dataesr/scientific-paragraphs-categorization huggingface dataset:
In the bottom panel circles are added for visual aid due to the small standard deviations. The inferred dynamics in state space of the three example nodes are on the right. The vector field is evaluated assuming zero network input and using the inferred region-and subject-specific parameters. (F) Inferred regional parameters colored by the ground truth values of the bifurcation parameter a i (top) and frequency f i (bottom). The bifurcation parameter correlates with inferred θ r 2 , while frequency correlates with θ r 1 , but only for regions in the oscillatory regime, i. e. where a i > 0. (G) Timeseries generated with the trained model and using the inferred parameters. Important features of the data are preserved both the level of single regions (amplitude, frequency) as well as on the network level (functional connectivity).
Acknowledgements This work was supported by a public grant overseen by the  French National Research Agency (ANR)  as part of the second " Investissements d'Avenir" program  (reference:  ANR-17-RHUS-0004 ) and by the  European Union 's  Horizon 2020 research and innovation programme  under grant agreement No. 945539  ( SGA3 ) Human Brain Project. Data were provided by the  Human Connectome Project ,  WU-Minn Consortium  (Principal Investigators:  David Van Essen  and  Kamil Ugurbil ;  1U54MH091657 ) funded by the 16  NIH Institutes  and Centers that support the  NIH Blueprint for Neuroscience Research ; and by the  McDonnell Center for Systems Neuroscience at Washington University. The authors wish to thank  Jayant Jha  and  Anirudh N. Vattikonda  for helpful discussions.
(11) Given that the right-hand side is real, the left-hand side must also be real, so sin(Rτ ) = 0, which leads to the condition Rτ = mπ with m ∈ Z. (12) Finally, substituting Eq. (  12 ) into Eq. (  11 ) and considering that the natural period is T = 2π/ω 0 , Eq. (  11 ) can be solved for K/ω 0 , which yields K ω 0 = ± 2 √ 3 m+2τ /T τ /T if m is even ± 2 √ 5 m+2τ /T τ /T if m is odd. (13) Therefore, the boundaries of stable incoherence (BSI) are periodic in the delay and only depend on the sum of the delays in the two pathways. This aspect was fully confirmed by the numerical analysis, with the correspondent parameters used listed in the Supplemental Material  [46]. The simulations were performed in MATLAB2020B, making use of the built-in function dde23 (Fig. 2 ) and also confirmed via the Euler method (not shown).
Total RNAs were extracted from the fat body in abdomen, the muscle from the thorax, head, digestive organs (including esophagus, crop, proventriculus, gut, malpighian tubule and rectum), reproductive organs (including testis, accessory gland, ejaculatory duct and ejaculatory bulb) and the whole flies, and RT-qPCR were performed. The values of fold induction for the indicated receptors in various tissues on day 3 relative to day 0 were obtained after the technical normalization with their internal control (Rp49). They were log10-transformed and represented by the heatmap. We obtained the data of head, muscle and fat body indicates from ~180 flies and of digestive system and reproductive system from ~360 flies. We used a total of 30 flies for the whole flies. Figure legends.
Acknowledgments We thank  Audrey Melignon  for excellent technical assistance,  Dr. Nelson Martins  for bioinformatic analyses,  Drs Jean-Paul Thiery , ( Guangzhou Institutes of Biomedicine and Health, Guangzhou ),  Giacomo Cavalli  ( Institut de Génétique Humaine, Montpellier ),  Caytano Gonzalez  ( Institute for Research in Biomedicine, Barcelona ) and  Alberto Mantovani  ( Humanitas, Milano ) for insightful discussions. We gratefully acknowledge the supports from  Guangzhou Medical University (Pr. Xinhua Wang)  to SFHI, the  China Overseas Expertise Introduction Plan  " 111" (D18010 ), Guangdong overseas teacher ( 2020A1414010343 & 2020A1414010306 ),  Science and Technology Planning Project of Guangzhou  ( 201707010030 ),  Chinese scholarship council, National Natural Science Foundation of China  ( 32000662 ) and  RiboBio Co.
Ltd. This study was also supported by  CNRS  ( UPR9022 -M3i ), INSERM (A. G. ), the  University of Strasbourg Institute for Advanced Study  (J. H and P. P. ) and the  Institut de génétique et de biologie moléculaire et cellulaire (IGBMC)  (' France Génomique'  consortium:  ANR-10-INBS-0009 ). A. R. acknowledges Pr. Maneesha Inamdar  ( JNCASR, Bangalore ) and  Le Centre Franco-Indien pour la Promotion de la Recherche Avancée  ( CEFIPRA ) for her 3-year fellowship.
Follow-up and clinical assessments At inclusion, socio-demographic data (gender, age, study level, employment status, substance use (tobacco, cannabis, alcohol), and body mass index (BMI)) were collected for both groups. Data on disease duration, potential psychiatric co-morbidities, therapeutic treatment, and previous antidepressant treatment characteristics, if any, were collected for the MD group. The severity of depression was evaluated using the HDRS  (Hamilton, 1960 (Hamilton, , 1967;; Guelfi, 1996)  heteroquestionnaire and the Beck Depression Inventory BDI  (Beck et al. , 1988)  auto-questionnaire. Only the BDI was administered to the control group for ethical reasons. A very good correlation between BDI and HDRS scores has already been demonstrated  (Milak et al. , 2010). The perceived deficits questionnaire was completed by both groups: this auto-questionnaire evaluates the frequency of perceived cognitive difficulties encountered by the participants using five questions  (Fehnel et al.
Statistical analyses The minimal sample size necessary to evidence a difference between clinical improvement groups according to the data already available about variations in serum BDNF levels, according to different studies in depressed patients with or without treatment compared to controls  (Shimizu et al. , 2003) , and especially to our experience with these assays  (Costa et al. , 2011 , Girard et al. , 2020 , Nubukpo et al. , 2017) , was evaluated: the basis of an alpha risk of 5%, a beta risk of 20%, a number of 18 evaluable subjects in each comparison group (improvement versus non-improvement) was required. Considering a proportion of 10% of subjects lost to follow-up or whose records will not be usable, a minimum of 21 subjects had to be included in each comparison group (with or without clinical improvement).
We thus included and used the data of the first 42 subjects fitting the criteria. The results are handled as exploratory thus without correction of type I error  (Jouan-Flahault et al. , 2004). Quantitative variables are described using mediane (± SD) and comparisons between groups were carried out using the Mann-Whitney U test, due to the non normal distribution of the variables. The paired samples Wilcoxon test was used to compare data in the MD group from a follow-up with the previous one (W3 to W0, W7 to W3). However, as the ANOVA tests are generally robust to the hypothesis of normality, considering the Central Limit Theorem, with a correct sample size (n = 30) and may be applied to not exactly normal data  (Santiago, 2015; Vaudor, 2015) , we used ANOVA in repeated measures to explore the evolution of our data along time.
Qualitative variables are described using frequencies and percentages, and the distribution between groups was analyzed by the Chi 2 test. The Spearman correlation coefficient was used to assess the correlation between BDNF levels and depression scales. ANOVA of repeated measures was used to explore the evolution of the BDNF and pro-BDNF levels and the BDNF/pro-BDNF ratio over time, with clinical improvement as the independent variable. Statistical analyses were performed using SPSS software (22. 0) and p < 0. 05 was considered statistically significance.
Hormone and accession number Primers i. e. , during the reproductive and resting seasons, respectively. The experiments conducted in February were performed with pituitaries of fish adapted to salinities of 37 or 4 salinities, and those in August with pituitaries of the 37 , salinity adapted fish. Data are expressed as the mean ± S. E. M. More details are provided in the figure legends and in Supplementary Figure  1. Total RNA Extraction, cDNA Synthesis, PCR and Real Time Quantitative PCR Total RNA from the pituitary glands was extracted using the TRIZOL reagent (Life technologies SAS; Saint Aubin, France) according to the manufacturer's instructions. The concentration and quality of the RNA was checked by spectrophotometry (Biophotometer, Eppendorf, Le Pecq, France) and after migration in a MOPS gel.
In order to ensure the specificity of the amplification, some controls also included running the obtained PCR products in an agarose gel, followed by extraction, sub-cloning and sequencing  (Sauzet et al. , 2008). The 2 -Ct method was used to determine the relative mRNA abundance  (Livak and Schmittgen, 2001) , with the L17 ribosomal protein mRNA as the reference gene  (Herrera-Pérez et al. , 2011). The primers (Table  1 ) were designed using the Light Cycler Probe Design software (Roche, Meylan, France). Their efficiency was tested using serial dilutions of cDNA from pituitary extracts; the calibration curves exhibited slopes and efficiencies close to -3. 32 and 100%, respectively.
ACKNOWLEDGMENTS We are grateful and address our deep thank to  Sandrine Sauzet , for her technical assistance and coaching of EP and MH, to the  SOMLIT (CNRS, Service d'Observation en Milieu Littoral ; http: //somlit. epoc. u-bordeaux1. fr/fr/)for providing the temperature data, and to  Gilbert Dutto  and  Eric Gasset  for their assistance in the management of the SW fish at the  IFREMER of Palavas-Les-Flots.
For more details, see Bowers et al. 26. Emotion experience assessment. Participants had to view 100 emotional pictures selected from the International Affective Picture System (IAPS) database  27  differing in valence (positive, negative, neutral) and arousal (ranging from calm to excited). During each presentation, the subject had to score her experience for the valence (on a scale from 1 "very negative" to 9 "very positive") and for the arousal sensation (on a scale from 1 "very calm" to 9 "very excited"). Pictures were presented in a same valence and arousal block design, alternating between emotional and neutral blocks, in the same order for all subjects. Self-report questionnaires. All subjects were asked to complete a French self-administered depression-scale named EHD  28  measuring two dimensions of depressive mood in MS: loss of emotional control and emotional blunting.
Statistical analysis. Statistical analyses were performed using Excel and SPSS-21. Non parametric statistical tests were used due to non-homogeneity of variance and non-normality of the distribution. A Mann-Whitney U test was performed for between-group comparisons of quantitative data and a Chi 2 or Fisher Exact test for qualitative data, also depending on application conditions. A Wilcoxon test for paired samples was used for intra-group comparisons. An alpha level < 0. 05 was considered statistically significant for between-group comparisons. Emotion recognition accuracy was calculated from the result of subtests 2-5 and the type of error from the result of subtests 3-5. For emotional experience, we analysed the mean scores (comparison of raw data) and the dispersion from those scores (analyse of the variability translated in distance to an attempted norm).
Both protocols were approved by the local ethics committees (CPP Ile-de-France VI for study one and CPP Ile de France IV for study two) and preregistered (clinicaltrials. gov NCT00894452 and NCT01569347, respectively), and by the relevant Institutional Review Board for further analyses of the combined sample [CEEI from the Institut de la Santé et de la Recherche Médicale (INSERM), IRB00003888 in July 2015]. All participants provided written informed consent, and study records were continuously monitored by the local research administration (Unité de Recherche Clinique) to ensure their conformity to the original protocols. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
Clinical assessments Data were obtained during a single interview conducted by trained psychologists or M. D. s. • Sociodemographic conditions were collected using a standard procedure, and included the number of years in education starting from elementary school, dichotomized employment and marital statuses, as well as history of homelessness, which was retained if the participant reported having spent at least three months living on the streets. We chose this stringent definition  28  since several recruitment centers dealt with particularly low-income populations, among whom brief or sheltered homelessness is common; • Past history of SA was characterized using the 'suicide' section of the Diagnostic Interview for Genetic Studies, v 4. 0 (DIGS 4. 0)  29  , where the screening question refers to "kill oneself", followed by the number of times the respondent endorses this affirmation then an assessment of the self-reported "worst attempt".
Taken altogether, this multipleitems assessment of SA history enhances data reliability, as previously reported in general population samples  30. This is of further relevance in SUD populations, where drug overdoses (which were assessed specifically in the study, data not shown) can be mistakenly considered as accidental  31. Along with the presence and the number of lifetime SA, the questionnaire also focused on what participants regarded as their worst SA ever, which was dichotomized into self-poisoning or violent means (jumping, hanging, shooting). For this particular SA, the degree of intentionality and age of occurrence were noted and the medical treatment that followed was also collected. Besides the presence of lifetime ('any') SA, two additional phenotypes were considered: • Serious SA was deemed present if the respondent's worst SA was either made with a violent method, or if a medical treatment was necessary (regardless of the method that was used), as previously defined  4, 32.
Psychiatric hospitalizations, which was coded present when participants reported at least one psychiatric hospitalization for any psychiatric indication; General population control sample 2,504 individuals of Caucasian ancestry genotyped at the Wellcome Trust Institute (UK Blood Service Control Group genotyped using the Affymetrix v6. 0 chip, dataset number EGAD00010000290, downloaded March 2019) were considered as a control sample to further assess population stratification, as in previous psychiatric genetics studies  41. The UK general population was deemed comparable to the French population regarding daily tobacco smoking (16-20% vs. 20-24%)  42  , use of other substances (alcohol, stimulants, opioids among respondents aged 15-34)  43  and importantly, prevalence of lifetime SA, which was 7% according to both countries' most recent surveys  44, 45.
Gene selection, SNP selection, and genome-wide quality control We applied, a priori, a custom selection of autosomal genes from the three main neurotrophin signaling pathways identified through the Online Mendelian Inheritance in Man (OMIM) database. We limited the selection to extracellular ligands/receptors, so as to avoid gathering too many unspecific genes from intracellular effectors. We included genes from (i) the ligands BDNF, NTF3, NTF4, NGFB, NGFA, CNTF and their receptors NTRK2, NTRK3, and CNTFR, (ii) the major regulator of BDNF function sortilin (SORT1) and (iii) SKA2, a gene involved in stress reactivity, recently and repeatedly associated with SAs  47, 48. Those eleven genes harbored 258 markers in our DNA array (see Fig. 1 ). HG19 was the reference human genome version. The full list of variant names, their correspondence with Illumina® positions, and gene length and coverage by the DNA array are listed in Supplementary Table  1.
Variants showing significant associations with any of those phenotypes were annotated for their biological function and plausible impact according to multiple online databases, as previously suggested 51 : (1) the Combined Annotation Dependent Depletion (CADD) database, where a scaled ('Phred') score ≥10 indicates that a given variant belongs to the 10% most deleterious substitutions of the human genome 52 , (2) brain expression and methylation quantitative trait loci (eQTL and mQTL) provided by GTEx portal  53  and mQTLdb (middle-age data  54  ) databases, respectively, and (3) the RegulomeDB database for non-exonic variants, which assesses their propensity to bind DNA enzymes and/or modify DNA conformation  55.
Statistical analyses Data are expressed by mean ± standard deviation (SD) or median and interquartile range (IQR) for continuous variables and counts and frequencies for nominal variables, as appropriate. For the sake of brevity, only descriptive values of the main clinical and sociodemographic variables are reported. These variables were tested one-by-one in bivariate tests with suicidal phenotypes. For 'any' lifetime SA, SNPs were tested under the genotypic, trend, allelic, recessive and dominant models, using PLINK-model specifier, gene-based tests using PLINK-set-test function. For 'serious' and 'recurrent' SA phenotypes, analyses were performed with Trinculo (allelic model) and R mlogit package (recessive model), since multinomial regression is not implemented in PLINK. Accordingly, regarding gene-based tests, binary phenotypes recoded as "serious vs.
none" and "recurrent vs. none". Genetic correlations between SA phenotypes were estimated using Bayesian analysis  56  , using joint summary statistics to provide posterior probabilities that a given SNP has cross-associations with several phenotypes [Cpbayes R package 57 ]; while also providing the Bayes Factor (BF) associated with the test to estimate the level of confidence in the associations  58. Adjusted regression models were then built for each SNP that was significantly associated with a given suicidal phenotype: binary logistic for the phenotype 'any' SA and multinomial regression for 'serious' and 'recurrent' SA. Other clinical and sociodemographic correlates of suicidal phenotypes were entered as cofactors or covariates. Collinearity between predictors was avoided by excluding variables with variance inflation factor (VIF) >2.
cog-genomics. org/plink/1. 9/assoc#perm). Hierarchical clustering, a method for unbiased classification of the data, was also used to assess how the different SA phenotypes would cluster together and with (i) clinically-relevant variables (gender, SUDs and CPD, number of psychotropic medications) and (ii) SNPs associated with any phenotype of SA according to the previous analysis steps. This method has been previously used for analyzing genetic associations in the case of multiple clinical endpoints that are likely to be interrelated  61. The R package pvclust was used, allowing for both visualizing data clusters and estimating the significance of their constitutive variables after permutation  62. Distance assessment used the D2-ward method. The Unbiased Approximation statistic chosen to address the strength of support of a given cluster by the data, as recommended  62  , with a p-value ≤0.
05 for considering significance. Eventually, to further control for population stratification and estimate whether genetic differences would be associated with SA or with the sample status, we performed two exploratory regressions by comparing (i) patients vs. controls samples status patients as cases, whatever their SA history and (ii) comparing SA patients to controls. These analyses were performed with 55 shared SNPs of the 'neurotrophic pathway', using the same permutation parameters. All downstream statistical analyses were performed using R software version 3. 5. 3 through R studio 1. 1. 463 63  running on Mac OS® X. 12. 6  64. This study follows the STREGA guidelines for the report of genetic studies  65. R session summary is available in the supplementary Fig. 2  (full R code available on demand from the authors).
38, is not scored in the regulomeDB and has no significant influence on BDNF expression in the brain according to the GTEx portal database (lowest p-value = 0. 031 for the putamen area, not significant after correction for multiple testing). rs10835210 has a CADD score of 17. 18, is scored 3a in regulomeDB (less likely to affect binding), and is significantly associated with increased levels of BDNF antisense (AS) mRNA by increasing expression of the BDNF-AS gene in the frontal cortex (normalized effect size = 0. 24).
Acknowledgements The authors would like to thank the investigators that were involved in building the present cohort. Gaël Dupuy  ( Assistance Publique-Hôpitaux de Paris, CSAPA Murger, Hôpital Fernand Widal, Paris ,  F75010 ),  Didier Touzeau  ( CSAPA Clinique liberté, Bagneux F-92220 ),  Cyrille Orizet  ( Assistance Publique -Hôpitaux de Paris, CSAPA Montecristo, Européen Georges Pompidou, Paris F-75015 ),  Philippe Coeuru  ( CSAPA Espoir Goutte d'Or-Aurore, Paris F-75018 ),  Pierre Polomeni  ( Assistance Publique-Hôpitaux de Paris, Service d'addictologie, Hôpital René Muret-Bigottini, Sevran F-93270 ),  Xavier Laqueille  ( Centre Hospitalier Sainte-Anne, CSAPA Moreau de Tours, Paris F-75014 ),  Elisabeth Avril  ( CSAPA, Gaia association, Paris F-75011 ),  Anne-Marie Simonpoli  ( Assistance Publique-Hôpitaux de Paris, ELSA, Hôpital Louis Mourier, Colombes, F-92700 ),  Pr.
05 M Tris-HCl) for subsequent ELISAs. Protein concentrations were determined using bicinchoninic acid assay (Thermo-pierce). Twenty L of each sample were added in Laemmli's loading buffer to obtain a final concentration of 1. 5 g/L and heated to 70 • C for 5 min. A total of 15-22. 5 g of proteins per sample were separated by SDS-PAGE and electroblotted onto PVDF membranes (Immobilon, Millipore). Membranes were blocked in 0. 5% BSA and 5% dry milk in PBS-0. 1% tween-20 and then incubated with primary (listed in Supplementary Table  2 ) and secondary (HRP goat anti-rabbit or goat anti-mouse, 1/50000, Jackson ImmunoResearch) antibodies. Band intensities (optical density, OD) were revealed with Luminata Forte (Millipore) and detected using myECL imager (Thermo Fisher Scientific). Quantifications were performed blindly on ImageLab software (Millipore), using a background subtraction when necessary and results were expressed as relative OD.
Quantitative real-time PCR (qRT-PCR) RNA from parietotemporal cortices was extracted using RNeasy lipid tissue mini kit (Qiagen). Two micrograms of RNA were reverse transcribed in cDNA (High capacity cDNA reverse transcription kit, Life technologies). Gene expression was measured using 80 nanograms of the resulting cDNA in duplicates and appropriate FAM-labeled Taqman primers (Taqman gene expression assays, IL1␤ (Mm00434228 m1), IL6 (Mm00446190 m1), TNF-␣ (Mm00443258 m1), GAPDH (Mm99999915 g1), Life technologies). Data were analyzed using the comparative threshold cycle method using GAPDH as a housekeeping gene. Results are expressed as relative fold change with untreated NonTg CD mice as the control group.
BH4 administration modulates cortical IL-1β cytokine expression according to the diet Given the importance of neuroinflammation in AD etiopathology  [5]  and because BH4 was shown to exhibit anti-inflammatory properties  [76] , we next investigated the gene expression of major pro-inflammatory cytokines in the parieto-temporal cortex of mice (Fig. 6 ). Results showed a significant reduced expression of IL-6 (Genotype effect, p < 0. 05) and TNF-␣ (Genotype effect, p < 0. 01) mRNA in 3xTg-AD mice, compared to NonTg. The exposition to HFD had no effect on mRNA expression of the 3 proinflammatory cytokines studied. BH4 administration only induced a significant increase in mRNA expression of IL-1␤ in NonTg mice fed the HFD (Kruskal Wallis χ 2 = 0. 05, Wilcoxon, p = 0. 02). No significant change of others pro-inflammatory markers such as the protein level measured by western blotting in the hippocampus of cyclooxygenase 2 (COX2), glial fibrillary acidic protein (GFAP), and superoxide dismutase (SOD1) were noted (data not shown).