dataesr/scientific-paragraphs-categorization huggingface dataset:
Transcriptomic profiles of major metabolite modification families in response to oxidative stress Previous transcriptomic analyses of catalase-deficient Arabidopsis lines have shown that genes encoding enzymes involved in metabolite modification can be strongly up-regulated by oxidative stress  [4, 6]. Such genes notably include members of the GST, UGT, and CYP families, some of which have been shown to play important roles in response to stress and/or to be among the best molecular markers of the intensity of oxidative stress  [5, 22, 23, 37]. To provide a comprehensive overview of the response of these three gene families to oxidative stress linked to enhanced intracellular H2O2, we compared how they were affected by the cat2 mutation in the three transcriptomic experiments. Data were retrieved for annotated CYPs, GSTs, and UGTs.
A complete list is shown in Supplemental Table  S1. Genes for which transcript data were available in all three experiments (146 CYPs, 52 GSTs, 78 UGTs) were analyzed for their expression patterns. Hierarchical clustering of these genes allowed a clear visual separation between the genotypes in all experiments, with all nine cat2 replicates clustering apart from the nine Col-0 replicates (Figure  1 ). Some clustering of replicates within each experiment was also observed but this contributed much less to the separation than the genotype, demonstrating that a marked, reproducible effect of oxidative stress can be observed by analysis of the transcripts of these gene families. The response of the different genes within these families is presented in the heatmap shown in Figure  2  (mean values for each genotype within each experiment).
This confirmed that alongside the H2O2 marker transcript, GSTU24, SA-dependent pathogenesis-related (PR) genes were markedly induced in cat2, as were the JA marker genes JAZ1 and VSP2 (Supplemental Table  S2 ). These data are consistent with previous findings that both pathways are activated together in cat2  [26] [27] [28]. To elucidate the impact of oxidative stress on the responses of genes involved in synthesis and metabolism of the two phytohormones and related compounds, we mined the same three transcriptomic datasets. This search was informed by available databases and current concepts in Arabidopsis (Supplemental Figures  S1, S2 , S4, S5) according to which the isochorismate pathway is the main route of stress-induced SA synthesis  [38]  but a phenylalanine-dependent pathway might also contribute, whereas JA is synthesized from linolenic acid via OPDA  [39].
05 in the microarray experiment. The clear induction of ICS1 by oxidative stress was confirmed by qRT-PCR in two independent experiments using parallel biological samples, and accompanied in the transcriptomic experiments by marked induction of EDS5 and PBS3 (Supplemental Table  S3 ), which encode a transporter and an enzyme downstream of ICS1 in isochorismate-dependent SA synthesis, respectively  [40]. Genes involved in converting chorismate to phenylalanine, and the latter to downstream compounds, were also induced in cat2 although again, this effect was clearer for the two RNAseq datasets than the microarray experiment. Alongside these effects, several genes involved in JA synthesis were induced in cat2, including isoforms of lipoxygenase, allene oxide cyclase, and acyl CoA oxidase, although few of these genes were induced in all experiments (Supplemental Table  S4 ).
Profiling of SA-and JA-related metabolites in response to oxidative stress To assess whether these changes in gene expression are associated with an impact on metabolite accumulation, we used a recently developed LC-MS method to measure SA, JA, and derived compounds  [36]. About twenty compounds could be detected and quantified on an absolute or relative basis (Supplemental Table  S5 ). The structural diversity of the different compounds is summarized in Figure  5. First, we quantified data for free SA and the two glucosylated forms (SAG, SGE) in Col-0 and cat2 by this method. Three independent experiments revealed an increase in all three forms in cat2. Quantitively, SAG was consistently the predominant form in cat2 (more than 5-fold free SA levels) while SGE was the least abundant form in both backgrounds (Figure  6 ).
Isochorismate and phenylalanine pathways of metabolite production SA accumulation and downstream responses triggered by the cat2 mutation require isochorismate synthase 1 (ICS1). This has been shown by abolition of SA-related gene expression and lesion phenotypes in a cat2 sid2 mutant, in which the sid2 (SA induction-deficient 2) mutation in ICS1 genetically blocks SA synthesis through this pathway  [25, 29]. This is consistent with the marked transcriptional up-regulation of the isochorismate pathway in cat2 reported here in several datasets. Although ICS1 is required for marked accumulation of SA in response to oxidative stress, we cannot exclude that the phenylalanine pathway also makes some contribution alongside the isochorismate pathway when the latter is activated. Indeed, the present datasets also show up-regulation of the phenylalanine synthesis pathway and downstream enzymes involved in production of phenylpropanoids, consistent with accumulation of Phe and trans-cinnamate in cat2 observed through GC-MS analyses  [5, 27].
Based on these observations, the data perhaps imply that the main players producing SA-glucosides in response to oxidative stress-driven accumulation of SA may be UGT76B1 (rather than or addition to UGT74F1) for SAG, and UGT74F2 for SGE. However, a contribution of UGT75B1 to SGE accumulation cannot be discounted, since this gene was 5 to 12 times more highly expressed in cat2, although induction was only significant in one of the two datasets in which transcripts could be quantified (Supplemental Table  S3 ).
Dihydrobenzoic acids and their glycosides in the oxidative stress response Alongside hydroxybenzoic acids and conjugates (SA, SAG, SGE, mHBA, pHBA), several dihydroxybenzoic acids (DHBAs) and their glycosides accumulated in response to intracellular H2O2 (Figure  7A ). Literature data suggest that the most markedly accumulated DHBAs are formed by hydroxylation of SA through the action of two Fe-dependent monooxygenases. The first, SA 3-hydroxylase (S3H), is active against SA  [45]  and was induced in cat2 in all experiments (albeit just above the significance threshold in one RNAseq dataset). S3H induction correlated with marked accumulation of 2,3-DHBA (>150-fold higher in cat2) and its xylose glycoside (2,3DHBA-3X: >20-fold higher in cat2). The second hydroxylase (S5H) can convert SA to 2,5-DHBA  [46].
Acknowledgements This work was supported by a PhD grant to  Mathias Cohen  from  IDEX Paris-Saclay, France  and  Ghent University, Belgium. Lug Trémulot  is supported by a PhD grant from the  Université Paris Saclay and MESRI (Ministère de l'Enseignement Supérieur, de la Recherche, et de l'Innovation), France. The GN laboratory is supported by the  French Agence Nationale de la Recherche   HIPATH  project ( ANR-17-CE20-0025 ) and by the  Institut Universitaire de France (IUF).
Discussion Data reported in this paper show that the substitution of S184 by a non-phosphorylatable residue A or V only induced a partial activation of Bax. When expressed in cellulo (in BaxS184V does not spontaneously bind to liposomes, contrary to BaxP168A. Flotation assays of BaxP168A and BaxS184V, mixed or not with liposomes, were done as described in the method section. After the gradients were fractionated, fractions were loaded on SDS-PAGE and revealed by Western-blot. The sizes of monomer (21,5kDa), dimer (43kDa) and oligomers (>65kDa) are indicated. While BaxP168A floated in the presence of liposomes, BaxS184V showing that it is not spontaneously inserted. However, it was inserted when cBid was present. mammalian cells or in yeast), these non-phosphorylatable mutants displayed a greater mitochondrial localization  (16, 18) , that is associated to a low rate of retrotranslocation  (21, 25).
, Nastus tsaratananensis A. Camus and Nastus perrieri A. Camus. This material represents the first modern collection of native flowering bamboos from the montane forest bamboo diversity hotpot on Madagascar's highest mountain, Tsaratanana. Fresh leaves were silica-gel-dried and stored for DNA extraction. Voucher specimens were deposited at herbaria in Parc Botanique et Zoologique de Tsimbazaza (TAN), Kunming Institute of Botany, Chinese Academy of Sciences (KUN), Royal Botanic Gardens, Kew (K), and Mus eum National d'Histoire Naturelle (P). Some experimental materials were sampled from specimens deposited at K and P. Data on collection provenance and voucher specimens are shown in Table  1.
Plastid genome assembly and annotation Plastid genomes were assembled using the GetOrganelle toolkit  (Jin et al. , 2020). We used Bandage v. 8. 0  (Wick et al. , 2015)  to visualize newly assembled plastome structure. Hickelia madagascariensis A. Camus was retrieved from GenBank (accession number: KJ_870994) and used as the reference plastome  (Wysocki et al. , 2015). Annotation was conducted in Geneious v. 9. 1. 4 using MAFFT  (Kearse et al. , 2012)  to align plastome sequences; annotations were transferred from the reference plastome. MAFFT was also used to align all plastomes. Annotations and alignments were checked manually. Gene maps of circular complete plastomes were drawn using OGDRAW  (Lohse et al. , 2013). Geneious v. 9. 1. 4 was used to inspect the boundaries between LSC, IRa, SSC, IRb and the GC content for each species.
Comparative genomic and phylogenetic analysis Using Hickelia madagascariensis (KJ_870994) as a reference, we compared the plastomes of the species sampled in this study. The assembled plastomes of Hickeliinae were aligned and plotted using the mVista program with LAGAN mode  (Frazer et al. , 2004). The rearrangement analysis of all plastomes was performed using Mauve alignment with default values for all parameters  (Darling et al. , 2004). The borders between LSC, IRa, SSC and IRb were investigated using IRscope  (Amiryousefi et al. , 2018). To determine the phylogenetic relationships of the species sampled and test the support for the relationships within the subtribe, maximum likelihood (ML) was used to reconstruct a phylogenetic tree using whole plastome sequences of all sampled species in RAxML v.
8. 2. 10 with the GTR þ G þ I model and 1000 rapid bootstrap replicates  (Stamatakis, 2014). Bayesian inference (BI) was carried out in MrBayes v. 3. 2. 6  (Ronquist et al. , 2012). Markov chain Monte Carlo (MCMC) chains were run for 2 Â 10,000,000 generations. Both analyses were performed on CIPRES Science Gateway  (Miller et al. , 2010). To root the tree, three species of Bambusa Schreb. were retrieved from GenBank and used as outgroup taxa (B. teres Buch. -Ham. ex Munro: NC_050751. 1, B. oliveriana Gamble: MK679792. 1 and B. vulgaris Schrad. ex J. C. Wendl: NC_050780. 1).
Acknowledgments We thank the curators of the herbarium of the  Royal Botanic Gardens, Kew (Richmond, UK) , the staff of the  Kew Madagascar Conservation Center (Antananarivo) , curators of the  Mus eum National d'Histoire Naturelle (Paris) , and staff of the  Parc Botanique et Zoologique de Tsimbazaza (Antananarivo)  for their help in fieldwork and all Malagasy authorities who granted the research permits. The authors sincerely thank the  Germplasm Bank of Wild Species  for bioinformatics and DNA analysis. This study was supported by the  National Natural Science Foundation of China  ( 31670396  and  32120103003 ), the  Program of Science and Technology Talents Training of Yunnan Province, China  ( 2017HA014 ), and the  Large-scale Scientific Facilities  of the CAS (2017eLSFGBOWSe02). Special thanks to the  University of Chinese Academy of Sciences  for the fellowship ( CAS-TWAS 2016 ) to the first author, who worked on this study as part of his doctoral studies.
Study protocol and patient enrolment Patients aged 12e29 years with newly diagnosed or recurrent intermediate or high-grade bone and soft tissue sarcoma were recruited. For newly diagnosed patients, the diagnostic biopsy and/or definitive resection specimen were analysed. For recurrent disease, tissue was from the latest recurrence. Clinico-pathological data were collected according to the EORTC-SPECTA protocol (NCT02834884)  [8] , open in 17 European countries.
2), using !0. 9 as a diagnostic threshold  [10]. A spectrum of molecular biomarkers were considered (derivation described in the study by Horak et al. [5] , Groschel et al. [11]  and Hubschmann et al. [12] ), and single base substitution mutational signatures  [13]  and homologous recombination repair deficiency phenotype (HRD) scores were derived as described previously  [5, 14, 15]. Germ line variants in a panel of cancer predisposition genes (described in the study by Horak et al. [5] ) were evaluated according to American College of Medical Genetics and Genomics criteria. Data are deposited on the European Genome-Phenome Archive (EGAS00001005840). Monthly MTBs included EORTC representatives, sarcoma oncologists, central review pathologists, DKFZ molecular leads and referring clinicians, producing clinically validated reports containing combined pathological/molecular final diagnoses, actionable molecular alterations and treatment recommendations, based on a schema as previously described (Supplementary Table  2  and  [5] ).
Patient characteristics Between April 2019 and July 2020, 71 patients were recruited (Fig. 1b ). Samples were inadequate for 23 patients (<10% tumour cell content or inadequate size, n Z 12) or poor quality nucleic acid (n Z 11): 25 newly diagnosed and 23 recurrent sarcomas were evaluable. Non-eligible patients had Ewing sarcoma (n Z 8), osteosarcoma (n Z 5), sarcoma not otherwise specified (NOS) (n Z 6) alveolar rhabdomyosarcoma (n Z 1) and other histotypes (n Z 3). No central review was performed for excluded patients. There were no significant differences in the proportions of eligible and ineligible patients between bone and soft tissue sarcomas or between Ewing sarcomas, osteosarcomas and other histotypes. Baseline characteristics are shown in Table  1. At database lock (17th February 2021), median follow-up 11.
Treatment implementation Nine patients died before molecular results were available (three patients were recruited at initial diagnosis who subsequently progressed, six patients were recruited at recurrence); 30 patients had potentially actionable mutations. At database lock, 19 patients had not progressed, and in eight patients, the treating clinician gave a different therapy at recurrence. Treatment was adapted for two patients and the molecular profile supported a third patient's treatment. The first adaptation was a 13-year-old boy with recurrent Ewing sarcoma who received first line chemoradiotherapy. Three sequential recurrences were treated with temozolomide and irinotecan, an LSD1 inhibitor and etoposide. Analysis revealed EWSR1/ERG fusion, SLFN11 overexpression and focal BRCA1 loss.
Acknowledgements The authors would like to thank the patients, physicians, nurses and trial coordinators who participated in the  SPECTA-AYA  project. From the EORTC headquarters, the authors would like to acknowledge  Christine Olungu  (data management),  Bianca Colleoni  (clinical operations) and  Marie-Sophie Robert  (project management). The EORTC SPECTA platform is supported by  Alliance Healthcare , a member of the Amer-isourceBergen group. The  AYA  project was supported by the  Walgreen Boots Alliance. Teresa de Roja 's work as Fellow at EORTC Headquarters was supported by a grant from  Fonds Cancer (FOCA)  from  Belgium  and by the  EORTC Cancer Research Fund (ECRF)  from  Belgium. IPO Porto collaboration was partially supported by the project 'P. CCC:  Centro Compreensivo de Cancro do Porto ' e  NORTE-01-0145-FEDER-072678 , supported by  Norte Portugal Regional Operational Programme  ( NORTE 2020 ), under the  PORTUGAL 2020 Partnership Agreement , through the  European Regional Development Fund (ERDF).
SantePublique France set up in 2018 a general population survey Unono Wa Maore ("About the Mahoran") to assess the population health needs and set up appropriate prevention and health promotion campaigns. For this study, blood samples were collected, and made available for a wide range of analyses, providing the opportunity to assess the seroprevalence of various arbovirus infections, among them CHIKV. Alongside biological sample data collection, participants were interviewed to collect socio-demographic information, and information on attitude and practices with regard to the prevention of vector-borne diseases. Here, we estimated the seroprevalence of past CHIKV infection in the population of Mayotte in 2018-2019. We also identified sociodemographic factors for CHIKV seropositivity, and described the association between attitudes and practices in arboviral disease prevention, and CHIKV seroprevalence.
Data collection Trained interviewers conducted face-to-face questionnaire interviews in French and two local languages, Kibushi and Shimaore. Two questionnaires were administered: one comprehensive questionnaire for the randomly selected first participant aged 15 and older included in the household, and a short one for the other participants of the same household. Both questionnaires explored participants' sociodemographic characteristics; alcohol, tobacco, and drugs use; perceived health; hygienic practices; vaccination; perception and behavior related to vector borne diseases. Only the comprehensive questionnaire collected data on family origin, socio-economic status and education, healthcare seeking behavior; food intake, and sexual behavior. Additionally, interviewers collected information on the type of dwelling as well as access to water.
For the descriptive analysis and bi-and multivariable analysis, we used the data obtained from all participants who answered to the comprehensive questionnaire. For the univariate analysis (binomial regression), we used anti CHIKV IgG seropositivity as binary outcome and calculated weighted Prevalence Ratios (svy-weighted analysis). We tested independent associations between serological status as binary outcome and explanatory variables using a Poisson model with robust variance, and computed weighted and adjusted prevalence ratios (w/a PR). We performed three different Poisson models exploring (i) all variables selected, (ii) sociodemographic factors only, (iii) and environmental/housing and knowledge and attitude on prevention and control of arboviral diseases. In these models, we included explanatory variables that were associated with seropositivity in the univariable analysis with a P-value �0.
20. Collinearity was checked via variance inflation factor (VIF) and Spearman's rank correlation test. Although the VIF test provided an average value of 1. 62 (therefore not suggesting collinearity), a few variables appeared to have slightly higher VIF values (around 2-3); therefore, we opted to run the Spearman's test. For the latter, when two variables had a pairwise correlation coefficient >0. 5  [26] , we combined them and reduced the number of categories to reach a final list of variables to be used in the three multivariable models (see also S6 File. Information on datasets, weights and variables used in the analysis, for further clarifications). In each of these models, a backward stepwise elimination  [27]  and retention procedure of covariables with a P value< 0. 05 with a svy-adjusted Wald test was used to finalize each model.
The study was registered at www. clinicaltrials. gov; registration number: NCT05278286. Results: A 3 (Condition) × 4 (Age) repeated measures ANOVA revealed that Crawli group infants had significantly higher Bayley-III gross motor development scores than Mattress and Control group infants. Crawli group infants also scored significantly higher on groups of Bayley-III items related to specific motor skills than infants in the other groups, including crawling at 9 months CA. We found significant differences in favor of the Crawli group in separate one-way ANOVAs at each of the ages we examined. A 3 (Condition) × 2 (Age) repeated measures ANOVA revealed that the Crawli group scored significantly higher than the Control group for the ASQ-3 total score and communication score and significantly higher for the fine motor score than the Control and Mattress groups.
Trial design The study was registered at www. clinicaltrials. gov; registration number: NCT05278286. Because of the limited number of subjects in our study due to the home-based nature of our intervention (see training protocol below), we chose not to include very preterm infants with major brain lesions because this would have required us to match lesion levels and locations across the three groups and we could not test a large enough sample to accomplish such matching. We randomly allocated forty-four very preterm infants without major brain lesions to one of three groups: Crawling training on the Crawliskate (Crawli), prone positioning on a Mattress training without the Crawliskate (Mattress), or standard care (Control), in which infants received pediatric checkups at 4, 9, 12, 18 and 24 months CA but no other treatment unless recommended by the pediatrician.
Gross and fine motor bayley assessments We administered the Bayley III gross and fine motor assessments at 2, 6, 9, 12, and a full Bayley III assessment at 24 months CA (BSID-III ed (  79 )) to assess general motor development and to evaluate the development of specific motor milestones, especially mature crawling, but also head control, sitting, standing and walking (note, we do not include the Bayley III data at 24 months in this report as we plan to publish those data in a later report on the long-term effects of the intervention). Two trained testers administered the assessments. They both had over 20 years of experience assessing infant development and 10 and 8 years of experience administering the Bayley assessments. Both were blinded to infants' group assignment. Scaled scores were calculated.
-Sitting: Item 22 "Sitting alone 5 s without support"; Item 26 "Sitting alone 30 s without support"; Item 27 "Sitting alone 60 s while manipulating an object"; Item 28 "Sitting alone while rotating the trunk to catch objects bilaterally". -Crawling: Item 30 "Belly-crawling for 1 meter"; Item 31 "Stand in a four-legged position" Item 34 "Crawling on his or her hands and knees over 5 feet". - To perform the item grouping analysis for each stage of gross motor maturation, we summed the raw scores of the items comprising each grouping. Because the data were not distributed normally, we used a non-parametric Kruskal-Wallis test. We weighted ranks by the age of the subject (the youngest child having the highest rank). For this analysis, we compared the data from the Crawli group with those from the Control group and those from the Mattress group.
Funding This work was supported by the grant  ANR-20-CE17-0014  from the  Agence Nationale de la Recherche , the grant Project -106  from the  SATT-Erganeo (Société Accélération des Transferts de Technologies)  and a fellowship (ED261) from the  French Government  to support the doctoral thesis of  Marie-Victorine Dumuids-Vernet.
One week later, ATP levels were measured by CellTiter-Glo 3D assay (Promega) and luminescence was quantified using Centro XS3 LB 960 (Berthold Technologies, Bad Wildbad, Germany) with Miko Win 2000 software. Cell viability values were normalized to control and treatment sensitivity was expressed as the average of two independent biological replicates. Viability curves were designed using GraphPad Prism software (version 9. 2. 0). The half-maximal inhibitory concentration (IC50) was computed for each PDTO model.