dataesr/scientific-paragraphs-categorization huggingface dataset:
Voxel-based morphometry For the present report, structural MR data of 2072 adolescents were available. We excluded all participants where the image quality was suboptimal, most likely due to movement. The visual quality control was carried out by 10 independent raters. Structural data acquired at age 14 years was preprocessed by means of the VBM8 toolbox (http://dbm. neuro. uni-jena. de/vbm. html) and SPM8 (http://www. fil. ion. ucl. ac. uk/spm) with default parameters. The VBM8 toolbox involves bias correction, tissue classification and affine registration. The affine registered grey matter (GM) and white matter (WM) segmentations were used to build a customized DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) template. Then warped GM and WM segments were created.
For this purpose, we ran separate two-part growth mixture models for each and every voxel of the brain and repeated this analyses for the grey and white matter maps separately. This approach is exploratory as no specific areas of the brain are extracted (as would be the case in the more traditional analyses of ROI). While it bears the risk of inflated type-II-errors, it also enables the investigation of links between brain structures and behavior that have not been strictly established yet. For each SEM that was generated with a specific voxel as covariate, we plotted the estimate/p-value of the regression path from brain to the slope back into the brain, to be able to plot the resulting image using R (the scripts can be obtained from the first author, more flexible functions that may be helpful in conducting similar analyses can be found in the 'neuropointillist' R package, https://github.
Acknowledgements This work received support from the following sources: the  European Union -funded  FP6  Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) ( LSHM-CT-2007-037286 ), the  Horizon 2020  funded  ERC Advanced Grant 'STRATIFY' (Brain network  based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the  Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways)  ( PR-ST-0416-10004 ),  BRIDGET  ( JPND: BRain Imaging, cognition Dementia and next generation GEnomics ) ( MR/N027558/ 1 ), the  FP7  projects  IMAGEMEND ( 602450 ;  IMAging GEnetics  for MENtal Disorders) and MATRICS ( 603016 ), the  Innovative Medicine Initiative Project EU-AIMS  ( 115300-2 ), the  Medical Research Council Grant 'c-VEDA' (Consortium on Vulnerability to Externalizing Disorders and Addictions)  ( MR/ N000390/1 ), the  Swedish Research Council FORMAS , the  Medical Research Council , the  National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London , the  Bundesministeriumfu ¨r Bildung und Forschung (BMBF  grants  01GS08152 ;  01EV0711 ; eMED SysAlc01Z Â 1311A;  Forschungsnetz AERIAL 01EE1406A ,  01EE1406B ), the  Deutsche Forschungsgemeinschaft (DFG  grants  SM 80/7-2 ,  SFB 940/ 2 ), the  Medical Research Foundation and Medical research council  (grant  MR/R00465X/1 ).
Further support was provided by grants from:  ANR  (project  AF12-NEUR0008-01 -WM2NA , and  ANR-12-SAMA-0004 ), the  Fondation de France , the  Fondation pour la Recherche Medicale , the  Mission Interministerielle de Lutte -contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the  Assistance-Publique-Hopitaux-de-Paris  and  INSERM  (interface grant),  Paris Sud University  IDEX 2012; the  National Institutes of Health, Science Foundation Ireland  ( 16/ERCD/3797 ),  U. S. A. (Axon, Testosterone and Mental Health during Adolescence ;  RO1 MH085772-01A1 ), and by  NIH Consortium  grant  U54 EB020403 , supported by a cross- NIH  alliance that funds Big Data to Knowledge Centres of Excellence. SK has been funded by a  Heisenberg grant  from the  German Science Foundation  ( DFG KU 3322/1-1 ,  SFB936/C7 ), the  European Union  ( ERC-2016-StG-Self-Control-677804 ) and the  Jacobs Foundation  ( JRF 2016 ( JRF -2018 )).
Background. The World Health Organization (WHO) adult glioma grading system is questionable in pediatric high-grade gliomas (pHGGs), which are biologically distinct from adult HGGs. We took advantage of the neuropathological review data obtained during one of the largest prospective randomized pHGG trials, namely HERBY (NCT01390948), to address this issue in children with newly diagnosed non-brainstem HGG. Methods. HGG diagnosis was confirmed by pre-randomization, real-time central pathology review using WHO 2007 criteria, followed by a consensus review blinded to clinical factors and outcomes. We evaluated association between WHO 2007 grade and other clinical/radiological/biological characteristics and the prognostic value of WHO 2007 grade, midline location, and selected biomarkers (Ki-67 index/Olig2/CD34/EGFR/p53/H3F3A K27M mutation) on overall survival.
5  There have been few trials evaluating pharmacological treatments in addition to radiotherapy for pHGG and most, if not all, evaluated drugs with known efficacy in adult gliomas. 6 The phase II, prospective, randomized controlled HERBY trial (study BO25041; clinicaltrials. gov NCT01390948) showed that the addition of bevacizumab to standard radiotherapy plus temozolomide did not improve event-free survival in pediatric patients with newly diagnosed HGG. 7 The HERBY trial was aligned with large studies testing bevacizumab efficacy in adults with HGG. 8, 9 n HERBY, all cases underwent expert neuropathological and radiological panel review, and an extensive molecular assessment was conducted in 80% of patients. 10 We used data from patients screened for this trial to evaluate the usefulness of the WHO glioma grading system.
Importance of the Study The new combined histomolecular WHO 2016 classification makes significant changes in the diagnosis of gliomas especially in pediatrics, but these modifications have not been accompanied by changes in the key elementary grading criteria. We took advantage of the neuropathological review dataset obtained during one of the largest prospective randomized pHGG trials named HERBY, including molecular and radiological central evaluation (phase II, multicenter, comparative study of the addition of an anti-angiogenic agent to radiotherapy and temozolomide in patients between the ages of 3 and 18 years with newly diagnosed non-brainstem HGG to analyze the prognostic value of key grading criteria and interobserver reproducibility. We show that (i) real-time central neuropathological review is feasible in a multicenter study and (ii) the different grading criteria and the resulting WHO grade have no prognostic value in pHGG.
Only midline location and a high Ki-67 index were associated with poor outcome. Informed consent was obtained from all individual participants included in the study. All patients screened for the HERBY trial at one of the 51 participating sites in 14 countries between October 2011 and February 2015 were eligible for the current analysis, including patients who were not enrolled in the randomized trial because of exclusion criteria (thereafter called "non-randomized patients"), provided that informed consent was signed. Three different patient subgroups were considered for the pathology data analyses: (i) All cases confirmed as HGG by central review were included in the interobserver agreement analysis of pathology assessment; (ii) those with a diagnosis of anaplastic astrocytoma, anaplastic oligoastrocytoma, or glioblastoma were included in the grading analysis; (iii) those enrolled in the randomized trial were included in the prognostic factor analysis.
Computerized Quantification of Ki-67 Index The Ki-67 index was quantitatively evaluated as the percentage of Ki-67+ nuclei among all detected nuclei using a computerized analysis of whole-slide images, NDPITools,  16  and in-house software (C programs and ImageJ). The tissue area was selected by excluding blurred spaces, tissue-free space, and clusters of red blood cells. 17, 18 Reference zones for the blue (hemalun) and brown (Ki-67) stains were selected automatically, and color deconvolution was performed by using the measured optical densities of the reference zones. 18 Objects (Ki-67+ and Ki-67-nuclei) were segmented based on automatically defined thresholds. Objects smaller than 6. 13 µm 2 were discarded to avoid false positives due to dust and impurities. The resulting masks of nuclei and unblurred tissue areas, along with digitized images of the samples, were converted to the OpenSeadragon image format using Vips  19  and uploaded to a web server where the pathologist could remotely review the segmentation quality.
20 in univariate analysis and <15% of missing data (main multivariable model). The proportional hazards assumption was tested using Schoenfeld residuals and no violation was observed. Heterogeneity of the prognostic value of grade according to tumor site and H3F3A K27M mutation status was assessed in multivariable models, including an interaction term. These analyses included only patients with HGG confirmed by central review who were enrolled in the randomized trial, as follow-up data were not available for the other patients. All tests were performed at a two-sided alpha = 5%; point estimates and 95% CIs were determined. All analyses were performed using SAS v9. 4.
Further details are shown in Supplementary Tables  3  and 4. Based on the consensus review, 12 additional patients were excluded for the grading analysis because the diagnosis of astrocytoma was not confirmed: 1 patient with a diagnosis of oligodendroglioma, 7 with a diagnosis of high-grade glioma not otherwise specified, and 4 with HGG confirmed but subtype not defined by the consensus pathologists. Follow-up data were not collected in patients who were finally not enrolled in the randomized controlled trial because they did not meet all eligibility criteria (clinical, radiological) for the trial. Consequently, those patients had to be excluded from the prognostic factor analysis.
30, 31 The prognostic value of glioma grading in the WHO 2016 integrated adult subgroups is also unclear, particularly since the differentiation of adult glioma by IDH1/2 gene mutation and 1p/19q chromosomal codeletion status. 3] [34]  This suggests that global improvements in prognostic value of the WHO 2016 guidelines is due to better histomolecular characterization, rather than clarifying grading elements. Grade III versus IV was included as a stratification factor in the HERBY study, due to its prognostic impact, as suggested in the CCG-945 trial. 12 However, we found no prognostic value for grade III versus IV established by the expert consensus panel, or for key grading criteria, particularly endothelial proliferation and necrosis. Furthermore, using the updated WHO 2016 grading guidelines and correcting the grading according to radiological data (ie, grade III reclassified as grade IV if necrosis and/or contrast enhancement present on central radiological review) failed to establish any prognostic value with WHO grading.
Acknowledgments The authors thank the local pathologists, their technical staff, and the  Sainte-Anne neuropathology department  for managing the real-time neuropathology review. They also thank the participating investigators, their study staff,  Louis Viviers , and the patients and their families who participated in this study. Third-party medical writing assistance, under the direction of the authors, was provided by  Thomas Burton ,  BMBS (Gardiner-Caldwell Communications, Macclesfield, UK). On behalf of the  European Innovative Therapies for Children with Cancer (ITCC) consortium , the  SIOP-E Brain Tumour Group , the  Australian Children's Cancer Trials Group , and  C-17 Council (Canada).
Data Source We used data from the French National Health Data System (SNDS). The SNDS database includes all French residents' health expenses. In France, the General Insurance Plan extends to all private and public sector employees and students, covering approximately 88% of the French population. The SNDS includes individual information on sociodemographic characteristics, the cause of death and all patients' health reimbursements including outpatient medical care, laboratory tests, dispensed drugs, and medical details (including any severe or costly medical condition). An anonymous, unique subject identifier links information from the database to the national hospital and discharge database which covers all public and private hospitals admissions and discharges. It contains data on the diagnoses (coded in the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10)) and type of surgical acts and treatments provided during hospital stays.
Exposure Definition Surgery in the six months following breast cancer diagnosis, as defined using the common classification of medical procedure codes (CCAM), was considered the date of inclusion (Table  S1  in supplement). The main exposure considered as the initial postsurgical treatment for BC was defined during the first year following inclusion as follows; Exposure to chemotherapy in the 6 months following surgery for BC, radiation therapy and hormonal therapy in the year following BC-surgery. Chemotherapy for BC is administered at hospitals and radiation therapy can be delivered either at hospitals or at specialized private centers. They are identified in the database using ICD-10 codes and CCAM (Table  S1  in supplement). Hormonal therapy is dispensed by pharmacies and is identified using anatomical therapeutic chemical classification system codes (ATC) (Table  S1  in supplement).
In a complementary adjusted multivariate Cox analysis, we considered chemotherapy and radiotherapy as single groups of exposure and we studied their effect on hematologic malignancies' risk. Their interaction with age were also investigated. Overall survival post-HM diagnosis was calculated for each type of HM as the time from HM diagnosis till death, loss to follow up or December 31, 2017 using the Kaplan-Meier method. Sensitivity analyses were conducted using Fine and Gray's method  [19]  considering patients who died before developing an HM as having a competing event. Cumulative incidence of HM comparing the four mutually exclusive groups were reported in the presence of death as competing risk. All analyses were performed with SAS software version 9. 4 (SAS Institute Inc. )).
A unique feature of our study, was the ability to quantify risks of ALL/LL after chemotherapy for breast cancer in the current treatment era. We found a 1. 7-fold increased risk of ALL/LL after chemotherapy while exposure to radiation therapy did not seem to be associated with an increased risk. Given the scarce frequency of ALL, most literature reported secondary ALL as case reports or case series  [11, 12]. Other studies could not confirm nor exclude a relationship between the use of chemotherapy and ALL/LL occurrence  [2, 29]  due to the low number of cases in their datasets. Yet, some cytogenetics studies have shown that the characteristics of secondary ALL are parallel to the well-recognized cytogenetic alterations found in secondary AML  [10, 11, 30]. Lymphomas had a small but significant 1.
The median interval time of 2. 7 to 2. 8 years between BC diagnosis and the onset of AML in patients receiving chemotherapy is very much comparable to other studies having the same follow-up time length as ours  [36]. Time proximity from primary BC could be an indicator of treatment-related disease. Hematologic malignancies in our BC survivors were associated with poor survival as reported by other studies  [24, 37, 38]. Survival for AML and ALL/LL in our study was measured in months, not years, making these leukemias the worst prognosis cancers. Accumulation of chromosomal aberrations and mutations from prior chemotherapies are thought to be the cause of the aggressive and treatment-resistant behavior  [39] [40] [41]. One of the study's limitations was the lack of data on chemotherapy agents and their actual doses.
Despite these limitations, our study is based on a nationwide population-based data with a relatively long-term follow up in the recent therapeutic era. We obtained complete real-life data on each patient with very homogeneous treatment strategies. We believe that this is the first study to measure and compare different types of secondary hematological malignancies post-breast cancer according to different postoperative treatment modalities. We were also able to answer questions involving rare outcomes with very bad prognostic features, which are of direct interest to patients, practicing oncologists, and cancer researchers. Finally, the risk of these hematologic malignancies secondary to BC treatment is dynamic and will hopefully decrease once precision medicine and molecular subtyping and targeting become the standard of care.
Patients We conducted a multicentric retrospective study in a cohort of patients including 367 patients followed for endometriosis between January 2012 and March 2018. In this cohort, data were collected prospectively when patients were suspected of having endometriosis. Patients were suspected of having endometriosis when they experienced chronic pelvic pain for a greater than six-month duration. This pain could be a severe dysmenorrhea, a deep dyspareunia, a cyclic pelvic pain and painful defecation with or without infertility. In this cohort, patients could have been explored with other radiological exams, such as MRI or endovaginal ultrasonography, at the discretion of the clinician. Endometriosis was finally diagnosed according to surgical and histological criteria. In our study, the inclusion criteria were patients aged over 18 with rectosigmoid endometriosis who underwent a surgery after a RS-EUS.
This study was conducted in orientation towards the guidelines of the Declaration of Helsinki and Good Clinical Practice. The protocol and all documents were approved by the Institutional Review Board (IRB) of Landesärztekammer Baden-Württemberg with the reference number F-2018-062. A written informed Consent Form was obtained from all participants prior to screening evaluations. The present study was registered with ClinicalTrials. gov (ID: NCT03,932,695).
The residuals of this model were checked for normality using the Shapiro-Wilk test with an alpha level of 0. 05. If applicable, data were log transformed prior to analysis. Multiple pairwise comparisons of least squares means of primary and secondary endpoints were adjusted by the method of Dunnett-Hsu in order to assess differences between the two active treatments and placebo. Data of the cross-over design are presented as least square means with 95% confidence interval (CI). Moreover, in the open-label study period, besides HbA 1c values, the homeostasis model assessment (HOMA) index and the Matsuda index were used to evaluate the impact of the study product intake during a longer period on insulin sensitivity, and comparisons were performed between the baseline and the end of intervention.
Additionally, during the open-label study period of 6 weeks, the pharmacokinetic endpoints after the challenge test were compared with placebo during the study phase I. Data were evaluated using a paired t-test. In case of non-normal distribution of data, a Wilcoxon signed-rank test was applied. Data of the open label phase are presented as means with 95% CI. All 21 subjects were included in the analysis. Statistical tests were performed two-sided, and p values < 0. 05 were statistically significant. Statistical evaluation, summary tables, and graphs were generated using GraphPad Prism software (La Jolla, CA, USA) and SAS V9. 4 statistical software (SAS Institute, Cary, North Carolina).
Subject Characteristics The investigated study population was a non-smoking prediabetic study group, on average 62. 4 years (95% CI: 60. 0-64. 9) old with a BMI of 28. 1 kg/m 2 (95% CI: 26. 3-30. 0). A total of 21 subjects (n = 13 women, n = 8 men) completed the study. Table  1  presents the participants' demographic data and screening data. Vital signs and blood routine parameters were within normal range. None of the subjects were vegetarian or vegan, and 52% of the participants practiced sports on a regular basis. Subjects were advised not to change their eating habits, which were controlled by a semi-quantitative nutrition habit questionnaire comprising 24 food categories. There was no significant change over intervention period (p = 0. 2148). Fasting baseline values of glucose and insulin did not differ among the single dose treatment days (p > 0.
Patients One hundred twenty-seven DM patients aged over 18 years were referred between 2000 and 2016 for an endocrine evaluation from the Reference Center of an area of 4 million inhabitants. Eleven patients were excluded, either due to their refusal of the evaluation (n = 8) or due to intolerance of the position required for the thyroid US (n = 3) (Fig. 1 ). Another one proved to be a DM2 form and was excluded. The data from the remaining 115 patients were retrospectively collected from their medical files.
Imaging The thyroid US evaluation was performed with linear high frequency probes (TOSHIBA Aplio XG™ SSA790A, -9 to 13 MHz). Nodules were classified according to the Thyroid Imaging Reporting and Data System Classification (TIR-ADS)  [16]. Fine-needle aspiration cytology (FNAC) with a 27-gauge needle was performed if nodule was: 1) TIRADS 5 and > 5 mm, 2) TIRADS 4B and > 7 mm, 3) TIRADS 4A and > 10 mm, 4) TIRADS 3 and > 20 mm. We analyzed the FNAC using the Bethesda (2010) classification.
Cup quality was assessed by six expert testers from Illy Caffè, with eight descriptors (aroma, flavor, aftertaste, acidity, body, balance, overall, and defects). A final score was assigned to each sample according to the Specialty Coffee Association (SCA) protocol (http://www. scaa. org/?page=resources&d=cupping-standards). To estimate the stability of Starmaya across the range of environments, productivity data were analyzed following the additive main effects and multiplicative interaction (AMMI) model. This model takes into account genotype and environment interactions  (Purchase et al. , 2000; Bose et al. , 2014; Darai et al. , 2017) , with the Agricolae package in R. AMMI analyses were used to partition genotype × environment deviations into different interaction principal component axes (IPCA).
The beans were then passed through a series of sieves, thereby being divided into classes of small (sieves 13 and 14), medium (15 to 17), and large (sieves 19 and 20) beans. The percentages of defects and exportable parchment coffee were evaluated for each cultivar following procedures routinely used by Exportadora Atlantic S. A factories at Sebaco in Nicaragua (ECOM group). Sensorial analyses of Marsellesa ® and Starmaya were performed twice with two trained tasters, based on the SCA protocol and using scales from 0 to 10 for the evaluated attributes. The Starmaya and Marsellesa ® cultivars where then compared with Caturra red cultivar harvested from a commercial plot located close to the experiment (200 m). The data corresponded to the mean of the two sensorial evaluations.
Potential Starmaya F1 Hybrid Seed Production of the Seed Garden Based on the results obtained from the CIR-SM01 and Marsellesa ® seed garden field, we found that natural pollination was efficient for producing Starmaya F1 hybrid seeds. In terms of seed production, an average of 100-150 kg of F1 hybrid seeds (data not shown) was harvested per year from this experiment (0. 5 ha). These quantities amounted to potential production of approximately half a million hybrid seeds per hectare of seed garden, which should enable the planting of over 100-120 ha of Starmaya F1 hybrid coffee each year. The sterile male CIR-SM01 produced poorly compared with commercial cultivars, which usually produce around two million seeds under similar agronomic conditions. The cost of the seed produced by this sterile male progenitor was estimated to be about 0.