Title Promoter Affiliations Abstract "WANDERING THE BLUE FIELDS OF LIMINALITY: An artistic research in the somatic effects of liminal experiences" "Arne DE WINDE" "ArcK, Media, Arts and Design" "WANDERING THE BLUE FIELDS OF LIMINALITY is an artistic investigation into liminal states and their sensory manifestations. It focuses on liminality in the form of subtle changes in the ordinary in order to reveal how artistic practices can lead to being physically immersed in liminal states, not in order to escape everyday life, but to expand it. The research focuses on affective liminality in the form of eros, despair, and mourning, sensory liminality in the form of sound and music, and liminal transitions in life in the form of mortality. By delving deeper into this myriad of possible everyday liminal spaces, the research seeks to explore the bodily effects they produce in those who access them. To this end, inspiration is sought from the field of (psycho)somatic care, questioning the ways in which such practices are too often perverted in the pursuit of increased effectiveness and productivity. Therefore, the project sets a clear non-utilitarian and non-therapeutic goal and instead seeks to expand the space for purposeful uselessness by bringing together cultural (artistic and academic) theories of liminality and psychosomatic medicine." "The effect of conservative treatment of temporomandibular disorders on somatic tinnitus." "Willem De Hertogh" "Movement Antwerp (MOVANT)" "Tinnitus, or ringing in the ears, is the phantom sensation of sound in the absence of an internal or external source for the sound which occurs in 10-15% of adults. Subjective tinnitus, influenced by the somatosensory system is called somatosensory tinnitus. In this subtype, the tinnitus can be influenced by impaired somatosensory input from the masticatory system or from the cervical spine.Our research group was able to demonstrate that non-invasive treatment of the cervical spine and of the masticatory system can lead to an improvement of tinnitus complaints (Michiels, Van de Heyning, Truijen, Hallemans, & De Hertogh, 2016; Van der Wal et al., 2020). Information on the underlying working mechanisms of these treatments is however lacking. This is important as it can shed light on tinnitus pathophysiology.We recently performed a mediation analysis and found that an improvement in temporomandibular disorder (TMD) was able to explain 35% of the observed treatment effect in patients with somatic tinnitus attributed to TMD (van der Wal et al., Submitted). TMD is however an umbrella term and further elaboration on the contribution of different components of TMD in tinnitus is needed. Of particular interest are the acting neurophysiological mechanisms. Also the assessment of a change in TMD over time needs to be improved.The current project is funded by remaining funds of a FWO TBM project and will be used to apply for.additional funding.ReferencesMichiels, S., Van de Heyning, P., Truijen, S., Hallemans, A., & De Hertogh, W. (2016). Does multi-modal cervical physical therapy improve tinnitus in patients with cervicogenic somatic tinnitus? Man Ther, 26, 125-131. doi:10.1016/j.math.2016.08.005Van der Wal, A., Michiels, S., Van de Heyning, P., Braem, M., Visscher, C., Topsakal, V., . . . De Hertogh, W. (2020). Treatment of Somatosensory Tinnitus: A Randomized Controlled Trial Studying the Effect of Orofacial Treatment as Part of a Multidisciplinary Program. J Clin Med, 9(3). doi:10.3390/jcm9030705van der Wal, A., van de Heyning, P., Gilles, A., Jacquemin, L., Topsakal, V., Van Rompaey, V., . . . de Hertogh, W. (Submitted). Is a reduction of somatic tinnitus severity mediated by an improvement in temporomandibular disorder? Hearing Research." "The effect of conservative treatment of temporomandibular disorders on somatic tinnitus." "Willem De Hertogh" "Movement Antwerp (MOVANT)" "This project aims to improve the quality of care for patients suffering from tinnitus attributed to a temporomandibular dysfunction (TMD). This by verifying the effect of TMD treatment on tinnitus. As a next step, underlying working mechanisms of the applied treatment will be investigated (mediating factors). Third, variables that predict the treatment outcome (responders/ non-responders) will be analysed (prognostic indicators). Our findings wil be of importance for general practitioners, ENT specialists, audiologists, dentists and physical therapists, since they all deal with patients suffering from tinnitus." "Somatic ribosome defects as target for cancer therapy" "Kim De Keersmaecker" "Laboratory for Disease Mechanisms in Cancer" "Mutations in different ribosomal proteins have been described in a series of inherited disorders, known as ribosomopathies. These syndromes come with a variety of symptoms, including hematopoietic defects and a predisposition to develop leukemia and solid tumors later in life. This transition from hypo- to hyperproliferation is a long-standing paradox in the field and the underlying mechanisms by which such ribosomal protein mutations promote transition to cancer in these diseases remain poorly understood. In the last decade, somatic ribosomal protein mutations have also been observed in a variety of cancer types, further consolidating the link between ribosomal protein defects and oncogenesis.First, we studied the RPL10 R98S mutation, found in pediatric T-ALL as a first example to explore the oncogenic mechanisms of ribosome-defective cancer cells. By analyzing exome sequencing data from a mouse lymphoid RPL10 R98S model and from ribosome mutant leukemia patients, and by performing cell biological experiments in lymphoid RPL10 R98S cell models, we came to a model in which oxidative stress due to ribosome dysfunction causes hypoproliferation in ribosome-defective cancer and ribosomopathies. This oxidative stress also increases DNA damage levels and promotes the acquisition of rescuing mutations that alleviate oxidative stress and stimulate hyperproliferation (e.g. NOTCH1). This model can thus explain the paradoxical transition from hypo-to hyperproliferation in ribosomopathies.Furthermore, by performing a differential proteomics analysis, we show that mouse lymphoid cells expressing RPL10 R98S as well as RPL10 R98S-positive T-ALL xenograft samples display elevated expression of JAK-STAT signaling components. These cells also display Jak-Stat pathway hyperactivation upon cytokine stimulation, reduced Jak1 degradation and enhanced sensitivity to JAK-STAT inhibitors. Next to transcriptional changes, we observed a reduced activity of the proteasome, increased sensitivity to clinically used proteasome inhibitors in RPL10 R98S expressing cells. We identified modulation of the JAK-STAT signaling cascade as a novel cancer-promoting activity of a ribosomal protein mutation.Finally, we looked with a broader scope at ribosomal lesions by generating an isogenic cell line panel by CRISPR-Cas9, representing the most frequently occurring ribosomal protein mutations associated to cancer. Proteomics and phosphoproteomics analyses revealed several cellular processes that are dysregulated in ribosome-defective cells such as the spliceosome, ribosome biogenesis, cell cycle regulation and the proteasome. These results were used to screen the cell line panel against a rationally designed drug library. We highlight several promising targets including exportin 1 in a Rps15 mutant (P131S/H137Y) background and agents impacting on DNA repair, such as PF477736 and AZ20 targeting CHK1/ATR kinase, in a Rpl5/Rpl10/Rpl11 mutant background. This study provides a strong foundation for further efforts aimed at understanding the oncogenic role of ribosomal protein mutations in cancer and at developing targeted therapy for ribosome-defective cancer." "Modal collocation and how delicate modal systems can be. A cognitive-functional corpus study of semantic and syntactic effects of collocation between modal verbs and modal adverbs in UK and US English." "Grammar and Pragmatics" "The research will investigate the dynamic nature of an aspect of language called 'modality', which enables speakers to assess the truth of what they say in terms of likelihood and obligations. Traditionally, the main recognised grammatical category of modality in English is built up of a paradigm of 'modal verbs' (can, could, will, would, shall, should, may, might and must). English, along with a large number of other languages, also has lexical ('more meaningful') means to express modality, for example 'modal adverbs' (probably, possibly, necessarily, certainly, well, ...)." "Influence of nuclear quantum effects on the static and dynamic properties of protic molecules in nanoporous materials" "Department of Applied physics" "Nanoporous materials, including zeolites and metal-organic frameworks (MOFs), make up a class of materials characterized by exceptional chemical and physical properties. Their use in various applications ranging from catalysis and selective adsorption to gas storage or separation –or the promise they hold within that matter, drives the necessity of a thorough understanding of their properties at the most fundamental level. Many processes within these materials are known to be affected by the specific loading pattern with water. However, to date, simulations mimicking these conditions rely on serious approximations where the nuclei are treated as classical particles, despite of the fact that nuclear quantum effects (NQEs) are believed to influence to a large extent the behavior of protic molecules in confinement. Within this project we wish to take a serious leap forward on the fundamental level by rigorously including NQEs using path integral based molecular dynamics simulations. Recent theoretical and computational developments have now opened the perspective for simulating water and small alcohols in materials of industrial relevance. This project should result in a proper understanding of structural properties and proton conductivity within zeolites and MOFs." "Modeling of non-linear effects in the design of reinforced concrete structures with static linear finite element" "Stijn Matthys" "Department of Structural Engineering and Building Materials" "The project aims to achieve a reasoned calculation of non-linear and time-dependent effects in the design of reinforced concrete structures. The mathematical model is developed with a view to the implementation of accounting software based on finite linear static (rod or plate) elements. The mathematical model allows to model non-linear effects via stepwise variable stiffness." "Somatic mutations explain missing risk of multiple sclerosis." "An Goris" "Laboratory for Neuroimmunology" "Somatic mutations explain missing risk in multiple sclerosisAn Goris, Laboratory for Neuroimmunology, KU Leuven1. State of the artMultiple sclerosis (MS) is an autoimmune disease of the central nervous system, affecting 2.5 millionpeople worldwide and leading to important physical and cognitive disability with typical onset duringyoung adulthood. A genetic component has long been demonstrated and through genome-wideassociation studies (GWAS) we have now identified 110 genetic risk factors1,2. Each of these isrelatively common in the population (>5%) and has a modest effect on disease risk (odds ratio of50% of variance in MS risk4. Novel categories of inherited genetic variantssuch as rare (10-20% in target cells(here B cells) and" "PhD in collaborative care for the elderly with psychological and somatic frailty" "Mieke Vermandere" "Academic Center for General Practice, Neuropsychiatry, Gerontology and Geriatrics" "More than two-thirds of older patients receiving psychiatric care have at least one general medical condition, and many of these patients have at least two. Management of multimorbidity requires integration of somatic and mental health care. Collaborative care is a complex intervention based on management models for chronic conditions and consists of four key elements: a multi-professional approach to care, a structured care plan, planned follow-up appointments for patients, and improved interprofessional communication. Collaborative care would be effective in managing mental illness in adults. However, there are still insufficient studies on the effect of collaborative care in mental illness in elderly people with somatic comorbidity. The objective of this project is the development and piloting of a collaborative care model for this target group in and around Leuven, in collaboration with, among others, the Leuven general practitioners, the University Psychiatric Center (UPC) KU Leuven, and the Geriatrics and Gerontology Department UZ/KU Leuven. This doctoral dissertation will be under the supervision of and a collaboration with a multidisciplinary research group." "Detection of somatic mutations and disease-defining methylation patterns in brain tissue and cerebrospinal fluid of patients with non-acquired focal epilepsy" "Björn Menten" "Department of Biomolecular Medicine" "The majority of non-acquired focal epilepsies (NAFE) have a presumed genetic etiology. However, the current yield of diagnostic genetic testing in affected patients is very low. This diagnostic gap is an important barrier to the broader use of gene-targeted therapies. Increasing evidence from resected brain tissue of individuals with NAFE points towards an important role of pathogenic somatic variants and methylation abnormalities. Most NAFE patients however do not undergo brain surgery, and the lack of brain tissue precludes a genetic and histopathological diagnosis. In this project, we aim to prove that cell-free DNA (cfDNA) circulating in cerebrospinal fluid (CSF) and serum of patients with NAFE, including individuals with malformations of cortical development (MCD), can be used to bridge this diagnostic gap. First, we will apply a deep- sequencing protocol to detect novel somatic variants in cfDNA from CSF. Second, we will use nanopore sequencing on native cfDNA to both identify somatic copy number changes and to classify patients using aberrant cfDNA methylation patterns consistent with different subtypes of MCD and focal epilepsy. By prioritizing patients who undergo epilepsy surgery for our study cohort, we will validate the detected somatic and epigenetic changes in paired brain tissue, thereby providing an estimate of reliability for our analytical approach. By identifying the genetic etiology and disease methylation profiles from cfDNA, we can improve diagnostic yield and clinical decision-making in this severely affected population.Promising and Challenging Fundamental Science: One third of epilepsy patients are therapy resistant, and a genetic diagnosis has been shown to enable more targeted treatment choices. However, two thirds of these patients remain without a definitive genetic diagnosis. In this project, we will unmask the hidden genetic causes of NAFE by implementing a first-of-its-kind approach that searches both for somatic single nucleotide or copy number variants, and their effective pathologic changes to DNA methylation patterns. This project pushes scientific and clinical boundaries: it will establish and validate novel sequencing methods that in turn pave the way for better diagnosis, classification, and treatment for the large group of drug-resistant focal epilepsy patients who do not undergo epilepsy surgery.Cross-Belgian Collaboration: This project brings together the expertise and clinical reach of top neurogenetic and neurological teams across four medical centers in Flanders and Wallonia. In doing so, this project gains access to a unique and well-phenotyped patient cohort that is integral to the success of this project."