise nanomaterials at the atomic scale. Often, the ultimate goal is to retrieve the three-dimensional structure, which is very challenging since small species are typically sensitive to electron irradiation. Nevertheless, measuring individual atomic positions is crucial to understand the relation between the structure and physicochemical properties of these (nano)materials. In this review, we highlight the latest approaches that are available to reveal the 3D atomic structure of small species. Finally, we will provide an outlook and will describe future challenges where the limits of electron microscopy will be pushed even further.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT)
Times cited: 8
DOI: 10.1080/23746149.2018.1480420
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Verhulst SL, de Backer J, Van Gaal L, de Backer W, Desager K (2008) Adenotonsillectomy as first-line treatment for sleep-disordered breathing in obese children. New York, 1399
Keywords: L1 Letter to the editor; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 13.204
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“Study of the variability in upper and lower airway morphology in Sprague-Dawley rats using modern micro-CT scan-based segmentation techniques”. de Backer JW, Vos WG, Burnell P, Verhulst SL, Salmon P, de Clerck N, de Backer W, The anatomical record: advances in integrative anatomy and evolutionary biology 292, 720 (2009). http://doi.org/10.1002/ar.20877
Abstract: Animal models are being used extensively in pre-clinical and safety assessment studies to assess the effectiveness and safety of new chemical entities and delivery systems. Although never entirely replacing the need for animal testing, the use of computer simulations could eventually reduce the amount of animals needed for research purposes and refine the data acquired from the animal studies. Computational fluid dynamics is a powerful tool that makes it possible to simulate flow and particle behavior in animal or patient-specific respiratory models, for purposes of inhaled delivery. This tool requires an accurate representation of the respiratory system, respiration and dose delivery attributes. The aim of this study is to develop a representative airway model of the Sprague-Dawley rat using static and dynamic micro-CT scans. The entire respiratory tract was modeled, from the snout and nares down to the central airways at the point where no distinction could be made between intraluminal air and the surrounding tissue. For the selection of the representative model, variables such as upper airway movement, segmentation length, airway volume and size are taken into account. Dynamic scans of the nostril region were used to illustrate the characteristic morphology of this region in anaesthetized animals. It could be concluded from this study that it was possible to construct a highly detailed representative model of a Sprague-Dawley rat based on imaging modalities such as micro-CT scans
Keywords: A1 Journal article; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 1.431
Times cited: 16
DOI: 10.1002/ar.20877
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“Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response”. De Backer J, Maric D, Zuhra K, Bogaerts A, Szabo C, Vanden Berghe W, Hoogewijs D, Antioxidants 11, 1548 (2022). http://doi.org/10.3390/antiox11081548
Abstract: Despite recent advances in melanoma treatment, there are still patients that either do not respond or develop resistance. This unresponsiveness and/or acquired resistance to therapy could be explained by the fact that some melanoma cells reside in a dedifferentiated state. Interestingly, this dedifferentiated state is associated with greater sensitivity to ferroptosis, a lipid peroxidation-reliant, iron-dependent form of cell death. Cytoglobin (CYGB) is an iron hexacoordinated globin that is highly enriched in melanocytes and frequently downregulated during melanomagenesis. In this study, we investigated the potential effect of CYGB on the cellular sensitivity towards (1S, 3R)-RAS-selective lethal small molecule (RSL3)-mediated ferroptosis in the G361 melanoma cells with abundant endogenous expression. Our findings show that an increased basal ROS level and higher degree of lipid peroxidation upon RSL3 treatment contribute to the increased sensitivity of CYGB knockdown G361 cells to ferroptosis. Furthermore, transcriptome analysis demonstrates the enrichment of multiple cancer malignancy pathways upon CYGB knockdown, supporting a tumor-suppressive role for CYGB. Remarkably, CYGB knockdown also triggers activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and subsequent induction of pyroptosis target genes. Altogether, we show that silencing of CYGB expression modulates cancer therapy sensitivity via regulation of ferroptosis and pyroptosis cell death signaling pathways.
Keywords: A1 Journal article; Pharmacology. Therapy; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Proteinscience, proteomics and epigenetic signaling (PPES)
Impact Factor: 7
DOI: 10.3390/antiox11081548
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“Optimal experimental design for the detection of light atoms from high-resolution scanning transmission electron microscopy images”. Gonnissen J, de Backer A, den Dekker AJ, Martinez GT, Rosenauer A, Sijbers J, Van Aert S, Applied physics letters 105, 063116 (2014). http://doi.org/10.1063/1.4892884
Abstract: We report an innovative method to explore the optimal experimental settings to detect light atoms from scanning transmission electron microscopy (STEM) images. Since light elements play a key role in many technologically important materials, such as lithium-battery devices or hydrogen storage applications, much effort has been made to optimize the STEM technique in order to detect light elements. Therefore, classical performance criteria, such as contrast or signal-to-noise ratio, are often discussed hereby aiming at improvements of the direct visual interpretability. However, when images are interpreted quantitatively, one needs an alternative criterion, which we derive based on statistical detection theory. Using realistic simulations of technologically important materials, we demonstrate the benefits of the proposed method and compare the results with existing approaches.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT); Vision lab
Impact Factor: 3.411
Times cited: 12
DOI: 10.1063/1.4892884
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Lin A, De Backer J, Quatannens D, Cuypers B, Verswyvel H, De La Hoz EC, Ribbens B, Siozopoulou V, Van Audenaerde J, Marcq E, Lardon F, Laukens K, Vanlanduit S, Smits E, Bogaerts A (2022) The effect of local non‐thermal plasma therapy on the<scp>cancer‐immunity</scp>cycle in a melanoma mouse model
Abstract: Melanoma remains a deadly cancer despite significant advances in immune checkpoint blockade and targeted therapies. The incidence of melanoma is also growing worldwide, which highlights the need for novel treatment options and strategic combination of therapies. Here, we investigate non-thermal plasma (NTP), an ionized gas, as a promising, therapeutic option. In a melanoma mouse model, direct treatment of tumors with NTP results in reduced tumor burden and prolonged survival. Physical characterization of NTP treatment in situ reveals the deposited NTP energy and temperature associated with therapy response, and whole transcriptome analysis of the tumor identified several modulated pathways. NTP treatment also enhances the cancer-immunity cycle, as immune cells in both the tumor and tumor-draining lymph nodes appear more stimulated to perform their anti-cancer functions. Thus, our data suggest that local NTP therapy stimulates systemic, anti-cancer immunity. We discuss, in detail, how these fundamental insights will help direct the translation of NTP technology into the clinic and inform rational combination strategies to address the challenges in melanoma therapy.
Keywords: University Hospital Antwerp; A1 Journal article; Pharmacology. Therapy; Engineering sciences. Technology; ADReM Data Lab (ADReM); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE); Proteinscience, proteomics and epigenetic signaling (PPES)
DOI: 10.1002/btm2.10314
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“Influence of Cell Type and Culture Medium on Determining Cancer Selectivity of Cold Atmospheric Plasma Treatment”. Biscop, Lin, Boxem, Loenhout, Backer, Deben, Dewilde, Smits, Bogaerts, Cancers 11, 1287 (2019). http://doi.org/10.3390/cancers11091287
Abstract: Increasing the selectivity of cancer treatments is attractive, as it has the potential to reduce side-effects of therapy. Cold atmospheric plasma (CAP) is a novel cancer treatment that disrupts the intracellular oxidative balance. Several reports claim CAP treatment to be selective, but retrospective analysis of these studies revealed discrepancies in several biological factors and culturing methods. Before CAP can be conclusively stated as a selective cancer treatment, the importance of these factors must be investigated. In this study, we evaluated the influence of the cell type, cancer type, and cell culture medium on direct and indirect CAP treatment. Comparison of cancerous cells with their non-cancerous counterparts was performed under standardized conditions to determine selectivity of treatment. Analysis of seven human cell lines (cancerous: A549, U87, A375, and Malme-3M; non-cancerous: BEAS-2B, HA, and HEMa) and five different cell culture media (DMEM, RPMI1640, AM, BEGM, and DCBM) revealed that the tested parameters strongly influence indirect CAP treatment, while direct treatment was less affected. Taken together, the results of our study demonstrate that cell type, cancer type, and culturing medium must be taken into account before selectivity of CAP treatment can be claimed and overlooking these parameters can easily result in inaccurate conclusions of selectivity.
Keywords: A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Times cited: 9
DOI: 10.3390/cancers11091287
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“Oxidation of Innate Immune Checkpoint CD47 on Cancer Cells with Non-Thermal Plasma”. Lin A, Razzokov J, Verswyvel H, Privat-Maldonado A, De Backer J, Yusupov M, Cardenas De La Hoz E, Ponsaerts P, Smits E, Bogaerts A, Cancers 13, 579 (2021). http://doi.org/10.3390/cancers13030579
Abstract: Non-thermal plasma (NTP) therapy has been emerging as a promising cancer treatment strategy, and recently, its ability to locally induce immunogenic cancer cell death is being unraveled. We hypothesized that the chemical species produced by NTP reduce immunosuppressive surface proteins and checkpoints that are overexpressed on cancerous cells. Here, 3D in vitro tumor models, an in vivo mouse model, and molecular dynamics simulations are used to investigate the effect of NTP on CD47, a key innate immune checkpoint. CD47 is immediately modulated after NTP treatment and simulations reveal the potential oxidized salt-bridges responsible for conformational changes. Umbrella sampling simulations of CD47 with its receptor, signal-regulatory protein alpha (SIRPα), demonstrate that the induced-conformational changes reduce its binding affinity. Taken together, this work provides new insight into fundamental, chemical NTP-cancer cell interaction mechanisms and a previously overlooked advantage of present NTP cancer therapy: reducing immunosuppressive signals on the surface of cancer cells.
Keywords: A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Laboratory for Experimental Hematology (LEH); Center for Oncological Research (CORE)
DOI: 10.3390/cancers13030579
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