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Toward dimensional body consciousness impairments in post-traumatic stress disorder and its dissociative subtype: a predictive processing approach
No full textInternational audienceCurrent models of post-traumatic stress disorder (PTSD) predominantly focus on emotional dysregulation, avoidance behaviors, and intrusive symptoms, with limited attention to disturbances in bodily self-consciousness. These frameworks do not fully account for how trauma may disrupt the integration of interoceptive and exteroceptive signals underlying the sense of embodied self. Building on recent advances in computational psychiatry, this review introduces a novel theoretical framework that differentiates between dissociative and non-dissociative forms of PTSD using the predictive processing paradigm. Body awareness, including the sense of body ownership (SBO) and the sense of agency (SoA), is framed within a Bayesian inference framework, where perception results from the interaction between prior beliefs and incoming sensory information. In non-dissociative PTSD, we suggest that hyperprecise trauma-related priors, coupled with increased interoceptive weighting due to amygdala and anterior insula hyperactivity, result in rigid self-representations and a diminished capacity for perceptual updating. Thus, we may consider PTSD as a state in which accuracy and reliability of cognitive processes are ranked as follows: [Prior > Interoception > Exteroception]. Conversely, in the dissociative PTSD subtype, emotional over-inhibition and anterior insula hypoactivity weaken priors and interoception, while exteroceptive inputs dominate. Therefore, we consider ranked cognitive processes in PTSD dissociative subtype as follows: [Exteroception > Interoception > Prior]. SoA impairements is specific to the dissociative subtype involving hyperactivity of the angular gyrus and glutamate hypofunction. On this basis, we propose an original dimensional model of body consciousness disruption across PTSD spectra. Therapeutic implications are explored, including top-down and bottom-up interventions
The association between collagen 1a1, NTproBNP and echocardiographic markers in patients with or at risk of HFpEF
No full textInternational audienceAim: Plasma collagen 1a1 (Col-1a1), part of the α1 chain of collagen type-1, may be a marker of fibrosis in patients with heart failure (HF) and at increased risk of HF. We assessed associations amongst Col-1a1, NT-proBNP and echocardiographic parameters of cardiac structure and function and their relationship to prognosis in HFpEF. Methods: We assessed 461 patients with HFpEF enrolled from the MEDIA-DHF cohort (mean age 74 [68, 80], 63 % women) and 516 those at risk of HF from the HOMAGE trial (mean age 73 [69, 79], 26 % women). Crude and adjusted linear regression models were used to evaluate the relationships amongst Col-1a1 (measured using proximity extension assay), NT-proBNP and echocardiographic measures. For the MEDIA-DHF study, the main outcome of interest was cardiovascular hospitalization and all-cause mortality. Results: In both cohorts, patients with higher Col-1a1 levels were more likely to have poorer renal function, lower hemoglobin, higher NT-proBNP and lower prevalence of diabetes. In the MEDIA-DHF cohort, higher Col-1a1 was associated with higher NT-proBNP (β = 1.39; 95 %CI 1.08-1.80; p = 0.012), left atrial volume index (LAVi) (β = 4.57; 95 %CI 1.00-8.14; p = 0.013) and pulmonary artery systolic pressure (PAPs) (ß = 4.42; 95 %CI 1.47-7.37; p = 0.004). These results were corroborated in the HOMAGE trial: higher Col-1a1 was associated with higher NT-proBNP (ß = 0.20; 95 %CI 0.05-0.34; p = 0.009) and LAVi (ß = 2.32; 95 %CI 0.25-4.39; p = 0.028). Col-1a1 was not associated with the risk of the composite outcome in the MEDIA-DHF cohort. Conclusion: Col-1a1 was associated with NT-proBNP and LAVi in HFpEF as well as in patients at high risk of HF but not with outcomes in HFpEF. Further studies are needed to understand what role, if any, Col-1a1 has as a marker of fibrosis or prognosis in patients with HFpEF.</div
Towards Pen-and-Paper-Style Equational Reasoning in Interactive Theorem Provers by Equality Saturation
No full textInternational audienceEquations are ubiquitous in mathematical reasoning. Often, however, they only hold under certain conditions. As these conditions are usually clear from context, mathematicians regularly omit them when performing equational reasoning on paper. In contrast, interactive theorem provers pedantically insist on every detail to be convinced that a theorem holds, hindering equational reasoning at the more abstract level of pen-andpaper mathematics. In this paper, we address this issue by raising the level of equational reasoning to enable pen-and-paper style in interactive theorem provers. We achieve this by interpreting theorems as conditional rewrite rules, and use equality saturation to automatically derive equational proofs. Conditions that cannot be automatically proven may be surfaced as proof obligations. Concretely, we present how to interpret theorems as conditional rewrite rules for a significant class of theorems. Handling these theorems goes beyond simple syntactic rewriting, and deals with aspects like propositional conditions and type classes. We evaluate our approach by implementing it as a tactic in Lean, using the egg library for equality saturation with e-graphs. We show four use cases demonstrating the efficacy of this higher level of abstraction for equational reasoning
Regioselective C-alkylation in a series of functionalized 1,2,3-triazoles: An unexpected preference over O-alkylation
No full textInternational audienceA series of novel 1,2,3-triazole derivatives were synthesized via Cu(I)-catalyzed click chemistry, introducing structural diversity at positions 1 and 4 of the triazole ring, to explore their reactivity toward alkylation. Attempts to perform O-alkylation on hydroxymethyl-substituted triazoles unexpectedly led to unreported regioselective C-alkylation at the methylene adjacent to the triazole ring. The C-alkylation was optimized using DBU and choline acetate in acetonitrile and subsequently examined across a range of alkyl and benzyl bromides to establish its scope and generality. The resulting racemic C-alkylated products were fully characterized, including confirmation of the regioselectivity by X-ray crystallography, and their enantiomers were separated by supercritical fluid chromatography. This work reveals a novel and synthetically valuable C-alkylation pathway for 1,2,3-triazoles, offering new opportunities for the development of structurally diverse and potentially bioactive triazole derivatives
Identifying high-risk relapse in early-stage I to II ovarian cancer using the CA125 ELIMination rate constant K (KELIM) score: a Gynecologic Cancer InterGroup individual patient-data meta-analysis.
No full textInternational audienceObjective: Despite curative surgery and adjuvant chemotherapy, a significant number of early stage I to II ovarian cancers relapse. The CA125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor intrinsic chemosensitivity in advanced epithelial ovarian cancer. We assessed the prognostic value of KELIM in patients with early-stage ovarian cancer, with respect to 5-year recurrence-free survival and overall survival, using the Meta-Analysis in Ovarian Cancer, which is the Gynecologic Cancer InterGroup individual patient-data meta-analysis of randomized trials evaluating different adjuvant chemotherapy regimens.Methods: Individual patient KELIM values were previously estimated in 5884 patients from the Meta-Analysis in Ovarian Cancer. The prognostic value of KELIM was assessed using univariable & multivariable analyses in patients with resected International Federation of Gynecology and Obstetrics stage I and II disease.Results: Overall, 1143 patients were identified, including clear cell (46.7%); serous (23.7%); endometrioid (12.4%); and mucinous carcinomas (3.9%). In multivariable analyses, a favorable KELIM score (≥1.0) was associated with higher 5-year recurrence-free survival (68.3% vs 55.9%; HR 0.61, 95% CI 0.48 to 0.77) and 5-year overall survival (80.7% vs 72.8%; HR 0.50, 95% CI 0.36 to 0.68), as was the histological sub-type. In exploratory analyses, KELIM score was a prognostic factor regarding 5-year recurrence-free survival and overall survival across all sub-types (especially clear cell carcinoma and serous, with HR ranging from 0.45 to 0.63) with baseline CA125 ≥15 IU/L, except for mucinous histology.Conclusions: The pragmatic KELIM score is an independent prognostic factor in patients with a non-mucinous stage I to II ovarian cancer optimally resected and treated with adjuvant chemotherapy. KELIM may help identify the patients at higher risk of relapse and death requiring closer follow-up or treatment intensification
Vascular homeostasis in suicidal behavior: from molecular mechanisms to clinical implications
No full textInternational audienceSuicidal behaviors (SB) remain a major global health challenge, reflecting persistent gaps in understanding their neurobiological underpinnings. The scarcity of validated biological markers for diagnosis, prediction, or treatment response impedes clinical progress. Emerging evidence implicates vascular dysregulation as a contributing factor in the pathophysiology of SB. This review critically synthesizes findings from clinical and preclinical studies to explore how disruptions in vascular homeostasis - including endothelial integrity, blood-brain barrier (BBB) permeability, platelet function, and microvascular flow - are associated with SB and related phenotypes. Epidemiological and genetic data further highlight shared vulnerability between SB and cardiovascular or neurovascular conditions. Additionally, individuals with SB exhibit signs of increased BBB permeability, platelet activation, nitric oxide dysregulation, altered kynurenine metabolism, elevated matrix metalloproteinase-9 activity, and white matter hyperintensities. These vascular disturbances may promote a pro-inflammatory and oxidative environment that impairs neuroplasticity, thereby heightening vulnerability to SB through cognitive and emotional dysregulation. Emerging molecular indicators of vascular dysfunction - such as claudin-5, thrombospondins, platelet-derived growth factors, and components of the nitric oxide system - show potential for improving diagnosis and guiding therapeutic development, though further replication is needed. While the current evidence remains preliminary and subject to limitations discussed herein, vascular dysfunction may serve as a dynamic indicator of both acute suicide risk and longer-term susceptibility. This review integrates vascular homeostasis into the broader biological framework of SB, alongside stress-response pathways, inflammation, and neural dysfunction, offering novel insights into SB pathophysiology and paving the way for developing targeted diagnostic tools and interventions
Immunization reveals a key role of Enterobacterial ClpB protein in the development of host anorexia
No full textInternational audienceAnorexia nervosa (AN) is a psychiatric disease of unknown etiology. Recently, caseinolytic protease B (ClpB), produced by Enterobacteriaceae, was identified as an antigen mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. Here, we studied the role of ClpB in the development of activity-based anorexia (ABA), a rodent model of AN. In two series of ClpB immunization experiments, we show that when ClpB was lowered by antibodies, mice were protected against ABA, showing lean mass preservation, an increase in food intake, and reduced feeding anticipatory activity. On the contrary, if antibody production was accompanied by an increase of ClpB, ABA was aggravated. A key role of anti-ClpB IgG in ABA protection was confirmed in ClpB-tolerized mice and by IgG inhibiting ClpB-and α-MSHactivation of melanocortin 4 receptor. ClpB immunization influenced clpB DNA abundance in ABA mice without affecting fecal microbiota diversity and energy content. These data support a key role of Enterobacterial ClpB as well as its control by the immune system in host anorexia and provide background for ClpB immunoneutralization as a putative biotherapy of AN
Improved Riemannian potato field: an Automatic Artifact Rejection Method for EEG
No full textInternational audienceElectroencephalography (EEG) signal cleaning has long been a critical challenge in the research community. The presence of artifacts can significantly degrade EEG data quality, complicating analysis and potentially leading to erroneous interpretations. While various artifact rejection methods have been proposed, the gold standard remains manual visual inspection by human experts—a process that is time-consuming, subjective, and impractical for large-scale EEG studies. Existing techniques are often hindered by a strong reliance on manual hyperparameter tuning, sensitivity to outliers, and high computational costs. In this paper, we introduce the improved Riemannian Potato Field (iRPF), a fast and fully automated method for EEG artifact rejection that addresses key limitations of current approaches. We evaluate iRPF against several state-of-the-art artifact rejection methods, using two publicly available EEG databases, labeled for various artifact types, comprising 226 EEG recordings. Our results demonstrate that iRPF outperforms all competitors across multiple metrics, with gains of up to 22% in recall, 102% in specificity, 54% in precision, and 24% in F1-score, compared to Isolation Forest, Autoreject, Riemannian Potato, and Riemannian Potato Field, respectively. Statistical analysis confirmed the significance of these improvements (p < 0.001) with large effect sizes (Cohen’s d > 0.8) in most comparisons. Additionally, on a typical EEG recording iRPF performs artifact cleaning in under 8 milliseconds per epoch using a standard laptop, highlighting its efficiency for large-scale EEG data processing and real-time applications. iRPF offers a robust and data-driven artifact rejection solution for high-quality EEG pre-processing in brain-computer interfaces and clinical neuroimaging applications
Selective Supra-Aortic Trunk Stenting During Endovascular Total Aortic Arch Repair in Patients With Residual Chronic Type A Dissection Treated With Double-Fenestrated Physician-Modified Endografts
No full textInternational audienceObjective: To assess the impact of selective supra-aortic trunk (SAT) stenting on aortic remodeling in patients with chronic type A aortic dissection (cTAAD). Methods: Patients treated from 2017 to 2024 with aortic arch repair using double-fenestrated physician-modified endografts (PMEGs) for cTAAD were retrospectively analyzed. The objectives are to compare aortic treatment and remodeling, SAT evolution, and overall outcomes according to SAT dissection status (before and after), total aortic arch repair using a double-fenestrated PMEG. Results: Among 42 cTAAD patients treated, 30 had SAT dissection. Thirty-five patients received a standard PMEG, while 7 underwent additional selective SAT stenting (3 LCCA, 1 brachiocephalic trunk (BT), 4 right subclavian artery (RSA), and 3 right common carotid artery (RCCA)). Technical success was 100%. At 30 days, 1 patient died from stroke, 1 from pneumonia post-discharge. During a median follow-up of 18.5 months (IQR: 38.8), no type Ia endoleaks occurred. Six type Ic endoleaks were observed; 3 patients underwent reintervention, while the remaining 3 were monitored with follow-up CT scans showing no evidence of aortic growth. Complete SAT dissection resolution occurred in 12 patients (40%), including 9 with standard PMEG. Positive aortic remodeling was seen in 32 patients (76%) with a median diameter reduction of −1% (IQR: 5.5%). Five patients died during mid-term follow-up, with no deaths related to the procedure. Positive aortic remodeling rates are 73% vs. 83% (p=0.7) between patients with and without initial SAT dissection, 83% vs 92% (p=1) between patients with initially no SAT dissection and those who healed, 61% vs 88% (p=0.07) between patients with persistent SAT dissection and the others. Patients on curative anticoagulation or dual antiplatelet therapy showed reduced positive remodeling. Conclusion: Double-fenestrated PMEGs are effective for treating residual cTAADs, with high SAT healing and favorable remodeling. Persistent SAT dissection may hinder remodeling and require additional intervention. Clinical Impact Aortic arch repair using fenestrated physician-modified endografts without systematic SAT stenting reduces SAT manipulation and may lower stroke risk, while promoting a high rate of SAT and aortic dissection healing. In cases where SAT dissection persists and aortic growth is reported, secondary complementary SAT intervention can be performed to enhance aortic remodeling
Neurocognitive Correlates of Food and Alcohol Disturbances: An Integrated Neuropsychological Investigation
No full textInternational audienceFood and Alcohol Disturbance (FAD) represents a functional relationship between alcohol use and eating behaviors, in which individuals engage in disordered eating to enhance alcohol intoxication and/or compensate for alcohol-related caloric intake. FAD is highly prevalent among young adults, particularly University students. While the biopsychosocial correlates of FAD are documented, its specific neurocognitive correlates remain unexplored, despite extensive literature describing the distinct neurocognitive correlates of alcohol consumption and eating disorders. We therefore investigated whether FAD is associated with neurocognitive correlates in university students and examined whether different FAD subdimensions relate to distinct cognitive profiles. We assessed FAD in 130 French university students using the CEBRACS scale and administered an extensive neuropsychological battery measuring visuospatial abilities, episodic memory, and executive functions. We compared cognitive performance between individuals who do and do not engage in FAD and then conducted exploratory multivariate regression analyses to identify variations in cognitive profiles across the CEBRACS subscales. The general comparison between individuals who do and do not engage in FAD did not reveal significant differences. Conversely, analyses of the CEBRACS subscales identified specific patterns: (1) dietary restraint was associated with poorer visuospatial abilities and verbal episodic memory; (2) purging behaviors were associated with lower executive functioning but improved visual episodic memory; (3) extreme fasting and self-induced vomiting were associated with poorer visual episodic memory performance but higher executive functioning. These findings suggest that FAD is an umbrella term encompassing various cognitive profiles according to the distinct eating behaviors involved and highlight the importance of considering the subcomponents of FAD when exploring its neurocognitive correlates