976 results on '"De Bruyne P"'
Search Results
2. New Tricarboxylate Plasticizers for Use in Polylactic Acid: Synthesis, Thermal Behavior, Mechanical Properties and Durability
- Author
-
De Bruyne, Anthony, Gómez, Kenneth Cerdán, O’Rourke, Galahad, Denayer, Mats, Vekeman, Jelle, De Proft, Frank, Stuyck, Wouter, Leinders, Jarne, Van Puyvelde, Peter, and De Vos, Dirk
- Published
- 2024
- Full Text
- View/download PDF
3. Association Between Automated 3D Measurement of Coronary Luminal Narrowing and Risk of Future Myocardial Infarction
- Author
-
Candreva, Alessandro, Lodi Rizzini, Maurizio, Calò, Karol, Pagnoni, Mattia, Munhoz, Daniel, Chiastra, Claudio, Aben, Jean-Paul, Fournier, Stephane, Muller, Olivier, De Bruyne, Bernard, Collet, Carlos, Gallo, Diego, and Morbiducci, Umberto
- Published
- 2024
- Full Text
- View/download PDF
4. Linear statistics for Coulomb gases: higher order cumulants
- Author
-
De Bruyne, Benjamin, Doussal, Pierre Le, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Mathematical Physics ,Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We consider $N$ classical particles interacting via the Coulomb potential in spatial dimension $d$ and in the presence of an external trap, at equilibrium at inverse temperature $\beta$. In the large $N$ limit, the particles are confined within a droplet of finite size. We study smooth linear statistics, i.e. the fluctuations of sums of the form ${\cal L}_N = \sum_{i=1}^N f({\bf x}_i)$, where ${\bf x}_i$'s are the positions of the particles and where $f({\bf x}_i)$ is a sufficiently regular function. There exists at present standard results for the first and second moments of ${\cal L}_N$ in the large $N$ limit, as well as associated Central Limit Theorems in general dimension and for a wide class of confining potentials. Here we obtain explicit expressions for the higher order cumulants of ${\cal L}_N$ at large $N$, when the function $f({\bf x})=f(|{\bf x}|)$ and the confining potential are both rotationnally invariant. A remarkable feature of our results is that these higher cumulants depend only on the value of $f'(|{\bf x}|)$ and its higher order derivatives evaluated exactly at the boundary of the droplet, which in this case is a $d$-dimensional sphere. In the particular two-dimensional case $d=2$ at the special value $\beta=2$, a connection to the Ginibre ensemble allows us to derive these results in an alternative way using the tools of determinantal point processes. Finally we also obtain the large deviation form of the full probability distribution function of ${\cal L}_N$., Comment: 19 pages
- Published
- 2023
5. PhD thesis 'Extreme value statistics and optimization problems in stochastic processes'
- Author
-
De Bruyne, Benjamin
- Subjects
Condensed Matter - Statistical Mechanics - Abstract
This thesis is devoted to the study of extreme value statistics in stochastic processes and their applications. In the first part, we obtain exact analytical results on the extreme value statistics of both discrete-time and continuous-time random walks. In particular, we focus on the gap statistics of random walks and exhibit their asymptotic universality with respect to the jump distribution in the limit of a large number of steps. In addition, we compute the asymptotic behavior of the expected maximum of random walks in the presence of a bridge constraint and reveal a rich behavior in their finite-size correction. Moreover, we compute the expected length of the convex hull of Brownian motion confined in a disk and show that it converges slowly to the perimeter of the disk with a stretched exponential decay. In the second part, we focus on numerically sampling rare trajectories of stochastic processes. We introduce an efficient method to sample bridge discrete-time random walks. We illustrate it and apply it to various examples. We further extend the method to other stochastic processes, both Markovian and non-Markovian. We apply our method to sample surviving particles in the presence of a periodic trapping environment. Finally, we discuss several optimization problems in stochastic processes involving extreme value statistics. In particular, we introduce a new technique to optimally control dynamical systems undergoing a resetting policy., Comment: 134 pages, 54 figures
- Published
- 2023
6. Innovative label-free lymphoma diagnosis using infrared spectroscopy and machine learning on tissue sections
- Author
-
Delrue, Charlotte, Hofmans, Mattias, Van Dorpe, Jo, Van der Linden, Malaïka, Van Gaever, Zen, Kerre, Tessa, Speeckaert, Marijn M., and De Bruyne, Sander
- Published
- 2024
- Full Text
- View/download PDF
7. AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies
- Author
-
Vandewalle, Niels, De Beule, Nathan, De Becker, Ann, De Bruyne, Elke, Menu, Eline, Vanderkerken, Karin, Breckpot, Karine, Devoogdt, Nick, and De Veirman, Kim
- Published
- 2024
- Full Text
- View/download PDF
8. Fueling CARs: metabolic strategies to enhance CAR T-cell therapy
- Author
-
Van der Vreken, Arne, Vanderkerken, Karin, De Bruyne, Elke, De Veirman, Kim, Breckpot, Karine, and Menu, Eline
- Published
- 2024
- Full Text
- View/download PDF
9. Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy
- Author
-
Wang, Yanmeng, Vandewalle, Niels, De Veirman, Kim, Vanderkerken, Karin, Menu, Eline, and De Bruyne, Elke
- Published
- 2024
- Full Text
- View/download PDF
10. Combining a prioritization strategy and functional studies nominates 5’UTR variants underlying inherited retinal disease
- Author
-
Dueñas Rey, Alfredo, del Pozo Valero, Marta, Bouckaert, Manon, Wood, Katherine A, Van den Broeck, Filip, Daich Varela, Malena, Thomas, Huw B, Van Heetvelde, Mattias, De Bruyne, Marieke, Van de Sompele, Stijn, Bauwens, Miriam, Lenaerts, Hanne, Mahieu, Quinten, Josifova, Dragana, Rivolta, Carlo, O’Keefe, Raymond T, Ellingford, Jamie, Webster, Andrew R, Arno, Gavin, Ayuso, Carmen, De Zaeytijd, Julie, Leroy, Bart P, De Baere, Elfride, and Coppieters, Frauke
- Published
- 2024
- Full Text
- View/download PDF
11. Innovative label-free lymphoma diagnosis using infrared spectroscopy and machine learning on tissue sections
- Author
-
Charlotte Delrue, Mattias Hofmans, Jo Van Dorpe, Malaïka Van der Linden, Zen Van Gaever, Tessa Kerre, Marijn M. Speeckaert, and Sander De Bruyne
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Abstract The diagnosis of lymphomas is challenging due to their diverse histological presentations and clinical manifestations. There is a need for inexpensive tools that require minimal expertise and are accessible for routine laboratories. Contrastingly, current conventional diagnostic methods are often found only in specialized environments. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy offers a nondestructive and user-friendly approach in the analysis of a wide range of samples. In this paper, we determined whether the technique coupled with machine learning can detect and differentiate lymphoma within lymphoid tissue samples. Tissue sections from 295 individuals diagnosed with lymphoma and 389 individuals without the disease were analyzed using ATR-FTIR spectroscopy. The resulting spectral dataset was split using a 70:30 train-test split. Partial least Squares Discriminant Analysis (PLS-DA) models were trained to distinguish non-malignant lymphoid tissue from lymphoma samples and to differentiate between subtypes. On the training set (n = 478), significant spectral differences were mainly identified in the 1800–900 cm–1 region, attributed to fundamental biochemical constituents like proteins, lipids, carbohydrates, and nucleic acids. On the independent test set (n = 206), the trained PLS-DA model achieved a promising AUC of 0.882 (95% CI: 0.881–0.884) in the differentiation between lymphoma and non-malignant lymphoid tissue. In addition, comparative analyses revealed spectral distinctions and notable clustering between the different lymphoma subtypes. This study provides valuable insights into the application of ATR-FTIR spectroscopy and machine learning in the field of lymphoma diagnosis as a non-destructive, rapid and inexpensive tool with the potential to be easily implemented in non-specialized laboratories.
- Published
- 2024
- Full Text
- View/download PDF
12. AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies
- Author
-
Niels Vandewalle, Nathan De Beule, Ann De Becker, Elke De Bruyne, Eline Menu, Karin Vanderkerken, Karine Breckpot, Nick Devoogdt, and Kim De Veirman
- Subjects
AXL ,Immunoregulation ,Therapy ,Acute Myeloid Leukemia ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Until recently, treatment options for patients diagnosed with Acute Myeloid Leukemia (AML) were limited and predominantly relied on various combinations, dosages, or schedules of traditional chemotherapeutic agents. Patients with advanced age, relapsed/refractory disease or comorbidities were often left without effective treatment options. Novel advances in the understanding of leukemogenesis at the molecular and genetic levels, alongside recent progress in drug development, have resulted in the emergence of novel therapeutic agents and strategies for AML patients. Among these innovations, the receptor tyrosine kinase AXL has been established as a promising therapeutic target for AML. AXL is a key regulator of several cellular functions, including epithelial-to-mesenchymal transition in tumor cells, immune regulation, apoptosis, angiogenesis and the development of chemoresistance. Clinical studies of AXL inhibitors, as single agents and in combination therapy, have demonstrated promising efficacy in treating AML. Additionally, novel AXL-targeted therapies, such as AXL-specific antibodies or antibody fragments, present potential solutions to overcome the limitations associated with traditional small-molecule AXL inhibitors or multikinase inhibitors. This review provides a comprehensive overview of the structure and biological functions of AXL under normal physiological conditions, including its role in immune regulation. We also summarize AXL’s involvement in cancer, with a specific emphasis on its role in the pathogenesis of AML, its contribution to immune evasion and drug resistance. Moreover, we discuss the AXL inhibitors currently undergoing (pre)clinical evaluation for the treatment of AML.
- Published
- 2024
- Full Text
- View/download PDF
13. Impact of coronary CT image quality on the accuracy of the FFRCT Planner
- Author
-
Andreini, Daniele, Belmonte, Marta, Penicka, Martin, Van Hoe, Lieven, Mileva, Niya, Paolisso, Pasquale, Nagumo, Sakura, Nørgaard, Bjarne L., Ko, Brian, Otake, Hiromasa, Koo, Bon-Kwon, Jensen, Jesper Møller, Mizukami, Takuya, Munhoz, Daniel, Updegrove, Adam, Taylor, Charles, Leipsic, Jonathon, Sonck, Jeroen, De Bruyne, Bernard, and Collet, Carlos
- Published
- 2024
- Full Text
- View/download PDF
14. Fueling CARs: metabolic strategies to enhance CAR T-cell therapy
- Author
-
Arne Van der Vreken, Karin Vanderkerken, Elke De Bruyne, Kim De Veirman, Karine Breckpot, and Eline Menu
- Subjects
CAR T cells ,Co-stimulus ,Drug repurposing ,Metabolism ,Mitochondria ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract CAR T cells are widely applied for relapsed hematological cancer patients. With six approved cell therapies, for Multiple Myeloma and other B-cell malignancies, new insights emerge. Profound evidence shows that patients who fail CAR T-cell therapy have, aside from antigen escape, a more glycolytic and weakened metabolism in their CAR T cells, accompanied by a short lifespan. Recent advances show that CAR T cells can be metabolically engineered towards oxidative phosphorylation, which increases their longevity via epigenetic and phenotypical changes. In this review we elucidate various strategies to rewire their metabolism, including the design of the CAR construct, co-stimulus choice, genetic modifications of metabolic genes, and pharmacological interventions. We discuss their potential to enhance CAR T-cell functioning and persistence through memory imprinting, thereby improving outcomes. Furthermore, we link the pharmacological treatments with their anti-cancer properties in hematological malignancies to ultimately suggest novel combination strategies.
- Published
- 2024
- Full Text
- View/download PDF
15. OPENPichia: licence-free Komagataella phaffii chassis strains and toolkit for protein expression
- Author
-
Claes, Katrien, Van Herpe, Dries, Vanluchene, Robin, Roels, Charlotte, Van Moer, Berre, Wyseure, Elise, Vandewalle, Kristof, Eeckhaut, Hannah, Yilmaz, Semiramis, Vanmarcke, Sandrine, Çıtak, Erhan, Fijalkowska, Daria, Grootaert, Hendrik, Lonigro, Chiara, Meuris, Leander, Michielsen, Gitte, Naessens, Justine, van Schie, Loes, De Rycke, Riet, De Bruyne, Michiel, Borghgraef, Peter, and Callewaert, Nico
- Published
- 2024
- Full Text
- View/download PDF
16. Blood Flow Energy Identifies Coronary Lesions Culprit of Future Myocardial Infarction
- Author
-
Lodi Rizzini, Maurizio, Candreva, Alessandro, Mazzi, Valentina, Pagnoni, Mattia, Chiastra, Claudio, Aben, Jean-Paul, Fournier, Stephane, Cook, Stephane, Muller, Olivier, De Bruyne, Bernard, Mizukami, Takuya, Collet, Carlos, Gallo, Diego, and Morbiducci, Umberto
- Published
- 2024
- Full Text
- View/download PDF
17. Epidemiology and molecular typing of multidrug-resistant bacteria in tertiary hospitals and nursing homes in Flanders, Belgium
- Author
-
van Kleef-van Koeveringe, Stefanie, Matheeussen, Veerle, Schuermans, Annette, De Koster, Sien, Perales Selva, Natascha, Jansens, Hilde, De Coninck, Dieter, De Bruyne, Katrien, Mensaert, Klaas, Kluytmans-van den Bergh, Marjolein, Kluytmans, Jan, Goossens, Herman, Dhaeze, Wouter, and Leroux-Roels, Isabel
- Published
- 2024
- Full Text
- View/download PDF
18. Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy
- Author
-
Yanmeng Wang, Niels Vandewalle, Kim De Veirman, Karin Vanderkerken, Eline Menu, and Elke De Bruyne
- Subjects
mTOR ,Multiple myeloma ,Protein synthesis ,Targeted therapy ,Medicine ,Cytology ,QH573-671 - Abstract
Abstract Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.
- Published
- 2024
- Full Text
- View/download PDF
19. Transport properties of diffusive particles conditioned to survive in trapping environments
- Author
-
Pozzoli, Gaia and De Bruyne, Benjamin
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We consider a one-dimensional Brownian motion with diffusion coefficient $D$ in the presence of $n$ partially absorbing traps with intensity $\beta$, separated by a distance $L$ and evenly spaced around the initial position of the particle. We study the transport properties of the process conditioned to survive up to time $t$. We find that the surviving particle first diffuses normally, before it encounters the traps, then undergoes a period of transient anomalous diffusion, after which it reaches a final diffusive regime. The asymptotic regime is governed by an effective diffusion coefficient $D_\text{eff}$, which is induced by the trapping environment and is typically different from the original one. We show that when the number of traps is \emph{finite}, the environment enhances diffusion and induces an effective diffusion coefficient that is systematically equal to $D_\text{eff}=2D$, independently of the number of the traps, the trapping intensity $\beta$ and the distance $L$. On the contrary, when the number of traps is \emph{infinite}, we find that the environment inhibits diffusion with an effective diffusion coefficient that depends on the traps intensity $\beta$ and the distance $L$ through a non-trivial scaling function $D_\text{eff}=D \mathcal{F}(\beta L/D)$, for which we obtain a closed-form. Moreover, we provide a rejection-free algorithm to generate surviving trajectories by deriving an effective Langevin equation with an effective repulsive potential induced by the traps. Finally, we extend our results to other trapping environments., Comment: 28 pages, 10 figures
- Published
- 2022
- Full Text
- View/download PDF
20. Enhancing pediatric attention-deficit hyperactivity disorder treatment: exploring the gut microbiota effects of French maritime pine bark extract and methylphenidate intervention
- Author
-
Anne-Sophie Weyns, Sarah Ahannach, Tim Van Rillaer, Tess De Bruyne, Sarah Lebeer, and Nina Hermans
- Subjects
polyphenols ,French maritime pine bark extract ,attention-deficit hyperactivity disorder ,methylphenidate ,gut microbiome ,prebiotics ,Nutrition. Foods and food supply ,TX341-641 - Abstract
IntroductionThe pathogenesis of Attention-Deficit Hyperactivity Disorder (ADHD) is thought to be multifactorial, with a potential role for the bidirectional communication between the gut microbiome and brain development and function. Since the “golden-standard” medication therapy with methylphenidate (MPH) is linked to multiple adverse effects, there is a need for alternative treatment options such as dietary polyphenols. These secondary plant metabolites exert antioxidant and anti-inflammatory effects, but much less is known about their impact on the gut microbiota. Since polyphenols are believed to modulate gut microbial composition, interventions might be advantageous in ADHD therapy. Therefore, intervention studies with polyphenols in ADHD therapy investigating the gut microbial composition are highly relevant.MethodsBesides the primary research questions addressed previously, this study explored a potential prebiotic effect of the polyphenol-rich French Maritime Pine Bark Extract (PBE) compared to MPH and a placebo in pediatric ADHD patients by studying their impact on the gut microbiota via amplicon sequencing of the full length 16S rRNA gene ribosomal subunit (V1-V9).ResultsOne interesting finding was the high relative abundance of Bifidobacteria among all patients in our study cohort. Moreover, our study has identified that treatment (placebo, MPH and PBE) explains 3.94% of the variation in distribution of microbial taxa (adjusted p-value of 0.011).DiscussionOur small sample size (placebo: n = 10; PBE: n = 13 and MPH: n = 14) did not allow to observe clear prebiotic effects in the patients treated with PBE. Notwithstanding this limitation, subtle changes were noticeable and some limited compositional changes could be observed.Clinical Trial Registrationdoi: 10.1186/S13063-017-1879-6
- Published
- 2024
- Full Text
- View/download PDF
21. Universal order statistics for random walks & L\'evy flights
- Author
-
De Bruyne, Benjamin, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We consider one-dimensional discrete-time random walks (RWs) of $n$ steps, starting from $x_0=0$, with arbitrary symmetric and continuous jump distributions $f(\eta)$, including the important case of L\'evy flights. We study the statistics of the gaps $\Delta_{k,n}$ between the $k^\text{th}$ and $(k+1)^\text{th}$ maximum of the set of positions $\{x_1,\ldots,x_n\}$. We obtain an exact analytical expression for the probability distribution $P_{k,n}(\Delta)$ valid for any $k$ and $n$, and jump distribution $f(\eta)$, which we then analyse in the large $n$ limit. For jump distributions whose Fourier transform behaves, for small $q$, as $\hat f (q) \sim 1 - |q|^\mu$ with a L\'evy index $0< \mu \leq 2$, we find that, the distribution becomes stationary in the limit of $n\to \infty$, i.e. $\lim_{n\to \infty} P_{k,n}(\Delta)=P_k(\Delta)$. We obtain an explicit expression for its first moment $\mathbb{E}[\Delta_{k}]$, valid for any $k$ and jump distribution $f(\eta)$ with $\mu>1$, and show that it exhibits a universal algebraic decay $ \mathbb{E}[\Delta_{k}]\sim k^{1/\mu-1} \Gamma\left(1-1/\mu\right)/\pi$ for large $k$. Furthermore, for $\mu>1$, we show that in the limit of $k\to\infty$ the stationary distribution exhibits a universal scaling form $P_k(\Delta) \sim k^{1-1/\mu} \mathcal{P}_\mu(k^{1-1/\mu}\Delta)$ which depends only on the L\'evy index $\mu$, but not on the details of the jump distribution. We compute explicitly the limiting scaling function $\mathcal{P}_\mu(x)$ in terms of Mittag-Leffler functions. For $1< \mu <2$, we show that, while this scaling function captures the distribution of the typical gaps on the scale $k^{1/\mu-1}$, the atypical large gaps are not described by this scaling function since they occur at a larger scale of order $k^{1/\mu}$., Comment: 40 pages, 11 figures
- Published
- 2022
22. EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis.
- Author
-
Adamo, Christin S, Beyens, Aude, Schiavinato, Alvise, Keene, Douglas R, Tufa, Sara F, Mörgelin, Matthias, Brinckmann, Jürgen, Sasaki, Takako, Niehoff, Anja, Dreiner, Maren, Pottie, Lore, Muiño-Mosquera, Laura, Gulec, Elif Yilmaz, Gezdirici, Alper, Braghetta, Paola, Bonaldo, Paolo, Wagener, Raimund, Paulsson, Mats, Bornaun, Helen, De Rycke, Riet, De Bruyne, Michiel, Baeke, Femke, Devine, Walter P, Gangaram, Balram, Tam, Allison, Balasubramanian, Meena, Ellard, Sian, Moore, Sandra, Symoens, Sofie, Shen, Joseph, Cole, Stacey, Schwarze, Ulrike, Holmes, Kathryn W, Hayflick, Susan J, Wiszniewski, Wojciech, Nampoothiri, Sheela, Davis, Elaine C, Sakai, Lynn Y, Sengle, Gerhard, and Callewaert, Bert
- Subjects
Animals ,Humans ,Mice ,Bone Diseases ,Metabolic ,Cutis Laxa ,Collagen ,Elastin ,Extracellular Matrix Proteins ,EFEMP2 ,EMILIN1 ,LOX ,aortic aneurysm ,arterial tortuosity ,collagen ,cutis laxa ,elastic fiber ,extracellular matrix ,fracture ,Rare Diseases ,Pediatric ,Congenital Structural Anomalies ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Underpinning research ,Aetiology ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.
- Published
- 2022
23. Combining a prioritization strategy and functional studies nominates 5’UTR variants underlying inherited retinal disease
- Author
-
Alfredo Dueñas Rey, Marta del Pozo Valero, Manon Bouckaert, Katherine A Wood, Filip Van den Broeck, Malena Daich Varela, Huw B Thomas, Mattias Van Heetvelde, Marieke De Bruyne, Stijn Van de Sompele, Miriam Bauwens, Hanne Lenaerts, Quinten Mahieu, Dragana Josifova, Genomics England Research Consortium, Carlo Rivolta, Raymond T O’Keefe, Jamie Ellingford, Andrew R Webster, Gavin Arno, Carmen Ayuso, Julie De Zaeytijd, Bart P Leroy, Elfride De Baere, and Frauke Coppieters
- Subjects
5’untranslated region (5’UTR) ,Upstream open reading frame (uORF) ,Non-coding variation ,Whole genome sequencing (WGS) ,Whole exome sequencing (WES) ,In silico prioritization ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background 5’ untranslated regions (5’UTRs) are essential modulators of protein translation. Predicting the impact of 5’UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5’UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs). Methods We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina. We evaluated the coverage of their 5’UTRs by different whole exome sequencing (WES) kits. The selected 5’UTRs were analyzed in whole genome sequencing (WGS) and WES data from IRD sub-cohorts from the 100,000 Genomes Project (n = 2397 WGS) and an in-house database (n = 1682 WES), respectively. Identified variants were annotated for 5’UTR-relevant features and classified into seven categories based on their predicted functional consequence. We developed a variant prioritization strategy by integrating population frequency, specific criteria for each category, and family and phenotypic data. A selection of candidate variants underwent functional validation using diverse approaches. Results Isoform-level re-quantification of retinal gene expression revealed 76 IRD genes with a non-canonical retina-enriched isoform, of which 20 display a fully distinct 5’UTR compared to that of their canonical isoform. Depending on the probe design, 3–20% of IRD genes have 5’UTRs fully captured by WES. After analyzing these regions in both cohorts, we prioritized 11 (likely) pathogenic variants in 10 genes (ARL3, MERTK, NDP, NMNAT1, NPHP4, PAX6, PRPF31, PRPF4, RDH12, RD3), of which 7 were novel. Functional analyses further supported the pathogenicity of three variants. Mis-splicing was demonstrated for the PRPF31:c.-9+1G>T variant. The MERTK:c.-125G>A variant, overlapping a transcriptional start site, was shown to significantly reduce both luciferase mRNA levels and activity. The RDH12:c.-123C>T variant was found in cis with the hypomorphic RDH12:c.701G>A (p.Arg234His) variant in 11 patients. This 5’UTR variant, predicted to introduce an upstream open reading frame, was shown to result in reduced RDH12 protein but unaltered mRNA levels. Conclusions This study demonstrates the importance of 5’UTR variants implicated in IRDs and provides a systematic approach for 5’UTR annotation and validation that is applicable to other inherited diseases.
- Published
- 2024
- Full Text
- View/download PDF
24. First-Passage-Driven Boundary Recession
- Author
-
De Bruyne, B., Randon-Furling, J., and Redner, S.
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We investigate a moving boundary problem for a Brownian particle on the semi-infinite line in which the boundary moves by a distance proportional to the time between successive collisions of the particle and the boundary. Phenomenologically rich dynamics arises. In particular, the probability for the particle to first reach the moving boundary for the $n^\text{th}$ time asymptotically scales as $t^{-(1+2^{-n})}$. Because the tail of this distribution becomes progressively fatter, the typical time between successive first passages systematically gets longer. We also find that the number of collisions between the particle and the boundary scales as $\ln\ln t$, while the time dependence of the boundary position varies as $t/\ln t$., Comment: 11 pages, 4 figure, for a special issue of JPA on resetting processes
- Published
- 2022
- Full Text
- View/download PDF
25. Optimal Resetting Brownian Bridges
- Author
-
De Bruyne, Benjamin, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We introduce a resetting Brownian bridge as a simple model to study search processes where the total search time $t_f$ is finite and the searcher returns to its starting point at $t_f$. This is simply a Brownian motion with a Poissonian resetting rate $r$ to the origin which is constrained to start and end at the origin at time $t_f$. We first provide a rejection-free algorithm to generate such resetting bridges in all dimensions by deriving an effective Langevin equation with an explicit space-time dependent drift $\tilde \mu({\bf x},t)$ and resetting rate $\tilde r({\bf x}, t)$. We also study the efficiency of the search process in one-dimension by computing exactly various observables such as the mean-square displacement, the hitting probability of a fixed target and the expected maximum. Surprisingly, we find that there exists an optimal resetting rate $r^*$ that maximizes the search efficiency, even in the presence of a bridge constraint. We show however that the physical mechanism responsible for this optimal resetting rate for bridges is entirely different from resetting Brownian motions without the bridge constraint., Comment: Main text: 6 pages + 3 figs, Supp. Mat.: 9 pages + 3 figs
- Published
- 2022
26. Resetting in Stochastic Optimal Control
- Author
-
De Bruyne, Benjamin and Mori, Francesco
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Optimization and Control - Abstract
``When in a difficult situation, it is sometimes better to give up and start all over again''. While this empirical truth has been regularly observed in a wide range of circumstances, quantifying the effectiveness of such a heuristic strategy remains an open challenge. In this paper, we combine the notions of optimal control and stochastic resetting to address this problem. The emerging analytical framework allows not only to measure the performance of a given restarting policy but also to obtain the optimal strategy for a wide class of dynamical systems. We apply our technique to a system with a final reward and show that the reward value must be larger than a critical threshold for resetting to be effective. Our approach, analogous to the celebrated Hamilton-Jacobi-Bellman paradigm, provides the basis for the investigation of realistic restarting strategies across disciplines. As an application, we show that the framework can be applied to an epidemic model to predict the optimal lockdown policy., Comment: 11 pages, 7 figures
- Published
- 2021
27. Statistics of the maximum and the convex hull of a Brownian motion in confined geometries
- Author
-
De Bruyne, Benjamin, Bénichou, Olivier, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We consider a Brownian particle with diffusion coefficient $D$ in a $d$-dimensional ball of radius $R$ with reflecting boundaries. We study the maximum $M_x(t)$ of the trajectory of the particle along the $x$-direction at time $t$. In the long time limit, the maximum converges to the radius of the ball $M_x(t) \to R$ for $t\to \infty$. We investigate how this limit is approached and obtain an exact analytical expression for the distribution of the fluctuations $\Delta(t) = [R-M_x(t)]/R$ in the limit of large $t$ in all dimensions. We find that the distribution of $\Delta(t)$ exhibits a rich variety of behaviors depending on the dimension $d$. These results are obtained by establishing a connection between this problem and the narrow escape time problem. We apply our results in $d=2$ to study the convex hull of the trajectory of the particle in a disk of radius $R$ with reflecting boundaries. We find that the mean perimeter $\langle L(t)\rangle$ of the convex hull exhibits a slow convergence towards the perimeter of the circle $2\pi R$ with a stretched exponential decay $2\pi R-\langle L(t)\rangle \propto \sqrt{R}(Dt)^{1/4} \,e^{-2\sqrt{2Dt}/R}$. Finally, we generalise our results to other confining geometries, such as the ellipse with reflecting boundaries. Our results are corroborated by thorough numerical simulations., Comment: 19 pages, 7 figures
- Published
- 2021
28. Generating stochastic trajectories with global dynamical constraints
- Author
-
De Bruyne, Benjamin, Majumdar, Satya N., Orland, Henri, and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We propose a method to exactly generate Brownian paths $x_c(t)$ that are constrained to return to the origin at some future time $t_f$, with a given fixed area $A_f = \int_0^{t_f}dt\, x_c(t)$ under their trajectory. We derive an exact effective Langevin equation with an effective force that accounts for the constraint. In addition, we develop the corresponding approach for discrete-time random walks, with arbitrary jump distributions including L\'evy flights, for which we obtain an effective jump distribution that encodes the constraint. Finally, we generalise our method to other types of dynamical constraints such as a fixed occupation time on the positive axis $T_f=\int_0^{t_f}dt\, \Theta\left[x_c(t)\right]$ or a fixed generalised quadratic area $\mathcal{A}_f=\int_0^{t_f}dt \,x_c^2(t)$., Comment: 32 pages, 7 figures
- Published
- 2021
- Full Text
- View/download PDF
29. Survival probability of random walks leaping over traps
- Author
-
Pozzoli, Gaia and De Bruyne, Benjamin
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability - Abstract
We consider one-dimensional discrete-time random walks (RWs) in the presence of finite size traps of length $\ell$ over which the RWs can jump. We study the survival probability of such RWs when the traps are periodically distributed and separated by a distance $L$. We obtain exact results for the mean first-passage time and the survival probability in the special case of a double-sided exponential jump distribution. While such RWs typically survive longer than if they could not leap over traps, their survival probability still decreases exponentially with the number of steps. The decay rate of the survival probability depends in a non-trivial way on the trap length $\ell$ and exhibits an interesting regime when $\ell\rightarrow 0$ as it tends to the ratio $\ell/L$, which is reminiscent of strongly chaotic deterministic systems. We generalize our model to continuous-time RWs, where we introduce a power-law distributed waiting time before each jump. In this case, we find that the survival probability decays algebraically with an exponent that is independent of the trap length. Finally, we derive the diffusive limit of our model and show that, depending on the chosen scaling, we obtain either diffusion with uniform absorption, or diffusion with periodically distributed point absorbers., Comment: 29 pages, 5 figures
- Published
- 2021
- Full Text
- View/download PDF
30. A Tale of Two (and More) Altruists
- Author
-
De Bruyne, B., Randon-Furling, J., and Redner, S.
- Subjects
Physics - Physics and Society ,Condensed Matter - Statistical Mechanics ,Quantitative Finance - Statistical Finance - Abstract
We introduce a minimalist dynamical model of wealth evolution and wealth sharing among $N$ agents as a platform to compare the relative merits of altruism and individualism. In our model, the wealth of each agent independently evolves by diffusion. For a population of altruists, whenever any agent reaches zero wealth (that is, the agent goes bankrupt), the remaining wealth of the other $N-1$ agents is equally shared among all. The population is collectively defined to be bankrupt when its total wealth falls below a specified small threshold value. For individualists, each time an agent goes bankrupt (s)he is considered to be "dead" and no wealth redistribution occurs. We determine the evolution of wealth in these two societies. Altruism leads to more global median wealth at early times; eventually, however, the longest-lived individualists accumulate most of the wealth and are richer and more long lived than the altruists., Comment: 16 pages, 6 figures, IOP format
- Published
- 2021
- Full Text
- View/download PDF
31. Targeting S100A9 protein affects mTOR-ER stress signaling and increases venetoclax sensitivity in Acute Myeloid Leukemia
- Author
-
Rong Fan, Hatice Satilmis, Niels Vandewalle, Emma Verheye, Elke De Bruyne, Eline Menu, Nathan De Beule, Ann De Becker, Gamze Ates, Ann Massie, Tessa Kerre, Marie Törngren, Helena Eriksson, Karin Vanderkerken, Karine Breckpot, Ken Maes, and Kim De Veirman
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Acute Myeloid Leukemia (AML) is a heterogeneous disease with limited treatment options and a high demand for novel targeted therapies. Since myeloid-related protein S100A9 is abundantly expressed in AML, we aimed to unravel the therapeutic impact and underlying mechanisms of targeting both intracellular and extracellular S100A9 protein in AML cell lines and primary patient samples. S100A9 silencing in AML cell lines resulted in increased apoptosis and reduced AML cell viability and proliferation. These therapeutic effects were associated with a decrease in mTOR and endoplasmic reticulum stress signaling. Comparable results on AML cell proliferation and mTOR signaling could be observed using the clinically available S100A9 inhibitor tasquinimod. Interestingly, while siRNA-mediated targeting of S100A9 affected both extracellular acidification and mitochondrial metabolism, tasquinimod only affected the mitochondrial function of AML cells. Finally, we found that S100A9-targeting approaches could significantly increase venetoclax sensitivity in AML cells, which was associated with a downregulation of BCL-2 and c-MYC in the combination group compared to single agent therapy. This study identifies S100A9 as a novel molecular target to treat AML and supports the therapeutic evaluation of tasquinimod in venetoclax-based regimens for AML patients.
- Published
- 2023
- Full Text
- View/download PDF
32. Comparative efficacy of materials used in patients undergoing pulpotomy or direct pulp capping in carious teeth: A systematic review and meta‐analysis
- Author
-
Athanasios Fasoulas, Georgios Keratiotis, Loukia Spineli, Nikos Pandis, Mieke A. A. De Bruyne, Roeland J.G. De Moor, and Maarten A. Meire
- Subjects
Biodentine ,calcium hydroxide ,direct pulp capping ,MTA ,pulpotomy ,vital pulp treatment ,Dentistry ,RK1-715 - Abstract
Abstract Objectives Different materials have been used for capping the pulp after exposure during caries removal in permanent teeth. The purpose of this study was to collate and analyze all pertinent evidence from randomized controlled trials (RCTs) on different materials used in patients undergoing pulpotomy or direct pulp capping in carious teeth. Materials and Methods Trials comparing two or more capping agents used for direct pulp capping (DPC) or pulpotomy were considered eligible. An electronic search of four databases and two clinical trial registries was carried out up to February 28, 2021 using a search strategy properly adapted to the PICO framework. Screening, data extraction, and risk of bias (RoB) assessment of primary studies were performed in duplicate and independently. The primary outcome was clinical and radiological success; secondary outcomes included continued root formation, tooth discoloration, and dentin bridge formation. Results 21 RCTs were included in the study. The RoB assessment indicated a moderate risk among the studies. Due to significant clinical and statistical heterogeneity among the studies, performing network meta‐analysis (NMA) was not possible. An ad hoc subgroup analysis revealed strong evidence of a higher success of DPC with Mineral Trioxide Aggregate (MTA) compared to calcium hydroxide (CH) (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 1.66−5.79). MTA performed better than CH in pulp capping (both DPC and pulpotomy) of mature compared to immature teeth (OR = 3.34, 95% CI: 1.81−6.17). The GRADE assessment revealed moderate strength of evidence for DPC and mature teeth, and low to very low strength of evidence for the remaining subgroups. Conclusions Considerable clinical and statistical heterogeneity among the trials did not allow NMA. The ad hoc subgroup analysis indicated that the clinical and radiographic success of MTA was higher than that of CH but only in mature teeth and DPC cases where the strength of evidence was moderate. PROSPERO Registration: number CRD42020127239.
- Published
- 2023
- Full Text
- View/download PDF
33. Illness-related parental stress and quality of life in children with kidney diseases
- Author
-
De Bruyne, Elke, Willem, Lore, Van Hoeck, Koen, Reynaert, Sarah, Vankerckhove, Sylvie, Adams, Brigitte, Leroi, Stéphanie, Collard, Laure, Michaux, Aline, Godefroid, Nathalie, Mekahli, Djalila, Knops, Noël, Eloot, Sunny, Raes, Ann, Walle, Johan Vande, Van Hoecke, Eline, Snauwaert, Evelien, and Levtchenko, Elena
- Published
- 2023
- Full Text
- View/download PDF
34. Generating constrained run-and-tumble trajectories
- Author
-
De Bruyne, Benjamin, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematical Physics ,Mathematics - Probability - Abstract
We propose a method to exactly generate bridge run-and-tumble trajectories that are constrained to start at the origin with a given velocity and to return to the origin after a fixed time with another given velocity. The method extends the concept of effective Langevin equations, valid for Markovian stochastic processes such as Brownian motion, to a non-Markovian stochastic process driven by a telegraphic noise, with exponentially decaying correlations. We obtain effective space-time dependent tumbling rates that implicitly accounts for the bridge constraint. We extend the method to other types of constrained run-and-tumble particles such as excursions and meanders. The method is implemented numerically and is shown to be very efficient., Comment: 21 pages, 7 figures
- Published
- 2021
- Full Text
- View/download PDF
35. Expected maximum of bridge random walks & L\'evy flights
- Author
-
De Bruyne, Benjamin, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematical Physics ,Mathematics - Probability - Abstract
We consider one-dimensional discrete-time random walks (RWs) with arbitrary symmetric and continuous jump distributions $f(\eta)$, including the case of L\'evy flights. We study the expected maximum ${\mathbb E}[M_n]$ of bridge RWs, i.e., RWs starting and ending at the origin after $n$ steps. We obtain an exact analytical expression for ${\mathbb E}[M_n]$ valid for any $n$ and jump distribution $f(\eta)$, which we then analyze in the large $n$ limit up to second leading order term. For jump distributions whose Fourier transform behaves, for small $k$, as $\hat f(k) \sim 1 - |a\, k|^\mu$ with a L\'evy index $0<\mu \leq 2$ and an arbitrary length scale $a>0$, we find that, at leading order for large $n$, ${\mathbb E}[M_n]\sim a\, h_1(\mu)\, n^{1/\mu}$. We obtain an explicit expression for the amplitude $h_1(\mu)$ and find that it carries the signature of the bridge condition, being different from its counterpart for the free random walk. For $\mu=2$, we find that the second leading order term is a constant, which, quite remarkably, is the same as its counterpart for the free RW. For generic $0< \mu < 2$, this second leading order term is a growing function of $n$, which depends non-trivially on further details of $\hat f (k)$, beyond the L\'evy index $\mu$. Finally, we apply our results to compute the mean perimeter of the convex hull of the $2d$ Rouse polymer chain and of the $2d$ run-and-tumble particle, as well as to the computation of the survival probability in a bridge version of the well-known "lamb-lion" capture problem., Comment: 31 pages, 6 figures
- Published
- 2021
36. Generating discrete-time constrained random walks and L\'evy flights
- Author
-
De Bruyne, Benjamin, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematical Physics ,Mathematics - Probability - Abstract
We introduce a method to exactly generate bridge trajectories for discrete-time random walks, with arbitrary jump distributions, that are constrained to initially start at the origin and return to the origin after a fixed time. The method is based on an effective jump distribution that implicitly accounts for the bridge constraint. It is illustrated on various jump distributions and is shown to be very efficient in practice. In addition, we show how to generalize the method to other types of constrained random walks such as generalized bridges, excursions, and meanders., Comment: 18 pages, 11 figures
- Published
- 2021
- Full Text
- View/download PDF
37. Wigner function for noninteracting fermions in hard wall potentials
- Author
-
De Bruyne, Benjamin, Dean, David S., Doussal, Pierre Le, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Condensed Matter - Quantum Gases ,Mathematical Physics - Abstract
The Wigner function $W_N({\bf x}, {\bf p})$ is a useful quantity to characterize the quantum fluctuations of an $N$-body system in its phase space. Here we study $W_N({\bf x}, {\bf p})$ for $N$ noninteracting spinless fermions in a $d$-dimensional spherical hard box of radius $R$ at temperature $T=0$. In the large $N$ limit, the local density approximation (LDA) predicts that $W_N({\bf x}, {\bf p}) \approx 1/(2 \pi \hbar)^d$ inside a finite region of the $({\bf x}, {\bf p})$ plane, namely for $|{\bf x}| < R$ and $|{\bf p}| < k_F$ where $k_F$ is the Fermi momentum, while $W_N({\bf x}, {\bf p})$ vanishes outside this region, or "droplet", on a scale determined by quantum fluctuations. In this paper we investigate systematically, in this quantum region, the structure of the Wigner function along the edge of this droplet, called the Fermi surf. In one dimension, we find that there are three distinct edge regions along the Fermi surf and we compute exactly the associated nontrivial scaling functions in each regime. We also study the momentum distribution $\hat \rho_N(p)$ and find a striking algebraic tail for very large momenta $\hat \rho_N(p) \propto 1/p^4$, well beyond $k_F$, reminiscent of a similar tail found in interacting quantum systems (discussed in the context of Tan's relation). We then generalize these results to higher $d$ and find, remarkably, that the scaling function close to the edge of the box is universal, i.e., independent of the dimension~$d$., Comment: 31 pages, 14 figures
- Published
- 2021
- Full Text
- View/download PDF
38. Long-Term Respiratory Outcome of Children with Empyema
- Author
-
Jalunis, Mohamed Mustakim, Hng, Shih Ying, Eg, Kah Peng, Gowdh, Nadia Fareeda Muhammad, Sanmugam, Anand, Nah, Shireen Anne, Nathan, Anna Marie, and de Bruyne, Jessie Anne
- Published
- 2024
- Full Text
- View/download PDF
39. Survival probability of a run-and-tumble particle in the presence of a drift
- Author
-
De Bruyne, Benjamin, Majumdar, Satya N., and Schehr, Gregory
- Subjects
Condensed Matter - Statistical Mechanics ,Condensed Matter - Soft Condensed Matter ,Mathematics - Probability - Abstract
We consider a one-dimensional run-and-tumble particle, or persistent random walk, in the presence of an absorbing boundary located at the origin. After each tumbling event, which occurs at a constant rate $\gamma$, the (new) velocity of the particle is drawn randomly from a distribution $W(v)$. We study the survival probability $S(x,t)$ of a particle starting from $x \geq 0$ up to time $t$ and obtain an explicit expression for its double Laplace transform (with respect to both $x$ and $t$) for an arbitrary velocity distribution $W(v)$, not necessarily symmetric. This result is obtained as a consequence of Spitzer's formula, which is well known in the theory of random walks and can be viewed as a generalization of the Sparre Andersen theorem. We then apply this general result to the specific case of a two-state particle with velocity $\pm v_0$, the so-called persistent random walk (PRW), and in the presence of a constant drift $\mu$ and obtain an explicit expression for $S(x,t)$, for which we present more detailed results. Depending on the drift $\mu$, we find a rich variety of behaviours for $S(x,t)$, leading to three distinct cases: (i) subcritical drift $-v_0\!<\!\mu\!<\! v_0$, (ii) supercritical drift $\mu < -v_0$ and (iii) critical drift $\mu=-v_0$. In these three cases, we obtain exact analytical expressions for the survival probability $S(x,t)$ and establish connections with existing formulae in the mathematics literature. Finally, we discuss some applications of these results to record statistics and to the statistics of last-passage times., Comment: 58 pages, 14 figures
- Published
- 2021
- Full Text
- View/download PDF
40. Implementando la vía clínica ANOCA
- Author
-
Thabo Mahendiran and Bernard De Bruyne
- Subjects
Internal medicine ,RC31-1245 - Abstract
En pocas palabras, el objetivo de la coronariografía diagnóstica es diferenciar el origen del dolor torácico de un paciente entre 1 de 4 endotipos: a) estenosis epicárdica; b) espasmo coronario; c) enfermedad microvascular coronaria (EMC); y d) igualmente importante, dolor torácico no coronario. Resulta imperativo señalar que este último es un diagnóstico por descarte y, por lo tanto, no puede confirmarse sin realizar una valoración formal de los demás mecanismos implicados (figura 1). A pesar de esta verdad palmaria, la interpretación de la mayoría de las coronariografías se limita a la mera «observación» de un «sombragrama». Un abordaje con un bajo rendimiento diagnóstico, ya que el 40% de los pacientes no presentan estenosis epicárdicas significativas, una entidad conocida como angina sin enfermedad coronaria obstructiva (ANOCA)1. A pesar de la presencia de angina típica o de la evidencia de isquemia durante las pruebas no invasivas, estos pacientes suelen quedar descartados sin más sin un diagnóstico formal. Figura 1. Se debe realizar un cateterismo con coronariografía a los pacientes que presentan dolor torácico intenso, recurrente y debilitante y, cuando sea necesario, pruebas de la función coronaria para averiguar el mecanismo desencadenante del dolor. El dolor torácico de origen no coronario es un diagnóstico...
- Published
- 2024
- Full Text
- View/download PDF
41. Implementing an ANOCA clinic
- Author
-
Thabo Mahendiran and Bernard De Bruyne
- Subjects
Medicine - Abstract
Simply stated, the goal of diagnostic coronary angiography is to distinguish the cause of a patient’s chest pain from 1 of 4 endotypes: a) epicardial stenosis; b) coronary spasm; c) coronary microvascular disease (CMD); and d) —equally important—noncoronary chest pain. Crucially, the latter is a diagnosis of exclusion and consequently cannot be confirmed without formal assessment of the other mechanisms (figure 1). Despite this truism, the interpretation of most coronary angiograms is limited to simple “eyeballing” of an epicardial “shadowgram”. This approach has a low diagnostic yield with 40% of patients found to have no significant epicardial stenoses—an entity known as angina with no obstructive coronary arteries (ANOCA).1 Despite the presence of typical angina or evidence of ischemia during noninvasive testing, these patients, are frequently nonchalantly dismissed without a formal diagnosis. Figure 1. Patients with compelling, recurring, and debilitating chest pain should undergo catheterization with coronary angiography and—when needed—coronary function testing to unravel the mechanism of their pain. Noncoronary chest pain is a diagnosis of exclusion and consequently can only be confirmed if the 3 other mechanisms have been assessed. FFR, fractional flow reserve; PPG, pullback pressure gradient. This very large group of patients is heterogeneous, and establishing the underlying cause of...
- Published
- 2024
- Full Text
- View/download PDF
42. Central nervous system manifestations of LRBA deficiency: case report of two siblings and literature review
- Author
-
T. C. Mangodt, K. Vanden Driessche, K. K. Norga, N. Moes, M. De Bruyne, F. Haerynck, V. Bordon, A. C. Jansen, and A. I. Jonckheere
- Subjects
Central nervous system ,LRBA deficiency ,Neurological ,Hearing loss ,Case report ,MRI ,Pediatrics ,RJ1-570 - Abstract
Abstract Background LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disease (PID) characterized by a regulatory T cell defect resulting in immune dysregulation and autoimmunity. We present two siblings born to consanguineous parents of North African descent with LRBA deficiency and central nervous system (CNS) manifestations. As no concise overview of these manifestations is available in literature, we compared our patient’s presentation with a reviewed synthesis of the available literature. Case presentations The younger brother presented with enteropathy at age 1.5 years, and subsequently developed Evans syndrome and diabetes mellitus. These autoimmune manifestations led to the genetic diagnosis of LRBA deficiency through whole exome sequencing with PID gene panel. At 11 years old, he had two tonic–clonic seizures. Brain MRI showed multiple FLAIR-hyperintense lesions and a T2-hyperintense lesion of the cervical medulla. His sister presented with immune cytopenia at age 9 years, and developed diffuse lymphadenopathy and interstitial lung disease. Genetic testing confirmed the same mutation as her brother. At age 13 years, a brain MRI showed multiple T2-FLAIR-hyperintense lesions. She received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) 3 months later. Follow-up MRI showed regression of these lesions. Conclusions Neurological disease is documented in up to 25% of patients with LRBA deficiency. Manifestations range from cerebral granulomas to acute disseminating encephalomyelitis, but detailed descriptions of neurological and imaging phenotypes are lacking. LRBA deficiency amongst other PIDs should be part of the differential diagnosis in patients with inflammatory brain lesions. We strongly advocate for a more detailed description of CNS manifestations in patients with LRBA deficiency, when possible with MR imaging. This will aid clinical decision concerning both anti-infectious and anti-inflammatory therapy and in considering the indication for allo-HSCT.
- Published
- 2023
- Full Text
- View/download PDF
43. Intravascular Imaging Findings After PCI in Patients With Focal and Diffuse Coronary Artery Disease
- Author
-
Hirofumi Ohashi, Takuya Mizukami, Jeroen Sonck, Frederic Bouisset, Brian Ko, Bjarne L. Nørgaard, Michael Mæng, Jesper Møller Jensen, Koshiro Sakai, Hirohiko Ando, Tetsuya Amano, Nicolas Amabile, Ziad Ali, Bernard De Bruyne, Bon‐Kwon Koo, Hiromasa Otake, and Carlos Collet
- Subjects
coronary artery disease ,fractional flow reserve ,optical coherence tomography ,pullback pressure gradient ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Following percutaneous coronary intervention (PCI), optical coherence tomography provides prognosis information. The pullback pressure gradient is a novel index that discriminates focal from diffuse coronary artery disease based on fractional flow reserve pullbacks. We sought to investigate the association between coronary artery disease patterns, defined by coronary physiology, and optical coherence tomography after stent implantation in stable patients undergoing PCI. Methods and Results This multicenter, prospective, single‐arm study was conducted in 5 countries (NCT03782688). Subjects underwent motorized fractional flow reserve pullbacks evaluation followed by optical coherence tomography‐guided PCI. Post‐PCI optical coherence tomography minimum stent area, stent expansion, and the presence of suboptimal findings such as incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were compared between patients with focal versus diffuse disease. Overall, 102 patients (105 vessels) were included. Fractional flow reserve before PCI was 0.65±0.14, pullback pressure gradient was 0.66±0.14, and post‐PCI fractional flow reserve was 0.88±0.06. The mean minimum stent area was 5.69±1.99 mm2 and was significantly larger in vessels with focal disease (6.18±2.12 mm2 versus 5.19±1.72 mm2, P=0.01). After PCI, incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were observed in 27.6%, 10.5%, and 51.4% of the cases, respectively. Vessels with focal disease at baseline had a lower prevalence of incomplete stent apposition (11.3% versus 44.2%, P=0.002) and more irregular tissue protrusion (69.8% versus 32.7%, P
- Published
- 2024
- Full Text
- View/download PDF
44. Antiviral Wolbachia strains associate with Aedes aegypti endoplasmic reticulum membranes and induce lipid droplet formation to restrict dengue virus replication
- Author
-
Robson K. Loterio, Ebony A. Monson, Rachel Templin, Jyotika T. de Bruyne, Heather A. Flores, Jason M. Mackenzie, Georg Ramm, Karla J. Helbig, Cameron P. Simmons, and Johanna E. Fraser
- Subjects
Wolbachia ,Aedes aegypti ,dengue ,flavivirus ,antiviral ,arbovirus ,Microbiology ,QR1-502 - Abstract
ABSTRACT Wolbachia are a genus of insect endosymbiotic bacteria which includes strains wMel and wAlbB that are being utilized as a biocontrol tool to reduce the incidence of Aedes aegypti-transmitted viral diseases like dengue. However, the precise mechanisms underpinning the antiviral activity of these Wolbachia strains are not well defined. Here, we generated a panel of Ae. aegypti-derived cell lines infected with antiviral strains wMel and wAlbB or the non-antiviral Wolbachia strain wPip to understand host cell morphological changes specifically induced by antiviral strains. Antiviral strains were frequently found to be entirely wrapped by the host endoplasmic reticulum (ER) membrane, while wPip bacteria clustered separately in the host cell cytoplasm. ER-derived lipid droplets (LDs) increased in volume in wMel- and wAlbB-infected cell lines and mosquito tissues compared to cells infected with wPip or Wolbachia-free controls. Inhibition of fatty acid synthase (required for triacylglycerol biosynthesis) reduced LD formation and significantly restored ER-associated dengue virus replication in cells occupied by wMel. Together, this suggests that antiviral Wolbachia strains may specifically alter the lipid composition of the ER to preclude the establishment of dengue virus (DENV) replication complexes. Defining Wolbachia’s antiviral mechanisms will support the application and longevity of this effective biocontrol tool that is already being used at scale.IMPORTANCEAedes aegypti transmits a range of important human pathogenic viruses like dengue. However, infection of Ae. aegypti with the insect endosymbiotic bacterium, Wolbachia, reduces the risk of mosquito to human viral transmission. Wolbachia is being utilized at field sites across more than 13 countries to reduce the incidence of viruses like dengue, but it is not well understood how Wolbachia induces its antiviral effects. To examine this at the subcellular level, we compared how different strains of Wolbachia with varying antiviral strengths associate with and modify host cell structures. Strongly antiviral strains were found to specifically associate with the host endoplasmic reticulum and induce striking impacts on host cell lipid droplets. Inhibiting Wolbachia-induced lipid redistribution partially restored dengue virus replication demonstrating this is a contributing role for Wolbachia's antiviral activity. These findings provide new insights into how antiviral Wolbachia strains associate with and modify Ae. aegypti host cells.
- Published
- 2024
- Full Text
- View/download PDF
45. Flow cytometry interference in patients treated with tafasitamab: Unraveling the diagnostic maze
- Author
-
Lisa Proost, Stijn Lambrecht, Mattias Hofmans, Ciel De Vriendt, Marijn Speeckaert, Carolien Bonroy, Barbara Denys, and Sander De Bruyne
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2024
- Full Text
- View/download PDF
46. Optimization and Growth in First-Passage Resetting
- Author
-
De Bruyne, B., Randon-Furling, J., and Redner, S.
- Subjects
Condensed Matter - Statistical Mechanics ,Condensed Matter - Soft Condensed Matter - Abstract
We combine the processes of resetting and first-passage to define \emph{first-passage resetting}, where the resetting of a random walk to a fixed position is triggered by a first-passage event of the walk itself. In an infinite domain, first-passage resetting of isotropic diffusion is non-stationary, with the number of resetting events growing with time as $\sqrt{t}$. We calculate the resulting spatial probability distribution of the particle analytically, and also obtain this distribution by a geometric path decomposition. In a finite interval, we define an optimization problem that is controlled by first-passage resetting; this scenario is motivated by reliability theory. The goal is to operate a system close to its maximum capacity without experiencing too many breakdowns. However, when a breakdown occurs the system is reset to its minimal operating point. We define and optimize an objective function that maximizes the reward (being close to maximum operation) minus a penalty for each breakdown. We also investigate extensions of this basic model to include delay after each reset and to two dimensions. Finally, we study the growth dynamics of a domain in which the domain boundary recedes by a specified amount whenever the diffusing particle reaches the boundary after which a resetting event occurs. We determine the growth rate of the domain for the semi-infinite line and the finite interval and find a wide range of behaviors that depend on how much the recession occurs when the particle hits the boundary., Comment: 31 pages in IOP format, 7 figures. Version 2: various additions and corrections; for publication in JSTAT
- Published
- 2020
- Full Text
- View/download PDF
47. Optimization in First-Passage Resetting
- Author
-
De Bruyne, B., Randon-Furling, J., and Redner, S.
- Subjects
Condensed Matter - Statistical Mechanics ,Mathematics - Probability ,Physics - Data Analysis, Statistics and Probability - Abstract
We investigate classic diffusion with the added feature that a diffusing particle is reset to its starting point each time the particle reaches a specified threshold. In an infinite domain, this process is non-stationary and its probability distribution exhibits rich features. In a finite domain, we define a non-trivial optimization in which a cost is incurred whenever the particle is reset and a reward is obtained while the particle stays near the reset point. We derive the condition to optimize the net gain in this system, namely, the reward minus the cost., Comment: 4 pages, 3 figures, revtex 4-1 format. Version 1 contains changes in response to referee comments. Version 2: A missing factor of 2 in an inline formula has been corrected
- Published
- 2020
- Full Text
- View/download PDF
48. Targeting S100A9 protein affects mTOR-ER stress signaling and increases venetoclax sensitivity in Acute Myeloid Leukemia
- Author
-
Fan, Rong, Satilmis, Hatice, Vandewalle, Niels, Verheye, Emma, De Bruyne, Elke, Menu, Eline, De Beule, Nathan, De Becker, Ann, Ates, Gamze, Massie, Ann, Kerre, Tessa, Törngren, Marie, Eriksson, Helena, Vanderkerken, Karin, Breckpot, Karine, Maes, Ken, and De Veirman, Kim
- Published
- 2023
- Full Text
- View/download PDF
49. Central nervous system manifestations of LRBA deficiency: case report of two siblings and literature review
- Author
-
Mangodt, T. C., Vanden Driessche, K., Norga, K. K., Moes, N., De Bruyne, M., Haerynck, F., Bordon, V., Jansen, A. C., and Jonckheere, A. I.
- Published
- 2023
- Full Text
- View/download PDF
50. ‘A radical operation’ – a thematic analysis of newspaper framing of bariatric surgery in adolescents
- Author
-
Lefere, Sander, Verghote, Kato, De Bruyne, Ruth, Provoost, Veerle, and Satalkar, Priya P.
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.