dataesr/scientific-paragraphs-categorization huggingface dataset:
The schema also shows the location of phosphosites below the domains. (E), Domain schema (top) of the human IRF8 protein showing the location of variants identified. The bottom left structure is the N-terminal helix-turn-helix (HtH) domain bound to DNA (modeled on mouse IRF1 PDB:1if1 selected to view the bound DNA). The central structure shows the structure of the SMAD domain (modeled using human IRF4 PDB:5bvi) and the location of Val287, which sits in a beta-strand region (which is less favored by Met) making mostly hydrophobic contacts, and Glu353, which sits in a pocket close to two positive amino acids (Lys/Arg) making a substitution to Lys unfavorable. The structure on the right shows how the C-terminal 8 amino acids (either containing or near to the six observed frameshifts, fs) are similar to two other peptides known to bind SPRY domains (blue = Asn/Gln; red = Asp/Glu, green = hydrophobic) according to the ELM database.
ACKNOWLEDGMENTS This study was supported by  Marató TV3-Cancer  ( 201904-30  to SB),  Fundación Asociación Española Contra el Cancer AECC/CIBERONC :  PROYE18020BEA  (to SB),  Generalitat de Catalunya Suport Grups de Recerca AGAUR  ( 2021-SGR-01293  to S. B. ),  Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, "Cofinanciado por la Unión Europea" and Fondos FEDER: European Regional Development Fund  " Una manera de hacer Europa ":  PI17/01061  (SB),  PI19/ 00887  (ALG and EG),  INT20/00050  to AL-G). CL is supported by postdoctoral  Beatriu de Pinós  grant from  Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya  and by  Marie Sklodowska-Curie COFUND program  from  H2020  ( 2018-BP-00055 ). EC is an  Academia Researcher of the "Institució Catalana de Recerca i Estudis Avançats" of the Generalitat de Catalunya.
- 6. 6 ) 66 FigureS8B]. Univariable Cox regression showed a negative impact on OS for FOXO1 mutations [HR = 4. 9 (95% CI 1. 1-22. 8), p = 0. 042, Supplementary FigureS8C], as well as a trend toward a poorer OS for the 8 cases with TMEM30A deletion [HR = 2. 9 (95% CI 0. 9-9. 5), p = 0. 076, Supplementary FigureS8D]. Our dataset was not powered to perform multivariable analyses, due to the low number of cases and the heterogeneity of baseline features.
F I G U R E 4 4 Selected protein altering variants on known/predicted structures. (A), Domain schema (top) of human CD79B protein showing the location of variants identified in the present study. The schema also shows the location of phosphosites and disulphides below the domains. The structure below shows the dimeric structure of the CD79B Immunoglobulin-like domains with the location of the mutated residues as spheres and their interacting residues as sticks. The insets on the right show the regions around the two variants inside this domain. (B), Domain schema (top) of the human PLCG2 protein showing the location of variants identified. The complete structure of PLCG2 (modeled based on the PLCG1 structure PDB:6pbc) and its variants. The inset structures zoom in on the location of specific mutated amino acids (labeled with numbers) and their interacting residues (labeled without numbers).
As defined in the EuroNet-PHL-C1 trial imaging manual, thymic volume was calculated using the formula V = (a*b*c)/2. 30, 31 ymic tissue structure was visually classified as homogeneous (Figure  1A ) or inhomogeneous (Figure  1B ). Areas with motion artifacts or beam hardening caused by high-concentrated contrast agents were excluded. Thymic shape was divided into three subtypes: triangular (Figure  1A ), rhomboid, or irregular-bulky (Figure  1C ). According to Yarom et al. , who described imaging characteristics of RTH,  12  data about size, structure, and shape were recorded. Additionally, we examined the presence of calcifications (Figure  1D )  32  and the occurrence of single (Figure  1A ) or multiple masses in the thymic space. 16 The evaluation and image interpretation was done without knowledge of the clinical course by an experienced radiologist (Friedrich Christian Franke).
In our multinational and multicenter approach, there was no standardized protocol for contrast agent dose or scanning delay. Unlike Zhen et al. ,  33  we therefore did not measure the thymic density in Hounsfield units (HU) nor did we measure growth rates. In all patients, clinical follow-up data (relapse dates, event-free survival, follow-up intervals, relapse sites) were obtained from the EuroNet-PHL-C1 trial database. In all patients with LR, an additional F I G U R E 1 (A) Measurement of typical thymus in a homogenous thymus with triangular shape, (B) inhomogeneous thymus, (C) bulky-shaped thymus, (D) thymus with calcifications. PET and morphological assessment of the thymus was re-evaluated in consensus by a radiologist (Dietrich Stoevesandt) and a nuclear physician (Lars Kurch), both experienced in the evaluation of pediatric HL.
Limitations Our data were based on a multicenter study. Therefore, CT imaging protocols and parameters such as slice thickness, application of contrast agent (e. g. , concentration and delay times) differed. We therefore could not include HU density in our assessed parameters. This study is not designed to calculate the incidence of RTH during follow-up because of selection bias. All cases in the study were assessed by central review directly after CTX, but submitting followup imaging to central review was optional, mainly used as service of second opinion in cases with unclear findings. Therefore, cases with relapse and other diagnostic dilemmas are probably enriched in this dataset. There was no histopathological proof of thymic hyperplasia in cases classified as RTH. Also, in most cases classified as thymic LR, the biopsy was done in extrathymic locations and bioptical proof of thymic involvement was not possible due to ethical and diagnostic concerns of performing needle biopsy in the anterior mediastinum in CHL.
quality and quantity of imaging data differed, as CT and MRI scans were obtained in 133 different study sites in 14 European countries. Downloaded from https://onlinelibrary. wiley. com/doi/10. 1002/pbc. 30421 by Erasmus University Rotterdam Universiteitsbibliotheek, Wiley Online Library on [14/06/2023]. See the Terms and Conditions (https://onlinelibrary. wiley. com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License.
quality and quantity of imaging data differed, as CT and MRI scans were obtained in 133 different study sites in 14 European countries. Downloaded from https://onlinelibrary. wiley. com/doi/10. 1002/pbc. 30421 by Erasmus University Rotterdam Universiteitsbibliotheek, Wiley Online Library on [14/06/2023]. See the Terms and Conditions (https://onlinelibrary. wiley. com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License There were different local imaging protocols, resulting in a variety of slice thickness, tube voltages, tube current, collimation, pitch, and application of contrast agent. Out of 1752 enrolled patients participating in central review, we included 291 patients with adequate follow-up imaging within 2 years after LRA in our study; 121 (42%) were female.
MCXD Although SXDM gives us a robust understanding of the delithiation mechanisms inside a single particle, to assess the dynamics of lattice reorientation on a bigger scale operando MCXD technique was also employed. MCXD measurement was conducted operando during the same experiment by switching to an unfocused beam defined by a slit. Analysis of the MCXD data consisted of obtaining the coordinates of each Bragg reflection (up to 20 for each scan) in the reciprocal space and fitting their profile along the Y and Z axis in the reciprocal space (along and perpendicular to the powder ring respectively) as shown in Figure  S5. The Q z coordinate defines the average d-spacing of a crystallite while Q y corresponds to the rotation (misorientation) of the particle. Besides the contribution from the finite size of the diffraction volume (defined by Scherrer equation) the width of the Bragg reflection also contains information on the strain (width along Q z ) and angular divergence (width along Q x and Q y ) of the particle.
The charge and discharge curves obtained during the operando experiment are presented in Figure  S6. The difference between charge and discharge capacities are related to non-ideal electrochemical performance of the operando battery cell during the discharge. SXDM and MCXD Synchrotron measurements were conducted at the ID01 beamline of the ESRF -The European Synchrotron. The X-ray wavelength was set to 1. 24 Å (10 keV), with a beam size of 80 nm, and a flux of 10 9 ph/s. For the SXDM experiment the beam was focused down to 80 nm using a Fresnel zone plate, while for the MCXD experiment, the unfocused beam size was controlled by the opening of the slits. The diffraction data was collected by a bidimensional Maxipix detector (512 x 512 pixels) positioned at a distance of 1. 6 m from the sample.
Detailed descriptions of the beamline  [6]  and SXDM mapping technique  [2]  have been presented previously. 2D images of the reciprocal space were collected at each point of the real space map to determine the local variation of the Bragg reflection across the crystal. These maps were measured at different points of the rocking curve (20 angles with a step size of 0. 02 • ) to produce a 5-dimensional dataset with each pixel of the 2D image corresponding to a 3D volume in a reciprocal space containing the Bragg reflection. One full 5D scan of a 8 × 12 µm 2 area took approximately 23 minutes. MCXD measurements were done after each SXDM scan by removing the focusing optics and cutting the beam size to 200×200 µm 2 with slits. 1. 2 • rocking curve with 20 steps was also performed to cover a larger portion of the reciprocal space.
The perovskite film was attached to an O-ring on one side of the plasma chamber that acts as the cathode. The perovskite film area analyzed was a 4 mm diameter disk. GIWAXS measurements were made using a microfocus X-ray source (IμS, Incoatec, Germany) producing Cu K radiation ( = 1. 54 Å). GIWAXS patterns were recorded with a 2D X-ray detector (Pilatus 100 K, Dectris, Switzerland) with an exposure time of 10 s. The incidence angle was set to 2°and the distance between sample and detector to 73 mm. The I-V and I-T performance of the PDs were tested using the Keithley 2410 digital sourcemeter. The laser diodes were used as light source for the PDs measurement. The light power intensity of incident irradiation was tuned and obtained by an optical powermeter. Statistical Analysis: This study had no preprocessing data and used Origin for all data analysis and processing.
Topic guide Data were collected with the use of a semi-structured topic guide, shaped by the research team during a workshop following a structured iterative process. The process was guided by the conceptual model of health literacy  15  and the logic model of developing parenthood preparation education programs  16. The workshop participants were provided with a template sheet representing a cross-tabulation of the domains of the two models -an example and more information about the process is given in Supplementary file Material 2. Briefly, after an initial independent brainstorming session, the suggestions were gathered in a round-robin session, prioritized by consensus in terms of importance and relevance based on the aims, and finally organized in a logical flow with attention to phrasing to align with the purposes of the study.
ACKNOWLEDGEMENTS We would like to thank all women who participated in the focus groups and express our gratitude to them for kindly sharing their experiences with the research team. We would also like to acknowledge the interviewers, translators and field researchers who assisted in the recruitment of participants, data collection and analysis process, as well as all women and health professionals who participated in any of the series of studies and activities designed to shape the Baby Buddy Cyprus webapp (www. babybuddy. com. cy). We would also like to acknowledge all associate partners of the  Baby Buddy Forward Consortium  and their individual members which actively participated in any of the project's activities -namely,  Cyprus Ministry of Health, Midwives Committee of the Cyprus Nurses and Midwives Association, Cyprus Gynaecological and Obstetrics Society, Cyprus Society for Perinatal Medicine and Cyprus Paediatric Society.
Macroglia fulfill essential functions in the adult vertebrate brain, producing and maintaining neurons and regulating neuronal communication. However, we still know little about their emergence and diversification. We used the zebrafish D. rerio as a distant vertebrate model with moderate glial diversity as anchor to reanalyze datasets covering over 600 million years of evolution. We identify core features of adult neurogenesis and innovations in the mammalian lineage with a potential link to the rarity of radial glia-like cells in adult humans. Our results also suggest that functions associated with astrocytes originated in a multifunctional cell type fulfilling both neural stem cell and astrocytic functions before these diverged. Finally, we identify conserved elements of macroglial cell identity and function and their time of emergence during evolution.
Ventricular patterning is conserved throughout life and evolution We next turned to quiescent RG (qRG) (Fig. 1B , green cluster). Conservative consensus-clustering followed by iterative cluster-merging based on differential expression identified 7 robust clusters (q1-q7) (Fig. 2A , Fig. S1C ). We further confirmed that this was not dictated by technical parameters and that clusters could be re-identified with a classifier (Fig. S2 ), and identified cluster-specific gene signatures (Fig. 2B ). There was little overlap between the clusters we identified and those proposed in a previous study  (25). We thus reanalyzed the previously published data and performed in situ hybridizations (ISH) on whole mount telencephala and on serial coronal slices to assess the validity of our results. Although we resolved fewer clusters in these reanalyzed data  (25)  than in our own, likely due to the significantly lower number of cells profiled in this previous study, the data structure and patterns of cluster-specific gene expression now appeared consistent between the two datasets (Fig.
Conserved and innovative features of adult neurogenesis Adult neurogenesis has been mostly studied in rodents which display some of the highest evolutionary rates. Analyzing a broader range of species can improve generalizability and highlight fundamental features of the neurogenic cascade  (5) (6) (7). By reanalyzing datasets published in amphibians  (11) , reptiles  (9, 29)  and mammals  (10, (30) (31) (32) (33) (34) (35)  we compared gene expression patterns along successive steps of neurogenesis progression, from qRG to pre-activated RG (close to activation, corresponding to q1 in zebrafish) and neuroblasts, to reconstruct their state in the last common ancestors of different taxa (Fig. 3 ). This revealed conserved expression of key regulators since the last common ancestor of osteichtyes.
For example, the regulation of the Notch pathway is such that one Notch receptor gene is expressed in, and likely maintains, qRG  (36, 37). Conversely, Notch1 is expressed in paRG and so is the Notch ligand gene DLL1  (38, 39). The SoxC genes SOX4 and SOX11 are turned on in paRG and reach their peak in neuroblasts, consistent with their described roles in hippocampal neurogenesis  (40). Likewise, the EMT regulator ZEB2, which was recently found to be necessary for neurogenesis in the SEZ  (41) , displays conserved expression in neuroblasts. SOX9, which is a broad and specific marker of astroglia in adult mice  (42)  was not detected in previous datasets. We found that this is due to poor annotation of sox9a and that SOX9 expression is conserved in qRG among osteichtyes. Conversely, we found stepwise additions to the neurogenic cascade during mammalian evolution.
ID transcription factors modulate the dynamics of Notch signaling. Among them ID4 is more efficient than other IDs at inducing a return to quiescence  (43) , is the only one positively regulated by Notch signaling in qRG  (44)  and is a tetrapod addition (Fig. 3 ). The switch from NOTCH3 to NOTCH2 in qRG likely happened early in the mammalian lineage, which, with the emergence of NOTCH2NL genes that potentiate NOTCH signaling in humans  (45, 46) , could explain some human features of adult neurogenesis (Supp. Text). We were unable to reconstruct neurogenic trajectories from large-brained animals  (33, 34) , possibly owing to sensitivity limits of untargeted scRNA-seq, although we confirmed evidence of ongoing adult neurogenesis when reanalyzing a large macaque dataset  (35). While our re-analysis suggested that the initially defined RGL and IPC_2 clusters in this dataset are likely multiplets and of myeloid origin respectively (Fig.
S6 ), these data did include progenitors not found in other datasets, allowing us to confirm the expression of some of the highly conserved genes in primates. In particular, IGFBPL1 and HES6 are highly and specifically expressed in IPCs and neuroblasts and thus represent promising markers to assess continued production of neurons in the human hippocampus (Fig. S6 ). Together, this integrative approach highlights putative critical neurogenesis regulators either conserved throughout evolution or on the contrary responsible for taxon-specific properties.
Evidence for quiescence depth heterogeneities in zebrafish qRG, and implications on the diversification of mammalian astroglia from ancestral RG We found that our qRG clusters were further separated according to their quiescence depth (Fig. S7 ). Separation along a quiescence to activation trajectory was also apparent in mouse SEZ datasets. We focused on a recent one which profiled a large number of cells from the different regions of the SEZ with high sensitivity  (10). To identify putative regulators of quiescence depth we developed a pseudo-ordering algorithm (Fig. S8A ), applied it to both datasets and identified genes that show a strong association with deeper or shallower quiescence independently of region or species (Fig. S9 ). Some of these are likely part of a core quiescent stem cell gene set such as HES1 which has been proposed to be a general marker of stemness  (47) , or those encoding the exosomal proteins CD9 and CD81 which are enriched in several types of quiescent cells  (48).
Among the genes associated with deeper quiescence in zebrafish RG, several of them were expressed in both qRG and astrocytes in mice. We also noticed that some of these genes were instead highly enriched in, or even specific of astrocytes across several datasets (Fig. S10-S13 )  (10, 30, 32, 49). This came as a surprise since besides mammals, most species are not thought to have astrocytes  (50) (51) (52). To further investigate the possible relationship between some qRG in zebrafish and mammalian astrocytes we focused on dorsal qRG (clusters q1 to q4, Fig. 2A ) to mitigate signals related to regionalization. We converted genes from zebrafish and mouse into a uniform nomenclature for orthologs (Methods) and mapped our pallial qRG to astroglia from mouse telencephalon (Fig. 4A ). This revealed that similarity with astrocytes in zebrafish RG increases with quiescence depth.
Next, we asked whether in zebrafish q4 astrocyte-like RG participate in adult neurogenesis or behave like radial astrocyte with no physiological NSC properties. The high level of transcriptome similarity among RG precluded lineage-tracing based on a specific q4 promoter. Instead, we analyzed the fate of clones from Dm genetically tagged with the Tg(her4:ERT2CreERT2) line (Fig. S14A )  (54). her4 is broadly expressed, enriched in q4 over q2 (Fig. S14B ), and cells from q4 could be sorted from Tg(her4:egfp) reporter fish using the same her4 promoter(25) (Fig. S14B ). We reasoned that the ratio between the proportion of q4 cells in Dm and the proportion of her4driven clones that do not produce neurons would allow us to infer whether q4 cells behave as NSC (Fig. S14C ). At 507 days of chase, the proportion of RG-only clones was much lower than the proportion of q4 cells estimated in situ with RNAScope or in the scRNAseq dataset (Fig.
Evolution of astrocyte-like cells across planulozoa Cell types similar to astrocytes appeared multiple times throughout evolution. Among vertebrates, the only class other than mammals where astrocytes are the major astroglial cell population are birds. Absence of astrocytes appears to be the basal state in reptiles, and turtles -the closest living relative to birds and crocodilians-do not have astrocytes either, suggesting that the cells described as astrocytes in birds evolved independently from those in mammals. We thus asked whether avian and mammalian astrocytes displayed a similar signature. We found that datasets generated from the high vocal center of zebra finch included both astrocytes and RG  (55) , with a substantial overlap between the top genes separating astrocytes from RG in birds and mammals (Fig.
S15 ), suggesting that avian and mammalian astrocytes likely evolved in a similar way, from the same ancestral RG population. The expression of a conserved astrocytic gene set in some zebrafish RG suggests that it emerged before the individualization of astrocytes as a cell type. Moreover, parenchymal glia associated with support functions are present in all major branches of bilaterians  (56). To estimate the time of emergence of this astrocytic gene set we asked whether its genes were expressed across planulozoa by recovering and analyzing datasets from over 20 species  (9-22, 29, 34, 35, 49, 55, 57) , identifying existing orthologs and assessing their expression in glial clusters or among ectodermal cells (Fig. 5 ). We found expression of the astrocytic gene set in all vertebrate RG, but not in Ciona ependymoglia (Fig.
Evolution of other macroglial cells Cells of the oligodendrocytic lineage and ependymocytes make up the macroglia alongside astroglia. We used our zebrafish telencephalon dataset to identify cells belonging to the oligodendrocytic lineage and compared expression of putative core regulators and effector genes across chordates (Fig. S18 ). Others recently proposed that cells expressing sox9b are zebrafish astrocytes  (59). We found that they are transcriptionally closer to cells of the oligodendrocytic lineage and express several genes associated with oligodendrocyte maturation such as c7b, rnd3a, ugt8, cadm4, gpr17, myrf and plp1b, as well as low levels of mbpb. These cells might thus correspond to maturing oligodendrocytes, similarly to a population in the larval spinal cord  (60). For inter-species comparisons, we grouped cells based on the expression of CSPG4 (and/or PDGFRA for tetrapods).
Lamprey glia express not only PLP1 but also MPZ, like jawed fish, suggesting that co-expression is the ancestral state, lost in tetrapods. Despite being commonly associated exclusively with PNS, myelin PMP22 was detected in most species besides mouse. PMP22 being restricted to the PNS is thus a derived trait in mice. The core gene set conserved across vertebrates is not present in Ciona suggesting that the emergence of glia with oligodendrocytic properties happened in vertebrates after they split from other chordates. Ependymocytes likely appeared as a cell-type later in vertebrate evolution. In the zebrafish telencephalon similar cells are restricted to a rostral and ventral area  (62)  and were not profiled in our dataset. We detected a few in lizard and birds  (9, 55)  where they have been observed in small numbers along the ventricles whereas in mammals they cover the whole ventricular surface and represent a much larger fraction of astroependymoglial cells in the niche.