dataesr/scientific-paragraphs-categorization huggingface dataset:
For instance, in quails sedated with 6 m/kg IM midazolam, the authors observed complete reversal following administration of 0. 1 mg/kg IM flumazenil in less than 2 min, without any resedation signs  [32]. The recovery of Pyrenean Capercaillies after the administration of flumazenil was not immediate. The administered flumazenil doses (ranging from 0. 06 to 0. 12 mg/kg) were very similar to those recommended for pet birds, i. e. , from 0. 01 to 0. 1 mg/kg  [43]. GPS positioning revealed that 13 individuals remained at the release site during an average time of approximately 18 h. Two birds remained at the release site until approached by a passer-by, 24 h post-capture. Such information was recorded after the GPS data analysis, once the birds had already moved away from the release site. Thus, one cannot affirm if this lack of movement occurred because the birds were not fully recovered yet or because they were unable to move normally after sedation.
Acknowledgments: Thank you to the Ministerio para la transición Ecológica y el  Reto Demográfico ,  Forestal Catalana ,  Paisatges Vius ,  Elena Vega ,  Carles Juan Sallés (Noah's Path), Parc Natural de l'Alt Pirineu, Agents de Miei Ambient, Cos d'Agents Rurals and Centre Tecnològic Forestal de Catalunya  for their administrative and technical support and collaboration in the Pyrenean Capercaillies captures and follow-up. We thank the reviewers for their comments and editions.
European Registry on H. pylori Management The Hp-EuReg is an international multicenter prospective non-interventional registry founded in 2013 and promoted by the European Helicobacter and Microbiota Study Group (www. helicobacter. org) that started in 2013. The Hp-EuReg protocol was approved by the Ethics Committee of La Princesa University Hospital (Madrid, Spain)  [13]  and was registered at ClinicalTrials. gov with code NCT02328131. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a prior approval by the institution's human research committee. Country selection criteria, national coordinators, and further details on the variables collected (including demographics, comorbidity, data on infection and diagnosis, previous eradication attempts, current treatment, compliance, adverse events (AEs) and effectiveness) are reported in the published protocol  [13].
Data Collection Data were collected in an electronic case report form (e-CRF), using the collaborative platform Research Electronic Data Capture (REDCap) hosted at "Asociación Española de Gastroenterología" (AEG; www. aegastro. es) [14]. All personal data were anonymized. Written, informed consent was obtained from each patient included in the study. All patients registered until June 2021 were included in the present analysis.
This is a key factor that has been associated with higher cure rates [2,30]. However, despite the fact that HDDT shows better tolerance than other recommended therapies in the different studies, better compliance was not necessarily reported  [8, 9, 11, 29]. In fact, one of the network meta-analyses places HDDT in the worst place in terms of compliance compared to bismuth-based, concomitant, and sequential quadruple therapies. HDDT is last in compliance in both total patients and in the Asian population sub-analysis  [27]. Our results and conclusions are based on data in the Hp-EuReg, a multicenter prospective registry that reflects routine clinical practice. The 60 patients included in our study, mostly registered in Spain, were treated with 3 g of amoxicillin per day divided into three doses, and most of them, plus a high-dose PPI regimen  [15, 16] , also distributed in three doses for 14 days.
Institutional Review Board Statement: The Hp-EuReg protocol was approved by the Ethics Committee of La Princesa University Hospital (Madrid, Spain)  [13]  and was registered at ClinicalTrials. gov with code NCT02328131. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a prior approval by the institution's human research committee. Informed Consent Statement: Written, informed consent was obtained from each patient included in the study.
| Data collection and selection Our analyses focused on age-and sex-specific variation in adult body mass from age 18 onwards to omit the phase during which elephants grow in height  (Mumby et al. , 2015)  and to focus only on adult body mass age-specific variations. We compiled a total of 3886 body mass measurements on 493 individuals (2570 body masses on 322 females, and 1316 body masses on 171 males). These data came from two sources: (i) body masses were either measured on elephants on the field or (ii) estimated using height to the shoulder and chest girth (method in Supplementary Information 1 and following  Chapman et al. , 2016). For the first source, we collected 1901 body masses of 347 elephants (1297 measurements on 230 females and 604 measurements on 117 males) and for the second source, we estimated 1,985 body masses on 342 individuals (1273 estimations on 226 females and 712 estimations on 116 males-a same individual can have both measured and estimated body masses).
| Statistical analyses We investigated the age-and sex-specific variation in body mass in R version 4. 1. 1 (R Core Team, 2021), using the body mass (logtransformed to reach normality of the variable and because of the allometric relationship between body mass and size) as a dependent variable with a normal error distribution. First, we tested in a single model, whether there were sex-specific ageing trajectories using an interaction term (Table  S2 ). Given that this interaction was statistically significant, we compared the sex-specific ageing trajectories for both sexes separately. We did these analyses using both general linear mixed models (GLMMs) and general additive mixed models (GAMMs) with cubic regression splines (but note that other spline functions gave similar conclusions as those shown here) using the functions "lmer" of the package "lme4" (v.
1. 1-27. 1, Bates et al. , 2015)  and "gamm" of the package "mgcv"  (v. 1. 8-36, Wood, 2011) , respectively. GAMMs allow more flexible ageing trajectories than GLMMs, but the more constrained ageing trajectories in GLMMs allow a more precise identification of differences in ageing trajectories (Figure  S1 ), and both approaches gave consistent conclusions (see results section). We identified the best-fitting models using the model selection approach based on the second-order Akaike Information Criterion (AICc) as implemented in the package "MuMIn"  (v. 1. 43. 17, Bartoń, 2021). In brief, the best-fitting model has the lowest AICc value, with other models within 7 ΔAICc being plausible and models becoming increasingly equivocal up to 14 ΔAICc, after which they become implausible  (Burnham et al.
We mean-centred and standardized "Δage" so that (i) individuals measured once all get a Δage = 0 and hence contribute to the variance of the Δage intercept but not to its slope and (ii) to avoid collinearity and to have comparable variance for Δage and Δage²  (Bolker, 2008; Zuur et al. , 2009). Among the 493 individuals of our data set, 105 individuals had only one measurement. We included these individuals by giving them Δage = 0 (i. e. mean-centred), so they do not contribute to the coefficient but contribute to the variance along the Y axis on Δage = 0, diminishing the likelihood of a false positive and contribute to the coefficient of the age at last measurement term, thereby avoiding a bias in the dataset from selecting only the longer-lived or most monitored individuals.
| Testing ageing trajectories We tested several within-individual ageing trajectories, first using GAMMs, which can provide curvilinear relationships and allow to describe trends, and using GLMMs, able to detect breaking points if necessary, by testing linear, quadratic, threshold and terminal models (Figure  S1 ), and we selected the ageing trajectory with the lowest AICc. For GAMMs, we identified the age at which maxima occurred based on the first-order derivative (= 0) using the function "fderiv" of the package "gratia" (v. 0. 6. 0, Simpson & Singmann, 2021). For threshold models (Figure  S1C ), we followed the approaches previously developed in  Briga et al. , (2019)  and  Douhard et al. , (2017). In brief, we first identified the best-fitting threshold age in a series of models, varying the threshold in the "Δage" term between -35 and 22 years with intervals of one Δage (a unit of the mean-centred Δage = 4.
| Accounting for temporal and spatial variation in body mass As body mass variation can be influenced by seasonal, spatial and within-individual factors, we tested whether body mass values were affected by (i) whether they were measured or estimated, (ii) whether individuals were alive or dead at the time of the analyses, (iii) whether individuals were captive-or wild-born, and (iv) the season during measurement. To this end, we used a model selection approach, using the function "dredge" of the package "MuMIn" (v. 1. 43. 17, Bartoń, 2021)  on the best-fitting ageing trajectories for each sex to test for confounding factors (Table  S3 ). In our models, we included as random intercepts individual identity to account for the repeated measurement of the same individual. We also included "township" to account for the spatial clustering of individuals across Myanmar, although actually adding township worsened the model fit in most cases (male GLMM: ΔAICc = +1.
Note 2: the original x-axis is Δage, but for simplicity, we presented here the x-axis as age. For the original figure, please see Figure  S2  differed between the sexes: whilst males began to lose mass from 48. 3 years old onwards, females lost body mass generally at an older age, namely in their last year of life. Compared with a previous study on growth curves of this population  (Mumby et al. , 2015) , we are now using a larger dataset, including older and a larger number of retired individuals. This allowed us to evidence body mass ageing in this species, which was not possible until now. Here, we discuss the implications of our results in the light of the classical theory of ageing  (Williams, 1957)  and of the management of Asian elephants. To the best of our knowledge, we describe for the first time a sex-specific pattern of body mass ageing in this species.
We found that females experienced a terminal body mass decline in the last year of life. Our data contain both males and females among the oldest ages (>50), hence sex-specific terminal decline is unlikely to emerge from differences in lifespan. In European badgers, a species in which females outlive males, both sexes displayed terminal body mass declines  (Beirne et al. , 2015). We evaluated the possibility that sex-specific ageing trajectories result from differences in sample sizes. For males, our post-peak data (starting at Δage = 1. 9, equivalent to an age of 48 years old) contain 47 observations on 14 individuals. For females, the dataset after a peak at the same age (Δage = 1. 4) contains 191 observations on 35 individuals. Thus, as is often the case in ageing studies, the sample sizes at older ages are relatively small, which is a limitation.
Literature review A systematic review of the literature that was in compliance with the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) was conducted for PSFB management in the MEDLINE, EMBASE, Scopus, and Web of Science databases. 6 Broad search strategies for "fungus ball" and all related terms in association with paranasal sinuses, nose, and related terms, were used on December 2, 2021 to look for studies in English, Italian, German, French, or Spanish that reported data obtained from human subjects. Supporting Information 1 reports the search strategies for all queried databases. Due to a lack of high-quality studies on the topic, the systematic review was extended from what had been originally been recommended for CCSs 5 (ie, guidelines and systematic reviews) to include all original studies published on the topic, with the exclusion of case reports and non-original articles (such as narrative reviews).
Histology and morphometric analysis of the liver and intestinal inflammatory granulomas A portion of each animal's right liver lobe and ileum was immersed in 10% formaldehyde prepared in phosphate-buffered saline (PBS). After dehydration in successive ethanol baths (50˚C to 100˚C) and xylene, tissue samples were paraffin-embedded. Five micrometer thick sections were stained with hematoxylin and eosin (H&E) for qualitative analysis of the liver and the granulomatous inflammatory reaction evaluation. The second set of slides was stained with picrosirius (PS) to highlight liver and ileal fibrosis characterized by collagen deposition around granuloma. Images were acquired at x10 and x20 using CMOS Digital Camera (IDS, Germany) connected to an optical microscope (Axiophot, Zeiss, Germany) and analyzed by PathScan Touch software (Excilone, France).
For quantitative measurement of liver and intestine granulomas, images were captured with an x10 objective at an x10 ocular magnification with a digital camera AmScope MD 500 (AmScope, USA) connected to a wild-type optical microscope and analyzed with Ima-geJ 1. 32 software (NIH, USA). All granulomas containing a single central egg with miracidia were selected for each mouse. Granulomas in which it was possible to observe more than one egg or granulomas in which the egg was not visible or destroyed were excluded from the analysis. The number of granulomas, as well as their volume, were determined. All granulomas per mouse were measured using the largest diameter and perpendicular diameter. The volume of each granuloma was calculated assuming a spherical shape using the following formula: V ¼ 4ðp � R 3 Þ 3 The radius R was obtained by dividing the main diameter of the lesion by two.
Serum levels of cytokines According to the manufacturer's recommendations, we used the mouse ProtocartaPlex 10-plex immunoassay kit (Thermofisher Scientific, Vienna, Austria) to measure cytokine levels in serum samples. We classified the immune mediators into five categories: proinflammatory mediator (Monocyte Chemoattractant Protein [MCP]-1), type 1 cytokines (IL-2, interferon [IFN]γ, and tumor necrosis factor [TNF]-α), type 2 cytokines (IL-4, IL-5, IL-10, and IL-13), a T helper 17 cytokine (IL-17), and a regulatory cytokine (Transforming Growth Factor [TGF]-β1). Data were acquired on the MAGPIX-Luminex XMAP technology (Merck Millipore, Darmstadt, Germany) using the Luminex XPONENT software solutions. The concentration (pg/mL) of each cytokine was obtained by interpolating MFI (median fluorescent intensity) of a dilution standard curve over seven dilution points supplied with the kit and calculated by the ProtocartaPlex Analyst 1.
Data are expressed as mean ± SEM (n = 6). ANOVA followed by Tukey multiple comparison test was also used for statistical analysis. ## p < 0. 01: values are significantly different from those uninfected mice (group HC). � p < 0. 05, �� p < 0. 001: values are significantly different from those of infected-untreated mice (group IC). α p < 0. 05, αα p < 0. 01: values are significantly different from those of infected mice treated with PZQ3 posology (group PZQ3). https://doi. org/10. 1371/journal. pntd. 0010382. g011 The gene expression of cytokines and chemokines involved in the immune response against schistosomiasis was evaluated in infected mice's livers. After 5 weeks of infection, the only significant difference was observed for MIP-1α, where infection led to a marked increase in mRNA levels, essentially reversed by PZQ3 treatment.
Standard curves were constructed with DNA from representative species of a concentration range of 10 2 -10 10 DNA copies per mL using 384-well plates in the Lightcycler R 480 instrument II (Applied Biosystems, Carlsbad, CA, USA). The microbial DNA extracted from the fecal samples and specific DNA from recombinant microbiota were quantified by RT-PCR. Reaction conditions were at 50 • C for 2 min, an initial denaturation step at 95 • C for 5 min, and then 20 s denaturation at 94 • C for 40 cycles, primer annealing at a species-specific temperature for 30 s, and primer extension at 60 • C for 1 min  (19). The specific primers for RT-PCR were synthesized by Sangon Biotech (Shanghai) Co. , Ltd. Data were analyzed using the Roche Lightcycler 480 software 1. 5. 0. Microbiota quantities were expressed as a logarithm of the number of microbe copies contained per gram of samples [lg (copies/g)].
Statistical Analyses Statistical data analysis was performed with one-way ANOVA using SPSS 18. 0 software (SPSS, Inc, Chicago, IL, USA). Levene's test for homogeneity of variance was used, followed by Duncan's multiple-range test (in the case of variance homogeneity). Values are expressed as means ± standard error (SE). P-values < 0. 05 were taken to indicate statistical significance, with a trend toward significance at 0. 05 ≤ P < 0. 10.
Furthermore, while international regulatory authorities (e. g. , at OECD level) have used predictive capacity as a key indication of whether a NAM is relevant and acceptable over the past 20 years, the predictive capacity has usually been determined through comparison to results from traditional animal test methods, for which reproducibility and human biological relevance were often assumed rather than empirically demonstrated. Additionally, many regulatory data requirements were written to be fulfilled by test methods available at the time (i. e. , traditional animal test methods). These statutes have complicated gaining regulatory acceptance of NAMs that may not provide identical information to the traditional animal test methods, even if the information provided by the NAMs may in fact be more human relevant and health protective.
Technical characterization Technical characterization of NAMs is conducted to ensure a NAM is high quality and robust. Below, we examine relevant considerations of technical characterization, namely the evaluation of accuracy, reproducibility, transferability (where applicable), applicability domain, associated reference chemicals and controls, and limits of detection and quantification. Some of these points have been recently discussed for the assessment of inhalation toxicity NAMs in  Petersen et al (2021a, b)  and, more recently and with a broader applicability, in  Petersen et al. (2022). The authors published a framework to add measurement quality features to in vitro and in chemico NAMs (including conceptual evaluation of the assay, intra-laboratory evaluation, statistical data analysis and reporting, and, on a case-by-case basis, inter-laboratory evaluation), to ensure that sources of variability are identified and mitigated  (Petersen et al.
• Traditional animal test method reproducibility can be used to derive confidence intervals that provide performance benchmarks for NAMs. If a NAM is compared to a traditional animal test method result, the NAM prediction falling within the data-driven confidence interval around the animal result would be considered to be concordant with the animal result. When the reference test method is demonstrated to have a low degree of reproducibility, the category assignments based on those results may be close to arbitrary for some chemicals. • When the accuracy of a NAM is determined by a comparison to existing data, it should be clarified whether it was compared to human (the gold standard) data or animal data. Use of publicly accessible curated databases allows for further assessments of reproducibility of traditional animal test methods, including the evaluation of statistical variability and the limits of detection  (Browne et al.
Reproducibility and transferability Reproducibility is the measurement of how closely results of a particular method agree when repeated using the same protocol and same substance (OECD 2005). To assess the reproducibility of a method, it may not always be necessary to perform an exhaustive assessment of inter-laboratory reproducibility, i. e. , a ring trial. It may be preferable, depending on the NAM and whether the NAM will be performed in more than one location, to assess reproducibility solely through the conduct of intra-laboratory reproducibility testing. The intra-laboratory reproducibility of a NAM should not be expected to exceed the reproducibility of the traditional animal test method, when the reproducibility of the animal method is known. While the reproducibility of the animal test method may be useful in identifying performance benchmarks for the NAM when the data exist, the advancement of NAMs should not be delayed if the reproducibility of the animal test method is unknown.
Uncertainties Uncertainty refers to all types of limitations on the available knowledge that may affect the range and probability of possible answers to an assessment question  (Benford et al. 2018). Uncertainties related to the data and methodological quality include limitations associated with the method's biological relevance, reproducibility, and completeness or comprehensiveness of the data (OECD 2020). To minimize these uncertainties, guidance on GIVIMP has been developed by the OECD (OECD 2018) to demonstrate best practices for execution and reporting. Other uncertainties are associated with the interpretation, extrapolation, and integration of data from the test method, and includes inter-or intra-species uncertainty factors, in vitro to human extrapolation, and gaps in knowledge of the endpoint of concern.
e. , coming from either dried previous diarrhea or normal crusted feces). Ocular secretions were noted as absent, serous (epiphora), or purulent (crusted or purulent). Nasal secretions were assessed for the presence or absence of purulent secretion. Ear position was assessed and defined as positive in case of bilateral ear droop. Evaluation of this scoring chart reliability was performed between the different operators performing the tests in a pilot study on a large local dairy farm and in auction market setting after training with 1 senior clinician with extensive experience on calf health (SB). A total of 19 calves were screened by 8 different persons during 2 training sessions although the auction data collection was mostly performed by 4 raters. With the exception of ear drop (0. 31), the percentage of agreement varied between 0.
ACKNOWLEDGMENTS This project was a specific addendum to a larger project supported by Programme de développement sectorial du Québec-Canada, the Producteurs de bovins du Québec (Longueuil, QC, Canada), and MITACS (Ottawa, ON, Canada). The authors also thank Réseau Encan Québec (QC, Canada) for their willingness to participate in the study, Jean-Philippe Pelletier, Nicolas Barbeau-Grégoire (St-Hyacinthe, QC, Canada) and  :1, 1:2; 1:5, 2:1, 5:1) in different colored lines. Different prevalence of calves <9 d old are presented using the original dataset (prevalence = 35%; panel A), then using a prevalence of 50% (panel B) obtained from downsampling the calves ≥9 d old and prevalence of 5% (panel C) and 20% (panel D) using internal resampling. Specific optimal decision thresholds at 0. 25, 0. 50, and 0.
This would allow bypassing the operator-dependent and time-consuming analyses that are necessary for the quantitative and qualitative studies of USVs. This challenge was successfully faced by de Chaumont et al. in this special issue, as they developed one open-access software to automatically study mouse USVs. Their system also allowed coupling the spectrographic analysis of USVs with the automatic labeling of several behaviors scored over a long timeperiod (i. e. , 3 days), thus providing an additional evaluation of the behavioral value of USVs in laboratory mice. The method was validated in C57BL/6J mice and also in mutants lacking the Shank3 gene, i. e. , a mouse model of autism, in both sexes and at multiple ages. Also Goussha et al. developed a new software, the HybridMouse, that is an audio analysis tool for automatically identifying, labeling, and extracting recorded USVs.