Miracle-dz/UniFAR-FTUs huggingface dataset:
Deferasirox–Iron Complex Formation Ratio as an Indicator of Long-term Chelation Efficacy in &bgr;-Thalassemia Major

Background: &bgr;-Thalassemia major patients with higher total drug levels [deferasirox (DEFR) plus its iron complex] do not yield better serum ferritin (SF) control. This study aimed to determine the concentrations of DEFR and its iron complex (Fe-[DEFR]2) in thalassemia patients to predict the chelation efficacy in terms of SF and cardiac T2* values. Methods: Patients' steady-state drug levels at trough (Ctrough) and 2 hours postdose (C2h) were determined. Because iron deposition may cause changes in the hepatic metabolism of amino acids, the concentrations of 40 amino acids in plasma were also assayed at 2 hours postdose. Results: A total of 28 patients either dosing daily or twice daily were recruited. After a 1-month DEFR maintenance therapy, 38.8% and 30% of patients from groups of once-daily and twice-daily, respectively, had a plasma DEFR–iron complex formation ratio higher than 0.05 [High Chelation Ratio, (HCR)]. After a 6-month follow-up, those patients who had a HCR (n = 10) at C2h showed more favorable median changes in SF and cardiac T2* values (−388.0, +10.1) than those with a low DEFR–iron complex formation ratio (Low Chelation Ratio; n = 18; +10.5; +4.5) compared with the baseline. The levels of plasma L-arginine, L-alanine, L-glycine, L-norleucine, and L-serine were significantly lower in patients with the low Chelation Ratio condition than the levels in HCR patients. Conclusions: This therapeutic drug monitoring study revealed that a DEFR–iron complex formation ratio at C2h might be an applicable indicator of the efficacy of long-term DEFR iron chelation therapy. A better iron-control response to DEFR was observed in the patients with HCRs. The trends for the ratio might have value in dose-setting and need to be validated in a larger cohort.
[Recurrent bacterial meningitis].

BACKGROUND Recurrent bacterial meningitis (RBM) is an unusual entity and usually poses a considerable diagnostic challenge. Different conditions can predispose for recurrence of episodes and the isolated pathogen can guide the diagnosis. The aim of this study was to characterize all RBM admitted to our tertiary paediatric hospital. METHODS Retrospective analysis of the medical records of all children with RBM, between January 1994 and December 2007 (14 years). RESULTS During this period, 107 children with bacterial meningitis (BM) were admitted. Among those, 10 (9.3%) had more than 1 episode of BM. Five (4.7%) had cerebrospinal fluid shunt. In the other 5 (4.3%), 11 episodes of BM were identified. S. pneumoniae was isolated in the majority of episodes (4) followed by N. meningitis (2). An anatomical defect, namely post-traumatic CSF leakage, was present in 3 children and S. pneumoniae was isolated in all. A predisposing condition has not yet been identified in 2 children and no anatomical defect or immunodeficiency was found despite full investigation. CONCLUSIONS It was identified a high proportion of RBM compared to other series, that could be explained by the fact of being a tertiary hospital. An anatomical defect was the most frequent cause and S. pneumoniae the most frequent bacteria. In cases without an obvious predisposing condition an exhaustive evaluation, including search for anatomical and immunological defects, was performed but no changes were identified.
Inhibitors of MEK1/2 Interact with UCN-01 to Induce Apoptosis and Reduce Colony Formation in Mammary and Prostate Carcinoma Cells

Recent studies have suggested that inhibition of the mitogen activated protein kinase (MAPK) pathway as well as abrogation of cell cycle check-point control can potentiate the lethal actions of chemotherapeutic drugs and radiation. We therefore investigated the impact of combined exposure to the check-point abrogator (UCN-01) in conjunction with MEK1/2 inhibitors upon survival of breast and prostate carcinoma cells. Treatment of cells with UCN-01 alone resulted in prolonged activation of the MAPK pathway. Inhibition of MEK1/2 caused modest reductions in basal MAPK activity and transiently suppressed UCN-01-stimulated MAPK activity below that of MEK1/2 inhibitor alone. Significantly, combined, but not individual, exposure of cells to UCN-01 and MEK1/2 inhibitors enhanced BAX association with mitochondria and triggered release of cytochrome c into the cytosol, accompanied by activation of effector pro-caspases, resulting in a greater than additive potentiation of apoptosis within 18-24h. Radiation exposure of drug treated cells did not further enhance apoptosis. Treatment of cells with both caspase 9 and caspase 8 inhibitors was required to completely inhibit apoptosis in carcinoma cells. Over- expression of Bcl-xL blocked cytochrome c release and cell killing induced by the drug combination. Colony forming assays demonstrated that cells exposed to both agents exhibited a substantial reduction in clonogenic survival compared to either drug alone; moreover, radiation further reduced clonogenic survival despite failing to promote additional apoptosis. Collectively, these data demonstrate that combined exposure of carcinoma cells to UCN-01 and MEK1/2 inhibitors induces apoptosis and interacts with radiation to further reduce clonogenic survival.
Cytokine responses in birds challenged with the human food-borne pathogen Campylobacter jejuni implies a Th17 response

Development of process orientated understanding of cytokine interactions within the gastrointestinal tract during an immune response to pathogens requires experimentation and statistical modelling. The immune response against pathogen challenge depends on the specific threat to the host. Here, we show that broiler chickens mount a breed-dependent immune response to Campylobacter jejuni infection in the caeca by analysing experimental data using frequentist and Bayesian structural equation models (SEM). SEM provides a framework by which cytokine interdependencies, based on prior knowledge, can be tested. In both breeds important cytokines including pro-inflammatory interleukin (IL)-1β, , IL-4, IL-17A, interferon (IFN)-γ and anti-inflammatory IL-10 and transforming growth factor (TGF)-β4 were expressed post-challenge. The SEM revealed a putative regulatory pathway illustrating a T helper (Th)17 response and regulation of IL-10, which is breed-dependent. The prominence of the Th17 pathway indicates the cytokine response aims to limit the invasion or colonization of an extracellular bacterial pathogen but the time-dependent nature of the response differs between breeds.
Increased production of IL-5 and dominant Th2-type response in airways of Churg-Strauss syndrome patients.

OBJECTIVE Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and asthma. We assessed the local immune response in airways of CSS patients with different activity of the disease. METHODS Concentration of IL-5, CCL17, CCL22 and CCL26 (ELISA) together with cell expression of T-helper-related genes (real-time PCR array) were measured in bronchoalveolar lavage fluid (BALF) sampled from 11 patients with active CSS, 11 patients with CSS in remission and 9 control subjects with bronchial asthma. RESULTS In active CSS, both BALF and blood eosinophil counts were increased (P<0.01). BALF cells in active disease were characterized by an increased expression of Th2 and regulatory-type transcripts: STAT6, STAT3, GATA3, IL4, IL5 and IL10 as compared with asthmatics, and STAT5A, CCR4, FOXP3, IL4, IL5 and IL10 when compared with inactive CSS. There was significant increase in BALF concentration of IL-5 and CCL26 in exacerbation of CSS. CCR4-active chemokines were detected more frequently in active disease. We found a strong positive correlation between clinical parameters of disease activity (BVAS, eosinophilia) and expression of IL4, IL5, IL10 and STAT5A. CONCLUSION These results indicate that as compared with asthma, active-CSS patients have much stronger local Th2 response in the airways. Airway cells may contribute to lung eosinophilia in CSS by producing IL-5 and eosinophil active chemokines.
The spectrum of lissencephaly: Report of ten patients analyzed by magnetic resonance imaging

Clinical data and magnetic resonance imaging scans from 10 patients with lissencephaly were reviewed. Although 6 of the 10 patients were less than 1 year old at the time of their most recent examination, those who were old enough for developmental assessment were, with a single exception, severely developmentally delayed. All patients had anatomical features compatible with impaired neuronal migration but normal myelination and, consequently, adequate glial migration. The severity of the lissencephaly did not seem to correlate with the severity of the clinical manifestations. One patient showed less delayed development than anticipated, perhaps because the most severely involved region of the brain was the prefrontal area.
Recent developments in adeno‐associated virus vector technology

Adeno‐associated virus (AAV), a single‐stranded DNA parvovirus, is emerging as one of the leading gene therapy vectors owing to its nonpathogenicity and low immunogenicity, stability and the potential to integrate site‐specifically without known side‐effects. A portfolio of recombinant AAV vector types has been developed with the aim of optimizing efficiency, specificity and thereby also the safety of in vitro and in vivo gene transfer. More and more information is now becoming available about the mechanism of AAV/host cell interaction improving the efficacy of recombinant AAV vector (rAAV) mediated gene delivery. This review summarizes the current knowledge of the infectious biology of AAV, provides an overview of the latest developments in the field of AAV vector technology and discusses remaining challenges. Copyright © 2008 John Wiley & Sons, Ltd.
Prague Czech-English dependency treebank: resource for structure-based MT

The Prague Czech-English Dependency Treebank (PCEDT) is a syntactically annotated Czech-English parallel corpus. The Penn Treebank has been translated to Czech, and its annotation automatically transformed into dependency annotation scheme. The dependency annotation of Czech is done from plain text by automatic procedures. A small subset of corresponding Czech and English sentences has been annotated by humans. First experiments in Czech-English machine translation using these data have already been carried out. The resources have been created at Charles University in Prague and released by Linguistic Data Consortium in 2004.
Semi-supervised Learning by Fuzzy Clustering and Ensemble Learning

This paper proposes a semi-supervised learning method using Fuzzy clustering to solve word sense disambiguation problems. Furthermore, we reduce side effects of semi-supervised learning by ensemble learning. We set classes for labeled instances. The -th labeled instance is used as the prototype of the -th class. By using Fuzzy clustering for unlabeled instances, prototypes are moved to more suitable positions. We can classify a test instance by the Nearest Neighbor (k-NN) with the moved prototypes. Moreover, to reduce side effects of semi-supervised learning, we use the ensemble learning combined the k-NN with initial labeled instances, which is initial prototype, and the k-NN with prototypes moved by Fuzzy clustering.
Specific [3H]Piflutixol Binding to CHAPS‐Solubilised Rat Striatal Preparations Involves Dopamine D‐2 but Not D‐1 Binding Sites

Abstract: [3H]Piflutixol binding to rat striatal membrane preparations identifies both D‐l and D‐2 sites. We used [3H]piflutixol to characterise those binding sites present in 3‐[(3‐cholamidopropyl)dimethylammonio]‐1‐propanesulfonate (CHAPS)‐solubilised rat striatal preparations. The specific binding of [3H]piflutixol, as defined using cis‐flupenthixol, to CHAPS‐solubilised rat striatal tissue was saturable and of high affinity. Specific [3H]piflutixol binding to the solubilised preparations was displaced stereoselectively by the isomers of butaclamol and to an equal extent by both cis‐flupenthixol and (±)‐sulpiride. A positive correlation was found between the capacity of a range of drugs to displace [3H]piflutixol binding and the displacement of [3H]spiperone to the same preparations. The Bmax of [3H]piflutixol binding was not different from that of [3H]spiperone binding to the same preparation. These studies suggest that, in contrast to specific binding of membrane preparations, the specific binding of [3H]piflutixol to CHAPS‐solubilised preparations involves mainly D‐2 sites. Specific [3H]piflutixol binding, in contrast to [3H]spiperone binding, showed only slow dissociation from soluble preparations. The binding of [3H]piflutixol to CHAPS‐solubilised preparations was retained during passage through a gel filtration column. This prelabelling of solubilised striatal preparations using [3H]piflutixol may aid in the purification of CHAPS‐solubilised rat striatal D‐2 sites.
Dual Vascularized Fibula Transfer on a Single Vascular Pedicle: A Useful Technique in Long Bone Reconstruction

The use of dual vascularized fibula transfer on a single vascular pedicle for reconstruction of long bone defect is described. This technique involves dividing one length of donor vascularized fibula into two segments, without cutting the vessels. The vessels are then folded, thereby supplying blood circulation to both bones. Since 1985 the authors have treated six cases of bone reconstruction using this method. Two of these six cases are reported, with follow-up periods of over one year.
The evolution of cooperation in games with multiple strategies under different update rules

Cooperative is essential for the maintenance of public resource, however, individual's selfish behavior will reduce cooperation level and public resource. Here, we investigate the two-person public goods game in finite populations with multiple strategies. Under weak selection, theoretical results are found to be in excellent agreement with simulation results. Two representative update rules are used in our model and their results are compared: under weak selection, the cooperative level is higher in the Moran process than that in the Wright Fisher process, which is up to the payoff function and the strategy's update frequency. Besides, we also investigate how mutation rate or enhancement factor influences the amount of public resource. Under strong selection, public resource is more insensitive to mutation rate, and raising enhancement factor alone is in vain until its value gets large enough. However, under weak selection, even at a very low mutation rate, there is a better linear relation existing between public resource and enhancement factor. These findings not only have practical significance, but also provide a guidance to improve the cooperation level.
Assessing Mental Workload During Laparoscopic Surgery

Although the use of performance efficiency measures (speed, movement economy, errors) and ergonomic assessments are relatively well established, the evaluation of cognitive outcomes is rare. This report makes the case for assessment strategies that include mental workload measures as a way to improve training scenarios and training/operating environments. These mental workload measures can be crucially important in determining the difference between well-intentioned but subtly distracting technologies and true breakthroughs that will enhance performance and reduce stress.
In-flight absolute calibration of the CCD / CBERS-2 sensor data

The success of any remote sensing program is directly related to the knowledge of both spectral and radiometric characteristics of the sensors involved. The Brazilian remote sensing user’s community has explored the relationship between orbital radiometric data and biophysical data since the beginning of the nineties using the Thematic Mapper (TM) sensor as the main source of data. Since the first images of the sensors onboard CBERS-2 were made available by INPE, users have asked information about the conversion of image digital numbers to physical data as radiance or reflectance. This paper describes the main steps that were carried out to calculate the in-flight absolute calibration coefficients for CCD images at level 2 (radiometric and geometrical corrections included) considering the reflectancebased method. It was also included some remarks about the preliminary evaluation of these coefficients application from a user point of view.
Risperidone for the treatment of delusional disorder

INTRODUCTION : The overlap between diagnostic criteria for schizophrenia and delusional disorder (DD) may cause diagnostic confusion. This is important if response to treatment differs. Risperidone, an atypical antipsychotic, is established in the treatment of schizophrenia, although less so in other psychotic conditions. METHOD : We report the case of a woman who developed DD, persecutory type, at the age of 50 years. Treatment with sulpiride 200-800 mg daily caused side-effects of drowsiness and 'hangover' and, consequently, non-compliance. Written informed consent was gained for a 24-week, randomized, double-blind, placebo-controlled, crossover trial of risperidone, initiated at 1 mg daily and increasing to 2 mg daily. RESULTS : Significant improvement was found, as assessed by the Brief Psychiatric Rating Scale, Positive and Negative Symptom Schedule and Maudsley Assessment of Delusions Schedule. CONCLUSION : We believe that this is the first case study reporting the resolution of persecutory DD with risperidone. A controlled clinical trial of risperidone in the treatment of patients with DD is warranted. (Int J Psych Clin Pract 2002; 6: 113-116)
Lymphocytic Leiomyositis and Myenteric Ganglionitis Are Intrinsic Features of Cystic Fibrosis: Studies in Distal Intestinal Obstruction Syndrome and Meconium Ileus

Background: Cystic fibrosis (CF) is a multisystem disorder intrinsically associated with inflammation of mucosal surfaces. Because inflammation can result in enteric neuromuscular dysfunction we hypothesized that terminal ileitis in patients with CF may predispose to distal ileal obstruction syndrome (DIOS). Methods and Patients: Full-thickness terminal ileal tissues from 6 children with CF and severe DIOS, 6 infants with complicated meconium ileus (MI), and 6 children with non-CF intestinal atresia were studied. Results: Lymphocyte-predominant mucosal and transmural ileal inflammation was present in 6 of 6 patients with DIOS. Lymphocytic ganglionitis was present in 4 of 6 although numbers of myenteric neurons were not decreased (5/5). Myocyte proteins were preserved (6/6). Mild submucosal fibrosis was common in DIOS (5/6) and transformation of submucosal fibroblasts to a myofibroblastic phenotype was noted in 4 of 6. Inflammatory changes were distinct from those described in fibrosing colonopathy. Antroduodenal manometry in an individual who had experienced MI/DIOS was consistent with a neuropathic pseudo-obstructive process. Submucosal or transmural lymphocyte predominant inflammation was also present in 6 of 6 infants with complicated MI, which, when coupled with submucosal myofibroblast proliferation (5/6), appeared highly predictive of CF rather than non-CF atresia. Histological findings at birth were similar, although milder, than those seen in DIOS, suggesting that these changes are a primary abnormality in CF. Conclusions: Submucosal or transmural inflammation of the ileum is common in newborns with CF and MI and older children with DIOS. Severe recurrent DIOS should be investigated with seromuscular and mucosal biopsy of the ileum to seek a transmural ileitis potentially amenable to anti-inflammatory therapies.
Ajoene inhibits the activation of human endothelial cells induced by porcine cells: implications for xenotransplantation

Abstract: Ajoene, is an organosulfur compound derived from garlic that strongly inhibit platelet aggregation, proliferation of human lymphocytes induced by phytohemagglutinin, and in general, blocks membrane‐mediated signaling of cell activation. As a thrombotic microangiopathy frequently complicates procedures designed to induce pig‐to‐baboon chimerism by infusion of large amounts of pig progenitor cells in baboons, it was thought that ajoene might be useful to prevent such complication. For such purpose, we studied the effects of ajoene on the activation of human umbilical vein endothelial cells (HUVEC) induced by pig peripheral blood mononuclear cells (p‐PBMC). Co‐cultures of p‐PBMC with HUVEC results in activation of the HUVEC as shown by over‐expression of E‐selectin and vascular cells adhesion molecule‐1 (VCAM‐1). Ajoene (25 μm) strongly inhibits HUVEC activation induced by tumor necrosis factor‐α (TNF‐α) or p‐PBMC as shown by a down regulation of VCAM‐1 and of E‐selectin expression. After 5 or 8 h of pre‐treatment with Ajoene, HUVEC incubated with TNF and p‐PBMC showed an E‐selectin or VCAM‐1 expression, respectively, at levels similar to the positive control indicating that the inhibitory effect is transient. Ajoene at concentration of 25 μm or lower did not affect HUVEC viability. Based on the finding that Ajoene has a strong, although transient, inhibitory effect on the activation of the endothelium induced by pig cells and its known anti‐platelet activity, it is suggested that this garlic compound could be useful to prevent the development of microangiopathy and thrombotic disorders seen in primates infused with pig cells.
On Computation of Battle-Lemarié's Wavelets

We propose a matrix approach to the computation of Battle- Lemarie's wavelets. The Fourier transform of the scaling function is the prod- uct of the inverse F(x) of a square root of a positive trigonometric polynomial and the Fourier transform of a B-spline of order m . The polynomial is the symbol of a bi-infinite matrix B associated with a B-spline of order 2m . We approximate this bi-infinite matrix B2m by its finite section As , a square ma- trix of finite order. We use As to compute an approximation \s of x whose discrete Fourier transform is F(x). We show that xs converges pointwise to x exponentially fast. This gives a feasible method to compute the scaling func- tion for any given tolerance. Similarly, this method can be used to compute the wavelets.