dataesr/scientific-paragraphs-categorization huggingface dataset:
LPAR5 and LPAR6 correlated to endothelial and inflammatory cell markers (dendritic cells, T lymphocytes, and macrophages) (Table  S2 ). (C) Evaluation of PLPP3 protein levels by mass spectrometry comparing plaques (CPs) with adjacent control arterial tissue (n = 18 matched samples), and plaques from S versus AS patients (n = 9 per group). Values are expressed in a. u. as mean ± SD. (D) Survival curves illustrating MACCE-free survival of patients during the followup period after surgery, based on PLPP3 mRNA expression in BiKE plaques above (black) and below (red) the median values (x axis, days of event-free survival). Each mark along the lines indicates an event. Total number of events in the cohort was n = 58. MACCE, major adverse cerebro-and cardiovascular event. These analyses were followed by in situ hybridization (ISH) and immunohistochemistry (IHC) of the LPARs in consecutive sections of human lesions, which generally confirmed the differential expression data and correlation pattern of the receptors (Figure  S1 ).
Human Material Atherosclerotic plaques were obtained from patients undergoing surgery for high grade (>50% North American Symptomatic Carotid Endarterectomy Trial [NASCET])  34  carotid stenosis at the Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden, and clinical data were recorded upon admission. Symptomatic patients (S) were defined based on the following symptoms: transitory ischemic attack (TIA), minor stroke, and amaurosis fugax (AF). Patients without qualifying symptoms within 6 months prior to surgery were categorized as asymptomatic (AS) and indication for CEA based on results from the Asymptomatic Carotid Surgery Trial (ACST). A mandatory examination of the carotid arteries (by duplex ultrasound [US] and/or computed tomography [CT] angiography) was performed prior to surgery.
The project was performed under the Swedish biobank regulations, and prospective sampling was approved with informed consent procedure (DNr 2009/512-31/2). BiKE is registered at Socialstyrelsen (The National Board of Health and Welfare) and Biobank of Karolinska and approved by the Swedish Data Inspection Agency (approval date/number 2002-09-30 DNr 916-2002). The BiKE database was merged with the Swedish Hospital Discharge Register and the Swedish Cause of Death Register for follow-up of major adverse cardiovascular, cerebrovascular, and vascular events (MACCEs). All samples were collected with informed consent from patients or organ donor guardians. This study involved 3 non-overlapping subsets of BIKE patients, where 2 sets of plaques were analyzed by Affymetrix microarrays (larger set with n = 127 plaques of which 87 were from S + 40 from AS patients and smaller set with n = 50 plaques where 40 from S + 10 from AS patients).
FTMSControl 3. 0 and FlexImaging 4. 2 software packages (Bruker Daltonics, Bremen, Germany) were used to control the mass and set imaging parameters. The visualization and statistical analysis of imaging data were performed using MultiImaging 1. 1 software (ImaBiotech, Lille, France). To combine and compare tissue staining with the lipid distribution, MALDI imaging acquisition was performed on adjacent carotid tissue sections and scanned using a 40Â magnification objective on an Olympus IX18 microscope (Olympus, Germany). Scans were then integrated in the MultiImaging software for a co-registration with imaging data to accurately correlate the distribution of molecular species with human plaque histological regions. Assignment of lipid species was performed by searching the accurate m/z values against the Lipidmap database using a mass tolerance of 3 ppm.
39 onformatics and Statistical Analyses RNA extracted from endarterectomy (CP) and control NA specimens was analyzed by Affymetrix microarrays. Robust multiarray average (RMA) normalization and correction for batch effect was performed, and processed gene expression data were returned in log2 scale. The microarray dataset is available with the following accession number from Gene Expression Omnibus: GSE21545. Target gene and protein analyses were performed with GraphPad Prism 6 using a two-sided Student's t test assuming non-equal deviation. Pearson correlations were calculated to determine the association between mRNA expression levels from microarrays, with Bonferroni correction for multiple comparisons. Survival analysis was done using the Cox regression model  40  with event-free survival as the response variable and log2transformed gene expression levels as the explanatory variable.
ACKNOWLEDGMENTS We thank  Germán Camejo  for carefully reading the manuscript and valuable comments. The research leading to these results has received major funding from the  European Union Seventh Framework Programme  ( FP7/2007-2013)  under grant agreement  602936  ( CarTarDis  project). This work was conducted with support from the  Swedish Heart and Lung Foundation , the  Swedish Research Council  ( K2009-65X-2233-01-3 ,  K2013-65X-06816-30-4 , and  349-2007-8703 ),  Uppdrag Besegra Stroke  ( P581/2011-123 ), the  Strategic Cardiovascular Programs of Karolinska Institutet and Stockholm County Council , the  Stockholm County Council  ( ALF2011-0260  and  ALF-2011-0279 ), the  Foundation for Strategic Research , and the  European Commission (CarTarDis, AtheroRemo, VIA, and AtheroFlux  projects).
Background: Palbociclib administered with endocrine therapy was tolerable when the overall incidence of toxicities was assessed separately for three PALOMA studies. This study analyzed pooled, longer-term PALOMA safety data longitudinally. Methods: Data were pooled from three randomized phase II and III studies (ClinicalTrials. gov: NCT00721409, NCT01740427, NCT01942135) of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer patients. Front-line patients were randomly assigned to receive letrozole with/without palbociclib (PALOMA-1) or letrozole plus palbociclib/placebo (PALOMA-2). In PALOMA-3, patients with prior endocrine resistance received fulvestrant plus palbociclib/placebo. The cumulative event rates of adverse events (AEs), reporting up to 50 months of treatment, were assessed over time.
Results: Patients who received endocrine therapy (n ¼ 1343) were included in this pooled analysis (872 were also treated with palbociclib, and 471 were not). The most common AEs with palbociclib plus endocrine therapy were neutropenia and infections (any grade, 80. 6% and 54. 7%, respectively), which were higher than in the endocrine monotherapy arm (any grade, 5. 3% and 36. 9%). The most common hematologic AEs (!15. 0% in the palbociclib arm) were more likely to be reported in the initial months of the study, after which time the cumulative event rate did not substantially increase. With palbociclib plus endocrine therapy, any grade AEs leading to permanent discontinuation over three years occurred in only 8. 3% of patients. Conclusions: Based on these long-term safety analyses, there is no evidence of specific cumulative or delayed toxicities with palbociclib plus endocrine therapy, supporting the ongoing investigation of palbociclib plus endocrine therapy in early breast cancer (NCT02513394).
Study Design and Patients This analysis includes safety data from the open-label, phase II PALOMA-1 study and the double-blind, phase III PALOMA-2 and -3 studies (ClinicalTrials. gov: NCT00721409  [9] , NCT01740427  [10] , NCT01942135  [11] , respectively). All three PALOMA study designs, briefly shown in Supplementary Figure  1  (available online), have been described previously  (1) (2) (3) (4). Across all PALOMA studies, written informed consent was provided before study procedures were initiated; institutional review boards at participating centers approved all study-related procedures, which complied with the International Conference on Harmonisation, guidelines for Good Clinical Practice, and the Declaration of Helsinki. Overall survival has been reported for PALOMA-1  (12) , and follow-up is in progress for the PALOMA-2 and PALOMA-3 studies.
Data and Statistical Analyses AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) v19. 0. The frequencies of maximum grade events for each patient during study treatments were summarized by treatment arms. Related preferred terms were aggregated into cluster terms (Supplementary Methods, available online). To evaluate the long-term safety of palbociclib combined with endocrine therapy, the cumulative event rates of hematologic and selected nonhematologic AEs-recognized as being of clinical relevance-were assessed using Kaplan-Meier estimates. Frequently reported AEs, in 15% or more of palbociclib-treated patients, were assessed at six-month intervals (0-<6, 6-<12, 12-<18, 18-<24, 24-<30, 30-<36 months). To assess the risk of having an AE in palbociclib-treated patients (compared with patients receiving endocrine monotherapy), hazard ratios for each AE of interest were estimated using a Cox model stratified by study.
The longest safety follow-up of any CDK4/6 inhibitor in the breast cancer setting is five years for palbociclib plus letrozole in the PALOMA-1 study (December 30, 2016, data cutoff), reported in conjunction with overall survival  (12). Although these data were used to assess cumulative incidence annually over five consecutive years to reveal no new safety concerns, as a single study, it included only 83 patients, and, although informative, it must be viewed in that context. This pooled analysis assesses AEs reported for 872 patients treated with palbociclib plus endocrine therapy across three phase III clinical trials after a follow-up of up to 50 months and represents the most comprehensive safety report of CDK4/6 inhibitor use for advanced breast cancer at this time. Some limitations may exist with respect to the generalizability of these safety findings.
The representation of blacks in this pooled analysis was 2. 5% or less of the study population in either arm; Asian patients constituted 16. 6% and 13. 6% of the women in the palbociclib-treated and endocrine therapy only arms, respectively. Additionally, patients with certain comorbidities or those taking certain concomitant medications were excluded from taking part in the clinical trials that formed the basis of our analyses; thus, the findings of our analyses may not be applicable to those patients who were excluded from these trials. Based on these long-term safety analyses, there is no evidence of specific cumulative or delayed toxicities resulting from prolonged treatment with palbociclib combined with endocrine therapy for HRþ/HER2-ABC, supporting the use of palbociclib plus endocrine therapy in the ongoing investigation of their utility in early breast cancer as adjuvant treatments (NCT02513394).
All authors were responsible for data interpretation, writing or revising the manuscript for intellectual content, and the decision to submit the manuscript for publication. The authors have no conflicts of interest. We thank the patients, investigators, and study personnel who participated in the PALOMA trials. PALOMA studies 1, 2, and 3 ( NCT00721409 ,  NCT01740427 ,  NCT01942135 , respectively) were sponsored by  Pfizer. Editorial support was provided by  Susan Reinwald, PhD , and  Johna Van Stelten, PhD , both of  Complete Healthcare Communications, LLC (West Chester, PA ), a  CHC Group Company , and was funded by  Pfizer.
Chorology and Origin of Taxa Two types of data were compiled in order to quantify the floristic diversity of the Iles Eparses: older floristic reports coming from bibliography (before 2004, date of the first inventories of the CBNM) and recently confirmed reports  (period 2004-2017, based  on field surveys by the CBNM). Older floristic reports were evaluated according to the observer's competence field, date of observation and general coherence, and were compared with recently confirmed floristic reports. After this evaluation, all dubious literature records for taxa not found on the Iles Eparses during the period 2004-2017 were ignored. Lists of taxa specific to each territory (Europa, Juan de Nova, Iles Glorieuses and Tromelin) will be presented according to the following fields: botanical name, family, general status (origin status on a given territory on the base of chorological, ecological and biological data defined in three statuses according to the terms defined by  Pyšek et al.
Moreover, according to the available data  (Camoin et al. , 1984; Camoin et al. , 1997; Virah-Sawmy et al. , 2009; Woodroffe and Horton, 2005)  the sea level has changed considerably since the likely formation of the Iles Eparses during the peak of the last interglacial, Marine Isotope Stage 5 (MIS5, 120,000 years ago). The islands probably peaked at a height of 120-140 m above sea level at the Last Glacial Maximum (LGM, 25,000 years ago). Deglacial sea levels rose irregularly in stages to present, with a maximum oscillation at about 7000-6000 years BP, to about 1-3 m higher than present sea level  (Camoin et al. , 1984; Camoin et al. , 1997). At that time Europa, Juan de Nova and Grande Glorieuse were not entirely submerged, but Tromelin undoubtedly and the Ile du Lys probably were. Yet some particular cases deserve to be noted.
While the first two were formerly cultivated on a large scale in order to produce vegetal fibers, the reasons leading to the cultivation of C. equisetifolia on Europa remain less obvious (timber production, soil erosion, shade, wind breaks or water tanks). The alien flora of Juan de Nova includes many naturalized taxa colonizing natural and semi-natural habitats, many of which are only cultivated on a small scale. These old practices reflect a tendency to artificialize the island and should be associated with Hector Patureau (manager of a guano and copra exploitation from 1952 to 1967) and other settlers. However, these plantations suffer mostly from the rough ecological conditions of this territory, notably those on sand during the dry season. Some native species of Juan de Nova have been cultivated as ornamentals (Dombeya greveana and Psiadia altissima) or for forestry exploitation (Cordia subcordata Lam.
ACKNOWLEDGMENTS This study was made possible thanks to the financial and technical support of the  Ministère de l'Écologie, du Développement Durable et de l'Énergie (MEDDE) , of the  Direction de l'Environnement, de l'Aménagement et du Logement de La Réunion (DEAL Réunion ), of the  CNRS-INEE , of the  Terres Australes et Antarctiques Françaises (TAAF) , of the  Forces Armées en Zone Sud de l'Océan Indien (FAZSOI)  and the entire staff of the CBNM -especially  Marie Lacoste ,  Christian Fontaine ,  Johnny Férard ,  Jérémy Beaurepaire ,  Benoit Dumeau ,  Betty Dufour ,  Antoine Chauvrat ,  Thibault Rochier ,  Frédéric Picot  and Hervé Fossy -whom we heartily thank. Our thoughts also go to the dozens of scientists and military people we met during our expeditions. Finally, we also thank  Frantz Hopkins  and especially  Brigitte Wiart-Boullet  and  John Thompson  for their assistance in translation.
In this study, we used a unique data set of 503 individual trees from 12 populations of Afzelia africana, a tropical tree distributed from the Sudano-Guinean to the Sudanian zones in Benin, to test the effects of pruning and debarking on the absolute growth rate while accounting for the ontogenetic tree growth trajectory. We assessed the effects of intraspecific variability in the leaf and wood economic spectrum on individual tree growth performance and tested the effects of the individual tree functional strategy on tree growth response to debarking and pruning.
Acknowledgements We are grateful to the  « Unité mixte de Recherche EcoFoG de Kourou » and Labex-Ceba  for offering I. O. A. the opportunity to attend the Thematic School on "Functional Ecology of Tropical rainforests in the context of  Climate Changes » at Kourou, French Guiana. We thank  A. C. Christian ,  D. -Z. Vincent ,  B. Sévérin ,  A. Dieudonné ,  A. Atchade ,  S. Boni  and  A. Nassirou  for field assistance. We are grateful to the editors and two anonymous reviewers for comments which improved an early version of this manuscript.
■ ACKNOWLEDGMENTS Financial support from the Swiss National Science Foundation (SNSF) (Ambizione Grant No. PZ00P2_167900; J. O. Z. and G. D. ) is gratefully acknowledged. S. W. and C. W. acknowledge financial support through the Army Research Office under Grant No. W911NF-15-1-0190. M. L. and W. T. acknowledge funding from Flanders Innovation & Entrepreneurship through the Plast-i-Com project (IWT 135100). W. T. also thanks the Provincie West-Vlaanderen for his Chair in Advanced Materials and Research Foundation Flanders for his Odysseus Fellowship (Grant G. 0C60. 13N).
| OMALIZUMAB AND PREG NAN C Y An observational study assessing the safety of omalizumab during pregnancy is also currently underway. The EXPECT omalizumab pregnancy registry (https://clinicaltrials. gov/ct2/show/NCT00373061) records the incidence of congenital anomalies babies born to asthmatic mothers who were exposed to ≥1 dose of omalizumab 8 weeks before conception or at any time during pregnancy. Interim analysis of the EXPECT study has revealed no increase in the prevalence of major anomalies in babies of asthmatic mothers who were exposed to omalizumab (via the feto-maternal barrier) compared with the general asthma population. 69 Observational data for the newborn are also collected at birth, and at 6 and 12 months post-delivery (and up to 18 months post-delivery if the infant is being breastfed).
studies assessing current asthma therapies in infants have been sparse. It is possible that omalizumab can modify disease or prevent disease progression, which are characteristics that will be evaluated in the Preventing Asthma in high Risk Kids (PARK) study in the United States (https:// clinicaltrials. gov/ct2/show/NCT02570984). In this study, which is due to commence in 2018, children aged 2-3 years with a history of 2-4 wheezing episodes in the previous year and positive aeroallergen allergy will receive omalizumab or placebo for 2 years and will be followed for an additional 2 years. The co-primary outcomes of the PARK study are (a) active asthma diagnosis and (b) asthma severity assessed by the validated composite asthma severity index (CASI), 65  which combines symptoms, medication use, and lung function into the score (time frame: final 12 months, during the 2-year observation period off the study drug).
Finally, a bone marrow examination with cytogenetic profiling should be performed if a change in the above evaluation is identified. 39 There is currently no formal data to recommend a repeat mutational panel during follow-up. 75 With respect to pivotal phase 3 clinical trials, we recommend as primary endpoints robust criteria such as OS, progression-free survival, or event-free survival and incorporation of the MDS/MPN criteria as secondary endpoints. Phase 2 clinical trials utilizing the MDS/MPN IWG criteria as the primary endpoint should be analyzed with caution, particularly when interpreting the proportion of patients whose response is improvement of myeloproliferative symptoms.
Remission induction chemotherapy There is a limited published dataset for intensive chemotherapy (IC) in patients with CMML. The main goal of IC is to reduce bone marrow blasts and aim for complete remission. 105 CMML is a fundamentally chemoresistant disease which does not appear to be curable with IC alone. Single center series describe poor long-term outcomes irrespective of the IC regimen, despite achieving up to 40% CR rate. Remission duration is short, and relapse appears inevitable, even when regimens are intensified. 126 n the other hand, as mentioned above, IC is generally recommended before HSCT for "short-term control" in patients with an excess of marrow blasts (especially CMML-2), despite the absence of prospective trials clearly demonstrated the role of IC in this context. When considering intensive chemotherapy as a "bridge to transplant," however, the benefits should be weighed against the risks of complications (eg, infections) or organ damage that may delay or definitively impair HSCT.
108, 131, 138, 145 Retrospective comparisons of patients treated with AZA versus DAC do not provide data to support the choice of one HMA over the other. 76, 134 rades 3 to 4 hematologic toxicity has been reported in 15% to 55% of the patients, including up to 15% infections. 137, 139 These figures compare favorably with those seen in MDS. 130 This could be due to lower toxicity notably the less frequent occurrence of neutropenia in patients with MP-CMML, although there is no data correlating myeloproliferative features and toxicity to HMAs in CMML. In patients eligible for HSCT, as mentioned above, the role of HMA prior to transplant is disputed, especially as CMML were often analyzed together with MDS. In MP-CMML patients ineligible for HSCT, a retrospective comparison suggests a survival benefit of HMA over HY, and previous HY exposure seems to reduce the response rate to HMAs 137 but this requires prospective confirmation, especially with the ongoing DACOTA trial (NCT02214407, EudraCT: 2014-000200-10), a European phase III trial randomizing frontline DAC versus HY in MP-CMML with adverse features (significant cytopenias, high neutrophil count, blast excess or splenomegaly, defined according to a previous randomized trial of HY in MP-CMML 2 ).
Development and validation of dedicated symptom scores would be instrumental in that aspect. HY should be tapered or withheld in case of onset or aggravation of transfusion dependency. Although it has no obvious impact on the abnormal clone(s) size,  53  HY is still widely employed in proliferative CMML, especially before the use of HMA. As mentioned above, an ongoing European randomized study compares HY with DAC in MP-CMML with high-risk features (DACOTA trial, NCT02214407, EudraCT: 2014-000200-10), and its results are not yet available. Finally, therapy with HY does not seem to affect the outcome of patients who later undergo HSCT. PANEL RECOMMENDATION. HY is recommended in proliferative CMML, in the absence of major cytopenias or excess of marrow blasts (evidence level 2, recommendation level A).
Management of thrombocytopenia Hypersplenism may contribute to thrombocytopenia in CMML patients with splenomegaly. Thrombocytopenia can also have a peripheral component in CMML, and this may be suspected notably when there is severe thrombocytopenia contrasting with the absence of anemia or excess of marrow blasts. Immune thrombocytopenia-like treatments, may be attempted in those cases, sometimes with success. 156 Thus, a short steroid course may be envisaged in those cases. A trial of the thrombopoietin (TPO) agonist eltrombopag is ongoing in thrombocytopenic CMML-0 patients (EudraCT 2013-001779-19, NCT02323178). Use of TPO mimetics outside of clinical trials in CMML is not recommended. Otherwise, the recommendations for platelet transfusion should be per the guidelines for MDS. 154 NEL RECOMMENDATION.
Other and new drugs Few phase I/II trials are exploring novel agents selectively in CMML (or in MDS/MPN). These include drug classes such as oral TPO agonists (eltrombopag, NCT02323178), JAK2 inhibitors (ruxolitinib, NCT01776723), farnesyltransferase inhibitors (tipifarnib, NCT02807272), histone deacetylase inhibitors (tefinostat, EudraCT 2015-002281-23), or the GM-CSF cytokine (lenzilumab, NCT02546284). However, a broader range of drug classes are being explored in more advanced, registration trials designed for MDS and/or AML, but that can include CMML subsets. This is for instance the case for the second-generation HMA guadecitabine (NCT02907359). Because the molecular spectrum of CMML is closely related to that of other myeloid neoplasms, trials exploring IDH inhibitors or spliceosome inhibitors (H3B-8800, NCT02841540) may be open to CMML.