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Catalytic Amination of Bisphenol F to Methylenedianiline via Tandem Hydrogenation-Amination-Dehydrogenation
No full textsponsorship: M.D., S.V.M., F.M., and D.E.D.V. acknowledge the support of Catalisti-VLAIO through the Moonshot project CoRe2 (HBC2019.0116) and the Fonds Wetenschappelijk Onderzoek (FWO-1SA0921N; FWO-1SHA524N) for the doctoral fellowships. The authors also express their gratitude to Jannick Vercammen and Robin Coeck for the discussions during the project. (Agentschap Innoveren en Ondernemen|HBC2019.0116, Fonds Wetenschappelijk Onderzoek|FWO-1SA0921N, Fonds Wetenschappelijk Onderzoek|FWO-1SHA524N)status: Publishe
Volgende-generatie cytogenetica voor uitgebreide genetische analyze van sarcomen in een diagnostische setting.
No full textOver the past few decades, several innovative molecular techniques have been introduced in clinical oncology practice. One of these tools is short-read next generation sequencing (NGS), a technique that led to a significant improvement in cancer diagnosis and treatment due to the identification of targetable driver mutations and/or gene fusions. However, NGS has mainly revolutionized clinical practice in common epithelial cancer types but remains unsatisfactory when applied to rare tumor types such as malignant soft tissue and bone tumors. These tumors, also called sarcomas, represent less than 2% of solid tumors with 1181 new diagnoses in Belgium in 2018 [1]. Sarcomas are highly heterogeneous in terms of histological presentation (> 100 subtypes to date), clinical disease course and underlying genetic aberrations. Accurate determination of genetic aberrations significantly adds to a correct diagnosis, which is strongly associated with patient treatment. However, genetic testing of sarcomas is not straight-forward today. Indeed, while some sarcoma subtypes carry a characteristic gene mutation or fusion, many remain poorly characterized or show multiple, complex genetic aberrations caused by chromothripsis or catastrophic chromosomal breakage [2,3]. These complex aberrations are difficult to detect by short-read NGS and typically include structural variants in which larger DNA segments undergo chromosomal perturbations such as translocations, deletions, duplications, insertions or inversions. Therefore, a combination of several cytogenetic techniques is currently required for the diagnostic workup of sarcomas including conventional karyotyping, array Comparative Genomic Hybridization (aCGH), and Fluorescent In Situ Hybridization (FISH), next to short-read NGS. This combined approach is needed because standard cytogenetic techniques have several shortcomings including limited resolution (karyotyping) or the inability to detect certain structural variants like balanced translocations (aCGH). As a result, genetic testing of sarcomas is labor-intensive, costly and requires a substantial amount of tumor tissue which is not always available. With this project, we aim to implement a novel technology called Optical Genomic Mapping (OGM). OGM is a non-sequencing based technology that allows genome-wide detection of structural variants and copy number alterations, and therefore has the potential to replace the above-mentioned standard cytogenetic techniques by one single test, as recently demonstrated by Neveling et al for hematological malignancies [4,5]. As compared to long-read sequencing methods such as PacBio or Nanopore, OGM has the advantage that it does not suffer from sequencing errors. Implementing OGM for sarcoma diagnostics will lead to more comprehensive and cost-effective genetic analysis, rapidly revealing structural variants and copy number variation in patient samples. This novel approach will not only result in improved diagnosis but may also reveal novel driver events in poorly characterized sarcomas.status: Accepte
De Rol van Pin1 bij Endotheeldisfunctie en Thrombose in CTEPH
No full textChronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism (PE), characterized by fibro-thrombotic material obliterating large pulmonary arteries. The incidence of CTEPH after PE is about 3%, with patients presenting at advanced stages with compromised haemodynamic profile and limited exercise capacity. Treatment is complex, involving surgery, angioplasty and drugs. There is an urgent need to i) understand why patients develop CTEPH after acute PE and ii) identify and treat patients at risk of post-surgery persistent pulmonary hypertension. Dysfunctional pulmonary arterial endothelial cells (ECs) play a key role in the pathogenesis of CTEPH, by producing factors targeting pulmonary arterial smooth muscle cells (SMCs). Peptidyl-Prolyl Cis/Trans Isomerase NIMA-Interacting protein 1 (Pin1) plays a crucial role in vascular and inflammatory diseases. Its inhibition attenuates tissue factor expression and activity in vascular cells in vitro, and reduces vascular remodelling in vivo. Noteworthy, our preliminary data shows that Pin1 levels are elevated in ECs and plasma from CTEPH patients. We hypothesized that Pin1 is a biomarker for CTEPH and that its inhibition might be beneficial for the prevention of vascular thrombotic diseases such as CTEPH. Therefore, the aims of the proposal are to investigate, using patient cells, tissue, and preclinical animal models whether i) Pin1 is a discriminating biomarker to identify individuals at risk and ii) Pin1 inhibition restores EC dysfunction, and reduce thrombosis in CTEPH. Expected results: Pin1 is a novel biomarker to identify individuals at risk for CTEPH and maybe a novel target in preventing CTEPH.status: Publishe
Are Intrusive Memories for False Event-Related Details Possible? A Study on Traumatic Event Memories Over Time
No full textstatus: Publishe
Unraveling tactile and proprioceptive upper limb function in children with unilateral cerebral palsy: a combination of robotic and clinical assessments
No full textPURPOSE: To map somatosensory impairments in the more-impaired and less-impaired upper limb of children with unilateral cerebral palsy (uCP) compared to typically developing children (TDC), using clinical and robotic assessments. Additionally, we explored which subgroups of children with uCP are more likely to experience somatosensory impairments. MATERIALS AND METHODS: This cross-sectional study included 49 children with uCP (11y11m ± 2y10m, 26 males) and 49 age- and sex-matched TDC (11y10m ± 2y10m). Tactile registration (Semmes-Weinstein monofilaments), tactile perception (stereognosis, two-point discrimination), and proprioception (clinical movement sense, ETH MIKE robot, and Kinarm exoskeleton) were assessed. Differences between groups and across manual ability levels and brain lesion types were analyzed using generalized estimating equation models. RESULTS: Children with uCP exhibited tactile impairments in both hands (more-impaired: 27-43%; less-impaired: 12-16%) and worse proprioception bilaterally compared to TDC (p ≤ 0.003). Lower manual ability was related to worse tactile perception (p ≤ 0.001) and proximal proprioception (p ≤ 0.045). Predominant grey matter lesions were correlated with worse tactile registration (p = 0.016), perception (p ≤ 0.009), and distal proprioception (p = 0.009). CONCLUSIONS: Our results underline the importance of including clinical and robotic assessments in the follow-up of children with uCP to identify bilateral somatosensory impairments. An international consensus on clinically relevant and well-defined assessment protocols is needed to enhance clinical translation.sponsorship: this work was supported by the Flemish Research Foundation (FWO-Vlaanderen) under an FWO Project (G0c4919N) and an FWO Research Fellowship to lK (11PP224N). (Flemish Research Foundation (FWO-Vlaanderen) under an FWO Project|G0c4919N, FWO Research Fellowship|11PP224N)status: Published onlin
Onderhandelen over koloniaal erfgoed. Het (co-)design van historische museumeducatie in postkoloniaal perspectief
No full text'Negotiating colonial heritage' examines how the meaning of colonial collections is negotiated in practices of history teaching in museum contexts. It pursues the threefold aim to examine what layers of meaning a diverse range of instructional actors add to curated exhibitions of colonial collections, how they integrate these into an educational design, and why they make particular choices in the design process.
Part of an interdisciplinary project, this dissertation focuses on 'Swahili-Arab' cultural heritage collections stored and exhibited in two Belgian museums: the AfricaMuseum in Tervuren, and the Royal Military Museum in Brussels. Part I describes the origins of these collections, largely 'collected' before, during and after the so-called 'Arab Campaign' (1892-1894) in Eastern Congo. From the end of the nineteenth century onwards, these collections were integrated in Belgian exhibitions. They transformed their original meaning as witnesses of interculturally hybrid societies into tools of colonial propaganda. Alongside newly created propaganda objects, the exhibition of these collections served the legitimization of the Belgian colonial enterprise in Congo throughout the twentieth century. The latter was framed as a humanitarian intervention aimed at the abolition of the slave trade in Eastern Congo, controlled by Swahili-Arab traders. In light of recent postcolonial debates in Belgian society, it is discussed how instructional actors may use these collections to - together with young people - interrogate longstanding and still widely resonating national and colonial master narratives. An extensive theoretical framework is elaborated, connecting insights from theory-formation around historical thinking and historical consciousness and from the fields of critical heritage studies and post- and decolonial studies.
Building on this framework, allowing for a critical engagement with colonial collections during museum education, parts II and III empirically examine how instructional actors engage with the Swahili-Arab collections on display in both museums. Part II - based on extensive design tasks and in-depth interviews - qualitatively analyses the individual educational design process of three profiles of instructional actors: prospective history teachers, experienced history teachers, and museum guides. It reveals how most instructional actors prioritise cognitive and historical disciplinary engagement with colonial collections above sparking emotional-affective reflection and experience. While the need for a critical engagement with colonial heritage in present society is recognised, participants generally struggled with integrating both historical complexity and meaningful present-day reflection on the legacies of colonial heritage and history among diverse student audiences. A complex configuration of educational and epistemological beliefs - stemming from diverging professional routines and educational backgrounds across different profiles - as well as the often-overlooked role of individual positionalities largely shape instructional actors' design choices.
Part III investigates a heterogeneous professional learning community (PLC) in which eight instructional actors collaboratively - in an attempt to cross the borders between history education in schools and museums - negotiated the educational use of colonial collections in museums. A qualitative framing analysis of interactions during a five-month professional learning program, including physical and online exchanges and expert lectures is presented. It demonstrates how dialogical and reflective educational collaboration significantly influences participants' web of beliefs on history teaching in a museum context, and their individual positionalities with regards to the value of critical reflection on colonial legacies in history education. It is emphasized how this negotiation process is shaped by broader and changing societal and political debates on mental decolonisation, specific institutional contexts, and persistent coloniality embedded in Western museums' functioning.
Overall, this dissertation adds to an emerging field of research on non-formal history teaching and heritage studies by innovatively foregrounding the often-overlooked perspectives and practices of those designing and mediating learning around colonial collections. It especially highlights the need to dynamically study the relationship between beliefs and practices of history teaching in situated contexts, with eye for individual positionalities. Its findings have important implications for teacher training and professionalization. This includes the need for an integrated conceptualization of cognitive and emotional-affective engagement in relation to history teaching, and an alignment of epistemological beliefs on heritage and history. Finally, based on the findings of the PLC study, it invites for reflection on the use of museums as places for the professional development of history teachers, and on the role different forms of expertise - also beyond academic expertise - may play in this development.status: Publishe
Learning Curve for Rat Intestinal Transplantation: Milestones From a Single Surgeon's Perspective
No full textINTRODUCTION: The rat intestinal transplant (ITx) model is associated with a steep and challenging learning curve (LC) due to the microsurgical skills it requires. Although benchmark values are well-defined in the literature, clear milestones guiding progression along this curve are lacking, which limits its widespread use. Here, we present our methodology for assessing LC progression and achievement. METHODS: We describe the experience of a single surgeon developing the rat ITx model without prior microsurgical training. The LC was divided into 3 stepwise milestones: (1) acquisition of microsurgical skills, (2) development of intestinal graft procurement, and (3) development of intestinal graft implantation. LC progression was assessed using surgical times (milestones 2 and 3) and survival rate (milestone 3), according to the number of procedures performed. Based on anastomosis time, a cumulative sum chart analysis was used to determine the number of procedures required to reach LC proficiency. RESULTS: After initial microsurgical training, chicken thighs and rat cadavers were used to practice the key steps of the ITx model. Subsequently, intestinal procurement and implantation in living rats were performed to ultimately complete the 3 defined milestones. Analysis of the cumulative sum chart indicated that 34 ITx procedures were required to reach anastomosis time targets (linear regression adjusted R2 = 0.95), which was directly associated with an increased 7-day survival rate. CONCLUSIONS: Our methodology, based on stepwise milestones, enabled the development of the rat ITx model. Following the completion of milestones 1 and 2, 34 ITx procedures were required to complete the LC.sponsorship: LJC is supported by a KU Leuven University Chair funded by Medtronic, a research grant from Research Foundation Flanders (FWO) (G090922N) and is appointed as senior clinical researcher by FWO (18E2B24N) . JP is supported by a KU Leuven University Chair funded by IGL. (KU Leuven University Chair - Medtronic, Research Foundation Flanders (FWO)|G090922N, FWO|18E2B24N, KU Leuven University Chair - IGL)status: Accepte
Amine-Catalyzed Aldol Addition of Dihydroxyacetone for Bio-Based Flame Retardants
No full textA new catalytic method was developed for synthesizing a sustainable phosphorus-based flame retardant (PFR) from dihydroxyacetone (DHA), a triose derived from hexoses or glycerol oxidation, e.g., for PUR applications. The study first investigates alkyl amine catalysts for self-aldol addition of DHA to form the branched hexose dendroketose. Short-chain, non-functionalized secondary and tertiary amines showed the best balance between aldol activity and branching selectivity. Triethylamine (Et3N) was chosen for process optimization, enabling scale-up to a 10 L process using 500 g/L DHA and 1 mol % Et3N, achieving a productivity of 109 g/(L·h)—approximately 7.5 times higher than the current state of the art. The resulting dendroketose was hydrogenated to produce dendroketol, a branched hexitol with three primary alcohol groups suitable for further functionalization. To prevent product loss during hydrogenation due to base-catalyzed retro-aldol addition, various amine neutralization methods were evaluated, with equimolar HCl addition proving most effective and economical. Finally, dendroketol was purified and phosphorylated with P2O5 to yield the PFR. Flame-retardant testing, conducted under EU standard BS 7175 (for bedding materials), confirmed compliance, underscoring the industrial potential of the process.sponsorship: This work was performed in the framework of the Catalisti cluster ICON project POLYFLAM ("Polyol based Flame retardants and lubricants", HBC.2018.0482), with the financial support of VLAIO (Flemish Agency for Innovation and Entrepreneurship). (VLAIO (Flemish Agency for Innovation and Entrepreneurship)|HBC.2018.0482)status: Published onlin
Human adenosine deaminase type 2 deficiency enhances NK cell activation but impairs maturation and function.
No full textNK cells, or natural killer cells, might be interesting players to investigate further in the disease process of patients with deficiency of ADA2, a rare, recently discovered inborn error of immunity.sponsorship: European Research Council|948959status: Published onlin
Manual Dexterity Abilities and Dual Tasking in Children With Developmental Coordination Disorder and Typically Developing Children
No full textUNLABELLED: Poor manual skills in children with Developmental Coordination Disorder (DCD) may be dependent on task complexity and due to difficulties in the automatization phase of the motor learning process. Increased task demands and the dual-task paradigm can be used to test these hypotheses. OBJECTIVES: We aim to investigate (1) manual dexterity abilities using increased levels of difficulty; (2) dual tasking using an experimental protocol of the Tyneside Pegboard Test (TPT). METHOD: Sixteen children with DCD and 16 age-matched typically developing (TD) children were included. Various experimental conditions of the TPT (unimanual, bimanual and dual task) were administered. The dual-task paradigm comprised a primary unimanual task and a cognitive task (auditory non-verbal task). Parents were asked to fill out the eConners questionnaire to report attentional difficulties. Repeated measures ANOVAs were used to compare possible differences in effects on the performance of the groups. Pearson correlation coefficients were calculated between dual-task performance and ADHD index of the eConners questionnaire. RESULTS: Children with DCD performed significantly worse in all task conditions (unimanual, bimanual, dual task) compared to TD children. In unimanual and bimanual conditions, they did no not present a higher impact of task constraints. Dual-task performances did not have a differential effect on groups and were not interfered by attentional difficulties. CONCLUSIONS: Children with DCD exhibit a general slowness in all TPT tasks. Our findings do not support the automatization deficit hypothesis.sponsorship: This study was partially funded by the Italian Ministry of Health, RC Linea 1, 2024-2025 (Italian Ministry of Health)status: Published onlin