dataesr/scientific-paragraphs-categorization huggingface dataset:
Furthermore, 4p was shown in these studies to exhibit a distinct antiproliferative effect at 20 µM against the breast cancer cell line MCF-7 and to have a favorable intestinal absorption profile as derived from the high apparent permeability coefficient Papp in Caco-2 assay  [33, 34]. Although 4p seems to be a promising CK2 targeting lead structure, there has been no thorough investigation of the compound's anticancer activities, its cellular target engagement, or pharmacokinetic properties. In this work, we evaluated the effects of 4p on three different cell lines, namely A431, A549, and LNCaP, which are representative models of skin, lung, and prostate cancers, respectively. These cell lines were found to be dependent on CK2 for their survival as retrieved from the cancer Dependency Map project (DepMap) database (https://depmap.
org/portal, accessed on 15 April 2021). The ability of 4p to inhibit cellular CK2 activity in these cell lines and the subsequent effects on cell proliferation, apoptosis, and migration were evaluated. Furthermore, the impact of 4p on the in- Although 4p seems to be a promising CK2 targeting lead structure, there has been no thorough investigation of the compound's anticancer activities, its cellular target engagement, or pharmacokinetic properties. In this work, we evaluated the effects of 4p on three different cell lines, namely A431, A549, and LNCaP, which are representative models of skin, lung, and prostate cancers, respectively. These cell lines were found to be dependent on CK2 for their survival as retrieved from the cancer Dependency Map project (DepMap) database (https://depmap. org/portal, accessed on 15 April 2021).
IncuCyte ® Cell Proliferation Assay A431, A549, and LNCaP cells were cultured in 96-well plates to a confluence of approximately 30%. Then, the culture medium in each well was removed and replaced with 100 µL fresh medium containing vehicle control (1% DMSO) or 4p in at least eight different concentrations. Afterward, cells were placed in an IncuCyte ® S3 live-cell imaging system (Sartorius, Ann Arbor, MI, USA) at 37 • C in a humidified atmosphere of 5% CO 2 for a total period of 48 h. Microscopic phase contrast images of all wells were taken at 2 h intervals with a ten-fold lens (four images per well). The percent cell confluence in each well was determined for all time points using the IncuCyte S3 2017A software. GraphPad Prism 5 software (GraphPad software, La Jolla, CA, USA) was used to determine the area under the obtained growth curves (AUC).
Fluorescence microscopy images of the wells were taken every 2 h with a ten-fold lens (four images per well) using the green fluorescence channel of the IncuCyte ® S3 live-cell imaging system (excitation 440-480 nm, emission 504-544 nm). The number of apoptotic cells was derived from the number of green fluorescent events determined with the IncuCyte ® 2017A Rev2 software.
IncuCyte ® Scratch Wound Migration Assay Image-lock plates with 96-wells (Sartorius, Ann Arbor, MI, USA) were coated with a collagen-I solution (300 µg/mL) in 0. 02 M acetic acid to study the migration of A549 lung carcinoma cells. Subsequently, 2. 5 × 10 4 A549 cells per well were seeded into the prepared image-lock plates. The cells were cultured at 37 • C and 5% CO 2 until 100% confluence was achieved. Next, a wound was created in the center of each well using a WoundMaker TM (Sartorius, Ann Arbor, MI, USA) followed by washing the wells twice with 120 µL of the pre-warmed medium. Wells then received 100 µL of fresh medium containing either vehicle (1% DMSO) or 4p at two different concentrations (1 and 10 µM). Microscopic phase contrast images were then taken at 2 h intervals over a 48-h period in IncuCyte ® S3 live cell imaging system and analyzed using the IncuCyte ® 2017A Rev2 software to calculate the relative wound density in each well at the corresponding time points.
5 mg/mL UDPGA was used beside NADPH to analyze glucuronidation representative for phase II metabolism. Samples were analyzed with a high-resolution LC-qToF-MS system (Bruker Daltonics, Billerica, MA, USA). The identification of metabolites of 4p was performed by determining molecular formulas from the exact masses of each metabolite using Data Analysis software (Bruker Daltonics, Billerica, MA, USA).
Statistical Analysis Levels of significance for comparison of two treatment groups in Figure  2b  or control and each treatment group in Figures 4b and 5b were determined using an unpaired Student's t-test. Comparison of the EC 50 values determined in the three cell lines studied (Figure  3b ) was performed by one-way ANOVA. The p-values are indicated in the corresponding figures as follows: * p < 0. 05, ** p <0. 01. All statistical analyses were performed using GraphPad Prism 5 Software.
According to this definition, 33% patients who did not offer a positive answer to the adherence questionnaire were considered adherent. In addition to the six questions of Girerd's questionnaire, the questionnaire (see Appendix) compiled the demographic data of patients (six questions), identified their pathologies of interest (type 2 diabetes, hypertension, and/or hypercholesterolemia, plus other chronic pathologies) and their duration (three questions), and details of treatment (five questions on the number of prescribed medications, daily doses, and injectable medicines). In addition, the questionnaire was designed to answer the research question about the place of intentionality in adherence. It thus included questions intended to test the role of intentional nonadherence, habit, and elements that could be assumed to explain both intentional and unintentional nonadherence, and features that could serve as classic determinants: age, attitudes of doctors, trust, treatment characteristics, and particularly, adverse effects.
Acknowledgments The authors are grateful to Mylan, a Viatris company that supported this study, and to Vivactis for its role in the organization of this study. Powered by TCPDF (www. tcpdf. org)Patient Preference and Adherence downloaded from https://www. dovepress. com/ by 88. 160. 195. 254 on 17-Sep-2021 For personal use only. Powered by TCPDF (www. tcpdf. org) Aventis,  Mylan-Viatris ,  Novo-Nordisk ,  Abbott ,  Takeda , and Timkl. LB has no conflicts of interest to declare. EB reports personal fees from  MSD, Akcea, Servier, Sanofi-Aventis, Amgem, Genfit, Regeneron, Mylan-Viatris, Danone ,  Silence Therapeutics ,  Novartis , and Ionis pharmaceuticals, and grants and personal fees from  Aegerion Amryt. JPK reports having received fees for consulting or lectures from  Novartis ,  Novo-Nordisk ,  Mylan-Viatris ,  Meda Pharma ,  Bayer ,  Boehringer Ingelheim , and  GlaxoSmithKline , outside the purview of the submitted work.
Limitations Our descriptive and exploratory survey, based on a large available database, provides information about the broad scene of "nepotistic journals," but it may miss some finer points, especially concerning the quality of articles published in these journals. The quality of a scientific article is a difficult concept to measure, and it cannot be easily summarized in quantitative metrics. We recommend a qualitative analysis of the papers published by the most prolific authors in journals flagged by these indicators, as well as an analysis of the relationship between this author and the editorial board. In addition, we restricted our analysis to journals indexed in the NLM under one or more of the existing broad terms. Some journals are registered without broad terms, requiring a manual pickup by the NLM.
Consequently, our survey may have preferentially included the more established journals indexed in the NLM, with a durable presence in the database, and hence likely to have a better-quality global and editorial conduct than nonindexed journals. Similarly, because we restricted our search to journals publishing a minimum of 50 papers in the 2015 to 2019 period, we may have missed smaller journals with less professional editorial staff and/or from publishers with different standards. Importantly, our automated calculations rely on the articles identified through an NLM search, and it is possible that not all journals list all articles within PubMed. Although this is likely rare, we cannot exclude that certain authors use somewhat different name (for instance, change of name after marriage).
Data extraction The eligibility criteria for the selection of journals were the following: (i) a biomedical journal referenced in the NLM in the MEDLINE database; (ii) having at least one "Broad Subject Term"; and (iii) having published more than 50 papers between January 2015 and December 2019. "Broad Subject Terms" are Medical Subject Headings (MeSH), terms used to describe a journal's overall scope, and they are defined by the NLM for journals in the MEDLINE database  [16]. Each journal was analyzed only once regardless of the number of "Broad Subject Term" associated with the journal (except in subgroup analysis by "Broad Subject Terms"). The 2015 to 2019 period was chosen, as this 5-year window enables a smoothing of random variations and description of recent practices. One author (AS) searched for changes to journal names during the 2015 to 2019 period and, in cases of renaming, pooled the articles published under the different names.
To identify eligible journals, we used the Entrez programming utilities (E-utilities), which enable queries to the National Center for Biotechnology Information (NCBI) databases. The search query-presented in S1 Text-was used to identify all biomedical journals in the NLM catalog having at least one of the "Broad Subject Terms" listed. Then, for each journal, article metadata was automatically collected with E-utilities. On account of technical restrictions, querying for article metadata was run from 2015 up to the date of extraction and then restricted to the period January 2015 to December 2019. To manage articles without an author name, the third selection criterion was slightly modified to focus on journals with at least 50 "authored articles"-i. e. , articles with at least one identified author-over the 2015 to 2019 period (see "Protocol changes").
Data analysis A descriptive analysis was performed using median, range, and quartiles for continuous variables, and counts and percentages for categorical variables. For both analyses, descriptions for the 100 outlier journals were computed overall and with respect to membership of any of the most prolific author(s) on the editorial board. Correlations were computed using Pearson's coefficient, with 95% confidence interval (CI). To explore field-specific variations, the distribution of the 2 indices within each "Broad Subject Term" was graphically displayed. The yearly and overall distribution of the percentage of papers by each author and the Lorenz curve-a graphic representation of the cumulative distribution of appearances as an author-were presented for each of the potential outliers identified above.
A significance level of 0. 05 (alpha) was chosen for statistical analysis of the Epsilon TM data. Comparisons of treatment and untreated sites were performed on differences to baseline scores using multifactorial analysis of variants (ANOVA) with product, subject and side as factors, and the baseline values as covariates. This was carried out with commercially available statistics software (Statgraphics Centurion 18). Subject self-assessment data analysis was shown as mean response for the baseline comparison between the sites and the VAS scores. In addition, the percentage of data in the top 2 box (+3 and +2) and bottom 2 box (-3 and -2) was calculated for the baseline data. Subject data were analyzed using Microsoft Excel 2016 and JMP v15.
By including subject questionnaires in the study, it is possible to obtain feedback on the use of topical products in addition to biophysical data, demonstrating how biophysical methods can be related to characteristics of the skin which the subjects can perceive  [30, 31]. overall consensus that their skin felt dry and rough and had reduced suppleness, as as looking dry and flaky. The limitations with regard to the study will now be discussed. The choice of permittivity scores for the different regions assessed here was carried out based on visual assessment of the images. Visual assessment of the images from the device showed that scores of 0 to 3 corresponded to regions where there was no contact between the skin and the sensor of the device, such as in the dermatoglyphic lines. Similar results were obtained with the use of scores between 0 and 2 instead of 0 to 3 (data not shown here).
Scheme Error! No text of specified style in document. Ortho-arylation of a BZD. The compounds were docked into the cryo-EM structure (PDB ID: 6HUP) of the α1β3γ2L GABAA receptor at the interfacial benzodiazepine binding site between the principal (+) α and complementary (-) γ subunit using Schrödinger Glide. [26] We evaluated their apparent binding affinity using the Glide score, which finds all the possible binding locations and positions of the ligands in the benzodiazepine binding site of the receptor and produces a set of initial ligand conformations. Different ligand poses can then be generated and ranked. Scoring is related to the strength of interaction between the ligand and the protein which is expressed as binding free energy. [27] herefore, more negative values represent tighter binders.
Performance-based managed entry agreements (PB-MEAs) might allow patient access to new medicines, but practical hurdles make competent authorities for pricing and reimbursement (CAPR) reluctant to implement PB-MEAs. We explored if the feasibility of PB-MEAs might improve by better aligning regulatory postauthorization requirements with the data generation of PB-MEAs and by active collaboration and data sharing. Reviewers from seven CAPRs provided structured assessments of the information available at the European Medicines Agency (EMA) Web site on regulatory postauthorization requirements for fifteen recently authorized products. The reviewers judged to what extent regulatory postauthorization studies could help implement PB-MEAs by addressing uncertainty gaps. Study domains assessed were: patient population, intervention, comparators, outcomes, time horizon, anticipated data quality, and anticipated robustness of analysis.
Sharing of such data across decision makers can also support pricing and reimbursement decisions in jurisdictions beyond the one where the data were collected and ultimately facilitate patient access. A reasonable first step in exploring the opportunities and obstacles of regulator-CAPR collaboration would be to assess what is already available. At the time of marketing authorization, regulatory agencies, like the European Medicines Agency (EMA), discuss and agree with manufacturers a plan for postauthorization evidence generation. For the EU, the result of such agreements is made public by the EMA and might help CAPRs in accepting and designing a PB-MEA for the product. We, therefore, conducted a survey, based on a sample of products recently authorized in the EU, with a view to  (1)  gaining insights into the reasons why, in the views of CAPRs, a PB-MEA might be beneficial in terms of addressing the uncertainty gaps and providing a framework for risk-sharing financial agreements, supporting a well-informed coverage decision, and what conditions need to be in place for a given product-indication pair for a PB-MEA to fulfill its objectives; (2) estimating how much of the information gleaned from regulatory postauthorization requirements could have been used to support implementing PB-MEAs; (3) defining what additional information would have been needed to inform a PB-MEA; (4) outlining what further concrete steps could be taken by CAPRs and regulators to improve the effectiveness of PB-MEAs in achieving their stated goals and to support regulators in delivering on their mission to monitor drug performance; (5) helping define a possible framework for collaboration and information sharing across CAPR and between regulators and CAPR, while respecting their respective roles and remits.
Acknowledgments. Orla Maguire ,  National Centre for Pharmacoeconomics (NCPE Ireland), Dublin, Ireland and Niamh Carey, National Centre for Pharmacoeconomics (NCPE Ireland), Dublin, Ireland and Trinity College Dublin, Dublin, Ireland , assisted in the descriptive analysis of the products as well as the review of the manuscript. Funding. This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.
Methods The present retrospective cross-sectional study examined all patients with acute poisoning hospitalized in the intensive care units of 5 Azar Hospital in Gorgan from the beginning of 2008 to the end of 2018. The diagnosis of poisoning was based on clinical examinations and laboratory findings in the medical records of patients. Inclusion criteria: a medical record in the intensive care units of 5 Azar Hospital and age 12 years and older. Therefore, the data was extracted from 631 patients' medical records admitted to intensive care units using a checklist consisting of 20 items. There were 6 items about demographic characteristics and 14 items about the type and cause of poisoning and the patient's clinical condition in the hospital. SPSS Statistics for Windows, version x. 0 (SPSS Inc.
Levamisole was initially prescribed for the treatment of intestinal worms. Because of immunomodulatory properties, levamisole has been used in inflammatory pathologies and in cancers in association with 5-fluorouracil. Levamisole is misused as a cocaine adulterant. Post-marketing reports have implicated levamisole in the occurrence of adverse drug reactions (ADRs) and its use is now limited in Europe and North America. In contrast, all other parts of the World continue to use single-dose levamisole as an anthelmintic. The aim of this study was to identify ADRs reported after levamisole exposure in VigiBase, the World Health Organisation's pharmacovigilance database, and analyse their frequency compared to other drugs and according to levamisole type of use. Methods: All levamisole-related ADRs were extracted from VigiBase.
52 Finally, with the emergence of the COVID-19 pandemic, levamisole has been proposed as a therapeutic strategy option on the basis of its immunomodulatory properties, which were thought to improve clinical status of patients with COVID-19. 53 In this context, we searched the WHO global pharmacovigilance database, VigiBase, for all the suspected ADRs reported after levamisole treatment. We then conducted disproportionality analyses considering the types of use. More specifically, the aims of this study were: (i) to identify new pharmacovigilance signals (increased reporting of suspected ADRs after treatment with levamisole compared to other treatments); (ii) to compare ADRs after levamisole according to its type of use (and therefore its regimen); and (iii) to assess, using all available information, the safety of a single dose.
| Data source Data were extracted from the WHO Global Individual Case Safety Report (ICSR) database VigiBase,  54  which includes >24 million cases of suspected ADRs reported by national pharmacovigilance centres in >130 countries participating in the WHO Program for International Drug Monitoring. 55 An ICSR is an anonymized report for a single individual who experienced adverse event(s) that may be linked to the use of 1 or more drugs. ICSR contains sociodemographic information (age, sex, reporter qualification, country of origin, year of report), information about the drug administration (frequency, dosage, comedications) and information about the reported adverse event(s). Primary analysis used all reports from VigiBase, comparing levamisolerelated ADRs to all ADRs reported in the database (any drugs).
| Study design We performed disproportionality analyses using the case-noncase method, which allows to identify disproportionate reporting, i. e. a higher-than-expected number of adverse reaction reports compared to other reactions recorded in the database by calculating reporting odds ratios (RORs). ROR compares the odds of exposure to levamisole between cases and noncases. 59, 60 ses were defined as reports of each suspected ADR of interest identified by a MedDRA PT. ADRs of interest were identified from the scientific literature or from the drug official information (summary of product characteristics) and include vasculitis, encephalopathies, peripheral neuropathy, convulsions, agranulocytosis, leucopenia, neutropenia, thrombocytopenia, vertigo, fever, tachycardia, failures (cardiac arrest, cardiorespiratory arrest, heart attack and chest pains), arthritis or synovitis, arthralgia or myalgia and hypothrombinaemia.
Our study has several strengths. First, we used the global ADRs database VigiBase to collect information on suspected ADRs from nearly all national pharmacovigilance systems in the world, allowing us to identify new pharmacovigilance signals for rare events with sufficient statistical power and to stratify on levamisole indication in secondary analyses. Second, our results are consistent with already known risks associated with levamisole (encephalopathy, agranulocytosis and vasculitis). Third, the analysis of real-life surveillance data with disproportionality analyses have already demonstrated their usefulness for detecting drug risks. 72, 73 e of the main limitations of this study, inherent to all studies using pharmacovigilance databases,  74, 75  is related to the potential missing information.
Primary analysis comparing levamisole-related cases with all cases reported in the World Health Organization pharmacovigilance database. Secondary analysis comparing adverse drug reactions (ADRs) after use of levamisole for an anti-infective indication with those occurring after use of mebendazole (control group). Secondary analysis comparing ADRs after use of levamisole for an immunomodulatory indication with those after its use for an anti-infective indication (control group). Secondary analysis comparing ADRs after use of levamisole for an adulterant action with those after its use for an anti-infective indication (control group). Johnson syndrome, toxic epidermal necrolysis or acute generalized exanthematous pustulosis.
Mechanisms of action of levamisole and their potential synergy of action with 5-fluorouracil and cocaine If clinical trials on the use of levamisole in patients with COVID-19 give good results, its benefit-risk balance as an immunomodulator in this infection will have to be re-evaluated to enable its use in hospital or ambulatory settings. In June 2021, 4 clinical trials evaluating levamisole in the management of COVID-19 were reported in ClinicalTrials. gov, and the results of 1 of them have been published. The authors conclude that levamisole could potentially improve the cough and dyspnoea of patients with COVID-19 but no benefit could be demonstrated on mortality or aggravation of the disease.
Primary analysis comparing levamisole-related cases with all cases reported in the World Health Organization pharmacovigilance database. Secondary analysis comparing adverse drug reactions (ADRs) after use of levamisole for an anti-infective indication with those occurring after use of mebendazole (control group). Secondary analysis comparing ADRs after use of levamisole for an immunomodulatory indication with those after its use for an anti-infective indication (control group). Secondary analysis comparing ADRs after use of levamisole for an adulterant action with those after its use for an anti-infective indication (control group). Johnson syndrome, toxic epidermal necrolysis or acute generalized exanthematous pustulosis. 015. 273. 432. 641 7. 2 (1. 4-35. 6) 3. 9 (0. 3-43. 3) No cases * No cases *** No cases *** 0.