dataesr/scientific-paragraphs-categorization huggingface dataset:
Protein sequence analyses. Sequence analyses were carried out on a database representing all Actinobacteria diversity present at the National Center for Biotechnology (NCBI) as of February 2021, containing 133 taxa (five species per class). To identify OdhA homologs, the jackhmmer tool from the HMMER package (v3. 3. 2) 53 was employed, using the GenBank 54 sequence BAB98522. 1 as the query. The hits were aligned with mafft (v7. 475)  55  accurate option linsi. The MSA was manually curated, removing sequences that did not align. A sequence logo of OdhA was created based on the MSA through the online tool WebLogo3 56. The secondary structure of protein OdhA was mapped on the MSA using the online tool ESPript 57. Centre: cartoon overview of the OdhA Δ97 homohexamer (one colour per chain), with the single protomers related by crystallographic symmetry.
Laterally, in anticlockwise sense, detailed views of: E2o-E1o interface, with surface highligthed for the E2o domain (arrow pointing to the short α-helix between residues Glu296-Leu302; see also Suppl. Fig. 4 ); E1o catalytic site at the protomer interface, the ThDP-Mg 2+ cofactor at the centre; E1o allosteric acetyl-CoA binding site; E2o CoASH binding site. Indicated in the gure and depicted as sticks are the side chains of either signi cant residues interacting with cofactor or ligands through hydrogen bonds, salt bridges or van der Waals interactions, or, in the case of the E1o catalytic site, with a predicted role in catalysis (namaly His543, His583, His747 and His1017, as reported for MsKGD 18 ). Resolution limits were determined by applying an anisotropic cut-off via STARANISO, part of the autoPROC data processing software  39  ; values in parentheses refer to the highest resolution shell.
Acknowledgements This work was funded by the  ANR  projects  SUPERCPLX  ( ANR-13-JSV8-0003 ) and  METACTINO  ( ANR-18-CE92-0003 ), both granted to M. B. , and by institutional funds from the  Institut Pasteur  and the  CNRS. We are grateful to the core facilities at the  Institut Pasteur C2RT (Centre for Technological Resources and Research)  and their respective staff, namely to  A. Haouz ,  P. Weber  and  C. Pissis  for performing crystallization screenings,  B. Raynal ,  S. Brûlé  and  S. Hoos  for their assistance in analytical ultracentrifugation and buffer optimization,  P. England  for his help with surface plasmon resonance experiments,  J. -M. Winter ,  S. Tachon  and  M. Vos  for assistance with EM data collection. We are also grateful to  N. Barilone ,  I. Miras  and  P. Vilela  for their initial work in plasmid generation and protein expression, and to  A.
Bezault ,  G. Péhau-Arnaudet  and  C. Rapisarda  for their help in grid preparation and EM data collection. We acknowledge the synchrotron sources Soleil ( Saint-Aubin, France ), and  ESRF (Grenoble, France)  for granting access to their facilities, and their respective staff for helpful assistance, in particular  E. Kandiah  for performing EM data collection on CM01 (ESRF). The  NanoImaging Core at Institut Pasteur  was created with the help of a grant from the  French Government 's ' Investissements d'Avenir' program  ( EQUIPEX CACSICE ,  ANR-11-EQPX-0008 ), and is acknowledged for support with cryo-EM sample preparation, image acquisition and analysis. L. Y. and A. B. have both been affiliated to the  Pasteur -Paris University (PPU)   International PhD program ; L. Y. was funded by the  Wuhan Institute of Biological Products Co.
| Background There are no prospective data supporting endoscopic resection of colonic NET and data here are taken from published case reports, small retrospective case series and extrapolation of data from larger databases. Our prior dogma was that NETs involving the colon are more aggressive than rectal NET and are felt to present at a later stage with metastases to regional lymph nodes. With this in mind, surgical resection with regional lymphadenectomy as in adenocarcinoma has been considered the mainstay of treatment. However, vs. 52% in 2016). 12 [26]  Techniques such as en bloc endoscopic submucosal dissection (ESD) resections or using devices to achieve full thickness resection have also been described, but only limited data are available. 27, 28 commendation: Endoscopic resection may be appropriate in selected cases for small (usually 10 mm of less) colonic NET G1.
Since there are little useful data on follow-up, discussion at a dedicated multidisciplinary team (MDT) post resection is warranted to decide on follow-up or further resection on a case-by-case basis. trends In all other cases as well as after incomplete endoscopic resection (R1), surgical resection is recommended. Level of evidence/grade of recommendation: Level 4 grade C. 0] [31] [32] [33]  An analysis of the national cancer database (NCDB) cohort of 17,448 rNET identified an incidence of lymph node metastasis of 2. 5% for tumours ≤10 mm versus 12. 8% for tumours 11-20 mm. 34 Another study evaluating 788 patients from the SEER database with T1 rNET reported an incidence of lymph node metastases of 1. 1% for tumours ≤10 mm versus 6. 6% in tumours 11-20 mm. 33  another study with 132 rectal NET ≤10 mm, the mean rate of lymph node metastases was 3% ranging from 0% in tumours ≤6 mm to 10.
Level of evidence/grade of recommendation: Level 4 grade C. Concerning distant metastases, the liver is the most common metastatic site (58%) followed by bone (9. 4%), mesentery, peritoneum (8. 4%) and lung (8%). 35 As for metastatic lymph nodes, the tumour size is the major parameter for the risk of developing distant non-nodal metastases. Data from a large American cohort of 3880 patients from the National Cancer Database (NCDB) showed that the optimal cut-off of tumour size for the presence of distant metastases was 11. 5 mm with an incidence of distant metastases reported at 13. 8% in tumours ≥11. 5 mm. 41 milar to other digestive NEN, abdominopelvic CT and  68   42  The role of PET-CT is mainly to assess the presence of metastatic spread or to assess eligibility/usefulness of subsequent treatment lines in metastatic disease.
| Which systemic treatments should be selected in patients with metastatic colonic and rectal NET? in the surufatinib group (HR 0. 33; p <. 0001). 69 A phase III trial of cabozantinib is running in the USA (NCT03375320). Recommendation: TKI may be used in patients with colorectal NET after failure of better-established treatment options (everolimus, PRRT, locoregional treatments), ideally within a clinical trial. More data are needed to define the role of TKIs in colorectal NET. Level of evidence/grade of recommendation for TKIs in colorectal NET: Level 2b (low quality randomised trials available including a small subcohort of colorectal NET), grade B.
| UNMET NEEDS AND FUTURE PERSPECTIVES As illustrated by the low levels of evidence for the recommendations in our guidance paper, colorectal NET is an under-researched area. There is still a lack of predictive markers that could be used for treatment decisions. First retrospective data report high response rates to PRRT in metastatic well-differentiated rectal NET (see above). 84 At the time of writing two international studies (NCT 03972488 and NCT 04919226) will analyse the efficacy of first line PRRT in NET G2 / G3. Hopefully, reports will include information on the subcohort of rectal NET patients. With the WHO classification 2019, the subgroup of NET G3 has been introduced also for gastrointestinal NET. 6 Most available data for NET G3 focus on pancreatic NET G3 and the best treatment approach for colorectal NET G3 is unclear.
ACKNOWLEDGMENTS We thank the members of the ENETS office for their support. The authors of this ENETS guidance paper are grateful to the  ENETS Advisory Board  members for their useful suggestions and comments in a common effort to improve the quality of the present manuscript. Following colleagues were participants of the ENETS guidance paper consensus meeting 13 October 2022:  Bartsch ,  D. K. ( Department of Visceral-, Thoracic-and Vascular Surgery Philipps-University Marburg, Marburg, Germany); Begum N. (Department for General-, Visceral-, Thoracic-and Endocrine Surgery, Johannes-Wesling-Klinikum Minden, University Hospital of the Ruhr-University Bochum, Germany ); Capdevila,  J. ( Medical Oncology Department, Gastrointestinal and Endocrine Unit, Vall d'Hebron University Hospital, Barcelona, Spain ); Caplin,  M.
Whereas most proteins with a RNB domain are acti v e nucleases, some have lost a catalytic activity during evolution but remain indirectly involved in RNA metabolism  ( 14 ). Database searches re v ealed the presence of another RNB domain-containing protein encoded by the human genome: HELZ2 (Helicase with Zinc Finger 2, also known as PDIP-1 or PRIC285). The presence of a RNB domain in HELZ2 has been o verlook ed in most studies involving this protein, possibly because of the emphasis given to its helicase and zinc finger domains in its HELZ2 acronym. Interestingly, howe v er, e xpression of HELZ2 has been shown to be induced by interferon in mammalian cells  ( 15 ) , a property conserved in fish cells  ( 16 )  as well as zebrafish embryo  ( 17 ). In agreement, mimicking a viral infection by transfecting RNA or double-stranded DNA in mouse embryonic fibroblasts also induces HELZ2 mRNA expression  ( 18 ).
These phenotypes have been explained by central leptin resistance and by the increase in leptin receptor mRNA in the li v er of the mutant mice, leading to a decrease in lipogenesis as well as an increase in fatty acid oxidation. To study the molecular contribution of HELZ2 to these processes, we decided to characterize the organization and activities of the human protein. Detailed analyses uncovered that human HELZ2 is longer than the sequence currently listed in databases as it is translated from a non-canonical start codon. Analysis of the full-length HELZ2 sequence re v ealed various domains including se v eral copies of tw o types of Zn fingers and tw o helicase domains, in addition to the RNB domain. Biochemical analyses demonstrate that, despite the presence of a non-consensus residue at a critical position of its RNB acti v e site, HELZ2 is an acti v e 3 -5 e xonuclease, in agreement with data from a recent study  ( 27 ).
Mass spectrometry data analysis Proteins were identified by database searching using Se-questHT (Thermo Fisher Scientific) with Proteome Discover er 2. 5 softwar e (PD2. 5, Thermo Fisher Scientific) on human FASTA database downloaded from UniProt (re vie wed, release 2022 10 27, 20607 entries, https://www. uniprot. org/ ). Precursor and fragment mass tolerances were set at 7 ppm and 0. 02 Da respecti v ely, and up to 2 missed cleavages were allowed. For all the da ta, oxida tion (M, +15. 995 Da) was set as variable modification, and Carbamidomethyla tion (C , + 57. 021 Da) as fixed modification. Peptides and proteins were filtered with a false discovery ra te (FDR) a t 1%. Label-free quantifica tion was based on the extracted ion chromato gra phy intensity of the peptides and realized with Perseus 1.
6. 15. 0 (Max Planck Institute of Biochemistry). Biological triplicates were analyzed. The measured extracted ion chromatogram (XIC) intensities were normalized based on median intensities of the entire dataset to correct minor loading differences. For statistical tests, not detectable intensity values were treated with an imputation method, where the missing values were replaced by random values similar to the 10% of the lowest intensity values present in the entir e dataset. Unpair ed twotailed t -tests, assuming equal variance, were performed on obtained log 2 XIC intensities.
Altogether, these results indicate that the GUG codon at position 152 can be used for translation initiation. We subsequently refer to the isoform initiated at this site as 'full-length HELZ2' and to the sequence present in full-length HELZ2 but absent from HELZ2 ␤ as 'extension'. To establish whether HELZ2 translation initiates in vivo from the GUG codon at position 152, we performed mass spectrometry e xperiments. Interferon-responsi v e HeLa cells were used for tandem mass spectrometry analyses using as r efer ence the human proteome present in the UniProt database completed by the sequence of the predicted extension. Biological triplicates of HeLa cells with and without interferon tr eatment wer e tested. Neither the HELZ2 ␤ nor the extension sequences were detected in cells growing in the absence of interferon.
Domain organization of human HELZ2 Database searches and multiple sequence alignments re v eal that human HELZ2 has a modular structure (Figure  1 A ). Full-length human HELZ2 contains six Zn finger or Zn finger-like domains at its N-terminus. These appear to be of both C2H2 and CCCH types. Some Zn fingers depart from the corresponding consensus but their characteristics, the alternating positioning of the two types, and the conservation of this arrangement in related proteins support these assignments (Supplementary Figure  S3 ). The 1st, 3rd and 5th Zn fingers are distantly related to C2H2 domains that have been found in a number of proteins involved in RNA metabolism  ( 36 , 37 ). Some of them were proposed to mediate interaction with double-stranded RNA. The alternating Zn fingers are of the CCCH family known to bind singlestranded RNA in a sequence-specific manner  ( 38 ).
The presence of a RNB domain prompted us to analyze the organization and function of the HELZ2 human protein. Careful compilation of available evidences, including transcript mapping data, ribosome profiling results, and comparati v e genomics suggested that the human HELZ2 protein contained a conserved N-terminal extension not annotated in current databases and that its translation initia tes a t a non-canonical GUG codon. This possibility was confirmed e xperimentally. Gi v en this observation, it will be worth reinvestigating whether the previously described HELZ2 ␣ and HELZ2 ␤ isoforms are also expressed, and if so the biological relevance of the different isoforms. Transla tion initia tion a t GUG codon has been r eported pr eviously in human cells for viral mRNAs as well as for specific cellular mRNAs such as DAP5 / eIF4G2  (48) (49) (50).
ACKNOWLEDGEMENTS We acknowledge members of our team for support and suggestions. We also thank them and  Dr P. Reilly  for critical reading of the manuscript. We are grateful to  Dr. T. Tomaru  for the gift of the p3XFLAG-CMV 7. 1 HELZ2 ␤ plasmid. Support of IGBMC platforms, particularly the Imaging and Mediaprep facilities, is greatly appreciated. Authors contributions : Experimental design, E. H. and B. S. ; initial experiments J. S. ; experiments realization E. H. ; mass spectrometry analyses, B. M. ; writing of original draft, E. H. and B. S. ; manuscript re vie wing, E. H. , J. S. , B. M. , B. S. ; funding and project supervision, B. S. FUNDING Ligue Contre le Cancer  ( Equipe Labellis ée 2020 ) [to B. S. ];  Projet IdEx  Exploratoire 2021 [to B. S. ];  Interdisciplinary Thematic Institute IMCBio , as part of the  ITI 2021-2028 program  of the  Uni v ersity of Strasbourg ,  CNRS  and  Inserm , was supported by  IdEx Unistra  [ ANR-10-IDEX-0002 ];  SFRI-STRAT ' US  project [ ANR 20-SFRI-0012 ];  EUR IMCBio  [ ANR-17-EURE-0023 ] under the framework of the Plan France 2030.
Corrections The extracted raw yields of Σ(1385) ± are normalized to the number of events of the corresponding centrality class and corrected for the detector acceptance (A), the reconstruction efficiency (ε rec ) and the branching ratio (BR)  [4]. The detector acceptance and reconstruction efficiency (called efficiency) are determined from a Monte Carlo simulation based on the HIJING event generator  [26]. The Σ(1385) ± signals are injected with a flat p T distribution in the range 0-10 GeV/c 2 into HIJING events. The generated particles and their decay products are propagated through the detector material using GEANT3 as transport code  [27]. The same criteria are applied to select the resonance decay products and the pairs as for the data analysis. The product A × ε rec ×BR is calculated as the fraction of the generated Σ(1385) ± at midrapidity, reconstructed and identified after the application of all selection criteria.
Estimation of pathogenic Leptospira spp. shedding load and shedding time Pathogenic leptospire cell counts were estimated according to the genome equivalent principle  [8]  based on the concentration of pathogenic leptospire DNA (from cows with positive qPCR results). The concentration was measured in a Nanoquant spectrophotometer (TECAN group, Männedorf, Schweiz) adjusted for a 10 8 dilution and the number of copies of the lipL32 target gene. The genome of L. interrogans serovar Hardjo (type Hardjo-Prajitno) was used as the reference of molecular weight (GenBank accession number EU357983. 1) and with it a standard curve was established to estimate the pathogenic leptospire numbers in the sample by a Roche 2. 0 real-time PCR system, according to a published equation  [8]. The estimated total shedding load (Tshed) for each cow was calculated by adding all samples leading to positive qPCR, the product of each urinary load times the number of elimination days, which was calculated as the number of days elapsed between two successive samplings.
Statistical analysis Descriptive statistics were used to summarize the main parameters. The cow was used as the experimental unit of analysis; however, animals were clustered by farm, therefore this dataset had some amount of hierarchical structure (cow within-farm), therefore, farm was included in the models as a random effect. A mixed negative binomial regression model accounting for non-negative integers as counts was used to assess differences in total shedding load (Tshed) between shedding patterns, age of the animals and vaccination status. The farm where the animal belonged was used as a random effect in the model. Random effects were used to model many sources of variation as well as subject-specific effects, avoiding biased inference on fixed effects. We also used an accelerate-to-failure time (AFT) model to assess how the TsheTi could differ between patterns.
For the AFT model, we checked several distributions (Exponential, Weibull, log-normal, log-logistic, Gompertz, gamma and generalized-gamma) and the generalized-gamma distribution was the one with the lower AIC and BIC indices, indicating the best fit. A P-value of 0. 05 was used as the threshold for a statistical significance of the differences. All statistics for the negative binomial regression mixed-model were calculated using R's lme4 package  [14]. For the AFT model, the package flexsurv was used for the calculations (V2. 1). All data and statistical analysis were processed using R software (version 9. 3) [15].
Mastcam Mastcam, or MCAM, is a pair of cameras on Curiosity's remote sensing mast (RSM), designed for monocular and stereo imaging of the mid-and far-field  [37, 38]. The Mastcam cameras each have a filter wheel, so they can acquire visual color images, and images in 12 narrow spectral bands. The multispectral image capability is described below. Mastcam images and reduced data are available in the NASA Planetary Data System (PDS) Analyst's Notebook (https://an. rsl. wustl. edu/msl/mslbrowser/an3. aspx, accessed on 7 July 2023).
APXS The APXS instrument is an X-ray fluorescence spectrometer, located on the end of Curiosity's arm. The APXS is similar in operation to those on the MER rovers  [41] [42] [43]  and can analyze for the major rock-forming elements (Na through Fe), and some trace elements of higher atomic numbers. O'Connell-Cooper, et al. [44]  describe its operation and some results for the Glen Torridon region. APXS provides bulk chemical analyses from its field of view, which is nominally a ~2 cm diameter circle on a rock or soil surface. APXS data are available in the PDS (https://an. rsl. wustl. edu/msl/mslbrowser/an3. aspx, accessed 7 July 2023). Many diagenetic features in Glen Torridon (and elsewhere in Gale Crater) are smaller than 2 cm in extent, so the APXS team developed a procedure to calculate elemental compositions of such smaller features  [43].
CheMin The CheMin instrument is an X-ray diffractometer, housed inside the body of the Curiosity rover. CheMin generates a collimated beam of CoKα X-rays, which is transmitted through a cell that contains powdered rock (or regolith), delivered by the drill assembly  [36, 61, 62]. Diffracted and fluoresced X-rays are detected by a charge-coupled device (CCD) imager, with data collection and readout timed so that very few CCD pixels receive more than one X-ray in a collection. Each such data collection yields a raw frame, a two-dimensional image of X-ray hits with the X-ray energy for each hit. Groups of raw frames are co-added on the rover to produce minor frames, which are all downlinked to Earth. Raw frames can be downlinked by explicit commands. Data returned for each frame (raw or minor) includes an image of diffracted X-ray hits (i.
As with the CheMin diffraction data, fluorescence histograms from all minor frames are typically co-added to produce a major frame histogram. CheMin data are available in the ODR repository (https://odr. io/chemin) and the NASA PDS (https://an. rsl. wustl. edu/msl/mslbrowser/an3. aspx, both accessed 7 July 2023). The Groken drill sample was acquired on mission sol 2910, and delivered to CheMin on sol 2912. The sample was analyzed in CheMin over four nights (sols 2912, 2914, 2922, and 2930), yielding a total of 60 minor frames of analyses (30 h of analysis). Refined cell parameters for plagioclase, c and the angle γ  [63] , were used to adjust the sample cell to detector distance calibration by -122 µm. CCD temperatures during data collection were near -50 • C. On the first three nights, the Groken sample vibrated in the normal intensity and pattern.
Mineral Stabilities Equilibrium mineral stabilities were calculated and graphed using Geochemists' Workbench © set of software tools  [69]  (GWB), and verified in some cases by manual calculations on spreadsheets. Graphs here are from the programs Act2 and Phase2. Act2 calculates stability diagrams, which show the most supersaturated solid (i. e. , greatest saturation index) or dominant aqueous ion which includes the target species for a given bulk elemental composition over a given range of pH and oxidation states. Phase2 calculates the equilibrium mineral assemblage for a given bulk elemental composition at the given pH and oxidation state. The thermochemical database of  [70]  was used for equilibrium calculations. That database is consistent with the recent work Mn-phosphates  [71]  and, for the most part, is consistent with the earlier compilation of  [72]  and yields results similar to those in other recent works  [45, 73].
Where thermochemical data for a phosphate mineral were not available, they were estimated using the ThermAp method  [74, 75] , which has been shown to yield adequately accurate values for many Mn-bearing minerals  [71]. Because we estimated phases other than apatites, we used the estimation parameters from  [71]. Please refer to the Supplementary Materials for specific thermochemical data and calculation methods applied here. Table  2  lists all the crystalline phases for which our thermochemical database gives solubility products. Several of these phases were not included in modeling because their solubility products imply far greater stability ranges than are known in comparable environments on Earth. For example, some compounds are predicted to be stable under Earth-surface conditions but are not known as minerals, e.
g. , Mn 2+ HPO 4 and Mn 2+ 3 (PO 4 ) 2. Others are predicted to be stable under a wide range of chemical conditions, like reddingite [Mn 2+  3 (PO 4 ) 2 •3H 2 O] and vivianite-Mn [Mn 2+ 3 (PO 4 ) 2 •8H 2 O] but are actually uncommon or rare in nature. A few others are not expected in low-temperature aqueous conditions (e. g. , hausmannite, Mn 2+ Mn 3+  2 O 4 , and jacobsite, Mn 2+ Fe 3+ 2 O 4 ). The calculated solubility products for laueite and strunzite are essentially identical (they differ only in degree of hydration, Table  2 ). These phases included in the database ThermoddemV1. 10_Groken. tdat (Supplementary Materials 2), augmented from that used by  [71].