dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2020). In addition, human variability in TK processes using the pharmaceutical database has been investigated for specific isoforms of phase I (e. g. CYP3A4, CYP2C9, CYP2C19, CYP2D6; PON1) and phase II enzymes (e. g. GSTs) by means of meta-analysis of parameters reflecting acute (Cmax) and chronic exposure (AUC)  (Testai et al. , 2021). The resulting variability distributions were combined with isoform-specific in vitro metabolism data for food relevant chemicals (e. g. pesticide active substances, contaminants) to predict their blood concentrations in humans by means of PBK and QIVIVE modelling. Finally, PBK-TD modelling has also been developed for specific pesticide active substances and endpoints such as acetyl-cholinesterase inhibition  (Kasteel et al. , 2020; Testai et al. , 2021). Such developments will allow the integration of quantitative mode of action and AOP information in chemical risk assessment.
, 2021). Finally, such a guidance document will provide a basis to derive reference points and health-based guidance values on an internal dose basis for risk characterisation through illustrative case studies. • To develop an EFSA harmonised guidance document on the use of NAMs in chemical risk assessment. The PPR panel recommends further integration of NAMs in chemical risk assessment (e. g. high-throughput techniques, in vitro, OMICs and in silico methods such as PBK and QIVIVE models) as currently investigated worldwide (OECD, US EPA, EFSA). Relevant examples include large open-source platforms such as the US-EPA CompTox Chemicals Dashboard, ECHA's REACH database and EFSA's OpenFoodTox and new QSAR models predicting TK and TD properties of chemicals such as the VEGA hub and the OPERA suite from US-EPA  (Dawson et al.
, 2011; Pelkonen et al. , 2015). There are no regulatory approved strategies to assess the potential role of reactive metabolites; in a case of suspected toxicological significance, a scientifically justified research strategy can be developed. Initial in silico/in vitro studies • Pre-screening for potential structural alerts using in silico methodology against existing databases (e. g. QSAR, Read-across, etc. ). • Use of various trapping agents in in vitro systems based on subcellular preparations or isolated/cultures cells, especially hepatocytes. • Detection of covalently (tightly) bound radioactivity in in vitro systems (i. e. coming from comparative in vitro metabolism studies, see Section 5) • Tentative identification of trapped/bound reactive metabolites by mass spectrometric techniques.
LOE3: In vivo metabolism and TK in rats or other test species. LOE4: In silico evidence in rats, test species or humans. Methods for weighing and integrating hazard evidence have been described elsewhere and include qualitative methods (listing, best professional judgement, semi-quantitative methods (causal criteria, logic); quantitative methods (scoring, indexing and quantification)  (Linkov et al. , 2009; EFSA Scientific Committee, 2017a). The methods of choice to be applied will depend on data availability, context of the assessment, complexity of the method, time constraints and resources and the assessor should provide a rationale for choosing a particular method. A key aspect for weighing and integrating the evidence is the assessment of the reliability, relevance and consistency of the evidence and the iterative nature of the process (EFSA Scientific Committee, 2017a).
ACKNOWLEDGMENTS We acknowledge the members of the  AEgIS (Antihydrogen Experiment: Gravity, Interferometry, Spectroscopy ) collaboration for fruitful discussions. This work was supported by the  Research Council of Norway  under Grant Agreement No. 303337  and by  Domaine d'Intérêt Majeur Science et Ingénierie en Région Île-de-France pour les Technologies Quantiques (DIM SIRTEQ)  grant  LAS-ANTI. LASANTI grant  from the PME 2020 call of the DIM (in French: Domaine d'intérêt majeur) SIRTEQ (in French:  SCIENCE ET INGNIERIE EN RÉGION ÎLE-DE-FRANCE POUR LES TECHNOLOGIES QUANTIQUES ) and from the  IQUPS project (in French: Ingénierie Quantique à l'Université Paris-Saclay ) which is an " Initiative de Recherche stratégique " of the  Université Paris-Saclay.
Etiology PDAC is a paradigm of complex disease. Known environmental risk factors explain only about 40% of the disease. [16] [17] [18] [19]  The growing prevalence of diabetes and obesity, mainly in Westernized countries (www. who. int/diabetes/global-report), may partly account for the increased incidence of PDAC. Many meta-analyses, carried out collecting datasets from studies including >3000 PDAC patients assessed that diabetic patients showed a 1. 8-fold increased risk of PC (95% CI 1. 5-2. 1). 14 Similarly, obesity and overweight at any age are associated with increased incidence of PDAC, with hazard ratio ranging from 1. 15 to 1. 53. In this context, a longer duration of BMI > 25 kg/m 2 is significantly associated with PDAC risk (HR per 10 years increment of duration: 1. 06 95% CI: 1.
Currently, extracellular vesicles (exosomes) are among the most promising candidates for early diagnosis of PDAC. 45 In these vesicles, several candidate markers for IPMN in exosomes such as KRAS mutations and glycipan have been proposed. 46 Apart from serum, several publications have proposed pancreatic juice as another promising source for molecular analysis for diagnosis of early lesions. 47 In addition to individual markers, panels of different markers are more likely to predict malignancy with sufficient diagnostic accuracy. Stemming from a study in serum protein profiling,  48  a panel of immunoregulatory marker proteins has been tested in PDAC patients. 49 A study in IAR testing this panel has finished recruiting (PANFAM, NCT03693378). Given the fact that many initially promising markers or combinations thereof have failed validation in large trials, it is evident that all of these approaches need confirmation in independent multi-center cross-national prospective trials requiring a pan-European network that utilizes all state-of-the-art methodologies including multi-omics platforms and artificial intelligence algorithms developed by academic centers and industry.
ACKNOWLEDGEMENTS John P. Neoptolemos  has received research funding from the  Dietmar Hopp Stiftung GmbH , the  Stiftung Deutsche Krebshilfe , and the  Heidelberger Stiftung Chirurgie , all of which were not related to the submitted work. Patrick Michl  is supported by the  German Research Foundation (DFG)  and  Eli Lilly & Co. , all of which are not related to the submitted work.
After imaging, place the plate back to the incubator. 85. Following image acquisition, image analysis can be performed using Columbus software (Data S1: Material analysis pipeline -Analysis Sequence 'SphereQuant_texture'). First, use texturebased pixel classification to identify the liver spheres from the background. This can be achieved by training texture-based classifier to distinguish between two classes (cell aggregate and background) by selecting multiple examples of pixels for each class (Figure  5 ). Next, generate an inverted image which can be used for sphere identification based on sphere size and texture using the 'Find Nuclei' block (Figure  5 ). Following this, an object classification can be used for sphere selection as a quality control step to ensure that only properly segmented spheres are analyzed (Figure  5 ).
In addition to associations from epidemiological studies, multiple mechanistic pathways through which alcohol can cause cancer have been proposed. In this review, we aim to summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-driven carcinogenesis. We searched the PubMed and Cochrane databases for reviews, umbrella reviews, meta-analyses, and Mendelian randomisation studies on total alcohol use and cancer risk and mechanisms of alcohol-related carcinogenesis published up until June 2021. We also searched the WCRF's Continuous Update Project reports for meta-analyses on alcohol consumption and cancer risk.
Acknowledgements L-C. S. H. thanks the  Ministry of Science and Technology of the Republic of China (MOST)  and the  German Academic Exchange Service (DAAD)  for his DAAD-MOST Sandwich fellowship. D. L. thanks the  Alexander von Humboldt Foundation  for his postdoctoral fellowship. J. R. H. and M. -H. H. thank  MOST  (Grant No. 109-2634-F-007-023 ) as well. The Macroarc group (ITCP,  KIT ) and the  Levkin lab (IBCS-FMS, KIT ) are gratefully acknowledged for access to SEC and DLS instruments, respectively.
The SENIOR study was the first randomized controlled trial (RCT) dedicated to evaluating the efficacy and safety of the second-generation BI analogue glargine 300 U/mL (Gla-300) compared with the firstgeneration BI analogue glargine 100 U/mL (Gla-100) in older adults (aged ≥65 years) with T2D. 6  However, no head-to-head comparisons have been made between Gla-300 and the other second-generation BI analogue (insulin degludec [IDeg]) in older individuals with T2D. BRIGHT (NCT02738151) was the first RCT to compare the efficacy and safety of Gla-300 and IDeg 100 U/mL (IDeg-100) in insulinnaïve people with T2D. 7  BRIGHT met its primary endpoint, showing non-inferior HbA1c reduction with Gla-300 versus IDeg-100 during the overall 24-week study period with a similar risk of hypoglycaemia over 24 weeks.
| Data analysis and statistics Efficacy assessments were performed in the intent-to-treat (ITT) population (all randomized subjects who received at least one dose of study BI, irrespective of the treatment being received). Safety assessments were performed in the safety population (all randomized participants who received at least one dose of study BI, regardless of the amount of treatment administered). Change in HbA1c over 24 weeks was analysed by a mixed-effect model with repeated measures (MMRM), using the missing at random framework, with fixed categorical effects of treatment, visit, treatment-by-visit interaction, and the continuous fixed covariates of baseline HbA1c value and baseline HbA1c value-by-visit interaction. Heterogeneity of treatment effect across age subgroups was assessed by adding an interaction term of treatment-by-age category.
(1. 4) A single cusp has the local isometry pseudo-group given by ℝ × ℝ which is realized by linear scaling and translations in the , variables , 0 ( , ) ∶= ( , + 0 ), (1. 5) or in , -variables , 0 ( , ) ∶= ( + , + 0 ). (1. 6) Using the , variables we can write ∈ * , as = + for ∈ ℝ and ∈ ℝ and the Riemannian norm of such a cotangent vector is given by | | = √ 2 + | | 2 ℝ. (1. 7) Elements ∈ * , of a cosphere fibre are thus in bijection with ∶= ( , ) ∈ ⊂ ℝ +1. In particular the cosphere bundle over the cusp is trivializable * ≅ ( , ) ×. The usual metric on * , the Sasaki metric (see e. g. [GK02]  for an easily accessible introduction), is not a product metric. However, one can check (see the expression of the Sasaki metric in [Bon16, Section C. 2]) that it is equivalent to the product metric ⊗ where is the usual metric on the sphere.
* Research partially supported by  EPSRC  grant  FptGeom  ( EP/N029143/1 ),  ANR  grant  ESIGMA  ( ANR-17-CE23-0010 ), the  LABEX MILYON  ( ANR-10-LABX-0070 ) of  Université de Lyon , within the program " Investissements d'Avenir"  ( ANR-11-IDEX-0007 ) operated by the  French National Research Agency (ANR) , the  ANR  Project  DISTANCIA  ( ANR-17-CE40-0015 ) operated by the  French National Research Agency (ANR) , and by the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation programme Grant Agreement 714704.
FUNDING TR, M-CH, and BP are financially supported by Agence Nationale de la Recherche (ANR) and Agence Francaise pour la Biodiversité(AFB) ("ChitoProtect" project, grant # ANR-19-ECOM-0008) and Institut Carnot Plant2Pro ("VitiLYKs" project, grant # C4520). TR, M-CH, DW, AZ, LD, and BP have been supported by the Ministère de l'Enseignement Supeŕieur, de la Recherche et de l'Innovation (MESRI). DW is supported by the MESRI, Investissements d'Avenir program, project "Initiatives Science Innovation Territoire Economie en Bourgogne-Franche-Comte" ("Structure, Function and Roles of Nitric Oxide Synthases in Algal Responses to Environemental Stresses (NOISELESS)" project, grant # RA18041. AEC. IS) and the ANR ("Algae-Nitric Oxide Synthases" project, grant # ANR-18-CE20-0022-02). LD is supported by grants from "La Ligue contre le cancer" Comitéde la Cote d'Or, the "Conseil Regional de Bourgogne-Franche-Comte", the ANR, ("Investissements d'Avenir" program, grant # ANR-11-LABX-0021) and the European Union program FEDER.
Materials and Methods is is a retrospective case series of 3 consecutive cases performed at Geneva University Hospital between November 2020 and March 2021. All patients signed an informed consent for the surgery and for research purposes during follow-up in accordance with the tenets of the Declaration of Helsinki. Data were retrieved from institutional electronic medical records. Inclusion criteria for scleral-fixated IOL were aphakia with no capsular bag and poor iris support (i. e. , iridodonesis or iris defect) and/or poor endothelial cell count (<1000 cells/mm 2 ). Exclusion criteria were pregnancy or inability to give informed consent.
Data Assessment. e following data were assessed: preand postoperative visual acuity (Snellen best corrected visual acuity: BCVA), slit lamp examination, intraocular pressure and fundus examination, and Scheimpflug imaging (Pentacam, Oculus, Wetzlar, Germany) at one month. Eyes were observed for modifications in astigmatism magnitude and axis, IOL centration, tilting, and any postoperative complications. Our operations are routinely recorded, and surgery time and technique of all three cases were reviewed after the cases were finished. Due to the low number of patients in the preliminary study, no statistical analysis was performed. (a) (b) (c) (d) (e) (f ) (g) (h) (i) (j) (k) (l).
Results ree patients were recruited in this retrospective study, two males (45 and 51 y. o. ) and one female (77 y. o. -patient 1). Aphakia resulted from ocular injury in the 2 male subjects and from a complicated cataract surgery for the female patient. Clinical data such as visual acuity (logMAR), refraction, intraocular pressure with Goldman applanation tonometry, and astigmatism are summarized in Table  1. Surgical data such as IOL centration, IOL tilting, and surgery time are summarized in Table  2. Lenses tilting assessed with the Scheimpflug tomography could retrieve only minor tilting as shown in Figure  2. ey were no peroperative complications such as hypotony, hemorrhage, or eye instability. One patient presented a conjunctival disinsertion of the limbus at week one and required a conjunctival suture in the OR to protect the 10-0 polypropylene threads.
Acknowledgements This collaborative study was made possible through the  EU Horizon 2020 research and innovation programme MOBILE FLIP 637020  and the  Swedish Bio4Energy Strategic Research Environment. The authors warmly thank  Markus Segerstr€  om for assistance with pelleting and characterisation at the  Biomass Technology Centre. The  French National Research Agency (ANR)  is acknowledged for partial funding of the GENEPI platform within the framework Investments for the Future (Ref:  ANR-11-EQPX-0019 ).
Therefore, measuring A CP (K 0 S K 0 S ) provides independent information which can help to elucidate the mechanisms of CP V in charm hadron decays. The current world average for the time-integrated CP asymmetry is A CP (K 0 S K 0 S ) = (0. 4 ± 1. 4)%  [9] , the precision of which is still insufficient for detecting an effect. In this work, a new measurement of this quantity, performed with proton-proton (pp) collisions collected from 2015 to 2018 (Run 2) by the LHCb experiment at the LHC at CERN, is reported. Data collected at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb -1 , are used. The subsample of data collected during 2015 and 2016 has been analyzed previously  [10]. In the present work a number of improvements in the analysis leads to a more efficient selection and a sizeable improvement in sensitivity.
Acknowledgements We express our gratitude to our colleagues in the CERN accelerator departments for the excellent performance of the LHC. We thank the technical and administrative staff at the LHCb institutes. We acknowledge support from  CERN  and from the national agencies:  CAPES ,  CNPq ,  FAPERJ  and  FINEP (Brazil) ;  MOST  and  NSFC (China) ;  CNRS/IN2P3  (France);  BMBF ,  DFG  and  MPG (Germany) ;  INFN (Italy) ;  NWO (Netherlands) ;  MNiSW  and  NCN (Poland) ;  MEN/IFA (Romania) ;  MSHE (Russia) ;  MICINN (Spain) ;  SNSF  and  SER (Switzerland) ;  NASU (Ukraine) ;  STFC  ( United Kingdom );  DOE NP  and  NSF (USA). We acknowledge the computing resources that are provided by  CERN ,  IN2P3 (France) ,  KIT  and  DESY (Germany) ,  INFN (Italy) ,  SURF (Netherlands) ,  PIC (Spain) ,  GridPP  ( United Kingdom ),  RRCKI and Yandex LLC (Russia) ,  CSCS (Switzerland) ,  IFIN-HH (Romania) ,  CBPF (Brazil) ,  PL-GRID (Poland)  and  NERSC (USA).
Study Design and Patient Population. After institutional review board approval (IRB 00009118), we conducted a retrospective analysis of a prospectively maintained database of ASD patients operated between 2015 and 2018. Prior to inclusion, every patient signed an informed consent. Inclusion criteria were as follows: all adult patients managed surgically for ASD with a posterior fixation that included all the lumbar spine (upper level instrumented vertebra L1 or above, lower instrumented vertebra S1 or below), primary surgery or revision case, pre and postoperative full spine X-rays available, and one-year minimal follow-up (including full spine X-rays). For each patient, demographic data, clinical scores (lumbar VAS and Oswestry Disability Index), and full spine X-rays (AP and lateral) were obtained preoperatively, in the immediate postoperative period, and at one-year of followup.
Statistical Analysis. Data were formulated as means and standard deviations. Comparisons were carried out using Student's t-test for normally distributed variables. e population was analyzed as a whole and then stratified according to the 1-year postoperative PI-LL mismatch. Patients were classified as the "aligned" group when postoperative PI-LL was below 10 °and "not aligned" otherwise. e two groups were compared with regards to radiographic parameters and mechanical complications. e relationship between PI-LL mismatch and lumbar lordosis distribution was investigated using Spearman correlation tests. e significance level was set at 95% (i. e. , p < 0. 05).
One of the most intriguing features of Plasmodium development is the closed mitosis strategy used for replication, which involves the formation, during schizogony and sporogony, of a syncytium followed by budding and cytokinesis  [17, 18]. Equally interesting is the gametogenesis where three rounds of rapid DNA replication occur within minutes to generate 8 fertile male gametes (Figure  1 ). As those processes rely on highly flexible, adaptable and parasite-specific mechanisms, they are of great interest for the malaria scientific community aiming to uncover Plasmodium-specific druggable pathways. Recently, with the massive technological improvement of reverse genetics, multi-omics tools, as well as the availability of databases to speed up data mining, major breakthroughs have been achieved in deciphering the role of phosphatases in the Plasmodium life cycle.
Acknowledgements The authors gratefully acknowledge  Gestamp Hardtech ,  Volvo Cars ,  Ionbond Sweden AB  and  Quaker Houghton  for contributing with experimental materials and for their keen interest in this work. The authors are grateful for the financial support from  Vinnova  to this project, through the  LIGHT  project (" Luleå University of Technology and Swedish Industry Group for High-performance Tribology research "), grant number  2017-05229.
We aim to convert the problem of clogging of the nozzle into an external operation, which can be performed when the machine is running. The 5S functionalities enable us to determine how this external operation can be performed by the user. To solve this problem, we have formulated all data about our problem. In Fig. 6 , we have used the problem graph for the problem formulation to identify the problems and partial solutions. We started with forming our initial problem of the clogging of the nozzle. Then, we look for the effects of this initial problem in terms of partial solutions, and thus the other problems that can be generated by the partial solution. In TRIZ, there are there types of contradictions: (1) Administrative contradiction: this contradiction describes a desire to improve a system without showing the direction.
TECHNIQUE The principle is to perform an adventitial aortic anastomosis with a prosthetic graft after a limited dissection of the anterior aortic wall, mimicking the final aspect of an end-to-side anastomosis. The anastomosis is then opened and stabilized using a covered stent, which provides a pulsatile flow into the graft. An educational video will allow vascular physicians to reproduce the technique (Video). All patients provided written informed consent before procedures. Institutional review board approval was not necessary for the present publication. Indications. Data from all patients with a contraindication to aortic clamping who underwent this technique of hybrid aortic clampless anastomosis were reviewed. These patients were considered poor candidates for endovascular treatment (Fig  1 ) based on preoperative computed tomography angiography revealing a highly calcified lesion beginning at the arteries ostia or a shaggy aorta.
Preoperative, intraoperative, and follow-up data were reviewed based on medical records and imaging modalities. Contraindications to aortic clamping are detailed in Table  I. Technical approach. Procedures were performed under general anesthesia with a conventional angiographic C-arm (Veradius Unity, Philips Healthcare, Amsterdam, the Netherlands) (Video). The anastomosis technique was standardized. A limited exposure of a healthy anterior aortic wall without major calcifications or thrombus was obtained (Fig  2, A ). A beveled prosthetic graft (Fusion, Maquet, Rastatt, Germany, or ringed PTFE Gore, Newark, Del, or Gelsoft, Vascutek, Inchinnan, UK) was quickly sutured to the aorta using 4/0 polypropylene sutures without any arteriotomy or clamping (adventitial running suture), mimicking the final aspect of an end-toside anastomosis (Fig  2, B ).
Proposed research for the roadmap To implement multigene panel testing using NGS approaches (targeted, WES or WGS) for CPD: single-step  sequencing of "diagnostic-grade" genes as the first-line diagnostic approach for patients with CPD may prove more time and cost-effective than traditional Sanger sequencing. The following steps are encouraged: development of guidelines related to informed consent documents and opt_in/opt_out possibilities for leukemia risk genes; to stimulate reporting variants in open access variant databases for improved variant classification; development of easy-to-use variant selection platforms; introduction of WGS in frontline clinical diagnostics. To establish registries of CPD patients with known pathogenic variants: systematic data collection supported by Findable, Accessible, Interoperable and Reusable (FAIR) data practices, to define the clinical consequences of pathogenic variants through the systematic investigation of large patient cohorts (including follow-up of clonal hematopoiesis in patients with mutations in RUNX1, ETV6, and ANKRD26).