dataesr/scientific-paragraphs-categorization huggingface dataset:
Role of the funding source This study was supported by F. Hoffmann-La Roche Ltd. It was designed by the funder (F. Hoffmann-La Roche Ltd. ) and academic authors. Data were collected by the academic authors and their research teams, and were interpreted by the authors and funder. All authors had full access to the study data. The funder provided medical writing support. The corresponding author had full access to all the study data and final responsibility for the decision to submit for publication.
That deep objective responses were observed in BCL2-high (2+/3+ by IHC) with both R-ADC combinations warrants further evaluation given recent data indicating that high levels of BCL2 expression were individually a negative prognostic factor in diffuse large B-cell lymphoma. 22 Finally, Rpina and R-pola demonstrated activity across diffuse large B-cell lymphoma COO subtypes with no apparent association between diffuse large B-cell lymphoma COO subtype and CD22 and CD79b expression. Unfortunately, we were unable to conduct analysis of double expressors according to IHC, or evaluate MYC plus BCL2 and/or BCL6 rearrangements (i. e. , double-or triple-hit lymphomas), which is a limitation of the study. Also, soluble CD22 was not measured in this study. The availability of two ADCs targeting B cells raised the interesting question of whether ADC resistance was mediated by target modulation versus MMAE resistance and, relatedly, whether there was clinical activity of crossover treatment.
Consequently, studies investigating pola in combination with other antilymphoma agents in patients with non-Hodgkin lymphoma are currently in progress. Results from a phase 1b/2 study of pola in combination with bendamustine and R (pola + BR) versus BR in patients with relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma showed a substantial benefit in the cohort receiving pola,  24  which resulted in the pola + BR combination being designated breakthrough therapy status by the US Food and Drug Administration and PRIME designation by the European Medicines Agency. Pola is also being investigated as first-line treatment in diffuse large B-cell lymphoma in combination with R, cyclophosphamide, doxorubicin, and prednisone (R-CHP) in the POLARIX study (NCT03274492). 25 -cell lymphoma treated with R-pina, and 19 and 16 patients with follicular lymphoma treated with R-pina and R-pola, respectively, were evaluable for IPI and FLIPI2 scores.
Acknowledgments The authors thank the patients and their families, the study investigators, study coordinators, and support staff. Medical writing support for this manuscript was provided by  Joanne Vaughan , CMPP, of  Envision Pharma Group , and funded by  F. Hoffmann-La Roche Ltd. Medical editorial support was provided by  Rachel Hubbard , MSc, of  Gardiner-Caldwell Communications , and was funded by  F. Hoffmann-La Roche Ltd. Janssen ,  Novartis, Pharmcyclics, Seattle Genetics , and  TG Therapeutics , and honoraria from  TG Therapeutics , outside the submitted work. OWP reported research funding from  Roche , honoraria from  BMS  and  Roche , and consultancy fees from  Bayer , outside the submitted work. GS reports personal fees for consultancy, advisory board participation, or speaking at symposia from  Amgen ,  BMS ,  Celgene ,  Gilead ,  Janssen ,  Kite ,  Merck ,  Morphosys ,  Novartis ,  Roche , and  Servier , and research funding from  Roche , outside the submitted work.
SGM-101 safety in dogs Six beagle dogs (three males, three females) (Marshall Farms) were equipped with telemetric transmitters (Data Sciences International, PA-C10). They were assigned to a single group that received first one intravenous infusion of 5 mg/kg SGM-101 during 4 h and then, after a wash-out period of at least 10 days, another infusion of 20 mg/kg SGM-101 for 4 h. The test item was administered as a solution in vehicle (PBS with 135 mM arginine). Cardiovascular (ECG, blood pressure) and respiratory recordings were performed on conscious animals using external telemetry monitoring. Cardiovascular parameters were assessed before the administration of each dose and at 0. 25, 0. 5, 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 h after the beginning of the infusion. ECG recordings were reviewed to evaluate the occurrence of arrhythmia at the analysis time points.
Grey cells: values < 5%. Others include skin, stomach, small intestine, colon, testis, tongue, pancreas, prostate, esophagus, skeletal muscle, bone, brain, eyes, and carcass. Beagle dogs evaluated the cardiovascular and respiratory functions after SGM-101 administration (at approximately 45 times the maximal intended clinical dose) and also included the analysis of several toxicology endpoints to collect additional data in a second animal species. No significant adverse reaction/toxicity was observed, with the exception of the occurrence of an infusion (likely anaphylactoid-type) reaction in some dogs that resolved spontaneously. Such infusion reactions are common when using biological medicinal products, particularly antibodies, and are usually clinically manageable  [30] [31] [32]. If this is considered as an adverse reaction, the NOAEL in the dog can be estimated at 5 mg/kg, or 100 mg/m 2.
The results of these toxicology studies helped to determine the starting dose of SGM-101 used in clinical trials (NCT02784028, NCT02973672). The NOAEL in the dog was evaluated at 5 mg/kg, or 100 mg/m 2 , and in the rat at 40 mg/kg or 240 mg/m 2. Therefore, a starting dose of 5 mg (3 mg/m 2 for a 1. 7 m 2 patient) was chosen, providing a significant, 33-fold safety margin relative to the NOAEL in the dog. The safety margin was still 11-fold for the highest anticipated dose (15 mg or 9 mg/m2). Being over the 10 fold excess typically recommended by health authorities prior to a first injection to a human subject, it was considered to be sufficient for this type of product. Indeed, an evaluation of the safety data was performed for the eighteen patients included in the NCT02784028 trial (patients with peritoneal carcinomatosis from CEA-overexpressing digestive cancers) and for the 46 ones included in the NCT02973672 trial (16 patients with primary and 30 patients with recurrent colorectal cancer).
Data collection The bacteriologist informed the interviewer in charge of the study of each case. The interviewer then met with patients to explain the study and ask for their informed consent in case they met the selection criteria. Patients were asked to fill out the EQ-5D-3 L  [19]  to describe their present state of health at the moment of the CDI episode (7 ± 2 days after diagnosis). Due to difficulties in arranging a new appointment with the patient after resolution of the current CDI episode because of hospital discharge or patient's death, a retrospective assessment of the patients' overall perception of health before the episode was also performed. Patients were asked to use the same instrument to describe retrospectively their state of health immediately before the present CDI episode (baseline).
In the EQ-5D-3 L, the health status is described by ticking off one of three levels of functioning ("no problems", "some problems" and "extreme problems") on five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Using a set of weights (value set or so called tariff ) for each level of functioning in each dimension, the descriptive information can be converted into a single utility score. Since this study was conducted in France, the French value set was used to calculate utility scores  [20]. Patients were also asked to rate their overall perception of health on the EQ-5D-3 L Visual Analog Scale (EQ-VAS), which ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). All relevant clinical data were collected from the patients' records: primary and secondary diagnoses as coded in the Hospital Discharge Database, length of stay, stay in ICU, immunosuppression, presence of any CDI episode within the previous 2-year period and all clinical data needed to characterize the severity of CDI episode.
A classical measure of CDI severity is the Zar score which ranges from 0 to 6 (6 indicating the most important severity)  [21]. This score is calculated by attributing one point to each of the following items: age > 60 years, temperature > 38. 3 °C, albumin level < 2. 5 mg/dL, or peripheral White Blood Cell count > 15,000 cells/mm3 within 48 h of enrollment. Two points are given for endoscopic evidence of pseudomembranous colitis or treatment in the intensive care unit. Patients with 2 points or more are considered by clinicians to have severe CDI. Regarding comorbidity, a revised version of the Charlson index  [22, 23] , based on the ICD-10 coding of primary and secondary diagnoses recorded in the hospital discharge database was used. This index is calculated on the basis of the presence or absence of 17 comorbidities weighted according to their potential influence on mortality.
Statistical analysis Mean and SD for utility scores and EQ-VAS were calculated at the time of the CDI episode and at baseline. The decrement of utility scores for each patient was calculated by subtracting the current utility score from the baseline value. No adjustment for missing data in the EQ-5D was performed. It was tested whether the decrements of score were respectively dependent on the following categorical factors (Student t-test): age (< 65 years versus ≥65 years), gender (M/F), severity of the episode (Zar score ≥ 3 versus < 3), presence of previous CDI episodes (yes/no), Charlson index (< 3 versus ≥3), EQ-5D at baseline (negative versus positive), presence of immunosuppression (yes/no). A multivariate linear regression analysis was performed using the SAS (SAS V9. 3) procedure PROC GLM to analyze the overall effect of these categorical variables.
Population and CDI episodes characteristics A total of 80 patients were included. Three patients died during hospital stay (for causes other than CDI) after having completed the survey and their data were included in the analysis. The population had a mean age of 69. 4 years (SD: 14. 5) and 55% were women. The characteristics of their hospital stays are presented in Table  1. The CDI was coded as primary diagnosis in 22. 8% of cases indicating that it was the reason for the patient's admission to the hospital. Other primary diagnoses were very diverse, the three most frequent being congestive heart failure (19 patients, 23. 8%), chronic pulmonary disease (16 patients, 20. 0%) and diabetes mellitus (14 patients, 17. 5%). The mean Charlson index was 5. 1 (SD: 2. 8) with a percentage of 60% of patients being ≥5 indicating a high risk of mortality associated with severe comorbidities.
Factors associated with utility decrement The utility decrement from baseline showed statistically significant increases according to the following characteristics of patients: Zar score of severity ≥3 (p = 0. 001), a positive utility score at baseline (p = 0. 032), being a woman (p = 0. 041) and having an age > 65 years (p = 0. 041) (Table  3 ). Conversely, the Charlson index, the presence of immuno-suppression or existence of a recurrence did not significantly modify this decrement. The same analyses performed with the EQ-VAS score were only significant for the Zar score of severity (p = 0. 0189). The SAS procedure PROC GLM was used with the same variables on the utility decrement with a global statistical significance (p = 0. 0025) (Table  4 ). It confirmed the previously documented results with the exception of the effect of gender which was no longer significant.
Hypoxia Promotes Apoptosis in Endothelial Cells HUVECs were exposed to simulated hypoxia for two hours. Cells were harvested to analyze the expression of cleaved caspase 3 at different times. Stress related to hypoxia resulted in a significant increase in apoptosis of HUVECs. Relative expression to the control group (T0) of cleaved caspase 3 was increased after 2 hours of hypoxia: T120: 1029 ± 181. 3% vs control group T0 2. 2. Hypoxic Stress Induces Overexpression of P2Y 6 , P2Y 11 , A 2A , A 2B , CD 39, and CD 73 mRNAs In our model, the expression of P2Y receptors, adenosine receptors, and ectonucleotidases mRNA was studied during two hours of hypoxia. P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2X 7 , P2X 4 , A 2A , A 2B , and A 3 receptors were expressed in HUVECs (data not shown). The relative expression to the control group (T0) was estimated as normalized mRNA levels using the following formula: 2 -∆∆C T of different conditions.
After blocking with skimmed milk 5% (m/v) in TBS-T (Tris-Buffered Saline and TWEEN 20 0. 05% (v/v)) membranes were incubated with the primary antibody overnight at 4 • C. After washing with TBS-T, membranes were incubated with appropriate horseradish peroxidase-labelled secondary antibodies (1 h, 30 min at room temperature) (Supplementary file 5). Immunoreactivity was detected with the Chemiluminescent HRP detection reagent (Millipore, Burlington, VT, USA). Quantification was performed by densitometric analysis using the Quantity One software of ChemiDoc XRS and ImageLab for reprocessing image and quantification (BioRad, Marnes-la-Coquette, France)  [15].
Normalised coverage tracks for genome browser visualization were generated with the functions bamCoverage and bam-Compare from the deepTools2 suite  (47). Coverage tracks from individual samples are expressed as reads per kilobase per million mapped reads (RPKM), whereas comparison tracks are expressed as the log 2 of the number of reads ratio. Raw read counts were extracted with the featureCounts tool from the R package Rsubread  (48) , using the yeast genome annotation as a reference. Similarity of biological replicates. The similarity of biological replicates was assessed with correlation analysis after log 2 transformation of the raw read expression matrix. The function heatpairs from the R package LSD (https:// CRAN. R-project. org/package=LSD) was used to generate a matrix of pairwise correlation scatterplots.
Chromatin immunoprecipitation (ChIP) Chromatin purification, immunoprecipitation, quantitative real-time PCR (qPCR) amplification and data analysis were performed as described  (44, 50, 51). Briefly, cells were grown overnight to saturation at 25 • C, then diluted to an OD 600 of ∼0. 2, and let them grow at 34 • C for ∼5 h until they reached an OD 600 of 0. 5-0. 6. Immunoprecipitated and purified chromatin was subjected to quantitative real-time PCR using the CFX96 Detection System (Bio-Rad Laboratories, Inc. ) and SYBR ® Premix Ex Taq™ (Takara Bio), following the manufacturer's instructions. Real-time PCR reactions were performed in duplicate from at least three independent ChIPs. Quantitative analysis was performed with the CFX96 Manager Software (version 3. 1, Bio-Rad). The values obtained for the IPed PCR products were compared to those of the total input, and the ratio of the values from each PCR product from transcribed genes to a non-transcribed region of chromosome VII was calculated.
ChIP-seq Library preparation, sequencing and quality control. For ChIP-seq experiments, anti-mouse or anti-rat IgG dynabeads (Invitrogen) were used to immunoprecipitate Rpb1 or Rpb1-Ser2P, together with 8WG16 and 3E10 antibodies, respectively. Each experiment was carried out in biological duplicates for a total of 12 samples. Library DNA was prepared from immunoprecipitated DNA and its corresponding input DNA following the manufacturer's instructions, and was sequenced in a Illumina HiSeq 2500 system to an output of 313 (1 × 50) million reads. The quality metrics of the fastq sequencing datasets were obtained with FastQC and visually inspected. Filtering, trimming and adapter clipping. These steps were carried out essentially as described for RNA-seq. Genome alignment and genome browser visualization.
Reproducibility of the replicates and merging of datasets. A matrix of read coverages for the entire genome was generated with all alignment files with the function multiBam-Summary from deepTools2. Briefly, the function takes the genome annotation and splits it in 10 kb bins. For each bin, the number of reads found in each bam dataset is counted. A correlation matrix heatmap plot was generated with the plotCorrelation function of the same package. Correlation values are calculated with the Spearman method as default (see below in Results section). Based on the high correlation values of the biological replicates, the two datasets from each sample were merged into one for average metagene representations around genomic regions with SamTools  (53). Metagene analysis. Normalised average density plots around genomic features were calculated with the ngs.
plot software  (54). The ChIP-seq mode and the statistical robustness parameter, which filters out 0. 5% of genes with the most extreme occupancy values, were applied to all calculations. ChIP-exo of Hmo1. Hmo1 ChIP-exo datasets (55) were downloaded from the Sequence read archive (SRA) repository, with accession number SRP041518. Raw fastq files were processed following a pipeline similar to the one described above for our ChIP-seq datasets.
The eluted peptides were then fragmented on the 5600 Triple-TOF mass spectrometer, thereby obtaining a high number of MS and MSMS spectra of the precursors (peptides) present in the sample. Raw data were exported, processed and used to launch a search against the Uniprot S. cerevisiae database using the MASCOT search engine. Peptide identifications with Mascot scores equal or >20 were exported and used to establish the statistical significance of the identifications. False discovery rates (FDR) were applied at different levels: spectrum, peptide and protein, among which the protein level was considered for analysis. As generally accepted, a FDR value was considered to be significant when smaller than--or equal to--1%.
ACKNOWLEDGEMENTS We are grateful to  Alberto Paradela  and  Adán Alpízar Mor  úa from the  Proteomic Department at the CNB, CSIC Madrid, Spain , for help with the mass spectrometry experiments. We thank people at the  Genomic Facility at the CRG in Barcelona. We also thank  David Lydall ,  Craig Peterson ,  Rolf Sternglanz  and  Steve Elledge  for the gift of strains. We also thank  Charles White  and  Maria Gallego  for helpful discussion and critical reading of the manuscript.
Anacardiaceae Lithraea molleoides (Vell. ) Engl. (≡ Schinus molleoides Vell. ) A Tn: Tunisia: Monastir, Monastir city, 35°46'25"N, 10°49'06"E, 21 m, within an old building, 21 May 2018, El Mokni (Herb. Univ. Monastir). -Lithraea molleoides is a tree up to 8 m tall native to South America, ranging from Argentina, Uruguay and Bolivia to the Cerrado vegetation of Brazil (see, e. g. ,  Lorenzi 2000; Zuloaga & al. 2008; López Patiño & al. 2012; Jørgensen & al. 2013). According to the Euro+Med Plant-Base  (Henning & Raab-Straube 2016+) , the taxon does not appear to have been reported in the Mediterranean region as yet. The African Plant Database (APD 2019) reported the occur-rence of the taxon as "naturalized-introduced" only in tropical Africa. Therefore, the citation here as a casual alien constitutes the first report of this taxon for the Tunisian and N African flora.
A single non-flowering individual was found within the cited area. (Galasso & al. 2018). For N Africa the taxon is cited as alien with unknown status for Algeria, Libya and Tunisia. The African Plant Database (APD 2019) lists the occurrence of the taxon in N Africa as present with cultivated status for Algeria, the Canary Islands, Morocco and Tunisia. The actual status of S. molle in Tunisia is defined here. Some sporadic subpopulations of few individuals have been observed growing and spreading mainly in the Monastir region since 2012; therefore, the species can be considered as naturalized in Tunisia. Monastir). -An evergreen shrub or small tree,  3 -10(-15)  m tall, native to C and E South America including Argentina, Brazil, Paraguay and Uruguay (USDA-ARS 2019). The plant has been widely introduced to many parts of North America, Africa, Australasia, Europe, the West Indies and Oceania and there are records of the species having naturalized and becoming invasive in each of these regions.
Schinus terebinthifolius In the African Plant Database (APD 2019), the species is cited as "Cult. /Adv. /Introd. ". The actual status of S. terebinthifolius in Tunisia is defined here. Opuntia robusta is an increasing weed problem in almost all areas where it was once introduced, for instance in Australia and South Africa  (Walters & al. 2011; Novoa & al. 2015)   -Cen taurea carduiformis was described from Western Armenia (now Turkey) and is also known from Georgia, Armenia, Azerbaijan, Syria and Iran  (Tzvelev 1963; Wagenitz 1975; Greuter 2006+). This species is rather polymorphic in phyllary appendages and corolla colour  (Gabrielyan 1995). According to  Mikheev (2000)    The deviant plants occur in clearly distinguishable, pure populations. Stems are strigose to strigillose in the lower half with hairs mostly ascending and only 0.
Finally,  Sennikov & Kurtto (2019)    America, Asia, Australia and Europe (see Verloove 2014). In Europe and the Mediterranean region the taxon is reported as alien with unknown status from Madeira, the Iberian Peninsula, the Baleares, Corse, Cyprus and Poland (Euro+Med 2006+). It also occurs in Italy  (Domina & al. 2018; Galasso & al. 2018 ). In N Africa, the taxon is reported from the Canary Islands, Morocco, Algeria and Egypt, also as alien with unknown status, and as cultivated on a large scale from Libya, but without any citation from Tunisia (Jiménez-Mejías & Luceño 2011+). Also the African Plant Database (APD 2019) does not report the occurrence of the taxon in Tunisia. Therefore, the citation here as a casual alien constitutes the first report of this taxon for the Tunisian flora, as an escape from former cultivation in an ornamental plantation.
Acknowledgements A. Fridlender  wishes to thank  Bouchra Douaihy  and  Jean Stephan  for their useful help during field exploration in Lebanon, and  Fabrice Paranque  for the English correction. R. Hand ,  S. Rätzel  and  H. Uhlich  thank  Ò. Sánchez-Pedraja  (Editor-in-chief of the Grupo botánico cantábrico (GBC),  Liérganes, Spain)  for confirmation of the determination of Phelipanche porto ilicitana and helpful hints. The latter two authors also thank  N. Fumeaux  ( Genève/G ) for support,  J. Krause  ( Berlin ) and  M. Ristow  ( Potsdam and Berlin ) for providing unpublished data, and  U. Raabe  ( Marl ) for joint field trips (with S. Rätzel). Finally, two anonymous reviewers are thanked for their comments on earlier versions of these Notulae.
It is commonly grown as an ornamental shrub • The current WCSP treatment (Govaerts & al. 2019, in arid climate types across the world, includ- accessed 21 Oct 2019) took note of the new name but ing the Mediterranean area. Its stem segments considered it as unplaced; break off easily which enables the species to • The African Plant Database (APD, version 3. 4. 0), escape wherever planted. In the past years it regularly updating the initial work by Dobignard & has been known as a naturalized escape from Chatelain (2010+), added the new name and con- the Canary Islands (Fuerteventura, Lanzaro- sidered it accepted as it was, while all the other spe- te, La Palma, Tenerife) and Italy (Korotkova cies of the group are still considered under the genus & von Raab-Straube 2017). In addition, it is Drimia.
is still lacking. In our 2016 paper, reviewers encouraged us to consider it under Charybdis, because this genus had a better consensus among Mediterranean taxonomists. Nevertheless, the main regional or global databases (Euro+Med 2006+; Dobignard & Chatelain 2010; Govaerts & al. 2019) still do not consider the small genus Charybdis and prefer to include it, also with Urginea s. s. , within Drimia in a broad sense. The resurrection of the species then became troublesome owing to lack of harmonization: • Euro+Med, based on the treatment of the World Checklist of Selected Plant families (WCSP 2010), still does not recognize the species, still has not incorporated the new name and keeps its basionym Scilla anthericoides as a synonym of Drimia maritima; cal brick walls, 30 Nov 2018, Zeddam (photo); ibid.