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A porohyperelastic scheme targeted at high-performance computing frameworks for the simulation of the intervertebral disc
(Elsevier, 2025) Lialios, Dimitrios; Eguzkitza, Ane Betriz; Houzeaux, Guillaume; Casoni, Eva; Baumgartner, Laura; Noailly, Jérôme; Muñoz-Moya, Estefano; Gantenbein, Benjamin; Vázquez, Mariano
Background and Objective: The finite element method is widely used for studying the intervertebral disc at the organ level due to its ability to model complex geometries. An indispensable requirement for proper modelling of the intervertebral disc is a reliable porohyperelastic framework that captures the elaborate underlying mechanics. The increased complexity of such models requires significant computational power that is available within high-performance computing systems. The objective of this study is to present such a framework, validated both against literature and experiments, aiming to enable intervertebral disc research to benefit from state-of-the-art computational resources. Methods: In the context of this work, we implement a biphasic model that captures the mechanical response of the intricate, tissue-dependent models of the solid phase along with the hydrostatic pressure effects of the fluid phase. The tissue-dependent models involve the hyperelastic ground substance, fibrillar reinforcement, and osmotic swelling. The derived porohyperelastic, staggered scheme is implemented in Alya, a finite element code targeted at high-performance computing applications. The formulation is subsequently verified and validated by comparing the results of consolidation simulations with literature data for simulations and experiments using either generic or patient-specific geometries. Additionally, in-house experiments are replicated, evaluating the model’s ability to simulate alternating loading. Finally, the implementation’s circadian response is compared to previous implementation of similar material models in commercial software. Results: Results align well with experimental and literature findings in terms of disc height reduction (4% error), intradiscal pressure (14% error) and disc bulging. Validating the patient-specific geometry results in 4% and 7% deviation in measuring height loss. Simulations show excellent agreement with in-house experimental results, with less than 1% error regarding height reduction. Finally, the comparison to similar, published, earlier implementation in commercial software unveils excellent agreement of less than 1% error for the water content during circadian simulations. Simulation times are reported at 4 min per circadian cycle in the supercomputer Marenostrum V. Conclusions: This work presents a clear and validated formulation for simulating porohyperelastic materials based on assumptions that comply with the non-linear elasticity theory. The implementation in Alya enables intervertebral disc research to benefit from high-performance computing systems.
Parallel networks to predict TIMP and protease cell activity of nucleus pulposus cells exposed and not exposed to pro-inflammatory cytokines
(Wiley, 2025) Baumgartner, Laura; Witta, Sandra; Noailly, Jérôme
Background. Intervertebral disc (IVD) degeneration is characterized by a disruption of the balance between anabolic and catabolic cellular processes. Within the nucleus pulposus (NP), this involves increased levels of the pro-inflammatory cytokines interleukin 1beta (IL1B) and tumor necrosis factor (TNF) and an upregulation of the protease families matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). Primary inhibitors of these proteases are the tissue inhibitors of matrix metalloproteinases (TIMP). This work aims at contributing to a better understanding of the dynamics among proteases, TIMP, and pro-inflammatory cytokines within the complex, multifactorial environment of the NP. Methods. The Parallel Network (PN)-Methodology was used to estimate relative mRNA expressions of TIMP1–3, MMP3, and ADAMTS4 for five simulated human activities: walking, sitting, jogging, hiking with 20 kg extra weight, and exposure to high vibration. Simulations were executed for nutrient conditions in non- and early-degenerated IVD approximations. To estimate the impact of cytokines, the PN-Methodology inferred relative protein levels for IL1B and TNF, reintegrated as secondary stimuli into the network. Results. TIMP1 and TIMP2 expressions were found to be overall lower than TIMP3 expression. In the absence of pro-inflammatory cytokines, MMP3 and/or ADAMTS4 expressions were strongly downregulated in all conditions but vibration and hiking with extra weight. Pro-inflammatory cytokine exposure resulted in an impaired inhibition of MMP3, rather than of ADAMTS4, progressively rising with increasing nutrient deprivation. TNF mRNA was less expressed than IL1B. However, at the protein level, TNF was mainly responsible for the catabolic shift in the simulated pro-inflammatory environment. Overall, results agreed with previous experimental findings. Conclusions. The PN-Methodology successfully allowed the exploration of the relative dynamics of TIMP and protease regulations in different mechanical, nutritional, and inflammatory environments in the NP. It shall stand as a comprehensive tool to integrate in vitro model results in IVD research and approximate NP cell activities in complex multifactorial environments.
Ex vivo and in vitro proteomic approach to elucidate the relevance of IL-4 and IL-10 in intervertebral disc pathophysiology
(Wiley, 2025) Bermúdez-Lekerika, Paola; Tseranidou, Sofia; Kanelis, Exarchos; Nüesch, Andrea; Crump, Katherine B.; Alexopoulos, Leonidas G.; Wuertz-Kozak, Karin; Noailly, Jérôme; Le Maitre, Christine L.; Gantenbein, Benjamin
Background. This study investigates the native presence and potential anabolic effects of interleukin (IL)-4 and IL-10 in the human intervertebral disc (IVD). Methods. Human nucleus pulposus (NP) cells cultured in 3D from trauma and degenerate IVDs and NP explants were stimulated with 10 ng/mL IL-4, IL-10, or each in combination with 1 ng/mL IL-1β stimulation. The role of IL-4 and IL-10 in the IVD was evaluated using immunohistochemistry, gene expression, and Luminex multiplex immunoassay proteomics (73 secreted) and phosphoproteomics (21 phosphorylated proteins). Results. IL-4, IL-4R, and IL-10R expression and localization in human cartilage endplate tissue were demonstrated for the first time. No significant gene expression changes were noted under IL-4 or IL-10 stimulation. However, IL-1β stimulation significantly increased MMP3, COX2, TIMP1, and TRPV4 expression in NP cells from trauma IVDs. Combined IL-4 and IL-1β treatment induced a significant increase in protein secretion of IL-1α, IL-7, IL-16, IL-17F, IL-18, IFNγ, TNF, ST2, PROK1, bFGF2, and stem cell factor exclusively in NP cells from degenerated IVDs. Conversely, the secretome profile of explants revealed an IL-4–mediated decrease in CXCL13 following treatment with IL-1β. Combined IL-10 and IL-1β treatment increased neurotrophic growth factor secretion compared with IL-10 baseline. Conclusions. The NP cell phenotype affects the pleiotropic role of IL-4, which can induce a pro-inflammatory response in the presence of catabolic stimuli and enhance the effects of IL-1β in degenerated IVDs. Environmental factors, including 3D culture and hypoxia, may alter IL-4's role. Finally, IL-10's potential neurotrophic effects under catabolic stimuli warrant further investigation to clarify its role in IVD degeneration.
Nucleus pulposus cell network modelling in the intervertebral disc
(Nature Research, 2025) Tseranidou, Sofia; Segarra-Queralt, Maria; Chemorion, Francis Kiptengwer; Le Maitre, Christine L.; Piñero González, Janet, 1977-; Noailly, Jérôme
Intervertebral disc degeneration (IDD) results from an imbalance between anabolic and catabolic processes in the extracellular matrix (ECM). Due to complex biochemical interactions, a comprehensive understanding is needed. This study presents a regulatory network model (RNM) for nucleus pulposus cells (NPC), representing normal intervertebral disc (IVD) conditions. The RNM includes 33 proteins, and 153 interactions based on literature, incorporating key NPC regulatory mechanisms. A semi-quantitative approach calculates the basal steady state, accurately reflecting normal NPC activity. Model validation through published studies replicated pro-catabolic and pro-anabolic shifts, emphasizing the roles of transforming growth factor beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra) in ECM regulation. This IVD RNM is a valuable tool for predicting IDD progression, offering insights into ECM degradation mechanisms and guiding experimental research on IVD health and degeneration.
A magnetic resonance image based atlas of the rabbit brain for automatic parcellation
(Public Library of Science (PLoS), 2013) Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Batalle, Dafnis; Soria Rodríguez, Guadalupe; Illa, Miriam; Prats-Galino, Alberto; Eixarch, Elisenda; Gratacós Solsona, Eduard
Rabbit brain has been used in several works for the analysis of neurodevelopment. However, there are not specific digital rabbit brain atlases that allow an automatic identification of brain regions, which is a crucial step for various neuroimage analyses, and, instead, manual delineation of areas of interest must be performed in order to evaluate a specific structure. For this reason, we propose an atlas of the rabbit brain based on magnetic resonance imaging, including both structural and diffusion weighted, that can be used for the automatic parcellation of the rabbit brain. Ten individual atlases, as well as an average template and probabilistic maps of the anatomical regions were built. In addition, an example of automatic segmentation based on this atlas is described.
PretoxTM: a text mining system for extracting treatment-related findings from preclinical toxicology reports
(BioMed Central, 2025) Corvi, Javier; Ronzano, Francesco; Centeno, Emilio; Capella Gutiérrez, Salvador Jesús, 1985-
Over the last few decades the pharmaceutical industry has generated a vast corpus of knowledge on the safety and efficacy of drugs. Much of this information is contained in toxicology reports, which summarise the results of animal studies designed to analyse the effects of the tested compound, including unintended pharmacological and toxic effects, known as treatment-related findings. Despite the potential of this knowledge, the fact that most of this relevant information is only available as unstructured text with variable degrees of digitisation has hampered its systematic access, use and exploitation. Text mining technologies have the ability to automatically extract, analyse and aggregate such information, providing valuable new insights into the drug discovery and development process. In the context of the eTRANSAFE project, we present PretoxTM (Preclinical Toxicology Text Mining), the first system specifically designed to detect, extract, organise and visualise treatment-related findings from toxicology reports. The PretoxTM tool comprises three main components: PretoxTM Corpus, PretoxTM Pipeline and PretoxTM Web App. The PretoxTM Corpus is a gold standard corpus of preclinical treatment-related findings annotated by toxicology experts. This corpus was used to develop, train and validate the PretoxTM Pipeline, which extracts treatment-related findings from preclinical study reports. The extracted information is then presented for expert visualisation and validation in the PretoxTM Web App. Scientific Contribution While text mining solutions have been widely used in the clinical domain to identify adverse drug reactions from various sources, no similar systems exist for identifying adverse events in animal models during preclinical testing. PretoxTM fills this gap by efficiently extracting treatment-related findings from preclinical toxicology reports. This provides a valuable resource for toxicology research, enhancing the efficiency of safety evaluations, saving time, and leading to more effective decision-making in the drug development process.
Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis
(Elsevier, 2024) Clària, Joan; Marcos Fa, Xavi; Giarracco, Emma; Cerutti, Andrea, 1965-; Moreau, Richard
Background & aims: Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections. Methods: Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV). Bulk and single-cell RNA sequencing (scRNA-seq) and flow cytometry were performed in peripheral blood mononuclear cells (PBMCs) from 20 patients with AD cirrhosis and 34 HV exposed to albumin. Albumin's effects on degranulation, phagocytosis, chemotaxis, and swarming of neutrophils from six patients with AD cirrhosis and nine HV were assessed by measuring myeloperoxidase enzymatic activity, the engulfment of fluorescent-labeled Escherichia coli and zymosan, and interactions of neutrophils with Candida albicans at single-cell resolution in microfluidic chambers, respectively. Whole blood RNA sequencing (RNA-seq) analyses were performed in 49 patients admitted for severe AD cirrhosis, of whom 30 received albumin during hospitalization. Results: Compared with HV, patients with AD cirrhosis showed severe lymphopenia and defective neutrophil antimicrobial function. Bulk and scRNA-seq analyses revealed significantly (false discovery rate [FDR] <0.05) increased signatures related to B cells, myeloid cells, and CD4+ T cells in PBMCs incubated with albumin. Changes in the B cell population were confirmed by flow cytometry. Neutrophils exposed to albumin also exhibited augmented chemotactic and degranulation responses, enhanced phagocytosis, and increased pathogen-restrictive swarming. RNA-seq data analysis in patients who had received albumin revealed specific upregulation of signatures related to B cells and neutrophils together with transcriptional changes in CD4+ T cells (FDR <0.05). Conclusions: The finding that albumin promotes the transcriptional reprogramming and expansion of the B cell compartment and improves neutrophil antimicrobial functions indicates mechanisms that may lower the incidence of infections in patients with severe AD cirrhosis receiving albumin therapy. Impact and implications: Patients with acutely decompensated cirrhosis receiving albumin as treatment have a lower incidence of infections. The reason for this protection is currently unknown, but the present study provides data that support the ability of albumin to boost the antimicrobial functions of immune cells in these patients. Moreover, these findings encourage the design of controlled clinical studies specifically aimed at investigating the effects of albumin administration on the immune system.
Social media feedback and extreme opinion expression
(PLOS, 2023) Konovalova, Elizaveta; Le Mens, Gaël; Schöll, Nikolas
On popular social media platforms such as Twitter, Facebook, Instagram, or Tiktok, the quantitative feedback received by content producers is asymmetric: counts of positive reactions such as 'likes,' or 'retweets,' are easily observed but similar counts of negative reactions are not directly available. We study how this design feature of social media platforms affects the expression of extreme opinions. Using simulations of a learning model, we compare two feedback environments that differ in terms of the availability of negative reaction counts. We find that expressed opinions are generally more extreme when negative reaction counts are not available than when they are. We rely on analyses of Twitter data and several online experiments to provide empirical support for key model assumptions and test model predictions. Our findings suggest that a simple design change might limit, under certain conditions, the expression of extreme opinions on social media.
Astroglial reactivity is a key modulator of Alzheimer's disease pathological progression
(Oxford University Press, 2024) Pelkmans, Wiesje; Gispert López, Juan Domingo
This scientific commentary refers to 'Association of glial fibrillary acid protein, Alzheimer's disease pathology and cognitive decline' by Peretti et al. (https://doi.org/10.1093/brain/awae211).
M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s disease
(eLife, 2020) Fernández-García, Sara; Conde-Berriozabal, Sara; García-García, Esther; Gort-Paniello, Clara; Bernal-Casas, David; García-Díaz Barriga, Gerardo; López-Gil, Xavier; Muñoz-Moreno, Emma; Soria Rodríguez, Guadalupe; Campa, Leticia; Artigas, Francesc; Rodríguez, Manuel José; Alberch, Jordi; Masana, Mercè
Huntington’s disease (HD) is a neurological disorder characterized by motor disturbances. HD pathology is most prominent in the striatum, the central hub of the basal ganglia. The cerebral cortex is the main striatal afferent, and progressive cortico-striatal disconnection characterizes HD. We mapped striatal network dysfunction in HD mice to ultimately modulate the activity of a specific cortico-striatal circuit to ameliorate motor symptoms and recover synaptic plasticity. Multimodal MRI in vivo indicates cortico-striatal and thalamo-striatal functional network deficits and reduced glutamate/glutamine ratio in the striatum of HD mice. Moreover, optogenetically-induced glutamate release from M2 cortex terminals in the dorsolateral striatum (DLS) was undetectable in HD mice and striatal neurons show blunted electrophysiological responses. Remarkably, repeated M2-DLS optogenetic stimulation normalized motor behavior in HD mice and evoked a sustained increase of synaptic plasticity. Overall, these results reveal that selective stimulation of the M2-DLS pathway can become an effective therapeutic strategy in HD.
The effect of age and sex on brain metabolites: from childhood to adulthood
(Elsevier, 2025) Ortuño, María; Fortea, Adriana; Valli, Isabel; Muñoz-Moreno, Emma; Borràs, Roger; Martínez-Serrano, Irene; Masias Bruns, Mireia; Camprodon-Boadas, Patricia; Vilajosana, Enric; Fortea, Lydia; Raduà, Joaquim; Serna, Elena de la; Baeza, Inmaculada; Castro-Fornieles, Josefina; Sugranyes, Gisela
Abnormalities in the concentration of brain metabolites have been found across neuropsychiatric conditions. This cross-sectional study set out to examine the relationship between levels of neurometabolites and age and sex —key modulators of brain function and structure—, continuously from childhood to early adulthood, in areas relevant to the study of psychiatric disorders. Magnetic resonance spectroscopy (¹H MRS) data was acquired in the dorsomedial prefrontal region (dmPF) and the medial temporal lobe (mTL) in 128 healthy individuals aged 7 to 34 years, 68.5 % females (ndmPF = 124; nmTL = 75). Absolute concentrations of glutamate (Glu), glutamate and glutamine (Glx), myo-inositol (mIns), N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), glycerophosphocholine and phosphocholine (tCho), and creatine and phosphocreatine (tCr) were determined, and tested for the effects of age, sex and their interaction. In the dmPF, there were linear, age-related decreases in Glu and Glx. The association between levels of both tNAA and tCr and age adjusted to a quadratic model, consisting of a positive association until ages 20.79 and 22.82, respectively, and a negative relationship thereafter. There was a significant effect of sex in the mTL, whereby concentrations of Glu, Glx and mIns were lower in females than in males. No age by sex interactions were detected. These findings highlight the importance of accounting for both linear and non-linear age-related effects and for the potential effect of sex when interpreting disease-related differences in ¹H MRS-quantified metabolites from childhood through to adulthood.
Poisson-like spiking in circuits with probabilistic synapses
(Public Library of Science (PLoS), 2014) Moreno-Bote, Rubén
Neuronal activity in cortex is variable both spontaneously and during stimulation, and it has the remarkable property that it is Poisson-like over broad ranges of firing rates covering from virtually zero to hundreds of spikes per second. The mechanisms underlying cortical-like spiking variability over such a broad continuum of rates are currently unknown. We show that neuronal networks endowed with probabilistic synaptic transmission, a well-documented source of variability in cortex, robustly generate Poisson-like variability over several orders of magnitude in their firing rate without fine-tuning of the network parameters. Other sources of variability, such as random synaptic delays or spike generation jittering, do not lead to Poisson-like variability at high rates because they cannot be sufficiently amplified by recurrent neuronal networks. We also show that probabilistic synapses predict Fano factor constancy of synaptic conductances. Our results suggest that synaptic noise is a robust and sufficient mechanism for the type of variability found in cortex.
Relation between belief and performance in perceptual decision making
(Public Library of Science (PLoS), 2014) Drugowitsch, Jan; Moreno-Bote, Rubén; Pouget, Alexandre
In an uncertain and ambiguous world, effective decision making requires that subjects form and maintain a belief about the correctness of their choices, a process called meta-cognition. Prediction of future outcomes and self-monitoring are only effective if belief closely matches behavioral performance. Equality between belief and performance is also critical for experimentalists to gain insight into the subjects' belief by simply measuring their performance. Assuming that the decision maker holds the correct model of the world, one might indeed expect that belief and performance should go hand in hand. Unfortunately, we show here that this is rarely the case when performance is defined as the percentage of correct responses for a fixed stimulus, a standard definition in psychophysics. In this case, belief equals performance only for a very narrow family of tasks, whereas in others they will only be very weakly correlated. As we will see it is possible to restore this equality in specific circumstances but this remedy is only effective for a decision-maker, not for an experimenter. We furthermore show that belief and performance do not match when conditioned on task difficulty – as is common practice when plotting the psychometric curve – highlighting common pitfalls in previous neuroscience work. Finally, we demonstrate that miscalibration and the hard-easy effect observed in humans' and other animals' certainty judgments could be explained by a mismatch between the experimenter's and decision maker's expected distribution of task difficulties. These results have important implications for experimental design and are of relevance for theories that aim to unravel the nature of meta-cognition.
The evolution of facultative symbiosis in stony corals
(Nature Research, 2025) Levy, Shani; Grau Bové, Xavier; Kim, Iana V.; Najle, Sebastián R.; Ksiezopolska, Ewa; Elek, Anamaria; Montes-Espuña, Laia; Montgomery, Sean A.; Mass, Tali; Sebé-Pedrós, Arnau
Most stony corals are obligate symbionts that are dependent on nutrients provided by the photosynthetic activity of dinoflagellates residing within specialized cells1. Disruption of this symbiotic consortium leads to coral bleaching and, ultimately, mortality2. However, a few coral species exhibit facultative symbiosis, allowing them to survive extended periods of bleaching3,4. Despite this resilience, the underlying biological mechanisms remain poorly understood. Here we investigate the genomic and cellular basis of facultative symbiosis in Oculina patagonica, a thermotolerant Mediterranean coral5,6. We sequenced and annotated a chromosome-scale genome of O. patagonica and built cell atlases for this species and two obligate symbiotic corals. Comparative genomic analysis revealed karyotypic and syntenic conservation across all scleractinians, with species-specific gene expansions primarily driven by tandem duplications. Single-cell transcriptomic profiling of symbiotic and naturally aposymbiotic wild specimens identified an increase in phagocytic immune cells and a metabolic shift in gastrodermal gene expression from growth-related functions to quiescent, epithelial-like states. Cross-species comparison of host cells uncovered Oculina-specific metabolic and signalling adaptations indicative of an opportunistic, dual-feeding strategy that decouples survival from symbiotic state.
A single composite index of semantic behavior tracks symptoms of psychosis over time
(Elsevier, 2025) Palominos, Claudio; Kyrdum, Maryia ; Nikzad, Amir H.; Spilka, Michael J.; Homan, Philipp; Sommer, Iris E.; Tang, Sunny X.; Hinzen, Wolfram
Semantic variables automatically extracted from spontaneous speech characterize anomalous semantic associations generated by groups with schizophrenia spectrum disorders (SSD). However, with the use of different language models and numerous aspects of semantic associations that could be tracked, the semantic space has become very high-dimensional, challenging both theoretical understanding and practical applications. This study aimed to summarize this space into a single composite semantic index and to test whether it can track diagnosis and symptom profiles over time at an individual level. The index was derived from a principal component analysis (PCA) yielding a linear combination of 117 semantic variables. It was tested in discourse samples of English speakers performing a picture description task, involving a total of 103 individuals with SSD and 36 healthy controls (HC) compared across four time points. Results showed that the index distinguished between SSD and HC groups, identified transitions from acute psychosis to remission and stabilization, predicted the sum of scores of the Thought, Language and Communication (TLC) index as well as subscores, capturing 65 % of the variance in the sum of TLC scores. These findings show that a single indicator meaningfully summarizes a shift in semantic associations in psychosis and tracks symptoms over time, while also pointing to variance unexplained, which is likely covered by other semantic and non-semantic factors.
Silent brain ischemia within the TAXINOMISIS framework: association with clinical and advanced ultrasound metrics
(Frontiers, 2024) Kigka, Vassiliki; Gramegna, Laura Ludovica; TAXINOMISIS Silent Ischemia Working Group
Introduction: The relationship between carotid artery stenosis (CAS) and ipsilateral silent brain ischemia (SBI) remains unclear, with uncertain therapeutic implications. The present study, part of the TAXINOMISIS project (nr. 755,320), aimed to investigate SBIs in patients with asymptomatic CAS, correlating them with clinical, carotid ultrasonographic data, and CFD analyses. Methods: The TAXINOMISIS clinical trial study (nr. NCT03495830) involved six vascular surgery centers across Europe, enrolling patients with asymptomatic and symptomatic CAS ranging from 50 to 99%. Patients underwent carotid ultrasound and magnetic resonance imaging (MRI), including brain diffusion-weighted, T2-weighted/FLAIR, and T1-weighted sequences. Brain MRI scans were analyzed for the presence of SBI according to established definitions. Ultrasound assessments included Doppler and CFD analysis. Only asymptomatic patients were included in this substudy. Results: Among 195 asymptomatic patients, the mean stenosis (NASCET) was 64.1%. Of these, a total of 33 patients (16.9%) had at least one SBI detected on a brain MRI scan. Specifically, 19 out of 33 patients (57.6%) had cortical infarcts, 4 out of 33 patients (12.1%) had ipsilateral lacunar infarcts, 6 out of 33 patients had (18.2%) subcortical infarcts, 1 out of 33 patients (3.0%) had both cortical and lacunar infarcts, and 3 out of 33 patients (9.1%) both cortical and subcortical infarcts. Patients with SBIs exhibited significantly higher risk factors, including a higher body mass index (28.52 ± 9.38 vs. 26.39 ± 3.35, p = 0.02), diastolic blood pressure (80.87 ± 15.73 mmHg vs. 80.06 ± 8.49 mmHg, p = 0.02), creatinine levels (93.66 ± 34.61 μmol/L vs. 84.69 ± 23.67 μmol/L, p = 0.02), and blood triglycerides (1.8 ± 1.06 mmol/L vs. 1.48 ± 0.78 mmol/L, p = 0.03). They also had a higher prevalence of cardiovascular interventions (29.6% vs. 13.8%, p = 0.04), greater usage of third/fourth-line antihypertensive treatment (50%vs16%, p = 0.03), and anticoagulant medications (60% vs. 16%, p = 0.01). Additionally, the number of contralateral cerebral infarcts was higher in patients with SBIs (35.5% vs. 13.4%, p < 0.01). Moreover, carotid ultrasound revealed higher Saint Mary’s ratios (15.33 ± 12.45 vs. 12.96 ± 7.99, p = 0.02), and CFD analysis demonstrated larger areas of low wall shear stress (WSS) (0.0004 ± 0.0004 m2 vs. 0.0002 ± 0.0002 m2, p < 0.01). Conclusion: The TAXINOMISIS clinical trial provides valuable insights into the prevalence and risk factors associated with SBIs in patients with moderate asymptomatic carotid stenosis. The findings suggest that specific hemodynamic and arterial wall characteristics may contribute to the development of silent brain infarcts.
Neurodevelopmental disorders: 2024 update
(University of Münster, 2024) Martínez de Lagrán Cabredo, María; Bascón-Cardozo, Karen; Dierssen, Mara
Neurodevelopmental disorders encompass a range of conditions such as intellectual disability, autism spectrum disorder, rare genetic disorders and developmental and epileptic encephalopathies, all manifesting during childhood. Over 1,500 genes involved in various signaling pathways, including numerous transcriptional regulators, spliceosome elements, chromatin-modifying complexes and de novo variants have been recognized for their substantial role in these disorders. Along with new machine learning tools applied to neuroimaging, these discoveries facilitate genetic diagnoses, providing critical insights into neuropathological mechanisms and aiding in prognosis, and precision medicine. Also, new findings underscore the importance of understanding genetic contributions beyond protein-coding genes and emphasize the role of RNA and non-coding DNA molecules but also new players, such as transposable elements, whose dysregulation generates gene function disruption, epigenetic alteration, and genomic instability. Finally, recent developments in analyzing neuroimaging now offer the possibility of characterizing neuronal cytoarchitecture in vivo, presenting a viable alternative to traditional post-mortem studies. With a recently launched digital atlas of human fetal brain development, these new approaches will allow answering complex biological questions about fetal origins of cognitive function in childhood. In this review, we present ten fascinating topics where major progress has been made in the last year.
Breast imaging readers' performance in the PERFORMS test-set based assessment scheme within the MyPeBS international randomised study
(Elsevier, 2025) Michalopoulou, Eleni; Darker, Iain; Iotti, Valentina; Slonim, Efrat; de Koning, Harry J.; Alcantara Souza, Rodrigo; Burrion, Jean-Benoit; de Montgolfier, Sandrine; Vissac-Sabatier, Cécile; Guindy, Michal; Pattacini, Pierpaolo; Delaloge, Suzette; Gilbert, Fiona J.; Chen, Yan; MyPeBS Consortium
Purpose: A survey conducted by the European Society of Breast Imaging (EUSOBI) in 2023 revealed significant variations in Quality Assurance (QA) practices across Europe. The UK encourages regular performance monitoring for screen readers. This study aimed to assess the variability in diagnostic performance among readers participating in a wider prospective randomised trial across multiple countries. Method: In this retrospective multinational study, breast imaging readers from the MyPeBS clinical trial examined a test set of 40 challenging breast screening cases using the PERFORMS software, from March 2021 to February 2022. The challenging set, enriched with biopsy-proven cancers, aimed to differentiate readers by their level of diagnostic performance. Cancer detection and correct return to screen rates were calculated for each participant. Results: A total of 110 readers from 6 countries completed the PERFORMS test set, while 88 also completed an accompanying questionnaire collecting information about their breast screening work and experience. The study revealed variability in cancer detection rates (M = 73.6 %, SD = 19.7 %, range 0.0 %-100.0 %) and correct return to screen rates (M = 79.7 %, SD = 10.5 %, range 46.4 %-100.0 %). Outliers with extremely low cancer detection (2.7 % of participants) and correct return to screen rates (1.8 % of participants) were also identified. Conclusions: Breast imaging readers' performance in test set-based assessments like PERFORMS can reflect real-world screening proficiency. The presence of outlier readers with low diagnostic performance on the test highlights the need for double reading and for standardised QA protocols to ensure patient safety and service efficiency.
Urinary tartaric acid as a biomarker of wine consumption and cardiovascular risk: the PREDIMED trial
(Oxford University Press, 2025) Domínguez-López, Inés; Lamuela-Raventós, Rosa M.; Razquin, Cristina; Arancibia-Riveros, Camila; Galkina, Polina; Salas Salvadó, Jordi; Alonso-Gómez, Ángel; Fitó Colomer, Montserrat; Fiol, Miquel; Lapetra, José; Gómez-Gracia, Enrique; Sorlí, José Vicente; Ruiz-Canela, Miguel; Castañer, Olga; Liang, Liming; Serra-Majem, Luis; Hu, Frank B.; Ros, Emilio; Martínez-González, Miguel Ángel, 1957-; Estruch, Ramón
Background and aims: Moderate wine consumption has been associated with lower cardiovascular disease (CVD) risk in older populations. However, wine consumption information through self-reports is prone to measurement errors inherent to subjective assessments. The aim of this study was to evaluate the association between urinary tartaric acid, an objective biomarker of wine consumption, and the rate of a composite clinical CVD event. Methods: A case-cohort nested study was designed within the PREDIMED trial with 1232 participants: 685 incident cases of CVD and a random subcohort of 625 participants (including 78 overlapping cases). Wine consumption was registered using validated food frequency questionnaires. Liquid chromatography-tandem mass spectrometry was used to measure urinary tartaric acid at baseline and after one year of intervention. Weighted Cox regression models were used to estimate hazard ratios (HRs) of CVD. Results: Tartaric acid was correlated with self-reported wine consumption at baseline [r = 0.46 (95% CI 0.41; 0.50)]. Five categories of post hoc urinary tartaric acid excretion were used for better representation of risk patterns. Concentrations of 3-12 and 12-35 μg/mL, which reflect ∼3-12 and 12-35 glasses/month of wine, were associated with lower CVD risk [HR 0.62 (95% CI 0.38; 1.00), P = .050 and HR 0.50 (95% CI 0.27; 0.95), P = .035, respectively]. Less significant associations between self-reported wine consumption and CVD risk were observed. Conclusions: Light-to-moderate wine consumption, measured through an objective biomarker (tartaric acid), was prospectively associated with lower CVD rate in a Mediterranean population at high cardiovascular risk.
Connectomics to semantomics: addressing the brain's big data challenge
(Elsevier, 2015) Arsiwalla, Xerxes D.; Dalmazzo, David; Zucca, Riccardo; Betella, Alberto; Brandi Hernández, Santiago; Martínez Bueno, Enrique; Omedas, Pedro; Verschure, Paul F. M. J.
Can semantic corpora be coupled to dynamical simulations in such a way so as to extract new associations from the data that were hitherto unapparent? We attempt to do this within neuroscience as an application domain, by introducing the notion of the semantome and coupling it to the connectome of the human brain network. This is implemented using BrainX3, a virtual reality simulation cum data mining platform that can be used for visualization, analysis and feature extraction of neuroscience data. We use this system to explore anatomical, functional and symptomatic semantics associated to simulated neuronal activity of a healthy brain, one with stroke and one perturbed by transcranial magnetic stimulation. In particular, we find that parietal and occipital lesions in stroke affect the visual processing pathway leading to symptoms such as visual neglect, depression and photo-sensitivity seizures. Integrating semantomics with connectomics thus generates hypotheses about symptoms, functions and brain activity that supplement existing tools for diagnosis of mental illness. Our results suggest a new approach to big data with potential applications to other domains.

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