dataesr/scientific-paragraphs-categorization huggingface dataset:
In our study, twenty ampicillin resistant environmental isolates were identified. From the nine sequenced isolates, a perfect match between the presence beta-lactamase genes and ampicillin resistance phenotype was observed. The clinical isolates showed similar resistance patterns as the environmental isolates. However, three of them (33%) were additionally resistant to the combination of amoxicillin and clavulanic acid. No such resistance was found for patient and environmental isolates from the North and Baltic Sea region  (Bier et al. , 2015) , but 19 of 42 environmental isolates from the Adriatic Sea (45%) and 3 of 9 Italian clinical isolates (33%) were resistant to the combination of penicillins and beta-lactamase inhibitors  (Ottaviani et al. , 2018). Nevertheless, prudent interpretation of the present data is required, as the three strains categorized as resistant to amoxicillin -clavulanic acid, displayed an inhibition zone diameter just below the susceptibility breakpoint.
This gene, a chromosome-encoded variant of the cat gene found in V. cholerae encodes for a chloramphenicol acetyltransferase and confers resistance to chloramphenicol  (Rowe-Magnus et al. , 2002). In contrast, none of the isolates was resistant to chloramphenicol. No gene conferring sulfonamide resistance (e. g. , sul2) and streptomycin (e. g. , strB) for V. cholerae was found using either CARD or ResFinder databases, although nearly all of our strains were tested phenotypically resistant to these two antibiotics. These findings indicate that current databases are partly incomplete for assessing antimicrobial resistance properties of V. cholerae non-O1/non-O139 strains on genotypic characterization alone. Despite the fact that WGS allows detection of a much higher number of resistance markers, the clinical relevance of most of them still needs to be determined.
Our results clearly showed that all isolates were susceptible to all important first-line and last-line treatment options. Widespread resistance was only observed against old antibiotics such as sulfonamides, streptomycin and ampicillin. The apparent lack of either known antimicrobial resistance traits or mobile genetic elements indicates that in cholera non-epidemic regions of the world, V. cholerae non-O1/non-O139 play only a minor role as reservoir of antibiotic resistance genes. Nonetheless, the observed discrepancies between the phenotypic and genotypic resistance data highlight the need for improvement of the resistance databases for V. cholerae non-O1/non-O139 to better understand how these pathogens acquire and disseminate resistance traits in the aquatic environment.
Ibrutinib, a once-daily oral inhibitor of Bruton's tyrosine kinase, is approved in the United States and Europe for treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The phase 3 RESONATE study showed improved efficacy of single-agent ibrutinib over ofatumumab in patients with relapsed/refractory CLL/SLL, including those with high-risk features. Here we report the final analysis from RESONATE with median follow-up on study of 65. 3 months (range, 0. 3-71. 6) in the ibrutinib arm. Median progression-free survival (PFS) remained significantly longer for Trial Registration: clinicaltrials.
Stratification was by purine analog refractory status (defined as no response to or relapse within 12 months of last dose of purine analog) and presence or absence of del(17p). Based on durable responses in the ongoing pivotal phase 2 study PCYC-1102,  18  a protocol amendment was instituted in August 2013 to allow patients on the ofatumumab arm to cross over to receive ibrutinib. Following study closure, eligible patients could continue to receive ibrutinib treatment in a long-term extension study (PCYC-1145-LT; clinicaltrials. gov number NCT03229200).
ACKNOWLEDGMENTS The authors thank the patients who participated in this study and their supportive families, as well as the investigators, subinvestigators, and coordinators at each of the study sites. The authors thank  Jerry Ping of Pharmacyclics LLC , an  AbbVie Company , for his contributions to the statistical analyses and  Joris Diels of Janssen  and  Suzy Van Sanden of Janssen-Cilag Ltd  for their contributions to the crossoveradjusted overall survival analysis using the rank-preserving structural failure time method. John C. Byrd  is supported by the  Four Winds Foundation, D. Warren Brown Foundation , Mr. and  Mrs. Michael Thomas ,  Sullivan CLL Research Foundation , and  R35 CA197734. Editorial support was provided by  Melanie Sweetlove, MSc , and was funded by  Pharmacyclics LLC , an  AbbVie Company.
2. 2 | 2 Study Design RESONATE was a randomized, multicenter, open-label, phase 3 study that evaluated the efficacy and safety of ibrutinib compared with ofatumumab in previously treated patients with relapsed or refractory CLL/SLL (clinicaltrials. gov number NCT01578707). Enrollment was from June 2012 to April 2013. Patients were randomly assigned 1:1.
Nonmetric multidimensional scaling (NMDS) was carried out on the whole (2015 and 2017) [quadrat × species] abundance matrix in order to detect the principal differences between management treatments according to their temporal trajectories. The total frequency of each species was calculated regardless of the management treatment. Species whose total frequency of occurrence was below 5% were removed from the database, whether they were targeted in the community or not. For each management treatment, the three most dominant species (i. e. , those with the highest average abundance) and the three species with the highest indicator values were selected (Table  S3 ). Indicator values were calculated using the indval function in the labdsv package  (Roberts, 2016). The indicator value (IndVal) is a quantitative index that enables identification of the species most characteristic of a group (in this case, a management treatment) based on its fidelity (i.
e. , the species is present in most plots of this group) and specificity (i. e. , the species is found mostly in this group rather than in other groups)  (Dufrêne & Legendre, 1997). All analyses were performed using R statistical software (version 3. 4. 3 R Development Core Team, 2017). Linear mixed effect models A ik = N ik ∕Σ S i=1 (N ik ) CSII = ⎡ ⎢ ⎢ ⎣ Σ i=1…S (n i -Δ i,j ) Σ i=1…S n i,j ⎤ ⎥ ⎥ ⎦ were run using the lmer function in the lmerTest package  (Kuznetsova, Brockhoff, & Christensen, 2016). When necessary, multiple comparisons were run using the CLD function from the emmeans package  (Lenth, Singmann, Love, Buerkner, & Herve, 2019). Nonmetric multidimensional scaling was performed using the metaMDS function from the vegan package  (Oksanen et al. , 2018) , and the results were plotted using the s.
Carbonate rocks are a peculiarity of the Earth relative to other planets in the solar system. Large terrestrial areas are covered by carbonate lithology, which actively reacts with atmospheric/biospheric CO2. Although carbonate rocks represent a major component of the global carbon cycle, their intensity and rates of chemical weathering have been overlooked. In this study, we examine three global databases of rivers and springs draining carbonate regions under various climate conditions (from -15°C to +30°C). Using Ca 2+ + Mg 2+ concentrations as a proxy, we show that carbonate weathering intensity depends upon land temperature according to a boomerang-type relationship, with maximum dissolution between 10 and 15 °C. We show that this pattern is primarily controlled by thermodynamics if we assume that the partial pressure of CO2 in soil (pCO2) increases from atmospheric-like levels under cold climate up to 100 times the present day atmospheric concentration under hot climate.
Recently,  Torres et al. (2017)  also proposed that carbonate weathering by sulphuric acid during glacial periods of the Quaternary was creating a negative feedback on the climate system by modulating atmospheric CO2 levels. These are some of the reasons suggesting that carbonate weathering is important for the Earth's surface regulation. The fast kinetics of carbonate weathering allows it to respond to changes at human timescales making it consequently an important component in future longterm climate models. As shown by the recent modelling paper from  Beaulieu et al. , (2012)  in the Mackenzie river basin, in response to a doubling of atmopsheric CO2 levels, the increase in carbonate weathering would be responsible for 70% of the CO2 consumption by rock weathering. The aim of this publication is to report a global database on carbonate dominated rivers spanning all types of climates and to review the factors potentially controlling carbonate weathering intensity.
We investigate the link between carbonate weathering intensity and climate (mostly temperature) and show that a relatively simple relationship exists between carbonate weathering intensity and land temperature. This bell-shaped relationship is proposed to result from the competitition between thermodynamic control on carbonate weathering and the variability in soil CO2 production by biomass at the global scale. While this conceptual framework is able to reproduce qualitatively the trend observed at the global scale, other factors explaining the important variability of data must be accounted for. To our knowledge, this study is the first reporting a global database of wellselected rivers draining relatively pure carbonate rocks and aims at stimulating further studies on carbonate weathering fluxes and controls at the surface of the Earth.
Origin and selection of data The map showing the carbonate dominated areas of the continents is given in Fig. 1. We have tried to select data from the different carbonate provinces of the world and from sites covering different climate types. We are naturally limited by the places of carbonate outcrops as well as by the limited number of published studies reporting all the required parameters. First, a database was assembled by harvesting literature data for river waters draining pure carbonate rocks (see footnotes of Table  1 ) and applying a series of criteria (detailled below). Mixed lithologies such as marls, calcareous shales were avoided. Table  1  is based on data from France (Jura Mountains, Seine watershed, Herault watershed, French Alps); Slovenia, Russia (Crimea and Siberia); Taiwan; China (Sichuan and Guizhou provinces); Nepal; Thailand; Fly basin, Papua New Guinea, Congo basin, Puerto Rico, USA (Florida and Pennsylvania) and from Canada (NWT).
When climate gradients were locally important, data were grouped and averaged by temperature range (Table  1  and Table S1 ). This database was completed by unpublished data of russian rivers. These latter data were collected in data reports from the former USSR (in Russian) and averaged by location (annual averages for the  years 1959 years , 1960 years , 1961 years and 1962 years for Chernaya, and 1957 years , 1961 years and 1962  for Olenek in Table  1 ). Other unpublished analyses from central China are also displayed in Table  1  and Table  S1. The Table  1  shows that the number of samples per locality is variable but usually small, with the exception of the Jura Mountains  (Calmels et al. , 2014). For each location and according to temperature ranges, Ca+Mg concentrations were calculated and averaged.
Instantaneous water discharge measured the day of sampling is reported for a number of catchments, essentially for locations in Northern America. No statistics were done on the GLORICH database, which is used here to illustrate the variability in Ca and Mg concentrations. Finally, a third dataset was used focusing on the 60 largest rivers of the planet, corrected for rain, silicate weathering and evaporite dissolution. Proportions of major elements from these sources are derived from the mathematical inversion of large river geochemistry  (Gaillardet et al. , 1999). These large rivers can not be directly compared to rivers and springs listed in Table  1  and the GLORICH database as they carry water that has drained various lithologies and not strictly carbonate rocks, but they will be used for comparison.
We only selected the rivers for which the proportion of Ca from carbonate was higher than 75% to best avoid this "dilution" effect. Locations are shown in Fig. 1. In order to gather and compare the different databases, we made sure that the selected rivers and springs were only draining pure carbonate lithologies (ie. no evaporitic rocks or silicates), that atmospheric/soil CO2 was the only significant acid providing protons for mineral dissolution and that the sites were not too much impacted by human activities. Although the subject is still a matter of debate, a couple of papers have shown that nitric acid, derived from nitrification processes, can provide protons and increase chemical weathering rates of carbonates  (Perrin et al. , 2008). Similarily, sulphuric acid formed by the action of oxygen on sedimentary sulphides (e.
This criteria was applied to include rivers influenced by dolostone dissolution and to discard rivers that may be impacted by silicate weathering (silicate dominated rivers have a much lower Ca/Na molar ratio, between  0. 3 and 0. 5, Négrel et al. , 1993). -Rivers with Cl/Na molar ratio higher than 2 as well as rivers with high nitrate concentrations (> 100 µmol/l) were discarded to avoid any strong agricultural impact. Cl -is often associated with fertilizer inputs and is therefore a good proxy for agricultural inputs  (Roy et al. , 1999; Floury et al. , 2017). -Rivers showing (Ca+Mg)/SO4 < 10 were discarded due to potential influence of sulphide oxidation (providing H + ions) or gypsum dissolution (providing an excess of Ca 2+ ). In the different databases used in this paper, we calculated and used Ca+Mg concentrations as a proxy for carbonate weathering intensity (Table  1 ).
Results The datasets used in this study cover a reasonable range of climate settings as illustrated in Fig. 1. The GLORICH database reports a high density of data from North America, Western Europe (mainly France), and South Africa and is therefore over-representing these regions of the word. Interestingly, the GLORICH database can be used to evaluate the variability of carbonate weathering intensity within a given climate zone. Overall, Ca + Mg concentrations in rivers draining carbonate lithologies show a wide range of variability, ranging from about 500 µmol/l for the less concentrated waters of the Mackenzie river basin, Siberia, and Fly River basin to 3000 µmol/l in the temperate region of the Jura Mountains or in the temperate carbonate provinces of North America (Table  1 ). Base cation concentrations (Ca+Mg) from the different databases are reported in Fig.
This decrease is approximately 120 µmol/°C between 10°C and 25°C for the three datasets. Below 10°C, the rising part of the boomerang has a variable slope depending upon the dataset considered (110 µmol/°C for the GLORICH database to 60 µmol/°C for the Table  1  and for the large rivers). However, it is important to keep in mind that the density of data is lower at low temperatures than at temperatures higher than 10°C. The GLORICH data show that the variability at a given temperature is important. For example, within the temperate zone Ca+Mg concentations can vary between 1500 and 3000 µmol/l, probably depending upon hydrological conditions and/or local geomorphic or environmental specificities. We plotted in Fig. 3  the carbonate weathering intensity as a function of runoff (discharge at the sampling date normalized to drained surface area) for a few catchments from the GLORICH database -those having more than 50 observations and instantaneous water discharge record -and also for rivers from Slovenia  (Szramek et al.
, 2007). The Fig. 3  shows generally that, with increasing runoff, concentrations are not following a pure dilution trend (in runoff -1 ) and either remain constant over the whole range of discharge or slightly decrease after a given catchment-specific threshold. Fig. 3  confirms the chemostatic behavior of carbonate-dominated rivers already pointed out by  Bluth and Kump (1994)  or  Zhong et al. (2017)  and suggests that part of the variability observed in the GLORICH database (and by extension in the three databases) at a given temperature can be due to hydrological factors. The GLORICH data also allows us to investigate the effect of the composition of carbonate bedrock on their dissolution intensity. From the data (n=2762), 538 samples have Ca/Mg lower than 1. 5 and are therefore impacted by dolomite dissolution whereas 561 samples have Ca/Mg higher than 10 and are therefore draining pure Ca-carbonates.
On Fig. 2 , it seems that a Ca/Mg ratio of 1. 5 represents a threshold value above which carbonate weathering intensity follows the general boomerang curve and below which the pattern of weathering intensity with temperature is more erratic. It is also interesting to note that none of the databases considered in this paper exhibit Ca-rich springs and rivers at low temperature, suggesting either that Ca-rich limestones are rare at high latitude or that there are mechanisms removing Ca from river and spring waters in low temperature zones (e. g. , freezing). Finally, large rivers also exhibit a bell-shaped pattern in the (Ca+Mg) vs. air temperature space. This pattern appears to be shifted to lower values when compared to the data from Table  1  and from GLORICH. This is easily understandable as these concentration, calculated from an inverse model, do not take into account the "dilution" effect due to the fact that large rivers collect water draining all lithologies and not only carbonate lithologies.
dat" database  (Parkhurst and Appelo, 1999). For the two working models (open and closed systems), calculations have been conducted by assuming Rb = 0. Table  1  shows that Rb can be positive or negative. For instance, in the Jura Mountains where Ca >> Mg, Rb generally varies between -200 and + 200 µequ/l. The effect of Rb is to increase the HCO3 -concentration at equilibrium. Predicted Ca concentrations will be lower when Rb is close to 0 than when Rb is positive or negative. We checked using PHREEQC that if Rb varies between -200 and +200 µequ/l, the propagated variations on Ca concentration at equilibrium are within 5%. Reaction constants and standard enthalpies are given in Table  2.
Other factors influencing carbonate weathering There are a number of other factors that may play a role on carbonate weathering intensity and therefore complicate the simple interpertation that we propose to explain the general bellshape relationship between carbonate weathering intensity and temperature at the global scale. These factors may also contribute to the wide range of scatter which is oberved when global databases are plotted as a function of temperature (Fig. 2 ). -A quite evident controlling factor is carbonate composition. All the above calculations were made using the calcite dissolution equation and equilibrium constant, but the presence of Mg in almost all natural sedimentary carbonates (and other impurities) may lead to different Ks values. It is well known that the Ca/Mg ratio of seawater has changed through time  (Holland, 2003) , but information on the weatherability of limestones as a function of Ca/Mg ratios is still lacking.
We observe from our dataset that mountaneous rivers tend to have lower weathering intensities than rivers from the lowland, suggesting a potential control by hydrological factors. We did not find however any relationship between the mean slope and the carbonate weathering intensity for the different data bases used in this paper. -Another source of variability in Ca+Mg concentrations could be the precipitation of secondary carbonates. During carbonate dissolution water equilibrates with higher pCO2 (in soils) than in the atmosphere, and when water starts to be in contact with the atmosphere during its transfer from the hydrological system to the ocean, dissolved CO2 tends to leave solution  (Raymond et al. , 2013). This CO2 degassing leads to an increase in pH which then subsequently promotes carbonate precipitation.
Carbonate precipitation would thus result in a decrease in Ca concentration. This degassing effect would be more pronounced for rivers draining high T regions because waters have originally equilibrated with higher soil pCO2 than in low-T regions (see Fig. 5 ). The degassing (and thus carbonate precipitation) would then be dependent on the difference between aqueous pCO2 (acquired in soils) and atmospheric pCO2. This difference is much higher in high-T regions than in low-T regions, which might explain part of the low Ca+Mg concentrations observed at high T. At low T, the enrichment in Mg that is visible in Table  1  and in the GLORICH database (Fig. 2) may be an indication of secondary calcite formation. In cold climates, freezing could be a mechanism responsible for the precipitation of Ca-carbonate and thus a lowering of Ca concentration in residual water  (Jessen et al.
g. Li et al. , 2008) , Northern Canada  (Calmels et al. , 2007)  and the Himalayas  (Galy and France-Lanord, 1999; Karim and Veizer, 2000). In South China,  Li et al. (2008)  had shown that 42% of the carbonate dissolution in the karstic province of Guizhou was due to sulphuric acid sources. However, from the investigated database, no relationship between Ca+Mg concentrations and SO4 concentration or Ca/SO4 was found with temperature, indicating that a control of carbonate dissolution by sulphuric acid addition is very unlikely. Finally, another possible source of acidity is provided by nitric acid (generated by nitrification processes). It has been shown by  Perrin et al. (2008)  that in some agrosystems, a significant part of carbonate dissolution might be due to protons coming from the transformation of ammonium into nitrate.
In details, none of the chosen curves for soil pCO2 are able to explain the whole dataset. The Brook et al. (1983) 's soil pCO2 prediction does show a bell-shape curve with maximum Ca+Mg concentrations found around 15°C in agreement with the data but fails to explain the highest temperature values. The NPP-controlled CO2 curve(Gwiadza and Broecker, 1994)     also reproduces a boomerang shape and shows a maximum carbonate weathering intensity at similar temperature than the river and spring datasets. However, it fails to quantitatively explain the observed concentrations at low and high temperatures. At cold and warm climates, soil pCO2 predicted byGwiadza and Broecker (1994)  is too high to explain the low Ca+Mg concentrations found in carbonate draining rivers. A better prediction, at least in terms of shape, is done by theRomero-Mujali et al.
dataset is one of the datasets used in this paper. The Jura Mountain is a foreland alpine carbonate range from Central Europe showing a climatic (and superimposed ecological) gradient from the plains to the Mountain ridges. Calmels et al. (2014)  have shown that carbonate weathering intensity along this gradient varies by a factor of 2. 5 between 300 m and 1200 m elevation. Using a coupled ecological and hydrological model run on the two years of the sampling period (the ASPECTS model, fromRasse et al. , 2001), Calmels et al. , (2014),.
Acknowledgement Oleg Pokrovsky ,  Jacques Schott ,  Yves Goddéris ,  Julien Bouchez ,  Nicole Fernandez  are thanked for their comments and carefull comments. We thank  Matthiew Wimmick  and  Pamela Sullivan  for constructive reviews. Funding for this work in Germany has been provided by  German Science Foundation (DFG)  through the  Cluster of Excellence   CLISAP2  ( DFG Exec177 ,  Universität Hamburg ), and  BMBF-project PALMOD (Ref 01LP1506C ) through the  German Ministry of Education and Science (BMBF) as Research for Sustainability initiative (FONA).