Miracle-dz/UniFAR-FTUs huggingface dataset:
Deferasirox Treatment Interruption in a Transfusion-Requiring Myelodysplastic Patient Led to Loss of Erythroid Response

showed a normal karyotype and a FISH panel did not detect the most common aberrations related to MDS [5q–, 7q–, +8 and del(20q)]. A diagnosis of refractory cytopenia with multilineage dysplasia (RCMD) according to WHO classification, with low-risk IPSS, was made. At that time, a CT scan revealed the presence of multiple calculi in the gallbladder. Treatment with erythropoietin was started in March 2007, but despite this treatment, the patient started to present a transfusional requirement and erythropoietin was definitively suspended after 3 months. At that time, the serum ferritin level was 650 ng/ml. The patient received only supportive therapy with a median transfusional requirement of 3 red blood cell units/month until May 2008, when serum ferritin increased to 4,640 ng/ml. Deferasirox treatment at the dose of 20 mg/kg was started in June 2008 and the patient experienced only a moderate skin rash during the first 2 weeks of treatment, which spontaneously resolved with no requirement of drug suspension or alternative treatments. We did observe a progressive decrease of serum ferritin, which reached 1,002 ng/ml after 6 months of treatment. Concomitantly, the transfusional requirement decreased and the Hb level increased up to 10 g/dl after 3 months of treatment. Transfusions were no longer required after 6 months of treatment. When the patient Deferasirox is a once-daily oral iron chelator with established dose-dependent efficacy in both adult and pediatric patients with transfusional iron overload [1] . Clinical trials have demonstrated the efficacy of deferasirox for up to 2 years of treatment in patients with myelodysplastic syndromes (MDS) [2, 3] . The drug is able to reduce key indicators of total body iron levels (serum ferritin, liver iron concentration and toxic labile plasma iron) and has also demonstrated a good tolerability profile, which renders it a suitable therapeutic option for patients with chronic conditions requiring ongoing iron chelation therapy. Current guidelines indicate to suspend deferasirox treatment in MDS patients once serum ferritin is below 1,000 ng/ml [4] . Some interesting observations have been reported on the effect of deferasirox on erythroid improvement, and it is still a matter of debate when the drug has to be suspended [5–7] . Here, we describe a MDS patient with a transfusional requirement, who under deferasirox treatment showed an erythroid improvement; however, after interruption of the drug lost the response, but regained it when the drug was resumed. A 50-year-old man was referred to our institution in November 2006 for fever, anemia (9 g/dl), thrombocytopenia (50 ! 10 9 /liter) and abdominal pain. Bone marrow morphological analysis showed trilinear dysplasia, with 4% of blast cells. Cytogenetic conventional analysis Received: March 11, 2010 Accepted after revision: May 5, 2010 Published online: July 9, 2010
Fabrication of Dicing-Free Vertical-Structured High-Power GaN-Based Light-Emitting Diodes With Selective Nickel Electroplating and Patterned Laser Liftoff Techniques

Through the use of selective nickel (Ni) electroplating, patterned laser liftoff technique, and surface roughing of the top n-GaN epilayer, a novel process for the fabrication of vertical-structured metal-substrate GaN-based light-emitting diodes (VM-LEDs) to avoid difficulties in Ni substrate dicing and improve device yield was proposed and demonstrated. In conjunction with a sidewall passivation with SiO2 and keeping the size of epilayer smaller than that of Ni island, a considerable improvement in yield and device performance were shown. As compared to conventional lateral-structured GaN-based LEDs, VM-LEDs show an increase in light output power about 174% at 350 mA with a significant decrease in forward voltage from 3.5 to 3.17 V
Intra-abdominal pressures during activity in women using an intra-vaginal pressure transducer

Abstract Strenuous physical activity has been linked to pelvic floor disorders in women. Using a novel wireless intra-vaginal pressure transducer, intra-abdominal pressure was measured during diverse activities in a laboratory. Fifty-seven women performed a prescribed protocol using the intra-vaginal pressure transducer. We calculated maximal, area under the curve and first moment of the area intra-abdominal pressure for each activity. Planned comparisons of pressure were made between levels of walking and cycling and between activities with reported high pressure in the literature. Findings indicate variability in intra-abdominal pressure amongst individuals doing the same activity, especially in activities that required regulation of effort. There were statistically significant differences in maximal pressure between levels of walking, cycling and high pressure activities. Results for area under the curve and first moment of the area were not always consistent with maximal pressure. Coughing had the highest maximal pressure, but had lower area under the curve and first moment of the area compared to most activities. Our data reflect novel findings of maximal, area under the curve and first moment of the area measures of intra-abdominal pressure, which may have clinical relevance for how physical activity relates to pelvic floor dysfunction.
Comparison of methods and optimisation of the analysis of fumonisins B1 and B2 in masa flour, an alkaline cooked corn product

A comparison study of different extraction and clean-up procedures for the liquid chromatographic analysis of fumonisins B1 (FB1) and B2 (FB2) in corn masa flour was performed. The procedures included extraction (heat or room temperature) with acidic conditions or EDTA-containing solvents, and clean-up by immunoaffinity or C18 solid-phase extraction columns. Thereafter an analytical method was optimised using extraction with an acidic mixture of methanol–acetonitrile–citrate/phosphate buffer, clean-up through the immunoaffinity column and determination of fumonisins by liquid chromatography with automated pre-column derivatisation with o-phthaldialdehyde reagent. Recovery experiments performed on yellow, white and blue masa flours at spiking levels of 400, 800 and 1200 µg kg−1 FB1 and of 100, 200 and 300 µg kg−1 FB2 gave overall mean recoveries of 99% (±6%) for FB1 and 88% (±6%) for FB2. Good recoveries (higher than 90% for both FB1 and FB2) were also obtained with corn tortilla chips. The limits of quantification of the method (signal-to-noise ratio of 10) were 25 µg kg−1 for FB1 and 17 µg kg−1 for FB2. The method was tested on different commercial corn masa flours as well as on white and yellow corn tortilla chips, showing fumonisin contamination levels (FB1 + FB2) up to 1800 µg kg−1 (FB1 + FB2) in masa flour and 960 µg kg−1 in tortilla chips. Over 30% of masa flours originating from Mexico exceeded the European Union maximum permitted level.
MTHFR Genotype and Colorectal Adenoma Recurrence: Data from a Double-blind Placebo-controlled Clinical Trial

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. We assessed the association between two common MTHFR variants, 677C>T and 1298A>C, and adenoma recurrence in the context of a randomized double- blind clinical trial of aspirin use and folate supplementation. We used generalized linear regression to estimate risk ratios and 95% confidence intervals (95% CI) for recurrence, adjusting for age, sex, clinical center, follow-up time, and treatment status. Neither MTHFR polymorphism was associated with overall or advanced adenoma recurrence. Compared with those with two wild-type alleles, the relative risk for advanced adenoma was 0.75 (95% CI, 0.36-1.55) for the MTHFR 677 TT genotype and 1.16 (95% CI, 0.58-2.33) for the MTHFR 1298 CC genotype. The effect of folate supplementation on recurrence risk did not differ by genotype. Our findings indicate that the MTHFR genotype does not change adenoma risk in a manner similar to its effect on colorectal cancer, and does not modify the effect of folate supplementation on metachronous adenoma risk. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2409–15)
Role of Viral Factor E3L in Modified Vaccinia Virus Ankara Infection of Human HeLa Cells: Regulation of the Virus Life Cycle and Identification of Differentially Expressed Host Genes

ABSTRACT Modified vaccinia virus Ankara (MVA) is a highly attenuated virus strain being developed as a vaccine for delivery of viral and recombinant antigens. The MVA genome lacks functional copies of numerous genes interfering with host response to infection. The interferon resistance gene E3L encodes one important viral immune defense factor still made by MVA. Here we demonstrate an essential role of E3L to allow for completion of the MVA molecular life cycle upon infection of human HeLa cells. A deletion mutant virus, MVA-ΔE3L, was found defective in late protein synthesis, viral late transcription, and viral DNA replication in infected HeLa cells. Moreover, we detected viral early and continuing intermediate transcription associated with degradation of rRNA, indicating rapid activation of 2′-5′-oligoadenylate synthetase/RNase L in the absence of E3L. Further molecular monitoring of E3L function by microarray analysis of host cell transcription in MVA- or MVA-ΔE3L-infected HeLa cells revealed an overall significant down regulation of more than 50% of cellular transcripts expressed under mock conditions already at 5 h after infection, with a more prominent shutoff following MVA-ΔE3L infection. Interestingly, a cluster of genes up regulated exclusively in MVA-ΔE3L-infected cells could be identified, including transcripts for interleukin 6, growth arrest and DNA damage-inducible protein β, and dual-specificity protein phosphatases. Our data indicate that lack of E3L inhibits MVA antigen production in human HeLa cells at the level of viral late gene expression and suggest that E3L can prevent activation of additional host factors possibly affecting the MVA molecular life cycle.
Identification of heterotrimeric G proteins in human sperm tail membranes

Heterotrimeric G proteins play important roles as signal transducing components in various mammalian sperm functions. We were interested in the distribution of G proteins in human sperm tails. Prior to membrane preparation, spermatozoa were separated from contaminating cells which are frequently present in human ejaculates. Enriched human sperm tail membranes were generated by using hypoosmotic swelling and homogenization procedures. Antisera against synthetic peptides were used to identify G proteins in immunoblots. AS 8, an antiserum directed against an amino acid sequence that is found in most G protein α‐subunits, and A 86, which detects all known pertussis toxin‐sensitive α‐subunits, reacted specifically with a 40‐kDa protein. Antisera against individual G protein α‐subunits failed to detect any specific antigens in enriched tail membranes AS 36, recognizing the ã2‐subunit of G proteins, identified a 35‐kDa protein in sperm tail membranes. Antisera against the 36‐kDa β1‐subunit did not detect any relevant proteins in the membrane fraction. Neither G protein α‐subunits nor G protein β‐subunits were found in the cytosol. ADP ribosylation of spermatozoal membrane or cytosolic proteins revealed no pertussis toxin‐sensitive α‐subunits. However, membrane preparations of nonpurified human spermatozoa contained α2 subunits, as shown immunologically and by ADP ribosylation; they most probably derived from somatic cells which are frequently present in human ejaculates. Our results stress the fact that spermatozoa need to be purified before sperm membrane preparation to avoid misinterpretations caused by contaminating cells. Furthermore, we suggest that G proteins in membranes of human sperm tails belong to a novel subtype of G protein α‐subunits; the putative β‐subunit was identified as a β2‐subunit. © 1995 Wiley‐Liss, Inc.
Reliability of computerized perimetric threshold tests as assessed by reliability indices and threshold reproducibility in patients with suspect and manifest glaucoma.

BACKGROUND High reproducibility of test measurements is often considered an indication of high reliability of test results. The aim of the current study was to analyse the role of the traditional perimetric reliability indices, False Negative and False Positive responses, and Fixation Losses, as indicators of test reliability in comparison with threshold reproducibility in patients with suspect or manifest glaucoma. METHODS Perimetry was performed in one eye in each of 76 patients. Each eye was tested twice within approximately one week using the Humphrey II 30-2 SITA STANDARD program. Frequencies of False Positive and False Negative answers, and rates of Fixation Losses were related to threshold reproducibility and to general field status as expressed by Mean Deviation from age-normal threshold values using stepwise multiple linear regression analysis. RESULTS Substantial field loss was associated both with low threshold reproducibility (p<0.0001) and with increased frequency of False Negative answers (p=0.047). The traditional reliability indices contributed marginally compared to amount of field loss when predicting threshold reproducibility; the coefficient of determination decreased non-significantly from 0.37 to 0.33 when excluding the three reliability indices as explanatory variables from the regression model. Frequencies of False Positive answers and Fixation Losses showed no association to field status or to threshold reproducibility. CONCLUSION Reliability of visual field test results in patients with glaucoma expressed as threshold reproducibility, can be predicted by amount of field loss alone, and traditional patient reliability indices contribute surprisingly little in this regard.
Cost-effectiveness of saxagliptin versus glimepiride as a second-line therapy added to metformin in Type 2 diabetes in China

acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication. Just Accepted by Journal of Medical Economics
Light and Scanning Electron Microscopic Structure of the Pecten Oculi in the Common Barn Owl (Tyto alba)

This study was carried out to investigate the structural properties of pecten oculi in the common barn owl (Tyto alba) by light and electron microscope. Fourteen eyeballs from seven owls were studied. The pecten oculi was located postero-anteriorly in the retina layer where the optic nerve enters the eye. The pecten oculi that was dark brown and pleated type consisted of 7 (n=4) or 8 (n=10) vascularised pectineal pleats. Histologically, there were numerous vessels of different size and melanocytes in the area of the pleats. Melanocytes were more frequently observed in the periphery of the pecten oculi’s pleats. Scanning electron microscopy showed hyalocytes on the surface of the pecten oculi. The results of the study indicated that the pecten oculi of the common barn owl was morphologically similar to that of other nocturnal birds.
Encapsulating legacy software for use in client/server systems

An alternative to migrating legacy software from the mainframe to a client/server platform is to encapsulate it by wrapping it on the host and accessing it from the new client programs. Recent technological achievements such as the OMG's Common Object Request Broker Architecture (CORBA) and IBM's System Object Model (SOM) have made it possible for distributed objects to communicate with existing applications on the mainframe. However as described here, some alterations have to be made to the old programs to make them accessible. Achieving this promises a new form of coexistence between monolithic legacy systems on the mainframe and object-oriented, distributed systems in the network. It also introduces a new mode of software reuse.
Role of Human Nucleoside Transporters in the Uptake and Cytotoxicity of Azacitidine and Decitabine

The nucleoside analogs 5-azacytidine (azacitidine) and 5-aza-2′-deoxycytidine (decitabine) are active against acute myeloid leukemia and myelodysplastic syndromes. Cellular transport across membranes is crucial for uptake of these highly polar hydrophilic molecules. We assessed the ability of azacitidine, decitabine, and, for comparison, gemcitabine, to interact with human nucleoside transporters (hNTs) in Saccharomyces cerevisiae cells (hENT1/2, hCNT1/2/3) or Xenopus laevis oocytes (hENT3/4). All three drugs inhibited hCNT1/3 potently (K i values, 3–26 μM), hENT1/2 and hCNT2 weakly (K i values, 0.5–3.1 mM), and hENT3/4 poorly if at all. Rates of transport of [3H]gemcitabine, [14C]azacitidine, and [3H]decitabine observed in Xenopus oocytes expressing individual recombinant hNTs differed substantially. Cytotoxicity of azacitidine and decitabine was assessed in hNT-expressing or hNT-deficient cultured human cell lines in the absence or presence of transport inhibitors where available. The rank order of cytotoxic sensitivities (IC 50 values, μM) conferred by hNTs were hCNT1 (0.1) > hENT1 (0.3) ≫ hCNT2 (8.3), hENT2 (9.0) for azacitidine and hENT1 (0.3) > hCNT1 (0.8) ⋙ hENT2, hCNT2 (>100) for decitabine. Protection against cytotoxicity was observed for both drugs in the presence of inhibitors of nucleoside transport, thus suggesting the importance of hNTs in manifestation of toxicity. In summary, all seven hNTs transported azacitidine, with hCNT3 showing the highest rates, whereas hENT1 and hENT2 showed modest transport and hCNT1 and hCNT3 poor transport of decitabine. Our results show for the first time that azacitidine and decitabine exhibit different human nucleoside transportability profiles and their cytotoxicities are dependent on the presence of hNTs, which could serve as potential biomarkers of clinical response.
Compound‐specific Na+ channel pore conformational changes induced by local anaesthetics

Upon prolonged depolarizations, voltage‐dependent Na+ channels open and subsequently inactivate, occupying fast and slow inactivated conformational states. Like C‐type inactivation in K+ channels, slow inactivation is thought to be accompanied by rearrangement of the channel pore. Cysteine‐labelling studies have shown that lidocaine, a local anaesthetic (LA) that elicits depolarization‐dependent (‘use‐dependent’) Na+ channel block, does not slow recovery from fast inactivation, but modulates the kinetics of slow inactivated states. While these observations suggest LA‐induced stabilization of slow inactivation could be partly responsible for use dependence, a more stringent test would require that slow inactivation gating track the distinct use‐dependent kinetic properties of diverse LA compounds, such as lidocaine and bupivacaine. For this purpose, we assayed the slow inactivation‐dependent accessibility of cysteines engineered into domain III, P‐segment (μ1: F1236C, K1237C) to sulfhydryl (MTSEA) modification using a high‐speed solution exchange system. As expected, we found that bupivacaine, like lidocaine, protected cysteine residues from MTSEA modification in a depolarization‐dependent manner. However, under pulse‐train conditions where bupivacaine block of Na+ channels was extensive (due to ultra‐slow recovery), but lidocaine block of Na+ channels was not, P‐segment cysteines were protected from MTSEA modification. Here we show that conformational changes associated with slow inactivation track the vastly different rates of recovery from use‐dependent block for bupivacaine and lidocaine. Our findings suggest that LA compounds may produce their kinetically distinct voltage‐dependent behaviour by modulating slow inactivation gating to varying degrees.
Evaluation of polymerization shrinkage, polymerization shrinkage stress, wear resistance, and compressive strength of a silorane-based composite: A finite element analysis study

Background: Understanding the mechanical properties is important in predicting the clinical behavior of composites. Finite element analysis (FEA) evaluates properties of materials replicating clinical scenario. Aim: This study evaluated polymerization shrinkage and stress, wear resistance (WR), and compressive strength (CS) of silorane in comparison with two methacrylate resins. Settings and Design: This study design was a numerical study using FEA. Materials and Methods: Three-dimensional (3D) models of maxillary premolar with Class I cavities (2 mm depth, 4 mm length, and 2.5 mm width) created and restored with silorane, nanohybrid, and microhybrid; Groups I, II, and III, respectively. Loads of 200–600 N were applied. Polymerization shrinkage was first determined by displacement produced in the X, Y, and Z planes. Maximum stress distribution due to shrinkage was calculated using AN SYS software. 3D cube models of composite resins were simulated with varying filler particle size. Similar loads were applied. WR and compressive stress were calculated: K W L/H and load/cross-sectional area, respectively. Statistical analysis done using one-way ANOVA, Kruskal–Wallis, and Tukey's honestly significant difference test (P < 0.05). Results: Polymerization shrinkage (0.99%) and shrinkage stress (233.21 Mpa) of silorane were less compared to microhybrid (2.14% and 472.43 Mpa) and nanohybrid (2.32% and 464.88 Mpa). Silorane (7.92×/1011 μm/mm3) and nanohybrid (7.79×/1011) showed superior WR than microhybrid (1.113×/1017). There was no significant difference in compressive stress among the groups. Conclusion: Silorane exhibited less polymerization shrinkage and shrinkage stress compared to methacrylates. Silorane and nanohybrid showed greater WR compared to microhybrid. CS of all groups was similar.
The limited unity of virtue

Rejetant la these de l'incompatibilite des vertus et la these de l'independance mutuelle des vertus, l'A. admet que la conception aristotelicienne de la vertu et de la sagesse pratique est plausible, mais qu'elle n'est valide qu'a l'interieur de certains domaines de l'existence de l'individu