@article{
 title = {Sustainable lignin modifications and processing methods: green chemistry as the way forward},
 type = {article},
 year = {2023},
 websites = {https://pubs.rsc.org/en/content/articlehtml/2023/gc/d2gc04699g,https://pubs.rsc.org/en/content/articlelanding/2023/gc/d2gc04699g},
 publisher = {The Royal Society of Chemistry},
 id = {cb0e371d-2985-3778-b1a6-910ed367a2e6},
 created = {2023-02-15T16:00:15.213Z},
 accessed = {2023-02-15},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2023-05-30T10:24:08.635Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {This review aims to assess the sustainability and greenness of the modification and processing of lignin feedstock using an adaptation of the CHEM21 Metrics Toolkit and includes a guide for green solvents and designing ionic liquids. The anthropologic impact on climate has reached a critical level given that society relies on non-renewable fossil resources for energy. Thus, to alleviate this, lignins can play a key role in the transition from petroleum-based chemistry towards a more sustainable and green approach. The commercially available lignins are to a large extent technical lignins, which are obtained from the soda, Kraft or sulfite process, and to a lesser extent, lignins from biorefineries ( i.e. , organosolv and hydrolysis lignin). However, solely the incorporation of lignins at the application level is insufficient to improve sustainability and increase the greenness of processes. In this case, the path from lignin biomass to the final product should also be considered. Therefore, in this review, initially we present an adaptation of the CHEM21 metrics toolkit to assess the greenness of valorization strategies based on strategically chosen criteria. Subsequently, we present a detailed evaluation of different solvents, demonstrating the greenness of a wide variety of solvents, which will be beneficial to readers. In addition, it can be used as an instrument to design green ionic liquids that can be applied during the valorization of lignins. Furthermore, green lignin modification and depolymerization strategies (to increase the solubility, reactivity and processability and improve the structural uniformity and alter functionalities) are evaluated based on green chemistry principles considering the adapted CHEM21 metrics toolkit. Finally, the methods for processing lignins ( i.e. , blending and polymer synthesis) are assessed to determine if they can be considered sustainable approaches.},
 bibtype = {article},
 author = {Jacobs, Bram and Yao, Yawen and Van Nieuwenhove, Ine and Sharma, Dhanjay and Graulus, Geert-Jan and Bernaerts, Katrien and Verberckmoes, An},
 doi = {10.1039/d2gc04699g},
 journal = {Green Chemistry}
}

This review aims to assess the sustainability and greenness of the modification and processing of lignin feedstock using an adaptation of the CHEM21 Metrics Toolkit and includes a guide for green solvents and designing ionic liquids. The anthropologic impact on climate has reached a critical level given that society relies on non-renewable fossil resources for energy. Thus, to alleviate this, lignins can play a key role in the transition from petroleum-based chemistry towards a more sustainable and green approach. The commercially available lignins are to a large extent technical lignins, which are obtained from the soda, Kraft or sulfite process, and to a lesser extent, lignins from biorefineries ( i.e. , organosolv and hydrolysis lignin). However, solely the incorporation of lignins at the application level is insufficient to improve sustainability and increase the greenness of processes. In this case, the path from lignin biomass to the final product should also be considered. Therefore, in this review, initially we present an adaptation of the CHEM21 metrics toolkit to assess the greenness of valorization strategies based on strategically chosen criteria. Subsequently, we present a detailed evaluation of different solvents, demonstrating the greenness of a wide variety of solvents, which will be beneficial to readers. In addition, it can be used as an instrument to design green ionic liquids that can be applied during the valorization of lignins. Furthermore, green lignin modification and depolymerization strategies (to increase the solubility, reactivity and processability and improve the structural uniformity and alter functionalities) are evaluated based on green chemistry principles considering the adapted CHEM21 metrics toolkit. Finally, the methods for processing lignins ( i.e. , blending and polymer synthesis) are assessed to determine if they can be considered sustainable approaches.

@article{
 title = {Hydrogels with reversible cross-links for improved localised stem cell retention: a review},
 type = {article},
 year = {2023},
 keywords = {Adaptable hydrogels,Biomaterials,Dynamic covalent chemistry,Physicochemical association,Stem cell retention},
 pages = {e202300149},
 volume = {n/a},
 websites = {https://doi.org/10.1002/cbic.202300149},
 month = {5},
 publisher = {John Wiley & Sons, Ltd},
 day = {23},
 id = {4247eafd-964c-3792-993f-3245bd44c453},
 created = {2023-05-30T10:24:08.474Z},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2023-05-30T10:24:08.474Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 source_type = {JOUR},
 notes = {https://doi.org/10.1002/cbic.202300149},
 private_publication = {false},
 abstract = {Successful stem cell applications could significantly impact the medical fields, where many lives are at stake. However, the translation of stem cells to the clinic could be improved by challenges in stem cell transplantation and in vivo retention at the site of tissue damage.  This review aims to provide the most recent insights into developing hydrogels that can deliver, retain, and accommodate stem cells for tissue repair. Hydrogels can be used for tissue engineering as their flexibility and water content makes them excellent substitutes for the native extracellular matrix. Moreover, the mechanical properties of hydrogels are highly tuneable, and recognition moieties to control cell behaviour and fate can quickly be introduced. This review covers the parameters necessary for the physicochemical design of adaptable hydrogels, the variety of (bio)materials that can be used in such hydrogels, their application in stem cell delivery and some recently developed chemistries for reversible cross-linking. Implementing physical and dynamic covalent chemistry has resulted in adaptable hydrogels that can mimic the dynamic nature of the extracellular matrix.},
 bibtype = {article},
 author = {Princen, Ken and Marien, Neeve and Guedens, Wanda and Graulus, Geert-Jan and Adriaensens, Peter},
 doi = {https://doi.org/10.1002/cbic.202300149},
 journal = {ChemBioChem},
 number = {n/a}
}

Successful stem cell applications could significantly impact the medical fields, where many lives are at stake. However, the translation of stem cells to the clinic could be improved by challenges in stem cell transplantation and in vivo retention at the site of tissue damage.  This review aims to provide the most recent insights into developing hydrogels that can deliver, retain, and accommodate stem cells for tissue repair. Hydrogels can be used for tissue engineering as their flexibility and water content makes them excellent substitutes for the native extracellular matrix. Moreover, the mechanical properties of hydrogels are highly tuneable, and recognition moieties to control cell behaviour and fate can quickly be introduced. This review covers the parameters necessary for the physicochemical design of adaptable hydrogels, the variety of (bio)materials that can be used in such hydrogels, their application in stem cell delivery and some recently developed chemistries for reversible cross-linking. Implementing physical and dynamic covalent chemistry has resulted in adaptable hydrogels that can mimic the dynamic nature of the extracellular matrix.

@article{
 title = {Changes in Metabolism as a Diagnostic Tool for Lung Cancer: Systematic Review},
 type = {article},
 year = {2022},
 keywords = {lung cancer,metabolite profile,metabolomics},
 pages = {545},
 volume = {12},
 websites = {https://www.mdpi.com/2218-1989/12/6/545/htm,https://www.mdpi.com/2218-1989/12/6/545},
 month = {6},
 publisher = {Multidisciplinary Digital Publishing Institute},
 day = {14},
 id = {11bbebff-6076-3f50-9641-b988ec052ca8},
 created = {2022-09-13T13:45:52.436Z},
 accessed = {2022-09-13},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-09-13T13:45:55.266Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Lung cancer is the leading cause of cancer-related mortality worldwide, with five-year survival rates varying from 3–62%. Screening aims at early detection, but half of the patients are diagnosed in advanced stages, limiting therapeutic possibilities. Positron emission tomography-computed tomography (PET-CT) is an essential technique in lung cancer detection and staging, with a sensitivity reaching 96%. However, since elevated 18F-fluorodeoxyglucose (18F-FDG) uptake is not cancer-specific, PET-CT often fails to discriminate between malignant and non-malignant PET-positive hypermetabolic lesions, with a specificity of only 23%. Furthermore, discrimination between lung cancer types is still impossible without invasive procedures. High mortality and morbidity, low survival rates, and difficulties in early detection, staging, and typing of lung cancer motivate the search for biomarkers to improve the diagnostic process and life expectancy. Metabolomics has emerged as a valuable technique for these pitfalls. Over 150 metabolites have been associated with lung cancer, and several are consistent in their findings of alterations in specific metabolite concentrations. However, there is still more variability than consistency due to the lack of standardized patient cohorts and measurement protocols. This review summarizes the identified metabolic biomarkers for early diagnosis, staging, and typing and reinforces the need for biomarkers to predict disease progression and survival and to support treatment follow-up.},
 bibtype = {article},
 author = {Mariën, Hanne and Derveaux, Elien and Vanhove, Karolien and Adriaensens, Peter and Thomeer, Michiel and Mesotten, Liesbet},
 doi = {10.3390/METABO12060545},
 journal = {Metabolites 2022, Vol. 12, Page 545},
 number = {6}
}

Lung cancer is the leading cause of cancer-related mortality worldwide, with five-year survival rates varying from 3–62%. Screening aims at early detection, but half of the patients are diagnosed in advanced stages, limiting therapeutic possibilities. Positron emission tomography-computed tomography (PET-CT) is an essential technique in lung cancer detection and staging, with a sensitivity reaching 96%. However, since elevated 18F-fluorodeoxyglucose (18F-FDG) uptake is not cancer-specific, PET-CT often fails to discriminate between malignant and non-malignant PET-positive hypermetabolic lesions, with a specificity of only 23%. Furthermore, discrimination between lung cancer types is still impossible without invasive procedures. High mortality and morbidity, low survival rates, and difficulties in early detection, staging, and typing of lung cancer motivate the search for biomarkers to improve the diagnostic process and life expectancy. Metabolomics has emerged as a valuable technique for these pitfalls. Over 150 metabolites have been associated with lung cancer, and several are consistent in their findings of alterations in specific metabolite concentrations. However, there is still more variability than consistency due to the lack of standardized patient cohorts and measurement protocols. This review summarizes the identified metabolic biomarkers for early diagnosis, staging, and typing and reinforces the need for biomarkers to predict disease progression and survival and to support treatment follow-up.

@article{
 title = {Investigating the Potential of Ethyl Cellulose and a Porosity-Increasing Agent as a Carrier System for the Formulation of Amorphous Solid Dispersions},
 type = {article},
 year = {2022},
 keywords = {amorphous solid dispersion,ethyl cellulose,insoluble carrier,porosity-increasing agent,ternary solid dispersions},
 pages = {2712-2724},
 volume = {19},
 websites = {https://pubs.acs.org/doi/full/10.1021/acs.molpharmaceut.1c00972},
 month = {8},
 publisher = {American Chemical Society},
 day = {1},
 id = {0778d66a-ca7d-35be-a25f-e2bc01f35837},
 created = {2022-09-13T13:46:26.689Z},
 accessed = {2022-09-13},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-09-13T13:46:26.851Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {In the present work, an insoluble polymer, i.e., ethyl cellulose (EC), was combined with the water-soluble polyvinylpyrrolidone (PVP) as a carrier system for the formulation of amorphous solid dispersions. The rationale was that by conjoining these two different types of carriers a more gradual drug release could be created with less risk for precipitation. Our initial hypothesis was that upon contact with the dissolution medium, PVP would be released, creating a porous EC matrix through which the model drug indomethacin could diffuse. On the basis of observations of EC as a coating material, the effect of the molecular weight of PVP, and the ratio of EC/PVP on the miscibility of the polymer blend, the solid state of the solid dispersion and the drug release from these solid dispersions were investigated. X-ray powder diffraction, modulated differential scanning calorimetry, and solid-state nuclear magnetic resonance were used to unravel the miscibility and solid-state properties of these blends and solid dispersions. Solid-state nuclear magnetic resonance appeared to be a crucial technique for this aspect as modulated differential scanning calorimetry was not sufficient to grasp the complex phase behavior of these systems. Both EC/PVP K12 and EC/PVP K25 blends were miscible over the entire composition range, and addition of indomethacin did not alter this. Concerning the drug release, it was initially thought that more PVP would lead to faster drug release with a higher probability that all of the drug molecules would be able to diffuse out of the EC network as more pores would be created. However, this view on the release mechanism appeared to be too simplistic as an optimum was observed for both blends. On the basis of this work, it could be concluded that drug release from this complex ternary system was affected not only by the ratio of EC/PVP and the molecular weight of PVP but also by interactions between the three components, the wettability of the formulations, and the viscosity layer that was created around the particles.},
 bibtype = {article},
 author = {Everaerts, Melissa and Cools, Lennert and Adriaensens, Peter and Reekmans, Gunter and Baatsen, Pieter and Van Den Mooter, Guy},
 doi = {10.1021/ACS.MOLPHARMACEUT.1C00972/ASSET/IMAGES/LARGE/MP1C00972_0010.JPEG},
 journal = {Molecular Pharmaceutics},
 number = {8}
}

In the present work, an insoluble polymer, i.e., ethyl cellulose (EC), was combined with the water-soluble polyvinylpyrrolidone (PVP) as a carrier system for the formulation of amorphous solid dispersions. The rationale was that by conjoining these two different types of carriers a more gradual drug release could be created with less risk for precipitation. Our initial hypothesis was that upon contact with the dissolution medium, PVP would be released, creating a porous EC matrix through which the model drug indomethacin could diffuse. On the basis of observations of EC as a coating material, the effect of the molecular weight of PVP, and the ratio of EC/PVP on the miscibility of the polymer blend, the solid state of the solid dispersion and the drug release from these solid dispersions were investigated. X-ray powder diffraction, modulated differential scanning calorimetry, and solid-state nuclear magnetic resonance were used to unravel the miscibility and solid-state properties of these blends and solid dispersions. Solid-state nuclear magnetic resonance appeared to be a crucial technique for this aspect as modulated differential scanning calorimetry was not sufficient to grasp the complex phase behavior of these systems. Both EC/PVP K12 and EC/PVP K25 blends were miscible over the entire composition range, and addition of indomethacin did not alter this. Concerning the drug release, it was initially thought that more PVP would lead to faster drug release with a higher probability that all of the drug molecules would be able to diffuse out of the EC network as more pores would be created. However, this view on the release mechanism appeared to be too simplistic as an optimum was observed for both blends. On the basis of this work, it could be concluded that drug release from this complex ternary system was affected not only by the ratio of EC/PVP and the molecular weight of PVP but also by interactions between the three components, the wettability of the formulations, and the viscosity layer that was created around the particles.

@article{
 title = {Unraveling the Rewired Metabolism in Lung Cancer Using Quantitative NMR Metabolomics},
 type = {article},
 year = {2022},
 keywords = {NMR (nuclear magnetic resonance),lung cancer,metabolism},
 pages = {5602},
 volume = {23},
 websites = {https://www.mdpi.com/1422-0067/23/10/5602/htm,https://www.mdpi.com/1422-0067/23/10/5602},
 month = {5},
 publisher = {Multidisciplinary Digital Publishing Institute},
 day = {17},
 id = {066407d6-876a-30a0-abf2-50b817ade00e},
 created = {2022-09-13T13:46:37.984Z},
 accessed = {2022-09-13},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-09-13T13:46:38.128Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Lung cancer cells are well documented to rewire their metabolism and energy production networks to enable proliferation and survival in a nutrient-poor and hypoxic environment. Although metabolite profiling of blood plasma and tissue is still emerging in omics approaches, several techniques have shown potential in cancer diagnosis. In this paper, the authors describe the alterations in the metabolic phenotype of lung cancer patients. In addition, we focus on the metabolic cooperation between tumor cells and healthy tissue. Furthermore, the authors discuss how metabolomics could improve the management of lung cancer patients.},
 bibtype = {article},
 author = {Vanhove, Karolien and Derveaux, Elien and Mesotten, Liesbet and Thomeer, Michiel and Criel, Maarten and Mariën, Hanne and Adriaensens, Peter},
 doi = {10.3390/IJMS23105602},
 journal = {International Journal of Molecular Sciences 2022, Vol. 23, Page 5602},
 number = {10}
}

Lung cancer cells are well documented to rewire their metabolism and energy production networks to enable proliferation and survival in a nutrient-poor and hypoxic environment. Although metabolite profiling of blood plasma and tissue is still emerging in omics approaches, several techniques have shown potential in cancer diagnosis. In this paper, the authors describe the alterations in the metabolic phenotype of lung cancer patients. In addition, we focus on the metabolic cooperation between tumor cells and healthy tissue. Furthermore, the authors discuss how metabolomics could improve the management of lung cancer patients.

@article{
 title = {Nanobodies for the Early Detection of Ovarian Cancer},
 type = {article},
 year = {2022},
 keywords = {early,epithelial ovarian cancer,human epididymis protein 4,nanobodies,progranulin,secretory leukocyte protease inhibitor,stage cancer detection},
 pages = {13687},
 volume = {23},
 websites = {https://www.mdpi.com/1422-0067/23/22/13687},
 month = {11},
 publisher = {Multidisciplinary Digital Publishing Institute},
 day = {8},
 id = {edcc98b8-99cf-366e-9bec-bf31ab10b475},
 created = {2022-11-09T12:41:50.128Z},
 accessed = {2022-11-09},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-11-09T12:41:50.256Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Ovarian cancer ranks fifth in cancer-related deaths among women. Since ovarian cancer patients are often asymptomatic, most patients are diagnosed only at an advanced stage of disease. This results in a 5-year survival rate below 50%, which is in strong contrast to a survival rate as high as 94% if detected and treated at an early stage. Monitoring serum biomarkers offers new possibilities to diagnose ovarian cancer at an early stage. In this study, nanobodies targeting the ovarian cancer biomarkers human epididymis protein 4 (HE4), secretory leukocyte protease inhibitor (SLPI), and progranulin (PGRN) were evaluated regarding their expression levels in bacterial systems, epitope binning, and antigen-binding affinity by enzyme-linked immunosorbent assay and surface plasmon resonance. The selected nanobodies possess strong binding affinities for their cognate antigens (KD~0.1–10 nM) and therefore have a pronounced potential to detect ovarian cancer at an early stage. Moreover, it is of utmost importance that the limits of detection (LOD) for these biomarkers are in the pM range, implying high specificity and sensitivity, as demonstrated by values in human serum of 37 pM for HE4, 163 pM for SLPI, and 195 pM for PGRN. These nanobody candidates could thus pave the way towards multiplexed biosensors.},
 bibtype = {article},
 author = {Tran, Lan-Huong and Graulus, Geert-Jan and Vincke, Cécile and Smiejkowska, Natalia and Kindt, Anne and Devoogdt, Nick and Muyldermans, Serge and Adriaensens, Peter and Guedens, Wanda},
 doi = {10.3390/IJMS232213687},
 journal = {International Journal of Molecular Sciences 2022, Vol. 23, Page 13687},
 number = {22}
}

Ovarian cancer ranks fifth in cancer-related deaths among women. Since ovarian cancer patients are often asymptomatic, most patients are diagnosed only at an advanced stage of disease. This results in a 5-year survival rate below 50%, which is in strong contrast to a survival rate as high as 94% if detected and treated at an early stage. Monitoring serum biomarkers offers new possibilities to diagnose ovarian cancer at an early stage. In this study, nanobodies targeting the ovarian cancer biomarkers human epididymis protein 4 (HE4), secretory leukocyte protease inhibitor (SLPI), and progranulin (PGRN) were evaluated regarding their expression levels in bacterial systems, epitope binning, and antigen-binding affinity by enzyme-linked immunosorbent assay and surface plasmon resonance. The selected nanobodies possess strong binding affinities for their cognate antigens (KD~0.1–10 nM) and therefore have a pronounced potential to detect ovarian cancer at an early stage. Moreover, it is of utmost importance that the limits of detection (LOD) for these biomarkers are in the pM range, implying high specificity and sensitivity, as demonstrated by values in human serum of 37 pM for HE4, 163 pM for SLPI, and 195 pM for PGRN. These nanobody candidates could thus pave the way towards multiplexed biosensors.

@article{
 title = {Detection of Lung Cancer via Blood Plasma and 1H-NMR Metabolomics: Validation by a Semi-Targeted and Quantitative Approach Using a Protein-Binding Competitor},
 type = {article},
 year = {2021},
 keywords = {DA classification,NMR metabolomics,OPLS,binding competitor,lung cancer diagnosis,maleic acid internal standard,metabolite profile,protein},
 pages = {537},
 volume = {11},
 websites = {https://www.mdpi.com/2218-1989/11/8/537/htm,https://www.mdpi.com/2218-1989/11/8/537},
 month = {8},
 publisher = {Multidisciplinary Digital Publishing Institute},
 day = {12},
 id = {ee9acba3-8ce8-3782-9ab3-bce259c60663},
 created = {2021-09-08T12:38:02.084Z},
 accessed = {2021-09-08},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:13.374Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Metabolite profiling of blood plasma, by proton nuclear magnetic resonance (1H-NMR) spectroscopy, offers great potential for early cancer diagnosis and unraveling disruptions in cancer metabolism. Despite the essential attempts to standardize pre-analytical and external conditions, such as pH or temperature, the donor-intrinsic plasma protein concentration is highly overlooked. However, this is of utmost importance, since several metabolites bind to these proteins, resulting in an underestimation of signal intensities. This paper describes a novel 1H-NMR approach to avoid metabolite binding by adding 4 mM trimethylsilyl-2,2,3,3-tetradeuteropropionic acid (TSP) as a strong binding competitor. In addition, it is demonstrated, for the first time, that maleic acid is a reliable internal standard to quantify the human plasma metabolites without the need for protein precipitation. Metabolite spiking is further used to identify the peaks of 62 plasma metabolites and to divide the 1H-NMR spectrum into 237 well-defined integration regions, representing these 62 metabolites. A supervised multivariate classification model, trained using the intensities of these integration regions (areas under the peaks), was able to differentiate between lung cancer patients and healthy controls in a large patient cohort (n = 160), with a specificity, sensitivity, and area under the curve of 93%, 85%, and 0.95, respectively. The robustness of the classification model is shown by validation in an independent patient cohort (n = 72).},
 bibtype = {article},
 author = {Derveaux, Elien and Thomeer, Michiel and Mesotten, Liesbet and Reekmans, Gunter and Adriaensens, Peter},
 doi = {10.3390/METABO11080537},
 journal = {Metabolites 2021, Vol. 11, Page 537},
 number = {8}
}

Metabolite profiling of blood plasma, by proton nuclear magnetic resonance (1H-NMR) spectroscopy, offers great potential for early cancer diagnosis and unraveling disruptions in cancer metabolism. Despite the essential attempts to standardize pre-analytical and external conditions, such as pH or temperature, the donor-intrinsic plasma protein concentration is highly overlooked. However, this is of utmost importance, since several metabolites bind to these proteins, resulting in an underestimation of signal intensities. This paper describes a novel 1H-NMR approach to avoid metabolite binding by adding 4 mM trimethylsilyl-2,2,3,3-tetradeuteropropionic acid (TSP) as a strong binding competitor. In addition, it is demonstrated, for the first time, that maleic acid is a reliable internal standard to quantify the human plasma metabolites without the need for protein precipitation. Metabolite spiking is further used to identify the peaks of 62 plasma metabolites and to divide the 1H-NMR spectrum into 237 well-defined integration regions, representing these 62 metabolites. A supervised multivariate classification model, trained using the intensities of these integration regions (areas under the peaks), was able to differentiate between lung cancer patients and healthy controls in a large patient cohort (n = 160), with a specificity, sensitivity, and area under the curve of 93%, 85%, and 0.95, respectively. The robustness of the classification model is shown by validation in an independent patient cohort (n = 72).

@article{
 title = {PEGylating poly(p-phenylene vinylene)-based bioimaging nanoprobes},
 type = {article},
 year = {2021},
 keywords = {Bioimaging,CPM-PPV-co-MDMO-PPV,Conjugated polymers,Nanoparticles,Optical properties,Protein corona},
 pages = {566-575},
 volume = {581},
 month = {1},
 publisher = {Academic Press},
 day = {1},
 id = {3d8523f0-2207-318a-b790-6b4d9850307f},
 created = {2021-09-08T12:46:08.654Z},
 accessed = {2021-09-08},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:46:11.905Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Hypothesis: Conjugated polymer nanoparticles (CNPs) have attracted considerable attention within bioimaging due to their excellent optical properties and biocompatibility. However, unspecific adsorption of proteins hampers their effective use as advanced bioimaging probes. Controlled methodologies made possible tailor-made functional poly(p-phenylene vinylene), enabling one-pot synthesis of CNPs containing functional surface groups. Hence, it should be feasible to PEGylate these CNPs to tune the uptake by cell lines representative for the brain without imparting their optical properties. Experiments: CNPs consisting of the statistical copolymer 2-(5′-methoxycarbonylpentyloxy)-5-methoxy-1,4-phenylenevinylene and poly(2-methoxy-5-(3′,7′-dimethoxyoctyloxy)-1,4-phenylenevinylene) were fabricated by miniemulsion solvent evaporation technique. Surface carboxylic acid groups were used to covalently attach amine-terminated polyethylene glycol (PEG) of different molecular weights. We investigated the effect of grafting CNPs with PEG chains on their intrinsic optical properties, protein adsorption behavior and uptake by representative brain cell lines. Findings: PEGylation did not affect the optical properties and biocompatibility of our CNPs. Moreover, a significant decrease in protein corona formation and unspecific uptake in central nervous system cell lines, depending on PEG chain length, was observed. This is the first report indicating that PEGylation does not affect the CNPs role as excellent bioimaging tools and can be adapted to tune biological interactions with brain cells.},
 bibtype = {article},
 author = {Peters, Martijn and Desta, Derese and Seneca, Senne and Reekmans, Gunter and Adriaensens, Peter and Noben, Jean Paul and Hellings, Niels and Junkers, Tanja and Ethirajan, Anitha},
 doi = {10.1016/J.JCIS.2020.07.145},
 journal = {Journal of Colloid and Interface Science}
}

Hypothesis: Conjugated polymer nanoparticles (CNPs) have attracted considerable attention within bioimaging due to their excellent optical properties and biocompatibility. However, unspecific adsorption of proteins hampers their effective use as advanced bioimaging probes. Controlled methodologies made possible tailor-made functional poly(p-phenylene vinylene), enabling one-pot synthesis of CNPs containing functional surface groups. Hence, it should be feasible to PEGylate these CNPs to tune the uptake by cell lines representative for the brain without imparting their optical properties. Experiments: CNPs consisting of the statistical copolymer 2-(5′-methoxycarbonylpentyloxy)-5-methoxy-1,4-phenylenevinylene and poly(2-methoxy-5-(3′,7′-dimethoxyoctyloxy)-1,4-phenylenevinylene) were fabricated by miniemulsion solvent evaporation technique. Surface carboxylic acid groups were used to covalently attach amine-terminated polyethylene glycol (PEG) of different molecular weights. We investigated the effect of grafting CNPs with PEG chains on their intrinsic optical properties, protein adsorption behavior and uptake by representative brain cell lines. Findings: PEGylation did not affect the optical properties and biocompatibility of our CNPs. Moreover, a significant decrease in protein corona formation and unspecific uptake in central nervous system cell lines, depending on PEG chain length, was observed. This is the first report indicating that PEGylation does not affect the CNPs role as excellent bioimaging tools and can be adapted to tune biological interactions with brain cells.

@article{
 title = {Plausibility and redundancy analysis to select FDG-PET textural features in non-small cell lung cancer},
 type = {article},
 year = {2021},
 keywords = {clinical value,feature selection,radiomics},
 pages = {1226-1238},
 volume = {48},
 websites = {https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/mp.14684,https://aapm.onlinelibrary.wiley.com/doi/abs/10.1002/mp.14684,https://aapm.onlinelibrary.wiley.com/doi/10.1002/mp.14684},
 month = {3},
 publisher = {John Wiley & Sons, Ltd},
 day = {1},
 id = {728a1dd2-9214-3802-9f18-8822c399971c},
 created = {2021-09-08T12:46:26.221Z},
 accessed = {2021-09-08},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:46:34.529Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Radiomics refers to the extraction of a large number of image biomarker describing the tumor phenotype displayed in a medical image. Extracted from positron emission tomography (PET) images, radiomics showed diagnostic and prognostic value for several cancer types. However, a large number of radiomic features are nonreproducible or highly correlated with conventional PET metrics. Moreover, radiomic features used in the clinic should yield relevant information about tumor texture. In this study, we propose a framework to identify technical and clinical meaningful features and exemplify our results using a PET non-small cell lung cancer (NSCLC) dataset. Materials and methods: The proposed selection procedure consists of several steps. A priori, we only include features that were found to be reproducible in a multicenter setting. Next, we apply a voxel randomization step to identify features that reflect actual textural information, that is, that yield in 90% of the patient scans a value significantly different from random texture. Finally, the remaining features were correlated with standard PET metrics to further remove redundancy with common PET metrics. The selection procedure was performed for different volume ranges, that is, excluding lesions with smaller volumes in order to assess the effect of tumor size on the results. To exemplify our procedure, the selected features were used to predict 1-yr survival in a dataset of 150 NSCLC patients. A predictive model was built using volume as predictive factor for smaller, and one of the selected features as predictive factor for bigger lesions. The prediction accuracy of the both models were compared with the prediction accuracy of volume. Results: The number of selected features depended on the lesion size included in the analysis. When including the whole dataset, from 19 features reflecting actual texture only two were found to be not strongly correlated with conventional PET metrics. When excluding lesions smaller than 11.49 and 33.10 mL (25 and 50 percentile of the dataset), four out of 27 features and 13 out of 29 features remained after eliminating features highly correlated with standard PET metrics. When excluding lesions smaller than 103.9 mL (75 percentile), 33 out of 53 features remained. For larger lesions, some of these features outperformed volume in terms of classification accuracy (increase of 4–10%). The combination of using volume as predictor for smaller and one of the selected features for larger lesions also improved the accuracy when compared with volume only (increase from 72% to 76%). Conclusion: When performing radiomic analysis for smaller lesions, it should be first carefully investigated if a textural feature reflects actual heterogeneity information. Next, verification of the absence of correlation with all conventional PET metrics is essential in order to assess the additional value of radiomic features. Radiomic analysis with lesions larger than 11.4 mL might give additional information to conventional metrics while at the same time reflecting actual tumor texture. Using a combination of volume and one of the selected features for prediction yields promise to increase accuracy and reliability of a radiomic model.},
 bibtype = {article},
 author = {Pfaehler, Elisabeth and Mesotten, Liesbet and Zhovannik, Ivan and Pieplenbosch, Simone and Thomeer, Michiel and Vanhove, Karolien and Adriaensens, Peter and Boellaard, Ronald},
 doi = {10.1002/MP.14684},
 journal = {Medical Physics},
 number = {3}
}

Background: Radiomics refers to the extraction of a large number of image biomarker describing the tumor phenotype displayed in a medical image. Extracted from positron emission tomography (PET) images, radiomics showed diagnostic and prognostic value for several cancer types. However, a large number of radiomic features are nonreproducible or highly correlated with conventional PET metrics. Moreover, radiomic features used in the clinic should yield relevant information about tumor texture. In this study, we propose a framework to identify technical and clinical meaningful features and exemplify our results using a PET non-small cell lung cancer (NSCLC) dataset. Materials and methods: The proposed selection procedure consists of several steps. A priori, we only include features that were found to be reproducible in a multicenter setting. Next, we apply a voxel randomization step to identify features that reflect actual textural information, that is, that yield in 90% of the patient scans a value significantly different from random texture. Finally, the remaining features were correlated with standard PET metrics to further remove redundancy with common PET metrics. The selection procedure was performed for different volume ranges, that is, excluding lesions with smaller volumes in order to assess the effect of tumor size on the results. To exemplify our procedure, the selected features were used to predict 1-yr survival in a dataset of 150 NSCLC patients. A predictive model was built using volume as predictive factor for smaller, and one of the selected features as predictive factor for bigger lesions. The prediction accuracy of the both models were compared with the prediction accuracy of volume. Results: The number of selected features depended on the lesion size included in the analysis. When including the whole dataset, from 19 features reflecting actual texture only two were found to be not strongly correlated with conventional PET metrics. When excluding lesions smaller than 11.49 and 33.10 mL (25 and 50 percentile of the dataset), four out of 27 features and 13 out of 29 features remained after eliminating features highly correlated with standard PET metrics. When excluding lesions smaller than 103.9 mL (75 percentile), 33 out of 53 features remained. For larger lesions, some of these features outperformed volume in terms of classification accuracy (increase of 4–10%). The combination of using volume as predictor for smaller and one of the selected features for larger lesions also improved the accuracy when compared with volume only (increase from 72% to 76%). Conclusion: When performing radiomic analysis for smaller lesions, it should be first carefully investigated if a textural feature reflects actual heterogeneity information. Next, verification of the absence of correlation with all conventional PET metrics is essential in order to assess the additional value of radiomic features. Radiomic analysis with lesions larger than 11.4 mL might give additional information to conventional metrics while at the same time reflecting actual tumor texture. Using a combination of volume and one of the selected features for prediction yields promise to increase accuracy and reliability of a radiomic model.

@article{
 title = {Direct Immobilization of Engineered Nanobodies on Gold Sensors},
 type = {article},
 year = {2021},
 keywords = {molecular dynamic simulations,nanobody,sensor,single-domain antibody,surface plasmon resonance},
 pages = {17353-17360},
 volume = {13},
 websites = {https://pubs.acs.org/doi/full/10.1021/acsami.1c02280},
 month = {4},
 publisher = {American Chemical Society},
 day = {21},
 id = {a9c8f6bb-2d3f-3bba-b4fa-47a51433e44d},
 created = {2021-09-08T12:46:29.665Z},
 accessed = {2021-09-08},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:46:41.361Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Single-domain antibodies, known as nanobodies, have great potential as biorecognition elements for sensors because of their small size, affinity, specificity, and robustness. However, facile and ef...},
 bibtype = {article},
 author = {Simões, Bárbara and Guedens, Wanda J. and Keene, Charlie and Kubiak-Ossowska, Karina and Mulheran, Paul and Kotowska, Anna M. and Scurr, David J. and Alexander, Morgan R and Broisat, Alexis and Johnson, Steven and Muyldermans, Serge and Devoogdt, Nick and Adriaensens, Peter and Mendes, Paula M.},
 doi = {10.1021/ACSAMI.1C02280},
 journal = {ACS Applied Materials & Interfaces},
 number = {15}
}

Single-domain antibodies, known as nanobodies, have great potential as biorecognition elements for sensors because of their small size, affinity, specificity, and robustness. However, facile and ef...

@article{
 title = {Mechanically versatile isosorbide-based thermoplastic copolyether-esters with a poly(ethylene glycol) soft segment},
 type = {article},
 year = {2021},
 keywords = {engineering plastics,isosorbide,polycondensation,segmented multiblock copolymers,thermoplastic copolyesters},
 id = {3cf1903e-973a-3c73-bee5-f36845e4ba00},
 created = {2022-03-14T13:58:13.194Z},
 accessed = {2022-03-14},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-03-14T13:58:13.194Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Segmented thermoplastic copolyether esters (TPEE's) with a partially renewable hard block containing isosorbide (ISB) and poly(ethylene glycol) (PEG) soft blocks were prepared by melt polycondensation. A range of compositions was accessible despite the relatively low reactivity of the sterically and electronically hindered ISB monomer. The small-scale reactions performed in the melt were limited in terms of achievable molar mass. This is attributed to the challenge of attaining stoichiometric balance in the feed and maintaining this balance throughout the high temperature (>200 C) reactions. Nevertheless, products were isolated that could be manipulated and melt-pressed into specimen for tensile testing. Varying the feed compositions gave rise to copolymers exhibiting a broad range of mechanical properties (elastic modulus from 1-66 MPa). These characteristics are consistent with a segmented polymer architecture with morphological features similar to commercially available TPEE counterparts. These results pave the way for more responsibly sourced building blocks being incorporated into materials with high market value potential.},
 bibtype = {article},
 author = {Monnery, Bryn D and Karanastasis, Apostolos and Adriaensens, | Peter and Pitet, Louis M},
 doi = {10.1002/pol.20210548}
}

Segmented thermoplastic copolyether esters (TPEE's) with a partially renewable hard block containing isosorbide (ISB) and poly(ethylene glycol) (PEG) soft blocks were prepared by melt polycondensation. A range of compositions was accessible despite the relatively low reactivity of the sterically and electronically hindered ISB monomer. The small-scale reactions performed in the melt were limited in terms of achievable molar mass. This is attributed to the challenge of attaining stoichiometric balance in the feed and maintaining this balance throughout the high temperature (>200 C) reactions. Nevertheless, products were isolated that could be manipulated and melt-pressed into specimen for tensile testing. Varying the feed compositions gave rise to copolymers exhibiting a broad range of mechanical properties (elastic modulus from 1-66 MPa). These characteristics are consistent with a segmented polymer architecture with morphological features similar to commercially available TPEE counterparts. These results pave the way for more responsibly sourced building blocks being incorporated into materials with high market value potential.

@article{
 title = {The polymeric glyco-linker controls the signal outputs for plasmonic gold nanorod biosensors due to biocorona formation},
 type = {article},
 year = {2021},
 pages = {10837},
 volume = {13},
 id = {df1d88e6-1abd-3ae5-b3c0-1ae1eb59a2ca},
 created = {2022-03-14T14:52:32.037Z},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-03-14T14:52:38.270Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Gold nanorods (GNRs) are a promising platform for nanoplasmonic biosensing. The localised surface plasmon resonance (LSPR) peak of GNRs is located in the near-infrared optical window and is sensitive to local binding events, enabling label-free detection of biomarkers in complex biological fluids. A key challenge in the development of such sensors is achieving target affinity and selectivity, while both minimizing non-specific binding and maintaining colloidal stability. Herein, we reveal how GNRs decorated with galactosamine-terminated polymer ligands display significantly different binding responses in buffer compared to serum, due to biocorona formation, and how biocorona displacement due to lectin binding plays a key role in their optical responses. GNRs were coated with either poly(N-(2-hydroxypropyl)methacryl-amide) (PHPMA) or poly(N-hydroxyethyl acrylamide) (PHEA) prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerisation and end-functionalised with galactosamine (Gal) as the lectin-targeting unit. In buffer Gal-PHEA-coated GNRs aggregated upon soybean agglutinin (SBA) addition, whereas Gal-PHPMA-coated GNRs exhibited a red-shift of the LSPR spectrum without aggregation. In contrast, when incubated in serum Gal-PHPMA-coated nanorods showed no binding response, while Gal-PHEA GNRs exhibited a dose-dependent blue-shift of the LSPR peak, which is the opposite direction (red-shift) to what was observed in buffer. This differential behaviour was attributed to biocorona formation onto both polymer-coated GNRs, shown by differential centrifugal sedimentation and nano-particle tracking analysis. Upon addition of SBA to the Gal-PHEA coated nanorods, signal was generated due to displacement of weakly-bound biocorona components by lectin binding. However, in the case of Gal-PHPMA which had a thicker corona, attributed to lower polymer grafting densities, addition of SBA did not lead to biocorona displacement and there was no signal output. These results show that plasmo-nic optical responses in complex biological media can be significantly affected by biocorona formation, and that biocorona formation itself does not prevent sensing so long as its exact nature (e.g. 'hard versus soft') is tuned.},
 bibtype = {article},
 author = {Pancaro, Alessia and Szymonik, Michal and Georgiou, Panagiotis G and Baker, Alexander N and Walker, Marc and Adriaensens, Peter and Hendrix, Jelle and Gibson, Matthew I and Nelissen, Inge},
 doi = {10.1039/d1nr01548f}
}

Gold nanorods (GNRs) are a promising platform for nanoplasmonic biosensing. The localised surface plasmon resonance (LSPR) peak of GNRs is located in the near-infrared optical window and is sensitive to local binding events, enabling label-free detection of biomarkers in complex biological fluids. A key challenge in the development of such sensors is achieving target affinity and selectivity, while both minimizing non-specific binding and maintaining colloidal stability. Herein, we reveal how GNRs decorated with galactosamine-terminated polymer ligands display significantly different binding responses in buffer compared to serum, due to biocorona formation, and how biocorona displacement due to lectin binding plays a key role in their optical responses. GNRs were coated with either poly(N-(2-hydroxypropyl)methacryl-amide) (PHPMA) or poly(N-hydroxyethyl acrylamide) (PHEA) prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerisation and end-functionalised with galactosamine (Gal) as the lectin-targeting unit. In buffer Gal-PHEA-coated GNRs aggregated upon soybean agglutinin (SBA) addition, whereas Gal-PHPMA-coated GNRs exhibited a red-shift of the LSPR spectrum without aggregation. In contrast, when incubated in serum Gal-PHPMA-coated nanorods showed no binding response, while Gal-PHEA GNRs exhibited a dose-dependent blue-shift of the LSPR peak, which is the opposite direction (red-shift) to what was observed in buffer. This differential behaviour was attributed to biocorona formation onto both polymer-coated GNRs, shown by differential centrifugal sedimentation and nano-particle tracking analysis. Upon addition of SBA to the Gal-PHEA coated nanorods, signal was generated due to displacement of weakly-bound biocorona components by lectin binding. However, in the case of Gal-PHPMA which had a thicker corona, attributed to lower polymer grafting densities, addition of SBA did not lead to biocorona displacement and there was no signal output. These results show that plasmo-nic optical responses in complex biological media can be significantly affected by biocorona formation, and that biocorona formation itself does not prevent sensing so long as its exact nature (e.g. 'hard versus soft') is tuned.

@article{
 title = {Repeatability of two semi-automatic artificial intelligence approaches for tumor segmentation in PET},
 type = {article},
 year = {2021},
 keywords = {Cardiac Imaging,Convolutional neural network,Imaging / Radiology,Nuclear Medicine,Oncology,Orthopedics,Repeatability,Textural segmentation,Tumor segmentation PET},
 pages = {1-11},
 volume = {11},
 websites = {https://ejnmmires.springeropen.com/articles/10.1186/s13550-020-00744-9,https://doi.org/10.1186/s13550-020-00744-9},
 month = {1},
 publisher = {SpringerOpen},
 day = {6},
 id = {b9589b1a-e537-3821-9df1-853d75eadbae},
 created = {2022-03-14T14:52:32.038Z},
 accessed = {2021-09-08},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-03-14T14:52:37.201Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Pfaehler, Elisabeth and Mesotten, Liesbet and Kramer, Gem and Thomeer, Michiel and Vanhove, Karolien and de Jong, Johan and Adriaensens, Peter and Hoekstra, Otto S. and Boellaard, Ronald},
 journal = {EJNMMI Research 2021 11:1},
 number = {1}
}

@article{
 title = {Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions},
 type = {article},
 year = {2020},
 keywords = {amorphous solid dispersions,miscibility,modulated differential scanning calorimetry,oxazoline)s,poly(2,solid,state nuclear magnetic resonance spectroscopy},
 pages = {3587},
 volume = {25},
 websites = {https://www.mdpi.com/1420-3049/25/16/3587/htm,https://www.mdpi.com/1420-3049/25/16/3587},
 month = {8},
 publisher = {Multidisciplinary Digital Publishing Institute},
 day = {6},
 id = {67bd46a6-53a9-305b-b172-b0608a25a795},
 created = {2021-09-08T12:36:38.277Z},
 accessed = {2021-09-08},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:36:49.436Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed. In this work, we present an alternative carrier system for ASDs where a water-soluble and water-insoluble carrier are combined to delay the drug release and thus prevent this onset of precipitation. Poly(2-alkyl-2-oxazoline)s were selected as a polymer platform since the solution properties of this polymer class depend on the length of the alkyl sidechain. Poly(2-ethyl-2-oxazoline) (PEtOx) behaves as a water-soluble polymer at body temperature, while poly(2-n-propyl-2-oxazoline) (PPrOx) and poly(2-sec-butyl-2-oxazoline) (PsecBuOx) are insoluble at body temperature. Since little was known about the polymer’s miscibility behaviour and especially on how the presence of a poorly-water soluble drug impacted their miscibility, a preformulation study was performed. Formulations were investigated with X-ray powder diffraction, differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy. PEtOx/PPrOx appeared to form an immiscible blend based on DSC and this was even more pronounced after heating. The six drugs that were tested in this work did not show any preference for one of the two phases. PEtOx/PsecBuOx on the other hand appeared to be miscible forming a homogeneous blend between the two polymers and the drugs.},
 bibtype = {article},
 author = {Everaerts, Melissa and Tigrine, Ali and Rosa, Victor R. de la and Hoogenboom, Richard and Adriaensens, Peter and Clasen, Christian and Mooter, Guy Van den},
 doi = {10.3390/MOLECULES25163587},
 journal = {Molecules 2020, Vol. 25, Page 3587},
 number = {16}
}

Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed. In this work, we present an alternative carrier system for ASDs where a water-soluble and water-insoluble carrier are combined to delay the drug release and thus prevent this onset of precipitation. Poly(2-alkyl-2-oxazoline)s were selected as a polymer platform since the solution properties of this polymer class depend on the length of the alkyl sidechain. Poly(2-ethyl-2-oxazoline) (PEtOx) behaves as a water-soluble polymer at body temperature, while poly(2-n-propyl-2-oxazoline) (PPrOx) and poly(2-sec-butyl-2-oxazoline) (PsecBuOx) are insoluble at body temperature. Since little was known about the polymer’s miscibility behaviour and especially on how the presence of a poorly-water soluble drug impacted their miscibility, a preformulation study was performed. Formulations were investigated with X-ray powder diffraction, differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy. PEtOx/PPrOx appeared to form an immiscible blend based on DSC and this was even more pronounced after heating. The six drugs that were tested in this work did not show any preference for one of the two phases. PEtOx/PsecBuOx on the other hand appeared to be miscible forming a homogeneous blend between the two polymers and the drugs.

@article{
 title = {Developing and Implementing GAPc, a Gamification Project in Chemistry, toward a Remote Active Student-Centered Chemistry Course Bridging the Gap between Precollege and Undergraduate Education},
 type = {article},
 year = {2020},
 keywords = {Acids/Bases,Aqueous Solution Chemistry,Computer-Based Learning,Distance Learning/Self Instruction,Electrochemistry,First-Year Undergraduate/General,High School/Introductory Chemistry,Inorganic Chemistry,Public Understanding/Outreach,Testing/Assessment},
 websites = {https://dx.doi.org/10.1021/acs.jchemed.9b00986},
 month = {8},
 publisher = {American Chemical Society},
 day = {11},
 id = {88f4a4d0-c9de-3f53-aeb0-b2c281e8a069},
 created = {2021-09-08T12:38:06.346Z},
 accessed = {2020-10-02},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:20.290Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {This paper describes the development and implementation of GAPc, a gamification project in chemistry. GAPc is an online active student-centered remedial teaching tool allowing prospective and enrolled students to electronically assess their knowledge of basic and advanced chemistry concepts via different game levels of expertise. This provides them with ways to correct potential shortcomings in view of academic education. A large number of exercises with different degrees of difficulty, links to additional sources of information, automated feedback, and the integrated grading center are key features of GAPc. Notwithstanding that GAPc is conceived as a distance learning and self-learning tool, it works equally well in a classroom setting. Indeed, GAPc was initially meant as a trajectory for precollege students to remediate their acquainted knowledge of chemistry by easy remote access. Today, on the Hasselt University Campus, GAPc is used in the chemistry summer school for senior high school students, and in chemistry courses for freshmen and sophomores enrolled in curricula with a major chemistry component.},
 bibtype = {article},
 author = {Brassinne, Kristien and Reynders, Monique and Coninx, Karin and Guedens, Wanda},
 doi = {10.1021/acs.jchemed.9b00986},
 journal = {Journal of Chemical Education}
}

This paper describes the development and implementation of GAPc, a gamification project in chemistry. GAPc is an online active student-centered remedial teaching tool allowing prospective and enrolled students to electronically assess their knowledge of basic and advanced chemistry concepts via different game levels of expertise. This provides them with ways to correct potential shortcomings in view of academic education. A large number of exercises with different degrees of difficulty, links to additional sources of information, automated feedback, and the integrated grading center are key features of GAPc. Notwithstanding that GAPc is conceived as a distance learning and self-learning tool, it works equally well in a classroom setting. Indeed, GAPc was initially meant as a trajectory for precollege students to remediate their acquainted knowledge of chemistry by easy remote access. Today, on the Hasselt University Campus, GAPc is used in the chemistry summer school for senior high school students, and in chemistry courses for freshmen and sophomores enrolled in curricula with a major chemistry component.

@article{
 title = {An Efficient Thermal Elimination Pathway toward Phosphodiester Hydrogels via a Precursor Approach},
 type = {article},
 year = {2020},
 keywords = {biomaterials,hydrogels,phosphodiesters},
 pages = {1900466},
 volume = {221},
 websites = {https://onlinelibrary.wiley.com/doi/abs/10.1002/macp.201900466},
 month = {3},
 publisher = {Wiley-VCH Verlag},
 day = {29},
 id = {8a364471-f1b1-32c5-8955-0e574f66b43f},
 created = {2021-09-08T12:38:07.045Z},
 accessed = {2020-09-28},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:05.481Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Phosphodiester hydrogels offer a wide range of fascinating properties. Not only do they exhibit excellent hemocompatibility and cellular compatibility, they also show a remarkable resistance to protein adsorption, thereby limiting the foreign body response. In this work, phosphodiester-crosslinked hydrogels are produced by a simple free-radical polymerization of a phosphotriester crosslinker. In a second step, this material is transformed to the phosphodiester, by heating it up to 60 °C in phosphate-buffered saline. Compared to earlier methods, there is no need for acids, bases, or oxidizing agents to achieve this final conversion to the phosphodiester. This method thus reduces the risk to damage or degrade any sensitive biomolecules that might be of interest to tissue engineers, such as various growth factors or other proteins. The phosphotriester crosslinker is readily synthesized out of common laboratory chemicals in multigram quantities with good yield and easy workup and purification.},
 bibtype = {article},
 author = {Dera, Rafael and Diliën, Hanne and Adriaensens, Peter and Guedens, Wanda and Cleij, Thomas J.},
 doi = {10.1002/macp.201900466},
 journal = {Macromolecular Chemistry and Physics},
 number = {5}
}

Phosphodiester hydrogels offer a wide range of fascinating properties. Not only do they exhibit excellent hemocompatibility and cellular compatibility, they also show a remarkable resistance to protein adsorption, thereby limiting the foreign body response. In this work, phosphodiester-crosslinked hydrogels are produced by a simple free-radical polymerization of a phosphotriester crosslinker. In a second step, this material is transformed to the phosphodiester, by heating it up to 60 °C in phosphate-buffered saline. Compared to earlier methods, there is no need for acids, bases, or oxidizing agents to achieve this final conversion to the phosphodiester. This method thus reduces the risk to damage or degrade any sensitive biomolecules that might be of interest to tissue engineers, such as various growth factors or other proteins. The phosphotriester crosslinker is readily synthesized out of common laboratory chemicals in multigram quantities with good yield and easy workup and purification.

@article{
 title = {A deeper understanding of the spontaneous derepression of the URA3 gene in MaV203 Saccharomyces cerevisiae and its implications for protein engineering and reverse two‐hybrid},
 type = {article},
 year = {2019},
 pages = {3437},
 websites = {https://onlinelibrary.wiley.com/doi/abs/10.1002/yea.3437},
 month = {8},
 day = {7},
 id = {59fd60cf-d8b3-3df4-9990-c0cd10365891},
 created = {2021-09-08T12:38:07.007Z},
 accessed = {2019-08-08},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:00.563Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Cortens, D. and Hansen, R. and Graulus, G.‐J. and Steen Redeker, E. and Adriaensens, P. and Guedens, W.},
 doi = {10.1002/yea.3437},
 journal = {Yeast}
}

@article{
 title = {Phosphodiester Hydrogels for Cell Scaffolding and Drug Release Applications},
 type = {article},
 year = {2019},
 keywords = {biomaterials,hemocompatibility,hydrogels,phosphodiesters},
 pages = {1900090},
 websites = {https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.201900090},
 month = {6},
 publisher = {John Wiley & Sons, Ltd},
 day = {5},
 id = {81ca35ad-3033-3014-99fd-c012488079af},
 created = {2021-09-08T12:38:07.039Z},
 accessed = {2019-06-12},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:04.546Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Dera, Rafael and Diliën, Hanne and Billen, Brecht and Gagliardi, Mick and Rahimi, Nastaran and Den Akker, Nynke M. S. and Molin, Daniel G. M. and Grandfils, Christian and Adriaensens, Peter and Guedens, Wanda and Cleij, Thomas J.},
 doi = {10.1002/mabi.201900090},
 journal = {Macromolecular Bioscience}
}

@article{
 title = {The Metabolic Landscape of Lung Cancer: New Insights in a Disturbed Glucose Metabolism},
 type = {article},
 year = {2019},
 volume = {9},
 websites = {https://www.frontiersin.org/article/10.3389/fonc.2019.01215/full},
 month = {11},
 day = {15},
 id = {d5402ad6-7dd9-3e3b-a5a1-be8bc157e2f5},
 created = {2021-09-08T12:38:07.070Z},
 accessed = {2019-12-05},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:54.790Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Vanhove, Karolien and Graulus, Geert-Jan and Mesotten, Liesbet and Thomeer, Michiel and Derveaux, Elien and Noben, Jean-Paul and Guedens, Wanda and Adriaensens, Peter},
 doi = {10.3389/fonc.2019.01215},
 journal = {Frontiers in Oncology}
}

@article{
 title = {A straightforward method for quantification of vinyl functionalized water soluble alginates via 13 C-NMR spectroscopy},
 type = {article},
 year = {2019},
 keywords = {Degree of substitution,Functionalized alginate,NMR spectroscopy},
 pages = {722-729},
 volume = {134},
 websites = {https://www.sciencedirect.com/science/article/pii/S0141813018355028?via%3Dihub},
 month = {8},
 publisher = {Elsevier},
 day = {1},
 id = {ddf565b2-1729-33ef-94c8-ccc72a6e67a5},
 created = {2021-09-08T12:38:07.203Z},
 accessed = {2019-06-12},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:12.243Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Alginates are fairly abundant in nature and possess many interesting properties, including their biocompatibility and ability to absorb large amounts of water. Hence, increasing interest in their derivatization has been observed and the determination of the number of newly introduced functionalities has become a key issue. For this purpose, literature generally reports on conventional 1 H‐NMR spectra, typically recorded at elevated temperatures and/or after hydrolysis of the alginate to circumvent line broadening effects resulting from the high viscosity. The present work reports on the modification of alginate with methacrylate functionalities and determination of the resulting degree of substitution (DS), i.e. the number of introduced methacrylate moieties relative to the initial amount of hydroxyl groups along the alginate backbone, via NMR spectroscopy. Freeze-drying and low power water presaturation were applied to improve the quality of the 1 H NMR spectra. Nevertheless, it remains a qualitative method, to be used only for mutual comparisons of samples. A new and accurate method for DS determination of methacrylated alginates, based on 13 C‐NMR spectroscopy, is proposed. Quantitative 13 C‐NMR spectra were recorded with reduced measuring times by addition of a paramagnetic relaxation agent. The proposed method will also be applicable for other water-soluble functionalized alginates and polysaccharides in general.},
 bibtype = {article},
 author = {Stubbe, B. and Graulus, G.-J. J. and Reekmans, G. and Courtin, T. and Martins, J.C. C. and Van Vlierberghe, S. and Dubruel, P. and Adriaensens, P.},
 doi = {10.1016/j.ijbiomac.2019.05.015},
 journal = {International Journal of Biological Macromolecules}
}

Alginates are fairly abundant in nature and possess many interesting properties, including their biocompatibility and ability to absorb large amounts of water. Hence, increasing interest in their derivatization has been observed and the determination of the number of newly introduced functionalities has become a key issue. For this purpose, literature generally reports on conventional 1 H‐NMR spectra, typically recorded at elevated temperatures and/or after hydrolysis of the alginate to circumvent line broadening effects resulting from the high viscosity. The present work reports on the modification of alginate with methacrylate functionalities and determination of the resulting degree of substitution (DS), i.e. the number of introduced methacrylate moieties relative to the initial amount of hydroxyl groups along the alginate backbone, via NMR spectroscopy. Freeze-drying and low power water presaturation were applied to improve the quality of the 1 H NMR spectra. Nevertheless, it remains a qualitative method, to be used only for mutual comparisons of samples. A new and accurate method for DS determination of methacrylated alginates, based on 13 C‐NMR spectroscopy, is proposed. Quantitative 13 C‐NMR spectra were recorded with reduced measuring times by addition of a paramagnetic relaxation agent. The proposed method will also be applicable for other water-soluble functionalized alginates and polysaccharides in general.

@inbook{
 type = {inbook},
 year = {2019},
 keywords = {Click chemistry,Intein,Nanobody,Protein functionalization},
 pages = {117-130},
 volume = {2033},
 publisher = {Humana Press Inc.},
 id = {4a577624-04a7-3721-813b-313e51205381},
 created = {2021-09-08T12:38:07.207Z},
 accessed = {2020-02-13},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:07.207Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {An expression strategy is presented in order to produce nanobodies modified with a clickable alkyne functionality at their C-terminus via the intein-mediated protein ligation (IPL) technique. The protocol focuses on the cytoplasmic expression and extraction of a nanobody–intein–chitin binding domain (CBD) fusion protein in E. coli SHuffle® T7 cells, in the commonly used Luria–Bertani (LB) medium. The combination of these factors results in a high yield and nearly complete alkynation of the nanobody at its C-terminus via IPL. The resulting alkynated nanobodies retain excellent binding capacity toward the nanobody targeted antigen. The presented protocol benefits from time- and cost-effectiveness and allows for a feasible upscaling of functionalized (here alkynated) nanobodies. The production of high quantities of site-specifically modified nanobodies paves the way to (1) novel biosurface applications that demand for homogeneously oriented nanobodies having their active site fully accessible for target (e.g., biomarker) binding, and (2) innovative applications such as localized drug delivery and image guided surgery by covalent “click” chemistry coupling of these alkynated nanobodies to a multitude of azide-containing counterparts as there are drug containing polymers and contrast labeling agents.},
 bibtype = {inbook},
 author = {Graulus, Geert Jan and Ta, Duy Tien and Tran, Huong and Hansen, Rebekka and Billen, Brecht and Royackers, Erik and Noben, Jean Paul and Devoogdt, Nick and Muyldermans, Serge and Guedens, Wanda and Adriaensens, Peter},
 doi = {10.1007/978-1-4939-9654-4_9},
 chapter = {Site-Selective Functionalization of Nanobodies Using Intein-Mediated Protein Ligation for Innovative Bioconjugation},
 title = {Methods in Molecular Biology}
}

An expression strategy is presented in order to produce nanobodies modified with a clickable alkyne functionality at their C-terminus via the intein-mediated protein ligation (IPL) technique. The protocol focuses on the cytoplasmic expression and extraction of a nanobody–intein–chitin binding domain (CBD) fusion protein in E. coli SHuffle® T7 cells, in the commonly used Luria–Bertani (LB) medium. The combination of these factors results in a high yield and nearly complete alkynation of the nanobody at its C-terminus via IPL. The resulting alkynated nanobodies retain excellent binding capacity toward the nanobody targeted antigen. The presented protocol benefits from time- and cost-effectiveness and allows for a feasible upscaling of functionalized (here alkynated) nanobodies. The production of high quantities of site-specifically modified nanobodies paves the way to (1) novel biosurface applications that demand for homogeneously oriented nanobodies having their active site fully accessible for target (e.g., biomarker) binding, and (2) innovative applications such as localized drug delivery and image guided surgery by covalent “click” chemistry coupling of these alkynated nanobodies to a multitude of azide-containing counterparts as there are drug containing polymers and contrast labeling agents.

@article{
 title = {Glutamine Addiction and Therapeutic Strategies in Lung Cancer},
 type = {article},
 year = {2019},
 keywords = {Glutamine,Glutaminolysis,Lung cancer,Metabolism,Pathways,Targeted treatment,glutamine,glutaminolysis,metabolism,pathways,targeted treatment},
 pages = {252},
 volume = {20},
 websites = {http://www.mdpi.com/1422-0067/20/2/252},
 month = {1},
 publisher = {Multidisciplinary Digital Publishing Institute},
 day = {10},
 id = {9a1dcf23-c9ed-37ad-ac9e-6b9fd18aa63f},
 created = {2021-09-08T12:38:07.223Z},
 accessed = {2019-01-14},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:13.064Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Lung cancer cells are well-documented to rewire their metabolism and energy production networks to support rapid survival and proliferation. This metabolic reorganization has been recognized as a hallmark of cancer. The increased uptake of glucose and the increased activity of the glycolytic pathway have been extensively described. However, over the past years, increasing evidence has shown that lung cancer cells also require glutamine to fulfill their metabolic needs. As a nitrogen source, glutamine contributes directly (or indirectly upon conversion to glutamate) to many anabolic processes in cancer, such as the biosynthesis of amino acids, nucleobases, and hexosamines. It plays also an important role in the redox homeostasis, and last but not least, upon conversion to α-ketoglutarate, glutamine is an energy and anaplerotic carbon source that replenishes tricarboxylic acid cycle intermediates. The latter is generally indicated as glutaminolysis. In this review, we explore the role of glutamine metabolism in lung cancer. Because lung cancer is the leading cause of cancer death with limited curative treatment options, we focus on the potential therapeutic approaches targeting the glutamine metabolism in cancer.},
 bibtype = {article},
 author = {Vanhove, Karolien and Derveaux, Elien and Graulus, Geert-Jan G.-J. and Mesotten, Liesbet and Thomeer, Michiel and Noben, J.-P. Jean-Paul and Guedens, Wanda and Adriaensens, Peter},
 doi = {10.3390/ijms20020252},
 journal = {International Journal of Molecular Sciences},
 number = {2}
}

Lung cancer cells are well-documented to rewire their metabolism and energy production networks to support rapid survival and proliferation. This metabolic reorganization has been recognized as a hallmark of cancer. The increased uptake of glucose and the increased activity of the glycolytic pathway have been extensively described. However, over the past years, increasing evidence has shown that lung cancer cells also require glutamine to fulfill their metabolic needs. As a nitrogen source, glutamine contributes directly (or indirectly upon conversion to glutamate) to many anabolic processes in cancer, such as the biosynthesis of amino acids, nucleobases, and hexosamines. It plays also an important role in the redox homeostasis, and last but not least, upon conversion to α-ketoglutarate, glutamine is an energy and anaplerotic carbon source that replenishes tricarboxylic acid cycle intermediates. The latter is generally indicated as glutaminolysis. In this review, we explore the role of glutamine metabolism in lung cancer. Because lung cancer is the leading cause of cancer death with limited curative treatment options, we focus on the potential therapeutic approaches targeting the glutamine metabolism in cancer.

@article{
 title = {The plasma glutamate concentration as a complementary tool to differentiate benign PET-positive lung lesions from lung cancer},
 type = {article},
 year = {2018},
 pages = {868},
 volume = {18},
 websites = {https://doi.org/10.1186/s12885-018-4755-1},
 month = {9},
 id = {5f74a48d-1250-3da4-a350-654d96db025c},
 created = {2021-09-08T12:38:06.717Z},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.717Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Vanhove2018},
 source_type = {article},
 private_publication = {false},
 abstract = {Pulmonary imaging often identifies suspicious abnormalities resulting in supplementary diagnostic procedures. This study aims to investigate whether the metabolic fingerprint of plasma allows to discriminate between patients with lung inflammation and patients with lung cancer.},
 bibtype = {article},
 author = {Vanhove, K and Giesen, P and Owokotomo, O E and Mesotten, L and Louis, E and Shkedy, Z and Thomeer, M and Adriaensens, P},
 doi = {10.1186/s12885-018-4755-1},
 journal = {BMC Cancer},
 number = {1}
}

Pulmonary imaging often identifies suspicious abnormalities resulting in supplementary diagnostic procedures. This study aims to investigate whether the metabolic fingerprint of plasma allows to discriminate between patients with lung inflammation and patients with lung cancer.

@article{
 title = {Identification of metabolic phenotypes in childhood obesity by 1 H NMR metabolomics of blood plasma},
 type = {article},
 year = {2018},
 pages = {4},
 websites = {www.future-science.com},
 id = {a61de7e5-a47e-3a3a-872c-366a33256aa2},
 created = {2021-09-08T12:38:07.166Z},
 accessed = {2019-01-07},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:53.785Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Aim: To identify the plasma metabolic profile associated with childhood obesity and its metabolic phenotypes. Materials & methods: The plasma metabolic profile of 65 obese and 37 normal-weight children was obtained using proton NMR spectroscopy. NMR spectra were rationally divided into 110 integration regions, which reflect relative metabolite concentrations, and were used as statistical variables. Results: Obese children show increased levels of lipids, N-acetyl glycoproteins, and lactate, and decreased levels of several amino acids, α-ketoglutarate, glucose, citrate, and cholinated phospholipids as compared with normal-weight children. Metabolically healthy children show lower levels of lipids and lactate, and higher levels of several amino acids and cholinated phospholipids, as compared with unhealthy children .Conclusion: This study reveals new valuable findings in the field of metabolomics and childhood obesity. Although validation should be performed, the proof of principle looks promising and justifies a deeper investigation of the diagnostic possibilities of proton NMR metabolomics in follow-up studies.},
 bibtype = {article},
 author = {Bervoets, Liene and Massa, Guy and Guedens, Wanda and Reekmans, Gunter and Noben, Jean-Paul and Adriaensens, Peter},
 doi = {10.4155/fsoa-2017-0146},
 journal = {Future Sci. OA},
 number = {06}
}

Aim: To identify the plasma metabolic profile associated with childhood obesity and its metabolic phenotypes. Materials & methods: The plasma metabolic profile of 65 obese and 37 normal-weight children was obtained using proton NMR spectroscopy. NMR spectra were rationally divided into 110 integration regions, which reflect relative metabolite concentrations, and were used as statistical variables. Results: Obese children show increased levels of lipids, N-acetyl glycoproteins, and lactate, and decreased levels of several amino acids, α-ketoglutarate, glucose, citrate, and cholinated phospholipids as compared with normal-weight children. Metabolically healthy children show lower levels of lipids and lactate, and higher levels of several amino acids and cholinated phospholipids, as compared with unhealthy children .Conclusion: This study reveals new valuable findings in the field of metabolomics and childhood obesity. Although validation should be performed, the proof of principle looks promising and justifies a deeper investigation of the diagnostic possibilities of proton NMR metabolomics in follow-up studies.

@article{
 title = {High Electronic Conductance through Double-Helix DNA Molecules with Fullerene Anchoring Groups},
 type = {article},
 year = {2017},
 pages = {1182-1188},
 volume = {121},
 websites = {http://pubs.acs.org/doi/10.1021/acs.jpca.7b00348},
 month = {2},
 publisher = {American Chemical Society},
 day = {16},
 id = {e22d33e4-b642-3fc6-b4c7-f1a4ebbd1027},
 created = {2021-09-08T12:38:06.055Z},
 accessed = {2018-04-05},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.055Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Determining the mechanism of charge transport through native DNA remains a challenge as different factors such as measuring conditions, molecule conformations, and choice of technique can significantly affect the final results. In this contribution, we have used a new approach to measure current flowing through isolated double-stranded DNA molecules, using fullerene groups to anchor the DNA to a gold substrate. Measurements were performed at room temperature in an inert environment using a conductive AFM technique. It is shown that the π-stacked B-DNA structure is conserved on depositing the DNA. As a result, currents in the nanoampere range were obtained for voltages ranging between ±1 V. These experimental results are supported by a theoretical model that suggests that a multistep hopping mechanism between delocalized domains is responsible for the long-range current flow through this specific type of DNA.},
 bibtype = {article},
 author = {Jiménez-Monroy, Kathia L. and Renaud, Nicolas and Drijkoningen, Jeroen and Cortens, David and Schouteden, Koen and Van Haesendonck, Christian and Guedens, Wanda J. and Manca, Jean V. and Siebbeles, Laurens D.A. and Grozema, Ferdinand C. and Wagner, Patrick H.},
 doi = {10.1021/acs.jpca.7b00348},
 journal = {Journal of Physical Chemistry A},
 number = {6}
}

Determining the mechanism of charge transport through native DNA remains a challenge as different factors such as measuring conditions, molecule conformations, and choice of technique can significantly affect the final results. In this contribution, we have used a new approach to measure current flowing through isolated double-stranded DNA molecules, using fullerene groups to anchor the DNA to a gold substrate. Measurements were performed at room temperature in an inert environment using a conductive AFM technique. It is shown that the π-stacked B-DNA structure is conserved on depositing the DNA. As a result, currents in the nanoampere range were obtained for voltages ranging between ±1 V. These experimental results are supported by a theoretical model that suggests that a multistep hopping mechanism between delocalized domains is responsible for the long-range current flow through this specific type of DNA.

@article{
 title = {Identification and Formulation of Polymers: A Challenging Interdisciplinary Undergraduate Chemistry Lab Assignment},
 type = {article},
 year = {2017},
 keywords = {Physical Properties,Polymer Chemistry,Polymerization,Problem Solving/Decision Making,Qualitative Analysis,Second-Year Undergraduate,Synthesis,Testing/Assessment},
 pages = {1756-1760},
 volume = {94},
 websites = {http://pubs.acs.org/doi/10.1021/acs.jchemed.7b00284},
 month = {11},
 publisher = {American Chemical Society and Division of Chemical Education, Inc.},
 day = {14},
 id = {8cbe4cf9-2768-33ba-bfc0-8af401a790eb},
 created = {2021-09-08T12:38:06.221Z},
 accessed = {2018-04-06},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.221Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Prior to the recycling process, raising awareness of plastic waste impact, e.g., polluting oceans worldwide, is undoubtedly a first attempt to tackle this pandemic environmental issue. With this in mind, the presented practical session is an effort to entice an interdisciplinary audience of science undergraduates toward a sustainable future. The associated assignment focuses on a collaboration of undergraduate chemistry students and engineering undergraduates with a minor program in chemistry. Acting on an adequate uncluttered mind map of practical guidelines, the students acquire and exchange multiple “good laboratory practice” skills. By this, engineering undergraduates get acquainted with chemicals, e.g., polymers, while future chemists get an impression of how economics is concerned to maintain a balance between economy and ecology, i.e., a circular economy. In a grand finale, the students present their interdisciplinary communication skills via a poster exhibition: “chemistry meets economics”. Moreov...},
 bibtype = {article},
 author = {Guedens, Wanda J. and Reynders, Monique},
 doi = {10.1021/acs.jchemed.7b00284},
 journal = {Journal of Chemical Education},
 number = {11}
}

Prior to the recycling process, raising awareness of plastic waste impact, e.g., polluting oceans worldwide, is undoubtedly a first attempt to tackle this pandemic environmental issue. With this in mind, the presented practical session is an effort to entice an interdisciplinary audience of science undergraduates toward a sustainable future. The associated assignment focuses on a collaboration of undergraduate chemistry students and engineering undergraduates with a minor program in chemistry. Acting on an adequate uncluttered mind map of practical guidelines, the students acquire and exchange multiple “good laboratory practice” skills. By this, engineering undergraduates get acquainted with chemicals, e.g., polymers, while future chemists get an impression of how economics is concerned to maintain a balance between economy and ecology, i.e., a circular economy. In a grand finale, the students present their interdisciplinary communication skills via a poster exhibition: “chemistry meets economics”. Moreov...

@article{
 title = {Cytoplasmic versus periplasmic expression of site-specifically and bioorthogonally functionalized nanobodies using expressed protein ligation},
 type = {article},
 year = {2017},
 keywords = {Click chemistry,CuAAC,Expressed protein ligation,Nanobodies,Periplasmic expression and extraction},
 pages = {25-34},
 volume = {133},
 month = {5},
 publisher = {Academic Press},
 day = {1},
 id = {eb181d0d-1c2e-3890-89bd-6a8f866c716e},
 created = {2021-09-08T12:38:06.967Z},
 accessed = {2017-12-18},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:07.592Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Site-specific functionalization of nanobodies after introducing bioorthogonal groups offers the possibility to biofunctionalize surfaces with a uniformly oriented layer of nanobodies. In this paper, expressed protein ligation (EPL) was used for site-specific alkynation of the model nanobody NbBcII10. In contrast to EPL constructs, which are typically expressed in the cytoplasm, nanobodies are expressed in the periplasm where its oxidizing environment ensures a correct folding and disulfide bond formation. Different pathways were explored to express the EPL constructs in the periplasm but simultaneously, the effect of cytoplasmic expression on the functionality of NbBcII10 was also evaluated. By using Escherichia coli SHuffle®T7 cells, it was demonstrated that expression of the EPL complex in the cytoplasm was readily established and that site-specifically mono-alkynated nanobodies can be produced with the same binding properties as the non-modified NbBcII10 expressed in the periplasm. In conclusion, this paper shows that periplasmic expression of the EPL complex is quite challenging, but cytoplasmic expression has proven to be a valuable alternative.},
 bibtype = {article},
 author = {Billen, Brecht and Vincke, Cécile and Hansen, Rebekka and Devoogdt, Nick and Muyldermans, Serge and Adriaensens, Peter and Guedens, Wanda},
 doi = {10.1016/J.PEP.2017.02.009},
 journal = {Protein Expression and Purification}
}

Site-specific functionalization of nanobodies after introducing bioorthogonal groups offers the possibility to biofunctionalize surfaces with a uniformly oriented layer of nanobodies. In this paper, expressed protein ligation (EPL) was used for site-specific alkynation of the model nanobody NbBcII10. In contrast to EPL constructs, which are typically expressed in the cytoplasm, nanobodies are expressed in the periplasm where its oxidizing environment ensures a correct folding and disulfide bond formation. Different pathways were explored to express the EPL constructs in the periplasm but simultaneously, the effect of cytoplasmic expression on the functionality of NbBcII10 was also evaluated. By using Escherichia coli SHuffle®T7 cells, it was demonstrated that expression of the EPL complex in the cytoplasm was readily established and that site-specifically mono-alkynated nanobodies can be produced with the same binding properties as the non-modified NbBcII10 expressed in the periplasm. In conclusion, this paper shows that periplasmic expression of the EPL complex is quite challenging, but cytoplasmic expression has proven to be a valuable alternative.

@article{
 title = {In situ monitoring and optimization of CuAAC-mediated protein functionalization of biosurfaces},
 type = {article},
 year = {2017},
 keywords = {Bio-orthogonal chemistry,CuAAC ‘click’ chemistry,Ellipsometry,Maltose Binding Protein,Protein surface functionalization,Staphylococcus aureus Protein A},
 pages = {992-1000},
 volume = {238},
 websites = {http://www.sciencedirect.com/science/article/pii/S0925400516311066?via%3Dihub,https://www.sciencedirect.com/science/article/pii/S0925400516311066?via%3Dihub},
 month = {1},
 publisher = {Elsevier},
 day = {1},
 id = {47265bbb-595c-3da8-8775-a5a543cd4d6a},
 created = {2021-09-08T12:38:06.992Z},
 accessed = {2017-01-18},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:10.035Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Vranken2017},
 notes = {<b>From Duplicate 1 (<i>In situ monitoring and optimization of CuAAC-mediated protein functionalization of biosurfaces</i> - Vranken, Tom; Steen Redeker, Erik; Miszta, Adam; Billen, Brecht; Hermens, Wim; de Laat, Bas; Adriaensens, Peter; Guedens, Wanda; Cleij, Thomas J.)<br/></b><br/>NULL<br/><br/><b>From Duplicate 3 (<i>In situ monitoring and optimization of CuAAC-mediated protein functionalization of biosurfaces</i> - Vranken, Tom; Steen Redeker, Erik; Miszta, Adam; Billen, Brecht; Hermens, Wim; de Laat, Bas; Adriaensens, Peter; Guedens, Wanda; Cleij, Thomas J.)<br/></b><br/><b>From Duplicate 3 (<i>In situ monitoring and optimization of CuAAC-mediated protein functionalization of biosurfaces</i> - Vranken, Tom; Steen Redeker, Erik; Miszta, Adam; Billen, Brecht; Hermens, Wim; de Laat, Bas; Adriaensens, Peter; Guedens, Wanda; Cleij, Thomas J.)<br/></b><br/>NULL},
 private_publication = {false},
 abstract = {With the current trend to miniaturize bioactive surfaces to micro- or nanometer scale, the strategy of immobilization becomes more important. Therefore, there is a growing need for protein immobilization techniques that create both stable and homogeneously covered surfaces in a reproducible way. One of the most promising methods to achieve this is the combination of biological receptors with ‘click’ chemistry, like the Copper catalyzed Alkyne Azide Cycloaddition (CuAAC). This work presents a full optimization of all aspects of the ‘click’ chemistry reaction between proteins and surfaces in order to create covalently and homogeneously covered biosurfaces. The coupling procedure is monitored by in situ ellipsometry, a unique characterization technique that offers the opportunity to quantify minute amounts of surface coupled protein mass in real-time. The optimization involves the azidification of a solid silicon support, the alkynation of two proteins, Staphylococcus aureus Protein A (SpA) and Maltose Binding Protein (MBP), as well as the development of a highly reproducible CuAAC ‘click’ coupling protocol. Using the here optimized protocol, active and reproducible biolayers can be created rapidly. The proposed surface biofunctionalization method combined with ellipsometry forms a unique and promising platform towards the development of highly sensitive, accurate biosensors.},
 bibtype = {article},
 author = {Vranken, Tom and Steen Redeker, Erik and Miszta, Adam and Billen, Brecht and Hermens, Wim and de Laat, Bas and Adriaensens, Peter and Guedens, Wanda and Cleij, Thomas J.},
 doi = {10.1016/j.snb.2016.07.071},
 journal = {Sensors and Actuators B: Chemical}
}

With the current trend to miniaturize bioactive surfaces to micro- or nanometer scale, the strategy of immobilization becomes more important. Therefore, there is a growing need for protein immobilization techniques that create both stable and homogeneously covered surfaces in a reproducible way. One of the most promising methods to achieve this is the combination of biological receptors with ‘click’ chemistry, like the Copper catalyzed Alkyne Azide Cycloaddition (CuAAC). This work presents a full optimization of all aspects of the ‘click’ chemistry reaction between proteins and surfaces in order to create covalently and homogeneously covered biosurfaces. The coupling procedure is monitored by in situ ellipsometry, a unique characterization technique that offers the opportunity to quantify minute amounts of surface coupled protein mass in real-time. The optimization involves the azidification of a solid silicon support, the alkynation of two proteins, Staphylococcus aureus Protein A (SpA) and Maltose Binding Protein (MBP), as well as the development of a highly reproducible CuAAC ‘click’ coupling protocol. Using the here optimized protocol, active and reproducible biolayers can be created rapidly. The proposed surface biofunctionalization method combined with ellipsometry forms a unique and promising platform towards the development of highly sensitive, accurate biosensors.

@article{
 title = {Metabolic profiling of type 1 diabetes mellitus in children and adolescents: a case–control study},
 type = {article},
 year = {2017},
 keywords = {Diabetes,Endocrinology,Metabolic Diseases},
 pages = {48},
 volume = {9},
 websites = {http://dmsjournal.biomedcentral.com/articles/10.1186/s13098-017-0246-9},
 month = {12},
 publisher = {BioMed Central},
 day = {26},
 id = {9ccce5c4-2cf9-3c26-ae96-b932c0bedab6},
 created = {2021-09-08T12:38:07.025Z},
 accessed = {2018-04-05},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:02.756Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Type 1 diabetes mellitus (T1DM) is one of the most common pediatric diseases and its incidence is rising in many countries. Recently, it has been shown that metabolites other than glucose play an important role in insulin deficiency and the development of diabetes. The aim of our study was to look for discriminating variation in the concentrations of small‑molecule metabolites in the plasma of T1DM children as compared to non‑diabetic matched controls using proton nuclear magnetic resonance (1},
 bibtype = {article},
 author = {Bervoets, Liene and Massa, Guy and Guedens, Wanda and Louis, Evelyne and Noben, Jean-Paul and Adriaensens, Peter},
 doi = {10.1186/s13098-017-0246-9},
 journal = {Diabetology & Metabolic Syndrome},
 number = {1}
}

Background: Type 1 diabetes mellitus (T1DM) is one of the most common pediatric diseases and its incidence is rising in many countries. Recently, it has been shown that metabolites other than glucose play an important role in insulin deficiency and the development of diabetes. The aim of our study was to look for discriminating variation in the concentrations of small‑molecule metabolites in the plasma of T1DM children as compared to non‑diabetic matched controls using proton nuclear magnetic resonance (1

@article{
 title = {Optical-quality controllable wet-chemical doping of graphene through a uniform, transparent and low-roughness F4-TCNQ/MEK layer},
 type = {article},
 year = {2016},
 pages = {104491-104501},
 volume = {6},
 websites = {http://dx.doi.org/10.1039/C6RA24057G},
 publisher = {The Royal Society of Chemistry},
 id = {58c8d8b1-67e2-3901-8409-113df89c2321},
 created = {2021-09-08T12:38:06.834Z},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.834Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Misseeuw2016},
 source_type = {JOUR},
 private_publication = {false},
 abstract = {Controllable chemical doping of graphene has already proven very useful for electronic applications, but when turning to optical and photonic applications, the additional requirement of having both a high transparency and a low surface roughness has, to our knowledge, not yet been fulfilled by any chemical dopant system reported so far. In this work, a new method that meets for the first time this optical-quality requirement while also providing efficient, controllable doping is presented. The method relies on F4-TCNQ dissolved in methyl ethyl ketone (MEK) yielding a uniform deposition after spin coating because of an extraordinary charge transfer interaction between the F4-TCNQ and MEK molecules. The formed F4-TCNQ/MEK layer exhibits a very high surface quality and optical transparency over the visible-infrared wavelength range between 550 and 1900 nm. By varying the dopant concentration of F4-TCNQ from 2.5 to 40 mg ml-1 MEK, the doping effect can be controlled between [capital Delta]n = +5.73 [times] 1012 cm-2 and +1.09 [times] 1013 cm-2 for initially strongly p-type hydrogen-intercalated graphene grown on 6H-silicon-carbide substrates, and between [capital Delta]n = +5.56 [times] 1012 cm-2 and +1.04 [times] 1013 cm-2 for initially weakly p-type graphene transferred on silicon samples. This is the first time that truly optical-quality chemical doping of graphene is demonstrated, and the obtained doping values exceed those reported before for F4-TCNQ-based graphene doping by as much as 50%.},
 bibtype = {article},
 author = {Misseeuw, Lara and Krajewska, Aleksandra and Pasternak, Iwona and Ciuk, Tymoteusz and Strupinski, Wlodek and Reekmans, Gunter and Adriaensens, Peter and Geldof, Davy and Blockhuys, Frank and Van Vlierberghe, Sandra and Thienpont, Hugo and Dubruel, Peter and Vermeulen, Nathalie},
 doi = {10.1039/C6RA24057G},
 journal = {RSC Advances},
 number = {106}
}

Controllable chemical doping of graphene has already proven very useful for electronic applications, but when turning to optical and photonic applications, the additional requirement of having both a high transparency and a low surface roughness has, to our knowledge, not yet been fulfilled by any chemical dopant system reported so far. In this work, a new method that meets for the first time this optical-quality requirement while also providing efficient, controllable doping is presented. The method relies on F4-TCNQ dissolved in methyl ethyl ketone (MEK) yielding a uniform deposition after spin coating because of an extraordinary charge transfer interaction between the F4-TCNQ and MEK molecules. The formed F4-TCNQ/MEK layer exhibits a very high surface quality and optical transparency over the visible-infrared wavelength range between 550 and 1900 nm. By varying the dopant concentration of F4-TCNQ from 2.5 to 40 mg ml-1 MEK, the doping effect can be controlled between [capital Delta]n = +5.73 [times] 1012 cm-2 and +1.09 [times] 1013 cm-2 for initially strongly p-type hydrogen-intercalated graphene grown on 6H-silicon-carbide substrates, and between [capital Delta]n = +5.56 [times] 1012 cm-2 and +1.04 [times] 1013 cm-2 for initially weakly p-type graphene transferred on silicon samples. This is the first time that truly optical-quality chemical doping of graphene is demonstrated, and the obtained doping values exceed those reported before for F4-TCNQ-based graphene doping by as much as 50%.

@article{
 title = {Detection of lung cancer through metabolic changes measured in blood plasma},
 type = {article},
 year = {2016},
 keywords = {1H-NMR spectroscopy,Blood plasma biomarker,Lung cancer,Metabolic phenotype,Risk model},
 pages = {516-523},
 volume = {11},
 websites = {http://linkinghub.elsevier.com/retrieve/pii/S1556086416003348},
 month = {4},
 publisher = {Elsevier},
 day = {1},
 id = {64bf959c-b03d-335c-a480-5f65cff2a394},
 created = {2021-09-08T12:38:06.953Z},
 accessed = {2018-04-11},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:39:06.396Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: Low-dose computed tomography, the currently used tool for lung cancer screening, is characterized by a high rate of false-positive results. Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. Therefore, this study aims to evaluate whether the metabolic phenotype of blood plasma allows detection of lung cancer. Methods: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 233 patients with lung cancer and 226 controls. The validity of the model was examined by classifying an independent cohort of 98 patients with lung cancer and 89 controls. Results: The model makes it possible to correctly classify 78%of patients with lung cancer and92%of controls, with an area under the curve of 0.88. Important moreover is the fact that the model is convincing, which is demonstrated by validation in the independent cohort with a sensitivity of 71%, a specificity of 81%, and an area under the curve of 0.84. Patients with lung cancer have increased glucose and decreased lactate and phospholipid levels. The limited number of patients in the subgroups and their heterogeneous nature do not (yet) enable differentiation between histological subtypes and tumor stages. Conclusions: Metabolic phenotyping of plasma allows detection of lung cancer, even in an early stage. Increased glucose and decreased lactate levels are pointing to an increased gluconeogenesis and are in accordance with recently published findings. Furthermore, decreased phospholipid levels confirm the enhanced membrane synthesis.},
 bibtype = {article},
 author = {Louis, Evelyne and Adriaensens, Peter and Guedens, Wanda and Bigirumurame, Theophile and Baeten, Kurt and Vanhove, Karolien and Vandeurzen, Kurt and Darquennes, Karen and Vansteenkiste, Johan and Dooms, Christophe and Shkedy, Ziv and Mesotten, Liesbet and Thomeer, Michiel},
 doi = {10.1016/j.jtho.2016.01.011},
 journal = {Journal of Thoracic Oncology},
 number = {4}
}

Introduction: Low-dose computed tomography, the currently used tool for lung cancer screening, is characterized by a high rate of false-positive results. Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. Therefore, this study aims to evaluate whether the metabolic phenotype of blood plasma allows detection of lung cancer. Methods: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 233 patients with lung cancer and 226 controls. The validity of the model was examined by classifying an independent cohort of 98 patients with lung cancer and 89 controls. Results: The model makes it possible to correctly classify 78%of patients with lung cancer and92%of controls, with an area under the curve of 0.88. Important moreover is the fact that the model is convincing, which is demonstrated by validation in the independent cohort with a sensitivity of 71%, a specificity of 81%, and an area under the curve of 0.84. Patients with lung cancer have increased glucose and decreased lactate and phospholipid levels. The limited number of patients in the subgroups and their heterogeneous nature do not (yet) enable differentiation between histological subtypes and tumor stages. Conclusions: Metabolic phenotyping of plasma allows detection of lung cancer, even in an early stage. Increased glucose and decreased lactate levels are pointing to an increased gluconeogenesis and are in accordance with recently published findings. Furthermore, decreased phospholipid levels confirm the enhanced membrane synthesis.

@article{
 title = {Metabolic phenotyping of human blood plasma: A powerful tool to discriminate between cancer types?},
 type = {article},
 year = {2016},
 keywords = {1H-NMR spectroscopy,Breast cancer,Lung cancer,Metabolic phenotype,Plasma},
 pages = {178-184},
 volume = {27},
 websites = {https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdv499},
 month = {1},
 publisher = {Oxford University Press},
 day = {1},
 id = {97afae9e-ef4f-37c1-b6e4-5317f6a204b7},
 created = {2021-09-08T12:38:07.095Z},
 accessed = {2018-04-05},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:57.806Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND: Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. However, up to now it is not clear whether different cancer types are characterized by a specific metabolite profile. Therefore, this study aims to evaluate whether the plasma metabolic phenotype allows to discriminate between lung and breast cancer. PATIENTS AND METHODS: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 80 female breast cancer patients and 54 female lung cancer patients, all with an adenocarcinoma. The validity of the model was examined by permutation testing and by classifying an independent validation cohort of 60 female breast cancer patients and 81 male lung cancer patients, all with an adenocarcinoma. RESULTS: The model allows to classify 99% of the breast cancer patients and 93% of the lung cancer patients correctly with an area under the curve (AUC) of 0.96 and can be validated in the independent cohort with a sensitivity of 89%, a specificity of 82% and an AUC of 0.94. Decreased levels of sphingomyelin and phosphatidylcholine (phospholipids with choline head group) and phospholipids with short, unsaturated fatty acid chains next to increased levels of phospholipids with long, saturated fatty acid chains seem to indicate that cell membranes of lung tumors are more rigid and less sensitive to lipid peroxidation. The other discriminating metabolites are pointing to a more pronounced response of the body to the Warburg effect for lung cancer. CONCLUSION: Metabolic phenotyping of plasma allows to discriminate between lung and breast cancer, indicating that the metabolite profile reflects more than a general cancer marker. CLINICAL TRIAL REGISTRATION NUMBER: NCT02362776.},
 bibtype = {article},
 author = {Louis, E. and Adriaensens, P. and Guedens, W. and Vanhove, K. and Vandeurzen, K. and Darquennes, K. and Vansteenkiste, J. and Dooms, C. and de Jonge, E. and Thomeer, M. and Mesotten, L.},
 doi = {10.1093/annonc/mdv499},
 journal = {Annals of Oncology},
 number = {1}
}

BACKGROUND: Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. However, up to now it is not clear whether different cancer types are characterized by a specific metabolite profile. Therefore, this study aims to evaluate whether the plasma metabolic phenotype allows to discriminate between lung and breast cancer. PATIENTS AND METHODS: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 80 female breast cancer patients and 54 female lung cancer patients, all with an adenocarcinoma. The validity of the model was examined by permutation testing and by classifying an independent validation cohort of 60 female breast cancer patients and 81 male lung cancer patients, all with an adenocarcinoma. RESULTS: The model allows to classify 99% of the breast cancer patients and 93% of the lung cancer patients correctly with an area under the curve (AUC) of 0.96 and can be validated in the independent cohort with a sensitivity of 89%, a specificity of 82% and an AUC of 0.94. Decreased levels of sphingomyelin and phosphatidylcholine (phospholipids with choline head group) and phospholipids with short, unsaturated fatty acid chains next to increased levels of phospholipids with long, saturated fatty acid chains seem to indicate that cell membranes of lung tumors are more rigid and less sensitive to lipid peroxidation. The other discriminating metabolites are pointing to a more pronounced response of the body to the Warburg effect for lung cancer. CONCLUSION: Metabolic phenotyping of plasma allows to discriminate between lung and breast cancer, indicating that the metabolite profile reflects more than a general cancer marker. CLINICAL TRIAL REGISTRATION NUMBER: NCT02362776.

@article{
 title = {Enhanced biosensor platforms for detecting the atherosclerotic biomarker VCAM1 based on bioconjugation with uniformly oriented VCAM1-targeting nanobodies},
 type = {article},
 year = {2016},
 keywords = {Biosensor,CuAAC,Expressed protein ligation,Uniformly oriented bioconjugation,VCAM1-targeting nanobody},
 pages = {1-17},
 volume = {6},
 month = {7},
 publisher = {Multidisciplinary Digital Publishing Institute},
 day = {5},
 id = {f45c7ec8-3e3d-3cb6-815a-08b553753989},
 created = {2021-09-08T12:38:07.098Z},
 accessed = {2017-12-18},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:57.292Z},
 read = {true},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids) usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1), an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL). Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) “click” chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR), respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets—a must for the development of advanced miniaturized, multi-biomarker biosensor platforms.},
 bibtype = {article},
 author = {Ta, Duy Tien and Guedens, Wanda and Vranken, Tom and Vanschoenbeek, Katrijn and Redeker, Erik Steen and Michiels, Luc and Adriaensens, Peter},
 doi = {10.3390/bios6030034},
 journal = {Biosensors},
 number = {34}
}

Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids) usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1), an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL). Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) “click” chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR), respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets—a must for the development of advanced miniaturized, multi-biomarker biosensor platforms.

@article{
 title = {Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers},
 type = {article},
 year = {2016},
 keywords = {Holger Patzke,John C van Swieten,Lieke H H Meeter,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC5040889,PubMed Abstract,doi:10.1159/000447738,pmid:27703466},
 pages = {330-340},
 volume = {6},
 websites = {https://pubmed.ncbi.nlm.nih.gov/27703466/},
 publisher = {Dement Geriatr Cogn Dis Extra},
 id = {4a5efd41-1b08-3c19-b90b-dd3e5dd69908},
 created = {2022-01-04T08:11:57.416Z},
 accessed = {2022-01-04},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2022-01-04T08:12:00.795Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Pathogenic mutations in the granulin gene (GRN) are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. Methods: Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls. Results: Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. Conclusions: Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.},
 bibtype = {article},
 author = {Meeter, Lieke H.H. and Patzke, Holger and Loewen, Gordon and Dopper, Elise G.P. and Pijnenburg, Yolande A.L. and Van Minkelen, Rick and Van Swieten, John C.},
 doi = {10.1159/000447738},
 journal = {Dementia and geriatric cognitive disorders extra},
 number = {2}
}

Background: Pathogenic mutations in the granulin gene (GRN) are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. Methods: Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls. Results: Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. Conclusions: Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.

@article{
 title = {Influence of preanalytical sampling conditions on the 1H NMR metabolic profile of human blood plasma and introduction of the Standard PREanalytical Code used in biobanking},
 type = {article},
 year = {2015},
 pages = {1197-1207},
 volume = {11},
 websites = {http://link.springer.com/10.1007/s11306-015-0774-y},
 month = {10},
 publisher = {Springer US},
 day = {17},
 id = {b756cb50-41c1-37ac-b297-6e0ec2db5374},
 created = {2021-09-08T12:38:06.596Z},
 accessed = {2018-04-05},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:36.905Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Bervoets, Liene and Louis, Evelyne and Reekmans, Gunter and Mesotten, Liesbet and Thomeer, Michiel and Adriaensens, Peter and Linsen, Loes},
 doi = {10.1007/s11306-015-0774-y},
 journal = {Metabolomics},
 number = {5}
}

@article{
 title = {An efficient protocol towards site-specifically clickable nanobodies in high yield: Cytoplasmic expression in Escherichia coli combined with intein-mediated protein ligation},
 type = {article},
 year = {2015},
 keywords = {CuAAC,VCAM1-targeting nanobody,bioorthogonal chemistry,cytoplasmic expression,intein-mediated protein ligation},
 pages = {351-363},
 volume = {28},
 month = {10},
 publisher = {Oxford University Press},
 day = {1},
 id = {8afa9f3c-17e1-360d-afcb-1bf049997af8},
 created = {2021-09-08T12:38:07.127Z},
 accessed = {2017-11-17},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:59.805Z},
 read = {true},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {In this study, several expression strategies were investigated in order to develop a generic, highly productive and efficient protocol to produce nanobodies modified with a clickable alkyne function at their C-terminus via the intein-mediated protein ligation (IPL) technique. Hereto, the nanobody targeting the vascular cell adhesion molecule 1 (NbVCAM1) was used as a workhorse. The highlights of the protocol can be ascribed to a cytoplasmic expression of the nanobody–intein–chitin-binding domain fusion protein in the Escherichia coli SHuffle® T7 cells with a C-terminal extension, i.e. LEY, EFLEY or His6 spacer peptide, in the commonly used Luria-Bertani medium. The combination of these factors led to a high yield (up to 22 mg/l of culture) and nearly complete alkynation efficiency of the C-terminally modified nanobody via IPL. This yield can even be improved to ∼45 mg/l in the EnPresso® growth system but this method is more expensive and time-consuming. The resulting alkynated nanobodies retained excellent binding capacity towards the recombinant human VCAM1. The presented protocol benefits from time- and cost-effectiveness, which allows a feasible production up-scaling of generic alkynated nanobodies. The production of high quantities of site-specifically modified nanobodies paves the way to new biosurface applications that demand for a homogeneously oriented nanobody coupling. Prospectively, the alkynated nanobodies can be covalently coupled to a multitude of azide-containing counterparts, e.g. contrast labeling agents, particles or surfaces for numerous innovative applications.},
 bibtype = {article},
 author = {Ta, Duy Tien and Steen Redeker, Erik and Billen, Brecht and Reekmans, Gunter and Sikulu, Josephine and Noben, Jean-Paul Paul and Guedens, Wanda and Adriaensens, Peter},
 doi = {10.1093/protein/gzv032},
 journal = {Protein Engineering, Design and Selection},
 number = {10}
}

In this study, several expression strategies were investigated in order to develop a generic, highly productive and efficient protocol to produce nanobodies modified with a clickable alkyne function at their C-terminus via the intein-mediated protein ligation (IPL) technique. Hereto, the nanobody targeting the vascular cell adhesion molecule 1 (NbVCAM1) was used as a workhorse. The highlights of the protocol can be ascribed to a cytoplasmic expression of the nanobody–intein–chitin-binding domain fusion protein in the Escherichia coli SHuffle® T7 cells with a C-terminal extension, i.e. LEY, EFLEY or His6 spacer peptide, in the commonly used Luria-Bertani medium. The combination of these factors led to a high yield (up to 22 mg/l of culture) and nearly complete alkynation efficiency of the C-terminally modified nanobody via IPL. This yield can even be improved to ∼45 mg/l in the EnPresso® growth system but this method is more expensive and time-consuming. The resulting alkynated nanobodies retained excellent binding capacity towards the recombinant human VCAM1. The presented protocol benefits from time- and cost-effectiveness, which allows a feasible production up-scaling of generic alkynated nanobodies. The production of high quantities of site-specifically modified nanobodies paves the way to new biosurface applications that demand for a homogeneously oriented nanobody coupling. Prospectively, the alkynated nanobodies can be covalently coupled to a multitude of azide-containing counterparts, e.g. contrast labeling agents, particles or surfaces for numerous innovative applications.

@article{
 title = {ZnO-Based Sunscreen: The Perfect Example To Introduce Nanoparticles in an Undergraduate or High School Chemistry Lab},
 type = {article},
 year = {2014},
 keywords = {Aqueous Solution Chemistry,Colloids,First-Year Undergraduate/General,Hands-On Learning/Manipulatives,High School/Introductory Chemistry,Inorganic Chemistry,Laboratory Instruction,Micelles,Nanotechnology,Precipitation/Solubility},
 pages = {259-263},
 volume = {91},
 websites = {http://pubs.acs.org/doi/10.1021/ed300851a},
 month = {2},
 publisher = {American Chemical Society and Division of Chemical Education, Inc.},
 day = {11},
 id = {09cc948c-c75b-3085-a6e7-34690394207a},
 created = {2021-09-08T12:38:06.225Z},
 accessed = {2018-04-05},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.225Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The experiment described in this article is designed for undergraduates as well as for high school students to help them understand nanoscience in a basic way. The attractive subject of a sunscreen is used to illustrate the properties of nanoparticles. The students prepare particles of Zn(OH)2 by the same reaction either in a microemulsion, a microemulsion contaminated with acetone, or in an aqueous solution. Hereby it is shown that Zn(OH)2 has different properties depending on its particle size. Furthermore, the students discover that, due to their higher surface-to-volume ratio, a nanopowder of ZnO dispersed in glycerin absorbs more UV light than the same mass of a micropowder ZnO dispersed in glycerin. Finally, a sunscreen based on a homemade hand cream containing ZnO particles is formulated, and its UV absorbing ability is demonstrated by an uncomplicated procedure. By incorporating more detailed characterization techniques and a more in-depth explanation, these laboratory experiments are also instruc...},
 bibtype = {article},
 author = {Guedens, Wanda J. and Reynders, Monique and Van den Rul, Heidi and Elen, Ken and Hardy, An and Van Bael, Marlies K.},
 doi = {10.1021/ed300851a},
 journal = {Journal of Chemical Education},
 number = {2}
}

The experiment described in this article is designed for undergraduates as well as for high school students to help them understand nanoscience in a basic way. The attractive subject of a sunscreen is used to illustrate the properties of nanoparticles. The students prepare particles of Zn(OH)2 by the same reaction either in a microemulsion, a microemulsion contaminated with acetone, or in an aqueous solution. Hereby it is shown that Zn(OH)2 has different properties depending on its particle size. Furthermore, the students discover that, due to their higher surface-to-volume ratio, a nanopowder of ZnO dispersed in glycerin absorbs more UV light than the same mass of a micropowder ZnO dispersed in glycerin. Finally, a sunscreen based on a homemade hand cream containing ZnO particles is formulated, and its UV absorbing ability is demonstrated by an uncomplicated procedure. By incorporating more detailed characterization techniques and a more in-depth explanation, these laboratory experiments are also instruc...

@article{
 title = {Formulation of itraconazole nanococrystals and evaluation of their bioavailability in dogs},
 type = {article},
 year = {2014},
 pages = {107-113},
 volume = {87},
 websites = {https://www.sciencedirect.com/science/article/abs/pii/S0939641113003986},
 month = {5},
 publisher = {Elsevier},
 day = {1},
 id = {ffe45db7-4cd0-3c5b-a7b2-0c44f972a16a},
 created = {2021-09-08T12:38:06.614Z},
 accessed = {2018-04-05},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.614Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {The aim of the study is to increase the bioavailability of itraconazole (ITRA) using nanosized cocrystals prepared via wet milling of ITRA in combination with dicarboxylic acids. Wet milling was used in order to create a nanosuspension of ITRA in combination with dicarboxylic acids. After spray-drying and bead layering, solid state was characterized by MDSC, XRD, Raman and FT-IR. The release profiles and bioavailability of the nanococrystalline suspension, the spray-dried and bead layered formulation were evaluated. A monodisperse nanosuspension (549±51nm) of ITRA was developed using adipic acid and Tween®80. Solid state characterization indicated the formation of nanococrystals by hydrogen bounds between the triazole group of ITRA and the carboxyl group of adipic acid. A bioavailability study was performed in dogs. The faster drug release from the nanocrystal-based formulation was reflected in the in vivo results since Tmax of the formulations was obtained 3h after administration, while Tmax of the reference formulation was observed only 6h after administration. This fast release of ITRA was obtained by a dual concept: manufacturing of nanosized cocrystals of ITRA and adipic acid via wet milling. Formation of stable nanosized cocrystals via this approach seems a good alternative for amorphous systems to increase the solubility and obtain a fast drug release of BCS class II drugs.},
 bibtype = {article},
 author = {De Smet, Lieselotte and Saerens, Lien and De Beer, Thomas and Carleer, Robert and Adriaensens, Peter and Van Bocxlaer, Jan and Vervaet, Chris and Remon, Jean Paul},
 doi = {10.1016/J.EJPB.2013.12.016},
 journal = {European Journal of Pharmaceutics and Biopharmaceutics},
 number = {1}
}

The aim of the study is to increase the bioavailability of itraconazole (ITRA) using nanosized cocrystals prepared via wet milling of ITRA in combination with dicarboxylic acids. Wet milling was used in order to create a nanosuspension of ITRA in combination with dicarboxylic acids. After spray-drying and bead layering, solid state was characterized by MDSC, XRD, Raman and FT-IR. The release profiles and bioavailability of the nanococrystalline suspension, the spray-dried and bead layered formulation were evaluated. A monodisperse nanosuspension (549±51nm) of ITRA was developed using adipic acid and Tween®80. Solid state characterization indicated the formation of nanococrystals by hydrogen bounds between the triazole group of ITRA and the carboxyl group of adipic acid. A bioavailability study was performed in dogs. The faster drug release from the nanocrystal-based formulation was reflected in the in vivo results since Tmax of the formulations was obtained 3h after administration, while Tmax of the reference formulation was observed only 6h after administration. This fast release of ITRA was obtained by a dual concept: manufacturing of nanosized cocrystals of ITRA and adipic acid via wet milling. Formation of stable nanosized cocrystals via this approach seems a good alternative for amorphous systems to increase the solubility and obtain a fast drug release of BCS class II drugs.

@article{
 title = {Development and characterization of mucoadhesive chitosan films for ophthalmic delivery of cyclosporine A},
 type = {article},
 year = {2014},
 pages = {10-19},
 volume = {472},
 websites = {https://www.sciencedirect.com/science/article/pii/S0378517314004372?via%3Dihub},
 month = {9},
 publisher = {Elsevier},
 day = {10},
 id = {bd21544d-8046-3405-982c-54dcb53fe6aa},
 created = {2021-09-08T12:38:06.899Z},
 accessed = {2018-04-05},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.899Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Ocular chitosan films were prepared in order to prolong ocular delivery of cyclosporine A. The mucoadhesive films were prepared using the solvent casting evaporation method. A 24 full factorial design was used to evaluate the effect of 4 preparation parameters on the film thickness, swelling index and mechanical properties. Moreover, uniformity of content and in vitro drug release were investigated. Possible interactions between the film excipients were studied by FTIR analysis. In vitro experiments were performed in order to evaluate the cytotoxicity and anti-inflammatory activity of the chitosan films. Film thickness, water uptake, mechanical properties and in vitro release of cyclosporine A were dependent on film composition, especially on the amount of plasticizer. Lower drug release was measured from chitosan films containing a higher amount of plasticizer as glycerol decreased the swelling of chitosan films. FTIR spectra suggest a reorganization of hydrogen bonds between chitosan chains in the presence of glycerol and cyclodextrins. None of the film formulations showed significant cytotoxicity as compared to the negative control using human epithelial cells (HaCaT). Cyclosporine A dispersed in the various film formulations remained anti-inflammatorily active as significant suppression of interleukin-2 secretion in concanavalin A stimulated Jurkat T cells was measured.},
 bibtype = {article},
 author = {Hermans, Kris and Van den Plas, Dave and Kerimova, Sabina and Carleer, Robert and Adriaensens, Peter and Weyenberg, Wim and Ludwig, Annick},
 doi = {10.1016/J.IJPHARM.2014.06.017},
 journal = {International Journal of Pharmaceutics},
 number = {1-2}
}

Ocular chitosan films were prepared in order to prolong ocular delivery of cyclosporine A. The mucoadhesive films were prepared using the solvent casting evaporation method. A 24 full factorial design was used to evaluate the effect of 4 preparation parameters on the film thickness, swelling index and mechanical properties. Moreover, uniformity of content and in vitro drug release were investigated. Possible interactions between the film excipients were studied by FTIR analysis. In vitro experiments were performed in order to evaluate the cytotoxicity and anti-inflammatory activity of the chitosan films. Film thickness, water uptake, mechanical properties and in vitro release of cyclosporine A were dependent on film composition, especially on the amount of plasticizer. Lower drug release was measured from chitosan films containing a higher amount of plasticizer as glycerol decreased the swelling of chitosan films. FTIR spectra suggest a reorganization of hydrogen bonds between chitosan chains in the presence of glycerol and cyclodextrins. None of the film formulations showed significant cytotoxicity as compared to the negative control using human epithelial cells (HaCaT). Cyclosporine A dispersed in the various film formulations remained anti-inflammatorily active as significant suppression of interleukin-2 secretion in concanavalin A stimulated Jurkat T cells was measured.

@article{
 title = {Protein engineering for directed immobilization},
 type = {article},
 year = {2013},
 pages = {1761-1777},
 volume = {24},
 month = {11},
 publisher = {American Chemical Society},
 day = {20},
 id = {4c2c28c5-6b2b-3448-b5d5-cadf1c2c2cde},
 created = {2021-09-08T12:38:06.949Z},
 accessed = {2018-04-05},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.949Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {SteenRedeker2013},
 source_type = {JOUR},
 notes = {<b>From Duplicate 1 (<i>Protein Engineering For Directed Immobilization</i> - Steen Redeker, Erik; Ta, Duy Tien; Cortens, David; Billen, Brecht; Guedens, Wanda; Adriaensens, Peter)<br/></b><br/>doi: 10.1021/bc4002823},
 private_publication = {false},
 abstract = {Much effort has been put into the optimization of the functional activity of proteins. For biosensors this protein functional optimization will increase the biosensor's sensitivity and/or selectivity. However, the strategy chosen for the immobilization of the proteins to the sensor surface might be equally important for the development of sensor surfaces that are optimally biologically active. Several studies published in recent years show that the oriented immobilization of the bioactive molecules improves the sensor's properties. In this review, we discuss the state of the art of the different protein immobilization strategies that are commonly used today with a special focus on biosensor applications. These strategies include nonspecific immobilization techniques either by physical adsorption, by covalent coupling, or by specific immobilization via site-specifically introduced tags or bio-orthogonal chemistry. The different tags and bio-orthogonal chemistry available and the techniques to site-specifically introduce these groups in proteins are also discussed.},
 bibtype = {article},
 author = {Steen Redeker, Erik and Ta, Duy Tien and Cortens, David and Billen, Brecht and Guedens, Wanda and Adriaensens, Peter},
 doi = {10.1021/bc4002823},
 journal = {Bioconjugate Chemistry},
 number = {11}
}

Much effort has been put into the optimization of the functional activity of proteins. For biosensors this protein functional optimization will increase the biosensor's sensitivity and/or selectivity. However, the strategy chosen for the immobilization of the proteins to the sensor surface might be equally important for the development of sensor surfaces that are optimally biologically active. Several studies published in recent years show that the oriented immobilization of the bioactive molecules improves the sensor's properties. In this review, we discuss the state of the art of the different protein immobilization strategies that are commonly used today with a special focus on biosensor applications. These strategies include nonspecific immobilization techniques either by physical adsorption, by covalent coupling, or by specific immobilization via site-specifically introduced tags or bio-orthogonal chemistry. The different tags and bio-orthogonal chemistry available and the techniques to site-specifically introduce these groups in proteins are also discussed.

@article{
 title = {Science Outreach Programs as a Powerful Tool for Science Promotion: An Example from Flanders},
 type = {article},
 year = {2012},
 keywords = {Collaborative/Cooperative Learning,Consumer Chemistry,Curriculum,Food Science,Hands-On Learning/Manipulatives,High School/Introductory Chemistry,Interdisciplinary/Multidisciplinary,Laboratory Instruction,Nanotechnology,Organic Chemistry},
 pages = {602-604},
 volume = {89},
 websites = {https://pubs.acs.org/doi/abs/10.1021/ed100886s,http://pubs.acs.org/doi/10.1021/ed100886s},
 month = {4},
 publisher = {American Chemical Society and Division of Chemical Education, Inc.},
 day = {10},
 id = {d6b3ac9e-2db3-3999-b58f-77ff52903faa},
 created = {2021-09-08T12:38:06.397Z},
 accessed = {2018-03-21},
 file_attached = {false},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:06.397Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Within the framework of the Lisbon Agreement, all European member states are encouraged to take measures to increase the number of science and technology students in higher education. To promote this educational model, a chemistry project was developed that focuses on high school students and especially on the involvement of their teachers by inviting both groups to attend science outreach programs at Hasselt University.},
 bibtype = {article},
 author = {Guedens, Wanda J. and Reynders, Monique},
 doi = {10.1021/ED100886S},
 journal = {Journal of Chemical Education},
 number = {5}
}

Within the framework of the Lisbon Agreement, all European member states are encouraged to take measures to increase the number of science and technology students in higher education. To promote this educational model, a chemistry project was developed that focuses on high school students and especially on the involvement of their teachers by inviting both groups to attend science outreach programs at Hasselt University.

@article{
 title = {Versatile post-polymerization functionalization of poly(p-phenylene vinylene) copolymers containing carboxylic acid substituents: development of a universal method towards functional conjugated copolymers},
 type = {article},
 year = {2010},
 pages = {1313},
 volume = {1},
 websites = {http://xlink.rsc.org/?DOI=c0py00086h},
 month = {9},
 publisher = {The Royal Society of Chemistry},
 day = {7},
 id = {8325bc08-e890-369e-bd01-9a1babac471b},
 created = {2021-09-08T12:38:06.687Z},
 accessed = {2018-04-05},
 file_attached = {true},
 profile_id = {eaba7b6f-fa85-31c0-b522-4deccdf5f08b},
 group_id = {624a87b2-6d51-35ae-90a4-09666c247b70},
 last_modified = {2021-09-08T12:38:28.286Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {A novel conjugated copolymer of poly(2-methoxy-5-(3,7-dimethyloctyloxy)-1,4-phenylene vinylene) (MDMO-PPV) and poly(1,4-(2-(5-carboxypentyloxy)-5-methoxyphenylene) vinylene) (CPM-PPV), which can be used as a platform for further post-polymerization functionalization, is presented. This copolymer is soluble in common organic solvents, such as CHCl3, CH2Cl2 and THF. Post-polymerization functionalization of the acid-groups of this copolymer has been successfully performed via an optimized DCC/DMAP-procedure with the desired alcohol. Several examples have been prepared to demonstrate the versatility of the developed functionalization methodology. PPV-copolymers have been prepared with vinyl groups, propynylphenyl groups, methacrylate groups, ATRP initiator groups, dithiocarbamate initiator groups and propargyl groups. The latter group can be utilized to do “click” chemistry, which has been demonstrated with an azide-functionalized reagent. In all cases, analytical data are consistent with a quantitative conversion of the functional groups. It is demonstrated that no substantial degradation of the conjugated system occurs even after consecutive post-polymerization functionalization reactions.},
 bibtype = {article},
 author = {Duchateau, Jan and Lutsen, Laurence and Guedens, Wanda and Cleij, Thomas J. and Vanderzande, Dirk},
 doi = {10.1039/c0py00086h},
 journal = {Polymer Chemistry},
 number = {8}
}

A novel conjugated copolymer of poly(2-methoxy-5-(3,7-dimethyloctyloxy)-1,4-phenylene vinylene) (MDMO-PPV) and poly(1,4-(2-(5-carboxypentyloxy)-5-methoxyphenylene) vinylene) (CPM-PPV), which can be used as a platform for further post-polymerization functionalization, is presented. This copolymer is soluble in common organic solvents, such as CHCl3, CH2Cl2 and THF. Post-polymerization functionalization of the acid-groups of this copolymer has been successfully performed via an optimized DCC/DMAP-procedure with the desired alcohol. Several examples have been prepared to demonstrate the versatility of the developed functionalization methodology. PPV-copolymers have been prepared with vinyl groups, propynylphenyl groups, methacrylate groups, ATRP initiator groups, dithiocarbamate initiator groups and propargyl groups. The latter group can be utilized to do “click” chemistry, which has been demonstrated with an azide-functionalized reagent. In all cases, analytical data are consistent with a quantitative conversion of the functional groups. It is demonstrated that no substantial degradation of the conjugated system occurs even after consecutive post-polymerization functionalization reactions.