dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments We thank  Romain Lorentz  and  Valérie Erbs  in the ICS genetic engineering team,  Sylvie Jacquot  and all members of the ICS genotyping team, and all ICS teams for their help in creating the mutant mouse model. We also thank  Loïc Lindner  and  Pauline Cayrou  for their help in ddPCR design and training. We thank the animal caretakers  Sophie Brignon ,  Charley Pinault , and  Dalila Ali-Hadji  at  PHENOMIN-ICS and IGBMC animal facility  for their services. We thank the team of  Marie-Christine Birling's laboratory  at  ICS  for generating this mouse model. Elodie EY  at  ICS  for her kind help for mice live tracking. Funding The Molecule-to-Man Pain Network has funded this work, a  European Commission Multi-Center Collaborative  Project, through the  European Union 's  Horizon 2020 research and innovation program  under the  Marie Skłodowska-Curie  grant agreement No.
Conclusions. -This study provides insight into training needs for MDs regarding healthcare pathways in ADHD and should support the implementation of health policies, such as a stepped healthcare access for ADHD. The study design and dissemination have been validated and will be available in France and other countries facing similar obstacles in care pathways for ADHD. Official recommendations on ADHD in children and adults are being updated in France, and our data and the survey design will be a starting point for their implementation.
A previously published research proposed a tool to provide a replicable approach to assess health professionals' knowledge in Ireland  [27]. Thus, we adapted this questionnaire to the French setting and had it translated and back-translated by the first author and external translators. This also allowed us to control metric values of the index of knowledge and attitudes through its application in our population study. The final questionnaire (see supplementary materials: questionnaire) was organised into five sections: 1) general information about the respondent (age, gender, tier-level, medical speciality, setting, and description of medical activity) (11 items); 2) local healthcare organisation and context, including potential referral routes available to the respondent (12 items); 3) level of expertise and training of respondents regarding ADHD (5 items); 4) attitudes about ADHD (7 items), and knowledge about ADHD (5 items about clinical facts, 5 items about treatment) based on a Likert scale ranging from entirely disagree (-2) to fully agree (+2), with reference on the values obtained through the script concordance test completed by a panel of experts (see below); 5) self-assessment of the degree of expertise in ADHD using a visual analogue scale (VAS) with a score ranging from 0 to 100.
The estimated time to respond to all 45 questions was 10 minutes. The questionnaire was circulated using SurveyMonkey ® software (SurveyMonkey Inc ® ). Tier levels were defined according to the national recommendations published by the French Haute Autorité de Santé and described in the questionnaire in appendix  [21]. We first performed a script concordance test  [28, 29]  with a panel of 12 ADHD experts to provide a/a "gold standard" of the response of experts for attitudes and knowledge on ADHD, b/reference values to be compared with individual responses to the survey (results in supplementary table* 1). Script concordance tests are assessment tools designed to determine whether respondents' knowledge is The composite scale and the VAS of expertise scores were used for the statistical analysis.
Univariate statistical analysis was used to compare groups of respondents according to demographic variables and professional status regarding the composite scale and VAS. Non-parametric tests were used when the sample did not follow a normal distribution. We also used regression models using the composite scale and VAS as response variables to identify predictors that could be relevant for future professional training. All statistical analyses were conducted with IBM SPSS 25 and Jamovi 1. 8. 1. Figs. 2  and 3  were designed using JMP ® , Version 17. SAS Institute Inc. , Cary, NC, 1989-2023. Descriptive analyses included frequency distributions, percentages, and mean and standard deviations. The significance level was set at P < 0. 01 for this analysis, as several statistical analyses were performed.
Discussion Our work is a unique study in France to offer a reproducible strategy of assessment of knowledge and representation in MDs involved in child ADHD and an evaluation of the current access to care in two regions covering 14 million inhabitants. These regions were chosen as healthcare networks on SLD have reached a complete territorial deployment and may serve as a model of a steady state situation in healthcare organisation. The response rate (9. 4%) might represent an overall estimation of the percentage of MDs potentially involved in child ADHD, as the survey was officially endorsed and extensively disseminated by both regional health agencies and unions of MDs. Our work provides baseline data previous national recommendations about childhood ADHD in France in 2023  [30]  and prior to the conclusions of a regional experimentation about a structured stepped care model  [21, 22].
Acknowledgements We gratefully acknowledge  Nadine Rémy ,  Nathalie Burdo ,  Dr Ivan Théis ,  Catherine Choma  ( ARS Occitanie ),  Fabienne Righetti  ( ARS Auvergne Rhône Alpes ) for their support in the diffusion of the survey to hospitals, medico-social institutions of their regions. Similarly, we are indebted to  Dr Maurice Bensoussan  and  Laetitia Habouch  ( URPS ML Occitanie ), to  Martine Ranc ,  Dr Jean Stagnara ,  Dr Pierre-Jean Ternamian ,  Dr Vincent Rébeillé-Borgella  ( URPS ML.
Acknowledgements. We would like to acknowledge the imaging facility MRI, member of the  France-BioImaging  national infrastructure supported by the  French National Research Agency  ( ANR-10-INBS-04 ,  «Investments  for the future»)". We also acknowledge the  Zebrafish International Resource Center  for providing KO zebrafish lines. The  Jopling lab  is part of the  Laboratory of Excellence Ion Channel Science and Therapeutics  supported by a grant from the  ANR. Work in the Jopling lab is supported by a grant from the  "la Fondation Leducq " and from the  ANR  (contract  ANR-20-CE14-003-02 MetabOx-Heart  and  ANR-22-CE14-048-02 IONIC  ).
Subsequently, we applied single-cell RNA sequencing (scRNA-Seq) on medium and small brain vessels to identify aging-associated transcriptional changes focusing specifically on VSMCs and pericytes (Figure  1C ). After data quality control (Supplemental Figure  1, A-C ; supplemental material available online with this article; https://doi. org/10. 1172/ JCI166134DS1), we clustered cells based on their expression profile using the Pagoda 2 pipeline (https://cran. r-project. org/ web/packages/pagoda2/index. html) and identified 12 clusters potassium transport (Atp1b1), and muscle structure (Myh11, Sgcd, Utrn) underscored disrupted contractility and altered VSMC identity. Similarly, upregulation of many matrix transcripts (Col3a1, Col8a1, Lgals1, Ogn, and Sulf1) indicated higher synthesis of matrix proteins with resulting stiffness/fibrosis of the vasculature.
Our data show a significant increase in the frequency of PAS + granules in CADASIL brains relative to matched controls (Figure  10, H  and I ). We also evaluated the presence of chondroitin sulfate proteoglycans of WT mice at 2 months and 24 months of age. While we did not detect chondroitin sulfate proteoglycans at 2 months, accumulation was noted in the perivascular space by 24 months (Supplemental Figure  13G ). The levels of such accumulation were more pronounced in the absence of Notch3 by 12 months (Supplemental Figure  13H ). Finally, scRNA-Seq evaluation of the neuronal constituency of Notch3 -/-at 12 and 24 months revealed progressive alterations in transcripts associated with neuroinflammation and neurodegeneration (Figure  11, A-F ). Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses highlighted multiple neurodegenerative diseases as signatures associated with Notch3 -/-aged mice (Figure  11, C  and F ).
For the generation of single-cell gel beads in emulsion, cells were loaded onto the Chromium single-cell instrument (10X Genomics) with an estimated targeted cell recovery of approximately 5,000 cells. Sequencing was performed on an Illumina Novaseq 6000. Libraries were processed using the Cell Ranger pipeline (10X Genomics) and analyzed using the R package Seurat  (54). The following R packages were used for data visualization in combination with Seurat: ggplot2, ggraph, igraph, and tidyverse.
Western blotting Lysates from aortic VSMCs were prepared in 8 M urea and run under denatured conditions on an SDS-PAGE 4%-12% gradient gel, transferred onto nitrocellulose membranes, and blocked and incubated overnight at 4°C with primary antibodies. Immunocomplex detection was performed with the enhanced chemiluminescence SuperSignal West Femto Maximum Sensitivity Substrate (Thermo Fisher Scientific) and SuperSignal West Pico Maximum Sensitivity Substrate (Thermo Fisher Scientific) using the ChemiDoc XRS+ Molecular Imager (Bio-Rad). Densitometry analysis was performed using ImageLab Software. Information on antibodies used is available in Supplemental Methods.
In vivo hemodynamics and vascular reactivity Under anesthesia, a pressure catheter (1. 0F, model SPR1000, Millar Instruments) was introduced into the right carotid artery and advanced to the ascending aorta of the animal. Each animal was allowed to acclimate for 5 minutes, at which time isoflurane was reduced to 1%. Pressures were recorded using Chart 8 software (ADInstruments) and analyzed from 1 to 4 minutes. For reactivity, a central venous catheter (Instech, PE-10 tubing) was placed in the jugular vein; in addition, an arterial pressure catheter (Millar Instruments) was used to measure continuous blood pressure Images were collected with the Nikon A1R confocal system with NIS Elements acquisition software and analyzed with Imaris software (9. 9. 0, Bitplane). A subset of samples were imaged using a Nanozoom RS digital slide scanner (Hamamatsu) (H&E) and analyzed with the companion NDP Viewer software or the Nikon Eclipse light microscope using a ×10 air objective (PAS).
Micro-CT scan and parameters and reconstruction Brain samples were scanned on a Bruker Skyscan 1276 system with voltage 50 kV, current 100 μA, and a 0. 25 mm Al filter. Image capture was set with a pixel size of 6 μm. Per scan, we acquired an average of 2,100 projection images at a 0. 2° rotation step over 360° total to improve the signal-to-noise ratio. Reconstruction of the data was generated with NRecon software (Bruker) for. bmp files for downstream processing by Imaris (9. 7. 2, Bitplane). Additional information on visualization and quantitative analysis is provided in Supplemental Methods.
Retinal VSMC coverage analysis Quantification of retinal VSMC coverage of arterial vessels was performed using the NIS Elements software to calculate the relative percentage of αSMA + area. Additional details and imaging parameters are provided in Supplemental Methods. Image analysis and fluorescent bead tracking Images were analyzed using ImageJ software. Fluorescent microsphere tracking was performed using individually acquired 1-minute single-channel recordings obtained across multiple intravital imaging sessions. Microsphere flow speed was measured by tracking of total perivascular distance traveled over time within a given series of frames and averaging of flow speed from 3 separate observed particles per recording. Dextran clearance experiments FITC-conjugated 70 kDa dextran (5 μL at 1% in aCSF) was infused into the cisterna magna of a mixed-sex cohort of 3-month-old C57BL/6J mice.
Intravital imaging of perivascular flow Imaging was performed using an Olympus BX-51WI Fixed Stage illuminator with a Yokogawa CSU-X1-A1 spinning disk, a Hamamatsu EMCCD C9100-50 camera, and a Modular Laser System with solid-state diode lasers with DPPS modules for 488, 561, and 640 nm and the appropriate filters as previously described  (56). Synchronization was managed by a Prosync 2 Controller. Z axis movement and objective positioning were controlled by a Piezoelectric MIPOS100 System. Fifteen minutes before intravital imaging, green fluorescent polystyrene microspheres (FluoSpheres, 1. 0 μm, 505/515 nm, 0. 4% solids in aCSF) were briefly sonicated and infused at 2 μL/min for 5 minutes through the cannula using an infusion pump. Images were collected with a ×20 water immersion objective using Volocity software.
Acknowledgments We thank the  UCLA Broad Stem Cell Research Center  for sequencing scRNA-Seq libraries and the  Mouse Histology and Phenotyping Core  and the  Small Animal Imaging Facility at Northwestern University. A special thanks to  Michelle Steel  for assistance with husbandry and mouse experimentation. This work was supported by  NIH  grants  R35HL140014  and  U01151203 ; the  Leducq Foundation (ReVAMP)  (to MLIA); the  Northwestern University Molecular and Translational Cardiovascular Training Program  ( T32HL134633 ;  SP0040691 ) (to MCR);  NIH  grant  F31HL165767  (to JS);  Howard Hughes Medical Institute Gilliam Fellowship  ( GT11560 ) (to GEH); and  American Heart Association   23POST1022462  (to AM). BAK was supported by  NIH   DIR HL006247. MMW was supported by grants from the  Department of Veterans Affairs  ( BX003824  and  NS099160 ).
Methods: The aim of the present study was to evaluate the pooled proportions of venous thromboembolism (VTE) recurrence, bleeding, and post-thrombotic syndrome (PTS) in patients with UEVT. A systematic literature review was conducted of PubMed, Embase, and the Cochrane Library databases from January 2000 to April 2023 in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. All studies included patients with UEVT and were published in English. Meta-analyses of VTE recurrence, bleeding, and of PTS after UEVT were performed to compute pooled estimates and associated 95% confidence intervals (CIs). Subgroup analyses of cancerassociated UEVT and catheter-associated venous thrombosis were conducted. Patients with Paget-Schroetter syndrome or effort thrombosis were excluded.
METHODS Search strategy. A systematic literature search of the PubMed, Embase, and Cochrane electronic databases were conducted with restrictions to adults aged >18 years and studies published in English. The search strategies were adapted for each database to include database-specific thesaurus terms and field names. The search queries were developed using combinations of subject headings and free text words, including upper extremity vein thrombosis, upper extremity deep vein thrombosis, thoracic outlet syndrome, upper extremity, axillary vein, subclavian vein, vascular access device, catheterization, peripheral, venous thromboembolism, postthrombotic syndrome, prevalence, bleeding, and recurrence. The search strategy is shown in the Appendix (online only). To identify additional relevant studies that met our inclusion criteria, the references of the relevant retrieved reports were also examined.
Criteria for study inclusion. Observational studies (cohort and case-control studies), randomized control trials, and case series were included if they included >10 patients. The included studies must have objectively diagnosed UEVT via venography, computed tomography, magnetic resonance imaging, and/or ultrasound and included only patients aged $18 years. UEVT was defined via ultrasound as incompressible material in the venous lumen or the lack of venous flow modulation for proximally located thromboses. For computed tomography and magnetic resonance imaging, UEVT was defined as endovenous material of a clot nature. Study selection and data extraction. Two reviewers (O. E. and B. P. ) independently examined the retrieved studies for possible inclusion by assessing the study title and abstract.
Any disagreements were resolved by consensus or consulting a third reviewer (O. S. ). The potentially relevant studies were marked for full-text review. The studies selected for further review were evaluated in detail in accordance with the inclusion criteria and outcome measures. Using a standardized data extraction form, three reviewers (O. E. , B. P. , A. R. ) independently collected data on the number of included patients with UEVT, the association of UEVT with secondary causes (ie, venous catheter [CVC], malignancy), choice of treatment (ie, anticoagulation, thrombolytic therapy), and the occurrence of PTS, recurrent VTE, and bleeding. Study data quality, including enrollment of patients, authors, year of publication, country, study design, and duration of follow-up for each study were also noted.
PTS was evaluated at the completion of follow-up. VTE recurrence was defined as a new UEVT in a previously unaffected venous segment, a new pulmonary embolism, or new lower limb deep vein thrombosis proven by computed tomography and/or ultrasound. Major, minor, and clinically relevant nonmajor bleeding events were analyzed when reported using the criteria of the International Society on Thrombosis and Haemostasis. 8, 9  The following data were extracted using predesigned forms: number of patients, study characteristics, followup duration, UEVT etiology, cancer, presence of a CVC, type of treatment, recurrent VTE, PTS, and bleeding complications during anticoagulant therapy. All clinical outcomes were extracted for the overall study population and for patient subgroups. Assessment of study quality.
Publication bias was evaluated using funnel plots of the logit event rate against standard error and an Egger's test at a 5% significance threshold. 13  Asymmetry patterns and estimate distortion were explored. All analyses were conducted in R with the {meta} package (R Foundation for Statistical Computing). Ethics and registration. This study is reported in agreement with the PRISMA (preferred reporting items for a systematic review and meta-analysis) statement. No ethical approval or patient informed consent was required. This meta-analysis was performed in accordance with the Cochrane's Handbook guidelines and MOOSE (meta-analysis of observational studies in epidemiology). 14  The protocol for this systematic review was registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD 42021249053).
RESULTS Study selection and characteristics. We identified 5036 citations (Fig  1 ) through our initial literature search and included 120 studies in our full-text review. A total of 55 studies met our inclusion criteria with relevant data on our outcomes and were included in the final metaanalysis. The 55 studies included 15,594 patients diagnosed with UEVT; 16 studies were prospective and 15 were multicenter studies. The characteristics of the included studies are presented in Supplementary Table  I  (online only). Of these, 50 studies reported data on the occurrence of VTE recurrence, 7,15-63 17 reported PTS,  [18] [19] [20] [21] [22] 26, 29, 32, 34, 39, 41, 45, 48, 58, 62, 64, 65  and 39 reported bleeding. 7, 15, 18, 23, [26] [27] [28] [30] [31] [32] 35, 36, [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [51] [52] [53] [54] [55] [56] [57] [58] [59] [61] [62] [63] [66] [67] [68] [69]  Only 10 studies evaluated VTE recurrence, bleeding, and PTS.
Study populations A total of 1450 participants were recruited into the on-going GUSTO mother-offspring cohort study (ClinicalTrials. gov identifier: NCT01174875); the study design has been detailed elsewhere  (Soh et al. , 2014). Briefly, pregnant women aged 18 years and above were recruited at <14 weeks' gestation from two main public maternity hospitals in Singapore between 2009 and 2010. The Chinese, Malay or Indian participants were Singapore citizens or permanent residents. Women receiving chemotherapy, psychotropic drugs or those with type I diabetes mellitus were excluded. This study was approved by the National Health Care Group Domain Specific Review Board (reference D/ 09/021) and the SingHealth Centralized Institutional Review Board (reference 2009/280/D). All research was performed in accordance with the relevant guidelines and written informed consent was obtained from all participants upon recruitment.
Neonatal abdominal adiposity Quantification of neonatal abdominal adiposity using magnetic resonance imaging (MRI) within two weeks of delivery in GUSTO has been described in detail elsewhere  (Tint et al. , 2016; Chen et al. , 2016). Briefly, non-sedated, fed, and swaddled neonates who were 5-10 min into their sleep were placed supine in an immobilization bag within an adult head coil and had their abdomen scanned. Subsequently, T1weighted water-suppressed axial fast spin echo sequences were acquired (GE Signa HDxt 1. 5 TMR scanner, Wisconsin, USA). The watersuppressed images were processed using an in-house semi-automated quantitative analysis software (MATLAB 7. 13; The MathWorks Inc. , Massachusetts, USA) based on morphological image analysis operations. From these operations, the volumes of total subcutaneous adipose tissues (SAT) (i.
Acknowledgements The authors would like to thank the  GUSTO study group , which includes  Allan Sheppard ,  Amutha Chinnadurai ,  Anne Eng Neo Goh ,  Anne Rifkin-Graboi ,  Anqi Qiu ,  Arijit Biswas ,  Bee Wah Lee ,  Birit F. P. Broekman ,  Boon Long Quah ,  Borys Shuter ,  Chai Kiat Chng ,  Cheryl Ngo ,  Choon Looi Bong ,  Christiani Jeyakumar Henry ,  Claudia Chi ,  Cornelia Yin Ing Chee ,  Yam Thiam Daniel Goh ,  Doris Fok ,  E Shyong Tai ,  Elaine Tham ,  Elaine Quah Phaik Ling ,  Evelyn Chung Ning Law ,  Evelyn Xiu Ling Loo ,  Fabian Yap ,  Falk Mueller-Riemenschneider ,  George Seow Heong Yeo ,  Helen Chen ,  Heng Hao Tan ,  Hugo P S van Bever ,  Iliana Magiati ,  Inez Bik Yun Wong ,  Ivy Yee-Man Lau ,  Izzuddin Bin Mohd Aris ,  Jeevesh Kapur ,  Jenny L. Richmond ,  Jerry Kok Yen Chan ,  Joanna D.
This research is supported by the  Singapore National Research Foundation  under its Translational and Clinical Research ( TCR) Flagship Programme  and administered by the  Singapore Ministry of Health's National Medical Research Council (NMRC) ,  Singapore -NMRC/TCR/ 004-NUS/2008 ;  NMRC/TCR/012-NUHS/2014. Additional funding is provided by the  Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR) , Singapore. K. M. G. is supported by the  UK Medical Research Council  ( MC_UU_12011/4 ) and the  National Institute for Health Research  ( NIHR Senior Investigator  ( NF-SI-0515-10042 ) and  NIHR Southampton Biomedical Research Centre  ( NIHR203319 )). L. W. C. is supported by a grant ( MOST110-2314-B-002-290-MY2 ;  P110A290 ) from the  Ministry of Science and Technology  (now the  National Science and Technology Council)  and receives further financial support from the  National Taiwan University Higher Education Sprout Project  ( 111L7304 ,  111L7306 ,  110L7418 ,  110L881002 ) within the framework of the  Higher Education Sprout Project  by the  Ministry of Education in Taiwan.
Acknowledgments We thank the  Histomics platform (Institut du Cerveau, Paris, France)  for tissue embedding and slide preparation that were performed for this study. 1  Sorbonne Université UMRS1135 ,  Faculté de Médecine Sorbonne Université, 75013 Paris, France. 2  Inserm   U1135 ,  75013   Paris ,  France. 3  Laboratory "Immune Microenvironment and Immunotherapy", Centre of Immunology and Microbial Infections, CIMI Paris , 75013  Paris ,  France. 4  Center for Interdisciplinary Research in Biology (CIRB) ,  Collège France ,  CNRS   UMR7241 ,  Inserm   U1050 ,  75231   cedex Paris ,  France. 5  Université Paris Sciences & Lettres ,  75231   cedex Paris ,  France.