dataesr/scientific-paragraphs-categorization huggingface dataset:
Chemical ionization was used as ionization, helium as carrier gas, and a HP-5MS column (30 m x 0. 25 mm, 0. 25 mm) was used for separation. Oven temperature was programmed from 180 C to 220 C at a rate of 8 C/min, from 220 C to 280 C at a rate of 2 C/min. And 10 C/min to 310 C. A full scan method was used to detected compounds. The majority of lipids detected were C16, C16:1, C18:0 and C18:1 FAs and thus, data are presented for these species. Extracellular flux analysis OCR and ECAR were measured using the XFe96 Extracellular Flux Analyzer (Seahorse Biosciences, Agilent). Agilent XFe96 Extracellular Flux Assay cartridges were hydrated overnight in pure water, and in the morning, water was replaced by 200 mL of Seahorse Calibrant and incubated at least 1h at 37 C (non-CO 2 ). T cells (1. 7-2e5)/well) were harvested at day 2 or 4 following TCR activation, resuspended in 50 mL Agilent XF media (buffered RPMI pH7.
ACKNOWLEDGMENTS We thank all members of our laboratories for discussions and scientific critique. We are indebted to  U ¨nal Coskun ,  Michal Grzybek ,  Alessandra Palladini , and  Triantafyllos Chavakis  for all their expertise and assistance with lipidomics analyses. We are grateful to  Myriam Boyer-Clavel  and  Stephanie Viala of the imaging facility MRI, member of the national infrastructure France-Bio-Imaging infrastructure  supported by the  French National Research Agency  ( ANR-10-INBS-04 ,  «Investments  for the future»). We are grateful to  Amal Makrini  of the SERANAD bioinformatics platform for her assistance with analyses. M. I. M. was funded by the  French Ministry of Health  and a fellowship from  ARC  and C. S. Y. by an  Australian Postgraduate Award ,  Cancer Therapeutics Australia  and  ARC.
C. G. was supported by the  ERICAN program of MSD Avenir  (J. C. M. ). S. T. is supported by funding from  Cancer Research UK  ( C596/ A17196  and  A23982 ). We are grateful to  MetaboHUB-MetaToul  (Toulouse, France) and  MetaboHUB - ANR-11-INBS-0010  for lipid tracing experiments. This research was in part supported by the  NIH   Intramural Research Program  of  NIAID  (S. A. M. ) and  NCI  (N. T. ). This work was supported by generous funding from the  ANR  research grants ( CHIC-20-CE14-0049 ,.
Although their occurrence tends to be spotty, they can be locally very abundant  [28]. Susceptibility to H. americana of fossarine lymnaeids from most of these areas is unknown. Our phylogenetic analysis showing other species of Galba as close relatives to G. cubensis and G. humilis suggests the possibility they too could potentially be infected by H. americana. through the 20th century  [30] , but as with other locations throughout the American west, they have since become much more abundant, particularly in urban areas. Elimination of predators, expanding agriculture and urbanization, and climate-related increases in available food all favor the spread of raccoons  [31]. A recent climate modeling analysis Additional taxa examined in New Mexico are from the MSB Parasite Division. Taxa are preceded with their corresponding GenBank accession number and followed by their collection locality (U.
S. state or country). See Table  1  for accession numbers and MSB numbers. suggested raccoons will expand their range northward but may diminish in numbers in more tropical areas of their known range  [32, 33]. This may help to explain the apparent absence of H. americana from areas south of Texas given that a permissive snail host, G. cubensis, is known from Mexico, South America, and Cuba. Alternatively, this apparent absence may reflect a lack of survey information. Recovery of H. americana from Utah and Indiana suggests it is not precluded from colder climates. Its closest relative, S. douthitti, occurs as far north as Alaska  [34]. The establishment of the mostly tropical species Schistosoma haematobium in Corsica has prompted the suggestion that schistosomes are "pre-adapted" to colder climates  [35].
Our results also suggest that H. americana from Moab may have originated from Texas. Further studies are needed to learn if the isolates from different states have diverged sufficiently to be considered different species. Fig. 6. Phylogenetic tree for relevant schistosomes, including Heterobilharzia americana, based on Bayesian analysis of cox1 with nodal support indicated on the branches by posterior probabilities as asterisk for >0. 98. The samples from this study are in bold and outlined in a gray box. Taxa names are preceded by their corresponding GenBank accession number and followed by their collection locality (U. S. state). See Table  1  for accession numbers and MSB numbers.
Museum vouchers, locality information, and GenBank Accession numbers of parasites and snails collected as a part of this study. The Louisiana isolate of H. americana and several of the G. humilis (and other lymnaeid) isolates are part of the existing collections of the Parasite Division, Museum of Southwestern Biology. Detailed information for each specimen is on the Arctos Database (http://arctos. database. museum/SpecimenSearch. cfm).
Acknowledgments The authors wish to thank  Patsy Wilmerding  for her hospitality and  Robin Loker  for assisting with collections. We thank the  Colorado State University Veterinary Histopathology Laboratory  for the provision of histological sections and associated photographs of the necropsied dog, and the  Gastrointestinal Diagnostic Unit of Texas A & M University  for identifying 10 Moab dogs with fecal samples positive for Heterobilharzia americana. We also thank  Ms. Karen Buehler  from  Tri-Core Laboratories in Albuquerque  for her timely assistance in producing histological sections of snails.
Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.
Very recently, molecular mechanisms were proposed that can explain the occurrences of predominant intestinal, predominant hepatic and mixed phenotypes  [15]. We compiled the clinical outcomes of 114 novel and previously reported patients with mostly biallelic MYO5B mutations and probed the dataset for genotype-phenotype correlation with respect to proposed disease mechanisms. Our study includes 44 novel patients with biallelic MYO5B mutations, of which 35 MYO5B mutations are novel. Novel data will be entered into the international online registry for patients with MYO5B mutations and their phenotype information (http://www. MVID-central. org) [16] ; this patient registry already contains incomplete phenotype or genotype information on a small number of patients reported in our study; our study enables straightforward complementation of these entries.
We then re-contacted the referring physicians to provide a standardized, questionnaire-based follow-up on their referrals. The following data were abstracted from the medical records of each patient: family history, sex, ethnicity, parental consanguinity, age at onset of diarrhea, failure to thrive, dependence on parenteral nutrition, single-or multi-organ transplantation, characteristic histological findings of duodenal biopsies, outcome at last patient contact. Routine hepatic function criteria were determined in patients with chronic diarrhea and with chronic liver involvement. Genomic DNA was isolated from patients' peripheral blood leukocytes by standard procedures. DNA samples from patients' healthy parents were obtained and tested for MYO5B variant segregation with disease. Targeted Sanger sequencing of the MYO5B gene was conducted in 42 patients as reported previously  [17, 18] ; MYO5B gene analysis was performed in whole-exome-sequencing (WES) data in the remaining 27 patients; WES was conducted and data processed as reported  [19] ; variant calling was restricted to the MYO5B region (chr18:47349156-47721542 in the hg19 reference sequence) in patients with a clinical diagnosis of MVID.
In five instances, MYO5B mutation analysis had been conducted initially in a collaborating diagnostic laboratory. In patients referred with a clinically indeterminate congenital diarrhea, the genomic regions of genes known to cause forms of congenital diarrhea and immune deficiency syndromes were evaluated (gene panel list available from the authors on request). Patients with cholestatic liver disease, in whom mutations in PFIC1-3 genes had been excluded, were evaluated for MYO5B variants. Categorization and interpretation of sequence variants were based on variant allele frequencies <0. 005 in public domain population databases, and predicted effects on protein function by in-silico evaluation using Polyphen2 and CADD programs  [20]. The nomenclature of identified variants and patients' genotype follows the Human Genome Variation Society guidelines (HGVS v 2.
Upon SARS-CoV-2 virions attachment to the host cells, viral spike protein shows a conformation change which mediates the viral envelope fusion with the host cell membrane via an endosomal pathway  [2]. Targeting viral entry has been proposed and clinical trial has started (https://clinicaltrials. gov/ ct2/show/NCT04352400)  [3]. However, the main consequence is the cytokine storm of the host cells Ivyspring International Publisher upon response to infection and followed by signalling pathways transduction to the downstream targets of cell death, cell cycle and others, which may crosstalk with cancer signaling as the similar common interleukin activators  [4]. For example, some cytokines transduce signals through JAKs and signal transducer and activator of transcriptions (STATs) whose mislocalization or super-activation may induce cancers  [5].
Based on different cohort of preclinical and clinical studies, it is urgently needed to analyze whole big data to get a systematic conclusion or prediction of new drugs for cancer patients infected with COVID-19. Here, we aimed to use network pharmacology tool to analyze the database of big data and explore the crosstalk pathways between whole kinases signaling and COVID-19, then to test the efficacy of the predicted drugs in a SARS-CoV-2 model system.
Construction of protein-protein interaction (PPI) crosstalk-networks between kinase, drug target and COVID-19 The drug targets of COVID-19 and kinases related targets were collected by searching databases of NCBI (https://www. ncbi. nlm. nih. gov), GenCLiP3 GeneCards, using key words above and "Homo sapiens" for human species plus the input of targets from recent published pool  [8]  followed by the application of venny 2. 1. 0 tool to explore of the intersection targets, of which were exported to the STRING database to construct protein-protein networks for further analysis and visualization through Cytoscape 3. 7. 2 tool  [10] [11] [12] [13]  (http://www. bioinformatics. com. cn). For capivasertib (AZD5363) based drug targets-COVID-19 PPI, the targets were identified based on the drug bank by dissociation constant (Kd) of 100 nM to 10 µM range of dose (https://lincs.
Network pharmacology analysis identified AKT signaling as potential top ranked kinase crosstalk with COVID-19 pathways Firstly, we searched a variety of databases for "COVID-19" and "kinase" targets from NCBI (https://www. ncbi. nlm. nih. gov), GenCLiP3 (http:// ci. smu. edu. cn/genclip3/GeneAssociation. php), Gene Cards (https://www. genecards. org/), databases, and Venny 2. 1. 0 (https://bioinfogp. cnb. csic. es/tools/ venny/) tool for mapping the common targets. We obtained the predicted encoding intersection targets suggesting the interaction proteins involved in kinase mediated COVID-19 infection, progression, and host cell reaction (Figure  1A ). Using the screened 1539 co-targets (18%), we then established the protein-protein interaction map and analyzed the most essential pathways by nodes, GO and KEGG of top ranking of gene counts (Figure  1C  and Figure  2 ).
AKT profiling in cancer overall survival Finally, we searched database of gene expression profiling of the targets and listed the poor outcome of overall survival which correlated to the gene overexpression encoding for AKT kinases. The significant cancer types are urothelial bladder carcinoma, kidney chromophobe carcinoma, prostate adenocarcinoma, uterine corpus endometrial carcinoma for AKT (Figure  5 ). Thus, our data suggest the identified kinase network related COVID-19 targets has poor prognosis in some types of cancer. The AKT inhibitor drugs, such as capivasertib, could be recommended for concurrent targeting both COVID-19 and the type of cancer in the pandemic era for unique treatment.
Acknowledgements We thank  Professor Huan Yan  ( State Key Laboratory of Virology, Wuhan University, China ) for providing a SARS-CoV-2 spike protein pseudotyped virus system and the recombinant vector pCAGGS-HA-spike. and  Technology Development Fund Macau SAR  (No. 0055/2019/A1 ),  Hubei Science Fund for Excellent Scholars  (No. 2020CFA015 ), and  Nazarbayev University Faculty-Development Competitive Research Grants Program ID :  15798117  ( 110119FD4531 ) and ID:  15874919  ( 110119FD4542 ).
Clinicians today take blood samples to nearside technology that gives data on electrolytes, glucose, gas exchange and pH homeostasis. These tests have become central to the decision-making process for patient care. Clinicians of the future will measure biomarkers with bedside mass-spectrometry to diagnose sepsis and predict risk, PCR to identify organisms and antimicrobial susceptibility and patient factors to determine suitable therapies. During treatment, bedside measurements of serum drug concentrations will allow rapid and widespread therapeutic drug monitoring for a greater range of medicines. Integration with prescribing software will then allow dynamic, real-time dose adjustment. This level of precision medicine will benefit the patient by maximizing treatment benefits and, by minimizing overexposure to unneeded antibiotics, will benefit society.
This study highlights important discrepancies between France and the Netherlands concerning the care of patients with psoriasis with non-biologic and biologic drugs. The implementation of national guidelines would be a key element in reaching evidence-based medicine in the field of psoriasis. Current management of moderate-to-severe psoriasis may be heterogeneous between European countries, probably due to differences in the organization of care. The aim of this study was to compare the utilization of systemic treatments for psoriasis between 2 countries. All adults with psoriasis who were registered in the French (SNDS) and the Dutch (VEKTIS) national health insurance databases between 2012 and 2016 were eligible for inclusion. In France, 105,035 (15%) of 684,156 patients and, in the Netherlands, 37,405 (28.
Data sources The French nationwide cohort study was based on health administrative data obtained from the French National Health Insurance scheme, covering approximately 67 million individuals linked with the national hospital discharge database (SNDS-PMSI) by means of a unique anonymous identifier, as described previously  (9) (10) (11). The Netherlands nationwide cohort study was based on health administrative data obtained from the Netherlands national health insurance scheme, covering approximately 17 million individuals (VEKTIS). In the Netherlands, inhabitants have an obligatory health insurance and immediate access to the healthcare system at all times. All diagnoses and treatments provided in the hospital are coded according to a national financial coding system. Insurance companies collect all hospital claims, which are registered centrally by the national centre for healthcare data and information from the national insurance companies (Vektis B.
Statistical analysis For descriptions of the study population, qualitative variables were reported as the number (percentage). Quantitative variables were reported as the median and/or the mean ± standard deviation (SD) or were converted to qualitative variables. The proportion of healthcare users with psoriasis was described over time in France and in the Netherlands, as well as the proportion of psoriasis healthcare users treated with systemic agents. First choice of systemic treatments was described in France and in the Netherlands. The top 5 sequences of non-biologic and biologic treatments, respectively, allocated to each patient with psoriasis in France and in the Netherlands were reported. Data were analysed using SAS Enterprise Guide 7. 1 (SAS Institute Inc. , Cary, NC, USA).
Study strengths and limitations Strengths of the present study include the large and unbiased sample size from 2 national representative databases, as discussed previously, and the 5-year study period. Among the study limitations is the absence of medical chart review to easily identify psoriasis cases. However, this study used a definition based on the dispensation of at least 2 topical vitamin D derivatives within a 2-year period. Topical vitamin D derivatives are the first-line treatment of psoriasis  (24)  and the current study definition has been used and validated in the Danish health insurance database  (12). Thus, the number of psoriasis cases in this study is probably under-estimated; however, on the one hand this misclassification should not be differential between the type of drugs, and on the other hand, we are confident about the specificity of our definition.
ACKNOWLEDGEMENTS This study was approved by the  French data protection agency Commission Nationale de l'Informatique et des Libertés (regulatory decision   DE-2015-165 ). ES was supported by the  French Society of Dermatology  and by the  French Teachers College , section dermatology CEDEF. CB, MM, AW, JR were employees of the  French National Health Insurance Fund. The present paper represents the opinions of the authors and does not necessarily reflect the position of their employers. The authors have no conflicts of interest to declare.
SUB Interaction with Histone H4 The functional ortholog of SUB in humans, AKR2, has been suggested to physically interact with the histone H3. 1 for chromatin remodeling and regulation of gene expression  [28]. This finding raised the question of whether SUB is also involved in chromatin remodeling in ticks. To address this question, we performed a histone peptide array analysis with histone peptides (Data S1). The results identified an H4but peptide (H4 K5,8,12but; amino acids 1-23; Ac-SGRGK(but) 5GGK(but) 8GLGK(but) 12GGAKRHRKVLR-Peg(Biot); butyrylated at lysines 5, 8 and 12) as being involved in a putative SUB-histone interaction (Figures  6A  and 6B ). Although the identified histone peptide was derived from human sequences, the I. scapularis histone 4 (Q4PM69) is 100% homologous to the human ortholog  [46].
SUB Interaction with Histone H4 The functional ortholog of SUB in humans, AKR2, has been suggested to physically interact with the histone H3. 1 for chromatin remodeling and regulation of gene expression  [28]. This finding raised the question of whether SUB is also involved in chromatin remodeling in ticks. To address this question, we performed a histone peptide array analysis with histone peptides (Data S1). The results identified an H4but peptide (H4 K5,8,12but; amino acids 1-23; Ac-SGRGK(but) 5GGK(but) 8GLGK(but) 12GGAKRHRKVLR-Peg(Biot); butyrylated at lysines 5, 8 and 12) as being involved in a putative SUB-histone interaction (Figure  6A, B ). Although the identified histone peptide was derived from human sequences, the I. scapularis histone 4 (Q4PM69) is 100% homologous to the human ortholog  [46].
Corroboration of SUB-Importin-α Interaction by Protein Pull-Down The synthetic I. scapularis histidine-tag recombinant SUB (Genbank accession number AY652654. 1) with optimized codon usage for Escherichia coli was produced in E. coli BL21 and purified to >95% purity by Ni affinity chromatography using 1 mL HisTrap FF columns mounted on an AKTA-FPLC system (GE Healthcare, Piscataway, NJ, USA) in the presence of 7 M urea lysis buffer as previously described  [51]. Recombinant SUB and I. scapularis recombinant Importin-α fused to glutathione-S-transferase (GST), also produced in E. coli (commercially synthesized by GenScript, Piscataway, NJ, USA), were incubated in 100 mM HEPES (pH 7. 5) and 10 mM imidazole (binding and wash buffer) for 1 h with shaking, at a concentration ratio of 2:1. HisLink Protein Purification Resin (Promega Corporation, Madison, WI, USA) was washed following the manufacturer's recommendations and blocked with 1% BSA (Thermo Fisher Scientific, Waltham, MA, USA) for 30 min with shaking.
Feeding units were made and set up as previously described by Krull et al. [52]. Bovine blood used was collected from cattle and directly supplemented with heparin (20 IU/mL) (Ratiopharm, Ulm, Germany). Blood was immediately refrigerated and stored at 4 • C for up to one week. The phagostimulant adenosine triphosphate (ATP, Carl Roth) (51 mg/mL), glucose (20. 5%), Vitamin B prepared following the recipe of Duron et al. [54]  and the broad-spectrum antibiotic gentamycin (Roth; 5 µg/mL) were added just before each use. Feeding units were placed in a water bath at 37 • C and ticks were fed as previously described  [52]. Data on the number of feeding females were recorded twice a day and engorged females that detached were weighed and stored individually in glass vials with pierced lids that were kept in a desiccator at approximately 90% relative humidity at RT.
Microarrays were scanned and analyzed using a Genepix Personal 4100 A microarray scanner (Molecular Devices, LLC. , San Jose, CA, USA) for measuring fluorescence in relative fluorescence units (RFU) (Data S1). Fluorescence was normalized against control empty spots (average of 87 technical replicates) and the values compared between SUB and HSP70 by Student's t-test (p < 0. 05) and One-Way ANOVA (https://goodcalculators. com/one-way-anova-calculator/, accessed on 12 October 2020; p < 0. 05) tests (n = 2 technical replicates).
Therefore, it is important to consider these individual findings in the context of the totality of the data, including meta-analyses, when evaluating potential impacts of ADA status on efficacy. Available safety data do not allow conclusions to be drawn on clinically relevant patterns of adverse drug reactions attributable to atezolizumab immunogenicity. Imbalances exist in the incidence of various AE categories between ADA subgroups in both directions, with certain types of AEs more frequent in ADA-patients and others more frequent in ADA+ patients. Imbalances in health and disease characteristics were observed at baseline (pretreatment) between ADA+ and ADA-patients. Due to difficulties to adjust for baseline covariates in a safety analysis, no formal analysis was performed. However, it is plausible that these imbalances may confound the safety data and contribute to higher incidences of grade 3-4 AEs and serious AEs in ADA+ patients.
ACKNOWLEDGEMENTS This study was sponsored by  F. Hoffmann-La Roche, Ltd. / Genentech, Inc. , a member of the  Roche Group. We thank the patients and their families. We thank  Veronica Craine  and  Dominik Heinzmann of Roche  as well as  Shengchun Kong  and  Joel Laxamana  of  Genentech  for their contributions to the statistical analyses. Medical writing assistance  Myers Squibb ,  Eisai ,  Ipsen ,  Lilly ,  Merck Sharp & Dohme ,  Roche , and  Sirtex ; has received research funding from  Bayer  and  Roche ; has provided expert testimony for Lilly; and has received travel or accommodation expenses from  AstraZeneca ,  Bayer ,  Bristol Myers Squibb ,  Eisai ,  Ipsen ,  Lilly , and  Roche. C. A. B. , M. B. , R. B. , V. Q. , A. V. , B. W. , and  N. S. are employees of Genentech, Inc/Roche  and  Roche  stockholders.