dataesr/scientific-paragraphs-categorization huggingface dataset:
Quantifying T-cell Infiltration and Intrapatient CAF Heterogeneity. For the intrapatient analysis, we created a separate QuPath project with all the desired scans to analyze. The images were cropped and exported, and then overlays were generated using an ImageJ script with the following steps: a. Deconvolution (hematoxylin, AEC, residual) b. Alignment on hematoxylin images c. Creation of transformation matrix and then application on AEC images d. Threshold to remove background and then "Stack of Images" The composite image was transferred back to QuPath for further analysis. Adjacent tissue regions on slides were excluded from the analysis, and in the region to analyze we used the "train pixel classifier" to annotate tumor nests versus stroma, whereas αSMA, FAP, and ADH1B areas were annotated using "QuPath train classifier.
Quantifying FAP + αSMA + CAF Correlation with Collagens IV, XI, and XII. After the images were cropped and exported, overlays were generated using an ImageJ script as described above. The composite image was transferred to QuPath software for further analysis. The train pixel classifier was used to annotate tumor nests versus stroma. In the stromal annotation, the train pixel classifier was used to annotate FAP + αSMA -, αSMA + , collagen IV + , collagen XI + , and collagen XII + regions. A dedicated script automated the tiling and quantification and resulted in a data file containing per tile annotation measurements for each marker. The resulting measurements were exported and analyzed in R. Quantifying FAP + α αSMA + CAF Tumor Islet Coverage. Each tumor IHC image was divided into 1,500-μm tiles using QuPath; in each tile, the fraction of tumor nest surface covered by FAP + αSMA + CAF was estimated.
S. Common Rule and the following protocols were reviewed and approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai: IRB Human Subjects Electronic Research Applications 10-00472 and 10-00135. Additional FFPE NSCLC samples were obtained from Institut Mutualiste Montsouris, Paris, in collaboration with Institut Curie, Paris. Collection of clinical NSCLC specimens at Institut Mutualiste Montsouris was conducted under the umbrella protocol of the pathologic department and biospecimen core facility, established under the reference EUdract 2017-A03081-52 and approved by the Ethics Committee CPP SUD-EST I. FFPE blocks from NSCLC tumors used in ref. 7 were obtained from Assistance Publique-Hôpitaux de Paris (Hôtel Dieu Hospital), with the approval of the IRB CPP Ile de France II, 2008-133 and 2012 06-12, No.
Lambrechts et al. (23)-Array-Express under accessions E-MTAB-6149 and E-MTAB-6653; Wu et al. (26)-Gene Expression Omnibus (GEO) database accession codes GSE13190712 and GSE99254; Kim et al. (24)-GEO database accession code GSE131907; and Laughney et al. (25)-GEO database accession code GSE123904.
Acknowledgments We thank the important contributions of patients who participated in this study. This project was supported by  Genentech, Inc. and carried out in collaboration with the Fondation ARC pour la recherche sur le cancer. The computational work was supported by the  Scientific Computing at the Icahn School of Medicine at Mount Sinai  and the  Office of Research Infrastructure of the NIH  under award number  S10OD026880. This manuscript was edited at  Life Science Editors , and the cartoon illustrations were created using BioRender. We thank the  Mount Sinai Flow Cytometry Core , the  Human Immune Monitoring Center, and the Biorepository and Pathology Core  for their support. We thank  Sarah Lagha ,  Anne-Sophie Tedesco ,  Agathe Seguin-Givelet , and  Isabelle Sauret  for their contribution to obtaining and studying additional FFPE NSCLC samples from  Institut Mutualiste Montsouris.
Considering previous evidence on the mechanisms of IBS acceptance on the relationship between GIspecific anxiety and QoL, it could be of interest to test the efficacy of third wave cognitive and behavioural therapies such as Acceptance and Commitment Therapy in improving acceptance of GI anxiety and reducing its impact on QoL. To our knowledge, only one pilot study has explored this, with positive results, and more research on the topic is certainly needed  [70]. Supplementary data to this article can be found online at https://doi. org/10. 1016/j. jpsychores. 2022. 110809.
5 mL min -1. The DB-225MS capillary column (0. 25 µm, 30 m × 0. 25 mm i. d. , Agilent Technologies, Wilmington, DE, USA) temperature was maintained for 5 min at 135 • C. The FID temperature was set to 180 • C. A solution composed of acetic (66. 6 mmol L -1 ), propionic (27. 0 mmol L -1 ), isobutyric (2. 8 mmol L -1 ), butyric (17. 0 mmol L -1 ), isovaleric (4. 9 mmol L -1 ), valeric (4. 8 mmol L -1 ), caproic (4. 3 mmol L -1 ), and caprylic (4. 3 mmol L -1 ) acids was used as external standard solution. The standard solution (1. 0 mL) was also mixed with pivalic acid and 25% phosphoric acid and injected into the GC-FID. VFAs were identified by comparing the retention times with the external standards. Lab Solution software 5. 71 (Shimadzu, Kyoto, Japan) was used to integrate the area under the curves for each VFA peak and quantification was achieved by adjusting peak areas to the area of pivalic acid and calibration with external standards.
Statistical Analysis Data generated from this experiment were subjected to analysis of variance according to the GLM procedure of SAS/STAT 15. 1 (SAS Institute, Cary, NC, USA) using the "Repeated Measure" model. The GLM Repeated Measure provides analysis of variance when the same measurement is performed several times on each subject or case. In this study, the model included the cropping system (Conven-A and Conser-A), the sampling period, and their interactions as independent variables. The animal was considered as a co-variable. Accordingly, all data were subjected to an LSMEAN test. The least square means obtained were linear combinations (sum) of the estimated effects (means) from the model. The model was described using the following equation: Y ijk = µ + A i + B j + (AB) k + e ijk , where Y is the dependent variable, µ is the overall mean, A i is the effect of the sampling period (i = 1-4 or i = 1-3), B j is the effect of the cropping system (j = 1-2), and (AB) k is the effect of the interaction between the cropping system and the sampling period.
We then measured the angle of the neural epithelium at the level of the predicted or present DLHP at the position of the 5th somite pair (STAR Methods), which constitutes the central region of the apoptotic domain. We found that the QVD-OPh treatment significantly impeded bending at the DLHP in 5-7 ss embryos and showed the same tendency in 8 ss embryos (Figures  1G-1L ). On the contrary, the bending at MHP is mostly unaffected in these conditions (Figure  S1H ), which is consistent with the fact that apoptosis appears in this region when MHP bending is already well advanced (Figure  1C ). These data identify the bending at the DLHP as a specific aspect of neural tube remodeling relying on apoptosis.
Position, displacement and velocity of nuclei A ratio was formed by calculating the distance of the center of the nucleus to the basal side divided by the overall apico-basal height of the epithelium. Ratio was calculated for nuclear position at the beginning and the end of displacement. Distances were measured using the Fiji software. Positions of control nuclei were calculated accordingly over a period of 10 time frames, which is the average number of time frames in apoptotic samples. To calculate the mean velocity, we tracked apoptotic nuclei over time between the beginning and end of apoptotic nucleus migration or over 10 time frames for control nuclei using the Fiji Manual Tracking tool. We then divided the displacement per time frame by the interval time (60 to 90sec).
Cell Orientation measurements In all movies, embryos have the same orientation (medial left / lateral right). Three different time points have been extracted from these movies. For apoptotic cells: before the beginning of apical constriction (T-15'), at complete apical constriction (T0), and at the same average duration between beginning to complete apical constriction (T+15'). For control cells, time points were chosen at equal intervals. The ROI manager was used to mark the same cell in all frames. By using the fit ellipse tool the anisotropy and cell orientation was calculated as the major/minor ratio defined by fit ellipse tool. In each movie, a central control or apoptotic cell was used as reference. With a homemade python script, we calculated the directional angle of the neighbouring cell to the reference cell.
Quantification of apical myosin Using the line tool in Fji and with help of a homemade macro a line was drawn along the apical side of the epithelium from the midline to the fusion point and the intensity was measured. A second line was drawn inside the epithelium. To normalize the levels of apical myosin the value of each position along the mediolateral axis was devided by the average value of a second line that was drawn inside the epithlium. We assumed stable myosin levels inside the epithelium. To make the measurements along the apical side comparable (the lines drawn on the apical side were of different lengths) the lines were fitted to a scale of 0 to 100 using a homemade Python script.
Statistical analysis and graphs Graphs and statistical data were generated in Prism (GraphPad), Excel (Microsoft) or Python. Statistical tests used, N and p values are described in the figure legends. Number of n: In Figures  1C  and ,1D : between 10 and 29 transversal sections per embryo (number of embryos at 3ss n=3, 4ss n=4, 5ss n=3, 6ss n=3, 7ss n=3, 8ss n=3). Figures 1H-1L: n=11 and 13 for 5ss; 13 and 8 for 6ss; 6 and 7 for 7ss and 3 and 4 for 8ss, for control and QVD experiment respectively. Figure  2H : n=5 embryos and 20 cuts for the control; 3 embryos and 17 cuts for the cable cut. Figures  3J  and.
ACKNOWLEDGMENTS We thank  Eric Theveneau ,  Alice Davy ,  Corinne Benassayag , and  Bruno Monier  for their constructive comments on the manuscript. M. S. 's lab is supported by grants from the  European Research Council (ERC)  under the  European Union   Horizon 2020 research and innovation program  (grant number  EPAF: 648001 ), from the  Institut National de la Santeet de la Recherche Medicale (Inserm , Plan cancer 2014-2019), and from the association Toulouse Cancer Sante(TCS, ApoMacImaging:  171441 ). S. T. had a  CIFRE fellowship  from the  ANRT  and now has a fellowship from the  Fondation pour la Recherche Medicale (FRM). The transgenic quail lines used in this project were generated thanks to the  European Research Council  under the European Union's  Seventh Framework Programme  ( FP7/2007-2013 ) and  ERC  grant agreement no:  337635  to J.
Tamsulosin hydrochloride, a selective alpha-adrenergic blocking agent has been previously associated with priapism. Priapism is a medically serious condition that, if not intervened, can cause permanent erectile dysfunction. This study was conducted to investigate whether the association of tamsulosin and priapism is causal. All currently available evidence such as experimental, biological, toxicological, published studies, and safety data mined from the WHO global pharmacovigilance database was systematically organized into the Austin Bradford Hill causality assessment framework. In the international pharmacovigilance database, a strong association between tamsulosin and priapism (IC 025 = 4. 1; PRR 025 = 19. 9; ROR 025 = 20) was observed. There were 122 cases of priapism associated with tamsulosin submitted to the database from 23 countries.
There are only single case reports recorded for this association. Triggered by a single locally reported case that ended up with erectile dysfunction, this investigation was carried out by the Eritrean Pharmacovigilance Centre to assess the causal link between tamsulosin and priapism. The assessment of causality was guided by the Austin Bradford Hill criteria using the publicly available information including preclinical, clinical, and epidemiological data as well as by analyzing the WHO global pharmacovigilance database. 19.
| Literature search and labelling Available unpublished and published information such as preclinical, clinical, epidemiological, biological, and toxicological data were explored and organized into the causality assessment framework to decide based on the totality of evidence. Literature search was made in Google Scholar, Scopus, Embase, Opengrey and PubMed/ Medline using the following search terms: "priapism" or "painful penile erection" or "prolonged erection" or "induced priapism" and "tamsulosin". The search was performed by YF and MR in the first week of November, 2020. Relevant articles from the bibliographical list of available studies that meet the eligibility criteria were included. All articles that directly associated tamsulosin with priapism were included in this study, whereas studies that described other possible alternative explanations or confounders for the occurrence of priapism were excluded.
| Data mining approach The WHO global database of ICSRs, VigiBase, was used as one data source. VigiBase is the world's largest pharmacovigilance database, which is developed and maintained by the Uppsala Monitoring Centre on behalf of the WHO. 19 The database has been pooling safety data of medical products from different countries since 1968, and during data mining (Nov 01, 2020), it had over 23. 5 million ICSRs. The main reason for the data mining was to capture information on the temporal relationship, strength of association, consistency of the cases, dechallenge and rechallenge, dose-response relationship, and the causal relationship of tamsulosin and priapism at individual level. 'Tamsulosin' as an active ingredient and 'priapism' as MedDRA (Medical Dictionary for Regulatory Activities) preferred reaction term were used as search criteria in VigiLyze, a data mining and analysis tool of VigiBase.
Based on the search criteria, both qualitative and quantitative information was retrieved. During data mining, the database was set at 'de-duplicate' to automatically remove all suspected/potential duplicates from the analysis. From the quantitative analysis, measures of strength of association such as reporting odds ratio (ROR), proportional reporting ratio (PRR) and/or information component (IC value) as well as cases with single suspect, number of reporting countries, cases with positive dechallenge and rechallenge, etc. , were obtained. ROR, PRR, and IC values are measures of association in the database. The qualitative data was exported to excel spreadsheets for descriptive analysis. In the excel spreadsheet, time to reaction onset (calculated as the difference between date priapism occurred and date of tamsulosin intake started), cases of priapism encountered with the sole administration of tamsulosin, outcome of priapism, median age, etc.
| Literature search and labelling Literature search, in the abovementioned databases, was performed in the first week of November, 2020. ] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]  One article was, however, excluded as the case could be explained by another alternative cause (had a potential confounder). The rest 12 published papers comprising 13 single case reports were hence subjected to further evaluation (Table  1 ). In the literature analysis, six of the 13 case reports demonstrate that tamsulosin was taken for benign prostatic hyperplasia. In the rest seven cases, tamsulosin was used off-label: for the management of renal calculi in four cases, for obstructive voiding symptoms in two cases, and for unspecified lower urinary tract symptoms in one case. In all cases, tamsulosin was used within the recommended dose.
| Reports in the WHO global database of individual case safety reports, VigiBase Since 1998, a total of 122 cases of priapism associated with tamsulosin were submitted from 23 countries to the global database, VigiBase. The cases were mainly reported from the US, the UK, Canada, Spain, France, and the Netherlands. Of the cases with documented source of primary reporters (101/122), 63% were reported by physicians and 17. 8% were from non-healthcare professionals. The rest, 17. 5%, were submitted by pharmacists and other healthcare professionals. The disproportionality measures or the measures of association between tamsulosin and priapism in  VigiBase was found to be IC 025 = 4. 1; PRR 025 = 19. 9; ROR 025 = 20. In 87. 7% of the cases, tamsulosin was marked as a 'sole suspect,' and in 50. 8%, it was reported as the only drug administered.
| Strength of the association The association of priapism and tamsulosin, based on the calculated IC value, ROR and PRR, was found to be very strong. The IC value is a measure of the disproportionality of a drug-adverse drug reaction pair in VigiBase. 28 A positive IC 025 value (the lower border of the credible interval for the IC value >0) is "a traditional threshold which indicates that a drug-ADR pair is reported more often than expected based on all reports in the database", thus, showing a statistical signal.
Yes Alpha-adrenergic blocking agents have been associated with penile erection and thus, priapism might be an exaggerated effect. Abbreviations: IC, information component; PRR, proportional reporting ratio; ROR, reporting odds ratio. with similar conclusions or observations. As there were no published epidemiological studies, we only considered published case reports and ICSRs submitted to the WHO global database, VigiBase. In many of the cases reported to VigiBase, the time to onset, clinical features and outcome of priapism showed similar clinical patterns. Several of the published case reports manifested within few days after the intake of tamsulosin and recovered shortly after 1-3 days following its discontinuation. In the majority of the published case reports, there was a prolonged painful erection that required aspiration of cavernosal blood, irrigation of the corpora cavernosa with saline solution, and administration of intracavernosal injection with phenylephrine or adrenaline.
The aim of ICI was to provide laboratories with an assessment of their analytical performance and reliability of their data in comparison with other laboratories (Esteban  López et al. , 2021). Four rounds were organized from August 2018 to December 2019 by the Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine (IPASUM) at the Friedrich-Alexander University of Erlangen-Nuremberg, with the requirement to pass at least 2 rounds to perform analysis under HBM4EU. Two different test samples consisting of ~3 mL serum or blood spiked with Cr (Cr ICP standard, ammonium dichromate in H 2 O, 1000 mg/L, J. T. Baker) at two different concentrations (low and high) were dispatched at each round (apart from the first round where 6 samples were distributed). Laboratory results were rated using Z-scores in accordance with ISO 13528 and ISO 17043.
The second group of parameters were related to the living environment of participants: home location (rural/urban), road traffic (related vehicle emissions) close to home (low/medium/high intensity), and presence of industrial plants close to home (yes/no). The last group of parameters were related to some specific occupational activities: exposure tasks frequencies (hours/week), and for welders, the welded material (iron, stainless, other), and the welding method when stainless steel was welded (Metal-arc active gas/Metal-arc inert gas/Manual metal arc welding/Tungsten inert gas/Other). Statistical analyses were performed using Stata Statistical Software (Version 16. 1, StatCorp, College Station, TX, USA). The statistical significance threshold was set at 5%.
Strenghts and limitations Our study has relevant strengths that deserve attention. These include the investigation of a number of workers, greater than the sample size achievable in national studies, coming from various European countries, and sharing harmonized HBM protocols. Enrolled workers were engaged in a series of different activities involving Cr(VI), and, although the subdivision of the different job tasks can limit the representativeness of the various group samples, this study represents a comprehensive attempt to define the contribution of different job practices in affecting the exposure levels and HBM results. The rich dataset obtained, in fact, allows the analysis of RBC-Cr and P-Cr in relation to the air concentration data, U-Cr, extraprofessional information, job procedures as well as information on the use of RPE.
Screening for HDAC10 inhibitors With a validated assay in hand we tested four sets of compounds for inhibition of HDAC10. The first compound set was compiled from reported HDAC inhibitors (see Table  1 ). This set contained unselective inhibitors (quisinostat (11), panobinostat (9), abexinostat (12) and vorinostat (  6 )), HDAC6-selective inhibitors tubastatin A (also HDAC10, 14), bufexamac (27)  [39]  and BRD9757 (  28 ),  [40]  the HDAC8-selective compound PCI-34051  (29)  [41]  and mocetinostat (13), a class I selective HDAC inhibitor. [42] We added further compounds from an in-house library to the set (30-34). Table  2  depicts the inhibitory data of cinnamic acid derivatives. This compound class was previously described as inhibitors of hHDAC6 and Schistosoma mansoni histone deacetylase 8 (SmHDAC8).
In order to rationalize the obtained biochemical data, docking studies were carried out using available crystal structures of drHDAC10 (PDB ID 6UHU)  [34]  as well as human HDAC6 (PDB ID 5EDU),  [28]  HDAC1 (PDB ID 5ICN)  [49]  and HDAC8 (PDB ID 2 V5X)  [50]  to account for the observed selectivity profile of some hits. Of note, crystal structures of drHDAC6 in complex with hydroxamic acid derivatives have shown that the inhibitors can chelate the catalytic zinc ion in either mono-or bidentate fashion. [28, 51] Hence, two different settings were used for docking of the hits into HDAC6 structure to investigate plausible binding modes. The pan HDAC inhibitors abexinostat (12), quisinostat (11) and panobinostat (9), which all bear a basic moiety in the capping group, were among the most active compounds tested against HDAC10.
Experimental Section Chemistry Starting materials and reagents were purchased from different suppliers. No further purification was done. For R f -determination thin-layer plates from Merck (TLC Silica gel 60 F 254 and TLC Silica gel 60 RP-18 F 254 s) were used and analyzed under UV light (254 nm). Mass spectrometry (MS) was performed on an Advion expression CMS spectrometer using an APCI ion source or ESI. Spectra for final compounds were recorded with high resolution mass spectrometry (HRMS) on an Exactive device (Thermo Fisher Scientific) operating in ESI mode. Theoretical masses were calculated with the Biological Magnetic Resonance Data Bank (www. bmrb. wisc. edu). 1 H NMR and 13 C NMR spectra were recorded on a Bruker Avance III HD spectrometer at 400 and 100 MHz by using the signal of the deuterated solvent as internal standard.
100 M NaH 2 PO 4 , 0. 100 M Na 2 HPO 4 , and 20 % (w/v) PEG3350] on a 96-well crystallization plate using a Mosquito crystallization robot (TTP Labtech). To each drop, 25 nL of microseed crystals in precipitant buffer were added. The drop was equilibrated against 80 μL of precipitant buffer in the well reservoir. Crystals formed in approximately one day. X-ray diffraction data for the HDAC10-48 a complex were collected on NE-CAT beamline 24-ID-C at the Advanced Photon Source of Argonne National Laboratory (Argonne, Il). Diffraction data were integrated using iMosflm2 and scaled with Aimless in the CCP4 program suite. [60] The initial electron density map was phased by molecular replacement using the atomic coordinates of the Y307F HDAC10-trifluoroketone inhibitor complex (PDB 5TD7)  [6]  using Phaser.