dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledment The authors gratefully acknowledge support from the  European Research Council  under grant  ERC-2012-StG-307215 LODE-STONE. This work has been carried out in the framework of the  S-band Polarization All Sky Survey (S-PASS ) collaboration. The Parkes Radio Telescope is part of the  Australia Telescope National Facility , which is funded by the  Commonwealth of Australia  for operation as a National Facility managed by  CSIRO. This research made also use of Astropy, a communitydeveloped core Python package for Astronomy (Astropy Collaboration et al. 2013) and its affiliated packages APLpy ( Robitaille & Bressert   2012 ), galpy (Bovy 2015) and pvextractor.
e. , rolling and tension along the previous rolling direction) with different mean grain sizes. The microstructural characterization was made by EBSD in an FEG-SEM. From each EBSD map, the equivalent diameter D g and the mean orientation of each grain were collected using a post-processing software (Channel 5 (v5. 11, Oxford Instrument, High Wycombe, UK) or ATEX  [25] ). In all the cases, the specimens were fully recrystallized. The specimens with the smallest mean grain size were close to the end of the primary recrystallization. Figure  2  shows examples of obtained grain size distributions for the two samples with the minimum and maximum mean grain size. In the top part of Figure  2 , the scales and the bin sizes used to plot the distributions were exactly the same in order to highlight the differences between the obtained microstructures.
Contributions: F. W. and C. C conceived and designed the experiments; C. C. performed the experiments; T. R. and F. W. conceived the model and performed the simulations; T. R. , F. W. , C. C. and L. S. T. analyzed the data; T. R. and F. W. wrote the paper. All the authors participated in the discussion and reviewed the paper. Funding: This research was funded by by the French State through the program "Investment in the Future" operated by the National Research Agency (ANR) and referenced by grant number [ANR-11-LABX-0008-01] (LabEx DAMAS).
Author Contributions: F. W. and C. C conceived and designed the experiments; C. C. performed the experiments; T. R. and F. W. conceived the model and performed the simulations; T. R. , F. W. , C. C. and L. S. T. analyzed the data; T. R. and F. W. wrote the paper. All the authors participated in the discussion and reviewed the paper. Funding: This research was funded by by the French State through the program "Investment in the Future" operated by the National Research Agency (ANR) and referenced by grant number [ANR-11-LABX-0008-01] (LabEx DAMAS).
AbstrAct Purpose To assess the incremental cost associated with the management of patients with primary non-squamous non-small cell lung cancer (NSCLC) with brain metastases at the time of diagnosis. Methods Data were extracted from the French Hospital medical information database (Programme de Médicalisation des Systèmes d'Information (PMSI)). Patients with non-squamous NSCLC were identified through a diagnosis of lung cancer and a prescription of bevacizumab or pemetrexed. All such patients hospitalised with lung cancer for the first time in 2013 and with metastases identified at the first hospitalisation were eligible. Two cohorts were identified, one with brain metastases (group B: n=971) and one with metastases at other sites (group A: n=1529). For each patient, total in-hospital medical resource consumption associated with the initial hospitalisation in 2013 and with any follow-up stays in the following 24 months was documented.
IntRoduCtIon Lung cancer is the most common cancer worldwide and the principal cause of cancer-related death. 1  In France, there were an estimated 45 000 incident cases of lung cancer and 30 500 lung cancer-related deaths in 2015. 2  In most cases, metastases are already present when lung cancer is diagnosed. The presence of metastases dramatically impacts survival since 5-year survival in patients with stage IV lung cancer is <5%. However, there may be some discrepancies in treatment and outcome according to where the metastases occur. In particular, central nervous system metastases are frequent in patients with lung cancer. Data from over 20 000 patients with lung cancer in the Swedish Family Cancer Database, an exhaustive nationwide database, reported that 56% of patients with lung cancer developed metastases, the most frequent site being the nervous system, accounting for 39% of all metastases.
5 owever, in the setting of oncogene addicted NSCLC, the recent development of inhibitors of the epidermal growth factor receptor (EGFR) or ALK, which penetrate the brain, has shown promise for the prevention and treatment of brain metastases. 5 etrospective studies of North American insurance claims databases have evaluated the economic burden of brain metastases in patients with primary lung cancer and have shown that direct health costs increase around fourfold following diagnosis of brain metastases. 8 9 In particular, use of stereotactic brain surgery may markedly increase the cost of treatment. 10 However, since the cost of management of lung cancer rises substantially following evolution to the metastatic stage, regardless of the site of metastasis,  11  it is not clear how much of the extra cost determined in these studies is inherent to management of metastases specifically arising in the central nervous system.
MateRIals and MetHods study design This retrospective study analysed data extracted from the French Hospital medical information database (PMSI). The study population consisted of all patients hospitalised for a non-squamous NSCLC in France in 2013. Data extraction and analysis followed the guidelines for exploitation of the PMSI database published by the French Health Ministry. 12 The study was conducted in accordance with relevant requirements. Use of the PMSI-MCO (Medicine, Surgery, Obstetrics) database for this type of study has been approved by the French national data protection agency (Commission Nationale de l'Informatique et des Libertés (CNIL); annual authorisation number 1419102 v7-2015-111111-56-18/order M14N056 and M14L056).
PMsI database The French PMSI-MCO is an exhaustive medico-administrative hospital discharge database which covers all overnight or day hospitalisations in the public and private sectors involving short-term stays in medical, surgical or obstetric facilities in France. 13 Individual patients can be tracked across multiple hospitalisations through a unique anonymous patient identifier. Outpatient consultations at hospitals are not documented in the PMSI. In 2013, almost 30 million stays by over 13 million patients were reported in this database. All hospital procedures are documented by hospital stay at the time of final discharge in the form of a standardised discharge summary (SDS), irrespective of the number and type of hospital departments in which the patient has been cared. For costing purposes, each stay is attributed to a diagnosis-related group (DRG) which reflects the reasons for hospitalisation.
These are identified by the physician through International Classification of Diseases, 10th Revision (ICD-10) codes,  14  either as principal diagnoses (PD: the condition for which the patient was hospitalised), related diagnoses (RD: any underlying condition which may have been related to the PD) or as significantly associated diagnoses (SAD: comorbidities or complications which may affect the course or cost of hospitalisation). Sociodemographic information (gender, age and residence code) and medical information on the PD/RD that led to hospital admission, the nature of treatments received and examinations carried out, underlying comorbidities and possible complications (SAD), are available for epidemiologic studies. Medication use is integrated into the DRG, and therefore cannot be individualised, except for expensive drugs, which are individually identified and recorded in a separate database (FICHCOMP), which can be linked to the PMSI-MCO database for individual stays.
Since the introduction of a DRG-based prospective payment system in 2005, the PMSI-MCO database has been used as the basis for the funding of services in all hospitals, with each hospital receiving DRG-based payments according to national tariffs. For this reason, expenditure on hospitalisations by public health insurance is expected to be well documented in the PMSI-MCO database. Information in the database is exhaustive (all public and private French hospitals are included, and no sampling is performed) and is of high quality, with limited coding errors.
study population All hospital stays in France with at least one ICD-10 code for lung cancer (code C34*: malignant neoplasm of bronchus and lung; online supplementary table  1 ) documented as a PD, RD or SAD were identified from the PMSI-MCO database between 1 January 2013 and 31 December 2013. Hospitalisations with at least one ICD-10 code for metastatic cancer (C77*, C78*, C79* codes; online supplementary table 2) documented in the SDS, but without any other primary cancers stated as a PD/ RD/SAD were also retained. Hospital stays for each patient admitted were extracted over a 12-month period before the initial index hospitalisation in 2013 (the retrospective period) and over a 24-month period following this index stay (the prospective period). For example, if the initial index hospitalisation was 1 April 2013, all hospital stays of this patient were extracted from 1 April 2012 until 30 March 2015.
Patients who had any primary or metastatic cancer, including lung cancer, during the 12-month retrospective period were excluded in order to restrict the study to patients with incident lung cancer with synchronous metastasis. Non-squamous NSCLC cannot be identified explicitly in the PMSI database as there is no equivalent ICD-10 code. For this reason, specific lung cancer therapy was used as a proxy marker. Patients who had received bevacizumab or pemetrexed at least once at the index hospitalisation or during the 24-month prospective period were considered to have non-squamous NSCLC. The justification for this is that these two agents were the only two agents licensed exclusively for the treatment of metastatic non-squamous NSCLC and documented in the FICHCOMP database. At the time of enrolment, the FICHCOMP databases where bevacizumab and pemetrexed could be tracked were only available for public hospitals.
Patients with metastatic non-squamous NSCLC treated with either of these drugs in private hospitals were therefore de facto excluded from the study. In the next step, two subgroups of patients were identified, namely (A) a reference group of patients with synchronous metastasis at the index hospitalisation in sites other than the brain, and (B) patients with synchronous brain metastases at the index hospitalisation. The database was searched for documentation of brain metastases documented in the SDS for the index hospitalisation SDS as a PD, RD or SAD (ICD-10 code C97. 3). Patients with documented brain metastases were assigned to group B. Due to potential undercoding of metastases, all hospital stays for patients in group A were reviewed both retrospectively and prospectively to identify any signs or symptoms of brain metastases or specific procedures for their treatment through the relevant DRG codes.
data collection The sociodemographic characteristics of patients were collected (age at inclusion, gender). For each hospital stay, the distribution per type of management was analysed based on the DRG codes: radiotherapy (stereotactic or standard), chemotherapy (including bevacizumab, pemetrexed and any other chemotherapy administered in hospital), palliative care, medical management, surgical procedures, interventional procedures and others. Total in-hospital medical resource consumption, including standard medication, associated with the initial index hospitalisation in 2013 and with any follow-up stays occurring in the 24 months following the index hospitalisation was documented. Medication prescribed or delivered during outpatient consultations at the hospital was not considered.
Costing Costing was restricted to direct costs and determined from the perspective of the French social security system (National Health Insurance, NHI). Costs were attributed from French national tariffs for medical acts applicable in France from 2013 to 2015, and were expressed in 2017 euros. A standard national tariff was applied to each hospitalisation based on the DRG code attributed in the PMSI database. These standard tariffs include medical and related procedures, nursing care, treatments (except specific expensive drugs), food and accommodation and investment costs for hospitalised patients. Additional costs per day of hospitalisation in an intensive care unit were added to the DRG tariffs when appropriate. For private hospitals, where physicians are reimbursed on a fee-for-service basis, physician fees were identified from the Echelle Nationale des Coûts à méthodologie Commune (the French observatory of real-world spending on healthcare) and added to the DRG tariffs.
Expensive drugs and implants were costed using the retail price for the public FICHCOMP database and the official tariff for the private FICHCOMP database (at the time of costing, the private FICHCOMP had just been made available). The costs per patient-month of all hospitalisations related to lung cancer or its metastases were determined for each cohort, with and without chemotherapy. The cost difference between the two cohorts was assessed. An analysis of the mean cost per patient for each month following inclusion was then performed for each cohort.
Identification of patients with non-squamous nsClC In 2013, a total of 84 158 patients with a C34* ICD-10 code for lung cancer were identified in the PMSI-MCO database, of whom 39 734 (47. 2%) had metastatic disease that could not be associated with another primary cancer at the index hospitalisation. After exclusion of patients who had already been hospitalised with lung cancer or any other primary or metastatic cancer during the previous year, 13 720 patients were identified as incident cases. Of these, 3575 patients had received bevacizumab or pemetrexed at the index hospitalisation or during the retrospective or prospective periods and were considered to have non-squamous NSCLC. These consisted of 971 patients with brain metastases at the index hospitalisation and 2604 patients without (figure  1 ).
2 million. This study has several limitations, many of which are inherent to database analyses of this type. In this study, we did not attempt to capture all patients with metastatic non-squamous NSCLC in the PMSI database, the aim being to identify two groups of patients with and without brain metastases who were matched in terms of time of diagnosis and metastatic status, who were treated with the same agents (bevacizumab and pemetrexed) and who were sufficiently numerous to generate costs with sufficient precision. Since bevacizumab and pemetrexed are the only treatments for non-squamous NSCLC identified in the FICHCOMP database, we were not able to identify patients receiving other therapies for this cancer type such as paclitaxel. Similarly, patients taking oral chemotherapy at home for non-squamous NSCLC bearing EGFR mutations (gefitinib or erlotinib) could not be retrieved.
Moreover, it was not possible to identify patients treated in the private sector, since the FICHCOMP database did not cover this sector at the time of the analysis. Given the reported prevalence of different lung cancer subtypes in France, around 10 000 incident cases of metastatic non-squamous NSCLC would be expected to arise each year, and on this basis, around a third of these were captured in the present study. Finally, it should be emphasised that the PMSI database contains no information on histological type or on staging, so it was not possible to identify patients with metastatic non-squamous NSCLC directly. For the same reason, it was not possible to identify subgroups of patients with EGFR mutations or ALK rearrangements. Moreover, treatment outcome cannot be followed in the PMSI database as no clinical information other than diagnosis is documented.
A previous study of costs documented in an insurance claims database in the USA compared costs before and after diagnosis of brain metastases in patients with ALK+NSCLC treated with crizotinib 9 and reported that monthly per capita costs rose from $5983 before diagnosis to $22 645 after. Unlike our study, these costs include community medicine costs and notably delivery of crizotinib. Nevertheless, even when considering inpatient costs only, an increase was observed in monthly per capita cost from $1174 before diagnosis to $6692 afterwards. This finding is not in itself surprising since the passage from non-metastatic to metastatic disease is known to be associated with a substantial rise in resource utilisation and associated cost. A recent study by Fernandes et al  23  is perhaps more comparable with our own, in that patients with lung cancer with synchronous brain metastases at diagnosis was compared with patients with metastases in other sites.
The study was again performed in a US insurance claims database and specifically evaluated patients  with EGFR+NSCLC. Postdiagnosis per capita monthly costs were $21 202 for patients with synchronous brain metastases and $11 190 for patients without. Both absolute costs and the incremental cost of brain metastases were considerably higher than in our study, although it should be noted that, unlike our study, community costs were also considered, including expensive oral chemotherapy in all patients enrolled. Most recently, a third US claims database study has been published, in which a similar approach was used evaluating patients prescribed ALK inhibitors. 24 In this study, costs were compared between patients who developed brain metastases and those who did not. Postdiagnosis per capita monthly costs were $29 497 for patients with brain metastases and $22 791 for patients without.
Computational chemistry methods can significantly reduce experimental costs in early stages of a drug development project by filtering out unsuitable candidates and discovering new chemical matter. Molecular alignment is a key pre-requisite for 3D similarity evaluation between compounds and pharmacophore elucidation. Relying on the hypothesis that the variation in maximal achievable binding affinity for an optimized drug-like molecule is largely due to desolvation, we explore herein a novel small molecule 3D alignment strategy that exploits the partitioning of molecular hydrophobicity into atomic contributions in conjunction with information about the distribution of hydrogen-bond donor/acceptor groups in each compound. A brief description of the method, as implemented in the software package PharmScreen, is presented.
The computational procedure is calibrated by using a dataset of 402 molecules pertaining to 14 distinct targets taken from the literature and validated against the CCDC AstraZeneca test set of 121 experimentally derived molecular overlays. The results confirm the suitability of MST basedhydrophobic parameters for generating molecular overlays with correct predictions obtained for 100%, 93%, and 55% of the molecules classified into easy, moderate and hard sets, respectively. The potential of this tool in a drug discovery campaign is then evaluated in a retrospective study with the aim to evaluate the correlations between activities and similarity score of a series of sigma-1 receptor ligands. The results confirm the suitability of the tool for Drug Discovery purposes finding the 67% of the most active ligands (≤10 nM) in Q1 of the ranking and the most active compound in position five.
Data: • 174 sigma-1 receptor ligands from existing publications analyzed • Public external references from RCSB Protein Data Bank: 5HK1 and 5HK2 1 , 2 , 3 Workflow: ➢ Library preparation ➢ Generation 3D structure, isomers, tautomers and conformers of the molecules (~20. 000 total molecules). ➢ As reference was used a ligand from a crystal structure external to the papers. ➢ Virtual screening with PharmScreen using hydrophobic and hydrogen bonds fields. • Ligands with higher activity found in the initial results.
The mean size 〈N〉 of the cluster ensemble was determined from the expansion parameters using an empirical formula  42. All experiments used a magnetic bottle spectrometer described in ref. 43  Briefly, it is designed with a drift tube of 0. 6 m adapted to the BESSY bunch period of 800 ns. The magnetic guiding field has a strong inhomogeneous component produced by a permanent magnet below the interaction region (magnetic field strength ≈0. 4 T) and a weak homogeneous field in the drift region, induced by a solenoid wound around the drift tube. The spectrometer enables the detection of normal PE and electron-electron coincidence spectra with a high efficiency  44  , determined as γ (E ICD ) = 0. 58 (4) for the data presented. The coincident detection scheme allows separation of the initially ionized photoelectrons from the secondary electrons.
The normal modes below 500 cm -1 were discarded, as the harmonic approximation is not valid in this region. The time step was 6 atomic units (0. 15 fs) and the length of each simulation was 10 fs. The statistics was collected over 100 independent trajectories. All dynamical calculations were performed using the ABIN program  47. To estimate the closing geometry of the ICD channel, the energy of both singlet and triplet doubly ionized states was calculated along each trajectory at the CASPT2(6,4)-SA6/6-31++G** level. When the energy of the inner-valenceionized state drops below the lowest doubly ionized state, ICD can no longer take place. The CASPT2 calculations were performed in the MOLPRO program  48, 49  while the MOM calculations were done in the QCHEM program  50. Few methods are available to calculate absolute electronic decay rates in clusters.
Acknowledgements We thank  Lasse Harbo  and  Evgeny Lugovoy  for help with data acquisition. This project has received funding from the  Research Executive Agency (REA)  under the European Union's  Horizon 2020 research and innovation program  Grant Agreement No. 705515 , and by the  Deutsche Forschungsgemeinschaft  via the Research Unit 1789. C. -M. S. acknowledges funding via the  Swedish Foundation for International Cooperation in Research and Higher Education (STINT). P. S. and D. H. thank the  Czech Science Foundation  (Project Number  18-23756S ). D. H. is a student of the  International Max Planck Research School  for ' Many-Particle Systems in Structured Environments '. N. S. acknowledges the financial support of the  LabEx MiChem part of French  state funds managed by the  ANR  within the  'Investissements d'Avenir' program  under reference  ANR-11-IDEX-0004-02.
Authenticity of Ancient DNA We evaluated the authenticity of the isolated DNA based on its harboring: (1) characteristic cytosine-to-thymine mismatches to the reference genome at the ends of the sequenced fragments, (2) point estimates of contamination in mtDNA below 5%  (Renaud et al. , 2015) , (3) point estimates of X chromosome contamination in males below 3%  (Korneliussen et al. , 2014) , and (4) point estimates of genome-wide contamination below 5% (N. N. , E ´adaoin Harney, S. M. , N. P. , and D. R. , unpublished data). We removed from analysis two individuals that we genetically determined to be first degree relatives of other individuals with higher DNA yields within the dataset but fully report the data for both here (Table  S3 ; STAR Methods).