Anthony Mézière
email: anthony.meziere@aphp.fr

Alizée Denis

Natacha Berchel

Caroline Moreau

Alexandra Perrot

Médecin Gériatre

Master VHMA Étudiante Staps En

Caroline Psychologue

Moreau

Impact psychologique de la Wii-habilitation chez le sujet âgé chuteur hospitalisé : étude pilote

Keywords: chute, estime de soi, exergames, qualité de vie, sujets âgés

En France, un tiers des sujets âgés de 65 ans et plus vivant à domicile chutent au moins une fois par an, et la moitié des plus de 85 ans font une ou plusieurs chutes par an [START_REF]Académie nationale de médecine. Épidémiologie, morbidité, mortalité, coût pour la société et pour l'individu, principales causes[END_REF]. La chute a des conséquences graves chez le sujet âgé en étant responsable de nombreuses hospitalisations et amenant à une surmortalité [START_REF] Thelot | La surveillance épidémiologique des chutes chez les personnes âgées[END_REF]. Certaines de ces conséquences sont psychologiques. En effet, la chute augmente la prévalence de la peur de chuter déjà élevée chez le sujet âgé [START_REF] Legters | Fear of falling[END_REF]. Trente pour cent des sujets âgés chuteurs hospitalisés présentent une peur de chuter [START_REF] Cumming | Prospective study of the impact of fear of falling on activities of daily living, SF-36 scores, and nursing home admission[END_REF]. Cette dernière associée à la chute entraînent également une baisse de l'estime de soi, désapprobation portée sur soi-même indiquant dans quelle mesure un individu se croit capable, valable et important [START_REF] Alaphilippe | Self-esteem in the elderly[END_REF][START_REF] Coopersmith | Inventaire d'estime de soi : S.E.I[END_REF]. La peur de chuter est enfin associée à une réduction de la qualité de vie des seniors définie par l'Organisation mondiale de la santé (OMS) comme la perception qu'a un individu de sa place dans l'existence, dans le contexte de la culture et du système de valeur dans lesquels il vit, et en relation avec ses objectifs, ses attentes, ses normes et ses inquiétudes [START_REF] Scheffer | Fear of falling: measurement strategy, prevalence, risk factors and consequences among older persons[END_REF][START_REF]Study protocol for the World Health Organization project to develop a Quality of Life assessment instrument (WHOQOL)[END_REF].

Plusieurs types d'interventions multifactorielles réalisés par différents professionnels sont mis en place pour améliorer l'état psychologique du sujet âgé hospitalisé [START_REF] Hopewell | Multifactorial and multiple component interventions for preventing falls in older people living in the community[END_REF]. De nouvelles interventions, telles que les exergames associant une sollicitation physique à une sollicitation cognitive issues des jeux vidéo, ont montré leur bénéfice sur le plan cognitif [START_REF] Maillot | La théorie de l'enrichissement cognitif à travers la stimulation physique : activité physique traditionnelle versus exergames[END_REF][START_REF] Maillot | Effets de la pratique des jeux vidéo sur le vieillissement cognitif[END_REF]. En effet, la Wii peut être détournée de sa fonction principale qu'est le jeu à des fins thérapeutiques de réadaptation, et s'inscrire dès lors dans des programmes de "Wii-habilitation" [START_REF] Halton | Rehabilitation with the Nintendo Wii: Experiences at a rehabilitation hospital[END_REF]. L'usage de la Wii en rééducation améliore l'équilibre et la marche [START_REF] Nicholson | Six weeks of unsupervised Nintendo Wii Fit gaming is effective at improving balance in independent older adults[END_REF]. Elle a également un effet positif sur la dépression et l'anxiété [START_REF] Rosenberg | Exergames for subsyndromal depression in older adults: a pilot study of a novel intervention[END_REF]. La revue de la littérature de Chao et al. de 2015 confirme ces résultats avec une amélioration de la fonction physique, de la cognition, de la qualité de vie, de la socialisation et de la motivation ainsi qu'une diminution de la dépression chez le sujet âgé par l'utilisation de la Wii [START_REF] Chao | Effects of using Nintendo Wii™ exergames in older adults: a review of the literature[END_REF]. L'objectif d'une étude est d'approfondir la connaissance des effets de la pratique des exergames chez des personnes âgées chuteuses hospitalisées, sur plusieurs paramètres psychologiques sensibles à la chute, à savoir la peur de chuter, la qualité de vie et l'estime de soi.

T1 Matériels et méthode T2 Design de l'étude

Il s'agit d'une étude comparative en ouvert, réalisée du 27 mars au 20 juin 2017, dans le service de soins de suite et de réadaptation (SSR) orthogériatrique de l'hôpital Charles-Foix (AP-HP, Groupe hospitalier Pitié-Salpêtrière -Charles-Foix, Ivry-sur-Seine, 94). Ce service compte 44 lits d'hospitalisation et est composé d'une équipe pluridisciplinaire ayant pour mission la rééducation, la réadaptation et la réinsertion du patient âgé en perte d'autonomie. L'étude avait pour objectif d'évaluer l'impact psychologique des exergames chez les sujets âgés chuteurs hospitalisés, en comparant par tirage au sort un groupe de patients bénéficiant de la prise en charge habituelle du service à un groupe de patients bénéficiant de la "Wiihabilitation" en complément de la prise en charge habituelle.

T2 Population étudiée

Était inclus tout patient âgé de 70 ans et plus, admis dans le service de SSR pour réhabilitation au décours d'une chute, ayant un score au Mini-Mental State Examination (MMSE) supérieur à 15/30 et ayant donné son consentement oral pour la participation à l'étude. En début d'hospitalisation en SSR, lors d'un entretien avec la psychologue du service, cette dernière évaluait l'état cognitif du patient en réalisant le MMSE et l'état thymique en réalisant la Geriatric Depression Scale (GDS) [START_REF] Folstein | The Mini-Mental State Examination[END_REF][START_REF] Yesavage | Development and validation of a geriatric depression screening scale: a preliminary report[END_REF]. Les patients atteints de surdité sévère incapables d'entendre les consignes, ceux avec un état médical jugé par le médecin hospitalier incompatible à la pratique de la Wii et ceux grabataires étaient exclus.

T2 Programme de "Wii-habilitation"

La Wii est une console vidéo, développée en 2006 par la société japonaise Nintendo. Elle se joue avec une manette, la Wiimote, contenant des accéléromètres, qui est sensible et reconnaît les mouvements latéraux, verticaux et les rotations. Elle se joue également avec la Wii Balance Board qui est une planche munie de capteurs de pression qui mesurent le centre d'équilibre du sujet positionné dessus.

Les patients du groupe "Wii-habilitation" bénéficiaient de séances d'exergames une heure par semaine durant leur séjour hospitalier, en groupe dans une salle dédiée. Ils étaient supervisés par un professeur en activités physiques adaptées. La séance débutait par une phase d'échauffement avec des exercices d'assouplissement. Ensuite le corps de séance était composé d'un exercice de Wii Sports, le bowling à 100 quilles, et ensuite d'un exercice de Wii Fit, le slalom à ski. Le bowling à 100 quilles permet de se mesurer aux autres sans pour autant être en compétition, tout en faisant travailler le maintien du buste droit et la projection des membres supérieurs d'arrière en avant lors des lancers. Le slalom à ski permet, quant à lui, de faire travailler l'équilibre dynamique. Ce jeu utilise les mouvements du centre d'équilibre du corps pour diriger l'activité à l'écran.

T1 Évaluation de l'impact psychologique

La peur de chuter chez les sujets âgés chuteurs hospitalisés a été mesurée à l'aide de la version française de la Falls Efficacy Scale-International (FES) [START_REF] Yardley | Development and initial validation of the Falls Efficacy Scale-International (FES-I)[END_REF]. Cette échelle évalue 16 items d'activités de base de la vie quotidienne réalisées en intérieur ou en extérieur, et 6 items d'activités sociales plus complexes. Le patient doit coter son degré d'inquiétude de 1 à 4, face à la possibilité de tomber quand il réalise une activité -1 : pas du tout inquiet, 2 : un peu inquiet, 3 : assez inquiet et 4 : très inquiet. Si le patient ne réalise pas l'activité, il doit s'imaginer la réaliser et coter alors son degré d'inquiétude. Cette évaluation a été réalisée par la psychologue du service en début et en fin d'hospitalisation chez chaque patient inclus. L'estime de soi a été évaluée par la version française de l'échelle de Rosenberg [START_REF] Vallières | Traduction et validation canadienne-française de l'Échelle de l'estime de soi de Rosenberg[END_REF]. Le questionnaire est constitué de 10 items dont 5 évaluent l'estime de soi positive et 5 l'estime de soi négative. La réponse varie selon une échelle de type Likert en quatre points allant de "Tout à fait en désaccord" -1 -à "Tout à fait en accord" -4. La qualité de vie liée à la santé a été évaluée à l'aide du profil de santé de Duke dans sa version française qui explore le fonctionnement physique, social et psychologique [START_REF] Guillemin | The DUKE health profile: a generic instrument to measure the quality of life tied to health[END_REF]. Ce questionnaire est composé de 17 items, répartis en 5 dimensions indépendantes : physique, mentale, sociale, santé perçue et incapacité. L'instrument est également composé de 5 autres dimensions résultant de la recombinaison d'items choisis parmi les précédents : estime de soi, anxiété, dépression, douleur et un score général. L'évaluation par l'échelle de Rosenberg et celle de Duke a été réalisée par la psychologue du service en début et en fin d'hospitalisation chez chaque patient inclus.

T2 Analyse statistique

Une analyse descriptive des données a été réalisée. Les caractéristiques sociodémographiques et médicales des sujets ont été analysées par la moyenne (M) et l'écart type (± ET) pour les données quantitatives et par l'effectif pour les données qualitatives. Pour ce qui est des analyses statistiques inférentielles, des analyses non paramétriques ont été réalisées au regard du faible nombre de sujets. Un test de Mann Whitney a tout d'abord été réalisé sur les deux échantillons au moment des prétests afin de vérifier si les deux groupes étaient comparables en début de protocole. Pour le groupe "Wii-habilitation", l'efficacité du programme a été évaluée à partir de la différence entre les post-tests et les prétests de chaque variable. Cette différence a ensuite été comparée avec la différence entre les post-tests et les prétests du groupe contrôle, à partir d'un test de Mann Whitney. Les valeurs de p < 0,05 ont été considérées comme statistiquement significatives.

T2 Aspects éthiques

Le fichier informatisé "Database OrthoGerontolRehab" créé avec les données recueillies lors de cette étude a été déclaré à la Commission nationale informatique et libertés (Cnil) sous le numéro 1547216 en date du 24 novembre 2011. Il a été anonymisé pour l'analyse des résultats.

T1 Résultats

T2 Description de la population

Le groupe "Wii-habilitation" était constitué de 10 participants, 8 femmes et 2 hommes, âgés de 88,1 ± 7,23 ans, avec au minimum 74 ans et un maximum de 102 ans. Le groupe contrôle était constitué de 7 participants, 5 femmes et 2 hommes, âgés de 86 ± 7,48 ans, avec un minimum de 73 ans et un maximum de 95 ans. Aucune différence significative n'était constatée sur l'ensemble des variables sociodémographiques et médicales, ainsi que les prétests sur les variables psychologiques étudiées entre les deux groupes, au début de l'étude (tableau 1).

T2 Efficacité

Parmi les sujets ayant accepté de participer à l'étude et intégrant le groupe "Wii-habilitation", 3 participants ont réalisé 4 séances, 3 autres 5 séances et enfin 4 en ont réalisé 6 durant leur hospitalisation en SSR qui était en moyenne de quarante jours. Ces sujets ont pratiqué en moyenne 4,7 ± 1,7 séances de "Wii-habilitation" durant leur séjour hospitalier en SSR. Les participants à la "Wii-habilitation" ont bénéficié durant 22,1 ± 7,9 jours de la pratique d'une séance par semaine d'exergames.

L'efficacité de la pratique de la Wii est présentée dans le tableau 2. Les résultats soulignent une efficacité significative du programme de "Wii-habilitation", comparé au groupe contrôle, sur le score général de qualité de vie du profil de santé de Duke (p < 0,05), ainsi que sur les scores partiels de santé physique (p < 0,001) et mentale (p < 0,05). Toutes les autres variables psychologiques ne se montrent pas significativement sensibles au programme de "Wiihabilitation", en comparaison avec le groupe contrôle.

T2 Discussion

Cette étude pilote a montré que la "Wii-habilitation" chez le sujet âgé chuteur hospitalisé apporte une amélioration de sa qualité de vie durant son hospitalisation en SSR, mais n'a pas d'impact sur sa peur de chuter et son estime de soi.

Un impact psychologique significatif du programme de "Wii-habilitation" a été retrouvé sur la qualité de vie liée à la santé, à travers les dimensions physique et mentale. Les patients qui ont suivi le programme en exergames se sentaient plus en forme physiquement, motivés, concentrés et rapportaient moins de douleurs, de problème de sommeil, de fatigue, de tristesse et de dépression. Ce résultat fait écho à de précédents travaux concernant l'impact de l'activité physique traditionnelle sur l'amélioration de la qualité de vie, mais surtout à plusieurs études sur les exergames rapportant également cet impact psychologique favorable [START_REF] Cassilhas | The impact of resistance exercise on the cognitive function of the elderly[END_REF]. L'étude de Rosenberg et al. évaluant l'impact de douze semaines d'entraînement, avec le même style de programme en exergames sur Wii Sports chez des personnes âgées de 63 à 94 ans avec symptômes dépressifs, avait mis en évidence des améliorations significatives au niveau des symptômes dépressifs, de la qualité de vie liée à la santé mentale, mais aucune amélioration au niveau de la qualité de vie liée à la santé physique, contrairement à notre étude [START_REF] Rosenberg | Exergames for subsyndromal depression in older adults: a pilot study of a novel intervention[END_REF]. Wollersheim et al. rapportaient également une amélioration du bien-être physique, social et psychologique chez des femmes socialement isolées, âgées entre 56 et 84 ans, après un programme de 12 séances de jeux sur Wii Sports et Wii Fit [START_REF] Wollersheim | Physical and Psychosocial Effects of Wii Video Game Use among Older Women[END_REF]. Maillot et al. soulignaient eux aussi, auprès de 8 personnes autonomes âgées de 65 à 78 ans, un impact significatif d'un programme de 24 séances d'une heure sur Wii Sports et Wii Fit, sur la dimension mentale d'un questionnaire de qualité de vie (Short Form 36) [START_REF] Maillot | Effets de la pratique des jeux vidéo sur le vieillissement cognitif[END_REF].

Toutefois, nos résultats n'ont pas révélé d'amélioration de l'estime de soi suite au programme en exergames. Le peu de littérature antérieure dans ce domaine ne nous permet pas de comparaison et donc d'interprétation de nos résultats. En effet, la méta-analyse de Chao en 2014, sur les effets de la Wii chez les personnes âgées ne présentait aucune donnée sur ce paramètre psychologique [START_REF] Chao | Effects of using Nintendo Wii™ exergames in older adults: a review of the literature[END_REF]. À notre connaissance, seuls Li et al. rapportaient un effet significatif sur l'estime de soi suite à la pratique d'un programme de six semaines, soit sur Wii Sport soit sur Wii Fit, chez 49 personnes âgées dépressives en foyer logement [START_REF] Li | Effect of Exergames on Depression: A Systematic Review and Meta-Analysis[END_REF].

De même, aucun effet positif du programme en exergames sur la peur de chuter n'a été retrouvé dans notre étude. Ce résultat va dans le sens de plusieurs précédents travaux. Williams et al. n'avaient pas constaté d'amélioration sur le FES après douze semaines de programme sur Wii Fit, et Chao en 2014 et 2015 ne soulignait aucune amélioration du FES de personnes âgées institutionnalisées après des programmes sur Wii Fit, respectivement de 16 et 8 séances [START_REF] Chao | Effects of using Nintendo Wii™ exergames in older adults: a review of the literature[END_REF][START_REF] Williams | EXercising with Computers in Later Life (EXCELL) -pilot and feasibility study of the acceptability of the Nintendo® WiiFit in community-dwelling fallers[END_REF]. Cependant, des effets positifs du programme en exergames sur la peur de chuter ont été constatés par Rendon et ses collaborateurs retrouvant une amélioration sur le questionnaire ABC après six semaines d'entraînement en Wii Fit, 3 fois par semaine chez des personnes âgées entre 60 et 95 ans institutionnalisés [START_REF] Rendon | The effect of virtual reality gaming on dynamic balance in older adults[END_REF][START_REF] Powell | The Activities-specific Balance Confidence (ABC) Scale[END_REF]. De la même façon, Jorgensen et al. avaient observé une sensibilité significative du FES I, après un programme de vingt semaines, sur Wii fit, auprès de personnes de plus de 75 ans avec des troubles de l'équilibre [START_REF] Jorgensen | Efficacy of Nintendo Wii training on mechanical leg muscle function and postural balance in community-dwelling older adults: a randomized controlled trial[END_REF]. Ces résultats discordants avec ceux de notre étude peuvent peut-être s'expliquer par des programmes plus longs -plusieurs mois -et plus intenses -plusieurs fois par semaine -menés dans ces travaux. Par ailleurs, le petit effectif de patients inclus, 10 dans le groupe "Wii-habilitation" et 7 dans le groupe contrôle, limite la pertinence de l'analyse et de l'interprétation des résultats obtenus. Enfin, notre étude n'a malheureusement pas évalué la faisabilité ni la satisfaction des sujets âgés hospitalisés concernant la pratique de la Wii, contrairement à d'autres travaux qui avaient souligné une forte attractivité et une importante accessibilité des exergames pour un public novice et âgé [START_REF] Maillot | Effets de la pratique des jeux vidéo sur le vieillissement cognitif[END_REF][START_REF] Graves | The physiological cost and enjoyment of Wii Fit in adolescents, young adults, and older adults[END_REF][START_REF] Nawaz | Usability and acceptability of balance exergames in older adults: A scoping review[END_REF].

T1 Conclusion

Cette étude pilote qui nécessite d'être approfondie par une étude de plus grande échelle met en lumière de premières tendances intéressantes sur l'impact psychologique de la pratique de la Wii chez les sujets âgés chuteurs hospitalisés. Les exergames se montrent ici comme un moyen de contribuer à la réussite d'un challenge de prise en charge, et ce par l'intermédiaire des bénéfices qu'ils sont capables d'engendrer sur la qualité de vie durant une hospitalisation souvent prolongée et souvent mal vécue par les sujets âgés.

Impact psychologique de la Wii-habilitation chez les sujets âgés chuteurs.

				Groupe "Wii-habilitation"	Groupe contrôle	Mann-Whitney
				n = 10			n = 7
				M	ET		M	ET	U	p
	Âge (années)		88,1	7,23		86	7,48	31	n.s
	Séances suivies (nombre)	5,1	0,88		-	-	-	-
	GDS (score)		5,6	3,89		5,14	2,79	33,5	n.s
	MMSE (score)		22,4	3,6		22,28	4,07	34	n.s
	Durée du séjour (jours)		40	28		43,43	20,06	29,5	n.s
	DUKE général prétest (score)	55,67	15,4		59,52	10,08	30,5	n.s
	Physique			37	21,11		55,71	19,2	18,5	n.s
	Mentale			62	25,73		64,29	16,18	33,5	n.s
	Sociale			68	19,32		58,57	16,76	22	n.s
	Santé perçue		70	42,16		50	50	27	n.s
	Incapacité			0	0		14,29	37,4	30	n.s
	Estime de soi		73	20,03		68,57	15,74	31	n.s
	Anxiété			63,33	21,59		66,67	18	29,5	n.s
	Dépression		52	26,16		67,14	14,96	18	n.s
	Douleur			55	36,89		71,43	39,34	26	n.s
	Rosenberg prétest (score)	33,4	3,75		29,67	2,76	15,5	n.s
	FES I prétest (score)		23,8	4,89		24,43	7,89	15,5	n.s
			Groupe "Wii-habilitation"	Groupe contrôle	Mann-Whitney
			Différence Post-/Prétests	Différence Post-/Prétests
			M	ET		M	ET	U	p
	DUKE (score)	général	11,67	7,74		-3,81	15,69	11	< 0,05
	Physique		12	16,87		-51,71	19,05	0	< 0,001
	Mentale		16	11,74		-20	36,51	10,5	< 0,05
	Sociale		7	14,18		14,29	12,72	23,5	n.s
	Santé perçue	-10	51,64		7,62	50,98	27	n.s
	Incapacité		0	0		35,71	74,8	20	n.s
	Estime de soi	8	19,32		18,57	58,43	27	n.s
	Anxiété		13,33	11,92		6,19	21,94	34	n.s
	Dépression	19	16,63		-0,48	20,9	19	n.s
	Douleur		-5	15,81		-2,86	26,9	29,5	n.s
	Rosenberg (score)	0,9	5,55		3,43	4,5	26,5	n.s
	FES (score)	I	1,6	1,35		1,14	2,61	19	n.s

GDS : Geriatric Depression Scale

; MMSE : Mini-Mental State Examination ; DUKE : profil de santé de DUKE ; Rosenberg : Échelle de Rosenberg ; FES-I : Falls Efficacy Scale-International. Tableau 2. DUKE : profil de santé de DUKE ; Rosenberg : Échelle de Rosenberg ; FES-I : Falls Efficacy Scale-International.

Remerciements

Les auteurs remercient Clotilde Carre, psychomotricienne ; Yannick Picou, médecin gériatre ; Claire Schonheit, médecin gériatre pour leur contribution à l'article.

Déclaration de liens d'intérêts

Les auteurs déclarent ne pas avoir de liens d'intérêts.

Références


Emmanuelle Clervil

Jean-Bernard Duchemin

Nadine Amusant

Edmond Wozniak

Didier Azam

Maïra Coke

Dominique Huteau

Rémy Le Guével

Hélène Solhi

Isabelle Dusfour

Emeline Houël
email: emeline.houel@cnrs.fr

Efficacy and selectivity of Sextonia rubra wood extracts and bio-based formulation for the management of insecticide resistant Aedes aegypti in French Guiana

Keywords: vector control, botanical insecticide, semi-field trials, non-target effects, oviposition

Sextonia rubra is an Amazonian tree known for the larvicide activity of its wood extracts against Aedes aegypti. However, the lipophilic character of this extract represents an obstacle to the development of vector management products. The purpose of this study was to assess the feasibility, efficacy and selectivity of a water-soluble formulation based on a S. rubra wood extract characterized by its content in the larvicidal compounds rubrenolide and rubrynolide. Using reference and wild strains, the larval mortality, oviposition behavior, hatching response, and fitness of the mosquitoes exposed to the extract were evaluated. Laboratory eco-and cytotoxicity bioassays were concurrently performed. The extract showed larvicide efficacy alongside with no repulsive effect on oviposition, thus supporting its interest for the treatment of breeding sites. The formulation exhibited strong acute toxicity, leading to 100% larval mortality in 2 to 4 days either in dry or rainy season at the test dose of 102 µg/ml under semioperational conditions, with a residual activity maintained during the 5 weeks of test.

The formulation allowed for a noticeable gain in selectivity compared with the extract, with lower immobilization rates for D. magna and C. riparius, and no significant toxicity towards human cells lines (IC 50 > 100 µg/ml). These results highlight the potential of a S. rubra-based formulation for the management of Ae. aegypti larvae, including strains showing resistance to conventional insecticides.

Introduction

Globalization and extensive urbanization have promoted a worldwide expansion of the anthropophilic invasive mosquito Aedes aegypti L. (Diptera, Culicidae), notably due to the proliferation of breeding sites that can retain stagnant water [START_REF] Carvalho | Why is Aedes aegypti Linnaeus so successful as a species?[END_REF]. This species is causing numerous human casualties as the main vector of several arboviruses [START_REF] Kellner | Temporal genetic stability of Stegomyia aegypti (= Aedes aegypti) populations[END_REF][START_REF] Jones | Novel control strategies for mosquito-borne diseases[END_REF]). In the absence of clinically approved vaccine or antiviral therapy, except in the case of yellow fever virus, the vector control strategies based on the use of insecticides are of crucial importance.

Dengue fever, and Zika or chikungunya viruses are in particular strongly circulating in French Guiana, where vector control strategies have followed one another [START_REF] Epelboin | Successes and failures of sixty years of vector control in French Guiana: What is the next step?[END_REF][START_REF] Bailly | Spatial distribution and burden of emerging arboviruses in French Guiana[END_REF][START_REF] De Thoisy | Ecology, evolution, and epidemiology of zoonotic and vector-borne infectious diseases in French Guiana: Transdisciplinarity does matter to tackle new emerging threats[END_REF]. Nowadays, this French overseas territory faces a strong resistance of Ae. aegypti populations towards pyrethroids as adult vector-control products [START_REF] Dusfour | Deltamethrin resistance mechanisms in Aedes aegypti populations from three French overseas territories worldwide[END_REF][START_REF] Faucon | In the hunt for genomic markers of metabolic resistance to pyrethroids in the mosquito Aedes aegypti: An integrated next-generation sequencing approach[END_REF][START_REF] Guidez | Spatiotemporal multiple insecticide resistance in Aedes aegypti populations in French Guiana: Need for alternative vector control[END_REF][START_REF] Senthil-Nathan | A Review of resistance mechanisms of synthetic insecticides and botanicals, phytochemicals, and essential oils as alternative larvicidal agents against mosquitoes[END_REF][START_REF] Epelboin | CYP450 core involvement in multiple resistance strains of Aedes aegypti from French Guiana highlighted by proteomics, molecular and biochemical studies[END_REF]. Bti (Bacillus thuringiensis var.

israelensis) is currently used to reduce the density of Ae. aegypti larvae, without the apparition of resistance phenomena [START_REF] Darriet | Field evaluation of pyriproxyfen and spinosad mixture for the control of insecticide resistant Aedes aegypti in Martinique (French West Indies)[END_REF][START_REF] Kumar | Mosquito larvicidal and pupicidal efficacy of Solanum xanthocarpum (Family: Solanaceae) leaf extract and bacterial insecticide, Bacillus thuringiensis, against Culex quinquefasciatus Say (Diptera: Culicidae)[END_REF]). However, the persistence of effect of this non-ecotoxic natural product in breeding sites should be explored [START_REF] Epelboin | Successes and failures of sixty years of vector control in French Guiana: What is the next step?[END_REF]. In an epidemiological and legislative context particularly unsteady, it is therefore essential to develop safe, innovative and environmentally friendly methods for vector control [START_REF] George | Present and future potential of plant-derived products to control arthropods of veterinary and medical significance[END_REF][START_REF] Gerwick | Natural products for pest control: An analysis of their role, value and future[END_REF][START_REF] Benelli | Research in mosquito control: current challenges for a brighter future[END_REF][START_REF] Benelli | Declining malaria, rising of dengue and Zika virus: insights for mosquito vector control[END_REF].

Due to constant interaction with herbivores, plants synthesize a large variety of molecules as part of their defense system [START_REF] Agrawal | On the study of plant defence and herbivory using comparative approaches: How important are secondary plant compounds[END_REF][START_REF] Richards | Phytochemical diversity drives plantinsect community diversity[END_REF][START_REF] Salazar | Origin and maintenance of chemical diversity in a species-rich tropical tree lineage[END_REF]. This makes plants a valuable source for novel insecticide compounds [START_REF] Miresmailli | Botanical insecticides inspired by plant-herbivore chemical interactions[END_REF][START_REF] Pavela | Plant extracts for developing mosquito larvicides: From laboratory to the field, with insights on the modes of action[END_REF][START_REF] Benelli | On a magical mystery tour of green insecticide research: Current issues and challenges[END_REF][START_REF] Silvério | Plant natural products for the control of Aedes aegypti: The main vector of important arboviruses[END_REF]. However, even if numerous promising results have been obtained, only few of these findings have made it to commercial applications as new botanical insecticides [START_REF] Isman | Botanical insecticide research: Many publications, limited useful data[END_REF][START_REF] Isman | Botanical insecticides in the twenty-first century-fulfilling their promise?[END_REF]). One of the major technological challenges for the development of larvicide botanical products is to allow their homogeneous dispersion in water, the natural mosquito-breeding medium, alongside with the increase of field performance through a better persistence of action [START_REF] Isman | Botanical insecticides in the twenty-first century-fulfilling their promise?[END_REF]. To overcome the applicability limitations, notably linked to the apolar nature of many natural substances or extracts, and without using organic solvents exhibiting toxic profiles, micro-and nanoemulsions stand in good place [START_REF] De Oliveira | Application of nanotechnology for the encapsulation of botanical insecticides for sustainable agriculture: Prospects and promises[END_REF][START_REF] Peng | Effect of an eco-friendly o/w emulsion stabilized with amphiphilic sodium alginate derivatives on lambda-cyhalothrin adsorptiondesorption on natural soil minerals[END_REF]. These techniques, which lead to the efficient aqueous suspension or dilution of low water-soluble substances, allow obtaining usable bioactive natural products against mosquito larvae [START_REF] Kanis | Larvicidal activity of Copaifera sp. (Leguminosae) oleoresin microcapsules against Aedes aegypti (Diptera: Culicidae) larvae[END_REF]Oliveira et al. 2016;[START_REF] Pavela | Encapsulation -A convenient way to extend the persistence of the effect of eco-friendly mosquito larvicides[END_REF][START_REF] Pavela | Encapsulation of Carlina acaulis essential oil and carlina oxide to develop long -lasting mosquito larvicides: microemulsions versus nanoemulsions[END_REF]). The lower effect on non-target organisms than conventional products also stands among the potential advantages of natural-products-based micro-and nanoemulsions as larvicide products, and low toxicity for humans is notably an important parameter to look after, due to the use of such products in the household area (Oliveira et al. 2016;[START_REF] Pavela | Plant extracts for developing mosquito larvicides: From laboratory to the field, with insights on the modes of action[END_REF][START_REF] Turchen | Plant-derived insecticides under meta-analyses: Status, biases, and knowledge gaps[END_REF][START_REF] Faustino | Larvicide activity on Aedes aegypti of essential oil nanoemulsion from the Protium heptaphyllum resin[END_REF][START_REF] Rodrigues | Development of nanoemulsions based on Ayapana triplinervis essential oil for the control of Aedes aegypti larvae[END_REF][START_REF] Machado | Nanoemulsion of Ocotea indecora (Shott) Mez essential oil: Larvicidal effects against Aedes aegypti[END_REF].

S. rubra (Mez.) Van der Werff is a common Lauraceae tree in the Guianas, Venezuela and in Amazonian Brazil. This species of high economic importance is used in the w s y F h G , wh s k w s " f " (Soulères 2021).

This industry however produces sizeable quantities of wastes, including sawdust during logs transformation. Moreover, previous studies performed by our group demonstrated that the crude wood extract and the purified compounds rubrenolide and rubrynolide displayed strong activity towards Ae. aegypti larvae, and that commercial sawmill residues of S. rubra can be considered as a valuable resource for the large-scale production of these larvicidal extracts [START_REF] Falkowski | Assessment of a simple compoundsaving method to study insecticidal activity of natural extracts and pure compounds against mosquito larvae[END_REF][START_REF] Falkowski | Towards the optimization of botanical insecticides research: Aedes aegypti larvicidal natural products in French Guiana[END_REF][START_REF] Clervil | Sextonia rubra (Mez.) van der Werff sawmills residues as a valuable resource for the production of larvicidal extracts against Ae. aegypti Linnaeus (Diptera: Culicidae)[END_REF].

We therefore embarked upon characterizing the larvicidal activity of the S. rubra wood extract on Ae. aegypti iso-female strains and their parent wild strain collected in French Guiana. We also evaluated the fitness of mosquitoes exposed to the extract, while concurrently assessing an aqueous-based formulation containing S. rubra wood extract in semi-field conditions. Eco-and cytotoxicity were investigated, in the objective of ascertaining the selectivity of the products towards aquatic species and human cells, and display a better picture of the potential of S. rubra material to develop novel botanical products displaying larvicidal activity against insecticide-resistant Ae. aegypti mosquitoes.

Materials & method

Mosquito strains and rearing

Five Ae. aegypti (Diptera: Culicidae) strains were used. The laboratory New Orleans (NO) strain is a reference strain susceptible to all insecticides and maintained for decades in an insectary at the Institut Pasteur de la Guyane, Cayenne, French Guiana.

The Cayenne (CAY) strain was collected in the eponym city, and larvae of the F1 progeny were used for all of the experimentations made in the laboratory and for the semi-field experimentations. This population is resistant to both pyrethroid and organophosphate insecticides. A parent population was obtained from wild-caught

v f I R y (IR), f h s s s f F h G (5.287˚ N; 52.590˚ W), 2015, h f s IR0115.
w s ss characterizes this area of collection. Two isofemale strains were obtained from this parent population, as previously described after isolation of one mated female [START_REF] Epelboin | CYP450 core involvement in multiple resistance strains of Aedes aegypti from French Guiana highlighted by proteomics, molecular and biochemical studies[END_REF]. The information concerning the five used strains are summarized in Table 1. Rearing was performed as previously described [START_REF] Touré | Aedes aegypti larvicidal sesquiterpene alkaloids from Maytenus oblongata[END_REF]. regression under a general linearized model using the MASS package in R software version 3.2.0 (https://www.r-project.org/) as previously described [START_REF] Falkowski | Assessment of a simple compoundsaving method to study insecticidal activity of natural extracts and pure compounds against mosquito larvae[END_REF].

Influence of S. rubra wood extract on the oviposition behavior of Ae. aegypti, hatching response, and assessment of mosquito fitness

Assessment of the influence of S. rubra wood extract on the oviposition behavior of the mosquito was performed as described in the literature, with some modifications (El (51.2 µg/ml) and LD 50 (18.6 µg/ml) of SrK extract used to obtain the formulation, and measured on the CAY wild strain after 48h of exposure. Formulation and formulation matrix effect on non-target species were compared at the semi-field trial dose of twice the SrK crude extract LD 90 (102 µg/ml). The impact of formulation, formulation matrix and the crude extract were concurrently assessed at the reference LD 50 of the crude extract. Eventually, the purified compounds rubrenolide and rubrynolide were tested at 2 µg/mL, representing around 10% of the extract LD 50 value, as each compound represented in average 10% of the extract [START_REF] Clervil | Sextonia rubra (Mez.) van der Werff sawmills residues as a valuable resource for the production of larvicidal extracts against Ae. aegypti Linnaeus (Diptera: Culicidae)[END_REF]). Three conditions were tested: water control, water and solvent control, and the dose of analysis, with five replicates per condition. The physicochemical measurements (pH, dissolved oxygen, conductivity) were performed with measuring devices (sensors). The remaining measures (chlorine, nitrites, nitrates, phosphates) were performed in the laboratory using colorimetric detection (spectrophotometer). Photoperiod and temperature were

s " h " h h h s , f h b
until the end of the exposure.

Cytotoxicity assays

Cell culture

Skin normal fibroblastic cells and HUVEC-Umbil Vein (umbilical cord cells) were purchased from Lonza (Basel, Switzerland), Caco-2 (colon), SHY5Y (human bone marrow neuroblasts), NCI-H295R (adrenal gland), HaCaT (skin keratinocytes) and HuH7D12 (liver) cancer cells lines were obtained from the ECACC collection (Porton, OK, USA). Cells were grown according to ECACC recommendations at 37°C and 5% CO 2 . All cultures were added with 10 % FBS (HyClone FetalClone III; Cytiva, H30109.03), penicillin-1% streptomycin (Sigma, P4333) and 2mM glutamine (Sigma, G7513).

Cytotoxic assays

Chemicals were solubilized in DMSO (Sigma, D4540) at a concentration of 20 mM or 100 mg/ml (stock solution) and diluted in culture medium to the desired final concentrations. The doses effect cytotoxic assays (IC 50 determination) were performed by s f h h (f w s: 0.3 μM -0.9 μM -3 μM -9 μM -25 μM -50 μM 1 μ / -3 μ / -9 μ / -28 μ / -83 μ / -250 μ / ). C s w 96 w s (4000 s/w ). Tw y-four hours after seeding, cells were exposed to chemicals. After 48h of treatment, cells were washed in PBS (Sigma D8537) and fixed in cooled 90% ethanol (Sigma 32221) / 5% acetic acid (Sigma A6283) for 20 minutes. Then, the nuclei were stained with Hoechst 33342 (B2261 Sigma). Image acquisition and analysis were performed using a Cellomics ArrayScan VTI/HCS Reader (ThermoScientific, Waltham, MA, USA). The survival percentages were calculated as the percentage of cell number after compound treatment over cell number after DMSO treatment. To evaluate the selectivity of the formulation, the selectivity index was used to highlight the results more clearly, as IC 50 were available in this case for the non-target cells. This value can be defined as the ratio of the toxic concentration of a product (considering in our case the 48h-IC 50 against human cell lines) against its effective bioactive (in our case, the larvicidal activity defined by the products 48h-LD 50 ) concentration [START_REF] Indrayanto | Validation of in-vitro bioassay methods: Application in herbal drug research[END_REF].

Results

Activity of S. rubra wood extract on Ae. aegypti strains displaying various degrees and mechanisms of resistance to deltamethrin

The investigation of the possibility of cross-resistance of S. rubra extract with pyrethroids was performed using the SrM extract (S. rubra sawdust collected in Montsinéry sawmill). Susceptibility tests on Ae. aegypti larvae indicated the lethal concentrations presented in Table 3. A strong larvicidal activity of S. rubra wood extracts against the susceptible Ae. aegypti strain NO was observed. Characterized resistant strains showed higher LD values than the susceptible strain. The insecticideselected isofemale strains showed, as CAY wild strain, the highest LD values. However, the hatching rate measured for the CAY strain eggs was not affected by the treatment. To determine whether the maturation of Ae. aegypti eggs on a S. rubra extractimpregnated substrate impact the fitness of the mosquitoes at larval, pupal and adult stage, the average number of individuals having developed at each stage from 50 larvae was counted (Fig. 3). For the NO strain, there is a significant decrease between the number of adults obtained from eggs laid in treated breeding sites (Student t-test: t = 5.2774, df = 6.9332, p-value = 0.0005935). For the CAY strain, the decrease of the number of adults obtained from eggs laid in treated breeding sites is not significant (Student t-test: t = -0.68374, df = 7.8959, p-value = 0.7431).

Preparation and preliminary evaluation of a S. rubra-based formulation

A prototype emulsifiable concentrate (EC) was developed to enhance the crude extract water solubility. The EC was titrated in 10% of S. rubra extract alongside with stabilizing and dispersing ingredients originating from green chemistry, as described in Table 2. The obtained product was visually stable, the clear brown viscous aspect obtained directly after mixing the ingredients and the extract was maintained during the two weeks of observation, without the apparition of a cloudy louche or insoluble. This concentrate was also easily dispersed in distilled water in 0.10% solution to reach a concentration of 100 µg/ml of S. rubra extract, leading to a homogeneous clear mixture even after 10 days. The visual aspect of the extract, emulsifiable concentrate (EC) and emulsion in distilled water (EW) are represented in Figure 4. The formulation was developed using the SrK extract (sawdust collected in Kourou sawmill), which was known to exhibit LD 50 values of 39.6 and 18.6 µg/mL at 24h and 48h, respectively, and LD 90 values of 118.2 µg/ml and 51.2 µg/ml at 24h and 48h, respectively, against the CAY strain, and to contain 10.5% and 8.9% (w/w) of the bioactive compounds rubrenolide and rubrynolide respectively [START_REF] Clervil | Sextonia rubra (Mez.) van der Werff sawmills residues as a valuable resource for the production of larvicidal extracts against Ae. aegypti Linnaeus (Diptera: Culicidae)[END_REF].

When tested in the laboratory against the CAY strain, the formulation led to LD 50 values of 48.0 ± 0.01 and 9.3 ± 0.05 µg/mL at 24h and 48h, respectively, and LD 90 values of 75.1 ± 0.02 and 39.6 ± 0.04 µg/ml at 24h and 48h, respectively. To ensure that this effect was not due to a toxic activity of the formulation matrix against Ae. aegypti larvae, we assessed the matrix and the formulation at 102 µg/ml prior to their evaluation in semi-field conditions. The results obtained for the matrix showed a mortality rate of 9.5 ± 4.8% after 24h of exposure, and 14 ± 2.1% after 48h, whereas the formulation led to 100% of larval mortality in each case.

Semi-field bioassays

The formulation was tested at the trial dose of 102 µg/ml for the final product, corresponding to 2xDL 90 of the crude extract. The obtained dispersion was homogeneous, without the formation of any oily layer under the water surface, residue, or formation of distinct phases during the whole duration of the assay, despite a certain milky appearance (Fig. 5). The overall results of semi-field bioassays are presented in Figures 6 and7. Figure 6 shows the larval survival of the 3 rd -instar larvae of the CAY strain from Ae. aegypti mosquitoes. The formulation killed larvae mosquito in less than three days during the dry season, and in less than four days during the rainy season, without any loss of activity during the nine to ten days of observation.

Impact on aquatic non-target organisms and human cell lines

The matrix and the formulation were tested at the dose used for the semi-field trial (102 µg/ml). At 24h and 48h, the matrix displayed in our test conditions no (at 24h) to low toxicity towards both organisms (16 ± 26% of immobilization for D. magna, and 12 ± 11% immobilization for C. riparius at 48h) (Figure 8). For the formulation, significant immobilization rates were observed after both 24h and 48h of exposure in the case of C. riparius, with 64 ± 2% and 92 ± 2% of immobilization respectively. The toxic effect appeared more slowly towards D. magna, with only 20 ± 3% of immobilization after 24h of exposure, but 100% of immobilized animals after 48h. The effect of extract, matrix and formulation was then assessed at a lower dose, chosen as the 48h-LD 50 (18.6 µg/ml) of the SrK extract used to prepare the emulsifiable concentrate. The compounds rubrenolide and rubrynolide were tested at a concentration of 2 µg/ml, which corresponds to around 10% of the 48h-LD 50 in consistency with the extract composition, which contains 10.5% of rubrenolide and 8.9% of rubrynolide [START_REF] Clervil | Sextonia rubra (Mez.) van der Werff sawmills residues as a valuable resource for the production of larvicidal extracts against Ae. aegypti Linnaeus (Diptera: Culicidae)[END_REF]). The overall obtained results are showed in Figure 9. No to very low effect was observed for the matrix towards both non-target organisms. The environmental effect of the formulation could be considered low in the case of C. riparius, with a maximum immobilization rate of only 28 ± 18% after 48h of exposure at a dose corresponding to the 48-h LD 50 of the extract. The effect of the EC towards D. magna was more important, with 68 ± 30% of immobilized animal after 48h.

The results obtained for the pure compounds rubrenolide and rubrynolide indicated a strong toxicity against non-target organisms, at a dose as low as 2 µg/ml. Rubrenolide was the most toxic compound, with 92 ± 18% immobilized D. magna and 88 ± 11% immobilized C. riparius as soon as 24h after exposure. At 48 hours, rubrenolide led to almost complete mortality of the two non-target organisms (100% for D. magna and 96 ± 9% for C. riparius). Rubrynolide acted more slowly, with immobilization values of 20 ± 0% and 48 ± 27% at 24h, and 96 ± 9% and 64 ± 30% at 48h for D. magna and C.

riparius respectively. Formulation matrix, full formulation (S. rubra extract emulsifiable concentrate) and S. rubra crude extract were tested at 18.6 µg/ml (S. rubra SrK extract 48-h LD 50 against 498 Ae. aegypti), and the pure compounds rubrenolide and rubrynolide at 2 µg/ml 499 500 Eventually, the cytotoxicity of all products was concurrently assessed towards a panel 501 of human cell lines (Table 4). 502 503 According to the standards proposed in the literature, the matrix, formulation and crude 509 extracts could be considered non-toxic when exhibiting IC 50 values > 100 µg/ml, this 510 endpoint being set at 25 µm in the case of pure compounds [START_REF] Cos | Anti-infective potential of natural products: How to develop a stronger in vitro " f-of[END_REF]. In this 511 perspective, both the matrix and the formulation only displayed slight cytotoxic effect 512 against kidney NCI-H295R cells (human carcinoma), with IC 50 values of 87 and 94 513 µg/ml respectively. The extract however could be considered cytotoxic against liver HuH7 cells (human hepatocellular carcinoma, IC 50 value of 32 µg/ml), and also led to a moderate effect against HUVEC (human umbilical vein endothelial cells), kidney and colon Caco2 (human colorectal adenocarcinoma) cells, with IC 50 values in the 70-93 µg/ml range. Concerning the pure compounds, rubrynolide did not display any cytotoxicity except against liver cells (IC 50 of 12 µg/ml). It was the only case when this compound was more toxic than rubrenolide, which exhibited a measurable effect towards liver, kidney and umbilical cord cells, even if above the 25 µM criteria (IC 50 in the 31-35 µM) range. Notably, no toxicity was observed against any of the products in the case of skin fibroblasts.

A selectivity index was calculated (Figure 10), except for human skin fibroblasts and human bone marrow neuroblasts, as the obtained IC 50 were > 250 µg/ml. Overall, the EC exhibited higher selectivity indices than the crude extract for all tested cell lines, with values from 10 (kidney human carcinoma NCI-H295R cells) to 20 (skin human immortalized keratinocytes HaCat).

Discussion

In a first step, the activity of S. rubra wood extract was assayed against Ae. aegypti strains displaying various degrees and mechanisms of resistance to deltamethrin.

These new results corroborated the previous efficacy measured against the susceptible Paea strain and the preliminary data obtained about the wild strain Cayenne [START_REF] Falkowski | Assessment of a simple compoundsaving method to study insecticidal activity of natural extracts and pure compounds against mosquito larvae[END_REF][START_REF] Falkowski | Towards the optimization of botanical insecticides research: Aedes aegypti larvicidal natural products in French Guiana[END_REF]. The overall results are in accordance to resistance pattern towards pyrethroids described in French Guiana [START_REF] Dusfour | Deltamethrin resistance mechanisms in Aedes aegypti populations from three French overseas territories worldwide[END_REF][START_REF] Faucon | In the hunt for genomic markers of metabolic resistance to pyrethroids in the mosquito Aedes aegypti: An integrated next-generation sequencing approach[END_REF][START_REF] Guidez | Spatiotemporal multiple insecticide resistance in Aedes aegypti populations in French Guiana: Need for alternative vector control[END_REF][START_REF] Senthil-Nathan | A Review of resistance mechanisms of synthetic insecticides and botanicals, phytochemicals, and essential oils as alternative larvicidal agents against mosquitoes[END_REF][START_REF] Epelboin | CYP450 core involvement in multiple resistance strains of Aedes aegypti from French Guiana highlighted by proteomics, molecular and biochemical studies[END_REF]. Besides lethality, the impact of active products on oviposition deterrence and repellence, as well as development, longevity or vitality of the target insect are also of great importance in the field of vector control [START_REF] Borges | Mosquiticidal and repellent potential of formulations containing wood residue extracts of a Neotropical plant, Tabebuia heptaphylla[END_REF][START_REF] Turchen | Plant-derived insecticides under meta-analyses: Status, biases, and knowledge gaps[END_REF][START_REF] Pavela | Encapsulation of Carlina acaulis essential oil and carlina oxide to develop long -lasting mosquito larvicides: microemulsions versus nanoemulsions[END_REF].

Plants and plant-derived substances are often known to possibly interfere with oviposition effect, leading to either repellent or attractant effect, notably at concentrations greater than 50 µg/ml [START_REF] Kanis | Standardized extract of Piper ovatum (Piperaceae) to control Aedes aegypti larvae (Diptera: Culicidae)[END_REF][START_REF] Maghrbi | Influence of some plant extracts on the ovi-position behavior of Aedes fluviatilis and Culex quinquifasciatus[END_REF][START_REF] Satho | Coffee and its waste repel gravid Aedes albopictus females and inhibit the development of their embryos[END_REF][START_REF] Seenivasagan | Plant infusions mediate oviposition of malaria, dengue and filariasis vectors: Push-pull approach for vector surveillance and control[END_REF]). In our case, the absence of repulsive effect concerning Ae. aegypti oviposition behavior is of importance when it comes to evaluating the potential of S. rubra extract as a larvicide used in stagnant water. A repulsive effect regarding oviposition would indeed lead the mosquitoes to lay eggs in other, untreated sites, and therefore at once make such treatment irrelevant and favor the dispersion of the vector [START_REF] Kanis | Standardized extract of Piper ovatum (Piperaceae) to control Aedes aegypti larvae (Diptera: Culicidae)[END_REF]. Concurrently, we observed that larval hatching response measured for the CAY strain eggs did not vary significantly depending on the breeding site medium type. Such a result had previously been observed for Culex molestus eggs, collected in standing water pools in Australia, and placed in breeding sites with different treatments (Methoprene and QN50, a sesquiterpene alcohol derived from Australian sandalwood Santalum spicatum A. DC.) [START_REF] Spafford | Laboratory determination of efficacy of a Santalum spicatum extract for mosquito control[END_REF]. Moreover, the chance to obtain pupae and adult Ae. aegypti EC is titrated in 10% of S. rubra extract. This could be due to an increased bioavailability because of the presence of tensioactive compounds in the EC, such as previously observed for controlled-release systems and nano-emulsions of essential oils [START_REF] Maia | Improved activity of thyme essential oil (Thymus vulgaris) against Aedes aegypti larvae using a biodegradable controlled release system[END_REF][START_REF] Rodrigues | Development of nanoemulsions based on Ayapana triplinervis essential oil for the control of Aedes aegypti larvae[END_REF]. Moreover, the mortality rates obtained for both the matrix and the formulation, comparatively, confirmed the relative innocuousness of the matrix against Ae. aegypti, and ensured that the semi-field bioassay would give us information on the S. rubra extract in the form of an EC as the only active product.

The efficiency of the tested formulation as a mosquito larvicide was demonstrated by our results, especially towards the CAY Ae. aegypti strain, exhibiting a strong resistance to conventional insecticides. The milky appearance of the aqueous media treated with the emulsifiable concentrate observed in semi-operational conditions can be due to the composition of the tap water used for the assay, although it was let 24h for dechlorination before use, or to the addition of larval food. Indeed, the presence calcium, sodium or chloride ions can modify the spontaneous formation of a microemulsion, and lead to a basic emulsion, while changing the translucent aspect for a cloudy one [START_REF] Egito | Microemulsion systems: from the design and architecture to the building of a new delivery system for multipleroute drug delivery[END_REF]. The strong and rapid acute toxicity can represent a technical advantage in the field. [START_REF] Darriet | Field evaluation of pyriproxyfen and spinosad mixture for the control of insecticide resistant Aedes aegypti in Martinique (French West Indies)[END_REF] The lasting residual activity suggests an effective potential of the formulation for vector population inhibition during dengue transmission periods, which is a key parameter for disease control [START_REF] Kanis | Standardized extract of Piper ovatum (Piperaceae) to control Aedes aegypti larvae (Diptera: Culicidae)[END_REF][START_REF] Kanis | Piper ovatum (Piperaceae) extract/starchcellulose films to control Aedes aegypti (Diptera: Culicidae) larvae[END_REF][START_REF] Maia | Improved activity of thyme essential oil (Thymus vulgaris) against Aedes aegypti larvae using a biodegradable controlled release system[END_REF]. Botanical products often have to face the problem of residual activity, due to a high biodegradability through photodegradation, abiotic oxidation or volatilization [START_REF] Amer | Persistency of larvicidal effects of plant oil extracts under different storage conditions[END_REF][START_REF] Isman | Botanical insecticides in the twenty-first century-fulfilling their promise?[END_REF]). In our case, this relatively long residual activity was obtained for a simple emulsion, without using slowrelease systems. This can be put in perspective with the previously demonstrated stability of the crude S. rubra extract in ambient conditions over time [START_REF] Clervil | Sextonia rubra (Mez.) van der Werff sawmills residues as a valuable resource for the production of larvicidal extracts against Ae. aegypti Linnaeus (Diptera: Culicidae)[END_REF].

Concerning the ecotoxicity of the matrix and the formulation under our experimental conditions, D. magna were overall more sensitive to the tested products than C. riparius, with high standard deviations observed, due to the protocol involving a low number of animals. For the matrix and the formulation at the dose used for the semifield trial (102 µg/ml), our results highlighted the harmlessness of the green formulation basis against non-targeted organisms, as observed towards Ae. aegypti larvae. These results are also consistent with suppliers, regulatory and literature data concerning the ecotoxicological assessment of the formulation matrix components [START_REF] Renkin | Rapeseed methyl ester ethoxylates: A new class of surfactants of environmental and commercial interest[END_REF][START_REF] Szwach | Comparative evaluation of environmental impact of selected ethoxylate fatty alcohols and ethoxylate fatty acid methyl esters as nonionic surfactants[END_REF]ECHA 2022a, b). At this dose, an Ae. aegypti larval mortality of 100% was obtained as soon as 24h when assessing the formulation in the laboratory. At 102 µg/ml, the formulation thus only showed selectivity towards both non-target organisms at 24h (5 times less mortality for C. riparius than for Ae. aegypti larvae at the same dose, and around 1.5 times less mortality for D. magna), this advantage being lost after 48h of exposure. However, when testing the effect of extract, matrix and formulation at the 48h-LD 50 (18.6 µg/ml) of the SrK extract used to prepare the emulsifiable concentrate, the formulation led to 1.5 less toxicity towards D. magna, and 3.4 less toxic effect towards C. riparius, when compared to the extract. Besides solving technological problems due to the solubilization of S. rubra lipophilic crude extract in water, the use of the formulation also allows to lower the toxicity of the active ingredient at the same dose, without losing larvicidal efficacy. Complementary assessments should now be performed in cooperation with public health workers to determine the useful dose of formulation in the field, and therefore identify the precise level of selectivity proposed by the S. rubra EC. The data obtained for rubrenolide and rubrynolide are consistent with the previous evaluation of these pure compounds against Ae. aegypti larvae, with higher toxic activity observed for rubrenolide than rubrynolide both on the laboratory strain Paea and the wild strain Cayenne [START_REF] Falkowski | Assessment of a simple compoundsaving method to study insecticidal activity of natural extracts and pure compounds against mosquito larvae[END_REF]. Thus, valuing the extract, and even more the formulation, rather than the pure compounds, can add a noticeable value when it comes to the ecotoxicological profile of the larvicidal products.

Eventually, except for the extract towards kidney cells, the cytotoxic effect of the tested product was overall moderate to non-significant in an acute toxicity assay. The data obtained for the pure compounds rubrenolide and rubrynolide are consistent with a previous study, in which the pure compounds exhibited IC 50 > 100 µg/ml against NIH-3T3 fibroblasts cells [START_REF] Rodrigues | Search for antifungal compounds from the wood of durable tropical trees[END_REF]. Even if a noticeable toxicity had been previously reported for rubrenolide (GI 50 in the 3.3-9.9 µg/ml range i.e., < 33 µM) against UACC-62 (human melanoma), MCF-7 (human breast cancer), HT-29 (human colorectal adenocarcinoma) and PC-3 (human prostate cancer) cell lines, most values in our assays remained out of the cytotoxic range [START_REF] Tófoli | Antiproliferative Butyrolactones from Mezilaurus crassiramea[END_REF]). However, complementary cytotoxic evaluation of the products in in vivo models would be a valuable asset. Th s v y f h h s , s SI ≥ 10 w s previously cited in the literature as a valuable criterion for selective samples [START_REF] Awouafack | Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae)[END_REF][START_REF] Houël | Therapeutic switching: From antidermatophytic essential oils to new leishmanicidal products[END_REF][START_REF] Peña-Morán | Cytotoxicity, posttreatment recovery, and selectivity analysis of naturally occurring podophyllotoxins from Bursera fagaroides var. fagaroides on breast cancer cell lines[END_REF]). These results therefore reinforce those obtained when comparatively assessing the ecotoxicity of the crude extracts towards the formulated products, as in both cases (eco-and cytotoxicity), a clear advantage is obtained when using the S. rubra EC.

Conclusion

This study aimed at the evaluation of S. rubra wood extract towards Ae. aegypti reference, laboratory and wild strains, concurrently to the assessment of a S. rubrabased formulated product for application in aqueous media. We demonstrated the efficiency of the wood extracts on Ae. aegypti larvae, notably resistant wild strains, and h h h h bs f s v ff f h w h s s oviposition behavior. A simple, stable, easy-to-produce and easy-to-use formulation, in the form of an emulsifiable concentrate titrated in 10% of S. rubra extract, was successfully obtained. The choice of the ingredients, derived from green chemistry, allowed both the application of a lipophilic botanical extract in water and the compliance with European standards and regulations. This formulation demonstrated strong larvicidal activity (acute toxicity and residual activity) through semi-field assays alongside with better selectivity towards non-target aquatic organisms and human cell lines than the crude wood extract. Following previous promising results on the larvicidal activity of S. rubra wood extract and the useability of sawmill residues for a large-scale production of the extract, in a biorefinery perspective included in circular economy objectives, this work aims to contribute to the development of novel solutions for the management of Ae. aegypti mosquitoes and the control of vector-borne diseases such as dengue fever and Zika or chikungunya viruses, while taking into account environmental and human health issues associated with the use of insecticide products.

  [START_REF] Maghrbi | Influence of some plant extracts on the ovi-position behavior of Aedes fluviatilis and Culex quinquifasciatus[END_REF][START_REF] Seenivasagan | Plant infusions mediate oviposition of malaria, dengue and filariasis vectors: Push-pull approach for vector surveillance and control[END_REF]. Holding cages (30 x 30 x 30 cm) were each filled with 40 adult females and 40 adult males (6 days old) of Ae. aegypti New Orleans strain (3 replicates) and Cayenne strain (3 replicates). Adult mosquitoes were continuously fed on cotton soaked in 10% sugar until one day before the blood meal. Two days after the female mosquito have been artificially blood fed (beef blood), two breeding sites consisting in laying cups were placed in each cage: a control site (100 ml untreated distilled water), and a site with water (100 ml) treated with SrM extract. Doses for the S. rubra treatment were adapted for each population and centered around the two respective 24h-DL 50 values (2 µg/ml of SrM S. rubra wood extract for New Orleans strain; 70 µg/ml of SrM S. rubra wood extract for Cayenne strain). A paper wick was placed in each breeding site on day 3 after the blood meal, and replaced each day during 5 days by a new one, dried, and the number of eggs laid on each paper was counted. The total number of eggs was used as a measure of oviposition response. To obtain a new generation of mosquitoes, each paper wick was put in clear water after 5 days drying, and the rearing performed as previously described[START_REF] Clervil | Sextonia rubra (Mez.) van der Werff sawmills residues as a valuable resource for the production of larvicidal extracts against Ae. aegypti Linnaeus (Diptera: Culicidae)[END_REF]. The numbers of hatched eggs were counted and 50 larvae coming from hatched eggs of each strain and each condition were placed into 5 different trays as five replicates. The daily survival and stage development follow-up (average number of individuals having developed to pupal and adult stages from 50 larvae according the strain and treatment) lasted until the complete emergence of all individuals. Student t-test was applied to measure the influence of the treated water all analyses, a p-value < 0.05 was taken to indicate statistical significance.Simulated field trialSemi-field trials were conducted on the grounds of the Institut Pasteur de la Guyane (French Guiana Pasteur Institute) in Cayenne. For the bioassays, only the Ae. aegypti natural population collected in Cayenne town (CAY) was used for testing the formulated products. The CAY strain was selected to provide a stringent context for an assay as close to the reality of the field as possible. Experiments were carried out in white plastic containers (70 l, Icko Apiculture, Bollène, France) filled with water (50 l) and placed undercover, out of direct sunlight and rainfall, and covered with mosquito nets to prevent oviposition by wild mosquitoes or other insects of the area, as well as falling debris during the experiment. Four test containers were used concurrently for each trial session, alongside with four negatives and four positive controls containers.For the test barrels, S. rubra formulation (50 g), titrated at 10 % of wood extract, were added to tap water (50 l), to obtain a final concentration of the active product in the barrel corresponding to twice the extract LD 90 against Ae. aegypti CAY larvae after 48h of exposure in the laboratory, i.e., a trial dose of 102 µg/ml. Negative control containers were filled with tap water only (50 l), and positive control containers were filled with the formulation matrix (40 g) dissolved in the water. During the experiment, tap water was regularly added in the containers to compensate evaporation and maintain a constant 50 l-volume. In each case, tap water was given 24h hours before use for dechlorinating and conditioning. Late third or early fourth-instar larvae from a first generation (F1) reared from wild-caught larvae (F0) were used in the tests. A pool of 100 larvae was initially added to each container at the beginning of the trial, and a new pool of 100 live larvae was released in each container after total emergence of the adults in the control containers (approximately every week). Larval food (yeast powder, 845 mg) was given to the larvae during the test. The larval, and adult survival were recorded every day until the total adult emergence of the controls. This experimentation was realized during both the dry season (August-September 2020; average maximum temperature 33.8°C; average temperature 27.8°C, average sunlight 239.5 hours; average rainfall 166.5 mm) and the rainy season (January-February 2021; average maximum temperature 30.8°C; average temperature 26.5°C, average sunlight 86.6 hours; average rainfall 507 mm) (infoclimat.fr, 2021, Cayenne). For data analysis, the time (in weeks) is recorded for the inhibition of adult emergence (%IE) to pass below the threshold value of 80%. For each treatment, %IE was estimated according to control containers by the following formula (World Health Organisation 2005; Darriet et al. 2010): Where C represents the average percentage emergence in the untreated (control) containers at a particular time and T represents the average percentage emergence in the treated containers in the same period. Ecotoxicological bioassays on non-target species: Daphnia magna and Chironomus riparius (O CD N . 235) f Chironomus riparius (Meigen, 1804). Each product (crude extract, purified compounds rubrenolide and rubrynolide, formulation, and formulation matrix) was tested at doses based on the beforehand established LD 90

Fig. 1

 1 Fig. 1 Oviposition responses of gravid females of Ae. aegypti to Sextonia rubra wood

Fig. 2

 2 Fig. 2 Hatching rate for the New Orleans strain (NO) and the Cayenne strain (CAY)

Fig. 3

 3 Fig. 3 Average number of individuals having developed to pupal and adult stages from

Fig. 4 S

 4 Fig. 4 S. rubra-derived larvicidal products: A) wood ethyl acetate crude extract; B)

Fig. 5

 5 Fig. 5 Comparison of the visual aspects of control (left) and treated (right) container

Fig. 6

 6 Fig. 6 Survival of Ae. aegypti mosquito larvae exposed or not to a formulation based on

Fig. 7

 7 Fig. 7 Simulated field trial performed during dry (upper graph) and rainy (lower graph)

Fig. 8

 8 Fig. 8 Comparative assessment of the immobilization percentage (and standard error)

Fig. 9

 9 Fig. 9 Immobilization percentage of non-target aquatic organisms Daphnia magna

Fig. 10

 10 Fig. 10 Selectivity indices calculated as SI = IC 50 (non-target cells) / LD 50 (Ae. aegypti Cayenne strain larvae) after 48 hours of exposure for Sextonia rubra extract (light blue) and formulation (dark blue). HBM: human bone marrow

Table 1

 1 Characteristics of the different Ae. aegypti mosquito strains used in the study

	acetate (EtOAc, RPE grade, Carlo Erba Reagenti SpA, Rodano, Italy) at a 1/20 ratio
	(w/v) at room temperature by maceration during 24h under stirring. After extraction, the
	solution was filtered and the solvent removed by evaporation under reduced pressure
	w h S	V ™		(S v	SPD121P, Th	S	f c). The resulting
	crude extracts (SrM, from Montsinéry sawdust, and SrK from Kourou sawdust) were
	s	f z	-18°C	ss y . Is	f b	(Re) and rubrynolide

a kdr: knock-down resistance Sextonia rubra wood extract and purified compounds S. rubra (Mez.) Van der Werff (Lauraceae) freshly obtained commercial sawmills wastes were collected in French Guiana. Sawdusts were obtained from Montsinéry (4°58 34" N 52°26 45" W; September 2017) and Kourou sawmills (5°08 54" N 52°41 20" W; March 2020) respectively. Mass distribution by particle size was measured as follows: 60% > 500 µm, 33% between 500 and 200 µm, and 6% < 200 µm for Montsinéry sawdust, and 74% > 500 µm, 21% between 500 and 200 µm, and 4% < 200 µm for Kourou sawdust. All samples were dried at room temperature (21°C, 65% relative humidity) until equilibrium humidity (H<13%). Any visible bark material was manually removed from crude wood powders, which were then extracted using ethyl invalidated if mortality in control was >20%. Lethal doses were obtained by a log-Probit

Table 3

 3 Lethal doses (µg/ml) for 50% and 90% (LD 50 and LD 90 respectively) of the population of Aedes aegypti strains, obtained with SrM extract, with associated The obtained results show that no statistically significant difference is observed for the oviposition behavior of Ae. aegypti within each strain, and notably the wild CAY strain, between the control breeding site and the treated breeding site (NO

	strain Student t-test: t = -1.2697, df = 7.3768, p-value = 0.2428; CAY strain Student t-
	test: t = 0.54894, df = 6.1733, p-value = 0.6023).

confidence interval (CI), after 24 and 48h of exposure Influence of S. rubra wood extract on the oviposition behavior of Ae. aegypti, hatching response, and assessment of mosquito fitness Parameters related to the mosquito fitness and life-history were assayed on respective DL 50 doses of SrM extract using the reference NO strain and the wild-type CAY strain. Figure 1 represents oviposition preferences of Ae. aegypti females in the presence of two eggs deposition sites (control, and treated with a sub-lethal dose (DL 50 ) of S. rubra wood extract).

Table 4

 4 Cytotoxic effect towards human cell lines after 48h of exposure to the 504 formulation matrix, full formulation (S. rubra emulsifiable concentrate), S. rubra crude 505 extract, and pure compounds rubrenolide and rubrynolide. IC 50 are expressed in µg/ml 506 for mixtures, and in µM for pure compounds 507

	IC 50 (µg/ml a or µM b )	Liver (HuH7)	Kidney (NCI-H295R)	Colon (Caco2)	Skin fibroblasts	Skin keratinocytes (HaCaT)	Bone marrow neuroblasts (SHY5YSY)	Umbilical cord (HUVEC)
	Matrix	143	87	120	> 250	184	> 250	214
	Formulation (EC) c	102	94	172	> 250	187	156	170
	S. rubra extract	32	93	91	> 250	135	> 250	70
	Rubrenolide	35	31	> 50	> 50	> 50	> 50	34
	Rubrynolide	12	> 50	> 50	> 50	> 50	> 50	> 50
	a For mixtures
	b For pure compounds
	c EC: emulsifiable concentrate
	508

Data availability

The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

mosquitoes is lowered when eggs are laid in treated sites in the case of the NO strain only, as no statistical difference was obtained in the case of the Cayenne wild strain. It would thus be interesting to assess such an effect on the formulation and on other wildtype strains collected in French Guiana, in order to evaluate the existence of a potential secondary beneficial effect of S. rubra extract and formulation in case of sublethal exposition of the larvae [START_REF] Silva Ll De | Exposure of mosquito (Aedes aegypti) larvae to the water extract and lectin-rich fraction of Moringa oleifera seeds impairs their development and future fecundity[END_REF].

The ingredients of the formulation were chosen in order to fulfill the regulation (EU) 528/2012 and directive 98/8/EC (Directive Biocide) concerning the making available on the market and use of biocidal products, or the regulation (EC) 1107/2009 concerning the placing of plant protection products on the market. Regulatory approvals represent an important barrier to the industrial implementation of botanical insecticides, and taking them into account in an early stage is therefore crucial (Villaverde et al. 2014;[START_REF] Isman | Botanical insecticides in the twenty-first century-fulfilling their promise?[END_REF]. Notably, natural-oil based esters, including methyl esters, have been recorded and patented for their noticeable solvency properties when used to solubilize various insecticides and obtain oil-in-water (EW) emulsions [START_REF] Taranta | Oil-in-water emulsion formulation of insecticides[END_REF][START_REF] Salimon | Industrial development and applications of plant oils and their biobased oleochemicals[END_REF][START_REF] Tan | A formulated solvent composition for pesticide[END_REF]. Surfactants were chosen among products obtained from renewable raw material, with non-ecotoxic characters in environmental conditions as well as high biodegradability properties (Rybinski and Hill 1998; [START_REF] Johansson | Surfactants based on fatty acids and other natural hydrophobes[END_REF][START_REF] Renkin | Rapeseed methyl ester ethoxylates: A new class of surfactants of environmental and commercial interest[END_REF]Zhang et al. 2011;[START_REF] Geetha | Alkyl Poly Glucosides (APGs) surfactants and their properties: A review[END_REF][START_REF] Peng | Effect of an eco-friendly o/w emulsion stabilized with amphiphilic sodium alginate derivatives on lambda-cyhalothrin adsorptiondesorption on natural soil minerals[END_REF].

The LD 50 and LD 90 values obtained in the laboratory for the formulation can lead to its categorization as a significant larvicidal agent [START_REF] Machado | Nanoemulsion of Ocotea indecora (Shott) Mez essential oil: Larvicidal effects against Aedes aegypti[END_REF]). The micro-and nano-encapsulation of active ingredients, notably botanical products, may lead to somewhat to noticeable increase of lethal concentrations value for the formulated products [START_REF] Kanis | Larvicidal activity of Copaifera sp. (Leguminosae) oleoresin microcapsules against Aedes aegypti (Diptera: Culicidae) larvae[END_REF][START_REF] Pavela | Encapsulation of Carlina acaulis essential oil and carlina oxide to develop long -lasting mosquito larvicides: microemulsions versus nanoemulsions[END_REF]. Such phenomena did not appear in our hands, with on the contrary the same range of activity for both the crude extract and the emulsifiable concentrate, and thus a gain of effect for the active ingredient, as the

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Author Contribution


Pauline Armary

Cheikh Brahim

El Vaigh

Ouassila Labbani Narsis

Christophe Nicolle

Christophe Nicolle Ciad

CIAD System for Geographical Entity Detection at TextMine'24

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

CIAD System for Geographical Entity Detection at

TextMine'24

Pauline Armary * , * * Cheikh-Brahim El-Vaigh, * Ouassila Labbani Narsis * Christophe Nicolle *

Introduction

Named Entity Recognition (NER) is a fundamental task in natural language processing that involves the identification and classification of named entities within textual data [START_REF] Liu | Overview of named entity recognition[END_REF]. Named entities are specific entities such as persons, organizations, locations, dates, and more, which carry significance in the given context. NER plays a crucial role in information extraction, and the process typically involves analyzing and annotating text to locate and classify named entities [START_REF] Liu | Overview of named entity recognition[END_REF][START_REF] Wang | Nested named entity recognition: a survey[END_REF].

NER has undergone significant advancements, with various approaches and techniques employed for identifying and classifying named entities in text. Initially, rule-based NER systems were used relying on predefined linguistic rules and patterns to identify named entities in text [START_REF] Collins | Unsupervised models for named entity classification[END_REF]. Then, machine learning algorithms, such as Conditional Random Fields (CRF) and Hidden Markov Models (HMM), have been applied to learn patterns and features from labeled data [START_REF] Patil | Named entity recognition using conditional random fields[END_REF][START_REF] Morwal | Named entity recognition using hidden markov model (hmm)[END_REF]. The advent of deep learning models, especially Recurrent Neural Networks (RNNs), Long Short-Term Memory networks (LSTMs), and Transformers has ushered in a new era of state-of-the-art performance for NER tasks [START_REF] Peters | Deep contextualized word representations[END_REF][START_REF] Chiu | Named Entity Recognition with Bidirectional LSTM-CNNs[END_REF]. Finally, with the success of transformers despite their huge training cost, fine-tuning pre-trained language models like BERT (Bidirectional Encoder Representations from Transformers) [START_REF] Devlin | Bert: Pre-training of deep bidirectional transformers for language understanding[END_REF] and GPT (Generative Pre-trained Transformer) has become a common practice.

In the context of the initiative TextMine 20241 , focusing on the identification of geographical entities through named entity processing from a French nautical instruction corpus [START_REF] Rawsthorne | Reconnaissance d'entités géographiques dans un corpus des instructions nautiques (2024) défi textmine'24)[END_REF], the application of NER becomes crucial for extracting entities from the text. TextMine 2024 is a EGC 20242 evaluation Lab. However, the inherent challenges of the geographical entities context make the NER task more intricate, given that the texts are of a small size and noisy. Moreover, the target entities are not fine-grained types but rather ambiguous. For example, in Tab. 1 which shows the statistics of the different entity types, the annotation name refers to a proper noun being it a Person, a Place, or an Organization, while in the standard NER these three categories are separated. Moreover, while NER is often seen as a multi-class classification task, in this evaluation the NER is both a multi-class and a multi-label classification problem, and for example, in Tab. 1, we have 2123 tokens that are both name and geogName.

This paper proposes two approaches for the NER task in Sec. 2. We first studied several pre-trained BERT models [START_REF] Devlin | Bert: Pre-training of deep bidirectional transformers for language understanding[END_REF] that we fine-tuned on the TextMine corpus and compared their accuracy (see Sec. 2.1). We also devised a graph convolutional network (GCN) [START_REF] Kipf | Semi-supervised classification with graph convolutional networks[END_REF] based approach that considers the tokens in the corpus as nodes and connects these nodes based on their co-occurrence in the same context. Moreover, labels are also seen as nodes and a token is connected to its labels from the train dataset. We then tackle NER as a node classification task using the standard GCN architecture (see Sec. 2.2). The code of our system is on GitHub3 . TAB. 1 -The different annotations present in the corpus.

CIAD's Systems

Fine-tuning BERT models

Fine-tuning a BERT model for a specific task is nowadays the state-of-the-art option for several NLP tasks, especially for NER. A BERT [START_REF] Devlin | Bert: Pre-training of deep bidirectional transformers for language understanding[END_REF] model is a Large Language Model (LLM) trained with an Encoder architecture on a very large corpus of documents. As with any LLM, the principle is to transform each word of the corpus into a vector within a large-dimensional space. This vector is reduced using a neural network architecture by optimizing the result to a specific task while reducing the number of dimensions of the vector space.

As part of the Transformer family, BERT uses an Encoder architecture trained on a maskedword prediction task. The Encoder Neural Network is trained to predict what is the correct word which was masked within a sentence. As such, the model uses the overall context surrounding the word to create a vector representing its meaning. For NER task, the model is fine-tuned as a Token Classification or Sequence classification task, with a corpus associating a label of each specific kind of entity (Person, Organization, Place, etc) to each word. For predicting the label of the corpus, we used a pre-trained BERT model on Sequence Classification for NER, which was pre-trained for recognizing different kinds of entities within the text. We fine-tuned the model to recognize the specific label of our corpus ("geoFeat", "geoName", "name"). We choose a Sequence Classifier as the data is presented as an ordered list of tokens. We fined-tuned the following models: BERT-Base-NER (BERT trained for NER in English), CamemBERT-NER (French BERT trained for NER in French), TinyBERT (refinement of the BERT model), and a NER model using GTP2 within a prompt-based learning setup.

Using GCN for NER

The Graph Convolutional Network (GCN) architecture was first proposed by [START_REF] Kipf | Semi-supervised classification with graph convolutional networks[END_REF] for node classification. In the context of Natural Language Processing, the text is first transformed into a graph representing the connections between the words that appear in the same context (a window of size 2). For NER, the words are also associated with their labels, each label and token representing a node in the graph. This architecture is often presented as more resilient to multi-label classification, as a node can easily be associated with multiple labels. Within the GCN, an embedding of each node is learned and a softmax layer is used to perform classification based on these embeddings. We used the GCN model to our classification task for geographical entities.

Experiments

Experimental validation was conducted on the TextMine 2024 French corpus to assess the quality of our system. We evaluate our system using the accuracy metric. The description of the TextMine corpus can be found in the challenge website. 4We discuss hereunder the performance of NER classifiers that we described in Sec. 2.1 and Sec. 2.2. We gathered in Tab. 2 the accuracy of the different classifiers on the test dataset (a.k.a "public score" on the Kaggle page of the challenge 5 ). One can see that BERT-based classifiers are the best, reaching an accuracy of 92.7%. Meanwhile, the difference between the smallest model (TinyBERT column 4 in Tab 2) and the largest model (BERT-base column 1 in Tab 2) is rather small (1.2%). This conclusion can be explained by the fact that, for the fine-tuning task, only a subset of the parameters is used (unfrozen parameters), therefore most the parameters of the model are kept as they are. We also show the accuracy of the GPT2 model using prompt learning (column 3 in Tab 2). We notice that this model shows a comparable performance to the BERT-based ones. Finally, the GCN NER classifier did not perform very well on the test dataset and its accuracy is only 77.9% (column 5 in Tab 2). The GCN classifier showed promising results on the training dataset, as most of the nodes are known and the underlying graph creation is straightforward. However, we noticed that this GCN tends to over-fit on the train data and could not generalize well. We believe this is due to the way the graph is created (connecting nodes that appear in the same context), as with the provided TextMine dataset, each word has only limited context. This approach is not suitable for small datasets as it will require different contexts for each word.

Conclusion

We built an entity processing system based on a BERT model for the NER task, exploiting the existing pre-trained models. Our system was evaluated on the TextMine 2024 French dataset. The proposed model achieved an accuracy of 92.7% being only 5% points away from the best model. We also proposed a GCN model that did not perform well due to the small size of the data. These results open new perspectives for taking into account BERT embedding in a GCN model for NER.

https://textmine.sciencesconf.org/resource/page/id/8

https://iutdijon.u-bourgogne.fr/egc2024/

https://github.com/elvaigh/textmine-ciad

https://textmine.sciencesconf.org/resource/page/id/8

https://www.kaggle.com/competitions/defi-textmine-2024/