dataesr/scientific-paragraphs-categorization huggingface dataset:
Other eligibility criteria included age $ 18 years; life expectancy $ 3 months; Eastern Cooperative Oncology Group performance status of 0-1; and adequate hepatic, renal (creatinine clearance. 30 mL/min per the Cockcroft-Gault formula or measured 24-hour creatinine clearance), and hematologic functions. Patients were not preselected on the basis of biomarkers, including PD-L1 expression on tumor cells or tumorassociated immune cells. Concurrent anticancer treatment, immunosuppressive or hormonal agents, or prior therapy with any antibody/drug ‡Thirty-seven patients were evaluable for PD-L1 expression. Nonevaluable specimens (n = 7) included those that were missing, of poor quality, or otherwise not available to provide results. targeting T-cell coregulatory proteins were not permitted. Patients with adrenal insufficiency could continue corticosteroids or topical steroids; patients were tapered off all other steroids and immunosuppressive agents before receiving study treatment (Data Supplement provides full inclusion and exclusion criteria).
Clinical activity was assessed by cross-sectional imaging (computed tomography or magnetic resonance imaging) performed at baseline and every 6 weeks and evaluated using RECIST version 1. 1 to determine best overall response and duration of response from the start of treatment until documented disease progression. Images were reviewed locally by the investigator and centrally by a blinded independent review committee. Stable disease at the first postbaseline tumor assessment after 6 weeks was required to qualify for a best response of stable disease. PD-L1 expression in archived or fresh tumor biopsies was assessed independently and blinded to any clinical data by immunohistochemistry using a proprietary assay (Dako, Carpinteria, CA) on the basis of an anti-PD-L1 rabbit monoclonal antibody clone (73-10), under license to Merck KGaA.
Outcomes The primary objective was to assess the safety and tolerability of avelumab, and the primary end point was occurrence of dose-limiting toxicities during the first 3 weeks of treatment in the initial dose-escalation part of the trial; these data are reported elsewhere. 20 Key secondary end points included best overall response according to RECIST by investigator assessment and independent review committee, duration of response, progression-free survival (PFS), OS, and evaluation of PD-L1 expression. Other secondary end points (pharmacokinetic and pharmacodynamic profile and immunogenicity of avelumab) will be analyzed across multiple cohorts of this phase Ib study and reported elsewhere. Subgroup analyses on the basis of patient and disease characteristics at baseline were conducted post hoc.
RESULTS Between September 3, 2014, and December 9, 2014, 66 patients were screened. Of these, 44 patients with metastatic urothelial carcinoma that had progressed following platinum-based chemotherapy were enrolled and treated at 24 sites in the United States and Europe (Data Supplement). No cisplatin-ineligible patients were enrolled. At the time of data cutoff on March 19, 2016, patients had been followed for a median of 16. 5 months (interquartile range [IQR], 15. 8-16. 7 months) and a minimum of 15. 0 months; six of 44 patients (13. 6%) remained on treatment. Disease progression was the most common reason for discontinuation (31 patients [70. 5%]; Data Supplement). The median age of patients was 68. 0 years (IQR, 63. 0-73. 0 years); 30 of 44 patients (68. 2%) were male (Table  1 ). The subsite of the primary tumor was in the lower tract (bladder or urethra) in 37 patients (84.
1 weeks (IQR, 6. 0-35. 1 weeks). Dosing was delayed in 17 of 44 patients (38. 6%), for 3-6 days in four patients (9. 1%), and for $ 7 days in 13 patients (29. 5%). The planned dose was reduced once in one patient (2. 3%). All patients had an AE (Data Supplement); 29 of 44 (65. 9%) had a TRAE (Table  2  and Data Supplement). The most common TRAEs of any grade were fatigue (n = 9 [20. 5%]), infusion-related reaction (n = 9 [20. 5%]), asthenia (n = 5 [11. 4%]), and nausea (n = 5 [11. 4%]). Symptoms of infusion-related reactions included chills/rigors, fever, hypertension, headache, flushing, dizziness, sweating, and leg cramps within 24 hours of infusion. Treatment modifications following infusion-related reactions were as follows: grade 1, infusion rate decreased by 50% with close monitoring for worsening; and grade 2, infusion stopped and resumed at 50% of the previous rate after resolution or decrease to grade 1, with close monitoring for worsening.
8%]; Table  2 ). There were no treatment-related deaths. Seven deaths (15. 9%) occurred that were not treatment-related, with six (13. 6%) as a result of disease progression and one (2. 3%) attributed to respiratory failure as a result of disease progression. On the basis of independent central review assessment, treatment with avelumab resulted in a confirmed ORR of 18. 2% (95% CI, 8. 2 to 32. 7) and a disease control rate of 52. 3%, including five patients (11. 4%) with a complete response, three patients (6. 8%) with a partial response, and 15 patients (34. 1%) with stable disease as best response (Table  3    Clinical activity of avelumab. (A) Time to response, duration of treatment, and duration of response to avelumab (eight confirmed responses and four unconfirmed responses as of data cutoff), with programmed death-ligand 1 (PD-L1) expression status indicated (on the basis of a $ 5% staining threshold on tumor cells; nonevaluable specimens [n = 7] included those that were missing, of poor quality, or otherwise not available to provide results).
One patient discontinued treatment as the result of a grade 2 infusion-related reaction. The mechanism leading to infusion-related reaction during avelumab treatment is currently unknown; detailed analysis across various tumor types is ongoing. In conclusion, findings from this study suggest that avelumab could become a potential treatment option for patients with advanced urothelial carcinoma. On the basis of the promising clinical activity seen in this cohort of the JAVELIN Solid Tumor trial, an additional expansion cohort of approximately 200 patients with urothelial carcinoma has been enrolled to further characterize the efficacy and safety of avelumab in this patient population. In addition, a randomized phase III trial of avelumab plus best supportive care versus best supportive care alone as maintenance therapy in patients with metastatic urothelial carcinoma not progressing after first-line platinum-based therapy is underway (NCT02603432).
Acknowledgment We thank the patients and their families, investigators, coinvestigators, and the study teams at each of the participating centers and at  Merck KGaA (Darmstadt, Germany)  and  EMD Serono  (Billerica, MA; a  US subsidiary of Merck KGaA ). We also thank  Dr Debra Hanks  ( Agilent Technologies, Carpinteria, CA ) for expert pathology support. This trial was sponsored by  Merck KGaA  and is part of an alliance between  Merck KGaA  and  Pfizer  (New York, NY). Medical writing support was provided by  ClinicalThinking (Hamilton, NJ)  and funded by  Merck KGaA and Pfizer.
Stability of the convergence to tumor cells. In what follows, we present the application of the stability criteria described in the previous section to the case of one tumor cell that attracts a significant number of immune cells and we analyze solely the trajectories of those cells that reach a distance from the tumor cell equal to (or shorter) than the physical interaction range of the TC. Our refined dataset consists of 8 immune cells attracted by the tumor cell (see Fig. 6 , bottom panel). In particular, we explicit the analysis of the previous section calculating the Lyapunov coefficients λ 1 and λ 2 linked to two different experimental outcomes arising from the measured parameters of the PBMC trajectories: a stable and a metastable behavior in the PBMC approach to the TC (see Fig. 6 , central panel); no evidence for a robustly unstable behavior is highlighted.
Methods Experimental set up. The data-set analyzed in the present paper is based on data described in a recent paper by Vacchelli et al. 1  that used the device shown in Fig. 1  to investigate the interactions between human PBMCs and doxorubicin treated human MDA-MB-231 breast cancer cells. PBMCs were obtained from healthy donors bearing the normal, most frequent FPR1 allele in homozygosis (CC), the RS867228 loss of function allele of FPR1 in heterozygosis (CA) and the RS867228 loss of function allele of FPR1 in homozygosis (AA).
Acknowledgements Authors thank  Anna Maria Masci  for the critical reading of the manuscript. GK is supported by the  Ligue contre le Cancer Comité de Charente-Maritime  (équipe labelisée);  Agence National de la Recherche (ANR)  -" Projets blancs ;  ANR  under the frame of E-Rare-2, the  ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC) ;  Cancéropôle Ile-de-France ;  Institut National du Cancer (INCa) ;  Institut Universitaire de France ;  Fondation pour la Recherche Médicale (FRM) ; the  European Commission (ArtForce) ; the  European Research Council (ERC) ; the  LeDucq Foundation ; the  LabEx Immuno-Oncology ; the  RHU Torino Lumiére , the  SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE) ; the  SIRIC Cancer Research and Personalized Medicine (CARPEM) ; and the  Paris Alliance of Cancer Research Institutes (PACRI).
E. B. is supported by a  DFG  fellowship through the  Graduate School of Quantitative Biosciences Munich (QBM). E. A and A. B acknowledge  GNFM-INdAM  (through  Progetto Giovani Agliari2016 ) and  Università del Salento  for partial financial support. F. M, G. S. are supported by the  Italian Ministry of Health  ( Finalized research program  project grant#  RF-2011-02347120 ). L. B. , F. R. B. , A. D. N. , are supported by the  Italian Ministry of Education, University and Research  (project  MIUR-PRIN2012  grant#  20125NMMLA ).
Methods and analysis The Epitopes-HPV02 study is a multicentre, single-arm phase II study. It was developed by the "National Institute of Health and Medical Research (INSERM), Unit 1098" and "Clinical Investigational Center (CIC) 1431", and is supported by GERCOR and FFCD collaborative oncologic groups. The study is coordinated by the "Department of Clinical Research and Innovation" of University Hospital of Besançon. The data management is undertaken by the "Methodology and Quality of Life Unit in Oncology"* of the University Hospital of Besançon, and the trial is registered on the clinicaltrials. gov database (NCT02402842), partly funded by a research grant from the University Hospital of Besançon, and conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice.
The quantitative variables will be described by the median, mean, standard deviation, the extreme values and interquartile ranges. For each variable, missing data will be described, and 95% CI will be reported. The median progression-free survival (PFS) and overall survival (OS), with its 95% CI will be determined by Kaplan-Meier method. PFS will be calculated between the inclusion date and the date of the first progression (local, regional, metastatic, second cancer) or the last follow-up date for alive patients without progression, and the OS will be calculated between the inclusion date and the date of death. The median follow-up will be calculated by reverse Kaplan Meier method. Exploratory investigations will be undertaken to identify the independent factor related to PFS (age, ECOG-PS, type of metastases, response to prior CRT, QoL…) using univariate and multivariate Cox models.
The correlation between the possible variables related to the event will be determined (correlation of rang, test of chi 2 or ANOVA depending on types of variables) before the construction of multivariate models. In case of several variables strongly correlated, only the variable displaying the higher correlation with PFS will be retained. QoL analysis: All analysis will be performed in a mITT (population with at least one QoL evaluation performed). After the generation of the scores following the EORTC recommendations, the scores will be described at each time of measure using median (Min-Max) and mean (standard deviation). Missing data and random property of these data will be studied. The analysis of the random property of missing data will be done by comparison of those patients who completed whole questionnaires at inclusion versus those patients with at least one missing data.
This comparison will be performed over the complete clinical and socio-demographic data recovered at inclusion. In case of a possible confounding factor, a multiple imputation of scores could be performed in the analysis of sensitivity taking into account these factors. A longitudinal analysis of the time until definitive deterioration of a score and the survival without deterioration of a score, will be conducted using the Kaplan-Meier method and described by median with its 95% CI. The time to deterioration of a score of QoL will be defined as the interval of time between the date of enrolment and the appearance of at least 10 points deterioration of the QoL score compared to the QoL score at baseline, without later improvement of more than 10 points compared to the QoL score at baseline, or death  [25].
Monitoring and safety A Data and Safety Monitoring Committee (DSMC) is implemented to safeguard participant safety. DSMC members are conformed by the study-independent pharmacovigilance department, methodologists, and the principal study investigator and coordinator. This committee will perform meetings in case of potential safety signals in the study population detected by the pharmacovigilance department. The information regarding adverse events (AEs) will be elicited at each contact with the participant, by appropriate questioning and examinations. All AEs will be declared if they occur between the signature of the consent form and 4 weeks after the last administration of the study treatment. AEs will also be recovered during the follow-up period if they are possibly related to the study, and at any time if they are possibly related to the study treatment.
Acknowledgments Current Affiliation:  Jyothis George 's current affiliation is  Boehringer Ingelheim Pharma GmbH, Ingelheim ,  55218 ,  Germany , and  Warwick Medical School , Coventry  CV4 7AL ,  United Kingdom. Correspondence:  Robert P. Millar, PhD ,  Centre for Neuroendocrinology, Room 5-80, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0084, South Africa. E-mail: robertpetermillar@gmail. com or  Jacques Young, MD, PhD ,  Reproductive Endocrinology Department, Bicêtre Hospital, Assistance-Publique-Hôpitaux de Paris , and  University Paris Sud ,  Le Kremlin-Bicêtre , F-94275, France. Email: jacques. young@aphp. fr. Disclosure Summary: The authors have nothing to disclose.
Screening and data abstraction We systematically screened titles and abstracts and retrieved studies for full text screening if they were deemed eligible or if the abstract lacked the detail to determine eligibility by at least one of the screeners. We reviewed the full text articles and summarized the findings stratified according to Table  1  and incorporated them into the GRADE EtD frameworks for each of the 22 guideline areas. We a priori broadened our inclusion criteria and included indirect evidence from other settings when we did not identify information specific for the Saudi Arabia setting.
Image processing The kidney was scanned with a high-resolution micro-CT imaging system (GE eXplore Locus SP), set to a 0. 016-mm effective detector pixel size. The apparatus used for imaging the vessels was the eXplore Locus Micro-CT scanner from General Electric Healthcare 1 with spatial resolutions of 36 to 7 μm, and used with the Scan Control 1 programs. Our acquisition protocol consisted of 360 views and 4 images per position, with a voxel volume of 16x16x16 μm 3. To achieve a consistent methodological approach, experimentally acquired voxel images were stored into standard DICOM format, which stands for Digital Imaging and Communications in Medicine. For image processing, we developed our own computational tools in C++ and Python, which are described in detail below and in S1 Appendix.
Automated extraction and characterization of the vascular tree In order to reconstruct the topology of the vascular network in a purely data-driven way, we developed a network-based approach for an automated reconstruction and hierarchical classification of the extracted 3D vascular skeleton. The reconstruction protocol is a two-stage hybrid script written in C++ and Python, using the NetworkX library  [34]. In the first stage the centerline and diameter data, extracted during the image segmentation described above, were imported to create individual nodes of the network (see Fig  1E). Each node was defined by a centerline point, which contained additionally the information about the corresponding average diameter. At this point, no edges were established between the nodes, meaning that all nodes had a node degree equal to 0.
Metrics for the characterization of the vascular network anatomy Pure centerline datasets (binary data) of individual samples were used to determine the fractal dimension D f and vessel diameter distributions. The fractal dimension was obtained by a standard box-counting algorithm  [1, 39]. Briefly, the vasculature was covered with N(x) equal boxes of sizes x, whereby each box contained at least one point of the object. Since the number of non-empty boxes depends on the box size, NðxÞex À D f , the fractal dimension can simply be estimated from the best fitting power law function. Additional quantifications where made on the reconstructed vasculature. Centerline points in the reconstructed vasculature are connected with cylinders. The length of the individual cylinders represents the Euclidean distance between adjacent centerline points.
The volume of the vasculature was correlated positively with the volume of the organ, but the fractal dimension, which is a scale-free parameter, did not correlate with the volume of the kidney. Individual data and linear regression analysis are given in the S2 Appendix. Topological scale analysis of the structure of the arterial vasculature Analyses of the properties of the vascular trees such as number, diameter and length of vessel segments, as well as branching angles, were performed with regard to the Diameter-Defined Strahler Orders (DDSO) taxonomy. Diameter and length of vessel segments. For the analysis, regarding the vessel segment diameters, we performed a standard frequency count, where the number of vessel segments within the diameter range of D k 2 [dD -D, D + dD] is given by N(D k ) (see Material and methods).
For the global analysis of the kidney vasculature, we calculated the total volume as well as the overall length of the vasculature. These global indexes provided quantitative data about the size of the vasculature, and were decreased by both Fzd4 and Fzd6 deletion compared with WT mice. Additionally, we calculated the fractal dimension of the vasculature. Fractal analysis is a very interesting tool to investigate a large variety of self-similar biological structures  [39, 44] , including the vasculature  [45, 46]. However, to the best of our knowledge, only two studies, published around 20 years ago, have calculated the fractal dimension of the kidney vasculature  [47, 48]. Cross et al. have calculated the fractal dimension of human kidney vasculature from angiograms, hence two-dimensional analysis, with a mean fractal dimension of 1.
Acknowledgments This work was supported financially by the French-Slovenian Hubert-Curien partnership Proteus n˚33325NL Endothelial planar cell polarity and vascular network structure and functionality. The authors thank  Sylvie Lorthois , from the  Fluid Mechanics Institute of Toulouse  ( UMR CNRS/INPT/UPS 5502 ,  Toulouse, France ) for her conceptual and methodological help.
They showed that pH and organic matter could be estimated effectively using Vis-NIR, but not N, P or K, and also found that the preprocessing of the data made a strong difference in the effectiveness of the system. Ref. [27]  described a tractor-driven system for real-time acquisition of Vis-NIR soil spectroscopy. They described the design and operation of the system, and demonstrated an error rate of 1. 22 g•kg -1 of soil organic carbon estimation. Physical attributes of soil can be rapidly assessed using mid-infrared spectroscopy (MIRS), as demonstrated by  [28]  who applied Partial Least Square (PLS) regression after first-order derivation and smoothing. The attributes assessed included liquid limit, air-dried moisture content and cation exchange capacity, all of which are also useful for agricultural purposes.
These gaps are filled by taking the mean intensity values of neighbouring values and inserting them into the gaps. See Figure  3  for a schematic explaining this process. The position of each column is therefore calculated along an arbitrarily-chosen scale of 1000, with 1 being the left-hand side of the bounding box and 1000 being the right-hand side. In practice, the number of columns in the bounding box is almost always between 700 and 800 pixels, resulting in small gaps, one character wide, in the data. These gaps are filled by taking the mean intensity values of neighbouring values and inserting them into the gaps. See Figure  3  for a schematic explaining this process. After the images have been captured, they are downloaded directly from the camera using a USB cable and processed using bespoke software developed using Microsoft Visual Studio 2010 (Microsoft, Redmond, WA, USA).
Vegetable Garden Samples In late June 2016, samples of different fruit and vegetable plants were imaged under natural lighting conditions at a community garden plot in Aberdeen. This imaging was carried out in one two-hour period, during which light levels were consistently high and mildly overcast. Leaves of four examples of twelve crops were imaged using PHYLIS, with two samples per plant taken from After the images have been captured, they are downloaded directly from the camera using a USB cable and processed using bespoke software developed using Microsoft Visual Studio 2010 (Microsoft, Redmond, WA, USA). This can be done in the field using a laptop, although it is easier in an office environment given the current "prototype" nature of the system. The software extracts the pixel intensity values (RGB-red, green, blue values in the range 0-255).
Acknowledgments: This work was funded by the  Scottish Government's Rural and Environmental Science and Analytical Services (RESAS) division. Author Contributions:  Matt J. Aitkenhead  conceived and designed the research, carried out the modelling work and wrote the paper;  Cathy Hawes  developed and manages the  CSC Research Platform ;  Graham J. Gaskin  designed and built the spectral equipment; and  Noemie Lafouge  carried out the field work and organized the data.
Alkali treatment was performed for all samples before gel loading (including zero time point) and resulted in complete splitting of AP-sites generated by hSMUG1. The solution was neutralized with an equivalent amount of hydrochloric acid and loaded on a 20% (w/v) polyacrylamide/7 M urea gel. Conversion of the substrate to the product was analyzed by autoradiography on an Agfa CP-BU X-ray film (Agfa-Geavert, Belgium) and quantified by scanning densitometry in the Gel-Pro Analyzer software, v. 4. 0 (Media Cybernetics, USA). The measurement error commonly did not exceed 20%.