Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomized double-blinded comparison of the antiemetic efficacy of ondansetron and droperidol in patients receiving high-dose interleukin-2.

Emesis and nausea are common toxicities seen during high-dose interleukin-2 (IL-2) therapy (720,000 IU/kg i.v. every 8 h). A growing list of randomized studies have documented the efficacy of ondansetron, a potent antagonist of the 5-hydroxytryptamine3 receptor, in preventing acute chemotherapy-induced emesis and nausea. However, no study has evaluated the efficacy of ondansetron in preventing IL-2-induced emesis and nausea. This double-blinded, randomized trial was performed to compare the antiemetic and antinausea efficacy of ondansetron with that of droperidol, a butyrophenone, in patients receiving high-dose IL-2 on protocols at the National Cancer Institute. Ondansetron or droperidol was given intravenously, 30 min prior to the first dose of IL-2 and then every 8 h for the duration of IL-2 treatment. No significant differences were seen between the two agents in complete freedom from emesis (p2 = 0.51), level of nausea (p2 = 0.17), antiemetic treatment failure (p2 = 0.89), and time to first emetic episode (p2 = 0.44). Equivalent doses of IL-2 were administered on each arm of the study, with a similar incidence of liver dysfunction (p2 = 0.15) and diarrhea (p2 = 0.64). Finally, there was no significant difference in the response rates to metastatic disease in either arm of the antiemetic study (p2 = 0.67), and these response rates were similar to those in other patients treated under immunotherapy protocols in the Surgery Branch of the National Cancer Institute with high-dose IL-2. We conclude that droperidol is equally effective in preventing emesis and controlling nausea when compared with ondansetron for patients receiving high-dose IL-2.
Influence de la dynamique mésoéchelle et submésoéchelle sur la compétition au sein d'un écosystème planctonique

L’ocean est un milieu fortement turbulent caracterise par des structures tourbillonnaires tres energetiques interagissant entre elles. Dans les couches de surface, les observations et les modeles montrent que cette dynamique meso- et submeso-echelle combinee a la dynamique de la couche melangee, contraint fortement la distribution des especes phytoplanctoniques. L’objet de cette these est de realiser une etude de processus en modelisation numerique afin de rationaliser l’effet de la turbulence meso- et submeso-echelle d’une part et du me��lange vertical d’autre part, sur la diversite phytoplanctonique. L’etude de la dynamique intrinseque d’un modele d’ecosysteme avec deux phytoplanctons a l’aide de la theorie des systemes dynamiques a tout d’abord permis de determiner les equilibres non-lineaires ainsi que leur stabilite en fonction des parametres. Nous avons montre ensuite que la diffusion verticale turbulente est un moteur de la coexistence phytoplanctonique. La sensibilite de ces resultats a ete testee a la fois vis a vis de la profondeur de la couche melangee, de l’intensite du melange et du nombre d’especes. Enfin, nous avons montre que la turbulence quasi-geostrophique de surface permet la coexistence de deux phytoplanctons sur une ressource limitante a l’equilibre statistique. Ce type de turbulence organise differemment les especes selon les structures les structures filamentaires sont favorables au grand phytoplancton alors que les tourbillons apparaissent comme des niches ecologiques pour le petit phytoplancton. Cette etude revele que les injections verticales de nutriments sont un facteur important induisant cette difference de distribution entre les especes.
The Effect of Mechanical Loading on the Size and Shape of Bone in Pre‐, Peri‐, and Postpubertal Girls: A Study in Tennis Players

Exercise during growth results in biologically important increases in bone mineral content (BMC). The aim of this study was to determine whether the effects of loading were site specific and depended on the maturational stage of the region. BMC and humeral dimensions were determined using DXA and magnetic resonance imaging (MRI) of the loaded and nonloaded arms in 47 competitive female tennis players aged 8–17 years. Periosteal (external) cross‐sectional area (CSA), cortical area, medullary area, and the polar second moments of area (IP, mm4) were calculated at the mid and distal sites in the loaded and nonloaded arms. BMC and IP of the humerus were 11–14% greater in the loaded arm than in the nonloaded arm in prepubertal players and did not increase further in peri‐ or postpubertal players despite longer duration of loading (both, p < 0.01). The higher BMC was the result of a 7–11% greater cortical area in the prepubertal players due to greater periosteal than medullary expansion at the midhumerus and a greater periosteal expansion alone at the distal humerus. Loading late in puberty resulted in medullary contraction. Growth and the effects of loading are region and surface specific, with periosteal apposition before puberty accounting for the increase in the bone's resistance to torsion and endocortical contraction contributing late in puberty conferring little increase in resistance to torsion. Increasing the bone's resistance to torsion is achieved by modifying bone shape and mass, not necessarily bone density.
Parallel programming and speed up evaluation of a NoC 2-ary 4-fly

In this paper we make the design, the simulation and the implementation of a NoC (Network on Chip) 2-ary 4-fly in order to evaluate the speed up of an application with different NoC sizes. For the conception of the NoC, we use the tool NoCcompiler from Arteris Company. To test the performance of this NoC we integrate it as an IP (Intellectual Property) into an EDK project where masters are 16 Microblazes processors and slaves are 16 blocks memories. As an application, we choose the parallel programming to compute a filter Harris of an image 256×256. This work is implemented on Eve platform emulation called Zebu UF4. Results have proved the efficiency of this parallel architecture with a reduction equal to 90% of the execution time. The non linearity of the speed up's curve is coherent with the theorical modelisation and simulation presented in[1].
Human herpesvirus 8 (HHV8) sequence variations in HHV8 related tumours in Okinawa, a subtropical island in southern Japan

Background: Although rare in mainland Japan, classic Kaposi’s sarcoma (KS) is frequently reported in Okinawa, a subtropical island in southern Japan. Human herpesvirus 8 (HHV8) has been identified in the tumours and geographical differences occur. Aim: To sequence HHV8 in classic and AIDS associated KS in Okinawa. Materials/Methods: Eight classic KS cases, one AIDS associated KS, five granuloma pyogenicum cases, two inflammatory pseudotumours, two Castleman’s disease cases, one angiosarcoma, and one primary effusion lymphoma (PEL) were studied. As a control, HHV8 positive cultured PEL cells (TY-1) were used. The presence of HHV8 sequences was evaluated by PCR and in situ hybridisation. PCR products were sequenced. Results: There were no histological differences among KS resulting from the different virus genotypes. HHV8 was detected in all cases of KS, in one PEL, and one granuloma pyogenicum. Eight classic KS cases and one granuloma pyogenicum were infected with HHV8 genotype II/C (K1 region) or subtype C (ORF26 region), which had a five amino acid deletion at K1 VR2 region. An AIDS associated KS and a PEL were infected with type I/A virus. Conclusion: In Okinawa, classic KS cases and one granuloma pyogenicum case were infected with HHV8 genotype II/C, also classified as subtype C. AIDS associated KS and PEL were infected with a different HHV8 (genotype I/A), similar to that found in the USA. In Okinawa, HHV8 infection is more than four times higher than in mainland Japan, resulting in many cases of KS because of HHV8 genotype II/C infection.
Protective effects of melatonin against caustic esophageal burn injury in rats

Abstract: Caustic ingestion is one of the most life‐threatening events in the pediatric age group, which requires the immediate management and subsequent treatment of its most significant complication, i.e. alterations in esophageal structure. We investigated whether melatonin could reduce the esophageal burn damage induced by sodium hydroxide. It was assumed that melatonin could be effective because of its function as a direct free radical scavenger, its antioxidative actions and its ability to diminish tissue hydroxyproline (HP) levels. Esophageal burns were induced in male rats by the administration of 10% sodium hydroxide. Lipid peroxidation (LPO) products were then measured at the following times: 0, 1, 6, 24, 48 and 72 hr after treatment. Tissue HP concentrations in the injured area were assessed at 14 days after the administration of sodium hydroxide. The groups received either systemic melatonin or normal saline. There were two, non‐ischemic, sham control groups treated with or without melatonin. LPO products, malondialdehyde (MDA) and 4‐hydroxyalkenal (4‐HDA), increased immediately after the administration of sodium hydroxide; this indicates the participation of free radicals in the development of damage. Melatonin diminished the oxidative response and the amount of HP in the late phase of the lesion. Melatonin reduced oxidative damage in the early phase of the esophageal burns induced by sodium hydroxide.
Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock.

We conducted a prospective, randomized, double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury, including the adult respiratory distress syndrome (ARDS), or improve mortality when administered early in septic shock. All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1, 1983 and August 29, 1986 were eligible for admission to the study if they had either (1) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values (in already hospitalized patients), or (2) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg (in newly admitted patients). Patients meeting these criteria were excluded if they (1) had severe immunodeficiency, (2) were less than 18 or greater than 76 yr of age, (3) had multilobar roentgenographic infiltrates, or (4) were already receiving corticosteroids. Eighty-seven patients enrolled in the study received either methylprednisolone, 30 mg/kg per dose, or mannitol placebo for a total of 4 doses every 6 h, following the presumptive diagnosis of septic shock. Of these patients, 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry. Thirteen of the patients who received methylprednisolone developed ARDS, compared to 14 patients who received placebo. Lesser degrees of parenchymal lung injury did not differ between the 2 groups. (ABSTRACT TRUNCATED AT 250 WORDS)
RANKL-mediated Reactive Oxygen Species Pathway That Induces Long Lasting Ca2+ Oscillations Essential for Osteoclastogenesis*

RANKL (receptor activator of NF-κB ligand) induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca2+ ([Ca2+]i). The [Ca2+]i oscillations activate calcineurin, which activates the transcription factor NFATc1. The pathway by which RANKL induces [Ca2+]i oscillations and osteoclastogenesis is poorly understood. Here we report the discovery of a novel pathway induced by RANKL to cause a long lasting increase in reactive oxygen species (ROS) and [Ca2+]i oscillations that is essential for differentiation of bone marrow-derived monocytes into osteoclasts. The pathway includes RANKL-mediated stimulation of Rac1 to generate ROS, which stimulate phospholipase Cγ1 to evoke [Ca2+]i oscillations by stimulating Ca2+ release from the inositol 1,4,5-trisphosphate pool and STIM1-regulated Ca2+ influx. Induction and activation of the pathway is observed only after 24-h stimulation with RANKL and lasts for at least 3 days. The physiological role of the pathway is demonstrated in mice with deletion of the Peroxiredoxin II gene and results in a mark increase is ROS and, consequently, a decrease in bone density. Moreover, bone marrow-derived monocytes in PrxII−/− primary culture show increased ROS and spontaneous [Ca2+]i oscillations. These findings identify the primary RANKL-stimulated pathway to trigger the late stages of osteoclastogenesis and regulate bone resorption.
Sorption kinetics of TNT and RDX in anaerobic freshwater and marine sediments: Batch studies

Examination of the partitioning of explosives onto sediment in marine environments is critical to predict the toxicological impacts of worldwide explosive‐contaminated sites adjacent to estuaries, wetlands, and the coastal ocean. Marine sediments have been identified as sites of enhanced munitions removal, yet most studies addressing these interactions focus on soils and freshwater sediments. The present study measured the kinetics of 2,4,6‐trinitrotoluene (TNT) and hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX) sorption onto 2 marine sediments of varying grain sizes (silt vs sand) and organic carbon (OC) content. Abiotic sediment sorption tests were performed at 23 °C, 15 °C, and 4 °C by spiking TNT and RDX solutions directly into anaerobic sediment slurries. Marine sediments showed significantly higher compound uptake rates (0.30–0.80 h−1) than freshwater silt (0.0046–0.0065 h−1) for both compounds, probably because of lower compound solubilities and a higher pH in marine systems. Equilibrium partition constants are on the same order of magnitude for marine silt (1.1–2.0 L kg−1 sediment) and freshwater silt (1.4–3.1 L kg−1 sediment) but lower for marine sand (0.72–0.92 L kg−1 sediment). Total organic carbon content in marine sediments varied linearly with equilibrium partition constants for TNT and was moderately linear for RDX. Uptake rates and equilibrium constants of explosives are inversely correlated to temperature regardless of sediment type because of kinetic barriers associated with low temperatures. Environ Toxicol Chem 2016;35:47–55. © 2015 SETAC
Subchronic dose-response study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley rats.

Toxic and biochemical potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied in a 13-week feeding study in female Sprague-Dawley rats. The diets were supplemented with 0, 0.2, 0.4, 0.7, 5, or 20 micrograms TCDD/kg diet. The estimated daily intakes were calculated to be 0, 14, 26, 47, 320, or 1024 ng TCDD/kg body wt/day. At the end of the study, TCDD concentrations were measured in liver and adipose tissue. The lowest estimated daily intake that caused an increase in liver weight was 320 ng TCDD/kg/day, while an intake of 47 ng TCDD/kg/day resulted in a decrease in plasma thyroid hormone concentrations and a decrease in body weight gain. Decreases in relative thymus weights, loss of hepatic retinoids, and induction of CYP1A1 and CYP1A2 activities were already found at 14 ng/kg/day, the lowest dose used. Therefore, 95% confidence limits for the no-effect levels (CNELs) were calculated from the corresponding dose-response relationships by using sigmoidal curve fittings (Hill, Weibull, and a Logistic model) and a probability level of p < 0.05. For increases in CYP1A1 and CYP1A2 activities, the right critical values for the CNELs ranged from 0.7 to 4 ng TCDD/kg/day (Hill and Weibull). Based on hepatic TCDD residue levels, these right critical values for the CNELs ranged from 0.06 to 0.4 ng TCDD/g liver (wet weight) (Hill and Weibull). The CNELs in this study agree very well with the no-observed-adverse-effects levels as reported before in chronic, carcinogenicity, and reproductive studies with rats and TCDD, i.e., 1 ng/kg/day.
Allergic contact sensitization in the general adult population: a population‐based study from Northern Norway

Few studies have so far addressed the prevalence and risk factors for contact sensitization in the general adult population; however, many such studies have been conducted in hospitals. We present the prevalence of contact sensitization in a general adult population and its relationship to potential risk factors like smoking, ear piercing and atopic diseases. 1236 adults (44.2% men and 55.8% women) were randomly selected from a cross‐section of the population in Sør‐Varanger municipality, Norway, and patch tested with TRUE Test (Pharmacia, Hillerød, Denmark). Contact sensitivity to at least 1 out of 24 allergens was found in 35.4% of the women and in 14.8% of the men. The most common allergens were nickel (17.6%), cobalt (2.8%), thiomersal (1.9%), fragrance mix (1.8%) and colophony (1.2%). All other allergens were observed in 1.0% or less. In women, ear piercing was an important risk factor for nickel sensitization. No such significant correlation was seen in men [in women relative risk (RR) = 3.30, 95% confidence interval (CI) = 2.01–5.43, and in men RR = 1.82, 95% CI = 0.66–5.00], and contact sensitivity was associated with atopic dermatitis (AD) [adjusted odds ratio (OR) = 1.58, 95% CI = 1.04–2.40] and smoking (adjusted OR = 1.42, 95% CI = 1.01–1.99) in women but not in men. The prevalence of contact sensitivity was common in this general population, especially in women. Smoking and AD might be a risk factor for contact sensitization.
Cost-effectiveness of polysaccharide pneumococcal vaccination in people aged 65 and above in Poland

Introduction: Invasive pneumococcal disease is associated with substantial morbidity, mortality and cost implications, which could be reduced by vaccination. Aim: To assess the cost-effectiveness of a 23-valent pneumococcal vaccine in the elderly (65 and older) in Poland. Methods: A Markov model with a 1-year cycle length was developed, allowing up to 10 cohorts to enter the model over the lifetime horizon (35 years). In the base case, costs and benefits were assessed using the public health care payer (NFZ) perspective. The analysis included routine vaccination of all elderly and high-risk (HR) elderly versus no vaccination. The analysis assumed that the government would reimburse 50% of the vaccine price. Costs and benefits were discounted 5%, with costs expressed in 2009 Polish Zloty (PLN). Extensive sensitivity analyses were carried out. Results: PPV23 vaccination targeting all elderly and HR elderly in Poland would avoid 8,935 pneumococcal infections, 2,542 hospitalisations, 671 deaths and 5,886 infections, 1,673 hospitalisations and 441 deaths respectively. The incremental cost per QALY gained would be PLN 3,382 in all elderly and PLN2,148 in HR elderly. Conclusion: Vaccinating adults 65 and older regardless of risk status with a 23-valent pneumococcal vaccine, is cost-effective, resulting in clinical and economic benefits including a non-negligible reduction of ambulatory doctor visits, hospitalizations and, deaths in Poland.
Mucin Genes Expression in the Intestine of Crohn's Disease Patients: a Systematic Review and Meta-analysis.

BACKGROUND AND AIMS The mucus layer of the intestinal tract is the main barrier between luminal microbes and the mucosa, and has an essential role in the body defense mechanisms. Previous research could not establish consistent results for mucin genes expression in Crohn's disease (CD) patients. In this meta-analysis we looked at the mucin expression in CD patients and compared it with healthy controls. METHOD English medical literature searches were conducted for mucin expression in the mucosa of the ileum and colon of CD patients and compared it with normal mucosa. Case-control studies were included. Meta-analysis was performed by using Comprehensive meta-anaslysis software. Pooled odds ratios and 95% confidence intervals were calculated. RESULTS We found 160 eligible studies. Twenty studies were rejected because they have been performed in animals or did not have full text, and 134 studies were excluded because of language, being editorials, review articles, or because of duplications. We were left with 6 case-control studies from 4 countries that fulfilled the inclusion criteria, published till 31.12. 2015. No significant heterogeneity was demonstrated: Q = 149.256, df (Q) = 40.00, I2= 73.2% (less than 75%). We found a decrease of 34% in the total mucin expression in CD patients (Odds Ratio 0.660, 95% CI 0.486-0.897, P = 0.008). We also found a significantly decreased expression in CD patients for MUC5AC, MUC5B and MUC7. CONCLUSION We demonstrated a global decrease in mucin expression in CD patients when compared with healthy controls.
Lipid-destabilizing properties of the hydrophobic helices H8 and H9 from colicin E1

Colicins are toxic proteins produced by Escherichia coli that must cross the membrane to exert their activity. The lipid insertion of their pf domain is linked to a conformational change which enables the penetration of a hydrophobic hairpin. They provide useful models to more generally study insertion of proteins, channel formation and protein translocation in and across membranes. In this paper, we study the lipid-destabilizing properties of helices H8 and H9 forming the hydrophobic hairpin of colicin E1. Modelling analysis suggests that those fragments behave like tilted peptides. The latter are characterized by an asymmetric distribution of their hydrophobic residues when helical. They are able to interact with a hydrophobic/hydrophilic interface (such as a lipid membrane) and to destabilize the organized system into which they insert. Fluorescence techniques using labelled liposomes clearly show that H9, and H8 to a lesser extent, destabilize lipid particles, by inducing fusion and leakage. AFM assays clearly indicate that H8 and especially H9 induce membrane fragilization. Holes in the membrane are even observed in the presence of H9. This behaviour is close to what is seen with viral fusion peptides. Those results suggest that the peptides could be involved in the toroidal pore formation of colicin E1, notably by disturbing the lipids and facilitating the insertion of the other, more hydrophilic, helices that will form the pore. Since tilted, lipid-destabilizing fragments are also common to membrane proteins and to signal sequences, we suggest that tilted peptides should have an ubiquitous role in the mechanism of insertion of proteins into membranes.