HAL Université de Tours
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Drugs associated with behavioral addictions: Real world analysis using the WHO pharmacovigilance database
No full textInternational audienceObjectivesBehavioral addictions (BA) are a newly recognized diagnostic entity. While some drugs are known to induce BA, some of them remains unknown. The aim of this study was to identify drugs for which B is not listed in the summaries of product characteristics.MethodsWe conducted a search on Vigibase to identify health professional's cases where drugs are “suspect” coded with the following preferred terms: (1) ‘behavioral addiction’, (2) ‘gambling disorder’, (3) ‘gaming disorder’, (4) ‘compulsive sexual behavior’, (5) ‘bulimia nervosa’, (6) ‘binge eating’ and (7) ‘compulsive shopping’. We selected drugs “suspect” in at least five cases for which the summaries of product characteristics do not mention BA. We applied a downward descriptive process (drug only suspect, positive dechallenge, well-documented cases) together with a disproportionality analysis and a PubMed search.ResultsWe identified 24 drugs across 7 pharmacological classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, psychostimulants, antidiabetics and retinoids. Olanzapine was the only accompanied by well-documented cases with positive dechallenges, exhibiting significant disproportionality analysis and associated with publications from the PubMed search.ConclusionOur results highlights that several drugs and notably olanzapine are associated with BA. Further research using definitions enabling the diagnosis of addictive disorders for various BA is warrante
AI-enhanced profiling of phage-display-identified anti-TIM3 and anti-TIGIT novel antibodies
No full textInternational audienceAntibody discovery is a lengthy and labor-intensive process, requiring extensive laboratory work to ensure that an antibody demonstrates the appropriate efficacy, production, and safety characteristics necessary for its use as a therapeutic agent in human patients. Traditionally, this process begins with phage display or B-cells isolation campaigns, where affinity serves as the primary selection criterion. However, the initial leads identified through this approach lack sufficient characterization in terms of developability and epitope definition, which are typically performed at late stages. In this study, we present a pipeline that integrates early-stage phage display screening with AI-based characterization, enabling more informed decision-making throughout the selection process. Using immune checkpoints TIM3 and TIGIT as targets, we identified five initial leads exhibiting similar binding properties. Two of these leads were predicted to have poor developability profiles due to unfavorable surface physicochemical properties. Of the remaining three candidates, structural models of the complexes formed with their respective targets were generated for 2: T4 (against TIGIT) and 6E9 (against TIM3). The predicted epitopes allowed us to anticipate a competition with TIM3 and TIGIT binding partners, and to infer the antagonistic functions expected from these antibodies. This study lays the foundations of a multidimensional AI-driven selection of lead candidates derived from high throughput analysis
Transcriptional dynamics during Heliothis zea nudivirus 1 infection in an ovarian cell line from Helicoverpa zea
No full textInternational audienceNudiviruses (family Nudiviridae) are double-stranded DNA viruses that infect various insects and crustaceans. Among them, Heliothis zea nudivirus 1 (HzNV-1) represents the rare case of a lepidopteran nudivirus inducing a sexual pathology. Studies about molecular pathological dynamics of HzNV-1 or other nudiviruses are scarce. Hence, this study aims to provide a transcriptomic profile of HzNV-1 in an ovary-derived cell line of Helicoverpa zea (HZ-AM1), during early (3, 6 and 9 h post-infection) and advanced (12 and 24 h post-infection) stages of infection. Total RNA was extracted from both virus- and mock-infected cells, and RNA-seq analysis was performed to examine both virus and host transcriptional dynamics. Hierarchical clustering was used to categorize viral genes, while differential gene expression analysis was utilized to pinpoint host genes that are significantly affected by the infection. Hierarchical clustering classified the 154 HzNV-1 genes into four temporal phases, with early phases mainly involving transcription and replication genes and later phases including genes for virion assembly. In addition, a novel viral promoter motif was identified in the upstream region of early-expressed genes. Host gene analysis revealed significant upregulation of heat shock protein genes and downregulation of histone genes. The identification of temporal patterns in viral gene expression enhances the molecular understanding of nudivirus pathology, while the identified differentially expressed host genes highlight the key pathways most hijacked by HzNV-1 infectio
Contributions of reading self-concept, intrinsic motivation, and reading value to sixth graders’ purposeful reading: the mediating role of the task model
No full textInternational audienceThis study explores the relationships between sixth graders' motivation for purposeful reading, their task understanding skills, and their comprehension of written texts. More specifically, we investigated the role of students' understanding of reading tasks as a mediator of the relationships between reading self-concept, intrinsic reading motivation, reading value, and comprehension performance. Two hundred thirty-one sixth graders completed a purposeful reading motivation questionnaire, four tasks assessing their understanding of reading tasks, and four tasks assessing their comprehension of written texts. Intrinsic motivation and self-concept predicted comprehension performance but did not predict task-modeling skills. Mediation analyses showed that task-modeling skills only mediated the relationship between reading value and comprehension performance. The contributions of various dimensions of adolescents' motivation for reading and their taskmodeling skills to their reading comprehension are discussed in light of current models of purposeful reading
Représenter la parole : une dimension fondamentale de la linguistique
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De disons à on va dire : modaliser le dire en micro-diachronie
No full textInternational audienceThis paper deals with the joint examination of disons and on va dire. The present study is based on the exhaustive exploration of a structured spoken corpus of around 1.3 million words extracted from the ESLO-corpus, collected over two periods 40 years apart. We focus the distribution of both forms according to external (micro-diachronic, diaphasic, diastratic) and internal variables. For that purpose, we provided a systematic annotation, including semanticpragmatic categories, of the 528 occurrences found in the corpus. We show that disons, more polyfunctional and capable of denoting several types of modalization linked to different degrees of assertiveness, has seen a clear decline in 40 years and is essentially maintained among older speakers, while on va dire, more frequently used to express approximation and reduced assertiveness, has established itself in micro-diachrony.Cet article porte sur l’examen conjoint de disons et on va dire. Basée sur l’exploration exhaustive d’un corpus oral structuré d’environ 1.3 million de mots extrait des ESLO, récolté sur deux périodes à 40 ans d’intervalle, l’étude repose sur un examen de la distribution des deux formes selon des variables externes (micro-diachroniques, diaphasiques, diastratiques) et se dote d’une annotation systématique, notamment sémantico-pragmatique des 528 occurrences relevées pour la prise en compte des variables internes. Nous montrons que disons, plus polyfonctionnel, et susceptible de dénoter plusieurs types de modalisation liés à différents degrés de prise en charge, connaît un net recul en l’espace de 40 ans et se maintient essentiellement chez les locuteurs plus âgés, tandis que on va dire, plus spécialisé dans l’approximation et la non-prise en charge énonciative, s’impose en micro-diachronie
Relationship between livestock intensification and feed-food competition in diverse European broiler and cattle farms
No full textInternational audienceLivestock production accounts for a significant share of global feed and land, raising concerns about resource competition with humans. Monogastrics are considered more feed efficient and land productive than ruminants. But this may vary with intensification and if we consider what can be used for human nutrition (arable land and human edible protein). This study aimed to assess feed efficiency and land productivity using different metrics in 213 farms— 82 broiler, 78 dairy, and 53 beef farms — from very diverse systems in 9 EU countries. Considering key farm inputs, we grouped farms according to their intensification level (6 broiler, 7 dairy, and 5 beef farm groups). We calculated protein efficiency as kg of protein produced per kg of total protein (PE1) or per kg of human- edible protein (PE2) in feed, and land productivity as kg of protein produced per ha of total land (LP1) or per ha of arable land (LP2). As expected, PE1 and LP1 were higher in broiler than in dairy and beef farms (Median: 0.41 vs. 0.22 vs. 0.09 and 410 vs. 248 vs. 86 kg/ha, respectively) and increased with intensification. However, PE2 was higher in dairy than in broiler and beef farms (0.94 vs. 0.43 and 0.39) and LP2 was higher in broiler and dairy than in beef farms (410 and 404 vs. 173 kg/ha). PE2 and LP2 increased with intensification in broiler farms but decreased in dairy farms; the most extensive dairy farms requiring no human edible protein. In conclusion, intensification enhances protein efficiency and land productivity and broilers are more efficient than cattle. But,when considering the use of human-edible feed inputs, dairy systems are more efficient than broilers and their efficiency is higher in low input systems. These results will be used in an overall assessment covering product quality, animal welfare, and environment
Moderating effect of NICTs on marketing effectiveness and export performance of African firms: the impact of gender and manager experience
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