dataesr/scientific-paragraphs-categorization huggingface dataset:
With this cohort-based study, we will generate a large longitudinal observational multi-modality clinical dataset that allows for a thorough analysis of which phenotypic components enable the best participant stratification for optimal treatment success. We will leverage the Danish healthcare system, which provides standardised treatment packages for all patients. Currently, group cognitive-behavioural therapy (CBT) constitutes the backbone of the treatment package with possibilities for initiation or changes in pharmacotherapy. The treatment package is nationally uniform and designed by Mental Health Services in the Capital Region. The treatment package was introduced in 2013 and revised in 2017 based on clinical and patient experience. However, while the treatment components in the package are research and evidence-based, the treatment effect in real life has not been examined.
Clinical depression symptom severity is assessed with the Quick Inventory of Depressive Symptomatology (QIDS) at baseline (T 0 ), and 6 (T 1 ), 12 (T 2 ) and 18 (T 3 ) months after treatment initiation (Fig. 1 ). The treatment package typically lasts six months. To examine disease trajectories, we will combine collected data with information from Danish national health and social registers, allowing us to further characterise and follow the patients before, during, and after treatment. Together, this might enable us to identify clinically relevant biomarkers and suggest treatment response algorithms, aiding treatment choices and improving patient care (Figure  1 ). Furthermore, synaptic loss and deficits in functional connectivity are hypothesized to contribute to depressive symptoms, i. e.
Inclusion and exclusion criteria for healthy controls Data from HCs for comparisons to patients with MDD are available on-site from recent and concurrent projects, stored in the Cimbi database described in  [32]  including the BrainDrugs-Epilepsy study  [33]. Apart from psychiatry-related issues (e. g. , no current or history of mental illness or unstable somatic condition), the HC meet the same inclusion and exclusion criteria as required for patients.
Additional exclusion criteria for subcohort I: • Use of psychotropic drugs • Exposure to radioactivity > 10 mSv within the last year • Pregnancy or breastfeeding Medical records and registry data Detailed medical information about previous illness, medication usage, hereditary dispositions, drug, tobacco, and alcohol intake will be acquired for all participants through interviews, self-report questionnaires, electronic medical records (EMR), and registry data. Data extracted from the EMR will include treatment codes from the MDD treatment package, dates for treatment package start and completion, psychiatric comorbidities; and standard clinical blood work (e. g. , HBA1c, TSH, CRP, and cholesterol). In addition, hormonal contraceptive and psychotropic medication prescription and usage (from 1995 onward) will be extracted from the Danish National Prescription Registry  [55, 56].
This information includes prescribed medication and dosage and when the patient redeems a prescription. We will retrieve information on lifetime comorbidity from The Danish National Patient Registry (DNPR)  [57]. From the Medical Birth Registry, we will obtain data on maternal and maternal perinatal health  [58]. We will also collect information on alcohol and drug abuse treatment from the National Registry of Alcohol Treatment and Registry of Drug Abusers Undergoing Treatment. From the social registers in Statistics Denmark, we add data on marital status, occupational history, ethnicity, and educational level  [59]. Cognitive testing All patients are assessed with a ~ 1-h neuropsychological test battery, including 'cold' (emotion-independent) cognitive tasks indexing reaction time; psychomotor speed; verbal learning and memory; working memory; and executive functions, as well as 'hot' (emotion-dependent) cognitive tasks from the Danish version of the EMOTICOM test-battery indexing emotion recognition; emotion detection; and moral emotions in social situations  [60].
Treatment and life events As the study is observational, we will not interfere with or delay treatment. EMR and registry data during treatment and until the 18 months from inclusion will be extracted to inform the individual treatment path, i. e. , what treatment the individual patient received, e. g. , amount of individual psychotherapy sessions and when, timing, type and dose of medication and switches, and participation in group therapy. Using registry data, we can also follow life events, e. g. , change of residence, divorce, and employment.
e. , new symptoms, dependency, stigma, hopelessness, and the experienced quality of treatment  [74, 75]. Both baseline characteristics and treatment experiences, e. g. , negative effects on the NEQ, will be used to investigate reasons for CBT and treatment package drop-out. Registry follow-up After the last 18-month follow-up, the study dataset will be sent to Statistics Denmark with a list of all invited participants to allow a non-participant analysis and long-term follow-up. The study data will be linked with data from the Danish Civil Registration System  [76]  e. g. , the DNPR  [57] , the Danish National Prescription Registry  [55, 56] , and other registries indexing, e. g. , hospital admittance, diagnosis-and treatment codes, prescription medications, employment status, living situation (e.
In the present study, we will first use machine learning to train classifiers based on broad non-imaging data collected from all patients in the cohort. Neuroimaging data from EEG, MRI, and PET in subcohorts I and II will subsequently be included, enabling us to make meaningful statements about the marginal improvement in model performance with or without specific neuroimaging measures. This is critical for optimising patient care with costs associated with data acquisition. Following the recommendations for best practice  [80, 81] , we will employ randomized k-fold nested cross-validation, i. e. , splitting the collected data into training and testing datasets that reported model performance measures are not upwardly biased due to data leakage. We will use latent class analysis to identify different MDD subgroups that share characteristics measured at baseline (hypotheses 1.
Hypothesis-driven analyses To answer hypothesis 3. 1, we will use [ 11 C]-UCB-J PET data from healthy controls (N = 40) currently available from the Cimbi database with [ 11 C]-UCB-J PET data collected from patients in the PET subcohort II (expected n = 60). These sample sizes will provide us with a statistical power of 0. 99 to detect group differences with a Cohen's d effect size of 0. 95 as reported in previous study  [85]. With the samples size and a statistical power of 0. 80 we can defect a group difference with a Cohen's d 0. 58 or higher using a significance threshold of p ≤ 0. 05 in a two-sample t-test. The previous study by Holmes et al. (2019) reported group differences in [ 11 C]-UCB-J binding between healthy controls and a small cohort with mixed psychiatric diagnoses, including MDD.
Ethics and data availability The study is conducted according to the principles of the seventh revision of the Declaration of Helsinki (2013) and was reviewed and approved by the Committees on Health Research Ethics in the Capital Region of Denmark (reference number: H-20083013). Before undertaking any study-related procedures, each participant receives verbal and written explanations of study aims, methods, potential hazards, and benefits from investigators and provides written informed consent. All participating patients are asked to consent to disclose relevant information from their EMR to extract health-related information relevant to the study. Data management and monitoring during the study adhere to the rules protecting personal data. Paper-based material (e. g. , cognitive test results) will be stored in a secured archive.
Identifiable electronic data files will be stored in password-secured files behind a firewall per regulations. Biological material will be coded with a unique identification number. Access to de-identification keys is restricted to authorised personnel only and stored in a temporary biobank located in secured areas in the laboratory facility. The biomaterial will later be analysed in batches to reduce noise, and potential extra material after the end of the study will be transferred to the CIMBI biobank  [32]. All biological material will ultimately be anonymised after 15 years after the end of the study. The study results will be presented following relevant reporting guidelines, i. e. , STROBE and TRIPOD  [86, 87]. After publication of results from our primary hypothesis, the data can upon request be made available to other scientists or consortia, through the Cimbi database (or similar platform).
Discussion MDD is a brain disorder with etiological heterogeneity in the interplay between biological, social, psychological, and behavioural factors and pathophysiology with several neurobiological mechanisms. In the BrainDrugs-Depression study, we employ a broad, multi-modal biopsychosocial characterisation of each patient. This, combined with a large sample size, follow-up over 18 months, and further complete follow-up in the social-and health registries, offers a unique opportunity to uncover potential single or combined predictors of treatment outcome, identify MDD subtypes, advance the understanding of MDD aetiology, and map neurobiological predictors of treatment response; ultimately paving the way for a precision medicine approach for optimised MDD treatment. Further, the ability to track and follow patients in the Danish health care system and registers provides a unique opportunity to obtain large amounts of data collected independent of the patient's mood and enables us to perform sensitivity analyses and account for selective participation and attrition.
The Borexino data selection The aim of data selection is to provide maximum exposure for the desired study with minimum background contribution. In the current analysis we search for neutrino-electron scattering, a reaction that has no specific interaction signature. Thus, the background has to be suppressed generically, as a reduction of the detector count rate per unit of exposure. Background composition of the Borexino experiment was carefully studied in the course of many years of research. In the current study we account for the following background component groups: -Short-lived cosmogenic backgrounds (τ ≤ 1 s) such as -External backgrounds present in the material of the inner nylon vessel such as 210 Pb and Uranium/Thorium decay chains. -Internal natural backgrounds contained in the bulk of the detector fluid such as 14 C, 85 Kr, 210 Bi and 210 Pb.
GW events, temporal window and neutrino spectra We have used the GWTC-3 database compiled by the LIGO and VIRGO collaborations for O1, O2 and O3 observing runs  [4]. This database contains information about possible sources of GW events, merger time of the event in GPS seconds, mass M1 and M2, chirp mass δ M, final mass M f in solar mass units, red-shift z, and distance information R. During the period of interest from September 2015 to March 2020, 93 GW events have been observed, 87 of which are black hole mergers(BHBH), 2 events of neutron star merge (NSNS) and 4 events of neutron star-black hole merge (NSBH). The nearest GW event is the most famous merger of two neutron stars GW170817 occurred at R = 40 +7 -15 Mpc. The biggest redshift z = 1. 18 +0. 73  -0. 53 (R = 8280 +6720 -4290 Mpc) was observed for GW190403-051519.
This allows to compare the obtained limits on the neutrino fluence for a different set of GW events. The neutrino fluence from i-th GW event assuming isotropic emission is Φ i = M rad i c 2 4π R 2 i E i , ( 7 ) where is a fraction of neutrino radiation and E i is the average neutrino energy. The obtained limits on the neutrino fluences can be converted to the limit on the value of. According to the GWTC-3 database for 70 BHBH GW events when the Borexino detector was in data taking mode, the distances to events R i lie in the range (0. 3-8. 3 Gpc) and an average distance is R i = 2. 1 Gpc. The corresponding radiative masses M rad i are inside (0. 3-9. 4) M interval with average mass M rad i = 2. 6M. Therefore, as a reference event, we define the "standard" event with M rad equals one solar mass M at a distance of one Gpc.
These values can be compared with the energy of solar mass M c 2 = 1. 8 × 10 54 erg. Accordingly, the restrictions on fraction of neutrino radiation become unnatural and exceed unity ( ν e ≤ 1. 0 × 10 9 and νe ≤ 2. 0 × 10 7 ). For comparison, we note that if GW170817 event occurred at the same distance as the supernova collapse SN1987A at 51 kpc from Earth, the sensitivity to the energy released in form of 10 MeV neutrinos would be M rad c 2 ≤ 8. 9 × 10 52 erg (0. 05 M ) and νe ≤ 1. 2. In the case of 26 most intensive BHBH GW events, the resulting fluence is: Φ tot = 26 i=1 M rad i c 2 4π R 2 i E i. ( 8 ) where the upper limit on the total fluence Φ tot = 1. 45 × 10 12 cm -2 (Fig. 7 ) and values M rad i and R i can be taken from the GWTC-3 database. Since for 26 GW events the average mass M rad = 11M as well as the average squared distance R 2 = 0.
Conclusion We have searched for signals of neutrino-electron scattering with visible energies above 250 keV within a time window of ± 1000 s centered at the detection moment of a particular GW event. Two types of incoming neutrino spectra were considered: a mono-energetic line and supernova neutrino spectrum given by modified Fermi-Dirac distribution for different effective neutrino temperatures. We searched for coincident neutrino-electron elastic scattering of ν e,μ,τ and νe,μ,τ and IBD of νe in the Borexino detector with the 74 GW events associated with the O1, O2 and O3 observing runs of the LIGO/VIRGO detectors. We looked for an excess in the number of Borexino events produced by neutrino-electron elastic scattering and the inverse beta-decay on protons correlated to 74 GW events from the GWTC-3 database.
Acknowledgements The Borexino program is possible by funding from  INFN (Italy) ,  NSF (USA) ,  DFG  and  HGF (Germany) ,  RSF  (Grant  21-12-00063 ) (Russia), and  NCN  (Grant No. UMO-2017/26/M/ST2/00915 ) (Poland). We acknowledge the generous hospitality and support of the  Laboratori Nazionale del Gran Sasso (Italy).
Study design This observational, descriptive study was carried out between November 2020 and January 2021. An online questionnaire was used to obtain information about the perceptions and feelings towards screening for lung cancer among the French general public. The study conformed to the General Rules on Data Protection (Règlement Général sur la Protection des Données; RGPD) and the Data Protection Act (Loi Informatique et Libertés), and the data collected were strictly anonymized. The study was based on the principles and rules of the Rapport Belmont, the Code of Conduct of Researchers of Caverni and the Declaration of Helsinki.
Tools To assess perceptions and feelings regarding lung cancer, lung cancer screening, and scans, a questionnaire comprising both open-ended and closed-ended questions was developed specifically for this study. It was distributed via an online platform. On average, participants took approximately 15 min to complete the questionnaire. Sociodemographic data including age, gender, marital status, presence of children at home, and socioeconomic category, were collected. For active smokers and former smokers, additional information was collected: age at which they started smoking, number of cigarettes smoked per day, and age at which smoking was stopped. Furthermore, the number of years of smoking was only collected for former smokers. The questionnaire is provided in the Additional file 1: Appendices.
Acknowledgements We thank the  AGATA collaboration  for its scientific support to this manuscript. This work has been supported in part by the  United Kingdom Science and Technology Facilities Council  under grants  ST/P004598/1  and  ST/V001027/1. The authors are grateful to the following laboratories where the research described in this manuscript was performed:  Laboratori Nazionali di Legnaro ,  Hubert Curien Multi-disciplinary Institute Strasbourg, Argonne National Laboratory, GANIL, Jyvaskyla laboratory, Daresbury laboratory  and  Lawrence Berkeley National Laboratory.
Overall, we observed a high degree of correlation between luminescence values and number of liver stage schizonts (Fig. 5h ; R 2 = 0. 90; 0. 95; 0. 96 for day 4, 5 and 6, respectively). In line with the larger size of the schizonts, luminescence values were higher at day 5 and 6 post infection in comparison with day 4 parasites. The combined data indicate that the GFP-NanoLuc reporter line can be a novel and powerful tool to evaluate the potency and efficacy of anti-malarial compounds against liver stage parasites. HTS of anti-malarial compounds using the Osaka University chemical library. To discover novel anti-malarial compounds against multi-stage P. falciparum, we performed HTS using the GFP-NanoLuc reporter line (Fig. 6a ). First, 1920 compounds from the Osaka University chemical library were screened at 2 µM using the asexual blood stage GFP-NanoLuc reporter line, of which, 30 compounds showing >80% inhibition of asexual parasite growth were subjected to subsequent gametocytocidal assays (Fig.
Images were captured with a DC500 digital camera using ColourPro software with the following exposure times: GFP 0. 7 s; mCherry 1 s; Hoechst 0. 2 s; bright field 0. 1 s (1× gain). For analysing reporter expression in mosquito-stage parasites (oocysts and sporozoites), A. stephensi mosquitoes were infected with day 14-17 gametocyte cultures using the standard membrane feeding assay (SMFA)  53, 54. The transgenic reporter lines were dissected and subjected to imaging via fluorescence microscopy, as previously described  16. For the oocyst stage, midgut samples isolated on days 8 or 10 after feeding were placed on a microscope slide mounted with a coverslip. Fig. 6  Screening of 1,920 compounds from the Osaka University chemical library using the GFP-NanoLuc reporter line. a Schematics of Osaka University chemical library drug screening.
e Determination of IC 50 value of the hit compound OU0074008 against the asexual blood stage. The GFP-NanoLuc reporter line was cultured in different concentrations of OU0074008, DMSO (negative control well) or 1 µM DHA (positive control well) on 96-well plates. The IC 50 value of OU0074008 was determined via non-linear regression from technical quadruplicate using GraphPad Prism 9. 0 software. f Determination of IC 50 value of the hit compound OU0074008 against the gametocyte stage. The GFP-NanoLuc reporter line was cultured in different concentrations of OU0074008, DMSO (negative control well) or 1 µM epoxomicin (positive control well) on 96-well plates. The IC 50 value of OU0074008 was determined via non-linear regression from technical triplicate using GraphPad Prism 9. 0 software. g Cytotoxicity of OU0074008 against HepG2 cells.
The cells were exposed for 72 h with indicated concentration of OU0074008 or DMSO (control well) on a 96 well plate and cytotoxicity assay using CCK-8 was performed. The IC 50 value of OU0074008 was determined via non-linear regression from technical quadruplicate using GraphPad Prism 9. 0 software. GFP expression was analysed using a Leica fluorescence MDR microscope (100× magnification). Images were captured with a DC500 digital camera microscope using Leica LAS X software at the following exposure times: GFP 0. 7 s; Hoechst-33342 0. 136 s; bright field 0. 62 s (1× gain). Collection of salivary gland sporozoites for counting numbers and GFP expression was performed 24 days after feeding. The salivary gland sporozoites were isolated for GFP expression by centrifugation (800 × g, 5 min). The pellet was suspended in 40 μL PBS, and sporozoites were stained with Hoechst-33342 (10 μM) for 30 min at 37 °C.
Of this solution, 5-10 μL was placed on a microscopic slide mounted under a coverslip, and the GFP fluorescence of live sporozoites was analysed using a Leica fluorescence MDR microscope (×100 magnification). Images were captured with a DC500 digital camera microscope using Leica LAS X software at the following exposure times: GFP 0. 7 s; Hoechst-33342 0. 136 s; bright field 0. 62 s (1× gain). For GFP live imaging in primary human hepatocytes, images of liver-stage parasites were obtained with the Axiovision software (Carl Zeiss) using a Leica DMI4000B fluorescent microscope. Images were analysed with ImageJ software. Analysis of mosquito stage development. For analysis of the mosquito stage, A. stephensi mosquitoes were fed with the culture of day 14-17 P. falciparum gametocytes using the standard membrane feeding assay (SMFA), as previously described  49.
After one day, the cells were overlaid with Matrigel (Corning). For infection, Matrigel was removed from hepatocyte culture and sporozoites were added before centrifugation at 560 × g for 10 min at RT and incubation at 37 °C, 5% CO 2. Three hours later, infected cultures were covered with Matrigel prior to the addition of fresh medium supplemented with amphotericin B. The medium was renewed every day, until cell fixation with 4% (w/v) paraformaldehyde solution. For liver-stage parasites count and size determination, infected cultures were stained with a polyclonal anti-Plasmodium HSP70 murine serum revealed with Alexa-Fluor 488-conjugated goat anti-mouse IgG (Invitrogen). DAPI was used to visualize nuclei. Parasite images were obtained with Axiovision software (Carl Zeiss) using a Leica DMI4000B fluorescent microscope and used to determine parasite number and size.
Parasite size was determined manually as parasite length in µm using a Cell Insight High Content Screening platform equipped with the Studio HCS software (Thermo Fisher Scientific) in Celis Platform (ICM, La Pitié-Salpêtrière, Paris) as described previously  56. NanoLuciferase assay. For the asexual blood stage, white 384-well plates were used for all NanoLuc assays. For the standard curve, a twofold serial dilution of the GFP-NanoLuc line number was added to a plate at 25 µL/well at 2% haematocrit, and the plate was stored at -20 °C for 24 h for RBC lysis. The following day, plates were thawed at room temperature. Subsequently, NanoLuc assays were performed with the Nano-Glo® Luciferase Assay System (Promega) and Luciferase Cell Culture Lysis 5× Reagent (Promega) according to the manufacturer's instructions, with slight modifications.
To this end, cryopreserved human hepatocytes were seeded in 96-well plates and infected with the transgenic line similar as described earlier  57. Medium containing different atovaquone concentrations was refreshed during the different maturation periods on a daily basis. For imaging, cells were fixed and stained with anti-HSP70 after 4-, 5-and 6-days post infection as described, and imaged on the ImageXpress PICO (Molecular devices). Images were analysed using CellReporterXpress software. For the luciferase assay infected hepatocytes were washed once with fresh hepatocyte medium on days 4, 5, and 6 post infection to remove extracellular NanoLuc, followed by the replacement of the medium with a 1:1 mix of hepatocyte medium and Nano-Glo® Luciferase Assay Substrate (Promega). Subsequently, the plates were incubated for 10 minutes on a shaker platform at 250 rpm, 37 °C and the luminescence was determined using a Biotek Synergy 2.