dataesr/scientific-paragraphs-categorization huggingface dataset:
The relative abundance of P. copri was increased at return only in a fraction of travelers reporting diarrhea (Supplementary Figure  3B ). The results obtained for the samples collected at return from travel were also confirmed by 23S analyses (Supplementary Figure  2B-E ). Most Enterobacteriaceae members associated with diarrhea mapped to 23S genes of Escherichia-Shigella, while in the 16S analysis the discriminating OTUs from Enterobacteriaceae were not classified at the genus level. Clostridiales included genera belonging to Ruminococcaceae (Ruminococcus), Bacteroidaceae (Bacteroides) and Lachnospiraceae (Roseburia; only for 16S dataset: Lachnospira and Blautia). We then investigated whether diarrhea had protracted effects on gut bacteria composition one month after the return. Therefore, we analyzed samples from 17 travelers who did not take antibiotics during the first month following the return.
(b) Barplot reporting log10transformed LDA scores from each OTUs resulting significant (p-value < 0. 05) from LEfSe analyses on samples from travelers MRE positive (yellow) and MRE negative (blue) one month after the return. Only OTUs with an absolute value of LDA score (scaled in log10) of at least 2. 5 were retained for graphic representation. (c) PCoA plot showing the distribution of samples from time points of travelers MRE negative and MRE positive one month after return. PCO1 (12. 7%) and PCO2 (8%) represent the degrees of variance of each axis. Samples are grouped in clusters delimited by ellipses. Represented centroids (spheres) capture the origin of each ellipsis. (d) Bar plots reporting the averaged relative abundance (/100) of phyla detected by mapping to 16S Greengenes database in travelers MRE negative (n = 11) and MRE positive travelers (n = 6) one month after return.
Acknowledgments We are grateful to  Dr. María-José Gosalbes  ( Área Genómica y Salud, FISABIO-Salud pública, Valencia, Spain ),  Pr Andrés Moya  ( Cavanilles Institute on Biodiversity and Evolutionary Biology, University of Valencia, Spain ) and to  Anaïs Gondoin  ( SATT Ile de France, Paris, France ) for their assistance in this project. Again, we thank all the travelers, who agreed to participate in this study, and the personnel of the international vaccination centers.
Measures Genome-Wide Genotype Data The IMAGEN blood samples were genotyped using either Illumina Human610-Quad Beadchip or Illumina Human660-Quad Beadchip. After quality control, 466 114 singlenucleotide polymorphisms (SNPs) entered the following analysis. Details of the genotyping and quality control are available in a publication  22  and in eMethods 1 in the Supplement.
Structural Image Data Structural magnetic resonance imaging (MRI) was performed on 3-T scanners from 3 manufacturers (Siemens: 5 sites; Philips: 2 sites; and General Electric: 2 sites) following the Alzheimer's Disease Neuroimaging Initiative protocol modified for the IMAGEN study. All data were preprocessed in Statistical Parametric Mapping, version 8 using the Voxel-Based Morphometry, version 8 toolbox, including segmentation, normalization, modulation, and smoothing (eMethods 2 in the Supplement).
Brain Expression Quantitative Trait Loci Database In the UK Brain Expression Consortium (UKBEC  23  ) database, gene expression data are available for 10 brain regions from 134 neuropathologically free participants. For any vGWASidentified mutation on a gene, we first tested whether this SNP was associated with expression of this gene. Second, we went on to test whether such an association was tissue specific and whether this SNP also had cisregulations on expressions of nearby (±1 Mb) genes. For this extended exploration, we corrected for multiple comparisons between the number of nearby genes and the number of brain areas (eMethods 7 in the Supplement).
Summary-Databased Mendelian Randomization For the identified brain structure, we conducted summarydatabased Mendelian randomization (SMR) analysis by a webbased application (MR-Base  25  ; eMethods 10 in the Supplement). Using Psychiatric Genomics Consortium 2014 GWAS results for schizophrenia  26  as the outcome, we tested whether the association between the identified brain structure and schizophrenia was significant and free of nongenetic confounders. 27 A significant SMR result may suggest an association between the exposure (brain volume) and the outcome (schizophrenia) using the exposure-associated genetic variant as an instrument because the random nature of genetic variation mimics the design of randomized clinical trials. 25 Although significant SMR results require further biological validation, nonsignificant results at least indicate a lack of association.
Association of rs13107325 With Lower Expression Level of SLC39A8 in Putamen Using the expression quantitative trait loci (eQTL) database from the UKBEC (n = 134, with 112 CC genotypes, 22 CT genotypes, and 0 TT at the SNP rs13107325), we found that the carriers of the risk allele (T) at rs13107325 showed lower expression of SLC39A8 (t 127 = -3. 87; 95% CI, -6. 51 to -1. 73; P =. 0002) in the putamen (Figure  2A  and B ). Furthermore, we found that despite brainwide expression of SLC39A8 (Figure  2C ), this eQTL association was specific for the putamen and was not detected in any of the other brain regions (P <. 0008, Bonferroni correction for 10 types of brain tissues and 6 neighboring genes) (Figure  2D ). In addition to gene SLC39A8 (eTables 13 and 14 in the Supplement), we also found associations of rs13107325 with lower gene expressions of NF-κB1 in the hippocampus (t 120 = -3.
Second, the identified brain associations of the other SNP rs7182018 were more stable across the life span, but there is no evidence to our knowledge to date that it is involved in the pathology of schizophrenia. Third, the identified gene-level eQTL result did not reach a genome-wide significance level in the UKBEC database, and rs13107325 was not associated with expression of SLC39A8 in the GTEx (http:// www. gtexportal. org). This may be partially owing to differences in the sex ratio and racial/ethnic composition between these 2 databases. Furthermore, other levels (expression of exon, junction, and transcripts) of eQTL analyses should also be conducted in the future. Animal studies to test these possible molecular mechanisms are also warranted.
Downloaded From: https://jamanetwork. com/ on 07/10/2020 IMAGEMEND (602450;  Imaging Genetics for Mental Disorders ) and MATRICS ( 603016 ), the  Innovative Medicine Initiative Project EU-AIMS  ( 115300-2 ), the  Medical Research Council Grant Consortium on Vulnerability to Externalizing Disorders and Addictions  ( MR/N000390/1 ), the  Swedish Research Council FORMAS , the  Medical Research Council , the  National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Services Foundation Trust and King's College London , the  Bundesministeriumfür Bildung und Forschung  (grants  01GS08152 ;  01EV0711 ; eMED SysAlc01ZX1311A; and  Forschungsnetz AERIAL ), the  Deutsche Forschungsgemeinschaft  (grants  SM 80/7-1 ,  SM 80/7-2 , and  SFB 940/1 ). Further support was provided by grants from  Agence Nationale de la Recherche  (project  AF12-NEUR0008-01 -WM2NA , and  ANR-12-SAMA-0004 ), the  Fondation de France , the  Fondation pour la Recherche Médicale , the  Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA) , the  Assistance-Publique-Hôpitaux-de-Paris  and  Institut National de la Santé et de la Recherche Médicale  (interface grant),  Paris Sud University  IDEX 2012; the  National Institutes of Health, Science Foundation Ireland  ( 16/ERCD/3797 ),  Axon, Testosterone and Mental Health during Adolescence  ( RO1 MH085772-01A1 ), and by  National Institutes of Health Consortium  grant  U54 EB020403 , supported by a cross-National Institutes of Health alliance that funds big data to  Knowledge Centres of Excellence.
Several examples of beneficial compounds from mushrooms have found their way into exploratory drug research projects  (Grothe et al. 2011). In addition, the recent integration of TCM and modern medicine has begun to solve multiple worldwide health problems. Many databases were evaluated to advance scientific formulations, chemical analysis, potential approaches, and other health targets. The World Health Organization (WHO) has also released a standard series for developing traditional medicines across the world, including medicinal mushrooms  (Tang et al. 2018). The discovery of biologically active compounds from medicinal mushrooms can impact the direction of future medical development, and also has broad market prospects in North America, Europe and other developed economies  (Lee et al.
Agricultural waste disposal Agricultural waste, the residue from planting until harvest, generally contains a mixture of plant waste, animal/insect waste, and toxic residues from the chemicals used as pesticides, insecticides, and herbicides. Asia is one of the world's most agriculture-intensive areas: from 2010 to 2016, 46. 9% of emissions in Asia came from crop residue, compared to 28. 2% and 16. 2% from America and Europe, respectively. According to the FAOSTAT 2 emissions database, 90. 6% of rice produced within Asia generated more than a hundred million tons of residual material. This agricultural waste accounted for over 50% of the nitrous oxide generated from the decomposition of crop residue on cultivated soils, one of the main contributors of the greenhouse gas effect and a cause of global warming.
Functional genomics and the search for novel anti-invectives Functional genomics is the approach used to study functions and interactions of genes and their products in a specific context  (Liu et al. 2010a; Buza and McCarthy 2013). This requires sequencing of the entire genome. Sequencing techniques have come a long way, since the release of the first whole fungal genome of Saccharomyces cerevisiae  (Goffeau et al. 1996). Today the combining of newly arising techniques like PacBio with Illumina to provide fully closed genomes has led to numerous fungal genome databases, such as the fungal genome initiative  (Haas et al. 2011) , comprising over 100 fungal genomes, or FungiDB  (Stajich et al. 2012 ) and Ensembl Fungi  (Kersey et al. 2010)  with over 1000 fungal genomes. Out of many examples that target various product categories, we will here only give some examples on what is feasible now for the secondary metabolite biosynthesis due to the employment of-OMICS and bioinformatics tools and synthetic biotechnology.
Hyde and Naritsada Thongklang would like to thanks to Thailand research fund grants "Domestication and bioactive evaluation of Thai Hymenopellis, Oudemansiella, Xerula and Volvariella species (basidiomycetes)" (Grant No. DBG6180033). K. D. Hyde thanks the financial support from the Visiting Professor grant at Chiang Mai University, Thailand and KIB. The authors acknowledge the contribution of M. M. Vasanthakumari, K. M. Manasa and P. Rajani, in various stages of preparation of the manuscript. Samantha C. Karunarathna thanks CAS President's International Fellowship Initiative (PIFI) for funding his postdoctoral research (Number 2018PC0006), and the National Science Foundation. Associate Professor R Jeewon thanks University of Mauritius for support. Binu C. Samarakoon offers her sincere gratitude to the "National Research Council of Thailand" (NRCT Grant No.
Absence of guidance on how to develop, implement, and maintain such systems limits their widespread adoption. A framework to develop algorithms for semiautomated surveillance, applicable to routine care data and not requiring complex data-driven modeling, may facilitate the development of reliable algorithms implementable on a larger scale. In this observational, international multicenter cohort study, we assessed the performance and feasibility of such a framework for pre-emptive algorithm development for semiautomated surveillance (Fig. 1 ) applied to the surveillance of deep incisional and organ-space SSIs after hip and knee arthroplasty (THA and TKA), cardiac surgery, and colon surgery. In addition, we evaluated the generalizability of algorithms between hospitals.
Hospital and patient inclusion European hospitals participating in the CLIN-NET network  14  were recruited for this study. We considered only hospitals with longterm experience with manual SSI surveillance after THA and TKA and cardiac surgery, and (optionally) other surgical procedures, from 2012 onward. In each hospital, the feasibility of data extraction from the EHR for the same period was assessed. Dates of (re)admission and discharge, surgical records, microbiology results, and in-hospital mortality were the minimum requirements for participation. Optional data included demographics, antibiotic prescriptions, outpatient clinic visits, temperature, other vital signs, radiology ordering, clinical chemistry, and administrative data. Data collection was performed retrospectively between July 2017 and May 2019.
Automated surveillance framework The framework was applied to each hospital by the coordinating center (University Medical Center Utrecht, The Netherlands) and consisted of the following steps: Step 1: Inventory of local surveillance and clinical procedures and availability of electronic routine care data. Centers completed a questionnaire for each targeted procedure collecting information on (1) local surveillance procedures (ie, SSI definitions, selection of the surveillance population), (2) clinical procedures regarding standard of care and diagnostic and therapeutic practice in case of SSI suspicion, and (3) the availability of relevant electronically routine care data (see the supplementary material online: Questionnaire SSI Surveillance Methods). If needed, hospitals were contacted for a follow-up discussion.
Inclusion of hospitals and surveillance characteristics Initially, 4 hospitals were recruited. However, the required EHR data extraction for 1 hospital was not possible, and this hospital was Note. SSI, deep incisional or organ-space surgical site infection; TKA, total knee arthroplasty; THA, total hip arthroplasty; CDC, Centers for Disease Control and Prevention  24  ; CABG, coronary artery bypass grafting. a Procedures included in surveillance that could be matched to routine care data extracted from electronic health records; this served as a reference population for comparison of the algorithm performance. b  The selection of surgeries (related to hip and knee prosthesis, cardiac surgery, or colon surgery) consists of a large number of procedure codes, not further specified in this table.
c Separate analyses were performed for hospital B for surveillance of 2016 and 2015-2016, because of data availability of data on antibiotics starting 2016. d Follow-up period 30 days for procedures without foreign material, for procedures with foreign material 365 days. therefore excluded from further analyses. The included hospitals were Amphia hospital (Breda, Netherlands), Dupuytren University Hospital (Limoges, France), the Bellvitge University Hospital (Barcelona, Spain), referred to as hospital A-C (random order). Table  1  provides an overview of the surveillance population, definitions used in manual surveillance, and the number of procedures that could be linked to EHR data and, hence, to serve as reference data to evaluate algorithm performance. In total, 4,770 THA and TKA procedures, 5,047 cardiac surgeries, and 3,906 colon surgeries, with 38 SSIs for THA and TKA, 94 SSIs for cardiac surgeries, and 230 SSIs for colon surgeries.
Acknowledgments. We thank  Erik Ribbers ,  Miranda van Rijen  ( Amphia hospital, Breda, Netherlands ),  Xavier Rodriguez  ( Bellvitge University Hospital, Barcelona, Spain ), and the infection prevention departments, IT departments, and surgical departments of all participating hospitals for their valuable contribution to this project. Financial support. This research was supported by the  EPI-Net   COMBACTE-MAGNET  project, funded by the  Innovative Medicines Initiative Joint Undertaking  (grant no. 115737 ), the resources of which included a financial contribution from the  European Union Seventh Framework Programme  (grant no. FP7/2007-2013 ) and the  European Federation of Pharmaceutical Industries and Associations  companies' in-kind contribution.
In the presence of PnTX-A, the amplitude of the ACh potential decreased in a time-dependent manner so after about 10-14 min (n = 3), no response could be evoked by ACh, as shown in the graph of Figure  9. This result clearly indicates that PnTX-A blocks the muscle-type α12β1δε nAChR subtype. Additional experiments were performed to determine whether the spiroimine component in PnTX-A is essential for the blocking action of EPP amplitudes. For this, experiments were performed with the synthetic PnTX-AK that includes an open form of the imine ring A. As shown in Figure  7a ,b, PnTX-AK had no action on nerve-evoked EPP amplitude at concentrations at which PnTX-A exerted 80% blockade of EPP amplitude. Similarly, no significant effect of PnTX-AK (5. 44 nmol/kg of mouse) was detected on the CMAP recorded from anesthetized mice in vivo (n = 3, data not shown).
In the presence of PnTX-A, the amplitude of the ACh potential decreased in a time-dependent manner so after about 10-14 min (n = 3), no response could be evoked by ACh, as shown in the graph of Figure  9. This result clearly indicates that PnTX-A blocks the muscle-type α1 2 β1δε nAChR subtype. Additional experiments were performed to determine whether the spiroimine component in PnTX-A is essential for the blocking action of EPP amplitudes. For this, experiments were performed with the synthetic PnTX-AK that includes an open form of the imine ring A. As shown in Figure  7a ,b, PnTX-AK had no action on nerve-evoked EPP amplitude at concentrations at which PnTX-A exerted 80% blockade of EPP amplitude. Similarly, no significant effect of PnTX-AK (5. 44 nmol/kg of mouse) was detected on the CMAP recorded from anesthetized mice in vivo (n = 3, data not shown).
The reduction of the amplitude of spontaneous mEPP, without significant change in the mEPP frequency, and the block of full-sized EPPs and ACh-evoked potentials strongly indicate that PnTX-A and G exert a selective action at the postsynaptic level of the neuromuscular junction by blocking the interaction between ACh and the α1 2 β1δε nAChR. Whether PnTXs have a presynaptic action was not directly investigated in our study. However, data obtained by measuring mEPP frequency, when there was about 50% block of mEPP amplitude, strongly suggests that PnTXs do not have a pre-synaptic action that would modify the quantal ACh release rate. Insight into the interaction between PnTX-A and PnTX-G and the muscle-type α1 2 β1γδ nAChR was previously obtained in competition binding studies using [ 125 I] α-bungarotoxin as a tracer.
Toxins and Chemicals PnTX-A, G and AK were synthesized, as previously reported  [31]. The purity of PnTXs and analogue was over 98%, as judged by NMR data and HPLC performed for final purification (Supplementary data). The µ-conotoxin GIIIB was obtained from Alomone Labs (Alomone Labs, Jerusalem, Israel). All chemicals, including ACh hydrochloride and 3,4-DAP, were purchased from Sigma-Aldrich (Saint Quentin Fallavier, France). The in vivo experiments were performed using a stock solution of PBS (1X, 100 µL) added to 1% methanol (vehicle) and either 28 µM PnTX-A or 20 µM PnTX-G. PnTX-A was studied at doses of 0. 54-5. 44 nmol/kg of mouse. PnTX-G was studied at doses of 1. 60-3. 20 nmol/kg of mouse.
Recordings from the Neuromuscular System of Anesthetized Mice In Vivo The multimodal excitability properties of the mouse neuromuscular system were assessed in vivo on females [weighting 26. 4 ± 1. 4 g (n = 26)], under isoflurane (AErrane, Baxter S. A. , Lessines, Belgium) anesthesia, by means of minimally-invasive electrophysiological methods using the Qtrac © software (Bostock H. , Institute of Neurology, London, UK), as previously described  [45]. Briefly, the CMAP was recorded using fine needle electrodes inserted into the tail muscle and connected to an amplifier (Disa EMG 14C13), in response to electrical stimulations delivered to the caudal motor nerve by two stimulators (A395, World Precision Instruments, Sarasota, FL, USA) via surface electrodes. To study the underlying mode of action of PnTX-A and G, intramuscular injections (5-µL maximal volume) of PBS containing 0.
Data acquisition and analysis were performed with the WinWCP v3. 9. 6 software program (John Dempster, University of Strathclyde, Scotland). Experiments were performed at constant room temperature (22 • C). For synaptic transmission measurements, either EDL or FDB nerve-muscle preparations were dissected and mounted in silicone-lined recording chambers with stainless mini-pins. The motor nerve was stimulated with a suction electrode, with pulses of 0. 1 ms duration and supramaximal voltage (typically 3-8 V). Both internal and external platinum wires of the suction electrode were connected to the isolation unit of a stimulator (S-44 Grass Instruments). Intracellular recordings were performed with 1. 2 mm (external diameter) borosilicate glass capillaries containing internal glass filaments (type GC120f; Clark Electromedical Instruments, Pangbourne, UK) pulled on a P-1000 puller (Sutter Instrument Company, Novato, CA, USA) and having a resistance of 6-12 MΩ when backfilled with a 3 M KCl solution.
Data and Statistical Analyses Sigmoid non-linear regressions through data points (correlation coefficient = r 2 ) were used to calculate theoretical dose/concentration-response curves, according to the Hill equation (GraphPad Prism version 5): Rt/Rc = 1/[1 + ([toxin]/X) nH ], where Rt/Rc is the response recorded in the presence of a given toxin (Rt) and expressed as percentage of the value obtained in absence of toxin (Rc), [toxin] is the toxin concentration, X is the toxin dose (ID 50 ) or concentration (IC 50 ) necessary to inhibit 50% of the response, and nH is the Hill number. EPP amplitudes (exceeding 3 mV) were corrected for non-linear summation according to McLachlan and Martin 1981  [50]. In the present study we have used an "f" factor of 0. 8, and an equilibrium potential for ACh of 0 mV in the calculation of EPP amplitudes in mouse EDL neuromuscular preparations.
Molecular Modeling A homology model of the extracellular domain of mouse (α1) 2 β1δε nAChRs subtype was constructed using Modeller  [51] , and the Aplysia californica acetylcholine binding protein (AChBP) crystal structure as template (Protein Data Bank code 2WZY)  [52]. Three-dimensional structures of PnTX-A and G were generated using Corina 3. 6 (Molecular Networks GmbH, Erlangen, Germany, 2018). The docking procedure was carried out at the interface α1-ε in a similar manner as previously described for PnTX-A at the interface α1-δ of Torpedo nAChRs  [31] , using Gold (Cambridge Crystallographic Data Centre, Cambridge, UK) and the GoldScore scoring function. The binding site, defined as a 20 Å radius sphere, was centred on the backbone oxygen atom of Trp147. All other parameters had default values.
A complete description of the methods can be found in Liquet et al. (31). Functional analysis of the immune signature was performed with Ingenuity Pathway Analysis software (IPA R , Qiagen, Redwood City, California, Spring Release March 2018) and CluePedia and ClueGO in Cytoscape  (32, 33). All microarray data is MIAME compliant and the raw and normalized data have been deposited in the MIAME compliant database Gene Expression Omnibus (http://www. ncbi. nlm. nih. gov/geo/, GEO Series accession number GSE46734).