dataesr/scientific-paragraphs-categorization huggingface dataset:
Prospective association analysis We extended our analysis to ADHD symptoms at the age of 16 years in IMAGEN. Hierarchical multiple regression was applied to identify significant association between the baseline features and ADHD symptoms 2 years later. In these regression models with covariates and corresponding baseline symptoms, the behavioral variables and GMVs of the significant clusters were entered one-by-one. A variable was retained in the model when it significantly elevated the model performance (i. e. a significant ΔR 2 with p<0. 05). Analysis of covariance was performed between the persistent group and the TD control group in IMAGEN while controlling for the sex, handedness, TIV and site. Significance of the results were given by 10,000 random permutations (reported as p-perm), and validated by the comparisons between wellmatched samples (healthy controls were selected by an R package MatchIt to match the sample size with the persistent group)  (46).
Polygenic analysis The latest genome-wide association meta-analysis of 20,183 patients with ADHD and 35,191 controls was used as the discovery dataset (47), the summary statistics were downloaded from the Psychiatric Genomics Consortium (http://www. med. unc. edu/pgc/results-and-downloads). The primary analyses are based on the threshold of p<0. 50 since it maximally captures phenotypic variance  (48) , using the PRS software (PRSice; http://prsice. info/) (49). Associations of PRS with the neuropsychological variables were tested by partial correlation analyses while controlling for age, sex and site, while its associations with GMV of the significant clusters were assessed by additionally controlling for handedness and TIV.
Further support was provided by grants from: ANR (project AF12-NEUR0008-01-WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-etles-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), U. S. A. (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence, and the NIHR Cambridge Biomedical Research Centre (Mental Health Theme).
The Historical Cohort To create a historical cohort of DYT1 patients treated with GPi DBS, a literature search was conducted using PubMed/Medline, Embase, and Cochrane databases in May 2019 with the following search terms: deep brain stimulation, neurostimulation, DBS, DYT1, and TOR1A. The search syntax is available in Supplementary Material. The reference lists for each of the identified articles were used to explore additional relevant publications. We considered both pure DYT1 cohorts and mixed cohorts including DYT1 patients for inclusion. The inclusion criteria were as follows: (1) DYT1 dystonia; (2) bilateral GPi DBS; (3) no history of prior stereotactic brain surgery other than DBS; and (4) preoperative clinical assessments with postoperative assessments at 1 year or longer. The minimum required information for individual patients was the age at onset, the age at DBS surgery, disease duration before DBS, and preoperative and postoperative motor scores according to either the BFMDRS-M or the UDRS.
DISCUSSION The present study aimed to investigate the clinical characteristics of a multi-country cohort of patients with DYT1 dystonia who experienced suboptimal responses to DBS. Because only a few cases of DYT1 dystonia are operated each year even in expert centers, this dataset, though difficult to obtain, is crucial for the field. A few retrospective studies and a recent meta-analysis of mixed cohorts of inherited or idiopathic isolated dystonia patients reported that the TOR1A mutation-positive status was associated with a better DBS response, whereas the reasons underpinning suboptimal responses remained mostly unexplored  (Vasques et al. , 2009; Andrews et al. , 2010; Borggraefe et al. , 2010; FitzGerald et al. , 2014; Moro et al. , 2017). Our findings suggest that a subset of DYT1 patients may have a relatively more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression before DBS, and cranial involvement.
Patients with this phenotype may be more likely to experience suboptimal responses to DBS. There is a surprising lack of published information on suboptimal responses to DBS in DYT1 dystonia despite a growing number of reported cases. Panov et al. (2013)  reported that 47 DYT1 patients experienced an improvement in BFMDRS-M by greater than 80% up to 7 years after surgery;   Data are presented as mean ± SD unless otherwise indicated. The two groups were compared using independent t-tests, Mann-Whitney U tests, chi-square tests, or Fisher's exact tests. a P < 0. 05 (significant). b Motor assessments were done using either BFMDRS-M or UDRS. c % improvement at the last follow-up compared with the preoperative scores. BFMDRS-M, Burke-Fahn-Marsden Dystonia Rating Scale motor score; DBS, deep brain stimulation; NA, not available; UDRS, Unified Dystonia Rating Scale.
Comparison between the suboptimal and good responders of the historical cohort. Data are presented as mean ± SD unless otherwise indicated. The two groups were compared using independent t-tests, Mann-Whitney U tests, chi-square tests, or Fisher's exact tests. a P < 0. 05 (significant). b Motor assessments were done using either BFMDRS-M or UDRS. c % improvement at the last follow-up compared with the preoperative scores. BFMDRS-M, Burke-Fahn-Marsden Dystonia Rating Scale motor score; DBS, deep brain stimulation; UDRS, Unified Dystonia Rating Scale.
KF reports grants from  NIH , and other funding from  Donnellan/Einstein/Merz Chair , during this study; grants and non-financial support from  Medtronic , grants from  St Jude, Functional Neuromodulation , and  Boston Scientific , and grants and other funding from  Neuropace. Additionally, KF has a patent US  8295935 B2  issued for a DBS cranial lead fixation device. MO serves as a consultant for the  National Parkinson Foundation  and has received research grants from  NIH ,  NPF , the  Michael J. Fox Foundation , the  Parkinson Alliance, Smallwood Foundation , the  Bachmann-Strauss Foundation , the  Tourette Syndrome Association , and the  UF Foundation. MO's DBS research is supported by  R01 NR014852  and  R01NS096008. MO has previously received honoraria, but in the past >60 months has received no support from industry.
All pK i a ,k value are obtained using the PROPKA3. 1 software. 37 ing this set of n i Hill factors, the workflow of the titrating residue selection goes as follows. First, we carry out a pK a calcula-tion on the most representative clusters extracted from a standard (fixed microstate) equilibrated MD trajectory. Second, a prelim-inary CpHMD run is performed considering a reduced set of 5 titrating residues. Afterwards, a new clustering is performed us-ing the CpHMD trajectories before to calculate new pK a values of all titratable residues. After examination of these pK a values, the final set of titrating residues is selected (14 to 16 residues, de-pending on the considered system, the list is given in ESI Section 2 †). Eventually a final CpHMD computation is performed.
QM/MM computations Considering 30000 equally spaced snapshots extracted from the CpHMD trajectories, we calculated their QM/MM transition energies. The QM/MM partitioning defined the analogue and AMP as part of the quantum mechanics (QM) subsystem and the pro-tein and solvent as part of the molecular mechanics (MM) sub-system. In order to describe the electrostatic interaction between QM/MM subsystems, we have included the MM external potential as extra diagonal elements in the semi-empirical PM7 Fock opera-tor. Vertical excitation energies and transition oscillator strengths have been obtained using the Multi-Electron Configuration Inter-action (MECI)  38  implemented in MOPAC 2016 program  39. The absorption spectra have been generated using the Newton-X 2. 0 package 40.
Study Design This multicentered prospective study was open and nonrandomized. Patients acted as their own controls. The study was registered in the U. S. National Library of Medicine clinical trial database (ID: NCT02966366). Data were collected in six French cochlear implantation centers between August 2013 and May 2017. The study was approved by the French health authorities (ANSM: 2012-A01453-40) and the Ile-de-France VI (Paris, France) ethics committee (IRB: 2012-A01453-40).
RESULTS Twenty-six patients were included. Of these, one patient had a severe accident 1 week after the CI activation and was excluded from measures post-CI. Two patients withdrew from the study after the 4-month visit: one patient experienced an aggravation of the tinnitus and one experienced no benefit from CI stimulation. All data collected on these two patients up to and including the 4month visit were kept for analysis. Twenty-three patients completed the 7-month visit and the final 13-month visit when speech audiometry and binaural effects were measured. Missing data were kept as missing and no data imputation took place. The sample included 17 men and nine women, with a mean age of 54. 2 AE 10 years. Table  1  summarizes  Tinnitus appeared with hearing loss for 19 patients (73%) and after hearing loss for the remaining seven patients (27%).
Subjects have given their written informed consent. The study protocol was approved by the research institute's committee on human research. The study was registered in the U. S. National Library of Medicine clinical trial database (ID:  NCT02966366 ). The study was carried out in accordance with the Helsinki Declaration and was approved by the French health authorities (ANSM:  2012-A01453-40 ) and the  Ile-de-France VI (Paris, France)  ethics committee (IRB:  2012-A01453-40 ). Conflicts of Interest and Source of Funding: The authors acknowledge the support of  Oticon Medical (Vallauris, France)  who provided the cochlear implant systems and their accessories. Four of the authors, M. A. , D. G. , M. H.
Here, we observe that there might be connections between ICA-reported networks. For example, ACC is part of the DMN. It is also known to be involved in several processes such as the balanced between behaviors, autonomous functions or nociception, and known to have a lot of connections with other areas including sensory and motor areas  [60, 61, 62]. ACC, as defined in our study, can therefore be involved in different networks. Some comparisons between graph-based analyses and the effect of GSR and ICA are given in  [44] , but it would be of interest to perform an entire study on the same dataset to compare and enhance the complementarities of the different methods.
Funding The MRI facility IRMaGe is partly funded by the  French program Investissement d'Avenir run  by the  French National Research Agency , grant  Infrastructure d'avenir en Biologie Santé  [ ANR-11-INBS-0006 ]. This project was partly funded by  NeuroCoG IDEX UGA  in the framework of the  Investissements d'avenir program  [ ANR-15-IDEX-02 ].
After washing, fluorescently labeled secondary antibodies (Cy ™ 3 AffiniPure Donkey Anti-Mouse IgG (H + L), Jackson ImmunoResearch) were incubated for 1 h at RT. Nuclei were stained with DAPI at 1 µg/mL. After three steps of washing with DPBS, cell monolayers on filters were mounted with Mowiol (Sigma-Aldrich) and analyzed with a Nikon Eclipse E600 microscope using the Nikon NIS-Elements BR3. 10 software (Nikon, Egg, Switzerland).
Funding This study was funded by the  Swiss National Science Foundation  ( CRSII3_154483 ,  Sinergia UnmetMS ) to BE, RM and FS, the  Bangerter-Rhyner Foundation  to BE, the  Swiss Multiple Sclerosis Society  to AM;  ECTRIMS Postdoctoral Research Exchange Fellowship  and the  Uehara Memorial Foundation  to HN and by the  Germaine de Stael PHC program  to FG and BE.
Acknowledgments We thank  Dr. Anne Marie Galibert  and  Dr. Brigitte Soula  ( CIRIMAT, Université de Toulouse, CNRS, F-31062, France ) for help in the work on raw carbon nanofibers. The authors acknowledge fundings from the  Agence Nationale de la Recherche  (  ANR-15-CE19-0 0 06  and  ANR-19-CE19-0 0 02-01  ). This work was supported by  French RENATECH network.
, 2019a). These initial studies provide solid grounds for the development of replication studies, meta-analyses, and multicenter consortia, the gold standards in evidence-based science. Presently, we aim to describe the current trends in the field and to examine how these impact the results and their comparability with the rest of the literature. While recommendations to enhance reproducibility exists for human neuroimaging  (Poldrack et al. , 2008) , a large number of acquisition and data processing aspects remain specific to animal imaging. We systematically assessed the animal fMRI literature for data acquisition and analysis procedures to provide an overview of the collective directions taken within the animal imaging community. We then reviewed the major considerations taking place in the study design, and how these impact results and their interpretability.
METHODS We searched the Pubmed database 1  on February 11, 2019 for the terms "functional magnetic resonance imaging, " "functional MRI, " or "fMRI" within the abstract or title, excluding studies in human and reviews, from 1990 onward, using the following command. "Search ((fMRI[Title/Abstract]) OR functional MRI[Title/Abstract]) OR functional magnetic resonance imaging[Title/Abstract] Sort by: Best Match Filters: Abstract; Publication date from 1990/01/01 to 2019/12/31; Other Animals. " The query returned 2279 entries. The title and abstract from these were manually screened to exclude studies that did not contain primary research using MRI to assess brain function in animals. In total, 868 research article were considered relevant and could be readily accessed. We recorded the type of study: resting-state or paradigm free RS-FC recordings, pharmacological-evoked, opto-/chemogenetic neuromodulation, deep-brain stimulation (DBS), or stimulus-evoked (including blocks-or events-related designs with sensory stimulation, gas challenge, etc.
). We recorded animals species, including strain, gender (male, female, both, N/A), number of animals used, animal preparation (awake, anesthetized free-breathing, anesthetized ventilated), anesthetic used for maintenance during fMRI, field strength, fMRI sequence and contrast, pre-processing softwares, and noted if the datasets were made available by the authors or in online repositories. The resulting table is made available in the Supplementary Material.
Experimental Design Animal fMRI presents the opportunity for new and creative directions in study design, but care must be taken to ensure that experimental changes in the fMRI signal are sufficiently robust FIGURE 1 | (A) A seed-based analysis of the anterior cingulate area in 98 resting-state fMRI scans reveals the topological distribution of the mouse default-mode network. The regions co-activating with the seed include the dorsal striatum, dorsal thalamus, retrosplenial, and posterior parietal areas. (B) The reproducibility of the default-mode network was assessed in 17 independent datasets consisting of 15 scans each. Overlapping one-sample t-test maps are summarized in a color-coded overlay. 12/17 datasets present converging topological features, the remaining five failed to present evidence of distal connectivity relative to the seed.
Efforts to develop unified open-source pre-processing pipelines for human fMRI, e. g. , fMRIPrep  (Esteban et al. , 2019) , have yet to reach widespread adoption. In animals, we observed that a large number of studies relied on custom made pre-processing functions (26%, Figure  6A ). SPM was the most common software package used for the analysis (27%). The preponderance of custom made software, as well as the combination of functions from several software suits in animal fMRI research, may be explained by the fact that specific functions were designed for the human brain. The pervasive use of ad hoc pipelines, encouraged by the lack of dedicated animal pipelines, is a major obstacle to results comparisons between centers.
Templates and Atlas Selection Registration of fMRI results to a common reference space is an integral part of the pre-processing and enables unbiased group-level statistical analysis at a voxel-wise level. In human neuroimaging, standard space and coordinate systems are routinely used to report results in both figures and tables. In animals, we found that the vast majority of the studies did not register fMRI data to standard space (64%) while 24% relied on FIGURE 6 | Software used for data analysis of animal fMRI and functional connectivity analysis. (A) Custom made software or combination of existing software pipelines remained the most common approach to animal fMRI data processing, while SPM was the most used software package used. (B) Resting-state fMRI in animals is mainly analyzed with seed-based analysis.
, 2014). Other methods can be used to look at the co-occurrence of the individual events that drive RS-FC  (Petridou et al. , 2013; Liu et al. , 2018)  or at large-scale repeated patterns of activity  (Majeed et al. , 2011; Grandjean et al. , 2017a; Belloy et al. , 2018) , offering the possibility of mapping RS-FC non-correlative terms. There are major methodological considerations to such analysis  (Laumann et al. , 2017; Liégeois et al. , 2017 ). Yet, some of the crucial confounds, specifically head motion, are less applicable to animal studies in anesthetized or paralyzed animals. It emerges that nonstationary patterns are reproducible in both human and rodent datasets  (Abrol et al. , 2017; Grandjean et al. , 2017a; Gutierrez-Barragan et al. , 2018). These represent promising emerging methods to investigate the RS-FC signal beyond the stationary hypothesis which characterizes the methods discussed above.
, 2009). There are a few explicit examinations of test-retest reproducibility in rodents that undergo the same experimental protocols, providing insight into the level of reproducibility that might be expected. Zerbi et al. (2015)  found an R 2  value of ∼ 0. 7 for optimally processed data from mice under medetomidine/isoflurane combination  (Zerbi et al. , 2015). Kalthoff et al. (2013)  showed that the spatial localization of ICA components shares a common core, particularly under medetomidine sedation. Converging ICA and seed-based maps derived from multiple-datasets are available in the mouse as quality assurance references  (Grandjean et al. , 2019a). Nevertheless, substantial variability in the correlation coefficients from different studies is present, depending on pre-processing steps, ROI definition, and other factors.
To overcome these limitations and to permit meta-analysis, NeuroVault  (Gorgolewski et al. , 2015)  offers a resource to publish statistical maps prior to statistical thresholds, leaving the users to explore, reinterpret, and repurpose these results. Unfortunately, such resources are not yet available to animal neuroimaging studies. The advent of RS-FC and network analysis is another source of dissension in the statistical analysis. With fine-grain ROI sets, the number of edges increases dramatically, hence the number of univariate tests and the need to correct for multiple comparisons. There, no consensus currently exists to effectively account for multiple comparisons and the heightened level of false positives ensuing. The growth of the human neuroimaging community has been fueled by large datasets made publicly available in online repositories  (Nichols et al.
, 2017). Making raw data available is becoming a requirement by the funding bodies, academic center, and the journals. In spite of these requirements, we only found 15 mentions of data availability, among 868 studies, seven of which upon reasonable request to the senior author. Publication of datasets on established repositories ensures lasting availability of the dataset and unbiased distribution. Databases such as XNAT 2  (Herrick et al. , 2016)  and Openneuro 3   (Poldrack et al. , 2013)  are becoming increasingly user-friendly, including standardized formats that allow for the easy organization and retrieval of functional and anatomical data  (Gorgolewski et al. , 2016). Importantly, potential reticence in human neuroimaging to share material to protect subject privacy do not apply in animal research.
Nonetheless, we report general trends which indicate some degrees of consensus. For instance, isoflurane and medetomidine and/or their combination represent an increasing proportion of the studies performed in anesthetized rodents, supported with increasing evidence from the literature. Sequences and contrasts are also reaching consensus, as the overwhelming majority of the studies were acquired using GE-EPI and BOLD contrast, predominantly at high fields such as 7T and 9. 4T. Importantly, a number of aspects emerge which are currently lacking within our community and which could easily be implemented to greatly ameliorate how results are interpreted. While modest, these first steps will be necessary for the adoption of standards, replication studies, and meta-analysis. Firstly, the systematic sharing of raw datasets upon publication is the easiest milestone to be achieved within our community.
Zheng lab (NW802 and NW958) did not show this labeling pattern. Both antibodies SC-22692 and NW802 are polyclonal and recognize the 50 and 20 first amino acids of the N-terminus extreme of the protein prestin in humans and mice, respectively, while NW958 recognizes the last 20 amino acids of the c-terminus extreme of the protein in mice. The gene for prestin has been fully sequenced for harbor porpoise (GenBank GU219842. 1), for bottlenose dolphin (GenBank GU217587. 1), common dolphin (GenBank GU219839. 1) and partially sequenced for mustached bat (GenBank JN315991. 1; the n-terminus extreme is not complete)  (14, 47). The full sequence has also been predicted by automated computational analysis using gene predicting method Gnomon, supported by mRNA evidence for beluga whale (NCBI reference sequence XM_022554419.
ACKNOWLEDGMENTS We would like to thank  Manfred Kössl  ( Institut für Zellbiologie und Neurowissenschaft, Goethe-Universität, Germany ) for sending us the bat samples, and for providing helpful advice on the manuscript, as well as  Edwin Rubel  ( Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle ) and  Régis Nouvian  ( Institute for Neurosciences of Montpellier ). The authors were grateful to  Jing Zheng  ( Northwestern University ), who kindly provided the prestin antibodies for this study (refs. NW802  and  NW958 ). Additionally, we would like to thank all the volunteers of the Dutch stranding scheme who reported and collected stranded harbor porpoises for postmortem investigation, and  Lineke Begeman  and  Liliane Solé  for their help in collecting the inner ears of harbor porpoises during post-mortem investigations at  Utrecht University.
FUNDING This study was funded by the  Natural Sciences and Engineering Research Council (NSERC)  of  Canada Discovery  and  Accelerator  grants  RGPAS 446012-13  and  RGPAN 312039-13  to RS,  NSERC  grant  RGPIN 155397-13  to  AV and Marie Skłodowska-Curie Individual Post-doctoral Fellowship   751284-H2020-MSCA-IF-2016  to MM.
However, if one considers a projective lattice N -hyperdistant from L 1 , it is a priori not preserved by such a projective linear transformation in PSL 2 (Z), but instead is mapped to another projective lattice N -hyperdistant from L 1 (since the right action of PSL 2 (Z) preserves the hyperdistance). The dessins d'enfants which correspond to the Hecke groups Γ 0 (N ) contains this data quite efficiently.