Argument Structure in TimeML

TimeML is a specification language for the annotation of events and temporal expressions in natural language text. In addition, the language introduces three relational tags linking temporal objects and events to one another. These links impose both aspectual and temporal ordering over time objects, as well as mark up subordination contexts introduced by modality, evidentiality, and factivity. Given the richness of this specification, the TimeML working group decided not to include the arguments of events within the language specification itself. Full reasoning and inference over natural language texts clearly requires knowledge of events along with their participants. In this paper, we define the appropriate role of argumenthood within event markup and propose that TimeML should make a basic distinction between arguments that are events and those that are entities. We first review how TimeML treats event arguments in subordinating and aspectual contexts, creating event-event relations between predicate and argument. As it turns out, these constructions cover a large number of the argument types selected for by event predicates. We suggest that TimeML be enriched slightly to include causal predicates, such as {it lead to}, since these also involve event-event relations. We propose that all other verbal arguments be ignored by the specification, and any predicate-argument binding of participants to an event should be performed by independent means. In fact, except for the event-denoting arguments handled by the extension to TimeML proposed here, almost full temporal ordering of the events in a text can be computed without argument identification

Solid-phase extraction and field-amplified sample injection-capillary zone electrophoresis for the analysis of benzophenone UV-filters in environmental water samples

A field amplified sample injection-capillary zone electrophoresis (FASI-CZE) method for the analysis of benzophenone (BP) UV-filters in environmental water samples was developed, allowing the separation of all compounds in less than 8 minutes. A 9- to 25-fold sensitive enhancement was obtained with FASI-CZE, achieving limits of detection down to 21-59 µg/L for most of the analyzed BPs, with acceptable run-to-run and day-to-day precisions (relative standard deviations lower than 17%). In order to remove water sample salinity and to enhance FASI sensitivity, an off-line solid-phase extraction (SPE) procedure using a Strata X polymeric reversed-phase sorbent was proposed, obtaining recoveries up to 72-90% for most of benzophenones. With the combination of off-line SPE and FASI-CZE, limits of detection in the range 0.06-0.6 µg/L in a river water matrix, representing a 2400- to 6500-fold enhancement, were obtained. Method performance was evaluated by quantifying a blank river water sample spiked at 1 µg/L. For a 95% confidence level, no statistical differences were observed between found concentrations and spiked concentrations (probability at the confidence level, p value, of 0.60), showing that the proposed off-line SPE-FASI-CZE method is suitable for the analysis of benzophenone UV-filters in environmental water samples at low µg/L levels. The method was successfully applied to the analysis of BPs in river water samples collected before and after industrialized and urban areas, and in some drinking water samples

Engineered microenvironments for synergistic VEGF - integrin signalling during vascularization

We have engineered polymer-based microenvironments that promote vasculogenesis both in vitro and in vivo through synergistic integrin-growth factor receptor signalling. Poly(ethyl acrylate) (PEA) triggers spontaneous organization of fibronectin (FN) into nanonetworks which provide availability of critical binding domains. Importantly, the growth factor binding (FNIII12-14) and integrin binding (FNIII9-10) regions are simultaneously available on FN fibrils assembled on PEA. This material platform promotes synergistic integrin/VEGF signalling which is highly effective for vascularization events in vitro with low concentrations of VEGF. VEGF specifically binds to FN fibrils on PEA compared to control polymers (poly(methyl acrylate), PMA) where FN remains in a globular conformation and integrin/GF binding domains are not simultaneously available. The vasculogenic response of human endothelial cells seeded on these synergistic interfaces (VEGF bound to FN assembled on PEA) was significantly improved compared to soluble administration of VEGF at higher doses. Early onset of VEGF signalling (PLCγ1 phosphorylation) and both integrin and VEGF signalling (ERK1/2 phosphorylation) were increased only when VEGF was bound to FN nanonetworks on PEA, while soluble VEGF did not influence early signalling. Experiments with mutant FN molecules with impaired integrin binding site (FN-RGE) confirmed the role of the integrin binding site of FN on the vasculogenic response via combined integrin/VEGF signalling. In vivo experiments using 3D scaffolds coated with FN and VEGF implanted in the murine fat pad demonstrated pro-vascularization signalling by enhanced formation of new tissue inside scaffold pores. PEA-driven organization of FN promotes efficient presentation of VEGF to promote vascularization in regenerative medicine applications

Where does purging disorder lie on the symptomatologic and personality continuum when compared to other eating disorder subtypes? Implications for the DSM

Objectives: To assess the clinical significance and distinctiveness of purging disorder (PD) from other eating disorder (ED) diagnoses. Method: Participants included 3127 women consecutively admitted to an ED treatment centre (246 PD, 465 anorexia nervosa restrictive [AN‐R], 327 AN‐binge purging [AN‐BP], 1436 bulimia nervosa [BN], 360 binge eating disorder [BED], 177 atypical AN and 116 unspecified feeding or eating disorder [UFED]) who were diagnosed according to DSM‐5 criteria. Additionally, 822 control participants were recruited from the community. All participants completed measures assessing ED symptoms (EDI‐2), general psychopathology (SCL‐90‐R) and personality (TCI‐R). Results: Patients with PD, when compared to controls, scored significantly higher on the EDI‐2 and SCL‐90‐R, and most TCI‐R dimensions. Most of the significant differences between PD and the other ED diagnoses emerged between PD and AN‐R, followed by Atypical‐AN, UFED, AN‐BP and BED, with patients with PD typically reporting higher scores on the EDI‐2 and SCL‐90‐R subscales. Significant differences between PD and BN were also present, but to a lesser extent. The findings for personality varied amongst the different ED diagnoses. Conclusions: PD is a clinically significant disorder, which seems to be more similar to BN than it is to AN and the other ED subtypes

Neuropsychological Learning Deficits as Predictors of Treatment Outcome in Patients with Eating Disorders

Eating disorders (EDs) are severe psychiatric illnesses that require individualized treatments. Decision-making deficits have been associated with EDs. Decision-making learning deficits denote a lack of strategies to elaborate better decisions that can have an impact on recovery and response to treatment. This study used the Iowa Gambling Task (IGT) to investigate learning differences related to treatment outcome in EDs, comparing between patients with a good and bad treatment outcome and healthy controls. Likewise, the predictive role of impaired learning performance on therapy outcome was explored. Four hundred twenty-four participants (233 ED patients and 191 healthy controls) participated in this study. Decision making was assessed using the Iowa Gambling Task before any psychological treatment. All patients received psychological therapy, and treatment outcome was evaluated at discharge. Patients with bad outcome did not show progression in the decision-making task as opposed to those with good outcome and the healthy control sample. Additionally, learning performance in the decision-making task was predictive of their future outcome. The severity of learning deficits in decision making may serve as a predictor of the treatment. These results may provide a starting point of how decision-making learning deficits are operating as dispositional and motivational factors on responsiveness to treatment in EDs

Brassica rapa hairy root based expression system leads to the production of highly homogenous and reproducible profiles of recombinant human alpha-L-iduronidase

International audienceThe Brassica rapa hairy root based expression platform, a turnip hairy root based expression system, is able to produce human complex glycoproteins such as the alpha—L—iduronidase (IDUA) with an activity similar to the one produced by Chinese Hamster Ovary (CHO) cells. In this article, a particular attention has been paid to the N‐ and O‐glycosylation that characterize the alpha‐L‐iduronidase produced using this hairy root based system. This analysis showed that the recombinant protein is characterized by highly homogeneous post translational profiles enabling a strong batch to batch reproducibility. Indeed, on each of the 6 N‐glycosylation sites of the IDUA, a single N‐glycan composed of a core Man3GlcNAc2 carrying one beta(1,2)‐xylose and one alpha(1,3)‐fucose epitope (M3XFGN2) was identified, highlighting the high homogeneity of the production system. Hydroxylation of proline residues and arabinosylation were identified during O‐glycosylation analysis, still with a remarkable reproducibility. This platform is thus positioned as an effective and consistent expression system for the production of human complex therapeutic proteins

Emotion regulation as a transdiagnostic factor in eating disorders and gambling disorder: Treatment outcome implications

Background: A first approach addressed to ascertain whether emotion regulation (ER) could be a transdiagnostic construct between eating disorders (EDs) and gambling disorder (GD) (through a joint clinical clustering analysis of both disorders) was performed by Munguia et al. (2021). Both conditions were represented by a severe, moderate, and low ER profile subgroups, according to the degree of ER difficulties. Results showed a linear relationship between the severity of ER difficulties and the severity of the disorder and the psychopathological state. Aims: Based on the aforementioned cross-sectional study, the objective of this longitudinal research was to explore the treatment response of the different ER subgroups. Methods: 459 adult patients (n = 277 ED; n =182 GD) were included. Several clinical variables, as well as outcome indicators (after completing 16 weeks of cognitive-behavioral therapy), were evaluated. Results: The three subgroups found in the previous cross-sectional study were taken for the performance of the present research. ED and GD distribution in each subgroup replicates the one exposed by Mungula et al. (2021), as well as their characterization, considering psychopathology, disorder severity and personality traits. The low ER subgroup reported a better response to treatment, whereas the severe group had the highest rates of non-remission and dropouts. Conclusions: Our results suggest that greater difficulties in ER lead to poorer treatment outcomes. Therefore, tailored treatments for patients with poor ER abilities would be recommended to improve adherence and treatment outcomes

Food addiction in anorexia nervosa: implications for the understanding of crossover diagnosis

Objective: Food addiction (FA) construct was introduced to reflect abnormal eating patterns that resemble behavioural ones found in substance use disorders. FA has been barely explored in anorexia nervosa (AN). This study evaluated FA occurrence and associated factors in a sample of patients with AN, distinguishing between restrictive and binge-purging subtypes and focussing on the influence of FA in the crossover diagnosis between them. Method: A sample of 116 patients with AN admitted for treatment seeking at an Bellvitge Hospital Eating Disorders Unit were included (72 restrictive [AN-R]; 44 binge-purge AN [AN-BP]), and eating-related, personality and psychopathological variables were assessed. Most participants were women (92.2%), mean age 27.1 years old (SD = 10.5). Results: FA was more prevalent in patients with AN-BP compared to the AN-R group (75.0% and 54.2%, respectively). The patients with AN-R FA+, presented more similar ED symptomatology, general psychopathology and personality traits, with the AN-BP patients, than with the AN-R FA-. Conclusions: Patients with AN-R FA+, exhibit more similarities with the AN-BP subgroup than with the AN-R FA-. Thus, it is possible to hypothesise that the presence of FA might be an indicator of the possible crossover from AN-R to AN-BP

Common and differential risk factors behind suicidal behavior in patients with impulsivity-related disorders: the case of bulimic spectrum eating disorders and gambling disorder

Background and aims: Mental disorders with high levels of impulsivity such as bulimic spectrum eating disorders (BSED) and gambling disorder (GD) are associated with high risk of suicidal behavior. The aim of the present study was to identify the common and differential vulnerability factors behind suicide attempts in a sample of patients with BSED compared to patients with GD. Methods: A total of 6,077 adults who sought treatment and met criteria either for BSED (n 5 2,391) or GD (n 5 3,686) were assessed at a specialized hospital unit. Personality traits, psychopathological symptomatology, lifetime history of suicide attempts and socio-demographic variables were evaluated. Results: The prevalence of suicide attempts was higher for BSED patients (26.2%) compared to GD patients (7.1%) being anorexia nervosa (Binge/Purge type) and bulimia nervosa the most affected subtypes. In the predictive model, the transdiagnostic vulnerability factors with the highest contribution to the risk of suicidal behavior both in BSED and GD were unemployment, early age of onset of the disorder, worse psychopathological state, and self-transcendence personality trait. However, specific risk factors for suicidal acts were identified in each disorder: longer duration of the disorder, lower education levels and reward dependence were exclusively associated with BSED while female gender, older age, and higher harm avoidance were associated with GD. Discussion: Patients with GD and BSED share certain vulnerability factors although certain factors are exclusive to each disorder. Conclusions: Interventions need to pay special attention to both common and specific vulnerability factors to mitigate the risk of suicidal acts in these disorders

DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma

Epigenetic deregulation has emerged as a driver in human malignancies. There is no clear understanding of the epigenetic alterations in hepatocellular carcinoma (HCC) and of the potential role of DNA methylation markers as prognostic biomarkers. Analysis of tumor tissue from 304 patients with HCC treated with surgical resection allowed us to generate a methylation-based prognostic signature using a training-validation scheme. Methylome profiling was done with the Illumina HumanMethylation450 array (Illumina, Inc., San Diego, CA), which covers 96% of known cytosine-phosphate-guanine (CpG) islands and 485,000 CpG, and transcriptome profiling was performed with Affymetrix Human Genome U219 Plate (Affymetrix, Inc., Santa Clara, CA) and miRNA Chip 2.0. Random survival forests enabled us to generate a methylation signature based on 36 methylation probes. We computed a risk score of mortality for each individual that accurately discriminated patient survival both in the training (221 patients; 47% hepatitis C-related HCC) and validation sets (n = 83; 47% alcohol-related HCC). This signature correlated with known predictors of poor outcome and retained independent prognostic capacity of survival along with multinodularity and platelet count. The subset of patients identified by this signature was enriched in the molecular subclass of proliferation with progenitor cell features. The study confirmed a high prevalence of genes known to be deregulated by aberrant methylation in HCC (e.g., Ras association [RalGDS/AF-6] domain family member 1, insulin-like growth factor 2, and adenomatous polyposis coli) and other solid tumors (e.g., NOTCH3) and describes potential candidate epidrivers (e.g., septin 9 and ephrin B2). Conclusions: A validated signature of 36 DNA methylation markers accurately predicts poor survival in patients with HCC. Patients with this methylation profile harbor messenger RNA-based signatures indicating tumors with progenitor cell features