dataesr/scientific-paragraphs-categorization huggingface dataset:
f Latency to EEG seizure onset (means ± SEM, n = 10 mice per group; twoway ANOVA with Tukey's multiple comparisons test). g Interictal frequency (means ± SEM; Gap43 fl/fl /Vehicle n = 9 mice, Gap43 fl/fl /THC n = 9 mice, Glu-Gap43 -/-/ Vehicle n = 10 mice, Glu-Gap43 -/-/THC n = 10 mice; two-way ANOVA with Tukey's multiple comparisons test). h Average spike duration (means ± SEM; Gap43 fl/fl / Vehicle n = 9 mice, Gap43 fl/fl /THC n = 9 mice, Glu-Gap43 -/-/Vehicle n = 10 mice, Glu-Gap43 -/-/THC n = 10 mice; n. s. by two-way ANOVA with Tukey's multiple comparisons test). Source data are provided as a Source data file. and M. G. take responsibility for their respective group's contribution, including preservation of the original data on which the paper is based; verification that the figures and conclusions accurately reflect the data collected, and that manipulations to images are in accordance with Nature journal guidelines; and minimization of obstacles to sharing materials, data, and algorithms through appropriate planning.
Literature search and selection The GWC performed a literature search in Medline (through PubMed), Embase, Clinical Trial databases, and the Cochrane Library up to July 2022. Reference checking and hand search by the GWC added other relevant literature. The GWC selected literature based on the following criteria: (1)    Language: English; (2) Level of evidence (table  1 ). (  3 ) Sample size: Larger studies were given more weight than smaller studies. (  4 ) Relevant articles published after the search date or in another language were included, but only if they were of paramount importance to this guideline.
Existing literature informing radiation exposure during endovascular procedures A literature review was conducted to identify published data on intra-operative radiation doses during endovascular procedures from Dec 2015 -July 2022 The review focused on standard endovascular aortic repair (EVAR), complex EVAR (fenestrated or branched endovascular aortic repair, F/BEVAR) and endovascular treatment of lower extremity peripheral arterial disease (LEPAD), respectively, because these are the most radiating and common procedures in vascular surgery. Deep vein recanalisation procedures were also included, as this is a rapidly developing area of activity on a population that includes young women of childbearing age who may be at particular risk with radiation exposure. The dose parameters collected were KAP (Gy.
traditional operating rooms using mobile C arms, to more complex procedures in dedicated facilities with fixed C arms. A Hybrid Operating Room is an advanced procedural space that combines a traditional operating room with an interventional suite that incorporates a fixed C arm along with a fluoroscopy capable surgical bed. These Xray machines are more powerful, operating at higher energies with larger beam sizes and detectors which can emit a 3 -10 fold higher procedural radiation dose compared with mobile C arms. 141, 224  Similar reductions have been reported during EVAR and TEVAR when moving from a mobile C arm to fixed systems. 57, 225  In a systematic review to identify studies reporting dose data during EVAR and complex abdominal aortic endovascular repair (F/BEVAR), the lowest DAP levels were identified in modern hybrid rooms with fixed systems.
Radiation dose reference levels Evaluation of the literature carried out for collation of these guidelines has shown a large variation in published radiation doses used for performing endovascular procedures. Two of the reasons for this variability are the endovascular operators' technique and the C arm equipment used. The expected radiation dose for a standard procedure should be better defined. This will come from standardised collection of procedure specific dose values for all endovascular operations. Two dosimetric parameters that should be routinely collected and are offered by most Xray guidance equipment regardless of the hardware and manufacturer are Air-Kerma Area Product and Air Kerma at the patient entrance reference point (see chapter 2. 2). Working groups can then use these data to set national DRLs (see chapter 2) for endovascular procedures and facilitate the use of radiation dosage as an additional quality metric for centres performing these procedures.
ACKNOWLEDGEMENTS On behalf of the  Public and Community Oversight Group (PCOG)  of the  Health Protection Research Unit in Chemical and Radiation Threats  and Hazards:  Ian Wright John Phipps Colette Kelly Robert Goundry Eve Smyth Andrew Wood Paul Dale  (also of the  Scottish Environment Protection Agency ) On behalf of the Society and College of Radiographers Patient Advisory Group:  Lynda Johnson Philip Plant Michelle Carmichael  -Specialist Senior Staff Nurse Guy's and  St Thomas '  NHS Foundation  trust.
2 2 Minimising radiation emitted by the C armAn understanding of basic C arm functions and the operator's interaction with the machine and surrounding environment is essential for reducing the dose of radiation emitted. Advances in imaging hardware and software have also helped to further reduce exposure. Several imaging modes may be used for Xray guided procedures that affect the amount of radiation used, including modes related to fluoroscopy, DSA and cone beam computed tomography (CBCT). CBCT refers to a modality, available in modern endovascular operating rooms, that allows cross sectional imaging whilst the patient remains on the operating table. Similar to standard CT data, the dataset of images can be processed on a 3 Dimensional (3D) workstation and represented in multiplanar reconstructions (MPR), 3D reconstructions or maximum and minimum intensity projection type reconstruction.
12  There are inconsistent data on whether brain TRX-1 levels are affected. 10, 13  Insulin resistance has been shown to increase the risk of developing Alzheimer's disease. 14  We measured ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP-2) (also known as autotaxin), since it has been proposed that increased CSF levels of ENPP-2 in Alzheimer's disease reflect aberrant brain glucose homeostasis. 15  ENPP-2 mechanism of action is to produce the bioactive lipid lysophosphatidic acid that exerts various functions in many tissues as well as in the central nervous system. 16  To assess neurovascular function, we analysed vascular endothelial growth factor (VEGF) and angiotensinogen (AGT). VEGF is mostly known for its involvement in angiogenesis, and besides participating in brain vasculature regulation, it influences neurogenesis and neuronal regeneration.
IL-12/IL-23p40, IL-15, VEGF and calprotectin IL-12/IL-23p40, IL-15, VEGF and calprotectin were measured using the ultrasensitive Mesoscale Discovery immunoassays (Mesoscale Diagnostics, Rockville, MD, USA). IL-12/IL-23p40, IL-15 and VEGF were selected from the preconfigured V-PLEX Human Cytokine Panel 1, and calprotectin was analysed using the R-Plex Human calprotectin antibody set, following the manufacturer's protocol. A 2-fold dilution was applied for IL-12/IL-23p40 and IL-15, yet samples for VEGF and calprotectin were run undiluted. Each array was scanned in an MSD QuickPlex 120, and concentration data were retrieved using Discovery Workbench 4. 0. Samples above the lowest limit of detection and with <20% intra-assay CV were considered for analysis. Inter-assay CV was <20% for all analytes.
Image acquisition and quantification Images of immunofluorescence-stained tissue sections were acquired using Zeiss LSM800 confocal microscope (Oberkochen, Germany) with ZEN 2 software (Blue, version 2. 3). Conditions were the same for image acquisition of each experiment. Images were captured from CA1 regions, when applicable, using a 20× objective and quantified using ImageJ software. 31  For co-localization analysis, first the number of p-tau+ cells was counted with the cell counter plugin, working on the single-channel image. The percentage of co-localization was calculated quantifying the number of p-tau+ cells that were showing co-staining with TRX-1 or AGT, out of the total p-tau+ cells. Biomarker profile clusters were identified using the twostep cluster analysis (SPSS Statistics/IBM Corp.
Patient clustering by biological mechanisms To assess distinct biomarker profiles within our cohort, we applied a two-step clustering analysis in the whole data set (n = 86, four samples were not eligible due to missing data). This data-driven unbiased clustering was based on the seven relatively unexplored biomarkers related to pathways conferring increased Alzheimer's disease risk. Two clusters were identified (Fig. 4A ), and the drivers of this stratification were mainly TRX-1, AGT and IL-15. Individuals assigned in Cluster 1 were characterized by parallel increases of CSF TRX-1 (P < 0. 0001), AGT (P < 0. 0001), IL-15 (P < 0. 0001), 27-OH (P = 0. 004) and IL-12/IL-23p40 (P = 0. 002; Fig. 4A  and Table  3 ) compared with Cluster 2. Cluster 1 (n = 32) contained 37% of the cohort population, including 30% of the subjective cognitive decline, 42% of the mild cognitive impairment and 40% of the Alzheimer's disease groups (Fig.
Funding This research was supported by  Vetenskapsrådet  (# 2017-06105 ),  Center for Innovative Medicine (CIMED) Sweden  (# FoUI-954431 ),  Margaretha af Ugglas foundation ,  National Institute on Aging of the National Institutes of Health  (# R01AG065209 ),  Alzheimerfonden ,  Swedish State Support for Clinical Research  (# ALFSTO-501484  and # ALFSTO-592522 ),  Gun och Bertil Stohnes Stiftelse ,  Karolinska Institutet fund for Geriatric Research ,  Stiftelsen för Gamla Tjänarinnor, Hjärnfonden  (# FO2020-0297 ),  Knut och Alice Wallenberg  (# 2015-0326 ) and  Sanofi Aventis. Instrumentation utilized in Swansea was funded by  Biotechnology and Biological Sciences Research Council  (# BB/S019588/1  to W. J. G. , # BB/L001942/1  to Y. W. ). H. Z. is a Wallenberg Scholar. Instrumentation and measures at  Sahlgrenska Academy  were supported by grants from  Vetenskapsrådet  (# 2018-02532 ) and the  Swedish State Support for Clinical Research  (# ALFGBG-71320 ).
fCidB 1-943 deletes a C-terminus part encompassing the full DUB domain, fCidB 1-737 stops after Nuf4 and fCidB 1-278 before Nuf2 (Fig  3A ). We noticed that these three fCidB mutants are inherently less stable than any others. fCidB 1-943 is imported to the nucleus but its GFP level decreases in time lapse experiments in a majority of cells to become faint perinucleolar foci only (S3 Fig). Remarkably, this mutant deleted of the DUB domain still induced 34% apoptotic events in time lapse experiments (n = 623, Figs  S2  and 3B ). Together, this dataset suggests that the deleted domain in fCidB 1-943 confers stability to CidB and confirms that the DUB domain is dispensable to CidB toxicity in cellulo. fCidB 1-737 and fCidB 1-278 are also imported to the nucleus, but in contrast to fCidB 1-943 do not induce apoptosis (Figs  3B  and S2 ).
The level of EdU incorporation in transfected cells was compared by FACS analyses to those obtained in their non-transfected counterparts and expressed as a ratio (Fig  7 ). S-phase progression in presence of fCidB with fCidA is undistinguishable from non-transfected cells and leads to a ratio of 1. In contrast, expression of fCidB alone reduces EdU incorporation levels, as does the expression of the DUB mutants fCidB C1023R and fCidB 1-943 although in a slightly milder manner. Expression of CidB CAD with fCidB 1-278 does not perturb S-phase progression unlike the DUB mutants. Together, this dataset indicates that CidB poisons S-phase progression, independently of the DUB domain, and this defect is likely to be the cause of S2R+ cell death.
Flow cytometry analyses Cell viability assays were conducted as previously described  [11]. Briefly, cells were analysed in three biological replicates at 2 and 4 days post-transfection and a growth rate calculated according to the following formula: Log2 (x at Day 4 / x at Day 2) where x is the proportion of fluorescent cells at the given time-point. A fold change equal or superior to 0 is observed when transfected cells grow at similar rate compared to non-transfected cells. In contrast, a negative fold change reflects a slower growth or cell death between day 2 and 4. Data were acquired with a Novocyte ACEA cytometer and analyzed with the NovoExpress (ACEA) software. Statistical analyses are based on an ordinary one-way ANOVA test followed by multiple comparisons: mKate2-sfGFP vs fCidB: P<0.
Acknowledgments We thank  Alice Namias  for critical reading of the manuscript. We acknowledge the imaging facility MRI, member of the national infrastructure  France-BioImaging  infrastructure supported by the  French National Research Agency  ( ANR-10-INBS-04 ,  «Investments  for the future»). We acknowledge the contribution of  Lyon SFR Biosciences  ( UAR3444/CNRS ,  US8/ INSERM ,  ENS de Lyon, UCBL) imaging facility (PLATIM)  and fly food production (Arthrotools).
This work was supported by several fundings from the  French Agence Nationale de la Recherche  (https://anr. fr/en/)«Investments for the future»:  ANR-16-IDEX-0006 -FL  and  MW -,  ANR-10-INBS-04 -BL , BH-; and a grant from the  Fondation Schlumberger pour l'Education et la  in both effectors. CidA transports, stabilizes and neutralizes CidB on the chromatin, preventing the toxin to otherwise block S-phase completion. FL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Only paired reads presenting an identical overlap region of at least 30 bp were kept. Finally, chimeric ASVs were identified and removed using the removeBimeraDenovo function and the resulting ASV were taxonomically assigned in Mothur software v. 1. 44. 3 (Schloss et al. , 2009)  using a local reference fish library (available at https://doi. org/10. 15454/AU8EZI) and the naïve Bayesian classifier method  (Wang et al. , 2007)  with a confidence score threshold of 75%. Local reference library construction and curation are detailed in  Rivera et al. (2021). Only ASVs belonging to fish (Teleostei) were kept for further analysis (Table  S3 ). The number of remaining reads after each bioinformatics step is detailed in Table  S4. After taxonomic assignment, further manual refining of the dataset was performed by completing taxonomic assignment of some taxa that could not be identified at species level and remained as "unclassified" (e.
g. , Coregonus "unclassified," Silurus "unclassified," Phoxinus "unclassified"). We were able to make these modifications because only one species of each of these different genera occurs at Lake Geneva, therefore avoiding any risk of misidentification. In addition, taxa from the same genus but assigned to difference species (e. g. , Salvelinus fontinalis, S. alpinus, and S. namaycush) were combined into one single species (S. alpinus) given that there is a single Salvelinus in Lake Geneva. Raw sequences of the mock community and the environmental samples are available at doi: 10. 5281/zenodo. 5864552. Details of the manual refining are available in Table  S5.
| Fish community composition derived from environmental biofilm samples Statistics were carried out in R software (R Core Team, 2020). Nonmetric multidimensional scaling (nMDS) was used to graphically evaluate the capacity of environmental biofilms to reveal fish community composition and to provide information on temporal and spatial changes. nMDS was performed based on Bray-Curtis distances in Vegan package  (Oksanen et al. , 2015)  using the metaMDS function. Bray-Curtis distances were calculated from fish relative abundances based on eDNA reads. Temporal changes in fish communities were assessed by grouping dates by season (autumn, winter, spring, and summer) and spatial changes were assessed by grouping samples according to the sampling site (harbor or beach). In both cases, a permutational multivariate analysis of variance (PERMANOVA) was performed using the pairwise.
| Effect of biofilm's substrate on fish community composition A Mantel test  (Legendre & Fortin, 2010)  was performed to evaluate the relationship between the fish community composition recovered from biofilms developing on natural and artificial substrates and their biomass. The test was performed between a Bray-Curtis dissimilarity matrix calculated for fish eDNA read abundances and a Euclidean distance matrix calculated for biofilm biomass in the statistical software PAST v. 3. 25  (Hammer et al. , 2001).
| Temporal differences between fish communities derived from biofilms samples Temporal differences in fish communities at the harbor and the beach were evaluated separately by grouping the data of each site according to the season. At the beach, fish communities detected during winter were different from those detected during fall (F = 5. 00, R 2 = 0. 277, p = 0. 01) and during spring (F = 5. 337, R 2 = 0. 348, p = 0. 02). The indicator species analysis showed that C. lavaretus was the main species detected at the beach site during winter (p = 0. 0199) while Perca fluviatilis was more abundant during fall and spring (p = 0. 02). At the harbor, fish communities detected during winter also differed from those detected during spring (F = 5. 756, R 2 = 0. 324, p = <0. 001), summer (F = 5. 337, R 2 = 0.
ACKNOWLEDGMENTS This work was supported by  Agence Nationale de la Recherche  ( ANR-21-CE47-0006-01 CONSULA ,  ANR-10-LABX-48-01 First-TF , and  ANR-11-EQPX-0033   Oscillator-IMP ), the  Région Bourgogne Franche-Comté  and the  EIPHI Graduate School  (contract  ANR-17-EURE-0002 ). The authors would like to thank  Gonzalo Cabodevila  for discussions on PLL characterization,  Vincent Giordano  for fruitful discussions and  Claudio Calosso  for careful reading of the manuscript.
/github. com/oscimp/digitalpllcharacterization," (2022). 36 H. Jiang, Development of ultra-stable laser sources and long-distance optical link via telecommunication networks, Theses, Université Paris-Nord -Paris XIII (2010). 37 A. Bercy, Liens ultra-stables par fibres optiques : déploiement vers plusieurs utilisateurs distants, étude des limites fondamentales et tech-nologiques et nouvelles applications, Theses, Université Paris 13 -Sorbonne Paris Cité (2015). 38 K. Manamanni, T. Steshchenko, F. Wiotte, R. L. Targat, M. Abgrall, O. Lopez, Étienne Cantin, P. Éric Pottie, A. Amy-Klein, V. Roncin, and F. Du-Burck, "Limitations due to residual interference in a fiber-based optical frequency reference at 1. 55 µm," (2022). "Oscillator IMP project, Digital PLL characterization: https:/.
Background This retrospective analysis of data from clinical trials in metastatic urothelial carcinoma (mUC) was conducted to determine baseline patient characteristics associated with long-term survival (LTS) following treatment with immune checkpoint inhibitors. Methods Data for this analysis were from patients with platinum-refractory mUC who received durvalumab or durvalumab plus tremelimumab in phase 1/2 studies. The primary outcome measure was LTS. Patients were categorised as overall survival (OS) ≥ 2 years (from first dose) or OS < 2 years. A univariable analysis assessed independent associations with LTS and multivariable logistic regression was employed including each variable with P ≤ 0. 05 as covariates.
5 g/dL, neutrophillymphocyte ratio (NLR) > 5 and liver metastases were used to derive a risk score for OS. Using patient-level data from clinical studies of atezolizumab, avelumab and durvalumab in platinum-refractory mUC, Sonpavde et al. [18]  developed a prognostic model for OS that includes ECOG PS (1 vs 0), liver metastasis, platelet count, NLR and lactate dehydrogenase (LDH) levels. The current retrospective analysis was undertaken to identify factors that may predict long-term benefit with ICIs in mUC. We evaluated several baseline characteristics among long-term and short-term survivors who received durvalumab (PD-L1 inhibitor) monotherapy or durvalumab combined with tremelimumab (anti-cytotoxic T-lymphocyte antigen 4 inhibitor) in the platinumrefractory setting.
Analysis population The primary analysis population included 192 patients from Study 1108 and 168 patients from Study 10 who were enrolled in the studies at the time of this analysis. Additional patients continued to be enrolled in Study 1108, however, these patients were not included in the current analysis. Study 1108 (NCT01693562) was a phase 1/2, multicentre, open-label study of durvalumab monotherapy at a dose of 10 mg/kg every 2 weeks for up to 12 months in solid tumors. Eligible patients could have disease that progressed on prior therapy or be treatment-naïve, had ECOG PS 0/1, and had adequate organ and bone marrow function. Patients were not eligible if they had received any immunotherapy or investigational anti-cancer therapy within the past 4 weeks (6 weeks for monoclonal antibodies) or if they were receiving any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer.
Patients who met these criteria and had locally advanced/metastatic UC and whose disease had progressed while they were receiving prior therapy or were ineligible for or refused any number of prior therapies were eligible for inclusion in the UC cohort. Patients from the UC cohort were included in the current analysis  [8, 10]. Study 10 (NCT02261220), was a phase 1, multicentre, open-label study of durvalumab at 20 mg/kg plus tremelimumab at 1 mg/kg every 4 weeks for 4 months, followed by durvalumab monotherapy at 10 mg/kg every 2 weeks for up to 12 months in solid tumours  [19]. Eligible patients had histologic confirmation of advanced solid tumours, recurrent/metastatic disease and may have previously been treated in the recurrent/metastatic setting. Patients were excluded if they had used any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment, had active or prior documented autoimmune disease within the past 2 years, or if there was current or prior use of immunosuppressive medication within 14 days.
Patients from this UC cohort were included in the current analysis. This is a post hoc analysis of data previously collected from Study 1108 and Study 10. The data involved included demographic, survival data and tumour response. Data were already available for analysis, with no new data collected from the patients and thus the original study consent forms covered this analysis. The inclusion of patients' data in this post hoc analysis was allowed under the Study 1108 and Study 10 consent forms. Study 1108 and Study 10 were conducted according to the Declaration of Helsinki and approved by the independent ethics committee or institutional review board at each of the participating centres (Supplementary Table  1 ), with written informed consent obtained from all patients. All methods were carried out in accordance with relevant guidelines and regulations.
The analysis population included all patients who received at least one dose of durvalumab, had received prior platinum therapy as first-line chemotherapy, had a baseline assessment with measurable disease (per blinded independent central review according to Response Evaluation Criteria in Solid Tumors, version 1. 1 [RECIST v1. 1]), and at least 24 weeks of follow-up at the time of data cutoff on September 22, 2020.
Data collection and outcome measures Demographic, clinicopathologic, radiologic and laboratory data at baseline were collected for all patients. The primary outcome measure was long-term survival, defined as OS of ≥ 2 years from the date of first dosing with durvalumab or durvalumab plus tremelimumab. OS was defined as the time from start of treatment to date of death from any cause. For patients who were alive at the time of data cutoff or lost to follow-up, OS was censored on the date when the patients were known to be alive. For the purpose of these analyses, patients were categorised as OS ≥ 2 years or OS < 2 years without consideration of censoring status. A sensitivity analysis was conducted where censored patients were excluded from the OS < 2 years subgroup. Long-term progression-free survival (PFS), defined as a PFS duration of ≥ 6 months from the start of treatment until objective progression or death, was a secondary outcome measure.