Miracle-dz/UniFAR-FTUs huggingface dataset:
Simpson-Golabi-Behmel syndrome and attention deficit hyperactivity disorder in two brothers

Editor—Simpson-Golabi-Behmel syndrome (SGBS, MIM 312870) is an X linked condition characterised by pre- and postnatal overgrowth, coarse facial appearance, large mouth, predisposition to embryonic neoplasia,1 and a variety of visceral and skeletal abnormalities. Psychomotor development in the syndrome is extremely variable, ranging from normal intelligence,2 to moderate impairment, to severe impairment evident from birth.3 4 We report the cases of two male sibs with normal psychomotor development, diagnosed at 6 and 7 years of age with SGBS, who manifest significant behavioural disturbances consistent with a diagnosis of attention deficit hyperactivity disorder (ADHD). This is the first report of an association between SGBS and a specific behavioural phenotype (ADHD). Case 1, the older of the two boys, was the first born to non-consanguineous, healthy, white parents. The pregnancy was complicated at 36 weeks by polyhydramnios and pregnancy induced hypertension. An ultrasound performed at this time discovered a left sided diaphragmatic hernia. No other fetal abnormalities were reported. Labour was induced at 39 weeks and the child was delivered by forceps assisted vaginal delivery. Birth weight was 4400 g (well above the 97th centile) and immediate transfer for stabilisation and surgical repair of the diaphragmatic hernia was undertaken. Other birth indices were not recorded. The primary surgical repair was successful but was complicated by a left pneumothorax on day 4 of life. This complication was successfully managed and the subsequent postsurgical course was uneventful. The child was discharged from hospital aged 14 days. At 5 months bilateral inguinal hernias were noted and surgically repaired. From 6 months onwards the child was noted to be extremely unsettled, seldom sleeping for more than two hours at a time. From 10 months onwards he began to wake screaming several times a night. His behaviour became increasingly unpredictable and aggressive over …
Detection and Classification of Anomalies in Network Traffic Using Generalized Entropies and OC-SVM with Mahalanobis Kernel

Network anomaly detection and classification is an important open issue of network security. Several approaches and systems based on different mathematical tools have been studied and developed. Among them, the Anomaly-Network Intrusion Detection System (A-NIDS), this monitors network traffic and compares it against an established baseline of “normal” traffic profile. Then, it is necessary to characterize the “normal” Internet traffic. This paper presents an approach for anomaly detection and classification based on: the entropy of selected features (including Shannon, Renyi and Tsallis entropies), the construction of regions from entropy data employing the Mahalanobis distance (MD), and One Class Support Vector Machine (OC-SVM) with different kernels (RBF and particularity Mahalanobis) for “normal” and abnormal traffic. Regular and non-regular regions built from “normal” traffic profiles, allow the anomaly detection; whilst the classification is performed under the assumption that regions corresponding to the attack classes have been characterized previously. Although, this approach allows the use of as many features as required, only four well known significant features were selected in our case. To evaluate our approach two different data sets were used: one set of real traffic obtained from an Academic LAN, and the other a subset of the 1998 MIT-DARPA set. The selected features sets computed in our experiments provide detection rates up to 99.90% with “normal” traffic and up to 99.83% with anomalous traffic and false alarm rate of 0.086%. Experimental results show that certain values of the q parameter of the generalized entropies and the use of OC-SVM improves the detection rate of some attack classes, due to a better fit of the region to the data. Besides, our results show that MD allows to obtain high detection rates with an efficient computation time, while OC-SVM achieved detection rates slightly higher but more expensive computationally.
Differential developmental toxicities of di‐n‐hexyl phthalate and dicyclohexyl phthalate administered orally to rats

The objective of this study was to evaluate the developmental toxic potential of di‐n‐hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague–Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg–1 per day, by gavage, on gestational days (GD) 6–20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg–1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose‐related developmental toxic effects, including marked embryo mortality at 750 mg kg–1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg–1 per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg–1 per day. DCHP produced fetal growth retardation at 750 mg kg–1 per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose‐related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg–1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP. Copyright © 2009 John Wiley & Sons, Ltd.
Toward Improving Content-Based Image Retrieval Systems by means of Text Detection

Recent advances in text detection allow for finding text regions in natural scenes rather accurately. Global features in content based image retrieval, however, typically do not cover such a high level information. While characteristics of text regions may be reflected by texture or color properties, the respective pixels are not treated in a different way. In this contribution we investigate the impact of text detection on content based image retrieval using global features. Detected text regions are preprocessed to allow for different treatment by feature extraction algorithms, and we show that for certain domains this leads to a much higher precision in content based retrieval.
Mode of action of alpha-dehydrobiotin, a biotin analogue

Alpha-Dehydrobiotin, like biotin, represses coordinately the 7,8-diaminopelargonic acid aminotransferase and the dethiobiotin synthetase enzymes that are encoded on the l and r strands, respectively, of the bioA operon. The rate of synthesis for both enzymes is inhibited about 80% in the presence of alpha-dehydrobiotin. Homobiotin and alpha-methylbiotin are less effective than alpha-dehydrobiotin in repressing the synthesis of the two enzymes. The selective repression of transcription from l and by alpha-dehydrobiotin and homobiotin, previously reported in hybridization experiments, is not observed at the enzyme level. A combination of equal concentrations of biotin and alpha-dehydrobiotin which was reported to enhance selectively the level of messenger ribonucleic acid transcribed from the l strand does not increase the rate of synthesis of the aminotransferase enzyme. Instead, the enzymes encoded on both strands are essentially completely inhibited as with biotin alone. Strain differences have been ruled out to account for the different results obtained by the two methodologies. Our evidence would suggest that alpha-dehydrobiotin acts like biotin, presumably as the co-repressor, in the repression of the bioA operon. The low rates of enzyme synthesis observed in the presence of the biotin analogue is the result of incomplete repression due to a lower affinity of either the analogue for the repressor or of the co-repressor/repressor complex for the operator. While our evidence would support the concept of a two promoter/operator complex, both would have to respond equally to biotin and its analogues. The evidence, however, does not rule out other possible alternative models for the regulation of the biotin operon.
Confirmation and Phylogenetic Analysis of Rabbit Hemorrhagic Disease Virus in Free-living Rabbits from the Netherlands

The number of free-living European rabbits (Oryctolagus cuniculus) in the Netherlands has declined dramatically in recent years. Although rabbit hemorrhagic disease virus (RHDV) infection has been implicated as a possible cause of this decline, the definitive diagnosis has not been reported. We examined three free-living rabbits found dead in the Netherlands in 2004 by use of gross pathology, histopathology, immunohistochemistry, and reverse transcriptase polymerase chain reaction. We subsequently compared the identified virus with RHDV from elsewhere in the world by phylogenetic analysis. There was widespread necrosis, hemorrhage, or both in liver, kidney, spleen, and lungs of all three rabbits, consistent with RHDV infection. The presence of RHDV in affected tissues was demonstrated by immunohistochemistry and reverse transcriptase polymerase chain reaction. The RHDV from the Netherlands showed the highest identity, 99%, with a strain from France in 2000, and fitted in genogroup G5. These results prove that RHDV infection causes mortality of free-living rabbits in the Netherlands and suggest that RHDV strains circulating in free-living rabbits in the Netherlands and France have a common source or that one has originated from the other.
[Myocardial dysfunction, neuropathy and nephropathy in long standing type 1 diabetic patients].

UNLABELLED Cardiovascular and renal complications among type 1 diabetic patients are predictive factors for sudden cardiac death and stroke. The aim of the study was to assess the prevalence of diabetic nephropathy and autonomic neuropathy in type 1 diabetic patients with and without diastolic dysfunction in echocardiographic examination. The study was performed in a group consisting of 37 patients with type 1 diabetes mellitus. Mean age of the study group equaled 37.24 +/- 10.85 years, duration of diabetes mellitus 21.3 +/- 9.55 years. All patients performed EKG, and cardiovascular autonomic test with ProSciCard according to Ewing battery. The following parameters were assessed: heart rate (HR), standard deviation of HR, RMSDD, VLF, LF, HF, deep breathing test, Ewing supine test and Valsalva maneuver. Systolic and diastolic function was assessed in echocardiography examination at rest. In all patients following laboratory parameters were assessed: HbA1c, total chol, LDL-chol, HDL-chol, triglicerides, uremic acid, glucose, albumin, creatinine, cystatin C, microalbuminuria. RESULTS mean heart rate in the examined group --78.38 +/- 15.54 /min, VLF--1.59 +/- 1.7; LF--4.22 +/- 1.51, HF--0.82 +/- 0.88, mean heart rate during deep breathing test --79.63 +/- 13.71, Ewing ratio--0.91 +/- 0.11. Cardiovascular autonomic neuropathy and diabetic neuropathy were diagnosed in 3 patients, these patients suffered also from proliferative retinopathy and diabetic nephropathy. The remaining group of 34 patients has normoalbuminuria. Calculated creatinine clearance according to Cockroft-Gault equation was 88.85 +/- 9.60 m/min, cystatin C concentration--0.97 +/- 0.22 ng/ml. In echocardiography exam, there were no abnormalities in systolic function, and diastolic dysfunction was diagnosed in 15 patients. Preliminary results showed that only the cystatin C level significantly differed patients with and without diastolic dysfunction in echocardiographic examination. Cystatin C could be the first sign of renal failure among these patients. Cardiovascular autonomic neuropathy and diabetic nephropathy were diagnosed only in 3 patients with left ventricular diastolic dysfunction in echocardiographic study.
Transport of L-[ 125 I]Thyroxine bY iN Situ Perfused Ovine Choroid Plexus: Inhibition by Lead Exposure

Lead (Pb) exposure hinders brain development in children by mechanisms that remain unknown. Previous evidence shows that sequestration of Pb in the choroid plexus lowers the production and secretion of transthyretin (TTR), a thyroxine (T 4 ) transport protein, from the choroid plexus into the cerebrospinal fluid (CSF). This study was undertaken to characterize the uptake kinetics of T 4 by the choroid plexus and to determine if in vivo Pb exposure altered the T 4 uptake in an in situ perfused ovine choroid plexus model. Sheep received ip injections of Pb acetate (20 mg Pb/kg) or Na acetate (as the controls) every 48 h for a period of 16 d. The [ 125 I]T 4 uptake was determined by a paired-tracer perfusion method using 0.5 w Ci [ 125 I]T 4 and 2 w Ci [ 14 C]mannitol at various concentrations of unlabeled T 4 (trace to 20 w M). The flux of [ 125 I]T 4 into the choroid plexus followed Michaelis-Menten kinetics with the maximum flux (V max ) of 56.6 nmol/min/g and half-saturation constant (K m ) of 10.7 w mol/L, suggesting an evident saturable influx of T 4 into the choroid epithelium. In vivo Pb exposure in these sheep resulted in a significant accumulation of Pb in the choroid plexus and hippocampus. Pb treatment diminished the V max by 63.7% of control, but did not alter K m . The maximal cellular uptake (U max ) and net uptake (U net ) in Pb-treated animals were 2.1-fold and 1.9-fold, respectively, lower than those of control. Exposure to Pb, however, did not significantly change the flow rate through the choroid plexus. Data suggest that the choroid plexus may serve as a significant site for T 4 transport into the CSF, and Pb exposure may hinder the influx of T 4 from the blood into the choroid plexus.
Whole-genome sequencing for national surveillance of Shiga toxin-producing Escherichia coli O157.

BACKGROUND National surveillance of gastrointestinal pathogens, such as Shiga toxin-producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. METHODS We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. RESULTS Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. CONCLUSIONS WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations.
Evolución de los estilos de aprendizaje de los estudiantes de farmacia en los últimos 6 años

We development one comparative study of the evolution of learning styles in a wide section of 4 th grade students of two universities Pharmacy Madrid (Spain) between 2003/2004 and 2009/2010 courses. To do this we used the questionnaire CHAEA. In both periods the students had the highest positive ratings in the style of reflexive and then styles theoretical, pragmatic and active. However, when comparing both periods, there is a clear decrease in the values of all learning styles, which reinforces the importance of the profound change Revista Estilos de Aprendizaje, no6, Vol 6, octubre de 2010 Review of Learning Styles, no6, Vol 6, october de 2010 Revista de Estilos de Aprendizagem, no6, Vol 6, outubro de 2010 Revue de Les Styles d ́apprentissage, no6,vol 6, octobre de 2010 2 they are currently in university studies to achieve greater motivation and learner involvement in learning.
Grb2 and Gads Exhibit Different Interactions with CD28 and Play Distinct Roles in CD28-Mediated Costimulation1

Although both CD28 and ICOS bind PI3K and provide stimulatory signal for T cell activation, unlike CD28, ICOS does not costimulate IL-2 secretion. CD28 binds both PI3K and Grb2, whereas ICOS binds only PI3K. We have generated an ICOS mutant, which can bind Grb2 by replacement of its PI3K binding motif YMFM with the CD28 YMNM motif, and shown that it induces significant activation of the IL-2 promoter. However, this mutant ICOS was insufficient to activate the NF-κB pathway. In this study, we show that Gads, but not Grb2, is essential for CD28-mediated NF-κB activation, and its binding to CD28 requires the whole CD28 cytoplasmic domain in addition to the YMNM motif. Mutagenesis experiments have indicated that mutations in the N-terminal and/or C-terminal PXXP motif(s) of CD28 significantly reduce their association with Gads, whereas their associations with Grb2 are maintained. They induced strong activity of the NFAT/AP-1 reporter comparable with the CD28 wild type, but weak activity of the NF-κB reporter. Grb2- and Gads-dominant-negative mutants had a strong effect on NFAT/AP-1 reporter, but only Gads-dominant-negative significantly inhibited NF-κB reporter. Our data suggest that, in addition to the PI3K binding motif, the PXXP motif in the CD28 cytoplasmic domain may also define a functional difference between the CD28- and ICOS-mediated costimulatory signals by binding to Gads.
Serial Review: Heme Oxygenase in Human Disease Serial Review Editor: Phyllis A. Dennery Heme oxygenase and the cardiovascular-renal system i

Heme oxygenase (HO) has been shown to be important for attenuating the overall production of reactive oxygen species (ROS) through its ability to degrade heme and to produce carbon monoxide (CO), biliverdin/bilirubin, and the release of free iron. Excess free heme catalyzes the formation of ROS, which may lead to endothelial cell (EC) dysfunction as seen in numerous pathological conditions including hypertension and diabetes, as well as ischemia/reperfusion injury. The upregulation of HO-1 can be achieved through the use of pharmaceutical agents, such as metalloporphyrins and some HMG-CoA reductase inhibitors. Among other agents, atrial natriretic peptide and donors of nitric oxide (NO) are important modulators of the heme–HO system, either through induction of HO-1 or the biological activity of its products. Gene therapy and gene transfer, including site- and organ-specific targeted gene transfer, have become powerful tools for studying the potential role of HO-1/HO2 in the treatment of various cardiovascular diseases as well as diabetes. HO-1 induction by pharmacological agents or gene transfer of human HO-1 into endothelial cells (ECs) in vitro increases cell-cycle progression and attenuates Ang II, TNF-, and heme-mediated DNA damage; administration in vivo acts to correct blood pressure elevation following Ang II exposure. Moreover, site-specific delivery of HO-1 to renal structures in spontaneously hypertensive rats (SHR), specifically to the medullary thick ascending limb of the loop of Henle (mTALH), has been shown to normalize blood pressure and provide protection to the mTAL against oxidative injury. In other cardiovascular situations, delivery of human HO-1 to hyperglycemic rats significantly lowers superoxide (O2 ) levels and prevents EC damage and sloughing of vascular EC into the circulation. In addition, administration ofhuman HO-1 to rats in advance of ischemia/reperfusion injury considerably reduces tissue damage. The ability to upregulate HO-1 through pharmacological means or through the use of gene therapy may offer therapeutic strategies for cardiovascular disease in the future. This review discusses the implications of HO-1 delivery during the early stages of cardiovascular system injury or in early vascular pathology and suggests that pharmacological agents that regulate HO activity or HO-1 gene delivery itself may become powerful tools for preventing the onset or progression of certain cardiovascular pathologies.
Is the European Pediatric Medicine Regulation Working for Children and Adolescents with Cancer?

The European Pediatric Medicine Regulation was launched in 2007 to provide better medicines for children. Five years later, the number of new anticancer drugs in early development in the pediatric population remains low, and most children with cancer are still largely denied access to innovative drugs in Europe, as compared with the United States. We analyzed individual pediatric investigation plan (PIP) and waiver decisions for oncology drugs and all oncology drugs that have been approved for marketing authorization since 2007 in Europe. Among the 45 approved PIPs, 33% concern leukemias and lymphomas, 29% solid tumors, 13% brain tumors, and 20% a drug for supportive care. No specific PIP exists for life-threatening diseases such as high-risk neuroblastoma, whereas there are several PIPs in extremely rare malignancies in children and adolescents such as gastrointestinal stromal tumor, melanoma, thyroid cancer, and chronic myeloid leukemia. This paradoxical situation is due to approval of a PIP being driven by the adult indication. Twenty-six of 28 authorized new oncology drugs have a potentially relevant mechanism of action for pediatric malignancies, but 50% have been waived because the adult condition does not occur in children. The most striking example is crizotinib. Implementation of the pediatric regulation should no longer be driven by the adult indication but should be guided instead by the biology of pediatric tumors and the mechanism of action of a drug. This change will be achievable through voluntary PIPs submitted by Pharma or revocation of the oncology class waiver list. Clin Cancer Res; 19(6); 1315–25. ©2013 AACR.
Epidemic thresholds and vaccination in a lattice model of disease spread.

We use a lattice-based epidemic model to study the spatial and temporal rates of disease spread in a spatially distributed host population. The prevalence of the disease in the population is studied as well as the spread of infection about a point source of infection. In particular, two distinct critical population densities are identified. The first relates to the minimum population density for a epidemic to occur, whilst the second is the minimum population density for long-term persistence to occur. Vaccination regimes are introduced that are used to measure the impact of spatially and nonspatially dependent intervention strategies. Specifically we show how a ring of vaccinated susceptibles, of sufficient thickness, can halt the spread of infection across space.