dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistics and data analysis Sample size for the 3 + 3 dose-escalation part was set to screen patients for major toxicity occurring in a large proportion of the target population. Based on binomial probabilities, there is a 90% probability of observing toxicity event in one or more patients, if that event occurs in at least 54% and 32%, in 3 and 6 patients respectively. Up to 18 patients were planned to be included (3 to 6 patients per dose level). Inclusion of 12 additional patients was scheduled for the expansion part, based on the first stage of a Gehan design allowing to quickly identify treatments with low efficacy: a sample size of 12 patients is needed to eliminate a treatment with response rate lower than 25%. If no clinical responses are observed among 12 patients, the probability that the response rate is greater than 25% will be less than 5%.
PFS was censored at the date of last tumor assessment for event-free patients at the time of the analysis. Median follow-up (min-max) was calculated by a reverse Kaplan-Meier estimate. Descriptive statistics were performed to describe patient demographics and clinical characteristics, occurrence of adverse events (AE). All analyses were performed using SAS (version 9. 4). The date of data cutoff for the final analysis was October 18, 2019.
Protist Abundances and Traits To disentangle potential effects of protist presence and abundance on microbial communities, we estimated protist population sizes through fluid imaging of 3 ml subsamples out of four microcosms from each treatment using a FlowCam (Fluid Imaging Technologies, Scarborough, ME, United States). Fluid imaging also yields high-resolution measurements of multiple cell traits like cellular volume and shape, and optical properties of the cells  (Gibert et al. , 2017; Wieczynski et al. , 2021). We used these trait data to assess potential responses of the protists to imposed experimental conditions as well as potential responses of the microbial communities to both protist traits and densities (detailed below). We focused on nine different phenotypic characteristics: five measurements of shape and size (length, area, volume, circularity, and aspect ratio) and four measurements of optical properties of the cells (sigma-intensity and three components of hue: Red/Green, Red/Blue, and Blue/ Green ratios).
These measurements were taken on days 12 and 24. We assessed whether protist population counts changed with either temperature or time using linear models, and we assessed whether protist phenotypes responded over time and with temperature using perMANOVA  (Anderson, 2001 (Anderson, , 2017) )  using the vegan package in R (v2. 5. 6; Oksanen et al. , 2019). The input data were checked for clear departures from normality and homoscedasticity, but none were found.
Amplicon Sequence Data Processing and Bacterial Community Structure Analysis We used 16S rRNA amplicon sequencing to examine the impacts of temperature, time, and protists on microbial community structure. After the incubation period (12 or 24 days), we collected the microbial communities by filtering 200 ml from each microcosm into gamma-irradiated 0. 2 μm nitrocellulose membranes (Advantec, Taipei, Taiwan) and stored the filters at -20°C until DNA extraction. Total genomic DNA was extracted from each filter using DNeasy PowerWater DNA Extraction Kits (Qiagen, Hilden, Germany), modified with a heating step (60°C) before the initial vortexing step to maximize lysis across different microbial cell types. We fluorometrically quantified the genomic DNA concentrations with Qubit (Thermo Fisher, Waltham, MA, United States) and sent an equimolar set of genomic DNA samples to the Research Technology Support Facility (RTSF) at Michigan State University for amplicon prep and sequencing.
We targeted the V4 hypervariable region of the 16S rRNA gene using the standard 515F/806R universal primers with 12 bp Golay barcodes  (Caporaso et al. , 2011). RTSF sequenced our samples with Illumina MiSeq (PE 250 bp, V2 chemistry) and returned 9,069,268 raw reads (average/sample: 62,981 reads), publicly available at EMBL-ENA with project accession numbers available upon request, and listed here upon publication. We processed the raw fastq sequence data through Dada2 (v1. 16. 0; Callahan et al. , 2016)  in R (v4. 0. 2; R Core Team, 2021), to trim and filter low quality sequence reads [full-length reads (250 bp) retained without ambiguous bases (maxN = 0), relaxed expected error in the reverse reads (maxEE = (2,5)); default phiX removal and truncation of reads where quality score drops below 2] and calculate error rates for denoising and merging the pair-ends into 3,801 non-chimeric representative amplicon sequence variants, or ASVs.
To examine the impacts of temperature, incubation time, and protists on the overall structure of the bacterial communities, we used principal component analysis on an abundance-weighted bray-curtis distance matrix of the VST table in vegan R (v2. 5-6;  Oksanen et al. , 2019). We tested for individual and interactive treatment effects with a perMANOVA using the adonis() function in vegan R (v2. 5-6;  Oksanen et al. , 2019). We performed multilevel pairwise comparisons of the community data using the pairwise. adonis() function in the pairwiseAdonis R package (v0. 0. 1; Martinez Arbizu, 2017). We also examined differences among group community variation-or spread in ordination space-using the betadisper() function (PERMDISP2;  Anderson et al. , 2006)  in vegan R (v2. 5-6;  Oksanen et al. , 2019) , which uses multivariate homogeneity of group dispersions, or the multivariate form of a Levene's test  (O'Neill and Mathews, 2000; Anderson, 2006).
Introduction: Thromboembolic events represent the most frequent complications of endovascular treatment of unruptured intracranial aneurysm using stent-assisted coilling or flow diverter stents. Dual antiplatelet therapy has become the standard to prevent these but remains unstandardized. We present here a single center experience of 3 standardized antiplatelet regimens during brain aneurysm treatment, while emphasizing the use of the Cangrelor. Method: We retrospectively reviewed data from patients treated using stent-assisted coilling or flow diverter stents from 2016 to 2021. We collected and compared safety and efficacy data within 6 months of three groups of patients corresponding to three antiplatelet standardized regimens: group T with Ticagrelor, with preprocedural preparation; group E with Eptifibatide, injected during procedure; group C with Cangrelor, injected during procedure.
Results: Data of 112 patients were analyzed and 76 belonged to group T, 21 to group E, and 15 to group C. Eleven events over the 14 recorded were adjudicated to be related to antiplatelets, their repartition did not differ between the 3 groups (p = 0. 43). All symptomatic events (N = 8) were not distributed significantly differently between the 3 groups (p = 0. 11) and asymptomatic events were also balanced (p = 1. 00). Of these, 6 subjects had a change in the mRS score at 3-6 months. Thrombo-embolic events represented the most encountered events in the sample: 2 acute ischemic strokes were recorded in group E and 1 in group T; 1 transient ischemic stroke was noted in group E; 4 silent infarcts were found on control MRI (2 belonged to group T, 1 to group E and 1 to group C). Among 3 intracranial bleeding events, 1 was symptomatic in group C, 2 were asymptomatic in group T.
Ethical Statement The use of Cangrelor was off-label in this study. In all cases no final alternative was found to intracranial stenting and the choice to treat these patients under Cangrelor was made multidisciplinary. Patients were informed before each treatment of the initial strategy and possible alternatives and gave verbal consent. The study and need for patient informed consent was conducted in accordance with actual laws and ethics and with the Helsinki Declaration and its revisions: as a non-interventional retrospective study, a commitment to compliance (Reference Methodology MR-3) was declared to the French national information science and liberties commission (CNIL), in respect to the General Data Protection Regulation. NCT04504695.
Functional Annotation and Enrichment of Functional Terms Functional analysis was performed with "Enrichr" to identify the biological processes and molecular function, in which genes are involved on the basis of "Gene Ontology" (GO) terms as well as the visualization of biological pathways from "KEGG" (Kyoto Encyclopedia of Genes and Genomes). We also checked the disease associated with these genes using DisGeNET, which is a discovery platform containing one of the largest publicly available collections of genes and variants associated with human diseases. The last database interrogated was the Mouse Gene Atlas from BioGPS to find cell line enrichment in mouse tissues. The p-value was computed using a standard statistical method used by most enrichment analysis tools: Fisher's exact test or the hypergeometric test.
This is a binomial proportion test that assumes a binomial distribution and independence for the probability of any gene belonging to any set. Then, a p-value using the Benjamini-Hochberg method for correction for multiple hypotheses testing was applied to select the significant terms and pathways. In addition, an enrichment analysis was performed using the KEGG database to visualize the pathways of genes, taking into account only the number of genes found. Q-values under 0. 05 were considered significant. To assess the functionality of LincRNA impact by a bioinformatics approach, we used the genomic regions enrichment of annotation tool (GREAT)  [47]. GREAT evaluates sets of cis-regulatory elements by assigning each element to its likely target gene(s).
Comparison of Published Lists of Human Differentially Expressed Genes with Mouse Differentially Expressed Genes Our mouse gene expression analysis was compared to human datasets published by Fairfax et al. [27]  and Davenport et al. [26]  Gene sets published were directly used in our analysis. Table  2  summarizes the characteristics of the studies. In addition, our mouse gene expression analysis was compared to conserved patterns of gene expression in humans and mouse models triggered by sepsis  [28]. Gene set enrichment analysis (GSEA) was performed using GSEA software  [48]. Given the gene sets previously published, we assessed whether the members of those gene sets were randomly distributed throughout the list of mouse differentially expressed genes, which were ranked on the basis of the SAM score.
Search strategy We performed systematic electronic searches of Pub-Med, Embase and the Cochrane Library (comprising the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and the Health Technology Assessment database). Search strategies were developed using Medical Subject Headings and free-text terms (Supplementary materials). All searches were performed for the period of 1 January 2010 through 30 April 2021 to ensure the inclusion of recently published data.
Data extraction and management Study characteristics and outcome data were extracted from the included studies and recorded using a Microsoft Excel template (Microsoft Corp. , Redmond, WA, USA). The following study characteristics were extracted: design (study duration, randomisation method, blinding), population (demographics, baseline disease activity, number of randomised participants, prior TNFi use, concomitant medication), interventions (type, dose, regimen), and prespecified outcome measures (see above 2. 2. 4; Additional file 1: Table  1 ).
Data synthesis and measures of treatment effect Data for each prespecified outcome of interest were pooled in two separate analyses for patients with CD or UC, respectively. Outcomes reported as proportions (n: event; N: population) were analysed, and the overall proportions from each study were combined using a random-effects meta-analysis. A meta-analysis was only performed if studies were deemed to have similar characteristics (e. g. , study populations and treatments). The I 2 statistic was used to evaluate heterogeneity among the trials included in each meta-analysis. All statistical analyses were performed using R (version 4. 0. 2).
Quality assessment Risk of bias and generalisability for the included studies were evaluated according to criteria defined in the Cochrane Handbook for Systematic Reviews of Interventions  [22]. The following domains were utilised in order to assess the risk of bias: random sequence generation; allocation concealment; blinding of participants and personnel, blinding of outcome assessment; incomplete outcome data; selective outcome reporting; and other bias. Each potential source of bias was rated as high, low, or unclear. Assessments were completed by an author (HGB) responsible for data extraction and checked by a second author (MJ).
Search results The selection of studies for inclusion is summarised in a PRISMA flow diagram to illustrate the flow of information for studies enrolling patients with CD (Fig. 1A ). We identified 2,661 records through the searches. After removal of duplicates, 2,019 records were screened (1,855 records excluded) and 164 full-text articles were assessed against the eligibility criteria (150 articles excluded). Six studies (reported in 13 articles) were included in the qualitative synthesis and in the quantitative synthesis, as follows: • Infliximab (four studies): NCT00094458 (SONIC)  [23] [24] [25] [26] , NCT02096861 (PLANET CD)  [6, 27] , NCT02148640 (NOR-SWITCH)  [28, 29] , NCT02883452 (CT-P13 SC trial)  [19]. • Vedolizumab (two studies): NCT00783692 (GEMINI 2)  [30] [31] [32] [33] , NCT01224171 (GEMINI 3)  [31, 32, 34].
A PRISMA flow diagram summarising the flow of information for studies enrolling patients with UC is presented in Fig. 1B. We identified 1,959 records through the electronic searches and one record from another source. Specifically, as data for ACT 1 and 2 study by  Adedokun et al. (2018)  was not utilizable in our analysis because the article did not evaluate the prespecified timeframe and outcomes of our interest  [35]. The current review evaluated ACT 1 and 2 data as more data were needed for UC in order to perform meta-analyses in some outcomes (Fig. 2A,    RCT data for the past decade. Thus, we instead have taken data from the reference list of the article as an exception  [5]. After removal of duplicates, 1,138 records were screened (894 articles excluded) and 244 full-text articles were assessed against the eligibility criteria (232 articles excluded).
Seven studies (reported in 12 articles) were included in the qualitative synthesis and quantitative analyses, as follows: • Infliximab (four studies): NCT00036439 (ACT1)  [5, 35] , NCT00096655 (ACT2)  [5, 35] , NCT02148640 (NOR-SWITCH)  [28, 29] , NCT02883452 (CT-P13 SC trial)  [19]. • Vedolizumab (three studies): NCT00783718 (GEM-INI 1)  [36] [37] [38] [39] [40] , NCT02497469 (VARSITY)  [41] , NCT02611830 (VISIBLE 1)  [42].
Studies contributing to CD analyses The design and eligibility criteria of the six studies that contributed data to the CD analyses were generally consistent (Additional file 1: Table  1 ). All six studies were randomised trials with a duration of ≥ 50 weeks: five studies included a double-blind period, and one study was conducted using an open-label design (CT-P13 SC trial). Two of the six studies included an open-label extension (NOR-SWITCH and GEMINI 3) and three studies (PLANET CD, NOR-SWITCH and CT-P13) included switching phases wherein participants switched between infliximab products. Five of six studies were multinational, whereas one study was conducted in Norway (NOR-SWITCH). Across studies, inclusion criteria required participants to be adults (aged ≥ 18) with a diagnosis of CD; four of six studies required participants to have a CDAI score of 220-450, one study (GEMINI 3) specified 220-400 and another (NOR-SWITCH) did not specify a CDAI score.
Studies contributing to UC analyses The design and eligibility criteria of the seven studies that contributed data to the UC analyses were generally consistent (Additional file 1: Table  1 ). All seven studies were randomised trials with a duration of ≥ 46 weeks, except for ACT2 (22 weeks): six studies included double-blind periods and one study was open-label (CT-P13 SC trial). Two studies included an open-label extension (NOR-SWITCH and VISIBLE 1). Three studies included switching phases wherein participants switched between infliximab products (NOR-SWITCH and CT-P13 SC trial) or between IV and SC vedolizumab (VISIBLE 1). Six of the seven studies were multinational, whereas one study (NOR-SWITCH) was conducted in Norway. Across studies, inclusion criteria required participants to be adults (aged ≥ 18 years) with active UC (Mayo score 6-12 and endoscopic sub-score ≥ 2) despite treatment with conventional therapies (e.
GEMINI 2, NOR-SWITCH, and PLANET CD were considered to be at high risk of 'other bias' because of the selective inclusion of induction responders in the maintenance phase; notably, this high risk of bias applies only to the maintenance-phase data for these studies as the induction phase included all enrolled patients. Figure  3B  presents a summary of the risk-of-bias assessment for studies contributing to the UC analyses. Across 49 assessments (seven studies and seven risk-ofbias domains), 36 were considered to be at low risk of bias, nine at high risk and four to have an unclear risk of bias. All seven studies were considered to be at low risk of bias for random sequence generation and selective reporting. Four studies were considered at low or unclear risk of bias for all domains (VARSITY, ACT 1, ACT 2, NOR-SWITCH).
Three studies had three domains considered to be at high risk of bias (GEMINI 1, VISIBLE 1, CT-P13 SC trial). The results from CT-P13 SC trial have the same risk of bias as CD such as having an open-label study design and did not fully categorised the safety outcomes. GEMINI 1 and VISIBLE 1 were considered to be at high risk of 'other bias' because of the selective inclusion of induction responders in the maintenance phase; again, this high risk of bias applies only to the maintenance-phase data for these studies as the induction phase included all enrolled patients.
Discussion The present study is the first systematic review to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe CD or moderate-to-severe UC in order to address a lack of evidence of a direct comparison between the treatments. Data were extracted and pooled for the prespecified outcomes of interest at the corresponding 6-week and/ or 50-to 54-week timepoints, respectively. Notably, the present evidence synthesis is the first to our knowledge to incorporate data for CT-P13 SC, an SC formulation of the infliximab. Our results show that infliximab yielded better efficacy than vedolizumab for all the efficacy outcomes in patients with CD or UC during the induction phase, and comparable clinical efficacies with overlapping 95% CI in both diseases during the maintenance phase.
Risk of bias in the included studies was principally considered to be low or was unclear (i. e. due to a lack of necessary information in the study reports). However, several studies were considered to be at high risk of 'other bias'. Notably, the GEMINI 1  [36] , GEMINI 2  [30] , VISIBLE 1  [42] , and PLANETCD  [6]  studies were considered to be at high risk of bias on the basis of only including patients in the maintenance phase if they had responded during the induction phase (i. e. at 6 weeks). This practice may potentially lead to overestimation of efficacy in the maintenance phase and overall safety, compared with studies in which both responders and non-responders were included in the maintenance phase. Therefore, the data relating to non-responders' efficacy in infliximab (NOR-SWITCH and PLANETCD) and vedolizumab (GEMINI 1, GEMINI 2, and VISIBLE 1) during maintenance phase may not be generalized.
Furthermore, some studies were excluded from the present review because the timepoints assessed did not match those prespecified in the review protocol. This omission of potentially valuable data highlights the need to standardise future study designs. The present review did not assess longer-term follow-up (i. e. , beyond 1 year) despite a sustained response being important to patients. Longer-term follow-up in larger real-world cohorts may also be more relevant to analyse safety. Finally, the included studies enrolled different proportions of patients with previous biological treatment failure (potentially accounting for between-study differences in efficacy and accounting for some of the observed heterogeneity). Different proportions of TNFi-experienced patients in vedolizumab treatment groups compared to infliximab treatment group, which consists of TNFnaïve patients only.
Additional file 1: Figs. 11, 12, 18), largely accounting for the fact that infliximab had few available A. Records identified through database Additional records identified through Identification searching (n = 2,661) other sources (n = 0) Records after duplicates removed (n = 2,019) Screening Records screened Records excluded (n = 1,855) Reasons for exclusion (n = 2,019) Abstract only Clinical trials Language other than English Systematic review & meta- Eligibility Full-text articles assessed for eligibility (n = 164) analysis Not an original article Irrelevant topic Ulcerative colitis only Full-text articles excluded N = 6 studies included in (n = 151) qualitative synthesis Reasons for exclusion (n = 13 articles) Inappropriate timepoint Included N = 6 studies included in No appropriate data reported quantitative synthesis (meta- analysis) (n = 13 articles) B.
IdenƟficaƟon Records idenƟfied through database searching (n = 1,959) AddiƟonal records idenƟfied through other sources (n = 1) Records aŌer duplicates removed (n = 1,138) Records excluded (n = 894) Screening Records screened (n = 1,138) Reasons for exclusion: Abstract only Clinical trials Language other than English SystemaƟc review & meta- analysis Not an original arƟcle Full-text arƟcles assessed for Irrelevant topic Crohn's disease only Eligibility eligibility (n = 244) Full-text arƟcles excluded N = 7 studies included in (n = 232) qualitaƟve synthesis (n = 12 arƟcles) Reasons for exclusion: Inappropriate Ɵmepoint Retracted arƟcle Included N = 7 studies included in quanƟtaƟve synthesis (meta-analysis) No appropriate data reported Subgroup analysis (n = 12 arƟcles).
For CAI CMS-1, in compiling data from 3 separate SIMS sessions, we found spots with 9 Be/ 11 B up to 80 via the IMS-1290, but our measurement uncertainties are large for these analyses (2SE errors on the 9 Be/ 11 B ratio in the range of 1-9%) because there were only $20 usable cycles per analysis; the primary beam sputtered into phases other than melilite (usually spinel) in some analyses, revealed by an increase in the boron ion intensity and a change in the boron isotope ratio. Thus, only a few measurement cycles could be used in such analyses, resulting in lower precision.
52 Â d 18 O) were typically ± 0. 5-1. 0 ‰. After the SIMS session, SEM images were taken of the analysis spots; only a few visibly overlapped cracks, small inclusions, or were too close to previous oxygen primary analysis spots (expected to result in more 16 O-rich measured compositions due to contamination by this primary beam composition); data from such spots were excluded from further consideration.