dataesr/scientific-paragraphs-categorization huggingface dataset:
In this test, mice freely explored two chambers, including one where aICBLA projection neurons were activated or inhibited, depending on the opsin expressed. Photoactivation of aIC-BLA projection neurons only tended to induce a preference for the light-paired side, compared to control mice (p=0. 07, Fig. 6a, b ), while photoinhibition of this same population, in another group of mice, induced a preference for the light-paired side compared to control mice (Fig. 6c, d ). Together, these data show that inhibition of aICBLA projection neurons can induce place preference, which suggests these neurons are involved in negative valence. To identify how aIC-BLA neurons encode emotional valence, we performed ber photometry recordings of this population during valence-related behaviors. Interestingly, during sucrose consumption, we observed a decrease of the calcium signal after mice licked the sucrose solution (Fig.
Together, these results suggest a functional role of pIC neurons in negative valence processing, while the contribution of aIC glutamatergic neurons in positive valence remains unclear. Seminal and modern studies highlighted the amygdala as a downstream target of the insula  24, 26, 27, 38, 39. Among the 12 regions of interest we assessed with anterograde mapping, we found that amygdala nuclei (BLA, CeL and CeM) receive the strongest projection from both anterior and posterior insular cortices. However, our data challenge the existence of two segregated insula-amygdala pathways (aIC-BLA and pIC-CeA)  27  , as we also found substantial aIC-CeA and pIC-BLA projections. We con rmed the existence of functional monosynaptic excitatory inputs from the IC onto BLA and CeM neurons, along with recruitment of polysynaptic inhibition.
Acknowledgements The authors acknowledge the entire  Beyeler Lab ,  Nadine Gogolla  and  Christian Lüscher  for insightful discussions and advice. We thank the  Bordeaux Imaging Center (BIC)  for the use of their confocal microscope. We thank  Sara Laumond ,  Julie Tessaire  and the technical staff of the animal housing facility of the  Neurocentre Magendie (INSERM 1215)  for their invaluable support.
Light-induced phase shift P8 retinal explants from Per2 Luc and Opn4 -/-::Per2 Luc mice were exposed to a 465 nm monochromatic light pulse (30 min, 10 14 photons/cm 2 /s, CT16) using bright LED light sources (Superbrightleds) with or without MMA supplementation. To avoid putative bias linked to retina development in culture, light stimulation was applied on the first PER2::Luc oscillation at CT16. Briefly, CT16 was determined based on the time of occurrence of the trough of the first PER2::Luc oscillation using the beginning of culture (CT12) as a reference as previously described  [27, 43]. Retinas from the same animal were either light-stimulated or used as a dark control. Phase shifts following light stimulation or MMA application were calculated as the difference between the trough time of the cycle after treatment compared to the trough time of the control retina from the same animal, as determined by Lumicycle Analysis software.
Data analysis Rhythm onset was defined when the first complete bioluminescence oscillation was observed (first trough and peak clearly distinguishables). The period and the amplitude of PER2::Luc oscillations were determined using SigmaPlot 12. 5 software by fitting a linearly detrended sinusoidal curve oscillating around a polynomial baseline to the first three complete oscillations from each sample as previously described  [23, 27, 43]. The equation used was: where a is the amplitude (difference between the peak and the mesor values in the detrented time series data), τ is the period (duration of a complete circadian cycle, time peak to peak), and φ the phase. The mesor represents the circadian rhythm-adjusted mean based on the parameters of the sinusoidal function fitted to the raw data.
Statistics Statistical analyses (Statistica Software) were performed using non parametric Kruskal Wallis one-way ANOVA followed when significant by the Mann-Whitney posthoc test in order to compare the period, the phase and the amplitude of PER2::Luc signals, pharmacological treatments, and the relative expression of DRs and Th mRNA during development in Per2 Luc mice. Non parametric Kruskal Wallis two-ways ANOVA, followed by the Mann-Whitney post-hoc test, were used to compare the clock parameters between Per2 Luc and Opn4 -/-::Per2 Luc mice during development. Data are represented as mean ± SEM, with consideration of p ≤ 0. 05 as the threshold of statistical significance.
Participants Fifty-nine adult participants with blindness participated in the study (28 totally blind, 31 with a sense of light) (initially, 64 blind participants were tested, but data from five individuals were rejected due to their uncertain visual status regarding visual memories -these participants lost their sight in early childhood). Two groups of people with blindness were tested: (a) congenitally blind (CB) (n = 30; 18 males, 12 females; 28 right-handed; aged 21-62 years, M = 34. 80, SD = 12. 34), i. e. , those who have not seen since the beginning of their lives and (b) adventitiously blind (AB) (n = 29; 17 males, 12 females; 27 right-handed; aged 18-61 years, M = 40. 83 years, SD = 12. 36), i. e. , those who lost their sight during their lives (when aged between 4 and 59 years; M = 20.
Data coding The indicator of the drawn size of the object (in millimetres) was measured by the length of the diagonal of the rectangle bounding the drawing (like in previous studies in this field:  Konkle & Oliva, 2011; Szubielska et al. , 2022; Szubielska & Wojtasiński, 2021; Szubielska, Wojtasiński et al. , 2020). In line with the previous studies, extraneous objects were ignored (e. g. , a fence next to the house; to identify these extraneous objects, we asked the participants about the presence of additional objects after they had made the drawings -"Have you drawn anything else in addition?"). Only the relevant object of interest was bounded around by a rectangle. As in the study by  Szubielska et al. (2022) , all drawings were scanned at a fixed resolution, the rectangle boundaries were determined using the Photoshop program, and custom software converted the dimension of the rectangle into millimetres and then -into diagonals.
Data acquisition and analysis On the day of the test, animals were fitted with the jacket, allowed to habituate for 1 h and then observed before dosing to establish baseline measurements, using a standardized battery with a list of 58 observations for the FOB testing (Table  1 ). The list fulfills the ICH S7A guideline that states: "Motor activity, behavioral changes, coordination, sensory/ motor reflex responses and body temperature should be evaluated. " Subsequently, animals were dosed in accordance with the order defined by the randomization plan and then they were subjected to repeated neurobehavioral observations at 1, 2, 4, and 6 h after dosing. At each time-point, the animal was observed individually. A brief observation was performed in the home cage for about 10 s just before removing and transferring into an arena (70 cm × 70 cm × 20 cm, LxWxH) where observations were continued.
The individual observation data were presented as a score attributed to each behavioral and clinical sign. This score took into account the intensity and significance of the sign observed. For observations with absence or presence, the group's data were presented as the number of animals presenting with the sign. For other observations based on scoring, the group's data were presented as the median value for each sign at each time of observation. Body temperature was expressed in • C. The respiratory inductive plethysmography (RIP), ECG and actimetry signals were collected with DECRO 2. 3. 0 software (ETISENSE, Lyon France). ECG signals, recorded via two external ECG electrodes placed under the jacket, were digitized at Hz / 24 bits, RIP signals at 200 Hz / 32 bits, and activity signals at 12.
5 Hz / 16 bits for X, Y and Z. All signals were transmitted to a receiver using Bluetooth Low Energy communication. Data were analyzed using DECRO software based on a built-in algorithm. More details have been described elsewhere  (Fares et al. , 2022). The following parameters were provided: heart rate (HR, in beats per min (bpm)), Activity Level (AL in mG (G being acceleration and m standing for "milli")), respiratory rate (RespR; in breaths/min), inspiratory time (IT; in s), expiratory time (ET; in s), tidal volume (TV, in mL), and Minute Ventilation (MV mL/min ). The TV calibration and MV calculation methods have been described elsewhere  (Fares et al. , 2022).
In case of "treatment" effect or "treatment X time" interaction, multiple comparisons of mean values were continued using the minimum detectable difference (MDD, α = 5%, β = 80%) calculated using the residual variance of the analysis of variance for repeated measurements. The calculated MDD was as follows: RespR: 39 breath per min; ET: 0. 046 s; IT: 0. 051 s; TV: 0. 39 mL; MV: 63 mL/min; HR: 45 bpm; AL: 23 mg. Statistical tests were processed using RS/1 software (release 6. 3, APPLIED MATERIALS. ). All calculations were made by using fully automated computer procedures, validated according to GLP.
Acknowledgments The authors would like to express their gratitude to  Marine Minard ,  Alexia Pouillot , and  Emmanuel Bracq  for their significant help in conducting this study and to the biotechnicians team of the  Animal Unit of the Department of Safety Pharmacology at ERBC , where the animal work was conducted. Finally, the authors would like to thank  Timothé Flenet  and  Charles Eynard from Etisense  for their unconditional and valuable help with the DECRO system.
Acknowledgments This work was supported by the  Centre National de la Recherche Scientifique CNRS UMR   8246 ,  INSERM   U1130 , the  Foundation for Medical Research  (FRM, Equipe FRM  DEQ2013326488  to PF), the  French National Cancer Institute  (Grant  TABAC-16-022 ,  TABAC-19-020  and  SPA-21-002  to PF), and French state funds managed by the  ANR  ( ANR-20   NICADO  to PF and JB,  ANR-19-CE16-0028 Bavar  to PF and NR). LMR was supported by a  NIDA-Inserm   Postdoctoral Drug Abuse Research Fellowship. CN was supported by a fourthyear PhD fellowship from the  Biopsy Labex. We are grateful for support from the animal facilities (IBPS) and  Otilia de Oliveira ,  Noemie Karakaplan-Dherbe  and  Emilie Tubeuf  at  ESPCI animal  facilities.
Background: Current guidelines recommend intramuscular botulinum toxin type A (BoNT-A) injection as first-line treatment for spasticity, a frequent and impairing feature of various central nervous system (CNS) lesions such as stroke. Patients with spasticity commonly require BoNT-A injections once every 3 to 4 months. We conducted a nationwide, population-based, retrospective cohort study, using the French National Hospital Discharge Database (PMSI), to describe BoNT-A use for spasticity in clinical practice in France between 2014 and 2020. The PMSI database covers the whole French population, corresponding to over 66 million persons.
Methods: We first searched the PMSI database for healthcare facility discharge of patients who received BoNT-A injections between 2014 and 2020, corresponding to the first set. For each BoNT-A-treated patient, we identified the medical condition for which BoNT-A may have been indicated. Another search of the PMSI database focused on patients admitted for acute stroke between 2014 and 2016 and their spasticity-related care pathway (second set). Overall, two subpopulations were analysed: 138,481 patients who received BoNT-A injections between 2014 and 2020, and 318,025 patients who survived a stroke event between 2014 and 2016 and were followed up until 2020. Results: Among the 138,481 BoNT-A-treated patients, 53. 5% received only one or two BoNT-A injections. Most of these patients (N = 85,900; 62.
Study design and data source We carried out a nationwide, population-based, retrospective cohort study between 2014 and 2020, using data extracted from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d'Information, PMSI). This study was conducted in compliance with all French laws and regulations and the Declaration of Helsinki, and was notified to the French Data Protection Agency (Commission Nationale de l'Informatique et des Libertés, CNIL). According to the French law and the CNIL, the study did not require formal ethical approval and persons' informed consents, as it did not involve direct participation of human individuals and all extracted data were anonymised. The PMSI database is a comprehensive claims database that includes information on diagnoses and procedures.
Diagnoses are coded according to the International Classification of Diseases version 10 (ICD-10), either as main diagnosis, related diagnosis, or significantly associated diagnoses. Medical procedures are coded according to the French Joint Classification of Medical Procedures (Classification Commune des Actes Médicaux, CCAM). PMSI is an exhaustive database that covers the whole French population, corresponding to over 66 million persons. It contains standardized discharge summary reports from all inpatients and outpatients discharged from public hospitals as well as from inpatients discharged from private hospitals in France. Each PMSI record provides the following information: administrative information including length of hospital stay and geographic location of the hospital; demographic data (sex, age); and therapeutic procedures coded during each stay.
In addition, for inpatients, there is information on medical diagnoses; comorbidities managed during the stay; and costly drugs and implantable medical devices that were administered. The PMSI database also includes an anonymous unique patient identifier, which allows to follow all hospital admissions and stays for each individual patient, even when the patient has been admitted to several healthcare facilities or hospital departments. The PMSI database does not contain patient charts and does not provide clinical information such as the dosage or effectiveness of administered drugs, the muscles injected, or the goal of the treatment. It also prevents any causal association from being drawn.
Study population 2. 2. 1. Patients who received at least one BoNT-A injection (first analysis set) We first searched the PMSI database for healthcare facility discharge of patients (both adult and paediatric) who received at least one intramuscular BoNT-A injection between 2014 and 2020, using the following CCAM codes: PCLB002 and PCLB003. Both codes refer to a single session of BoNT-A injection(s) within striated muscles. For each patient treated with at least one intramuscular BoNT-A injection, we extracted data on all inpatient diagnoses, and inpatient and outpatient stays and performed medical procedures. The conditions for which BoNT-A may have been indicated were then identified using ICD-10 codes from a primary, related, or significantly associated diagnosis. Figure  1  illustrates in a flow chart the process of selection of patients by reason for BoNT-A injection.
Our selection approach consisted of a step-by-step verification from the most to the least certain diagnosis, in order to minimise data loss and data redundancy/ duplication. For instance, from the overall population, i. e. , patients who received at least one coded BoNT-A injection, we classified those having simultaneously a coded CNS lesion. Then, we applied another selection criterion to the remaining population to select those who had a CNS lesion coded at any hospital stay between 2014 and 2020 different from the one during which the BoNT-A injection was administered. When BoNT-A was administered in relation to more than one condition in a single patient, only the most frequently coded condition was retained. Hence, each patient had only one condition justifying BoNT-A administration recorded in our analysis.
Patients who survived a stroke event between 2014 and 2016 (second analysis set) The second search of the PMSI database was focused on patients presenting with stroke between 2014 and 2016 to ensure a longitudinal post-stroke care pathway. We identified all patients (both adult and paediatric) who were admitted at least once for acute stroke, and excluded those who died within 6 months of their admission for this event. Patients with stroke who survived after 6 months were followed up until 2020.
Statistical analysis Descriptive analyses were performed using number and percentage for categorical variables, and mean, standard deviation, median, and first and third quartiles (Q1-Q3) for continuous variables. All data underlying this publication were provided by the Agence Technique de l'Information sur l'Hospitalisation (ATIH). Data analyses were performed by the second author, a biostatistical expert, using the SQL server software. Of note, the expert who carried out the analyses has followed and validated the mandatory training for access to PMSI data. The expert has also made a commitment to the CNIL regarding the confidentiality and independence of the research laboratories and design offices provided for by the decree of July 17, 2017.
Our analysis of the comprehensive French PMSI database aimed to reflect a broad range of BoNT-A treatment practices between 2014 and 2020. To the best of our knowledge, this is the first published study evaluating BoNT-A use on such a large scale, as the PMSI database is one of the world's largest continuous homogeneous claims databases, covering the whole French population, i. e. , over 66 million persons  (19). Several informative findings were noted in the present analysis.
Moreover, the quality of PMSI data depends on the accuracy and completeness of the information system. PMSI data usually relate to events such as hospital admissions or attendances and not individual patients. Another limitation of the PMSI database is that it does not contain data from outpatients discharged from private hospitals. Furthermore, we did not have access to data regarding BoNT-A dosage or effectiveness. Nevertheless, our analysis is strengthened by a large, representative, and contemporary patient population, with exhaustive data collection on BoNT-A use. To the best of our knowledge, this study is one of the few studies to have used a national exhaustive database to explore real-life BoNT-A treatment practices. Such approach minimises selection and reporting biases inherent to expert center cohorts and questionnaire-based studies, while contributing to improve clinical practice.
Conclusion This population-based analysis of the exhaustive PMSI database highlights a broad range of BoNT-A treatment practices in France between 2014 and 2020. Although BoNT-A is a recommended firstline pharmacological treatment of spasticity that should be injected once every 3-4 months, BoNT-A treatment initiation and re-administration were low in the present study, particularly in patients with post-stroke spasticity. Further research into the limited use of BoNT-A among patients with CNS lesions in France is warranted. Future investigations should also target specific actions to improve spasticity-related care pathway.
The following items were scored: presence (present or absent) and severity (mild, moderate, and severe) of a movement disorder, dominant movement disorder, other associated movement disorders, five most informative parts of the neurological examination with respect to the presence of a movement disorder (from 1 [most important] to 5), and suggested treatment of the movement disorder. Severity of a movement disorder was based on the impression of the rater. The design of the data collection is shown in Figure  S1.
Statistical Analysis Video fragments were ranked based on their contribution to movement disorder identification and pattern recognition as reported by the specialists, irrespective of the movement disorder phenotype. Consensus about the presence of a movement disorder and the phenotype of the (dominant) movement disorder was defined as an agreement of at least two of three raters. This information was used for further analysis on treatment and severity. In addition, Fleiss-kappa inter-rater agreement and cluster analyses were performed using SPSS (version 26) to define the inter-rater agreement on the presence of a movement disorder and the specific (dominant) movement disorder phenotype. Kappa ranges from 0 to 0. 20 were considered as slight agreement, 0. 21 to 0. 40 as fair, 0. 41 to 0.
Acknowledgments: We thank everyone who contributed to this study, especially all the patients and their relatives, and  Catharina Gerigk  for making the illustrations of the screening tool. Several authors of this publication are members of the  European Reference Network for Rare Neurological Diseases  (project  ID  no. : 739510). Common and  Uncommon Presentations  ( Cambridge University Press , 2017). He has received honoraria/personal compensation for participating as consultant/scientific board member from  Ipsen and Allergan  and honoraria for speaking at meetings from  Allergan ,  Ipsen , and the  International Parkinson's Disease and Movement Disorders Society. Pascale Cavillon  and  Lorraine Cuffe  are employed by  Ipsen. M. F. C. : travel support: BostonScientific. Advisory board: Medtronic (fees to institution).
Acknowledgements: We wish to thank  A Casali  and  T Preat  for fly stocks. This project has received financial support from  CNRS  ( MITI-80prime interdisciplinary programs  to FM, FMP and JM),  Fondation ARC contre le Cancer ( PJA 20181208078  and  ARCPJA2022060005236  to JM),  French league against Cancer  ( M27218  to JM) and  French Government  (fellowships  MENRT 2020-110  to PD). We acknowledge the sequencing and bioinformatics expertise of.
Data extraction Two reviewers (LC and CA/AL) independently extracted data; any disagreements were resolved by discussion with a third reviewer (AD). Two data collection forms were developed and used: one for meta-analyses and one for individual trials. For each meta-analysis, the following data were extracted: • General characteristics: date of publication, journal, funding sources • Number of events and analyzed patients in each group for the incidence of delirium • Mean, standard deviation, and number of analyzed patients in each group for the duration of delirium and number of delirium-and coma-free days. When the mean and standard deviation were not available, we extracted the median and interquartile range and converted them to mean and standard deviation  [16]. Data for RCTs were extracted directly from the RCT report.
If the full text was not available, we contacted the authors, and in case of no answer, we collected the data from the meta-analysis. The risk of bias was extracted from meta-analyses. Because meta-analyses used different tools, we relied on the Cochrane RoB1 tool because it is a reference tool and was the most frequently used. We re-evaluated the risk of bias from the RCT report by using this tool when another tool was used in the meta-analysis.
Definition of delirium in included RCTs Of the 149 RCTs, 109 (73. 1%) used a validated definition for delirium and 40 (26. 8%) did not. The validated definitions were the DSM criteria in eight RCTs (5. 4%), the CAM-ICU in 83 (55. 7%), the ICDSC in 13 (8. 7%), the NEECHAM scale in three (2. 0%) and the DRS-R98 for two (1. 3%). Regarding the other trials, three (2. 0%) used a non-validated scale (RASS for two, and one did not report the scale used), four (2. 7%) a set of symptoms, two (1. 3%) left the definition to the physician appreciation and 31 (20. 8%) did not report how the delirium was evaluated (Fig. 1 ). When extracting the data in RCTs, we found some discrepancies with what was reported in the meta-analyses. Twelve RCTs included in six meta-analyses did not report delirium as an outcome and the authors of the meta-analyses interpreted the delirium as confusion and/or agitation, and/or disorientation, and for six RCTs included in four meta-analyses, which data they considered was not clear.