dataesr/scientific-paragraphs-categorization huggingface dataset:
The resulting label maps encompassed the entire brain, so that region segmentations would cover the entire length of a given structure over multiple image slices. The T2 relaxation times (ms) and volumetric data were extracted based on the final curated segmentation. All diffusion data were reconstructed using FMRIB Software Library's DTIFIT where DTI metrics were extracted using the transformed label maps (FSL v5. 0; FMRIB, Oxford, UK)  [5, 73]. FA, MD, RD and AD diffusivity maps were used for final data acquisition. Hippocampal subregions (CA1, CA2, and CA3) and basal forebrain cholinergic circuit components (SI, substantia innominate (including ventral palladium); NB, nucleus basalis; MS, medial septal nucleus) were examined in detail.
Slides were kept at 4 °C. Slides were scanned at 10 × magnification using a slide-scanner (Hamamatsu Nanozoomer 2. 0HT, Bordeaux Imaging Center, Bordeaux, Fr). Confocal images were taken at 40 × magnification using a Nikon Eclipse Ti inverted laser scanning microscope with a Nikon acquisition software (NIS-Element, NIS). Settings were kept constant amongst experimental groups within each batch of experiments. Antibodies diffuse through the section approximatively on 10 μm thickness on each side of section. Hence, the confocal acquisitions were done on 10 μm thickness corresponding to the part of the tissue closer to the surface. Image analysis was performed using FIJI software  [59]  in a blinded manner on 2 brain sections containing the region of interest hippocampus and SI/NB in the ispi-and contralateral hemisphere to the impact.
For each region, 3 different images were taken either at 20X or 40X using a confocal microscope (Nikon Eclipse Ti inverted laser scanning microscope). Given the irregular anatomy of the SI/NB, the region was manually delineated within each section to obtain values within the region of interest. For quantification of the APP staining in the hippocampus, APP images were acquired at 20X using Nikon Eclipse Ti inverted laser scanning microscope with a Nikon acquisition software (NIS-Element, NIS). Using FIJI software, stack images were reconstructed using Z-stack function. The resultant stack was first treated with "Bandpass" filter without autoscale after filtering, followed by "Unsharp mask (Radius: 1. 0 pixel-Mask Weight: 0. 9). Filtered images were then binarised after thresholding (6-7% to delineate the thin processes).
Statistical analysis GraphPad Prism 3. 05 (GraphPad Software Inc. , USA) was used for statistical analysis. For comparison of single features between two groups, an unpaired t-test was used. For comparisons of several features or a feature across several regions of interest, a two-way ANOVA followed by Tukey post-hoc test was used. Linear regression was applied to assess correlations between two parameters. Significance was reported at p < 0. 05. All data are presented as the mean ± standard error of the mean (SEM) and followed a normal distribution (Shapiro-Wilk test). Whole-brain analysis of T2 and DTI data were analyzed with GraphPad Prism 7. 00 using an unpaired t-test with Welch's correction for each ROIs. All MRI data were examined for sample outliers using 1. 5 interquartile range (IQR) testing.
In agreement with our findings, a single mTBI to the developing brain is sufficient to alter memory retention 12 months post-injury supporting the notion that the developing brain is more sensitive to injury and results in longterm alterations. An emerging decrease in anxiety-like behavior was observed in jmTBI group with increased time spent in the center of the arena and in the open arms of the elevated plus maze test. Even then the direct comparison of our data to clinical observations is not straightforward. Neurophysiological changes in relation with postconcussive symptoms (PPCS) after pediatric mTBI have not been well characterized. Children with PPCS exhibited decreased cortical activation on fMRI in working memory tasks at one-month post-injury  [33]. Similarly, resting state fMRI showed hyperconnectivity and hypoconnectivity in sport related concussions that were associated with altered memory performance up to 21 days  [43].
Background: Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i-treated patients. Severe cutaneous irAE do not often occur but could be life-threatening and may persist despite treatment discontinuation. Methods: We aimed to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real-world, phase IV, post-marketing study using a follow-up questionnaire. Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma and cutaneous adverse events, supported by EADO.
M ATER I A L S A N D M ETHODS Data on patients with advanced melanoma since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma patients and cutaneous adverse events, supported by the European Association of Dermato Oncology (EADO). The study complies with the ethical standards resulting from the Declaration of Helsinki. An information sheet was given to each patient to collect their consent to the study, and none of them refused to participate. The The inclusion criteria were as follows: • Patients with unresectable stage IV melanoma • Patients treated with anti-PD-1 or combination therapy • Patients who experienced cutaneous irAE with the administered immunotherapy. We only included patients in whom the drug was started for clinical indication in real life experience.
Atezolizumab, cemiplimab and avelumab delivered in melanoma clinical trials (n = 10/130) have been excluded. Patients who received intravenous anti-PD-1 or a combination of PD-1 and anti-CTLA4 or anti-LAG3 were selected and the type, occurrence of cutaneous adverse events were analysed thanks a questionnaire. All cutaneous adverse events have been registered. It is a prospective study for which a questionnaire was filled in to characterize the dermatosis and follow its evolution. Data were collected by an oncodermatologist at onset of the cutaneous adverse event (i. e. at inclusion of patients) and at 3, 6 and 12 months after the onset. Templates are given in Appendix 1. The cutaneous adverse events reported were pooled into four categories as follows: Grades III and IV cutaneous IrAEs were pooled in the analysis.
Melskintox database gathers data from 21 participating centres in different European countries (France n = 39, United Kingdom n = 21, Italy n = 20, Serbia n = 17, Austria n = 15, Greece n = 4, Belgium n = 2 and Germany n = 2) represented by different dermatological unit all around Europe as Nantes (n = 33), Rome Catholic University (n = 19), Belgrade (n = 17), London NHS (n = 16), Vienna (n = 13), Paris APHP (n = 6), London (n = 5), Athens (n = 4), Brussel (n = 2), Graz (n = 2), Tuebingen (n = 2) and Modena (n = 1).
PA is a cognitive process that allows individuals to manipulate language syllables, rhymes, or phonemes  [27]. In the dyslexic population, it is mainly the manipulation of phonemes that is affected  [28]  and is thus referred to as phonemic awareness. RAN refers to the rapid retrieval of phonological information from a word presented as a picture, followed by its immediate oral production. RAN and phonological awareness are two distinct phonological processes directly involved in dyslexia  [29]. In a more recent study  [30] , phonological awareness was identified as a predictor of word decoding skills and RAN as a predictor of word recognition and reading comprehension. Other researchers agree that the phonological processing deficit in dyslexia is the result of a more fundamental deficit in the perceptual processing of auditory information.
Global or local visual analysis SIGL© software  [59]  assesses the ability to focus the attention on a global or on a local visual information analysis mode. The stimuli are hierarchized drawings displayed during 175 ms. The software calculates the gap of performance between the control condition and the interference condition in order to assess the local and global interference. Results are given in response times and in error percentages. To determine the interference asymmetry, the local interference effect is subtracted from the global interference effect.
Objectives The main objective is to compare the effect on the phonological abilities of HIP-DD subjects of an intensive intervention combining training in categorical perception (CP), rapid automatized naming (RAN), and phonemic analysis (PA) versus a standard remediation program, at the end of the training program and at 6 weeks post-training. Main Hypothesis: We assume that intensive training coupled with standard dyslexia remediation will significantly improve participants' phonological skills. Two secondary objectives were identified:.
Descriptions of specific interventions Categorial perception-rapdys© Categorical perception training is carried out at home: 10 min per day, 5 times per week for the whole duration of the phase using RAP-DYS©  [43]. This software proposes a series of training sessions allowing the patient to discriminate more and more finely between two phonemes with different voicing (e. g. /d/ and /t/). The stimuli used depend on the level of difficulty: 5 levels based on the difference in VOT (Voice Onset Time) between the stimuli. Training consists of two tasks: identification and discrimination. In the identification task, the participant listens to a sound stimulus and has to determine which phoneme was heard. In the discrimination task, the participant hears two phonemes in a row and has to say whether they were the same or different.
Rapid automatized naming-naming speed The rapid automatized RAN training is performed at home: 10 min per day, 5 days per week for the whole duration of the phase, using the Naming Speed program. This program was created by Karine Harrar Eskinazi, Julie Nothelier, and Marine Versio for the needs of the forthcoming study "Developmental dyslexia and method of remediation (DDMR): Multimodal intervention in French children aged from 8 to 13 years''  [45]  because no other software for rapid naming training was available in French. This program was inspired by the Italian software "Run the RAN"  [42]. Five black and white drawings of objects from the LEAD lexicon database  [64]  are displayed on the screen and repeated on horizontal lines randomly displayed in boards of 20 to 60 stimuli. The patient must name, as quickly and accurately as possible, all the images presented, from left to right (in the direction of reading) following an imposed cadence; a red frame is automatically displayed on the screen and gives the patient the naming rhythm.
The score is the percentage of correct answers and will be the judgment criterion for this measure. Rapdys© Assessment Rapdys© Phoneme counting To assess phonological analysis skills, a list of 10 logatomes is presented to patients from an oral input. The examiner reads the logatome to the child and asks for a count of the phonemes composing it. For example, for the logatome /pabou/, the participant has to segment the phonemes and count them: /p/-/a/-/b/-/ou/ = four phonemes. The child has to answer four. The logatome lists were generated from the free software Logatron  [58]. In order to obtain 10 different logatomes in each of the 30 repeated measurement sessions, a list of 300 bisyllabic logatomes was generated. The logatomes in this list follow the phonotactic rules of French. Some of them contain complex phoneme groups (consonant clusters) and others are simpler.
Training supervision and treatment integrity The daily training sessions are carried out at the patient's home, and the parents or legal guardians are asked to fill in protocol monitoring forms. These forms contain both simplified training instructions for the parents and charts to record the child's scores each day. However, the weekly speech and language therapy sessions also provide an effective way to ensure proper completion of the protocol and compliance with the training instructions. Therefore, these records will be checked at each weekly speech and language therapy appointment to confirm that the training program is correctly followed. The RapDys© software will also provide a record of the dates and results of each training session. The measurements will be assessed by a member of experimental teams after each weekly speech therapy session.
Background Chlamydia (C. ) psittaci, the causative agent of avian chlamydiosis and human psittacosis, is a genetically heterogeneous species. Its broad host range includes parrots and many other birds, but occasionally also humans (via zoonotic transmission), ruminants, horses, swine and rodents. To assess whether there are genetic markers associated with host tropism we comparatively analyzed whole-genome sequences of 61 C. psittaci strains, 47 of which carrying a 7. 6-kbp plasmid. Results Following clean-up, reassembly and polishing of poorly assembled genomes from public databases, phylogenetic analyses using C. psittaci whole-genome sequence alignment revealed four major clades within this species. Clade 1 represents the most recent lineage comprising 40/61 strains and contains 9/10 of the psittacine strains, including type strain 6BC, and 10/13 of human isolates.
A large number of genome assemblies of varying quality from all Chlamydia spp. were published in the last decade. Given the steady advance of sequencing technologies and bioinformatics tools, it is not surprising that these genome assemblies differ significantly in quality, e. g. in scaffold numbers between 1 and 851 and N50 values between 1 Mbp (genome size) and 725 bp. In addition, the quality of gene annotations depends on the quality of the underlying assembly, the used annotation approach, software versions and parameters, as well as the reference database, which still represents a bioinformatics bottleneck even when high-quality genome assemblies are available  [22]. These deficiencies in genome quality and annotation status can seriously hamper comparative studies. Several genomic studies dealt with the comparison of whole-genome sequences among the major Chlamydia species  [23] [24] [25].
In a recent comparative study comprising 33 strains of 12 different Chlamydia spp. , including 10 strains of C. psittaci, we distinguished genomic features characteristic for C. psittaci, i. e. (i) a relatively short plasticity zone (PZ), (ii) an Inc protein set comprising IncA, B, C, V, X, Y, (iii) the largest chlamydial SinC protein sized 502 amino acids, and (iv) an elevated number of subtype G Pmp proteins (n = 14)  [24]. In the present paper, we report the findings of a comparative analysis of 61 C. psittaci genomes that were deposited in public databases and met our quality requirements. For the latter, we set the maximum number of scaffolds tolerated per genome to 50 with an N50 value of at least 100,000 bp, and required at least one-third of the annotated ORFs to be complete, meaning an alignment length ratio of 1.
Improvement of genome assemblies and annotation By February 1, 2021, 71 genome assemblies of C. psittaci strains had been uploaded to the NCBI and ENA databases. To ascertain data consistency and comparability, we removed any duplicates and finally included only whole-genome sequences fulfilling the quality criteria stated below. We re-assembled raw sequencing data available for 38 C. psittaci strains to achieve a better genome and annotation quality. After all cleaning steps, 11 re-assemblies achieved a better quality and were used instead of the original NCBI genomes in our final genome collection (Supplemental Table  S1 ). We set the maximum number of scaffolds to be tolerated to 50 to ensure consistency among the finally used assemblies, e. g. , for detection of the PZ. In addition, we checked assembly metrics such as the N50 value and the number of potentially fragmented ORFs (using IDEEL plots as described in  [38] ) to finally include genome assemblies of 61 strains in this study.
Among them, 37 had completely assembled genome sequences (one sequence), 20 consisted of 2-8 scaffolds and another four genomes had 16, 19, 28 or 44 scaffolds, respectively (Table  S1 ). This is a considerable improvement compared to the assembly states appearing in the respective NCBI and ENA entries. The reassembled genomes are deposited in the OSF repository: https:// osf. io/ rbca9/. In Supplemental Figure  S1 , we compare all re-assembled and original genomes regarding their genome contiguity and N50 values, while the IDEEL plots in the OSF repository show the improvement regarding fragmented ORFs. Moreover, re-annotation of all genomes using recent software versions and reference databases helped to reduce the proportion of non-annotated genome features designated hypothetical proteins to 25% (average 251 of 994 CDS, see Table  S1 ).
Creating a comparable sequence dataset To ensure accurate annotation and correct genome analysis our initial efforts we initially improved the assembly status of those whole-genome sequences that were poorly assembled or still in draft state. The limitations posed by incompletely assembled genomes are well known  [45, 46] , particularly their negative impact on annotation quality  [22]. Using state-of-the-art algorithms we decontaminated and re-assembled the raw reads of those chlamydial genomes that were of insufficient quality. The resulting harmonized genome set was validated using QUAST, Icarus, and IDEEL plots (see Figure  S1  and the OSF repository). Subsequent annotation of this dataset yielded better comparability among the genomes included in this study. To have a closer look at the divergence of specific loci in C.
The toxB gene product is an ortholog of lymphostatin/EFA-1, a toxin known from E. coli (EPEC and EHEC) and also Citrobacter rodentium. This protein carries three enzymatic activities attributed to motifs of glycosyltransferase (D-X-D), protease (C, H, D) and aminotransferase (TMGKALSASA) motifs  [49]. Therefore, the molecule is often annotated as LifA/Efa1-related large cytotoxin  [50]  or cysteine protease YopT-type domain protein  [51]. Additionally, based on homology to Clostridioides difficile, the 150-aa segment near the N-terminus carrying glycosyltransferase activity is designated TcdB toxin N-terminal helical domain protein in the U. database  [52]. While these features render the large cytotoxin a straightforward candidate for virulence factor, experimental evidence in a chlamydial context has yet to be obtained.
Phylogeny and host tropism Although the topic of host preference of C. psittaci was addressed in previous studies  [24, 62] , many questions have remained unanswered to date. It seems certain that there is no single genomic locus determining host predilection, but rather a panel of genes or gene products. In the present study, we observed a remarkable similarity in the topology of different phylogenetic trees reconstructed from genomic data, i. e. whole genomes, core genes, SNPs, PZ and OmpA (Figs. 1A, S2, S3, S4, S5). With a few exceptions, membership of the major clades or lineages proved stable among these trees, thus indicating that all five datasets reflect phylogeny. In contrast, analysis of plasmid sequences revealed some strain-to-strain relationships reminiscent of genome-based phylogeny, such as the clustering of Clades 3 and 4, but also marked differences among Clade 1 strains.
trachomatis plasmid was distinguished by its own specific SNP frequency, which implies a high potential for sequence variation in the course of evolution. Szabo et al. , who included 16 strains of C. psittaci in their study (14 of which are also part of our study), defined three plasmid genotypes M, N and O of this species  [72]. Regarding these 14 strains, our outliers M56 and NJ1 were assigned genotype M, whereas CP3 and WC were N, and 6BC, Cal10, DD34, RD1, 84/55, CB7, VS225, WS-RT-E30, Frances, and MN were genotype O. The results of our own comparative analysis (Figure  S5 ) are in line with the plasmid genotype classification by Szabo et al. , but future studies will show whether the introduction of more plasmid genotypes of C. psittaci is necessary. As only whole-genome sequences deposited in public databases could be included in our study, the present choice of C.
Chlamydial strains We included C. psittaci strains whose genome sequences, including raw data, were available from the NCBI or ENA databases on February 1, 2022 and had less than 50 scaffolds after reassembly using our own procedure described below. Strain designations, host organisms and assembly states are given in Table  S7. A more detailed overview with basic characteristics and database accession numbers of all 61 C. psittaci strains is given in Table  S1.
Reassembly, clean-up and normalization of genome sequences To reduce technical bias, the same tools and software versions were used to quality-control and de novo assemble all single and paired short-read data sets. For paired-end data sets, the respective input parameter settings were adjusted for each tool. First, reads were quality-trimmed using fastp v0. 20. 1  [77]  with parameters -5 -3 -W 4 -M 20 -l 15 -x -n 5 -z 6. Subsequently, de novo assembly was performed using SPAdes v3. 14. 1  [78]  with parameters --careful --cov-cutoff auto. Afterwards, the initial assemblies were subjected to two additional polishing rounds using Pilon v1. 23  [79]. We used BWA-MEM v0. 7. 17  [80]  to map the quality-controlled short reads to each respective assembly as input for the polishing steps. Finally, we used Bandage v0.
8. 1  [81]  to examine the assembly graphs and their contiguity. We used the decontamination workflow Clean (https:// github. com/ hoelz er/ clean v0. 2. 0) before and after reassembly to remove foreign sequences from the genomes in public databases, with sequences of Homo sapiens, Chlorocebus sabeus, Gallus gallus, Macaca nemestrina, phiX and Chlamydia psittaci plasmids being considered to be potential foreign contaminants. After reassembly, all strains with more than 50 scaffolds were discarded. We justify this cut-off based on our additional assessment of assembly quality. First, we used QUAST v5. 2. 0  [82]  to calculate various metrics between the original and reassembled genomes and in particular visualized contig N50 and assembly contiguity using the built-in Icarus tool  [83]. Secondly, to assess ORF quality and compare it in the original and re-assembled genomes, we ran a Snakemake pipeline3 implementing an approach called IDEEL as previously presented  [38].
Briefly, annotated ORFs were translated into proteins and compared against a reference database to plot their completeness. To facilitate genome comparison, whole-genome sequences of all finally included 61 strains were normalized using a custom python script (located as helper script in the RIBAP repository; https:// github. com/ hoelz er-lab/ ribap/ tree/ master/ bin/ helper/ rearr ange), so that the hemB (delta-aminolevulinic acid dehydratase) gene appeared in the initial position.
Annotation and processing of genome sequences All refined genome sequences were processed using the Roary ILP Bacterial Annotation Pipeline (RIBAP) v0. 6. 2 (https:// github. com/ hoelz er-lab/ ribap), which was recently developed in our group  ([24]. This pipeline performs annotation, core gene set calculation, alignments and phylogenetic reconstructions of homologous genes in RIBAP groups. As an initial operation, annotation was conducted using Prokka v1. 14. 5  [84]  with the --proteins option and the annotated GenBank file of C. psittaci 6BC (CP002549. 1) as reference to ensure consistency in gene denominations. After calculating an initial core gene set with Roary v3. 13. 0  [85] , RIBAP performs a less stringent all-versus-all MMSeqs2 v10. 6d92c  [86]  approach to find potential homologous genes missed by Roary.