dataesr/scientific-paragraphs-categorization huggingface dataset:
Moreover, to carry out a worldwide, multicentric, prospective study to assess the bleeding complications of surgery; to promote systematic surveys on the efficacy of prophylactic platelet transfusions before surgery or delivery and develop guidelines; to investigate modulating factors of clinical severity other than the causative pathogenic variants. To identify new genes responsible for unexplained CPD: supplementation of WES or WGS datasets of unexplained patients with platelet RNA-sequencing and proteomics data; to stimulate gene discovery programs on specific platelet disorder groups that still have very low diagnostic yields; to promote additional case reports with variants in recently discovered genes for CPD that still require confirmation. To use cell-based models to study platelet formation and function for disease modeling as well as preclinical studies of novel therapies: to promote the use of disease models based on patient-derived hematopoietic stem cells and inducible pluripotent stem cells.
Acknowledgements A. W. E and A. S. contributed equally to the work. We acknowledge support from the  Knut and Alice Wallenberg Foundation  through the  Wallenberg Centre for Quantum Technology (WACQT). A. W. E. acknowledges support from  Vetenskapsrådet Starting Grant  (Ref:  2016-03905 ). A. W. E. and I. E. Z. acknowledge support from the  ATTRACT  project funded by the  EC  under Grant Agreement 777222. S. S. acknowledges support from the  Swedish Research Council (Vetenskapsrådet)   Starting Grant  (ref:  2019-04821 ).
For SS-J3 specimens, a minimum of 6 indents per sample were measured to provide an average hardness value of each steel. All the irradiated samples were tested because Vickers hardness measurements can serve as a cross-check on the sample temperatures by highlighting any material showing abnormal hardness behavior. Tensile tests. Tensile tests were carried out on type SS-J3 miniature tensile specimens using a strain rate of 10 -3 s -1 in shoulder loading configuration and using the machine stroke for estimating elongation, following the standard procedure guidelines provided in ASTM E8/E8M-15a. Tests were performed at room temperature (RT) and 300 • C using an Instron 3367 tensile machine equipped with a 5 kN load cell. Elevated temperature tests were conducted in high vacuum environment. Load and strain data were digitally recorded and analyzed.
Tensile properties 3. 3. 1. Tensile tests Tensile tests were performed on SS-J3 tensile specimens before and after irradiation. The measured Yield Strength (YS), Ultimate tensile Strength (UTS), Uniform Elongation (UE) and Total Elongation (TE) are presented in Fig. 6  for tests at 300 • C. Data of the EUROFER97/2 reference material with a standard heat treatment are added for comparison. It is evident that all the steels hardened after irradiation, reflected by an increase in the YS and UTS. This was accompanied by a decrease in UE and TE. As expected previously from the Vickers hardness results, Kand L-series steels are the strongest materials, with UTS above 800 MPa before irradiation and above 900 MPa after irradiation. The rest of the material present YS in the range 330-460 MPa in the unirradiated state, and 510-640 MPa in the irradiated state, which proves them all softer than EUROFER97/2, especially after irradiation.
Fracture toughness Fracture toughness measurements were performed on subminiaturized specimens with application of the master curve approach. The values of the transition temperature T 0Q before and after irradiation are reported in Fig. 9. Considering that the irradiation of bend bars on materials M and N failed, these results are not shown here. Data of the EUROFER97/2 reference material are added for comparison. Also, values of the DBTT from Charpy impact tests on KLST specimens of unirradiated materials are reported on the figure. The results in Fig. 9  show clearly the irradiation-induced upward shift in T 0Q. For the reference material EUROFER97/2, the upward shift is expected to be of about +110 • C after irradiation at 300 • C to 2. 5 dpa  [2]. Materials E (sub-optimum reference), K, and L showed a similar degree of irradiation embrittlement as the standard EUROFER97/2.
Acknowledgements This work has been carried out within the framework of the  EUROfusion Consortium  and has received funding from the  Euratom  research and training program 2014-2018 and  2019-2020  under grant agreement No  633053. The views and opinions expressed herein do not necessarily reflect those of the  European Commission. SCK CEN acknowledges the financial support of  FOD grant  provided for fusion R&D. The authors also wish to thank  T. Bergfeld  ( KIT ) for the chemical analysis and  D. Bolich  ( KIT ) for the material preparation and heat treatments.
TREATMENT Antithrombotic Strategy The optimal antithrombotic treatment in patients with AAA remains uncertain. In patients with ischemic stroke and AAA, several antithrombotic strategies have been tested to prevent recurrence. They included aspirin, combination of antiplatelets, warfarin, and combination of low-intensity warfarin with aspirin. Retrospective studies showed a potential benefit of warfarin over aspirin  (17, 53). However, these data were not confirmed in match control studies or clinical trials  (54) (55) (56) (57) (58). There has been only one prospective randomized trial conducted specifically in patients with AAA and stroke. The Aortic Arch Related Cerebral Hazard Trial (ARCH) compared Aspirin plus Clopidogrel (A + C) vs. warfarin with target International Normalized Ratio (INR) 2.
ACKNOWLEDGMENTS SK acknowledges the  Science and Engineering Research Board  (SERB),  Department of Science and Technology, Government of India , for financial support through project no. CRG/2020/000892. Joint Advanced Technology Center, IIT Delhi , and Director,  LASTEC Delhi  are also acknowledged for support through EMDTERA#5 project. Mr. Akash Kumar  and  Dr. P. K. Muduli  are thanked for their help during the material synthesis using UHV sputtering. One of the authors (Sandeep Kumar) acknowledges the  University Grants Commission, Government of India for Senior Research Fellowship.
The most significant configurations are shown in Fig. 2  we aim to counterbalance the threshold voltage increase at 77K to achieve high performance at a reduced drain voltage while benefiting from the steeper sub-threshold slope, keeping the leakage current low. To this effect, the most suitable configuration is the flip-well architecture with forward back-gate-biasing (FBB), i. e. , positive (resp. negative) bias on N-WELL (resp. P-WELL) for NMOS (resp. PMOS)  [15]. Test dies cleaved from a wafer were mounted on a sample holder in a tabletop Lakeshore cryogenic probe station with four adjustable contact needles connected to Source/Measurement Units. The chamber was cooled down under continuous helium flow with temperature regulation between 300 and 77K. The data acquisition was performed using a semiconductor parameter analyzer (HP 4156) with a noise floor of 50 fA.
D. Performance analysis Performance of flip flops can be quantified in terms of the setup time, hold time, and Clk→Q delay metrics. The setup time requirement arises due to finite delay for the data to traverse the primary latch before the arrival of the clock at the secondary latch's transmission gate. The setup time for the pseudo-static flip-flop is quantified by measuring the time delay for data arrival at the second transmission gate in the presence of process variations. Fig. 12 (a) presents setup Fig. 11. The voltage at SN drops down to 0. 1V in 1ms, assuming the worstcase scenario of DIN' pulled low, CLK' node driven high, and SN is high. This voltage drop is restored using a refresh MUX. In the pseudo-static flip-flop design, the data must traverse a MUX path (designed using transmission gates) → inverter → Transmission Gate → Inverter before reaching the N2 node.
ACKNOWLEDGEMENTS Funding. The interview and Rapid Service Fee were funded by  Sanofi, France. Medical Writing and/or Editorial Assistance. We thank  Pierre-Alain Boyer, PhD , for medical writing assistance on behalf of Springer Healthcare, France. Institutional support for editorial assistance from  Springer Healthcare , France, was provided by  Sanofi. Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Acknowledgements MB thanks  E. Mussard  and  J. Viémon-Desplanque  ( GenPhySE, INRAE, Toulouse, France ) for their contribution to the rabbit organoid cell monolayer culture and polarity reversal in pig organoids (Figures 4B and5). CC would like to thank  A. Bruneau ,  N. Daniel  and  V. Brochat  ( Micalis and Breed Labs, respectively, INRAE, France ) for the micro-injection experiments and  C. Le Poupon  for the 3D staining in pig intestinal organoids (Figures  4C and6 ). EG, FB and GE thank  J. Rivière  and  M. Vilotte  ( @BRIDGe facility, GABI, INRAE, AgroParisTech, Paris-Saclay University ) for histology and virtual slide scanner (Figure 4). SL-L and AW thank  A. Gagneux  and  O. Bernardi  for their contribution to the chicken organoid culture and  J. Burlaud-Gaillard  ( Plateforme IBiSA de Microscopie Electronique, Université de Tours et CHRU de Tours ) for transmission electron microscopy analysis (Figure  4F ).
Text formatting All manuscripts should be submitted in a Word format, they should be single column and 1. 5 spaced. Margins should be one inch at the top, bottom and sides of the page. Font size should be 11-pt or 12-pt, standard font in 'Arial', 'Times New Roman' typeface Or another standard font. Manuscripts should be formatted in full justified paragraphs and headings should be leftaligned. Maths should be editable text.
Acknowledgements We acknowledge funding from  European Commission  through the  Graphene Flagship , the  ERC  Grants  SUPRA2DMAT  ( GA-833707 ),  FUTURE-PRINT  ( GA-694101 ), Hetero2D, GSYNCOR, the  EU Grant Neurofibres , the  Agence Nationale de la Recherche  through the  Labex projects CSC  ( ANR-10-LABX-0026 CSC ) and  NIE  ( ANR-11-LABX-0058 NIE ) within the  Investissement d'Avenir program  ( ANR-10-120 IDEX-0002-02 ), the  International Center for Frontier Research in Chemistry (icFRC) ,  EPSRC  Grants  EP/K01711X/1 ,  EP/K017144/1 ,  EP/N010345/1 ,  EP/L016057/1 , and the  Faraday Institution. The HAADF-STEM characterization was carried out in the  Advanced Microscopy Laboratory (Dublin) , a  Science Foundation Ireland (SFI)  supported centre.
Study population. The study population included 29 patients from the Nephrology ward from Hospital Clínico Universitario Lozano Blesa (Zaragoza, Spain). Inclusion criteria were (i) 18-year-old (or older), (ii) having a diagnosed ESRD pathology and (iii) undergoing HD at least three times per week (with venous or cannula access). Table  1  shows the population characteristics. The study protocol was approved by the Aragon's research ethics committee (CEICA, ref. PI18/003) and all patients and/or their legal guardians signed informed consent. All the procedures and all the methods were performed in accordance with the Helsinki Declaration. The database collection is still ongoing, with the current size significant enough for a pilot study  21, 22. Data collection. General information. Sex, age, concomitant therapies (e.
1 ). [K + ] was computed as in (23). + denotes outliers. Table  4. Intra-patient Spearman's ( ρ ) and Pearson's (r) correlation coefficients between [K + ] , and time- warping based markers, and T w and T S/A , in all cases evaluated from the first PCA transformed lead, and from standard single leads II, V3, V4, V5 and V6. Values are expressed as median (IQR). [K + ] , at least in our dataset. Moreover, this finding gives validity to the proposal of the dw,c presented in this work, which assumes no correlation between HR and [K + ]-related changes on T-wave morphology.
Nevertheless, time warping analysis was applied in recent studies  19, 20  to investigate both hypo-and hyperkalemia on a extremely heterogeneous pool of simulated cases, performing equally well in all the cases and proving its adaptability, at least in silico simulated ECGs, probably due to its personalize profile as being comparative with a reference. Therefore, we hypothesized that the proposed methodology for [K + ] monitoring could be applied to investigate a wide range of populations and experimental sets. Other recent studies developed deep-learning models and tested them on large datasets to screen for hyperkalemia in patients with CKD, reporting a more robust recognition of severe hyperkalemia, thus potentially reducing the risk of sudden cardiac death in those patients  50, 51. However, in our study we aim, not just to detect hyperkalemia, but also in continuous [K + ] quantification.
Extension of the database will open the door to use deep learning techniques, which will allow proper comparison with the methodology here proposed. The main limitation of this work concerns the reduced amount of blood tests (only six) took from each patient during the 48-h ECG recording, which provided an accurate representation of the [K + ] time evolution only during HD, but not during the ambulatory period. On this basis, it was possible to investigate the relationship between the proposed markers and the [K + ] only during the therapy but not through the remaining hours. Moreover, the course of HD procedures can be accompanied by ischaemia  [52] [53] [54]  , which can also be associated with changes in the T-wave, independently from HR, therefore reflected on d w,c. Elucidation of its impact in monitoring normal-life outside the HD process needs to be explored in a dedicated study.
Acknowledgements This work was funded by  Products & Technology S. L. (Castellbisbal, Barcelona, Spain) , and by  AGAUR, Generalitat de Catalunya (Spain)  grant  DI001-2018  and  CIBER-BBN  ref: " DEKOALE ". The work was also supported by project  PID2019-104881RB-I00 , and  PID2019-105674RB-I00  funded by  Spanish Ministry of Science and Innovation (MICINN)  and  FEDER , by  Gobierno de Aragón  (project  LMP124-18  and  Reference Group Biomedical Signal Interpretation and Computational Simulation (BSICoS)   T39-20R ) co-funded by  FEDER 2014-2020 "Building Europe from Aragón ", and by  European Research Council (ERC)  through project  ERC-StG 638284. The computation was performed at the  High Performance computing  platform of the  NANBIOSIS ICTS. J. Ramírez  would like to thank the support from the  Marie Sklodowska-Curie Grant  No.
2bwas selected. Note that for this patient, the Holter recording did not reach the planned 48h. Panel (b) shows the median and IQR for each observing i-th segment, computed by using the values from all the available patients for d u w , d w and dw,c and d NL w (this latter refers to the right axis, while the others to the left). Time trends (expressed as median and IQR) for d a and d NL a , referring to the left and right axes respectively are in panel (c). Panels (b) and (c) give an overview of the time evolution for these biomarkers along the ECG acquisition from the HD beginning onward. Only the first 44 h were depicted being that the average ECG duration in our database.
001). In the latest review, the authors pointed out that PRLT resulted in a 1. 3 times higher rate of median PSA decline ⩾50% than treatment with abiraterone, enzalutamide, mitoxantrone, or cabazitaxel (p = 0. 00001), as well as a 1. 1 times higher 6-month rate of median radiographic progression-free survival. In a non-randomized phase II study conducted by a group at Peter MacCallum Cancer Centre in Melbourne, Australia, the reported overall response rate to PRLT as defined by (Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 71% (complete response and partial response). 19 The Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group has recently reported the results of TheraP, a phase II open label, randomized, multicentre trial that enrolled patients with mCRPC, aiming to determine the activity and safety of 177 Lu-PSMA compared to cabazitaxel in men with progressive mCRPC previously treated with docetaxel (NCT03392428, TheraP).
20 Of 291 men who were screened, 200 were eligible on PET imaging combining FluoroDeoxyGlucose (FDG) PET and PSMA-PET criteria. Since the presence of FDG-positive/PSMA-negative disease was an exclusion criteria for this trial but not used in most other series, the results obtained in TheraP may not be reproduced in other series that do not use both tracers for patient selection. PSA50 was significantly higher with 177 Lu-PSMA-617, 66% versus 37%, while grade 3-4 adverse events were also lower, 35% versus 54%. 11 In seven patients who demonstrated an exceptional response based on PSA and complete metabolic response on post-treatment scintigraphy, treatment was paused; however, patients were allowed to re-commence up to the maximum of six cycles of PRLT upon subsequent progression. The multi-national phase III VISION trial (Endocyte, NCT03511664) enrolled 831 patients with mCRPC in a 2:1 ratio to receive either six cycles of 7.
The ENZA-P clinical trial (NCT04419402) is currently testing this hypothesis in a randomized phase II design comparing enzalutamide to the combination of 177 Lu-PSMA-617 and enzalutamide in a high-risk mCRPC population. Combination therapies. Checkpoint inhibitors in prostate cancer have very little activity. 49 However, combining radiotherapy and checkpoint inhibitors may be synergistic and improve efficacy, through an increased expression of tumorassociated antigens and activation of cytotoxic T cells in the TME. The benefit of the association of immunotherapy with 177 Lu-PSMA in patients with mCRPC will be evaluated in two prospective phase I/II trials, NCT03658447 in Australia and NCT03805594 in the United States. The American team has reported encouraging first results in an abstract at the ASCO 2021 congress: 177 Lu-PSMA-617 followed by pembrolizumab was well tolerated in 18 patients and led to durable responses in four patients with mCRPC who did not have high mutational burden or microsatellite instability, suggesting a possible immunogenic priming effect of radioligand therapy.
53  The NCT04443062 trial will evaluate the benefit of PRLT in oligometastatic patients defined on the 18 F-PSMA PET has having up to five lesions. The NCT04430192 trial will even address the 20 expected patients to two cycles of PRLT in neo-adjuvant situation. 54  Part 2: PSMA-targeted immunotherapy Led by immune checkpoint inhibitors, immunotherapy has revolutionized the landscape of oncological treatment and is now standard of care in many cancers. Unfortunately, as discussed, immune checkpoint inhibitors have limited efficacy in prostate cancer. 55  This modest activity is thought to be multifactorial, related to an immunosuppressive TME, associated with low levels of PD-L1, a low tumor mutation burden, and other poorly understood factors. 56  However, the promise of complete responses and sustained benefit from immuno-oncological approaches in other cancers, along with the survival benefit observed with the use of autologous cellular immunotherapy sipuleucel-T, continues to drive research aimed at making immunotherapy effective in prostate cancer.
Literature search and analysis We searched the PubMed database from January 1 st , 2000, to April 30 th , 2021, with logical combinations of the following terms (in English only): levothyrox*, LT4, L-T4, Abstracts were screened for relevance. If an abstract was found to be relevant, the full text article was retrieved and reviewed. We excluded case reports, reviews, and editorials. We arbitrarily classified factors influencing the relationship between the prescribed oral dose of LT4 and the drug's clinical effectiveness into three broad categories: pharmaceutical factors (the dosing regimen, the time of day taken, the administration route, the pharmaceutical formulation), pathophysiological factors (aetiology, type of hypothyroidism, disease status, concomitant diseases or comorbidities, anthropometric variables, genetic variants, etc.
showed that concomitant administration of ciprofloxacin was associated with a significantly lower area under the plasma T4 concentration-time curve  [71]. Drugs that modify the stomach's acidity have also been linked to LT4 malabsorption, although the effect is subject to debate. There is a large body of evidence (from general practice patient databases, electronic medical record reviews, and clinical trials) to indicate that PPIs are prominent interfering substances that raise TSH levels and/or the LT4 dose requirement  [63, 72, 73]. In contrast, various clinical studies of one week of treatment with pantoprazole  [74] , 3 months of treatment with omeprazole  [75] , and a week's treatment with esomeprazole  [76]  did not find significant intergroup differences in the TSH or thyroid hormone levels.
Nevertheless, it has been suggested that thyroid status should be reassessed in euthyroid pregnant women infected by SARS-CoV-2 in their first trimester of pregnancy, notably if they are at high risk of thyroid dysfunction or have a history of thyroid autoimmune disease  [162, 163]. The present study had a number of limitations. Firstly, only the PubMed database was searched. Secondly, only publications in English were screened. Perspectives for further research include the broader application of in silico simulations of oral drug absorption and the effect of drug interactions  [164]. There is also scope for better evaluating the risk of malabsorption in newly treated patients, using rapid screening questionnaires. For example, Bellastella et al. recently developed and tested a seven-question "Evaluation of Malabsorption in Patients with Hypothyroidism" (EMPATHY) questionnaire  [165].
Moreover, greater autonomy  [21] [22] [23]  in materials discovery is demonstrated by integrating predictive  [24]  or generative models  [25, 26]  based on ML and DL techniques. The level of autonomy  [27]  in the framework of materials discovery is determined by the degree of integration of automated tasks, degree of reduction of human intervention (e. g. , as shown in early work by Nikolaev et al. )  [28]  and the degree of materials intelligence. Despite successful examples of material discoveries  [29, 30]  and a rapidly growing number of materials databases such as High-Throughput Experimental Materials database, Citrination platform, and the Materials Data Facility, the sheer vastness of the chemical space requires more efficient exploration techniques. Moreover, solid state materials and certain molecules pose challenges due to limited available data, lack of available invertible representation,  [26]  and costly exploration of monolithic, fixed libraries.
[86, 87] here are two outlets of the valve, which are connected with mix vessel and waste, respectively. Between the dispensing of different electrolyte components, the valves will be flushed or cleaned to avoid mixing components. With a series of flowthrough devices this platform is capable of mixing complex electrolyte solutions and characterizing physical and electrochemical performance in a semicontinuous fashion. Dave et al. built a system named "Otto" to enable HT automated formulation and characterization for liquid aqueous battery electrolytes. [88, 89] Compared to traditional low throughput experiments, this system allows much faster formulation of 140 electrolytes within 40 h. In addition, the machine learning method coupled with automated evaluation of the acquired datasets enables inverse material design.