MSc Elena M Bonke
email: elena.bonke@med.uni-muenchen.de

PhD Amanda Clauwaert
email: amanda.clauwaert@kuleuven.be

Stefan M Hillmann
email: stefan.hillmann@med.uni-muenchen.de

MD Uta Tacke
email: uta.tacke@ukbb.ch

PhD Caroline Seer
email: caroline.seer@kuleuven.be

Eukyung Yhang
email: eukyungyhangeyhang@bu.edu

Yorghos Tripodis
email: yorghos@bu.edu

MD Stian B Sandmo
email: stianbs@nih.no

Tim L T Wiegand
email: tim.wiegand@med.uni-muenchen.de

MD David Kaufmann
email: david.kaufmann@uk-augsburg.de

MD Elisabeth Kaufmann
email: elisabeth.kaufmann@med.uni-muenchen.de

PhD Sutton B Richmond
email: sutton.b.richmond@gmail.com

MSc Malo Gaubert
email: malogaubert@gmail.com

MD Johanna Seitz-Holland

PhD Alexander Leemans
email: a.leemans@umcutrecht.nl

PhD Stephan P Swinnen
email: stephan.swinnen@kuleuven.be

MD Roald Bahr
email: roaldb@nih.no

PhD Ofer Pasternak

Florian Heinen
email: florian.heinen@med.uni-muenchen.de

MD Inga K Koerte
email: inga.koerte@med.uni-muenchen.de

MD Michaela V Bonfert
email: michaela.bonfert@med.lmu.de

PhD Jolien Gooijers
email: jolien.gooijers@kuleuven.be

MD Florian Heinen

Sylvain Bouix

Martha E Shenton

Alexander P Lin

Fanny Dégeilh

Alexandra Gersing

Felicitas Heinen

Leonard Jung

Janna Kochsiek

Marc Muehlmann

Paul S Raffelhueschen

Paula C M Schorlemer

Bettina Schwarz-Moertl

Alexandra A C Silva

Lisa Umminger

Alberto De Luca

Serafien D ' Hooghe

Doron Elad

Thor Einar Andersen

Audun Erling Hisdal

Holm Torgersen

Martin Cente

Igor Jurisica

Katarina Matyasova

Sara Porubska

Jozef Hanes

Nir Sochen

Neurological soft signs are associated with reduced medial-lateral postural control in adolescent athletes

Keywords: Neurological Soft Signs, Postural Control, Adolescent Athletes, Diadochokinesis, Maturation, Minor Neurological Dysfunction

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

Introduction

Neurological soft signs (NSS) are minor deviations from the norm in motor performance and sensory-motor integration [START_REF] Dazzan | Neurological soft signs in first-episode psychosis: A systematic review[END_REF]. In contrast, major (also called hard) signs are rated as pathological and include findings such as hyperreflexia and spasticity [START_REF] Martins | A longitudinal study of neurological soft signs from late childhood into early adulthood[END_REF][START_REF] Sanders | The neurologic examination in adult psychiatry: From soft signs to hard science[END_REF]. Even though not considered pathological, and also present in healthy adults [START_REF] Kennard | Value of equivocal signs in neurologic diagnosis[END_REF], investigating NSS in adolescents is clinically relevant because it was found to be associated with an increased vulnerability for mental disorders [START_REF] Mayoral | Longitudinal study of neurological soft signs in first-episode early-onset psychosis[END_REF][START_REF] Obiols | Neurological soft signs in adolescents with poor performance on the continuous performance test: Markers of liability for schizophrenia spectrum disorders?[END_REF]. More specifically, there is initial evidence for NSS being a non-specific marker for developing developmental deficiencies such as attentiondeficit hyperactivity disorder and schizophrenia spectrum disorder [START_REF] Chan | Neurological Soft Signs in Schizophrenia: A Meta-analysis[END_REF][START_REF] Whitty | Diagnostic specificity and predictors of neurological soft signs in schizophrenia, bipolar disorder and other psychoses over the first 4 years of illness[END_REF][START_REF] Patankar | Neurological soft signs in children with attention deficit hyperactivity disorder[END_REF]. NSS are typically assessed using a clinical neurological examination [START_REF] Ojagbemi | Neurological Soft Signs[END_REF]. Commonly used rating systems are qualitative and include the Neurological Examination Scale (NES) [START_REF] Buchanan | The neurological evaluation scale (NES): A structured instrument for the assessment of neurological signs in schizophrenia[END_REF], the Cambridge Neurological Inventory (CNI) [START_REF] Chen | The Cambridge Neurological Inventory: A clinical instrument for assessment of soft neurological signs in psychiatric patients[END_REF], the Heidelberg NSS Scale (HS) [START_REF] Schröder | Neurological soft signs in schizophrenia[END_REF],

and the age-dependent assessment of Minor Neurological Dysfunction (MND) [START_REF] Hadders-Algra | The assessment of minor neurological dysfunction in infancy using the Touwen Infant Neurological Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY Examination: Strengths and limitations[END_REF][START_REF] Hadders-Algra | Examination of the Child with Minor Neurological Dysfunction[END_REF] (for review of NSS rating systems see [START_REF] Chrobak | How soft are neurological soft signs? Content overlap analysis of 71 symptoms among seven most commonly used neurological soft signs scales[END_REF]). With some minor differences, most rating systems comprise tests of coordination, fine motor skills, and postural control [START_REF] Bombin | Assessment tools for soft signs[END_REF]. Importantly, these assessments are based on the examiners' observation and therefore are qualitative rather than quantitative by nature. Particularly when it comes to subtle alterations as it may be the case for physically trained adolescent athletes, the addition of instrumented investigations such as force plate measures assessing postural control, which are considered to be the "gold standard" for assessing postural stability [START_REF] Richmond | Leveling the playing field: Evaluation of a portable instrument for quantifying balance performance[END_REF], may provide valuable insights by quantitatively detecting variability in performance that might not be detected visually.

Postural control is considered a milestone of physiological development and allows individuals to engage in various static and dynamic activities [START_REF] Dinkel | Postural Control Strategies Differ in Normal Weight and Overweight Infants[END_REF]. It can be described as the maintenance of the center of pressure inside the base of support and is defined by Bartlett and Birmingham as the ability to maintain internal stability (e.g., to stand upright) and to Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY anticipate and avoid instability in response to an external perturbation [START_REF] Bartlett | Validity and Reliability of a Pediatric Reach Test[END_REF]. Generally, motor performance and postural control development take place according to two stages. First, young children, approximately until the age of five years, follow an open-loop strategy, characterized by the explorative activity of the nervous system exploring all motor possibilities. This strategy is also referred to as the ballistic strategy and is characterized by a greater displacement of the center of pressure (COP) and thus greater instability [START_REF] Blanchet | Development of postural stability limits: Anteroposterior and mediolateral postural adjustment mechanisms do not follow the same maturation process[END_REF]. Around the age of eight years, children transfer to using a closed-loop strategy (or sensory strategy) where they use various movement possibilities in each specific situation, resulting in better postural control [START_REF] Blanchet | Development of postural stability limits: Anteroposterior and mediolateral postural adjustment mechanisms do not follow the same maturation process[END_REF][START_REF] Kirshenbaum | Non-linear development of postural control and strategy use in young children: A longitudinal study[END_REF]. As children age further, their nervous system adapts, and multisensory integration is improved. More specifically, older children integrate information from different modalities (e.g., visual and somatosensory system) more successfully to control posture, making them better equipped to function in a changing environment [START_REF] Kirshenbaum | Non-linear development of postural control and strategy use in young children: A longitudinal study[END_REF][START_REF] Peterka | Sensorimotor integration in human postural control[END_REF].

However, any disturbances of this maturation process will likely result in less optimal or nonoptimal postural control. Of note, postural control has been shown to mature later along the ML compared to the AP axis [START_REF] Blanchet | Development of postural stability limits: Anteroposterior and mediolateral postural adjustment mechanisms do not follow the same maturation process[END_REF][START_REF] Kirshenbaum | Non-linear development of postural control and strategy use in young children: A longitudinal study[END_REF][START_REF] Peterka | Sensorimotor integration in human postural control[END_REF]. Currently, there is no clear consensus in the literature regarding at what age adolescents reach their peak performance in postural control. Some studies suggest that adolescents have not yet reached an adult-like performance in postural control at the age of 14 years [START_REF] Barozzi | Reliability of postural control measures in children and young adolescents[END_REF] while others found that processes underlying the maintenance of an optimal postural stability are mature much earlier [START_REF] Rival | Developmental changes of static standing balance in children[END_REF]. In adolescent athletes, this developmental process was reported to be ongoing until the age of 19 years as shown by normative Balance Tracking System (BTrackS) data of more than 10 000 adolescent athletes between 8 and 21 years [START_REF] Goble | Normative data for the btracks balance test concussion-management tool: Results from 10045 athletes aged 8 to 21 years[END_REF].

To the best of our knowledge, no study has yet used a combined approach of observerbased neurological examination and quantitative assessment of postural control to comprehensively assess motor maturation between the ages of 13 and 16 years. Thus, to date it remains unknown whether the findings of both assessments are interrelated. Therefore, this Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY 13 study aims to provide information on the additional use of force plate measures in a clinical setting. It is expected that a lower qualitative NSS score derived from a neurological examination is reflected in reduced postural control performance. The use of force plates as an objective measure will allow for a detailed quantification of higher-order motor functioning in addition to clinical observer-based assessments. This will add relevant information when investigating motor functioning in a clinical setting.

Materials and Methods

Study design and participants

Participant data were extracted from the multi-site study REPIMPACT (Repetitive Subconcussive Head Impacts -Brain Alterations and Clinical Consequences; 2017-2020).

The study enrolled male adolescent athletes aged 13-16 years between July 2017 and April 2020 from three study sites (Oslo, Norway; Leuven, Belgium; Munich, Germany). Included athletes participated in various sports that were primarily soccer, but also swimming, track and field, cross-country skiing, cycling, tennis, biathlon, and rowing. Participants and their legal guardians at all three data acquisition sites provided written informed consent in accordance with the local ethics board approvals and the Declaration of Helsinki.

In short, inclusion criteria for participating in the study were: (1) 13-16 years of age, (2) male, (3) participation in sports at a competitive level with training at least three times per week in the respective sport, and (4) fluent language skills of the respective country of citizenship (i.e., German, Dutch, or Norwegian). For more details on the REPIMPACT study design, see [START_REF] Koerte | REPIMPACT -a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer[END_REF].

Participants were excluded from the analysis in case of (1) history of serious medical condition (history of encephalitis: n = 3), (2) incidental finding on a magnetic resonance imaging scan (periventricular gliosis: n = 1, subependymal heterotopia: n = 1), (3) premature Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY 14 birth (i.e., < 37 weeks of gestation) (n = 3), (4) diagnosed attention deficit disorder (n = 1), [START_REF] Mayoral | Longitudinal study of neurological soft signs in first-episode early-onset psychosis[END_REF] neurological hard signs as evident by neurological examination (n = 0), or [START_REF] Obiols | Neurological soft signs in adolescents with poor performance on the continuous performance test: Markers of liability for schizophrenia spectrum disorders?[END_REF] no performed neurological examination as part of the REPIMPACT project (n = 17). This resulted in an included sample of 141 participants (Table 1). The neurological examination and the postural control assessment were performed at the same visit.

Neurological examination assessing NSS

A standardized pediatric neurological examination based on the William DeMyer's Neurological Examination was performed [START_REF] Biller | DeMyer's: The Neurologic Examination[END_REF]. This examination included the evaluation of NSS in line with the distinct age-related rating framework published within the MND concept [START_REF] Hadders-Algra | The assessment of minor neurological dysfunction in infancy using the Touwen Infant Neurological Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY Examination: Strengths and limitations[END_REF]. We decided to follow the MND concept because it has proven useful when investigating developmental cohorts [START_REF] Kikkert | Early Human Development Minor neurological dysfunction and cognition in 9-year-olds born at term[END_REF][START_REF] Galić | Minor neurological dysfunction in children aged 5 to 7[END_REF][START_REF] Jong | Minor neurological dysfunction in children with autism spectrum disorder[END_REF]. Of note, compared to other assessments such as the NES, CNI, HS, the MND concept considers the developmental status of a child and assesses performance with respect to age [START_REF] Hadders-Algra | The assessment of minor neurological dysfunction in infancy using the Touwen Infant Neurological Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY Examination: Strengths and limitations[END_REF][START_REF] Hadders-Algra | Two distinct forms of minor neurological dysfunction: Perspectives emerging from a review of data of the Groningen Perinatal Project[END_REF] . Using an age-dependent concept allows to detect even subtle changes which is particularly helpful in a cohort of physically trained adolescent athletes that are expected to perform well in tasks assessing motor performance.

The MND examination consists of 64 tests grouped as eight functional clusters. More details are published elsewhere [START_REF] Hadders-Algra | Examination of the Child with Minor Neurological Dysfunction[END_REF]. In our examination, 28 out of these 64 tests were performed, assessing six functional clusters: (1) Fine motor skills (e.g., finger-opposition test:

tapping the tip of the thumb with each finger of the same hand in a specific sequence), ( 2)

Coordination & balance (e.g., diadochokinesis test while standing: quick antagonistic proand supination movements of the forearm), (3) Posture & tone (e.g., posture while sitting, standing, or walking), (4) Involuntary movements (e.g., sitting/standing choreatic movements or tremor) (5) Associated movements (e.g., in didochokinesis or finger-opposition test), and (6) Sensory function (e.g., graphesthesia, kinesthesia).

The performance of every test was rated as either optimal or non-optimal based on the neurological optimality score (NOS), indicating how many items are performed in an optimal way [START_REF] Hadders-Algra | Examination of the Child with Minor Neurological Dysfunction[END_REF][START_REF] Jong | The Groningen LCPUFA study: No effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years[END_REF]. Optimal performance is based on predefined criteria, meaning that failing a test indicates not meeting the specific predefined criteria of the respective test.

A non-optimal performed cluster is defined as a cluster that includes a number of nonoptimal performed tests that exceeds a specific threshold. If one or more clusters were rated as Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY non-optimal, a participant was assigned to the group with NSS (NSS+ group), and otherwise in the group without NSS (NSS-group). In addition to the overall group categorization, participants were categorized as optimal/non-optimal performing on the cluster-level and on the test-level, respectively.

In a second step, an additional continuous NSS score was calculated because this qualitative clinical categorization approach does not allow to differentiate between participants with higher and lower NSS scores within a specific group. This score is in alignment with the NOS and is referred to as the total NSS score. For instance, a score of 26

indicates that the participant performed optimal in 26/28 tests. Consequently, a higher NSS score indicates better neurological functioning.

In Germany, the assessment was performed by experienced pediatric neurologists.

Examiners from Norway and Belgium were trained by experienced pediatric neurologists from Germany before performing the examination independently. In addition, examinations from Norway and Belgium were videotaped and recorded and were then re-assessed independently by three pediatric neurologists from Germany.

Assessment of postural control using BTrackS

Postural control was assessed at all study sites using a validated portable force platform, BTrackS (Balance Tracking Systems Inc., San Diego, CA, USA) [START_REF] Richmond | Leveling the playing field: Evaluation of a portable instrument for quantifying balance performance[END_REF][START_REF] Goble | A point of application study to determine the accuracy, precision and reliability of a low-cost balance plate for center of pressure measurement[END_REF][START_REF] O'connor | Validating the BTrackS Balance Plate as a low cost alternative for the measurement of sway-induced center of pressure[END_REF], consisting of a 0.4m x 0.6m force platform. A 25 Hz sampling rate was used to capture the ground reaction forces of the postural control assessments, which was registered as resulting COP and was filtered with a second-order, low-pass Butterworth filter (cut-off frequency of 4 Hz) prior to export. Postural control was tested both on a rigid and a compliant (foam) surface. The compliant surface consisted of a 6 cm thick Airex Balance Pad (Alusuisse Airex AG, Switzerland) placed on the force plate.

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Participants performed all postural assessments without shoes and with socks.

Following plate calibration, participants were instructed to stand on the force plate with their head in an upright position and as still as possible with eyes closed, hands on the hips, and feet apart at shoulder width. The start and end of each trial were indicated with an auditory tone. Each trial lasted 20 seconds and was repeated to obtain a total of three trials per condition (i.e., rigid and foam) per participant. All participants performed the rigid trials first, followed by the foam trials. A trial was repeated if a participant did not perform the task correctly (e.g., when a participant kept his eyes open).

The mean/total displacement of the COP, in addition to anterior-posterior (AP) and medial-lateral (ML) directional components, were used to quantify postural stability among participants. Utilizing COP-based equations developed by Thomas Prieto and colleagues in a custom MATLAB [START_REF]Computer Software[END_REF] script [START_REF] Prieto | Measures of postural steadiness: Differences between healthy young and elderly adults[END_REF], three traditional postural metrics were derived for each axis (Mean/AP/ML): (1) path length (PL), which informs about the COP trajectory magnitude, (2) root mean square (RMS) amplitude deviations which represents the standard deviation of the displacement of the COP, and (3) sway area, or the COP displacement between the beginning and end of trial across axes [START_REF] Palmieri | Center-of-pressure parameters used in the assessment of postural control[END_REF]. The three dependent variables were chosen to describe the spatial-temporal and variability aspects of postural performance, respectively. For all measurements, higher values are indicative of poorer static postural control.

Statistical analyses

Statistical analyses were performed using the software R (version 4.0.1) [START_REF] Core | A Language and Environment for Statistical Computing[END_REF]. In the first analysis, a categorical approach using a cut-off criterion based on clinical diagnostic practices was used. Participants were categorized into two groups: a group with and without NSS (NSS+ and NSS-) and groups with optimal/non-optimal performance in the fine motor skills and coordination & balance cluster, as well as in the finger-opposition test and the Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY diadochokinesis test. We selected these two clusters and two tests (1) because based on clinical experience, the performance of fine motor skills and coordination is highly relevant and commonly assessed, and (2) they were the most often non-optimal performed clusters/tests in our cohort. The sample size of participants that performed non-optimal in the other clusters/tests was too small (n < 20) to categorize reasonable groups. It was evaluated whether these groups differ in performance on the postural control tasks. However, while clinically relevant, this approach does not allow for a differentiation between participants with higher and lower NSS scores within a specific group. Therefore, for the second analysis, the continuous total NSS score was correlated with the postural control performance.

Differences in demographical variables between the NSS+ and NSS-group

Chi-Square tests were used to evaluate whether the distribution of participants from the three study sites was similar in the NSS+ and NSS-group. Moreover, to test whether the NSS+ and NSS-group include similar populations, demographical variables such as age, height, and weight and the total NSS score were assessed using independent t-tests.

Differences in postural control between groups

Data from the three acquired trials for each condition (rigid and foam) and each postural control variable (PL, RMS, sway area) were averaged. Outliers were visually inspected and removed if they were most likely caused by a technical error, resulting in an exclusion of one trial of n = 1 participant in the rigid condition. In this case, the remaining two trials were averaged.

Between-group differences (NSS+ and NSS-) in postural control performance in the rigid and foam condition for the variables of interest path length, root mean square, and sway area were calculated using ANCOVAs with age at the time of the neurological examination as a covariate. Additional analysis including study site as a covariate (not shown here), did not change the results. Multiple comparisons were corrected for 14 variables (PL (Mean/AP/ML),

Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY RMS (Mean/AP/ML) and sway area in both rigid and foam condition) using the Bonferroni method. The level of significance was set to α = .05.

Correlation between postural control and total NSS score

Spearman correlation coefficients were used to test whether the total NSS score was associated with postural control performance in the rigid and the foam condition. Spearman correlation was used because the total NSS score was not normally distributed, with more participants scoring on the higher end, meaning better overall performance.

Results

Demographic differences between the NSS+ and NSS-group

Table 1 summarizes the demographic information for both groups (NSS+ and NSS-).

Based on the neurological examination, 26 (18.4%) participants were categorized as NSS+ and 115 (81.6%) participants as NSS-. Of the 141 participants, 115 (81.6%) participants performed optimal in all six clusters (NSS-group), 24 (17.0%) performed non-optimal in one cluster, 1 (0.7%) performed non-optimal in two clusters, and 1 (0.7%) in four clusters. The cluster that most often was performed non-optimal was fine motor skills, performed nonoptimal by 24 participants (17.0%), followed by a non-optimal performance of 3 participants in associated movements (2.1%), of 2 participants in coordination & balance (1.4%) and of 1 participant (0.7%) in posture & tone. Of note, none of the participants performed non-optimal in the sensory function cluster.

There was a significant between-group difference for study site (p = .014) with a greater proportion of participants in the NSS+ group coming from Norway compared to Belgium and Germany. Furthermore, there was a significant between-group difference for age (p = .006), with the NSS+ group being significantly younger than the NSS-group. In addition, there was a significant between-group difference for the total NSS score (p < .001). Height and weight

Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY 20 did not differ significantly between the NSS+ and NSS-group (all p > .05). Moreover, apriori analyses revealed no statistically significant between-group differences regarding the type of sports (soccer versus non-contact) and concussion history (no previous concussion, probable concussion, physician-diagnosed concussion) in the prevalence of NSS (all p > .05) and in the postural control performance (for each dependent variable and condition; all p > .05).

No difference in postural control between the NSS+ and NSS-group

There were no significant differences in postural control for any of the variables of interest, neither in the rigid nor the foam condition between NSS+ (n = 26) and NSS-group (n = 115) (all p > .05; see Table A 1).

No difference in postural control between groups performing optimal/non-optimal on the cluster-level

There were no significant differences in postural control for any of the variables of interest, neither in the rigid nor the foam condition between the groups of participants with optimal and non-optimal performance in the fine motor skills cluster or the coordination & balance cluster (all p > .05).

Significant difference in postural control between groups performing optimal/non-optimal on the test-level

There were no significant differences in postural control for any of the variables of interest, neither in the rigid nor the foam condition, between the groups of participants with optimal (n = 105) and non-optimal (n = 36) performance in the finger-opposition test (all p > .05). The group that performed non-optimal in the diadochokinesis test (n = 33), however, had significantly higher sway area (p = .003), mean path length (p = .022), path length in the ML Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY 21 direction (p = .002), mean root mean square (p = .044), and root mean square in the ML direction (p = .002) in the rigid condition compared to the group that performed optimal in this test (n = 108). Path length and root mean square postural performance in the AP direction, as well as all variables in the foam condition, were not significantly different between groups after correcting for multiple comparisons (p > .05). Differences in postural control between the groups performing optimal/non-optimal in the diadochokinesis test are illustrated in Figure 1 and listed in Table 2. Abbreviations. AP = anterior-posterior, ML = medial-lateral, PL = path length, RMS = root mean square, SD = standard deviation 3 show the correlations between postural control and the total NSS score.

Significant correlation between postural control and total NSS score

The correlations were statistically significant for path length (p = .016) and root mean square in the ML direction in the rigid condition (p = .011), and for path length in the ML direction in the foam condition (p = .025). No significant correlations between postural control in the other variables were detected (all p > .05).

PL

ACCEPTED MANUSCRIPT / CLEAN COPY

This study aimed to investigate the association between an objective quantitative assessment of postural control using force plates and an observer-based neurological examination in a cohort of adolescent athletes. Such associations have not been assessed before, but are of critical importance for clinicians as it provides a more comprehensive assessment of motor maturation between the ages of 13 and 16 years. It was assumed that lower NSS scores would be reflected in reduced postural control performance.

Our results revealed that participants performing non-optimal in the diadochokinesis test showed significantly reduced postural control. More specifically, this effect was only observed in the rigid condition of the postural control measurement, and primarily in the ML direction. No significant between-group differences in postural control were found in the foam condition.

Moreover, we found that the continuous total NSS score was, indeed, correlated with postural control performance. The results revealed a significant correlation between total NSS score and postural control in the ML direction, suggesting that those with lower performance in the neurological examination also tended to produce more ML COP movement in the force plate assessment.

A multi-method approach to NSS evaluation

In the clinical context, postural control is commonly assessed using observer-based tools such as classical neurological tests (i.e., Romberg stance, one-legged stance, tight rope walk).

Particularly when it comes to subtle alterations, instrumented tools such as force plates may

Association of NSS with postural control in medial-lateral direction

Our findings of lower postural control in the ML direction being significantly correlated with a lower total NSS score, and being significantly reduced in the group of participants performing non-optimal in the diadochokinesis test is in alignment with previous literature on motor development [START_REF] Blanchet | Development of postural stability limits: Anteroposterior and mediolateral postural adjustment mechanisms do not follow the same maturation process[END_REF][START_REF] Kirshenbaum | Non-linear development of postural control and strategy use in young children: A longitudinal study[END_REF][START_REF] Hadders-Algra | Variation and variability: Key words in human motor development[END_REF]. It has been shown that AP and ML postural adjustments follow different maturation processes. More specifically, there is evidence that postural control along the ML axis matures later than along the AP axis, possibly being caused by [START_REF] Dazzan | Neurological soft signs in first-episode psychosis: A systematic review[END_REF] earlier maturation of antigravity muscles responsible for AP control, (2) daily life experience that is expected to be greater in the AP direction, and (3) earlier development of the ankle strategy involved in AP postural control than the hip strategy involved in ML postural control [START_REF] Blanchet | Development of postural stability limits: Anteroposterior and mediolateral postural adjustment mechanisms do not follow the same maturation process[END_REF][START_REF] Kirshenbaum | Non-linear development of postural control and strategy use in young children: A longitudinal study[END_REF][START_REF] Hadders-Algra | Variation and variability: Key words in human motor development[END_REF]. We did not observe an association between postural control in the AP axis and NSS scores. While the existence of such an association cannot be ruled out with certainty based on these data, the pattern that we observed is compatible with the possibility that the maturation along the AP axis is already fully developed in our sample.

Moreover, among the neurological tests, the performance of antagonistic forearm movements in quick succession, as examined in the diadochokinesis test, has been shown to mature later than other tests assessing upper-limb motor proficiency [START_REF] Fietzek | Development of the corticospinal system and hand motor function: Central conduction times and motor performance tests[END_REF]. Of note, the two tasks are based on similar underlying functional mechanisms. Both tasks involve higher-order motor networks that control the alternation and timing of muscle activity in agonist and antagonist muscles as a result of cortical excitatory and inhibitory neuronal activity [START_REF] Fietzek | Development of the corticospinal system and hand motor function: Central conduction times and motor performance tests[END_REF].

Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY deal with less stability. Indeed, our data showed a greater variance of postural sway between participants and within the trials of individual participants in the foam condition compared to the rigid condition. Thus, the effects detected in the standardized, rigid condition may have been absent in the foam condition due to individual differences in response to the alteration of tactile inputs (decrease plantar pressure sensations) and stimulation of proprioceptive inputs (instability). Moreover, the foam condition was always performed after the rigid condition and thus, may have been affected more by potential training effects. However, we do not anticipate strong learning effects as only 3 trials of the rigid condition were performed.

Strengths and limitations

It is important to note that in our sample, the NSS+ group was significantly younger than the NSS-group. Preliminary evidence shows that by reaching puberty, the prevalence of NSS decreases due to several factors, including hormonal changes and brain maturation processes [START_REF] Hadders-Algra | Two distinct forms of minor neurological dysfunction: Perspectives emerging from a review of data of the Groningen Perinatal Project[END_REF][START_REF] Soorani-Lunsing | Minor neurological dysfunction after the onset of puberty: association with perinatal events[END_REF]. Therefore, we explicitly controlled our group analyses for a potential age effect.

Correcting or not correcting for age resulted in similar findings. This additional analysis confirmed that in our sample, the age difference between groups did not explain the differences in postural control. Moreover, we replicated our analysis in a sub-sample only including participants from Germany and Norway and excluding participants from Belgium that turned out to be older (~5 months) than the rest of the cohort. Again, our results did not change compared to our main analyses, further confirming that our findings were not merely the result of an age difference between groups.

The fact that we performed an adapted version of the neurological examination to maximize the cost-benefit ratio, leaves the possibility that we may have missed potentially relevant tests in one of the clusters, in particular, the coordination & balance cluster. Such tests, in addition to the performance in the diadochokinesis test, may have correlated with the objective postural control assessment. Moreover, given that the sample size of some non-Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY optimal performed clusters and tests was too small for further analyses, we cannot interpret the association of these motor functions with postural control performance.

In addition to investigating an understudied population, another strength of the current study is that we were able to recruit athletes from various disciplines and three different study sites, resulting in a comparably large sample of this specific population. While this multi-site approach required differences in the NSS assessment setup (i.e., video vs. in-person evaluation), this decision allowed for relying on a comprehensive multi-rater approach to score the video examinations.

Conclusion

The current study demonstrated that the presence of NSS, and in particular non-optimal performance in the diadochokinesis test, is related to objective postural control performance in male adolescent athletes. Our

  Abbreviations. B = Belgium, G = Germany, N = Norway, NSS = neurological soft signs, SD = standard deviation, SE = standard error, X 2 = Chi Square

Figure 1 .

 1 Figure 1. Significant difference between groups performing optimal/non-optimal in the

Figure 2

 2 Figure 2 and Table3show the correlations between postural control and the total NSS score.

Figure 2 .

 2 Figure 2. Scatterplots showing negative correlations between postural control and the total

  add additional and objective information to what even an experienced clinician can detect by eye. Using force plates in addition to a neurological examination may, thus, support clinicians by providing a more comprehensive and personalized assessment of motor maturation. Indeed, in the current study, the instrumented assessment of postural control revealed that Journal Pre-proof ACCEPTED MANUSCRIPT / CLEAN COPY reduced performance in postural control along the ML axis was associated with a lower total NSS score. Nonetheless, more research is needed to determine the common underlying neurodevelopmental substrates of the quantitative and qualitative findings and whether other instruments or test conditions can quantitatively reflect other tasks derived from the NSS assessment.

  Abbreviatio

Table 1

 1

	. Cohort Characteristics
		NSS+ (n = 26)	NSS-(n = 115)	Statistical test
				X 2 = 8.540, df =
	Study site	B (2), G (5), N	B (32), G (38), N
				2,
	(n)	(19)	(45)
				p = .014 *
	Age [years]			t (139) = -2.798,
		14.70 (0.67)	15.14 (0.74)
	Mean (SD)			p = .006 *
	Height [cm]			t (135) = -1.861,
		170.32 (10.01)	173.62 (7.50)
	Mean (SD)			p = .065
	Weight [kg]			t (134) = -1.130,
		58.19 (10.35)	60.39 (8.55)
	Mean (SD)			p = .260
	Total NSS score Median	21.50 (0.55)	25.30 (0.19)	t (139) = -7.912,
	(SE)			p < .001 *
	Note. * Indicates significant difference between groups at p < .05.

Table 2 .

 2 Difference in Postural Control between Groups Performing Optimal/Non-Optimal in

			Journal Pre-proof
	the Diadochokinesis Test
	Postural	Non-optimal	Optimal
	control	diadochokinesis	diadochokinesis	F	p
		Mean (SD)	Mean (SD)
	Rigid
	PL	30.82 (10.34)	25.11 (7.93)	F (1, 136) =	p = .022
				10.429	*
	PL ML	16.77 (7.55)	12.34 (4.28)	F (1, 136) =	p = .002
				15.651	*
	PL AP	21.79 (6.97)	18.99 (6.67)	F (1, 136) =	p = .526
				4.410
	RMS	0.63 (0.24)	0.51 (0.16)	F (1, 136) =	p = .044
				9.060	*
	RMS ML	0.27 (0.10)	0.20 (0.08)	F (1, 136) =	p = .002
				15.185	*
	RMS AP	0.56 (0.23)	0.47 (0.15)	F (1, 136) =	p = .187
				6.279
	Sway area	0.28 (0.21)	0.17 (0.10)	F (1, 136) =	p = .003
				14.756	*
	Foam
	PL	66.41 (20.72)	60.96 (13.95)	F (1, 136) =	p > .999
				2.093
	PL ML	30.73 (8.90)	27.71 (7.89)	F (1, 136) =	p > .999
				2.515

ACCEPTED MANUSCRIPT / CLEAN COPY

Note. * All p-values were corrected for 14 variables at p < .05.

YT receives funding from ERA-NET Neuron [01EW1707] and from the National Institutes of Health [NIH R01 HL141774-02] and [NIH R01 HD090191]. EK receives royalties for book chapters and recieved speaker honoraria and travel support from Medtronic, UCB, Livanova, and Eisai and has participated in clinical trials for Medtronic, UCB and Precisis, all unrelated to the submitted work. JSH receives funding for a Fellowship Award from Harvard Medical School Livingston and for a Young Investigator Grant sponsored by Mary and John Osterhaus and the Brain & Behavior Research Foundation. IKK receives grant funding from the National Institutes of Health (USA), the European Research Council, and the German Ministry of Education and Research. IKK receives funding for a collaborative project and serves as a paid scientific advisor for Abbott. She receives royalties for book chapters. Her spouse is an employee at Siemens AG. Funding: Funding was provided through the framework of ERA-NET Neuron [01EW1707]. The individual national funding agencies are the German Ministry for Education and Research (Germany), the Research Foundation Flanders [G0H2217N] and Flemish Government (Sport Vlaanderen, D3392), Slovak Academy of Sciences and Ministry of Education of Slovak Republic [APVV-17-0668], the Dutch Research Council (NOW), the Norwegian Research Council (NFR), and the Ministry of Health, Israel [#3-13898]. This work was also supported by the European Research Council [ERC Starting Grant 804326].

Thus, our unique finding of reduced postural control along the ML axis in a group of participants that performed non-optimal in the diadochokinesis test aligns with already existing knowledge. The performance in postural control and diadochokinesis movements may thus serve as indicators of motor maturation.

Adolescent competitive athletes receive extensive physical training during a crucial period of physiological motor development. Accordingly, one may expect that adolescent athletes will be more skilled in motor tasks, including postural control, than the general adolescent population. Indeed, it has been demonstrated that increased sensorimotor experience in sensitive developmental periods can improve motor proficiency [START_REF] Penhune | Parallel contributions of cerebellar, striatal and M1 mechanisms to motor sequence learning[END_REF][START_REF] Bieć | Postural control in 13-year-old soccer players[END_REF].

Interestingly, Bieć & Kuczyński have shown that in sports disciplines such as soccer which requires bodyweight transfers along the ML axis, 13-year old soccer players had better postural control in the ML direction in comparison with a control group [START_REF] Bieć | Postural control in 13-year-old soccer players[END_REF]. Moreover, a recently published study found a positive effect of special sensorimotor training in kicking sports on medio-lateral performance in postural control (REFERENCE). Thus, differences in postural control performance depending on the participants' athletic background may be assumed. Unfortunately, we were unable to compare sport disciplines (e.g., soccer, swimming, etc.) in our sample due to insufficient sizes of subsamples. It may be interesting for future studies to evaluate the association between postural control along the ML axis and NSS in athletes from different disciplines and compare with a non-athlete population.

Group differences in the rigid but not foam condition

We detected group differences only in the rigid, but not the foam condition. Moreover, fewer variables in the foam condition compared to the rigid condition were significantly correlated with the total NSS score. While the rigid condition is a well-validated method that is often used in research [START_REF] O'connor | Validating the BTrackS Balance Plate as a low cost alternative for the measurement of sway-induced center of pressure[END_REF], the foam condition may have resulted in a greater variability, or in other words random noise, of postural control performance e.g., due to differences in the ability to Journal Pre-proof

ACCEPTED MANUSCRIPT / CLEAN COPY


Joachim Schöpfel
email: joachim.schopfel@univ-lille.fr

Hélène Prost
email: helene.prost@cnrs.fr

Open Science as an Opportunity for Academic Grey Literature -A Systematic Review

Keywords: Open science, open access, open repositories, grey literature

Introduction

What is the future of academic grey literature? A couple of papers have made assumptions in the past about the perspectives of grey literature, for instance, regarding the impact of new technologies or of research policies. Some predicted an unprecedented increase of the volume of grey literature, with global and unrestricted accessibility [START_REF] Mackenzie Owen | Expanding the Horizon of Grey Literature[END_REF], while others did not observe an unusual growth of grey documents (Artus, 2005) or projected a greater diversity of grey literature and convergence between grey and white [START_REF] Schöpfel | Observations on the Future of Grey Literature[END_REF]. In GreyNet's 2021 online survey on the future of grey literature, two-third of the respondents among GreyNet's own community of practice agreed that "in academic institutions, the affirmation of open science and open access principles significantly favor the production, publication, and retrieval of grey literature" [START_REF] Schöpfel | Data from "Exploring Next Generation Grey[END_REF] As for grey literature in repositories, one respondent wondered "(…) if it is still grey literature (because) published grey literature is no more grey". The boundary between white and grey is still a matter of discussion, such as the distinction between data and documents. Probably it is the very concept of grey literature that is at stake, being often, especially in systematic reviews, described as "unpublished" and "non-reviewed research" (Schöpfel & Prost, 2021) which is not exactly its meaning in library and information sciences, where the focus is on dissemination and acquisition [START_REF] Schöpfel | Are Electronic Theses and Dissertations (Still) Grey Literature in the Digital Age? A FAIR Debate[END_REF].

Forecasting the future of grey literature may appear hazardous in an environment of constant and rapid change. Our paper takes a somewhat different approach, insofar we try to find out how (and if) some essential topics of the actual debate on open science have been linked to the field of grey literature. Based on a systematic review, we assessed the topics of bibliodiversity (production), of open repositories (dissemination), of research assessment (evaluation) and of FAIR principles (processing). Some results confirm what we already know; others are more surprising.

The paper is a contribution to the analysis of the development of grey literature in the academic research environment of the 21 st century. It is also a rejoinder to GreyNet's panel discussion on the "Next Generation Grey" in 2021.

Methodology

We conducted a systematic review on relevant studies published between 2018 and 2022 on grey literature and open science in two bibliographic databases (Web of Science, Scopus), in the Grey Guide repository and with two academic discovery tools (Dimensions, Google Scholar). The review was conducted on August 2, 2022. The retrieval strategies and filters are described in the appendix. Figure 1 shows the results of the systematic review.

Results

The call for bibliodiversity (production)

Open access to scientific information is a main pillar of open science. There is no doubt that grey literature plays a significant role in the development of open access (OA), as many repositories contain grey literature (figure 1) where it represents up to 30% of the content (Schöpfel et al., 2020). However, the academic and political debate on open access mainly concerns journals and seems to ignore grey literature, as the main challenge is the business model of OA journal publishing and its economic and political impact. In the usual conceptualization of OA publishing, grey literature is more or less invisible, somewhere in the small field of non-peer reviewed items, free for readers and for authors, protected by copyright, along with preprints (figure 2). Even if the main concern of the Jussieu Call is journal and book publishing, its scope is larger as it explicitly invites for innovation and experimentation in the field of dissemination of research results and academic publishing. Our systematic review retrieved recent papers that highlight the richness and the diversity of unconventional academic literature, (partly) non reviewed and (partly) published outside of the usual commercial channels: servers and repositories contributes to the knowledge of the field, including deadlocks [START_REF] Lombardi | Every Document is Born 'Grey' -Some Documents Can Become 'Open[END_REF]. The Japan Atomic Energy Agency (JAEA) brings up the issues of long-term preservation and permanent access of conference proceedings and technical reports published in electronic media such as CD/DVD-ROM and flash memory [START_REF] Kumazaki | Published Electronic Media are Becoming Grey[END_REF]. Providing long-term preservation and improving discoverability of reports is also the purpose at Columbia University Libraries [START_REF] Bielskas | Technical Reports in the Repository: Syncing a Unique Grey Literature Collection in Multiple Columbia University Library Systems[END_REF]; in a similar approach, Cirkovic et al. ( 2019) argue for digitization, curation, preservation, and dissemination via open repositories of scientific heritage material, like older theses and dissertations.

Other categories and elements of grey literature have been put forward, in different domains:

• Law: Williams (2020) discusses the place of grey literature in the realm of legal materials (primary and secondary sources) and the challenges of discoverability of various types of grey legal materials. • Linguistics: A study from the Italian CNR assesses the presence of a large variety of grey literature in the CLARIN Virtual Language Observatory, including translations, agreements, press releases, notebooks, and bulletins [START_REF] Goggi | Providing Access to Grey Literature: The CLARIN Infrastructure (Poster)[END_REF] 4 . • Open educational resources (OER): [START_REF] Puccinelli | Open Educational Resources and Library & Information Science: Towards a Common Framework for Methodological Approaches and Technical Solutions[END_REF] provide a framework for the management of OER characterized by "openness, flexibility, innovative approaches, digital dimension, liquidity and high granularity" and insist on the development of "validated and certified platforms, for providing quality levels in shared contexts, and persistent identification systems, for guaranteeing resources integrity (and) traceability". • Another paper describes grey literature outside of academy, as extra-academic and/or professional documents, such as expert, CRM, R&D or corporate annual reports, market studies, executive directives, memoranda, white papers, and hearings, with examples in the fields of nuclear energy, aeronautics, archaeology and library and information sciences and four major challenges, i.e., monitoring, standardization, data, and preservation [START_REF] Schöpfel | Grey Literature and Professional Knowledge Making[END_REF].

Assuming that "traditional publishing streams of books and journals capture just a fraction of the content (…) contextualized in open science", Gelfand & Lin (2020) provide a taxonomy of new forms of scholarship including theses, preprints, lab manuals, interviews, and other multimedia materials, and demonstrate how, in the context of open science, the research process contribute to "outputs, innovation and new forms of grey literature". A similar, large range of resources has been identified by a scientometric study on systematic reviews and other articles making use of grey literature (Schöpfel & Prost, 2021).

Obviously, there is a common ground where both concepts, bibliodiversity and grey literature, overlap.

As the Jussieu Call admits, the "means to achieve the goal of Open Access are yet to be discussed". Our suggestion is that the signing institutions -research organizations and scientific communities, scientific and technical information professional associations and organizations, learned societies, scientific journals and editors -explicitly consider grey literature when they refocus "the issue of business models (...) in the broader perspective of the editorial processes and methods upon which research and innovation will rely in the future", for the benefit of a "very broad bibliodiversity".

The GreyNet community of practice, on the other side, should seize the opportunity of the Open Science initiatives for bibliodiversity, such as the Jussieu Call, for advocacy and promotion of the richness and diversity of grey literature which are in constant need for attention, curation, funding, and innovation, in order to increase its findability and accessibility.

The development of open repositories (dissemination)

More than ten years ago, Daniela Luzi reviewed the development of institutional repositories and stated that "grey literature is at home in open archives" [START_REF] Luzi | Grey Documents in Open Archives[END_REF]. Which are the issues of grey literature in open repositories today, and how do repositories impact the dissemination of grey literature?

Like Daniela Luzi, most retrieved papers express the conviction, based on evidence, that repositories are good for grey literature and that grey literature, as an essential part of scientific output, should be part of repositories. "Archiving in a repository is the way to let grey literature to become open" [START_REF] Lombardi | Every Document is Born 'Grey' -Some Documents Can Become 'Open[END_REF]. Based on a study on grey literature in repositories of Balkan countries, an invited paper of the 2018 UNESCO International Conference on Digital Presentation and Preservation of Cultural and Scientific Heritage recommends that universities and academic libraries "should direct their efforts towards the creation of institutional repositories, allowing the preservation of and free access to the results of scientific studies performed at the institution, to its theses and dissertations, as well as to other kinds of grey literature" [START_REF] Pavlovska | Grey Literature" in Electronic Archives[END_REF].

A survey at the University of Minnesota concludes that "endorsing the depositing of materials into (institutional repositories) is a step in the direction of efficiency". Because many researchers are using Google and Google Scholar to locate grey literature, librarians should encourage the deposit grey literature into repositories in order to "mitigate the web instability factor to which grey literature falls prey" and to increase accessibility "when Google crawls (institutional repositories)" [START_REF] Cooper | Grey Literature: Use, Creation, and Citation Habits of Faculty Researchers across Disciplines[END_REF]. Based on many years of interdisciplinary research on grey marine literature, MacDonald et al. ( 2020) demonstrate how open practices can increase the impact of grey literature on political decisionmaking processes; yet, MacDonald and his colleagues also alert that this impact can be affected by (too) massive quantity, multiplicity of formats and content, and by (perceived) uncertain quality.

Similar results on the dissemination of grey literature via open repositories can be found in studies from Algeria [START_REF] Babori | Increasing the Visibility of Grey Literature in Algerian Institutional Repositories[END_REF], France [START_REF] Schöpfel | Going Green. Publishing Academic Grey Literature in Laboratory Collections on HAL[END_REF](Schöpfel et al., , 2020(Schöpfel et al., and 2021)), the United States [START_REF] Lipinski | How Open Access Policies Affect Access to Grey Literature in University Digital Repositories: A Case Study of iSchools[END_REF][START_REF] Mack | Open Access in the Academy: Developing a Library Program for Campus Engagement[END_REF], and from the BRICS countries [START_REF] Bansal | Grey Literature Archiving Pattern in BRICS Open Access Repositories[END_REF] Other papers describe the role of academic and national libraries [START_REF] Richardson | Capturing Gray Literature for the Institutional Repository[END_REF][START_REF] Kingsley | The 'Impact Opportunity' for Academic Libraries through Grey Literature[END_REF][START_REF] Vandepontseele | Grey Literature and Legal Deposit: The Approach of the Royal Library of Belgium[END_REF][START_REF] Marsolek | Grey Literature: Advocating for Diverse Voices, Increased Use, Improved Access, and Preservation[END_REF], with special attention on the need for identification, capture and deposit of grey literature into institutional repositories, for metadata curation, and for advocacy and awareness raising among the scientific communities. A comparison between institutional repositories and national aggregator systems insists on the need for advocacy and promotion on the institutional level: without the researchers' practice of self-archiving, the repositories will remain empty (Cernohlavkova & Vycitalova, 2018).

The main argument of Marsolek and her colleagues from the University of Minnesota is that grey literature increases the richness and the diversity of the libraries digital collections which is crucial for the quality of systematic reviews. Also, they conclude with a kind of pro-grey pleading: "Librarians have done and continue to do the important work of collecting GL, preserving it, and providing access to it.

For those who are collecting GL, in solidarity we thank you and ask you to please continue the work (…)

We encourage those who are not collecting GL to begin talking with your colleagues about how collecting it could be an opportunity for your organizations (…)" [START_REF] Marsolek | Grey Literature: Advocating for Diverse Voices, Increased Use, Improved Access, and Preservation[END_REF].

A final, general comment, based on two very different papers. The first paper, an introduction into the field and concept of grey literature, emphasizes its importance and dynamic nature and concludes that "technology has played a catalytic role in eradicating the issues and problems (of) grey literature" [START_REF] Gul | Is Grey Literature Really Grey or a Hidden Glory to Showcase the Sleeping Beauty[END_REF], where technology means above all repositories (platforms) and search engines. A second paper presents results of a needs assessment for improving library support for dentistry researchers: 80% of participants use grey literature for their research (primarily, conference and seminar proceedings, and theses and dissertations), none of them consider it as "very important", and only 20% indicate that they found it somewhat easy to search for and access it. Also, the authors of the study conclude that more and better library support is needed (He et al., 2018).

Taken together, these recent papers on grey literature in open repositories seem to confirm what has already been observed more than ten years ago [START_REF] Schöpfel | Open is Not Enough: A Case Study on Grey Literature in an OAI Environment[END_REF]: repositories are essential for the dissemination, visibility, and use of grey literature, and their technology has contributed to expand its impact; but repositories have not (with the words of [START_REF] Gul | Is Grey Literature Really Grey or a Hidden Glory to Showcase the Sleeping Beauty[END_REF]) "eradicated the issues and problems of grey literature", and they have not "white-washed" it. Open access or even accessibility is still not enough. More efforts and investment are required, to improve the curation of grey literature (metadata, including persistent identifiers) and to increase the assurance regarding quality and longterm archiving. The situation has not fundamentally changed since then; even if today, these questions are addressed (and reformulated) in terms of the FAIR principles (see below The reverse is true. All these declarations and reports have in common that they recommend diversity and inclusivity as fundamental criteria for research assessment. DORA (which has been signed by more than 22,000 institutions and individuals in 159 countries and is supported by the European Commission) recommends that funders and institutions consider, for the purposes of research assessment, "the value and impact of all research outputs (including datasets and software) in addition to research publications". The EC Scoping report asks that research assessment should acknowledge the "diversity of research activities and practices, with a diversity of outputs", while the Paris Call promotes the concept of bibliodiversity (see above), which means to consider "all scientific productions", including for instance, preprints.

The UNESCO paper is more precise; starting from the assumption that "evaluation systems should take into account the wide breadth of missions within the knowledge creation environment (and that) these missions come with different forms of knowledge creation and communication, not limited to publishing in peer reviewed international journals", the UNESCO recommends that research assessment should include all kind of scientific publications such as, among others, peer-reviewed journal articles and books, research reports and conference papers, disseminated by publishers and/or deposited in open repositories.

Our review retrieved only few papers that explicitly deal with this topic. The most relevant one is perhaps the case study by [START_REF] Giannini | Grey Literature and Research Assessment exercises: From the current criteria to the Open Science models[END_REF] 9 who analyzed the Italian research assessment exercises 2004-2010 and 2011-2014 and concluded that

• Both exercises did not explicitly include or mention grey literature;

• Yet, a detailed and time-consuming assessment allows the identification of some types of grey literature among the cited references of research products (output); • This identified grey literature represents less than 1% of all cited output; • This percentage is slightly increasing, from 0.61% (2004-2010) to 0.74% (2010-2014);

• The relative importance of grey literature varies between disciplines. These findings are not optimistic but appear realistic, and they are compliant with the general observation that grey literature is "usually ignored in research evaluations" [START_REF] Bickley | Can the impact of grey literature be assessed? An investigation of UK government publications cited by articles and books[END_REF]. However, without any other empirical evidence (we could not retrieve any other paper like this one), it is impossible to say if these findings are representative for the research assessment in large research organizations, and if there have been changes since then.

A recent paper by [START_REF] Reed | Evaluating impact from research: A methodological framework[END_REF] proposes a conceptual framework of research assessment exercises. Based on a systematic review, the authors identify five different approaches of research impact evaluation; but only one design explicitly includes grey literature, i.e., "evidence synthesis approaches" which provide summative evidence of research as a sufficient cause of impact (figure 5). Following [START_REF] Reed | Evaluating impact from research: A methodological framework[END_REF], such evidence synthesis "typically takes place at the programme level and draws on bodies of work emerging from multiple projects"; it is "a process of carrying out a review of existing data, literature and other forms of evidence with pre-defined methodological approaches, to provide a transparent, rigorous and objective assessment of whether something arising from research is a sufficient cause of impactful outcomes (…)". As systematic reviews generally include grey literature, they are (or should be) part of this kind of research assessment. However, the authors are aware of the potential issues of including grey literature into evidence synthesis: "it is time and labour intensive as it requires considerable consultation with likely end-users and searching of unpublished and grey literature, often by hand and often at geographically disparate locations".

If the interest of grey literature for systematic reviews is largely accepted [START_REF] Bonato | Searching the grey literature: a handbook for finding reports, working papers, and unpublished research[END_REF][START_REF] Hoffecker | Grey Literature Searching for Systematic Reviews in the Health Sciences[END_REF]Schöpfel & Prost, 2021), the related problems have been identified, like the lack of persistent identifiers and of rich metadata, reduced findability and accessibility, issues that limit the grey literature's usefulness for monitoring and altmetrics and make it still more difficult to conduct scientometric assessment with grey literature than with journal articles or books [START_REF] Bickley | Can the impact of grey literature be assessed? An investigation of UK government publications cited by articles and books[END_REF][START_REF] Roos Lindgreen | Exploring the effectiveness of grey literature indicators and life cycle assessment in assessing circular economy at the micro level: a comparative analysis[END_REF]Schöpfel & Prost, 2020;[START_REF] Valles | An Altmetric Alternative for Measuring the Impact of University Institutional Repositories' Grey Literature[END_REF]. Also, when [START_REF] Kenfield | Measuring reuse of institutionally-hosted grey literature[END_REF] tried to develop a framework for the reuse assessment of grey literature in institutional repositories, they observed different barriers, such as "lack of best practices, documented workflows, assessment training, and staffing". "Improper indexing and bibliographic control" are other barriers to the reuse (citation) and assessment of grey literature [START_REF] Shrivastava | Analysis of the usage and diversity of grey literature in addiction research: a study[END_REF].

Obviously, we can observe a kind of paradox: while the international initiatives to transform quantitative and journal-based research assessment explicitly call for more diversity of research outputs, the role and importance of grey literature for research assessment remain marginal, so far. Is this definitive and inherent to the characteristics of grey literature? Not sure. But without any doubt, advocacy and promotion of diversity will not be enough to raise awareness for the interest of grey literature for research assessment, if it is not (more) compliant with the fundamental values and principles of open science, including FAIR. The UNESCO recommendation is very clear: research assessment should make use of repositories and other platforms "that are supported and maintained by an academic institution, scholarly society, government agency or other well-established not-forprofit organization devoted to common good that enables open access, unrestricted distribution, interoperability and long-term digital preservation and archiving"; and it should ensure diversity in "scholarly communications with adherence to the principles of open, transparent and equitable access and supporting non-commercial publishing models and collaborative publishing models with no article processing charges or book processing charges". To increase its role for research assessment, grey literature must be open, accessible, and findable, and it must be disseminated on trustworthy platforms and with FAIR data and metadata.

The application of FAIR principles (processing)

Are the FAIR principles relevant for the processing of grey literature, and if so, which ones and in which way? Initially developed for research data repositories [START_REF] Wilkinson | The FAIR Guiding Principles for scientific data management and stewardship[END_REF], they have been progressively applied to all kind of infrastructures, procedures, and resources, including items belonging to grey literature10 . Our systematic review reveals that above all, two FAIR principles are an issue for grey literature, i.e., findability and accessibility.

Findability: Grey literature is relevant if not a must-have for systematic reviews (see for instance [START_REF] Whaley | Recommendations for the Conduct of Systematic Reviews in Toxicology and Environmental Health Research (COSTER)[END_REF]also, Schöpfel & Prost, 2021); yet, the inclusion of grey literature in reviews is generally considered as more time-consuming and costly as for journal articles [START_REF] Enticott | Finding 'Hard to Find' Literature on Hard to Find Groups: A Novel Technique to Search Grey Literature on Refugees and Asylum Seekers[END_REF], mainly because grey resources have less standardized publication formats [START_REF] Landerdahl Stridsberg | Gray Literature in Evaluating Effectiveness in Digital Health and Health and Welfare Technology: A Source Worth Considering[END_REF]. A couple of papers make recommendations how to improve findability of grey literature, especially through the enrichment of metadata and indexing [START_REF] Jamoulle | Indexing grey literature in General Practice: Family Medicine in the Era of Semantic Web[END_REF][START_REF] Marsolek | The Types, Frequencies, and Findability of Disciplinary Grey Literature within Prominent Subject Databases and Academic Institutional Repositories[END_REF] and the minting and usage of persistent identifiers, namely DOI but also ISSN, ORCID and ROR [START_REF] Farace | AccessGrey: Securing Open Access to Grey Literature for Science and Society[END_REF]2021;[START_REF] Price | An Institutional Repository Publishing Model for Imperial College London Grey Literature[END_REF][START_REF] Reynolds | ISSN Is for Black, White, and Many Shades of Grey[END_REF]. Careful curation is required to improve the visibility and searchability of grey literature; or with the words of [START_REF] Marsolek | The Types, Frequencies, and Findability of Disciplinary Grey Literature within Prominent Subject Databases and Academic Institutional Repositories[END_REF], an "increased level of collection development of grey literature in institutional repositories would facilitate preservation and increase the findability and reach of grey literature".

Accessibility: Open access with no or less restrictions remains an issue for grey literature, even if the deposit of theses and dissertations, conference proceedings, working papers and reports on open repositories improved their dissemination and impact. As said above, many repositories contain grey literature (figure 1) where it represents up to 30% of the content. However, other platforms are useful for different types of grey literature, such as PubMed Central and Clinicaltrials.gov from the US National Library of Medicine [START_REF] Sheehan | Open Science and the Transformation of Scholarly Communication[END_REF] or ConfIDent, the conference platform from the German National Library for Scientific and Technical Information [START_REF] Hagemann-Wilholt | ConfIDent -An Open Platform for FAIR Conference Metadata[END_REF]. On the other hand, embargo periods can reduce the accessibility of grey resources on institutional repositories [START_REF] Rasuli | Reasons for Embargoing Academic Publications in Institutional Repositories. Case Study of Theses and Dissertations[END_REF]. Figure 6. Embargo policies in universities (source: [START_REF] Rasuli | Reasons for Embargoing Academic Publications in Institutional Repositories. Case Study of Theses and Dissertations[END_REF] We can make two recommendations, and they are not really new: The producers of academic grey literature (research organizations, universities…) and repository managers should systematically attribute persistent identifiers to grey literature (dissertations, reports, working papers, conference papers…), especially when these documents are deposited in institutional repositories. On the other hand, institutions and repositories should create a framework (= technical, political, social, and legal environment) that fosters openness and accessibility of grey literature

Perspectives

The findings of our review reflect a continuing scientific and professional interest in grey literature, inand outside of the GreyNet community of practice, as reflected by special issues in academic journals (Dyas-Correia & Mering, 2021;[START_REF] Garousi | Introduction to the Special Issue on: Grey Literature and Multivocal Literature Reviews (MLRs) in software engineering[END_REF], by handbooks [START_REF] Bonato | Searching the grey literature: a handbook for finding reports, working papers, and unpublished research[END_REF] and by a steadily growing number of systematic reviews (Schöpfel & Prost, 2021). The main issue of grey literature today is not typology but FAIRness.

Open science improves the openness of grey literature, its visibility, and its accessibility especially in open repositories. However, as our findings show, open science also emphasizes and exacerbates the usual shortfalls of grey literature, the lack of persistent identifiers, problems with the quality and the richness of metadata, and with the long-term conservation. According to some recent research, these issues are not specific to grey literature; inconsistent implementation of unique identifiers are key challenges for open access books [START_REF] Laakso | Open access books through open data sources: Assessing prevalence, providers, and preservation[END_REF], and open access journals can simply vanish from the web [START_REF] Laakso | Open is not Forever: A Study of Vanished Open Access Journals[END_REF]. But the lack of long-term conservation, of findability (i.e., non-efficient search and retrieval) and of standards are serious threats to the sustainability of grey literature [START_REF] Savic | The Impact of Digital Transformation on the Sustainability of Grey Literature[END_REF]. Thus, open science is an opportunity as well as a challenge for grey literature. One way to face the challenge is the continuous work on the concept of grey literature: "Taking into consideration the volume and speed of (grey literature) creation, there seems to be a need to revisit the old definition of GL by refocusing on quality, intellectual property, curation, sustainability and usability (so that) proper attention can be focused on relevant (…) issues and solutions" [START_REF] Savic | Rethinking the Role of Grey Literature in the Fourth Industrial Revolution[END_REF]. This conceptual work is not simple, as there are contradictory arguments and perspectives; but as open science is here to stay, grey literature should be "completely integrated in the emerging open science infrastructures, as open as possible (and just as closed as necessary), easily retrievable and accessible and largely reusable by (machines)" [START_REF] Schöpfel | Are Electronic Theses and Dissertations (Still) Grey Literature in the Digital Age? A FAIR Debate[END_REF].

In the previous sections we made some recommendations for grey literature producers and services. Our final suggestion for the GreyNet community of practice would be a kind of grey literature observatory, a virtual place for information professionals, researchers and service provides, to analyze and discuss the impact of open science on grey literature and to contribute to its integration into this new landscape, with advocacy, information, and training.

Figure 1 .

 1 Figure 1. PRISMA 2020 flow diagram of the systematic review on grey literature We were looking on recent, original research work on the impact of open science on grey literature, with relevant insights on the production and dissemination of grey literature, on its role for research assessment and on the application of FAIR principles. Initially, we identified 25,580 records. Most records have been discarded because they mentioned grey literature only as part of systematic reviews; others have been excluded because they were not original research or not relevant for open science. Half of the 53 included studies are papers presented at the International Conferences on Grey Literature and/or published by GreyNet's The Grey Journal, i.e., products of the GreyNet's community of practice.

Figure 1 .

 1 Figure 1. Content types overview in open repositories (N=5,971) (source: OpenDOAR, October 23, 2022)

Figure 2 .

 2 Figure 2. Different types of open access in scholarly publishing (source: Wikipedia Open Access 1 ) Recently, a couple of initiatives have been taken against the development of a dominant OA publishing model based on article processing charges (APC). While some focus on journals, such as the Action Plan for Diamond Open Access 2 promoted by Science Europe and the cOAlitionS, others are more open and inclusive, like the Jussieu Call for Open Science and Bibliodiversity 3 launched in 2017 by French scientists and professionals and promoting open access to scientific publications that encourages bibliodiversity and innovation and does not imply the exclusive transfer of subscriptions to APCs.

Figure 3 .

 3 Figure 3. Network of interlinked research objects (source: Sheehan, 2021)

Figure 4 .

 4 Figure 4. Part of grey literature in the HAL repository (source: Schöpfel et al., 2021)

Figure 5 .

 5 Figure 5. Five types of impact evaluation designs (Source: Reed et al., 2021)

Table 1 .

 1 . It remains uncertain, however, what this exactly means, and if open science is an opportunity or a threat for grey literature, or just another challenge that needs awareness and further action, or all together (table 1). Scenarios for grey literature

	Scenario	Examples
	Opportunity	More grey documents
		More diversity
		Better visibility
		More impact
	Challenge	Curation of metadata
		Persistent identifiers
		Openness
	Threat	Less grey documents
		Less impact

  We try to sum up what is known about grey literature and open science and to make clear what is questionable and what needs more insight.

  . Our own research in France shows that grey literature represents about 30% of the national repository's content. While[START_REF] Mack | Open Access in the Academy: Developing a Library Program for Campus Engagement[END_REF] provides a model for the development of a campus-based open access program with a special focus on grey literature, Babori & Aknouche (2020) make recommendations how to improve the deposit, visibility, and usage of grey literature in institutional repositories.[START_REF] Lipinski | How Open Access Policies Affect Access to Grey Literature in University Digital Repositories: A Case Study of iSchools[END_REF] assess the open access policies of 22 US iSchools, show how these policies can affect access to grey literature, and recommend best practices for grey literature in institutional repositories.

  ). One interesting example how the situation can be improved on the top of open repositories is presented by Vicary & Pettman (2020), capitalizing "on the opportunities presented by Open Science and new technologies". How do the recent initiatives for a new system of research assessment affect the grey literature? Do they? Neither the San Francisco Declaration on Research Assessment (DORA) 5 , nor the recent European Commission Scoping report Towards a reform of the research assessment system 6 , nor the UNESCO Recommendation for Open Science 7 , nor the Paris Call on Research Assessment presented at the Open Science European Conference (OSEC)8 , organized in the context of the French Presidency of the Council of the European Union, specifically mention grey literature. Does this mean that grey literature plays no (or only a marginal) role when it comes to transform the actual system dominated by journal-based metrics like the impact factor?

	The transformation of research assessment (evaluation)

This paper was retrieved because the communication was published in the conference proceedings in 2018.

DORA (2012) https://sfdora.org/

EC Scoping report (2021) https://op.europa.eu/en/publication-detail/-/publication/36ebb96c-50c5-11ec-91ac-01aa75ed71a1/language-en

7 UNESCO Recommendation (2021) https://en.unesco.org/science-sustainable-future/openscience/

recommendation 8 OSEC (2022) https://osec2022.eu/paris-call/

This paper was retrieved because the communication was published in the conference proceedings in 2018.

See for instance the recent NDLTD conference on the FAIRness of electronic theses and dissertations at Novi Sad, Serbia https://etd2022.uns.ac.rs/

Appendix

We searched for publications in English, published between 2018 and 2022.

Web of Science:

We searched in the WoS Core Collection for "grey literature" or "gray literature" in title, abstract and keywords. Review articles were excluded. We then filtered with the following terms