dataesr/scientific-paragraphs-categorization huggingface dataset:
The databases associated with each technique are regularly updated, which enables retrospective analysis without a new blood extraction, together with screening for more molecules. The LC-MS/MS database contains 181 molecules, whereas the one associated with liquid chromatography -quadrupole time of flight contains several hundreds of them. Conducting a toxicological screening in cases of NET with no evident cause could impact the disease course and improve prognosis because early withdrawal of the causative medication is associated with a reduced mortality. 9 Moreover, had the patient survived, it would have been essential to identify the source of CBZ exposure to ensure life-long avoidance of the drug together with exclusion of other aromatic anticonvulsants (phenytoin, fosphenytoin, and phenobarbital) and other tricyclic aromatics antiepileptics (oxcarbamazepine or eliscarbazepine).
MATERIALS AND METHODS All tests performed in this prospective descriptive study were part of routine investigations in patients who had been referred for investigation of DH, and no additional tests were carried out. Information on the methodology used to carry out the drug IDT was collected from databases of 11 departments in Europe with special interest in DH. The following data were recorded: age and gender of the patients, the method for filling the syringe, the injected volume of saline and amoxicillin (AX), the injection site, and the diameter of Wi and 20 min post-injection. For AX (20 mg/ml), the parenteral AX powder (the manufacturer may vary depending on the center and dispensed by local hospital pharmacy) was dissolved in sterile isotonic saline and used within 2 h of the IDT as recommended  (9).
Muscle grip strength It is a non-intrusive, in vivo method, used to measure the muscle strength by placing the mouse on a metal bar or horizontal grid (Bioseb, Chaville, France). Muscle strength was measured for both hind limbs; ipsilateral and contralateral. A mean of 3 readings with a 30 s latency period was taken for each mouse and the data of the treatment group were compared to the normal group to evaluate the functional recovery  [14, 19]. A time interval of five minutes was taken between successive readings for the same animal.
The Collected Data The addictovigilance center in Nantes has sensitized practitioners concerned with slam practice to collect, in the course of notification, important data related to drug risk evaluation in this particular context. According to the French National Agency for Medicines and Health Products Safety (ANSM) notification form, the three types of information collected regarded sociodemographic characteristics, medical history, and drug use; drug use was defined according to the substance disorder diagnostic criteria of the DSM-IV  (28)  for the Nots before 2013 and the criteria of the DSM-5  (29)  for all other Nots. In this context of the analysis of mandatory Nots, which is one of the main duties of the French addictovigilance centers, no permission to use a database was required  (23).
Nots collected at the addictovigilance center of Nantes between January 2012 and October 2019 were extracted using the keyword "slam" in the center's database. The data were as follows: • Sociodemographic characteristics (age, family status, employment status); • Medical history (HIV status, HCV status, lifetime and current substance use disorder, lifetime, and current psychiatric disorder); • Information related to drug use (drug name and family drug name, dose by intake and frequency of administration, routes of administration, effects sought, effects felt, unpleasant symptoms felt after taking drug, perceived negative consequences on health and in the socioprofessional environment, tolerance, weaning, craving, desire to stop, and risk taking related to use). The data were collected and analyzed with Microsoft ® Excel software.
Furthermore, this was a cross-sectional study that makes it very difficult to measure changes in the practices of slam users. Unfortunately, the notification form of the ANSM does not capture information relevant to behavioral addictions because it was designed to contribute to a pharmacological database. However, slamming is a complex behavior because it involves both substance use and sexual activity at the same time, with the drug use being at the service of the sexual behavior; sex and drugs are strongly entangled. Psychostimulant drugs make sexual practice more intense, more compulsive, and less controllable  (4, 32, 59). These elements are also strongly suggestive of hypersexuality or sex addiction in slammers, but there are no data in the international literature regarding sex addiction in slammers (or chemsexers), probably because it can be difficult to distinguish between substance use disorder and sex addiction.
Acknowledgements The authors wish to thank the staff of the  Ministry of Science and Technology, Lao PDR , especially  Mrs Keophayvanh Douansavanh , general secretary of the Cabinet of the  Lao Academy of Science and Technology  and  Mr Phouthasack Vichitra , director of the Cabinet. Also, the staff in Science and Technology at provincial and district level for all their support and help during our field work in Lao PDR. We are grateful to Assist. Prof. Dr Vichith Lamxay ,  Mr Sengmany Bouta  and  Miss Kobkeo Phethsomphou  for their help. Mrs Youleang Peou ,  Mr Sovanrith Nheb  and  Miss Kunthea Chieb  of the  Department of Biology, Royal University of Phnom Penh , and  Miss Sunisa Sangvirotjanapat ,  Chulalongkorn University, Bangkok  assisted us greatly during our Cambodian field work. Mrs Agathe Haevermans  made the beautiful drawings.
Interactions between GSTs and wood extracts To set up the experimental design, heartwoods of 17 species from French Guiana tropical forest have been selected (Table  1 ). Data obtained with the heartwoods from Andira coriacea, Bagassa guianensis, Dicorynia guianensis, Hymenaea courbaril, Peltogyne venosa, Sextonia rubra and Tabebuia serratifolia have been previously published  (Perrot et al. , 2018). Heartwoods from Abarema jupunba, Bocoa prouacensis, Hirtella bicornis, Oxandra asbeckii, Parkia nitida, Parkia pendula, Pouteria decorticans, Protium gallicum, Swartzia canescens and Vouacapoua americana were from commercial origin (Degrad Saramaca's sawmill, Kourou, French Guiana) or harvested as described in  Lehnebach et al. (2019). All these woods belong to the DEGRAD database (Beauch ene, 2012).
The DEGRAD database contains wood density and wood durability data for more than 300 tree species from French Guiana tree species. Among the 17 chosen woods, four are classified as very durable (x < 10%, x being the relative mass loss obtained after the soil tests), five as durable (10% < x < 25%), five moderately durable (25% < x < 45%) and three non-durable (x > 45%) (Table  1 ). From the 17 selected species, molecules from corresponding heartwoods have been sequentially extracted using four solvents exhibiting different polarities (dichloromethane, acetone, toluene/ethanol, and water). From this step, we obtained a collection of 68 wood extracts. Glutathione transferases, as other drug metabolizing enzymes, possess the ability to bind structurally unrelated molecules  (Atkins, 2019) , suggesting that they could be good candidates to test the proposed reverse chemical approach.
GSTs and wood durability Wood durability is usually estimated from long-term soil bed tests  (XP CEN/TS, 2006. 2006; Meyer et al. , 2014). To constitute the DEGRAD database, soil tests have been performed incubating wood blocks in French Guiana soils in 2010/2012 in controlled laboratory conditions as mentioned in  Amusant et al. (2014). Mass losses (%) have been measured after 6 incubation months. Data from DEGRAD database were used to quantify wood durability of the seventeen species used in this experiment. 68% of the variability (P < 0. 006) of the measured mass losses could be explained by a model (linear regression) set-up from the four 'GST reactivity variables' as shown in Table  2  (%mass loss = 19 + 6. 6 ΣDTdA À 1. 6 ΣDTdD À 6. 3 ΣDTdTE À 4. 5 ΣDTdW; R 2 = 0. 679, P < 0. 006). This significant correlation supported the hypothesis that 'GST reactivity' could reflect at least partially the wood durability of the considered species.
Wood durability (%mass loss), wood density and GST reactivity obtained from the 17 woods of French Guiana forest. ΣDTd A: GST reactivity obtained with the acetonic extract of the considered wood species. ΣDTd D: GST reactivity obtained with the dichloromethane extract of the considered wood species. ΣDTd TE: GST reactivity obtained with the dichloromethane extract of the considered wood species. ΣDTd W: GST reactivity obtained with the dichloromethane extract of the considered wood species. 'GST reactivity' (ΣDTd) for each extract has been calculated adding the absolute values (using reduced centered data) obtained with the six TvGSTOs. Durability classes: VD very durable; D durable; MD moderaly durable; ND non durable. a. Values extracted from the DEGRAD database.
Cells were then gently rinsed with water, and absorbance was measured at 590 nm using a Biochrom Assays UVM 340 microplate reader, following extraction of the dye using an acetic acid 33% solution. The inhibitory concentration 50% (IC 50 ), defined as the concentration of Xn that inhibits cell proliferation by 50%, were calculated using a four-parameter nonlinear regression with GraphPad Prism version 6 software (GraphPad Software, La Jolla, San Diego, CA, USA).
Combination Index Analysis SW480 cells were seeded into 96-well plates. After overnight incubation, cells were pretreated for 24 h with increasing Xn concentrations (starting concentration, 100 µM; four two-fold serial dilutions). The medium was then removed and replaced with fresh medium containing increasing SN38 concentrations (starting concentration, 25 µM; eight two-fold serial dilutions) for 48 h before crystal violet staining as described above. Drug interactions were quantified using the Chou-Talalay method  [32, 33]. Thanks to data of drug combination and single-drug inhibition experiments (dose-effect curves), the synergism, additivity, and antagonism of the different combinations of the two drugs were calculated using CompuSyn version 1. 0 software (ComboSyn, Inc. Paramus, NJ, USA), on the basis of the multiple drug effect equation and quantification by the combination index (CI).
Statistical Analysis Data are represented as mean ± standard deviation (SD) or standard error of the mean (SEM) of at least three independent experiments. Statistical analysis was conducted using GraphPad Prism version 6 software (GraphPad Software, La Jolla, San Diego, CA, USA). The comparison of continuous data was performed using one-way or two-way ANOVA as appropriate followed by Tukey's multiple comparison test after having checked data for normal distribution and variance homogeneity. All p values are two-tailed; p values < 0. 05 were considered significant (* p < 0. 05, ** p < 0. 01, and *** p < 0. 001).
Xanthohumol Synergized with SN38 to Inhibit SW480 Colorectal Cancer Cell Proliferation In order to assess the potential use of Xn as a chemosensitizing agent able to reduce drug resistance, we studied the potential synergistic effect of Xn with SN38, a widely used chemotherapeutic drug for colorectal cancer. SW480 cells were thus pretreated for 24 h with increasing Xn concentrations. The medium was then removed and replaced with fresh medium containing increasing SN38 concentrations for 48 h before cell viability assay using crystal violet staining. Interactions between these two drugs were then analyzed by determining the combination index (CI) thanks to the Chou-Talalay equation, where CI < 1 indicates synergism, CI = 1 shows additivity, and CI > 1 antagonism. Afterwards, CI for all combination data points were calculated and plotted against Fraction Affected (FA), defined as growth inhibition potency.
MP-in uced seems rare, but the reintroduction of this drug in the majority of reported cases illustrates the under-recognition of this effect. In 2016, a case of high-dose MP-induced acute hepatitis in a 27-year-old with multiple sclerosis notified to the pharmacovigilance centre of Lyon (France)  (8)  led us to retrospectively analyse all cases of liver damage associated with the use of IV or oral MP registered in the French pharmacovigilance database (FPVD); a particular focus was made on the route of MP administration.
Methods This study was performed in the FPVD, in which spontaneously reported cases have been registered since 1985 by 31 French pharmacovigilance centres. The present dataset analysis was approved by 31 regional pharmacovigilance centres and the French medicines agency (Agence nationale de sécurité du médicament et des produits de santé, ANSM), which manages the database and helped us with data extraction. For each reported ADR, information on patient (e. g. age, gender), description of the ADR (e. g. date of occurrence, progression) and drug exposure (e. g. dates of introduction and withdrawal, dose) are recorded in the FPVD, along with a summary of the clinical report. The regional pharmacovigilance centre analyses each ADR (coded according to the Medical Dictionary for Regulatory Activities, MedDRA -version 21  (28)  ) and evaluates the relationship between drugs and ADR.
The distribution of liver injury types was similar to that observed in the total population analysis: 79. 2% hepatocellular and 11. 7 % of both cholestasis and hepatocellular. Most cases were of grade 1 (45. 5%, n=35) or 2 (28. 6%, n=22) irrespective of injury type; higher grades (≥3) were found in 5 cases (Table  3 ). Clinical signs were observed in 18 cases (23. 3%) and were mainly asthenia (27. 8%) and digestive disorders (38. 9%). Among the 38 cases with data available the duration of liver injury was a median of 38 days (range: 4-140 days); two of these patients died, but only one death could be related to MP (see above). Liver biopsy was performed in 13 patients (16. 9%). It was not contributory in 2 cases and found mainly fibrosis (n=1), necrosis (n=1), lymphocytic infiltrate (n=2), undefined infiltrate (n=2), inflammatory disorders (n=1).
In 2 cases, histology was compatible with autoimmune hepatitis despite a negative auto-immune blood tests, but also with a toxic event for one of them owing to centrolobular damage and eosinophils. Non drug-related causes were investigated in 51 cases (66. 2%), without success: viral serology was measured in 43 cases (all were negative), abdominal ultrasound was performed in 36 cases (all without abnormalities), and auto-immune blood tests in 17 cases (all negative). Data regarding MP rechallenge were available for 19 patients (24. 7%); MP was not reintroduced for 6 patients, and was re-introduced for 13 patients. Among the latter, 10 had a new episode of liver injury (76. 9%). One recurrence was reported for 5 patients, and ≥ 2 recurrences for the remaining 5 patients (4 in one patient); there were a total 18 recurrences in 10 patients.
8, 95% CI [1. 2; 2. 6]) (38). A similar finding was found in a study conducted in the World Health Organization database; liver injuries occurred in 3. 6% of those receiving high-doses IV MP (≥2g) versus 0. 9% of those receiving low-doses (≤1g)  (39). Some authors have proposed a systematic monitoring of liver enzymes during and after the administration of MP bolus  (7, 38)  , because of the delayed discovering of the liver injury. In our study, liver injuries were discovered after discontinuation of MP in 46. 8% of patients receiving MP intravenously and in 35. 3% patients receiving MP orally. In the setting of long treatment protocols, such as for thyroid-induced orbitopathy for which weekly MP infusions (500 mg) are given for 6 weeks, followed by another 6 weeks at 250 mg  (40)  , early identification during treatment of increased liver function test values may allow prompt withdrawal of MP.
In Tables  8  and 9 , data from selected studies are described quickly in terms of the biocompatibility, entrapment efficiency, transcorneal permeation of drug, aqueous humor's drug concentration, and anti-inflammatory effect in vitro and/or in vivo in the scope of the management of anterior segment inflammation. α-CD: α-cyclodextrin, βCD: β-cyclodextrin, γCD: γ-cyclodextrin, HPβCD: hydroxypropyl-β-cyclodextrin, HPγCD: hydroxypropyl-γ-cyclodextrin, RMβCD: randomly methylated-β-cyclodextrin, PEG: polyethylene glycol, PLGA: poly(lactic-co-glycolic acid), Poly[Lac(Glc-Leu)]: poly(lactide-co-glycolide-leucine), PVA: polyvinyl alcohol, PVP: polyvinylpyrrolidone, EDTA: ethylenediaminetetraacetic acid, HCl: hydrochloric acid, NaOH: sodium hydroxide. No cytotoxic effect in vitro ≈ 5. 1-fold higher corneal penetration of nanoparticles than marketed formulation in vivo  [143]  Despite the fact that nanocarriers for ocular drug delivery appear very promising for the treatment of the anterior segment of the eye, only two clinical trials are reported on ClinicalTrials.
According to the European Pharmacopeia 10th (EP) or the US Pharmacopeia (USP), the ophthalmic preparation meets the requirements if the average number of particles present in the units tested does not exceed the appropriate value listed in the Table  12. The morphology of particles can be examined by transmission electron microscopy (TEM) or scanning electron microscopy with negative staining. Briefly, the samples are prepared by wetting a carbon-coated copper grid with a small drop of diluted formulation (5-10 µL). Upon drying, they are stained with 1% uranyl acetate and 2% phosphotungstic acid, air-dried at room temperature, and viewed by TEM. Imaging viewer software is used to perform the image capture and analysis  [197]. CryoTEM is also used  [198].
When the cells adhered, compounds at different concentrations were added to every well. After incubation for another 72 h, MTT solution (5 mg/mL) was added into each well and cells were incubated for an additional 4 h. The viable cells were stained with MTT and scanned with an electrophotometer at 570 nm. Each concentration treatment was done in triplicate wells. The half maximal inhibitory concentration (IC 50 ) values were estimated by fitting the inhibition data to a dose-dependent curve using a logistic derivative equation.
Real-Time Polymerase Chain Reaction RNA was isolated using Trizol Reagent (Invitrogen, Carlsbad, California, USA). cDNA was made via the manufacturer's instructions with the first chain of a cDNA synthesizing kit (Fermentas, Lithuania). Real-time polymerase chain reaction (RT-PCR) was performed on a Da An Gene DA7600 Real Time machine using Da An Gene incorporation (ZhongShan, China). The 2 -∆∆CT method was used to calculate the relative levels of gene expression using Da An Gene DA7600 QPCR software v3. 00 (Da An Gene). The GAPDH (human) expression was used as the internal control. A standard melting-curve cycle was used to confirm the quality of amplification. The reactions were performed in triplicate for each sample. The gene-specific primers were designed with the Primer5 BLAST software by GenScript Co.
Two interviewees said that pharmaceutical compa nies had tried to end the trials prematurely. According to one of the interviewees: "The trial was negative, and the company refused once they had an early look at the data, which they weren't supposed to do. they basically stopped the support and followup, so we had an incomplete database and we actually had a lot One interviewee described how pharmaceutical companies influenced followup analyses: "We often get supplemental contracts with industry to do secondary analyses of clinical trials. so, if the trial is positive and the drug is going to be approved, they will fund lots of secondary analyses. if the trial is negative they won't" (interviewee 7). Another interviewee described a situation where an academic researcher, a specialist in the intervention tested in the trial, tried to spin (eg, overly favourable interpretation) the trial report.
You can make a suggestion and they will say: 'no we're going to do it this way', and that's it" (interviewee 20) Choice of research agenda-pharmaceutical and device companies funded trials that potentially provide a positive result that they consider commercially interesting "You know, the sponsors clearly have a result that they want to get. we work together to design trials that will answer the questions that they want to answer. They have a certain answer that they want. I have never felt pressured into getting that answer. But we only conduct trials that will potentially answer the questions that industry wants to answer" (interviewee 7) conduct Manipulation of the randomisation process-trial collaborators opened envelopes before the patients were enrolled "What [several]* † centres did was open the envelopes in advance and gave the younger patients the new treatment and the older patients the old treatment" (interviewee 5) Prematurely stopped the trial-the funder terminated a trial early "They wanted to save money because they didn't see the drug being a big seller and so they tried to shut the study down" (interviewee 17) analysis Blocking data access-the funders blocked the academic researchers' access to the trial database "The trial was prematurely terminated by the data safety monitoring board because of the drug actually was harmful and the company refused.
to transfer the database to us. They basically blocked our access to the data" (interviewee 18) Multiple unplanned analysis-the lead academic researcher wanted additional analyses to be conducted so that results would look more positive "I have had examples of. chief investigators who have kind of come back and asked for additional analysis or ways of presenting data that would make it look more positive then it was" (interviewee 10) Fabrication of data-the lead academic researcher wanted to insert fabricated values in trial database "The administrator. came to see me and said; 'I have just been told by the chief investigator if there was a missing rating, I should just copy in the other rating'" (interviewee 10) reporting Spin-one of the academic researchers wanted to present the trial result in an overly positive way "And then this researcher.
not providing treatment for the control group. because the enthusiasm would be different" (interviewee 11) analysis Data access-a copy of the entire database was sent to the academic researcher "Our contracts with the sponsor, the pharmaceutical company, usually state. that we will get a copy of the database" (interviewee 7) Independent analysis-analysis was done by an independent academic statistician "We're going to give the data. to independent academics who have absolutely nothing to do with the trial" (interviewee 4) Exclusion-trial collaborators with conflicts of interest were excluded from involvement in the analysis "We cannot use tables that they [pharmaceutical company] provide, they [the tables] have to be done by our statisticians" (interviewee 18) reporting Transparency-detailed reporting if the protocol was not adhered to "Sometimes you will do analyses that are not pre-specified.
November 2020 by guest. Protected by copyright. http://www. bmj. com/ BMJ: first published as 10. 1136/bmj. m3764 on 27 October 2020. Downloaded from doi: 10. 1136/bmj. m3764 | BMJ 2020;371:m3764 | the bmj of trouble getting the database from them to report it" (interviewee 12).
on 15 15 November 2020 by guest. Protected by copyright. http://www. bmj. com/ BMJ: first published as 10. 1136/bmj. m3764 on 27 October 2020. Downloaded from doi: 10. 1136/bmj. m3764 | BMJ 2020;371:m3764 | the bmj of trouble getting the database from them to report it" (interviewee 12).