dataesr/scientific-paragraphs-categorization huggingface dataset:
Indirect methods combining NMR, partial acid hydrolysis, acetylation, methylation, SEC-MALLS and enzymatic hydrolysis are used to provide structural information enabling the reconstruction of an average structure. In parallel, the number of solved 3D structures of GH70 family enzymes, which remains low, should increase. These multi-domain enzymes remain difficult to crystallize especially in complex with large size oligosaccharides but with the rapid development of cryoelectron microscopy, we may have access in the near future to more informative highresolution images of GH70 enzymes bound to longer polysaccharide structures, even during the polymerization reaction. Feeding the databases with new 3D structures of BRS and high molar mass dextran forming dextransucrases will certainly give new insights on structural determinants controlling enzyme activity and specificity.
, 2002). A cut was made from the duodenum opening to the oesophageal opening exposing the stomach interior. Stripping of the longitudinal and circular muscle was done under a ZEISS Stemi DV4 stereomicroscope with a blunted watchmaker #5 tweezers. Tissue mucosae were mounted in the Ussing chambers with a circular diameter area of 0. 63 cm 2 , attached to circulation reservoirs and bathed bilaterally with 5 ml KH at pH 7. 4  (Fattah et al. , 2020). The system was maintained at 37 • C and gassed with 95% O 2 /5% CO 2. To determine tissue viability in chambers over time, electrical parameters were recorded using a Voltage Clamp system  (Fattah et al. , 2020). Analogue signals were digitized with a PowerlabⓇ data acquisition unit and analyzed with LabChartⓇ (v8. 1. 8 2017) software from AD Instruments (UK), thereby allowing transepithelial electrical resistance (TEER, Ω.
In the presence of 20 mM and 40 mM SNAC, the P app value of both markers trended higher compared to control. On the contrary, 30 mM C 10 induced 2. 4-fold and a 3. 2-fold statistical increases in the P app values of FD4 and [ 14 C]-mannitol respectively (Fig. 2B, D ). These data are summarized in Table  1. Overall, C 10 was more efficacious than SNAC at similar concentrations in jejunal mucosae. Histological analysis was carried out following 120 min exposure to SNAC and C 10 on jejunal tissue mucosae (Fig. 2D ). In control tissue, mostly normal morphological features were observed with an intact epithelium and some mucus production. The overall structure of the submucosa appeared intact, but the tissue lacked definition. Mild histological damage was observed following exposure to SNAC and C 10.
Rheology of porcine small intestinal mucus exposed to SNAC and C Rheological studies were then carried out using porcine small intestinal mucus exposed to SNAC or C 10. First, the linear viscoelastic C. Twarog et al. region (LVR) of the intestinal porcine mucus was determined (Suppl. Fig. 1 ). Across the strain range (0. 01-10%) the predominance of elastic behavior (G') over viscous behavior (G'') indicated gel-like character. As a consequence, a constant strain of 1% corresponding to a small deformation within the LVR was selected for the frequency sweep and viscosity ramp test. The change of mucus viscoelastic properties in terms of G', G", the complex modulus (G*), and the damping factor were then evaluated in the presence of both PEs. For control mucus, G' was consistently higher than G" by a factor of 4 across the frequency range, with no tendency to flow at low frequencies, consistent with previous data for porcine small intestinal mucus  (Nordgård and Draget, 2015).
Permeability experiments were also conducted in the rat non-everted jejunal and colonic gut sac models. This study confirmed that exposure of sac lumens to SNAC or C 10 in concentrations up to 100mM for 90 min led to permeation enhancement for FD4. There was no difference in efficacy, potency, and fold increases in FD4 flux between the PEs in sacs from either region, although basal flux and the absolute basolateral concentrations of the PE-induced fluxes were higher for jejunum. Overall, the sac studies supported most of the data obtained in isolated mucosae for the two PEs. We examined potential mucosal damage that could arise from SNAC and C 10 exposure across the different bioassays and found little difference. Qualitative morphological examinations of the gross histology in our study revealed only minor damage following exposure to both agents in ex vivo mucosae and sacs as well as in in situ jejunal instillations.
Sensory analysis techniques are important tools for product characterization, in developing and reformulating food products or in the definition of consumer preferences  (van Kleef et al. , 2006; Bruzzone et al. , 2015). Sensory profiles performed by trained assessors are used to describe precise qualities of a product. These data correlated with consumer preferences make it possible to explain and understand the dynamic of the hedonic appreciation of products. Nevertheless, other alternative methods can be considered to directly link consumer's perception and product characteristics. By using consumer opinions, it is possible to obtain a sensory description of the products and better understand consumer preferences  (Ares et al. , 2017; Caspia et al. , 2006; Drake et al. , 2009). For this reason, consumer tests often include, in addition to overall liking, supplementary questions such as attribute liking questions, intensity rating questions, open-ended questions or just-about-right questions about the product attributes.
Mineral water (Evian, France) and unsalted crackers were served to rinse the mouth during the test. Samples were coded using 3digit random numbers. Each sample was presented monadically according to a Latin square design at an individual booth. Five samples were analysed per one-hour session. Two replicates of each cheese sample were evaluated by each panelist. All tests took place in individual sensory booths designed in accordance with ISO 8589  (ISO, 2007)  and the room temperature was controlled at 21 ± 1°C. Data acquisition for the sensory profile was carried out using Tastel software (ABT Informatique, Rouvroy-sur-Marne, France).
Hedonic test A total of one hundred and fifty-two consumers were recruited to participate in this study. They were recruited from previous databases and by e-mail. They were selected according to their consumption of any type of raw milk cheese, more specifically Cantal, Salers and Laguiole and to their ages (adults over 18 years old). The tests were carried out at home because the initial protocol had to be adapted due to the Covid19 sanitary crisis. It consisted of two tasting sessions at the participants' homes according to a defined protocol. Firstly, each participant selected for consumer tests picked up a bag containing: ten anonymized cheese samples of 100g (wrapped in aluminum foil and labelled with three-code numbers), an information sheet with the tasting instructions and two questionnaires called Sensory questionnaire and Survey questionnaire.
ACKNOWLEDGMENTS This work was funded by  FEADER  and the  Regional council Auvergne-Rhône-Alpes in the framework of Rural Development Program (RDP)  for the project entitled " Innovation Fromagère pour Tradition Salers ". The authors thank the collaboration of different experts who took part in the study: the  Tradition Salers association  for supplying cheese samples, René Lavigne and  René Magneval  (cheese-making practice experts) and  Annick Lebecque  (sensory analysis expert). The authors thank also the sensory panel and consumers for their participation.
A B C his parents identified a de novo heterozygous nonsense mutation (c. 6037C>T p. Q2013X) in the SPTB gene. This gene encodes a member of the spectrin family, involved in the stability of erythrocytes membranes. Mutations in this gene have been associated with hereditary spherocytosis and hemolytic anemia. 5 While most symptoms of the proband were consistent with hereditary spherocytosis, the non-regenerative anemia, together with the presence of ring sideroblasts and extra-hematological signs remained unexplained, suggesting that additional mutations were involved in his phenotype. According to this hypothesis, we identified in the proband two compound heterozygous missense variants (c. 1031 G>A p. R344Q and c. 1205 G>A p. R402H) in the SARS2 gene (cDNA accession number: NM_017827. 4, transcript ID: ENST00000221431), each inherited from one of two parents.
SARS2 is an ubiquitously expressed nuclear gene encoding a mitochondrial aminoacyl-tRNA synthetase (mt-aaRS) whose function is to catalyze the specific ligation of serine to two mitochondrial tRNA isoacceptors: tRNA Ser(AGY) and tRNA Ser(UCN). 6 Both SARS2 variants were reported to be rare in public human genetic variant databases (GnomAD_exomes MAF: T=0. 000012 and T=0. 000008 respectively). As they affect highly conserved amino acid residues located in the core catalytic domain of the protein and are predicted to be damaging by in silico softwares, biallelic SARS2 mutations identified in the proband were very likely to result in loss-of function. Sanger validation of the mutations in SPTB and SARS2 are shown in the Online Supplementary Figure  S1C  and Figure  1C. 8] [9]  Another SARS2 variant (homozygous splicing mutation in exon 14) was reported in a single case suffering from progressive spastic paresis instead of HUPRA syndrome,  10  in agreement with the known phenotypic heterogeneity of mutations involving mitochondrial machinery.
colin@hotmail. frdoi:10. 3324/haematol. 2021. 279138Received: May 11, 2021. Accepted: July 26, 2021. Pre-published: August 19, 2021. Disclosures: no conflicts of interest to disclose. Contributions: EC, OH and LC designed the study; HT, ML-L, MdM, LDC and RS were responsible for patient management and collection of clinical and laboratory data; MR conducted histopathological analyses; EC, GC and JP designed experiments; EC performed experiments; EC and LC analyzed data and co-wrote the manuscript. All the authors reviewed the manuscript and approved the final version. Funding: this study was supported by grants from  Laboratory of Excellence GR-Ex , reference  ANR-11-LABX-0051. The labex GR-Ex is funded by the  IdEx program  " Investissements d'avenir " of the  French National Research Agency , reference  ANR-18-IDEX-0001.
Patient identification All medical records of patients listed for LT alone or combined (liver-kidney, liver-heart) in the Liver Transplant program of Pitié-Salpêtrière University Hospital, Paris, France, were prospectively collected in an institutional digital database since 2003. The whole cohort of 1704 patients was regularly followed-up as per our local protocols. We identified the nested cohort of adult patients who had undergone simultaneous SLKT from 1st January 2003 to 31st December 2018. Patients who underwent sequential liver or kidney transplantation (in other words, during two different surgical interventions with an in-between interval longer than 24 h) were excluded. In addition, any SLKT patients who lacked cross-sectional imaging two months before, or one week after SLKT were also excluded.
Patients were seen weekly during the first postoperative month, twice a month during the second month and then once every month for the first 6 months. The outpatient clinic consultation included blood and urinary testing as well as any imaging (Doppler ultrasound, CT or MRI) if clinically indicated. All data involving the patient's post-operative course such as complications, re-hospitalisation, primary disease recurrence or deaths were also collected. The follow-up duration was life-long.
Secondary outcomes We compared sarcopenic and non-sarcopenic patients in terms of the impact on patient and graft (liver and kidney) survival, on the infection rate and infection-free survival. Curves for each outcome were plotted by the same Kaplan-Meier method and compared by using the log-rank test. Given the small sample size, no imputation method was used. All variables with p < 0. 05 were considered statistically significant. We performed two-tailed analyses of all data. Analyses were performed with R software (3. 6. 1; www. cran. r-project. org, Vienna, Austria). The study was designed in March 2019. Data collection was done from March to June 2019. From July to August 2019, we performed all data analyses. The reporting of this study is based on the STROBE Statement and guidelines  [19].
Sarcopenia data and outcomes In our study, 9. 3% (n = 4) of patients were defined as underweight (body mass index; BMI < 18. 5 kg/m 2 ). The median TPA of all patients was 1138 (926-1510) ± mm 2. Sarcopenia was observed in 72% of patients (n = 31). Besides BMI and TPA, no other clinical or biological differences were observed between the sarcopenic and non-sarcopenic groups (Table  1 ). After SLKT, the overall rate of postoperative complications was 65. 6%. However, there was no difference in post-operative complication-free survival at 6 months: 50% (95%CI: 0. 284-0. 880) vs. 53%, (95%CI: 0. 3791-0. 745) in the sarcopenia vs. non-sarcopenia groups, respectively (p = 0. 61) (Fig. 2 ). The most common complications are summarized in Table  2   The overall rate of infections post-transplantation was 63%.
MS data processing After analyzing the spirit samples on the Q-Exactive Plus, Thermo RAW files were exported to the open source software package MZmine 2 (2. 38 version) for data processing  (Pluskal et al. , 2010). The protocol implemented includes five major steps: peak detection (mass detection), chromatogram builder, peak deconvolution, isotope suppression and peak list alignment. Each chromatogram was deconvoluted into individual chromatographic peaks with the "baseline cut-off" algorithm, which recognizes each chromatographic peak that has an intensity above a given minimum level (2. 10 3 ) and spans over a given minimum time range (0. 01-1. 00 min). Chromatograms were deisotoped using the isotopic peaks grouper algorithm with a m/z tolerance of 10 ppm and a RT tolerance of 0. 1 min.
Statistical analyses All the statistical analyses were carried out using the open-source software R Statistical (Foundation for Statistical Computing, Vienna, Austria). Results were interpreted by one-way analysis of variance (ANOVA), using vintage as factor. The values were previously transformed into logarithms in order to improve the homogeneity of the variances, a condition for applying the ANOVA. The normal distribution of the data was tested using the Shapiro-Wilk test. PCA was performed on normally distributed data. K-means clustering was also established for data classification (package ClassDiscovery). Pearson correlations were then carried out (α < 0. 05, correlation coefficient r greater than 0. 8) and allowed the creation of groups of compounds with a similar evolution depending on the vintages.
Centrifugal partition chromatography fractionation CPC was performed on a Spot prep II LC coupled with an SCPC-100 + 1000 (Armen Instrument, Saint-Avé, France), both controlled by Armen Glider Prep V5. 0 software. A 100-mL rotor (11 discs, 90 twin cells of 0. 101 mL per disc) was used to fractionate samples weighing less than 1 g and a 1-L rotor (21 discs, 72 twin cells of 0. 555 mL per disc) was employed for samples weighing more than 1 g. The solvent was pumped into the column by a 4-way quaternary high-pressure gradient pump. The samples were introduced into the CPC column via an automatic high-pressure injection valve. All the experiments were conducted at room temperature, with UV detection at 254 and 280 nm. The choice of an appropriate biphasic system of solvents was based on the study of the partition of extract compounds in both phases according to the procedure described by  Marchal et al.
NMR experiments NMR experiments were conducted on a Bruker UltraShield® System Avance 600 NMR, spectrometer ( 1 H at 600. 27 MHz and 13 C at 150. 95 MHz) equipped with a 5 mm TXI probe. All 1D (proton) and 2D ( 1 H-1 H COSY, 1 H-1 H ROESY, 1 H-13 C HSQC, and 1 H-13 C HMBC) spectra were acquired at 300 K in methanol-d 4 , which gave as reference the solvent signal ( 1 H δ 3. 31; 13 C δ 49. 00). Data analysis was performed with the NMRnotebook software (NMRTEC, Illkirch-Graffenstaden, France).
After the HPLC-HRMS analysis, the data were processed according to the metabolomic strategies implemented for the research of natural products  (Wolfender et al. , 2019) , with the use of MZmine 2 software. Thanks to these treatments, a peak list of 47,243 positive ions was obtained between m/z 100 and 1500, then filtered into a peak list of 1,293 ions having an associated data-dependent MS 2 spectrum. These results revealed the chemical diversity and complexity of cognac, which is consistent with previous studies on different spirits  (Kew et al. , 2017; Roullier-Gall et al. , 2020). The rest of this work was carried out on this set of ions. It is important to note that the data reduction essential for statistical analyses is also likely to cause data loss, which could constitute a major limitation to this type of approach.
Acknowledgements Delphine Winstel 's grant is supported by  Remy-Martin  and  Seguin-Moreau. Analytical techniques were funded by  Biolaffort. The authors are also grateful to  Dr. E. Frérot  for performing LC-MS/MS experiments. We thank  Dr. J. -C. Mathurin  and  Dr. L. Urruty  for providing samples and  Dr. Ray Cooke  for proofreading the manuscript.
Therefore, here, we evaluated changes in urine calcium levels in patients taking or not vitamin D supplementation during EBC treatment. Urinary calcium excretion is an important biomarker for understanding the phosphorus-calcium metabolism, and the 24-h urinary calcium excretion is routinely used to guide mineral supplementation in Europe  [19]. However, there was no data on this parameter during chemotherapy, thus limiting the generalization of high dose vitamin D supplementation in these patients. In the present study, we detected baseline hypercalciuria in 15% of patients, in agreement with data in the general population (10%)  [20]. Our results highlighted that hypercalciuria is frequent during chemotherapy (35%), but always clinically asymptomatic. The absence of symptoms might be due to the fact that urine calcium elevation in our patients was generally moderate, and clinical symptoms might appear only with chronic hypercalciuria (i.
Calcium urinary level was not assessed at 6 months after chemotherapy completion in our study. Almost all patients received sequential chemotherapy (anthracyclines and taxanes), associated with systematic corticosteroids. Nevertheless hypercalciuria occurred more frequently in patients receiving docetaxel (44%) than in those receiving paclitaxel (21. 4%), which might be explained by a higher cumulated dose of corticosteroids during the course of their treatment than in the paclitaxel group. Finally, dietary changes, including those associated with chemotherapy, have been reported to induce hypercalciuria  [22] [23] [24] [25] [26]. One limitation of the present study is the lack of dietary data from our patients during the study. Although hypercalciuria had no clinical impact in our patients, it remains a classical contra-indication to vitamin D supplementation, and therefore the identification of baseline variables associated with hypercalciuria occurrence could allow the selection of patients with low hypercalciuria risk for high dose vitamin D supplementation.
Methods A comprehensive ("non-systematic") review was performed. Five distinct literature searches (see Supplemental Data S1: Search Terms) for in vitro models, in vivo animal models, empirical and semi-mechanistic models, PBPK models and the effect of maternal conditions on the macro-nutrient composition of breast milk were performed searching PubMED between September 2019 and December 2019. In addition, Embase was searched for the in vitro and in vivo models. Articles were excluded if no full text was available or if they were not written in English. The selection of the articles for the in vitro models and PBPK models was performed using Rayyan  [3].
Garessus et al. [89]  used in vivo data, including an AUC based M/P ratio, obtained from literature. AUC based M/P ratios are preferred over single M/P ratios, since single M/P ratios vary over time. Some of the in vivo data were re-calculated to match their population. Partition coefficients were calculated according to an algorithm from Schmitt et al. [96] , which was also used by Partosch et al. [88]. Both Garessus et al. [89]  and Willmann et al. [86]  used adult clearance values fitted from in vivo data, whereas the neonatal clearances were in vivo values obtained from literature. Willmann et al. [86]  used a range of M/P ratios based on several in vivo values reported in literature for both morphine and codeine. Partosch et al. [88]  used physiological data from literature. In vivo clearance values were obtained from literature.
For ethambutol, the M/P ratio was based on two in vivo data pairs from literature. For rifampicin, an algorithm to estimate the M/P ratio was used, because it was not clear how the measurements were done for the sparse available in vivo data  [88]. Olagunju et al. [87]  used an in vivo M/P AUC ratio. They used anthropometric values to predict organ weight and blood flows based on a HIV positive cohort of breastfeeding women. For the maternal PBPK model, CYP450 abundances were taken from in vivo data. For the neonatal PBPK model, data from human liver microsomal samples were used.
Acknowledgements The research leading to these Results was conducted as part of the  ConcePTION consortium. This paper only reflects the personal views of the stated authors. The  ConcePTION  project has received funding from the  Innovative Medicines Initiative 2 Joint Undertaking  under grant agreement No  821520. This Joint Undertaking receives support from the  European Union 's  Horizon 2020 research and innovation programme and EFPIA. Figures were created with BioRender. com.
Data source and population This study uses data from the EPICE (Effective Perinatal Intensive Care in Europe) population-based cohort of births occurring between 22+0 and 31+6 weeks of gestation in 2011/2012 from 19 regions in 11 countries. 12 Perinatal and neonatal data until discharge home were abstracted from medical records using a common, predefined protocol. Data on the child's health, development and the family's social characteristics were collected using a parental questionnaire at 2 years of corrected age (CA). 13 untry teams obtained local ethical approvals and informed consent for the follow-up study; the European database was approved by French agencies governing use of health data in medical research (CCTIRSN°13. 020 and CNILN°DR-2013-194). The study population was children surviving to two years' CA and included in the followup.
5 μL of primers (0. 3125 M), 0. 3 μL of cDNA (1. 5 ng/μL) and Nuclease free water for a total volume reaction of 10 μL. All primers were designed and checked for optimal efficiency (>90%) in the qPCR reaction under our experimental conditions. The relative expression of each gene was calculated using the standard 2 -ΔCt method  [31] , normalized with respect to the average of β-ACTIN as internal housekeeping control gene. All reactions were performed in triplicate. qPCR was run on a CFX96® Thermo Cycler (BioRad, Hercules, CA, USA). We assessed that all qPCR reactions yielded only one amplification product using the melting curve method. We used the following primer pairs for different human gene transcripts validated by the National Center for Biotechnology Information (NCBI) Primer-Blast method.