dataesr/scientific-paragraphs-categorization huggingface dataset:
Data collection The data to be collected in order to derive HBM-GVs refer to the following: -Toxicological data on the substance, i. e. toxicokinetic and toxicodynamic information on the parent compound including information on its mode of action (MOA). By definition, studies examining the toxicokinetics (TK) of a chemical substance are conducted to obtain adequate information on its absorption, distribution, biotransformation (i. e. metabolism) and excretion, to aid in relating concentration or dose to the observed toxicity  (OECD, Test No. 417, 2010). The term "toxicodynamic" on the other hand, refers to the process of interaction of chemical substances with the body and the subsequent reactions leading to adverse effects (EFSA glossary). -Information on the specificity and toxicology of the potential biomarker(s) and the factors that may affect interpretation of the HBM results of the chosen biomarker(s) (co-exposure to other substances for example): a biomarker is defined as any substance, structure or process that can be measured in the body or its products and influences or predicts the incidence of outcome or disease.
Cohort-and case-control studies may provide powerful evidence of associations between adverse effects and long-term exposure, if the exposure is well characterized and potential bias and confounding factors are well controlled. Indicators calculated in these studies, e. g. the relative risk (RR) for cohort studies as ratio between the occurrence of an event in the exposed group and in the non-exposed group, or the odds ratio (OR) for case-control studies as equivalent of the RR in case of rare diseases, can be used to derive HBM-GVs. Clinical trials and case reports may be considered as supporting evidence in a weight of evidence approach (ANSES, 2014). Meta-analysis, which consist in a statistical analysis of data collected in separate but similar studies, lead to the estimation of the magnitude of an effect and the associated confidence interval.
Second option: HBM-GV derivation based on a defined external toxicity reference value or on a defined occupational exposure limit If human data are not sufficient and/or not adequate for deriving an HBM-GV, then a toxicologically justified external exposure guidance value (toxicity reference value -TRV) proposed by a European or relevant non-European institution (e. g. TDI, OEL, see also Table  1  und 2) can be translated into a corresponding HBM-GV. This approach has been previously proposed by  Hays et al. (2007 Hays et al. ( , 2008) )  through the setting of BEs and also by the German HBM Commission with a variant for deriving HBM-I values  (HBM Commission, 2007; Angerer et al. , 2011)  (see also Fig. 1 ). The date of the value's establishment, the critical effect underlying the setting of the value, the POD and the AFs determine the TRV selection for the HBM-GV derivation.
This is a hint to check the database also for other population groups and to revise the default values assumed for the daily urinary flow rate per kg body weight, where necessary. The concentration of a substance in urine will depend on the rate of urine production, but also e. g. on the hydration status or the fluid loss via perspiration. Therefore, correction of results based on creatinine concentration or urine density (specific gravity) may be necessary to compensate for the state of dilution and for variability related to the person's age and weight  (Viau et al. , 2004). However, the creatinine adjustment approach does not achieve a complete compensation for different volumes of excretion per time  (Barr et al. , 2005; HBM Commission, 2005)  and is not necessarily adequate for substances that are not following the urinary excretion pattern of creatinine.
g. the duration of exposure or the workload  (ANSES, 2014). If adequate data are available, the translation of an OEL to a corresponding concentration of the selected biomarker(s) is also possible by using TK modelling (compartment model, PBTK model), whereby uncertainties have to be assessed in individual cases. In any case, a thorough understanding of the toxicokinetics of a chemical, for which different routes of exposure contribute to the overall exposure, is necessary to derive a reasonable HBM-GV Worker (e. g. Ougier et al. , 2020 submitted). The selection of (one or more) specific, traceable biomarker(s) of exposure is a crucial step for deriving HBM-GV Worker and the TK and toxicodynamic parameters of potential biomarker(s) in biological media determine the most appropriate sampling times.
Third option: Derivation based on a critical effect observed in experimental animal studies If the database on the substance of concern does not allow the derivation of an HBM-GV based on the two previous options, a third option consists in extrapolating a critical dose (POD) identified in a key animal study into a human internal concentration of a selected biomarker, thereby applying default AFs to account for uncertainties in the extrapolation process and whenever available toxicokinetic data and models to reduce uncertainty. This approach, which includes different variants, is also part of the concepts developed by  Hays et al. (2007 Hays et al. ( , 2008) )  and by the German HBM Commission  (HBM Commission, 2014; Apel et al. , 2017). The variant via a "TRV-like" value (see Fig. 1 ) follows acknowledged rules for toxicological data assessment, as required for example under the REACH procedure  (ECHA, 2012).
g. on absorption, first-pass effect etc. ) is required. Generally, differences in the toxicokinetics between routes will be taken into account when deriving HBM-GVs. Selecting a key study also requires the assessment of the study quality, which is related e. g. to the method used, the reporting of the results and the conclusions that are drawn. Elaborated tools providing comprehensive criteria and guidance for reliability evaluations of toxicological data are available, as e. g. the software-based "ToxRTool" (Toxicological data Reliability Assessment Tool) developed by the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM;  Schneider et al. , 2009)  and the Science in Risk Assessment and Policy (SciRAP) web-based platform  (Beronius et al. , 2018). For the choice of the POD, the dose-effect curve, the toxicological mechanisms as well as the severity and type of effect are to be taken into account.
Level of confidence attributed to the derived HBM-GVs An overall level of confidence is attributed to each derived HBM-GV aiming to reflect the uncertainties related to its derivation. Therefore, the individual criteria described below are assessed and given a high, medium or low confidence level (or their intermediates). By equally combining the confidence levels of each individual criteria, an overall level of confidence is set and described in detail in the respective substance dossier. The option chosen for deriving the HBM-GV will directly influence the overall level of confidence attributed: as human data are considered more reliable over animal studies, HBM-GVs derived by option 1 will have higher levels of confidence than HBM-GVs derived by option 2 or 3. Even if guidance is provided here below to assess the reliability of the data and of the calculation method, levels of confidence are relying on expert judgment.
Results and discussion The growing availability of European HBM data generated within the HBM4EU program according to standardized methods, allows in principle for conducting health risk assessments based on the measured aggregated internal exposures. However, for the broader use of HBM data in health risk assessment, it is regarded necessary to develop scientifically sound health-related HBM-GVs at EU and/or global level (e. g. WHO, FAO), preferably with at least some regulatory recognition  (Louro et al. , 2019). Such kind of health-related assessment values (BEs from Summit Toxicology and Health Canada or HBM values from the German HBM Commission) are already available for a variety of substances such as metals and trace elements, plasticizers, flame retardants or active substances in crop protection agents; they also have been used for the screening of national population data, whereby for instance chemical-specific hazard quotients and/or cancer risk estimates were constituted to support prioritization and risk management efforts  (Aylward et al.
Acknowledgement This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, and received co-funding from the author's organisations. The authors thank all other participants that contributed to this work. ) Molar mass: symbol M, is a physical property characteristic of a given substance (chemical element or chemical compound), namely its mass per amount of substance [g/mol] 8) Identification of the selected biomarker(s): type of biomarker (exposure or effect biomarker(s)), specificity 9) Molar mass of biomarker(s) 10) Half-life of selected biomarker(s): excretion half-life of the biomarker(s) in the selected biological matrix, in hours or years (indication of the underlying TK study providing the data) 11) Factor for metabolic conversion (F ue ): in case of urinary biomarker(s), fraction of the biomarker(s) excreted compared to the total dose of the parent compound absorbed (indication of the underlying TK study providing the data) 12) Derivation method selected: either option 1 (internal dose-effect relationship from human study/studies) or option 2 (existing TRV) or option 3 (animal POD) 13) Key study, Authors, Year: name, authors and year of publication of selected key study/studies (for option 2: key study underlying the selected TRV derivation) 14) Species 15) Type of study: route of exposure (oral, dermal or inhalation study) 16) Study length: duration of the human or animal study 17) Exposure duration: exposure conditions in hours per day and days per week 18) Critical endpoint: selected critical adverse effect observed in the study and used for derivation of the HBM-GV ("either the adverse effect that first appears in the dose response curve, or an effect known to be a precursor of the first adverse effect") 19) Point of departure (POD): the dose corresponding to a given effect.
A fully ac FBBA with harmonic modulation of the magnet to be centered was proved for the first time at ALBA by centering the beam into skew quadrupoles, which are trim coils mounted on the main sextupoles and feature ac capabilities. Besides the fact of being an even faster operation, this analysis aligns automatically also the sextupole magnets onto which the skew quadrupole coils are installed, with benefits to the machine optics. A fast acquisition archiver (FA) providing synchronous BPM data at 10 kHz rate originally developed at Diamond  [11]  was installed in ALBA  [12]  and other synchrotron light sources since 2011. OCMs can be then excited in parallel in both planes and at different frequencies. The motion induced by any steerer in each plane can be isolated and analyzed separately from the harmonic analysis of FA data during the OCM modulation by looking at the spectral peaks generated at those (known) frequencies.
Even though FA data contain position data synchronized among all 120 BPMs, this is not the case for the ac OCMs. Their currents are either not archived (as in the case of ALBA) or not suitable for conversion into strengths, also their calibration factors are frequency-dependent and not known a priori. This requires some preliminary mathematical gymnastics of the original BBA formulas to remove any dependence of the observables on the OCM strength. The formalism developed to this end accounts also for the presence of an arbitrarily large betatron coupling, OCM tilt, and BPM roll. The paper is structured as follows: the FBBA is presented in Sec. II. In Sec. III the experimental set-up is described. The error analysis based on the alignment tolerances and the expected accuracy are evaluated in Sec.
B. Multi-frequency and dual-plane ac excitation The analysis presented in the previous section does not depend on the frequency of the ac OCM excitation. In order to fully exploit the ac nature of this approach and to speed up the overall measurement, quadrupole offset in both planes can be obtained in a single measurement by a simultaneous excitation of horizontal and vertical OCMs at different frequencies. The FA data stream will contain the beam response to both excitations, and so a Fourier analysis can be performed to decouple the two responses. In Eq. (2) the y l ðtÞ signal contains the orbit response both from the dc OCM strength and the (not observable) ac OCM excitation v j ðtÞ. When the beam is excited by two OCMs (horizontal and vertical) at different frequencies, both dc and ac originated components need to be isolated and summed up before applying the method described in the previous section.
V. FBBA METHOD VALIDATION In this section experimental results with the different FBBA methods introduced in Sec. II are presented. In Sec. VA offsets measured via the standard quadrupole BBA are compared to the ones obtained via the novel FBBA, ignoring betatron coupling in the latter. In Sec. V B, the impact of the corrections included in the FBBA to account for coupling is evaluated on the same data sets. Finally in Sec. V C, outcomes from the skew quadrupole FBBA via dc and ac excitation are examined. The ALBA storage ring comprises 32 combinedfunction-bending magnets, 112 quadrupoles, 32 skew quadrupoles, 88 OCMs per plane and 120 BPMs. Both FBBA and BBA aim to align the 120 BPMs (or a subgroup in the case of the skew quadrupoles) to their neighboring magnets. Even though each BPM has at least one quadrupole next to it, there are some quadrupole triplets with no BPM in between.
VI. CONCLUSIONS We have developed a new method (called fast beam based alignment-FBBA) to align the beam through the center of the storage ring quadrupoles by using an ac excitation of the OCMs and the 10 kHz BPM data acquisition-a standard hardware in most synchrotron light sources. The mathematical treatment presented in this paper allows to perform dual plane BBA (horizontal and vertical), includes betatron coupling, BPM roll and OCM tilt effects, and extends this method to both normal and skew quadrupole magnets. With a careful choice of the experimental setup parameters, the technique speeds up the BBA at ALBA by about a factor 30 (10 min vs 5 hours), and reaches the same level of precision. Furthermore and as shown for the case of the skew quadrupole magnets, the method could still gain a factor two in speed if the quadrupoles could be excited with an ac modulation.
, 2010). PtdIspn is not detectable when trophozoites are cultured in 8 mM of L-cysteine, used in standard culture medium  (Husain et al. , 2010). The phospholipid alteration is reflected in changes in membrane integrity and fluidity, which may affect protein translocation across the plasma membrane  (Husain et al. , 2010). Enzymes involved in Kennedy pathway are reported in the E. histolytica genome in KEGG database: ethanolamine kinase (EHI_148580), ethanolamine phosphate-cytidyl-transferase (EHI_095120) and ethanolamine phosphotransferase (EHI_045570) (Table  3 ). In addition, the hypothetical genes for the alternative routes involving sphingolipids (SL) metabolism are also present in the E. histolytica genome. Sphingolipids metabolism is related to the PC and PE synthesis. First, sphingomyelin (SM) is catabolized by sphingomyelinases (SMA) to produce phosphocholine, which follows the Kennedy pathway  (Gulati et al.
, 2007). Then, G3P is dephosphorylated to form PG by PGP phosphatase. PG could be transformed into its LBPA isomer by the action of transacylases and phospholipases  (Hullin-Matsuda et al. , 2007; Vance, 2015). The synthesis pathway of LBPA in E. histolytica is unknown. We have not found in the genome database the enzymes involved in the conversion of PGP to PG. However, the amoebic enzymes lysophospholipid acyltransferases (EHI_086180) and a putative 1-acyl-glycerol-3-phosphate acyltransferase (EHI_155730) are located in the KEGG database. As in other cases, experimental results will elucidate whether these enzymes are involved in LBPA synthesis in the parasite, as it happens in mammals. On the other hand, in other eukaryotes, PG can also receive an additional phosphatidyl group to form the cardiolipin (CL) by the CL synthases action  (Gohil et al.
(ii) Then, ceramide synthase (Cer S) acylates dihydrosphingosine, forming dihydroceramide, which is desaturated to ceramide  (van Meer and Holthuis, 2000). (iii) Finally, ceramides are transported to Golgi to be transformed in complex SL by SL synthase  (van Meer and Holthuis, 2000). Ceramides are different in mammals, plants, fungi and protozoa, thus, SL synthases are not the same in all eukaryotes  (Merrill, 2011). In mammals, there is only one enzyme known as SM synthase  (Merrill, 2011). Plants, fungi, and protozoa have other, called ceramide inositol phosphoryl ceramide (IPC) synthase  (Holthuis and Menon, 2014; Mina and Denny, 2018). IPC has not been identified in E. histolytica and we did not find it in KEGG data base. Acid sphingomyelinases (ASM) are enzymes that participate in the ceramides synthesis, by the hydrolysis of long chain SM  (Kitatani et al.
Endolysosome vesicles possess Niemann-Pick type C1 and C2 proteins (NPC1 and NPC2), which bind and transport cholesterol and SL to the cellular organelles  (Davies, 2000). Alteration of these proteins causes the Niemann Pick diseases in humans. E. histolytica needs cholesterol and phospholipids to carry out the biosynthesis of internal and plasma membranes and for other functions. However, the parasite is unable to synthesize cholesterol  (Das et al. , 2002). Trophozoites take this lipid from the milieu in cultured cells and from the intestine and liver cells of live organisms  (Bansal et al. , 2005; Serrano-Luna et al. , 2010). According to the KEGG database, Homo sapiens has 25 enzymes for the sterols biosynthesis, D. discoideum 18, and A. castellani 21. In contrast, E. histolytica does not present any.
CONCLUDING REMARKS Lipids are essential in cellular processes and pathogenesis of E. histolytica. Lipid metabolic characterization in this parasite has been growing using complex technologies approaches: Genomes databases, gene silencing, transcriptomic, and proteomic analysis are giving important information about the enzymes and metabolites in parasite during infection. In this review, we took advantage of the available data to analyze the current knowledge of lipids in E. histolytica. This protozoan has a particular lipid composition. Its differences with mammals provide excellent targets for diagnosis and vaccine strategies that, up to date, have been poorly explored. E. histolytica has 27 putative enzymes involved in the lipid metabolic pathways, reported in KEGG database, the majority poorly studied.
Laurenius and colleagues reported a modified use of the Sigstad's score, at 15-min intervals during an OGTT, and the area under the curve distinguished patients with or without symptoms of dumping syndrome after RYGB  66. Whether this method was superior to the classic score was not reported; in addition, no diagnostic cut-offs were identified. Taking these findings together, the Sigstad's score correctly identifies a substantial group of patients with dumping syndrome after all types of surgeries; however, there are insufficient data to compare the diagnostic efficacy of Sigstad's scoring system after bariatric surgery versus cancer or peptic ulcer surgery. In the dumping severity score developed by Arts and colleagues, symptoms of early and late dumping syndrome (which have eight and six symptoms, respectively) are scored on a four-point Likert scale 17 (box 2).
nature. com/nrendo e v i d e n c e -B a s e d g u i d e l i n e s and below. From an extensive database analysis, the majority of hypoglycaemia episodes above 3. 5 mmol/l remained asymptomatic, and it was concluded that values between 3. 5 mmol/l and 4. 0 mmol/l are probably of minor importance, and that a cut-off of 3. 4 mmol/l (54 mg/dl) is appropriate in the setting of patients with diabetes mellitus treated with insulin  77. Ambulatory glycaemia monitoring studies used lower cut-off levels for hypoglycaemia (3. 1 mmol/l and even 2. 2 mmol/l), but no consensus is currently reached on thresholds  78. The 2. 2 mmol/l threshold was proposed as this level of hypoglycaemia leads to notable and sustained cognitive impairment (from the UK Hypoglycaemia Study Group)  79. In summary, no consensus on the glucose concentration that defines hypoglycaemia is available from the literature (either literature on dumping syndrome or the broader literature).
DIC has been used for the study of asphalt concretes cracking behavior  [32]  and rarely for the study of interfaces  [33]. It has proved to be a consistent tool in the study of deformations of many materials such as cement concrete  [34, 35] , glass  [36]  or metals  [37]. For 3D DIC, two pictures of the same surface taken from different angles are needed at each state of deformation. An algorithm between the two pictures associates a spatial position to any pixel of the images. Displacements in the three dimensions are found using the correlation algorithm between reference and deformed states on one image of each pair  [38]. The Vic-3D ® software developed by Correlated Solutions is used for 3D DIC measurements in the 2T3C HCA. It computes displacements in the three dimensions on the hollow cylinder surface and expresses them in the cylindrical coordinate system related to the hollow cylinder (ur, uθ, uz, Z being the axis of the cylinder).
| Pre-treatment of future temperature data Because temperature-related parameters (Table  1 ) were retrieved from both observation-based (i. e. for the contemporary period) and GCMbased data (i. e. for the three future periods), our projections may be altered. To assess possible bias, we performed Taylor diagrams  (Taylor, 2001 ) using a common time period  (i. e. 2006-2017)  to estimate the consistency between current and future climate data (Supplementary Material 2): the correlation coefficient, the root-mean-square difference (RMSD) and the standard deviation (SD) difference were calculated for each temperature-related parameter (Table  1 ). For each GCMs, RCPs, and geographical cell, we therefore estimated the difference between the two datasets and corrected the model-based temperature data accordingly.
Material and Methods The study is based on data collected within the framework of a survey of NATURA 2000 sites and species organised and financed by the State Forests National Forest Holding in the years 2006-2007. The survey was connected with Poland's accession the EU and implementation of legal regulation on species and habitat conservation. The survey covered all forest districts in Poland and was conducted and supervised by a group of specialists affiliated to Polish universities or conservation organizations. The body of data was submitted to the authors of this paper for corroboration and analysis. This information was verified and confirmed during field work in later years (up to 2018). The data were combined with the information contained in the "Bank Danych o Lasach" database  23.