dataesr/scientific-paragraphs-categorization huggingface dataset:
13, 14 Monitoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin is also recommended to assess hepatic function. While hepatic dysfunction may occur, most increases in aminotransferase levels are not drug related and correlate with iron load. 5, 10, 15 Deferasirox treatment has been associated with liver fibrosis reversal or stabilization in most iron-overloaded patients with thalassemia. 15 However, abnormal liver function tests have been more frequently reported in children receiving deferasirox,  16  highlighting the necessity for close monitoring, particularly pediatric patients. Of the 1,005 patients enrolled in the registration studies, only 83 (8. 3%) were 2 to less than 6 years old; therefore, further collection of efficacy and safety data in young patients was deemed necessary.
Study design and patient population Male and female patients aged 2 to less than 6 years with transfusional hemosiderosis, eligible for deferasirox treatment according to local prescribing information, were enrolled and followed prospectively for 5 years in this observational study (ENTRUST; ClinicalTrials. gov identifier: NCT00466063). Retrospective data were collected for patients who started on deferasirox less than or 12 months prior to enrollment (i. e. , data were collected from the start of deferasirox treatment for 5 years). Patients were excluded if they were involved in other iron chelator trials. The study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki and was approved by independent ethics committees at participating sites. Patients' parents/guardians provided written, informed consent prior to enrollment.
The most frequently reported AE with suspected relationship to deferasirox was increased ALT alongside increased AST. In this observational study, the overall drug-related gastrointestinal disorders were less frequently reported than in previous studies, although it has been recently incorporated into the deferasirox label that children aged 2-5 years are at higher risk of experiencing diarrhea compared with the overall patient population. Therefore, further analyses of the current dataset are warranted and are ongoing. Previous long-term studies of deferasirox in pediatric patients with -thalassemia and SCD  10, 11  have indicated that growth and sexual development are not impaired and progress normally. Owing to the young age of patients enrolled in this study, long-term effects of deferasirox therapy on sexual development could not be definitively assessed.
Acknowledgements: The course authors refer to in this paper - Laboratorio di Sintesi Finale P5 (Final Graduation Lab -3 rd year Bachelor Degree ) -was delivered at the  Design School of Politecnico di Milano  by  Professor M. Ferrara  (Course Coordinator);  Prof. R. De Paolis ;  Prof. P. Bartoli  and  Prof. F. Lucchese , during the 1 st semester of A. Y. 2016/2017.
Skills-based course curriculum The IBT course curriculum comprised an introduction to various bioinformatics topics that H3ABioNet's Education and Training Working Group identified as important for molecular biologists in African research institutions who would like to become basic "bioinformatics users" (as described by the International Society for Computational Biology's [ISCB] core bioinformatics competencies  [8] ). Modules include the following: an introduction to bioinformatics, bioinformatics databases, and resources; genomics; Linux; sequence alignment; protein structural bioinformatics; and phylogenetics (http://training. h3abionet. org/IBT_2016/?page_ id=273). These priority topics were selected as essential for African scientists who often face population-level epidemic threats and hence need to develop skills in using bioinformatics resources to rapidly tackle the local global health challenges.
Acknowledgments The authors thank the volunteer staff from all 20 of the IBT_2016 classroom sites (i. e. , teaching assistants, system administrators, and classroom principal investigators https://training. h3abionet. org/IBT_2016/?page_id=130),Vula help team at the  University of Cape Town  (http://vula. uct. ac. za/), the Mconf help team at the  South African National Research Network (SANREN , http://www. sanren. ac. za/south-african-nren/), and the  H3ABioNet Education and Training Working Group: Nicola Mulder 1 , Shaun Aron 2 , Sumir Panji 1 , Kim Gurwitz 1 , Judit Kumuthini 3 , Shakuntala Baichoo 4 , Segun Fatumo 5 , Oyekanmi Nash 5 , Jonathan Kayondo 6 , Faisal M. Fadlelmola 7 , Samar Kassim 8 , Jean-Baka Domelevo Entfellner 9 , Samson Pandam Salifu 10  ,  Winston Hide 11 , 12  ,  Kais Ghedira 13  ,  Amel Ghouila 13  ,  Lerato Magosi 14  ,  Alia Benkhala 13  ,  Victoria Nembaware 1  ,  Mary Piper 11  ,  Radhika S.
The great review work performed by the members of the AIMS Technical Program Committee as well as additional reviewers is greatly acknowledged. Thanks also to Thomas Bocek and Martin Drašar for organizing the lab sessions. Additionally, many thanks are extended to the local organizers for handling logistics and hosting the AIMS 2017 event. Finally, the editors would like to express their thanks to Springer, especially Anna Kramer, for the smooth cooperation in finalizing these proceedings. Additionally, special thanks go to the AIMS 2017 supporters, University of Zürich UZH, Communication Systems Group CSG, Research Institute for Cyber Defense and Smart Data CODE, München, Germany, and the European FP7 NoE FLAMINGO under Grant No. 318488.
The forward primers were 5' labeled with the fluorescent dye 6-Carboxyfluorescein amino hexy FAM. The different alleles were resolved after capillary electrophoresis on automated DNA sequencer (ABI 3130xl Genetic Analyzer, Applied Biosystems) and analyzed with the GeneMapper ® 4. 0 software (Applied Biosystems). Selected samples from each genotype were sequenced in order to confirm the length of each allele. Genotyping of HIF1A (G/A) rs11549467 and NFKB1-94ins/delATTG (rs28362491) was performed on the Light Cycler 480 System (Roche, Barcelona, Spain) using a pre-designed TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA, United States) as previously described  [21, 22]. PCR was carried out in a total reaction volume of 5 μL with the following amplification protocol: initial denaturation at 95 ℃ for 3 min followed by 50 cycles of denaturation at 95 ℃ for 3 s, and annealing/extension at 60 ℃ for 20 s.
Statistical analysis Genotype and allele distributions among patients with CD, UC and IBD versus healthy controls were compared using the χ 2 test or Fisher test as appropriate. Odds ratios (ORs) with a confidence interval (CI) of 95% were assessed to measure the strength of association. Statistical power was calculated using Power Calculator of Genetic Studies 2006 software (http://www. sph. umich. edu/csg/abecasis/CaTS/). A chi-square test was used to test for deviation from Hardy-Weinberg equilibrium (HWE). Statistical analyses were performed with Plink software V1. 07 (http://pngu. mgh. harvard. edu/purcell/plink/). P value<0. 05 was considered to be statistically significant. Bonferroni correction was applied to significant P values of NOS2A polymorphisms to correct by the number of comparisons.
In this regard, DTC genetic testing has already been used by several million people to determine their ancestry  [30]. The results of these tests, which are usually provided commercially, enable the consumer to match relatives 'on-line'. This strategy has also already been broadly used by adoptees and foundlings  [34]. Moreover, the current affordable costs of DTC genetic testing make it accessible to the majority of consumers in Europe and beyond. With the growing use of DTC genetic testing, the anonymity of gamete donors can no longer be guaranteed  [30, 35]. It does not suffice for the donors to refrain from entering genetic data into the databank. If any of their relatives do, the donor's family can be 'collaterally' identified. Also children whose parents did not disclose that they were donor-conceived may inadvertently find out about their donor origin.
Funding Participation in the meeting from which this article arose was funded by  European Society of Human Reproduction and Embryology and European Society of Human Genetics. M. M. was supported by  IP00064203/6003 ,  CZ. 2. 16/3. 1. 00/24022 , CZ. 02. 1. 01/0. 0/0. 0/16_013/0001634  and  LM2015091  from the  Czech Ministry of Health and Czech Ministry of Youth, Education and Sports.
Material and Methods Qualitative methods were employed in order to understand the experience of UAB from a patient perspective. Semi-structured interviews were conducted with a purposive sample of male and female patients with a primary diagnosis of DU. Patients with DU alone and in combination with other common co-existing urological conditions, were interviewed to ensure the relevance of the PRO instrument to all patients with the condition. The primary objective to the interviews was to elicit the symptoms, signs and impact of UAB, with an emphasis on capturing key idiomatic expressions and language used to describe their symptoms. Interviews were conducted by trained qualitative researchers either in-person at the patient's home, in situ at the hospital, or over the phone. Informed written consent was obtained to participate and audio record the interviews, which were then transcribed verbatim and organised using qualitative research software package NVivo v10.
A strength of this study is that all patients were clinically verified to have a primary diagnosis of DU by PFS. In addition, those with co-existing urological conditions were included to ensure the relevance of the PRO measure to the whole spectrum of DU patients. The study is not intended to produce representative epidemiological data but to elicit the overall patient experience of UAB. The further elucidation of symptom prevalence and bother will be possible later in the PRO measure development process. This study also cannot be used to link UAB to urodynamic DU. Further interviews with patients from the United States and Japan are scheduled in order to explore potential differences in how patients from other cultures and ethnicities describe UAB symptoms.
Individual studies  [7] [8] [9] [10] [11] [12] [13] [14]  and a pooled analysis of 8 studies in patients receiving background statin therapy  15  have shown that alirocumab produces significant reductions in LDL-C compared with placebo or ezetimibe in patients at high cardiovascular risk. The data for this analysis included 10 completed ODYSSEY studies in a broad range of patients with hypercholesterolemia: 8 studies including alirocumab administered to patients treated with background statin, the majority of whom received maximally tolerated statin, or other lipid-lowering therapies, and 2 studies involving alirocumab administered to patients without background statin. The main aim of the analysis was to investigate the effect of alirocumab on levels of non-HDL-C and apoB.
Trial length ranged from 24 to 104 weeks. Efficacy analyses within each pool were performed to the time point for which data were available for all trials in that pool. For safety analyses, treatment-emergent adverse events (TEAEs) were defined as events occurring from the first dose of study treatment and up to 70 days after the last dose. All subcutaneous injections (alirocumab 75, 150 mg, or placebo) used a 1 mL injection volume. Patients provided written informed consent before their participation. The trial protocols were reviewed and approved by institutional review boards and independent ethics committees. The primary efficacy end point for each of these trials was the percent change in calculated LDL-C levels from baseline to Week 24. Secondary end points included percent change in LDL-C at Week 12 and percent change from baseline in non-HDL-C, apoB, HDL-C, and triglyceride levels.
3, 4 he definition of cardiovascular risk in the Phase 3 studies included in this analysis varied by study. Detailed definitions can be found within Data S1. Given that the specified non-HDL-C goals are defined in guidelines according to the estimated degree of ASCVD risk for a given individual, our analysis of non-HDL-C goal attainment was performed for the entire population regardless of individual risk as well as stratification by very-high and high cardiovascular risk (the vast majority of patients in the present analysis were at veryhigh or high cardiovascular risk). Analysis of apoB goal attainment was performed for the entire population regardless of individual risk. Statistical analyses were based on intention-to-treat (ITT) principles (including all data regardless of adherence to treatment) and the on-treatment (modified ITT) population.
Data on other lipid parameters (calculated LDL-C, HDL-C, and fasting triglyceride) from pools 1 to 3 (patients receiving background statins) were reported previously. 15 Briefly, treatment with alirocumab 75/150 mg Q2W or 150 mg Q2W added to statins resulted in significantly reduced LDL-C levels at Week 24 compared with both placebo and ezetimibe in all patient pools (P<0. 0001; Table  S2 ). In pool 4, in which patients did not receive statins, LDL-C was significantly    S2 ). Alirocumab also produced a significant increase in HDL-C and decrease in fasting triglyceride compared with placebo at Week 24 (P<0. 0001; Table  S2 ). Combined data from all patients in all 10 trials showed that average LDL-C, non-HDL-C, and apoB levels were highly correlated with one another throughout the treatment period (Pearson correlation coefficients ≥0.
2-79. 0% of patients achieved these risk-based LDL-C goals. 15 DL-C in isolation may be an inadequate measure of total ASCVD risk, as it fails to account for cholesterol carried by other lipoproteins, such as triglyceride-rich lipoproteins. When triglyceride levels are high, the levels of remnant atherogenic lipoproteins are also elevated; in these circumstances, the risk predicted by LDL-C alone is underestimated. 1 1] [22]  For example, the Very Large Database of Lipids 2 study showed that, among patients achieving an LDL-C goal of ≤70 mg/dL, 15% may still have a non-HDL-C level ≥100 mg/dL, increasing to 22% among patients with high triglyceride levels (150-199 mg/dL). 22 uch discordance means that residual ASCVD risk may be overlooked with LDL-C-centric treatment. 1 4] [25] [26] [27] [28] [29]  Indeed, some studies suggest that apoB levels may have the strongest association with risk.
MONO (NCT01644474) • 24 weeks • Alirocumab, n=52 • Ezetimibe, n=51 • 78 weeks * • 24 weeks  ‡ • Alirocumab, n=167 • Alirocumab, n=103 Studies • Placebo, n=82 • Ezetimibe, n=101 Alirocumab dose 75/150 mg Q2W § 150 mg Q2W 75/150 mg Q2W § 75/150.
Thus, neutralizing antibodies are unlikely to discriminate between closely related SFSV isolates. Recent seroprevalence studies showed high seroprevalence rates for SFSV neutralizing antibodies in dogs in Portugal (50. 8%)  (7) , Tunisia (38. 1%-59. 2% depending on the region)  (8) , and Greece (71. 9%) and Cyprus (60. 2%)  (11). Our results are congruent with data from continental Greece, with rates in the same order of magnitude  (12). All these findings verify the high prevalence of SFSV in the Mediterranean basin. Because of the nature of this study, the serum was collected and stored under conditions that prevented attempts to detect viral RNA and isolate viral strains. SFSV remains an important human pathogen, as recently highlighted in Africa and Turkey  (12, 13). Published data about the distribution of sand flies and species identification are old and scarce; Phlebotomus papatasi, P.
This work was supported in part by the  European Virus Archive Goes Global project , which has received funding from the  European Union 's  Horizon 2020 research and innovation program  under grant agreement no. 653316 ; the EDENext FP7-no. 261504   European Union  project and this paper is catalogued by the EDENext Steering Committee as EDENext469 (http://www. edenext. eu). The work of N. A. and R. N. C. was conducted under the frame of EurNegVec COST Action TD1303. N. A. is supported by the  Fondation Mediterranee Infection. Ms. Ayhan  is a PhD student at  Aix Marseille University. Her research interests include phleboviruses transmitted by sand flies in the Old World.
* This material is based upon work supported by the  Center for Brains, Minds and Machines (CBMM) , funded by  NSF   STC award   CCF-1231216. The research of  Guillaume Garrigos  was partially supported by the  Air Force Office of Scientific Research, Air Force Material Command, USAF , under grant number  F49550-1 5-1-0500. L. Rosasco  acknowledges the financial support of the  Italian Ministry of Education, University and Research FIRB  project  RBFR12M3AC. S. Villa  is member of the  Gruppo Nazionale per l'Analisi Matematica, la Probabilità e le loro Applicazioni (GNAMPA) of the Istituto Nazionale di Alta Matematica (INdAM).
Data variables, sources of data and data collection Anonymised data were abstracted from health facility and district registers into a structured proforma and entered into a data file using EpiData Entry v. 3. 1 (Epi-Data Association, Odense, Denmark). The variables collected included TB registration number, age, sex, disease classification (PTB, EPTB), type of treatment (new, previously treated), bacteriological status at treatment initiation, HIV serological status, ART uptake status, CPT uptake status and treatment outcomes.
Data analysis and statistics Data cleaning and analysis were performed using STATA 13 software (Stata Corp, College Station, TX, USA). Comparisons between age group and other categorical variables were done using the χ 2 test, or Fisher's exact test when the assumptions were violated. The primary outcome was an unfavourable outcome as defined by the WHO (treatment failure, died, lost to follow-up and not evaluated) at the end of anti-tuberculosis treatment. 2 Crude and adjusted relative risks and their 95% confidence intervals (CIs) were determined through log binomial regression to compare differences in unfavourable outcomes by age group and determine other unfavourable outcome-related factors. Potential confounding variables adjusted for in multivariate regression included sex, HIV status, type of TB, TB category and uptake of ART and CPT.
In addition, we found that SR144528 is a very effective antagonist of CB 2 R-mediated modulation of cAMP signalling, but less so on other signal transduction pathways of the same receptor (GIRK and pERK). This signalling-specific inhibition should also be taken into account when studying CB 2 R agonists that preferably act through these mechanisms. To determine off-target activity of the cannabinoid reference library, we tested them on a customized panel of proteins that are associated with cannabinoid ligand pharmacology, including GPR55, proteins involved in the biosynthesis and metabolism of endocannabinoids (DAGL-a, NAPE-PLD, MAGL, ABHD6, ABHD12, COX-2, FAAH and endocannabinoid transporter activity) and the TRP ion channel family. In combination with the additional off-target data we collected using the CEREP panel, we found that most ligands displayed a rich polypharmacology (see for a summary of all off-targets per compound Fig.
The growth medium was exchanged with Krebs Ringer bicarbonate buffer with 1 mmol l À 1 3-isobutyl-1-methylxanthine (IBMX), 0. 1% fatty acid-free BSA and incubated at 30 °C for 60 min. Agonist was added to a final assay volume of 100 ml and the mixture was incubated for 30 min at 30 °C. The assay was stopped by the addition of 50 ml 3 Â lysis reagent and shaken for 2 h at room temperature. The time-resolved energy transfer was measured using an LF502 Nanoscan FLT (IOM, Berlin, Germany), equipped with a laser as excitation source. cAMP content was determined from the function of a standard curve spanning from 10 to 0. 13 nmol l À 1 cAMP. Data analysis of functional assays. All experimental data were analysed using the nonlinear regression curve fitting program GraphPad Prism 6. 0 (GraphPad Software, Inc.
The effects of compounds were normalized against the response to ionomycin (4 mM) in each experiment. The increases in fluorescence in wild-type HEK293 cells (that is, not transfected with any construct) were used as baseline and subtracted from the values obtained from transfected cells. Efficacy was defined as the maximum response elicited by the compounds tested and was determined by comparing their effect with the analogous effect observed with 4 mM ionomycin (Cayman), while the potency of the compounds (EC 50 ) was determined as the concentration required to produce half-maximal increases in [Ca 2 þ ] i. Curve fitting (sigmoidal dose-response variable slope) and parameter estimation were performed with GraphPad Prism (GraphPad Software Inc. , San Diego, CA, USA). Antagonist/desensitizing behaviour was evaluated by adding the test compounds in the quartz cuvette 5 min before stimulation of cells with agonists.
Data are obtained from single experiments measured with multiple time-points. Plasma protein binding. Pooled and frozen plasma from selected species were obtained from commercial suppliers (The pooled and frozen plasma from human (HMPLEDTA, Lot BRH1060627) and mouse (MSEPLEDTA3-C57, Lot MSE196204) were obtained from BioreclamationIVT (NY, USA). )  64, 65. The Teflon equilibrium dialysis plate (96-well, 150 ml, half-cell capacity) and cellulose membranes (12-14 kDa molecular weight cutoff) were purchased from HT-Dialysis (Gales Ferry, CT, USA). Both biological matrix and phosphate buffer pH are adjusted to 7. 4 on the day of the experiment. The reference substance is diazepam. The determination of unbound compound is performed using a 96-well format equilibrium dialysis device with a molecular weight cut-off membrane of 12-14 kDa.
The integrity of membranes is tested in the HTDialysis device by determining the unbound fraction values for the positive control diazepam in each well. At equilibrium, the unbound drug concentration in the biological matrix compartment of the equilibrium dialysis apparatus is the same as the concentration of the compound in the buffer compartment. Thus, the percent unbound fraction (fu) can be calculated by determining the compound concentrations in the buffer and matrix compartments after dialysis as follows: %fu ¼ 100 Â buffer conc after dialysis/matrix conc after dialysis. The device recovery is checked by measuring the compound concentrations in the matrix before dialysis and calculating the percent recovery (mass balance). The recovery must be within 80-120% for data acceptance. P-glycoprotein binding.
9% (5/5/90%)). Formulations were injected i. v. using a 30G needle in the lateral tail vein of mice using a volume of 50 ml in the dose indicated. For p. o. applications animals were gavaged using a volume of 100 ml in the dose indicated. At the following time points blood was drawn into EDTA: 0. 08, 0. 25, 0. 5, 1, 2, 4, 7 h (for p. o. the first time point was omitted). Six animals were used for each compound in vivo experiment. Animals were distributed randomly over the time course and at each time point, a volume of 100 ml of blood was taken. Quantitative plasma measurement of the compound was performed by LC-MS/MS analysis. Pharmacokinetic analysis was performed using Phoenix WinNonlin 6. 4 software using a non-compartmental approach consistent with the route of administration. For assessment of the exposure Cmax, Tmax and AUC were determined from the serum concentration profiles.