Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of PEG‐interferon alfa‐2a plus ribavirin as treatment for chronic HCV hepatitis in a child cured of ALL

To the Editor: The natural history of and the treatment options for chronic hepatitis C (HCV) infection, in longterm leukemia survivors, have not been well characterized. Several reports showed the efficacy of combination therapy with peginterferon (PEG-IFN) alfa-2a and ribavirin in immunocompetent adults with chronic HCV infection [1]. There are no data regarding the use of combination therapy with PEG-IFN in children [2]. We report on the administration of PEG-IFN alfa-2a in combination with ribavirin in a child who had chronic HCV infection acquired during treatment for acute lymphoblastic leukemia (ALL). She was treated for ALL in our institution at the age of 3. She had a 10-years history of high serum alanine aminotransferase concentration. She was subsequently diagnosed with HCV genotype-1b positive chronic active hepatitis. After a year of IFN-alfa administration, at the age of 14, she presented with high levels of both serum alanine aminotransferase concentration and baseline viral load. A percutaneous liver biopsy showed a moderate intralobular inflammation/necrosis. Therefore, according to a recently described treatment tailored for adults [1], we administered 180 mg of PEGIFN alfa-2a subcutaneously once weekly, plus daily ribavirin 1,000 mg for a total of 48 weeks. We adopted this dosage based on the fact that she had almost adult size (height 165 cm; weight 48 kg). The Institutional review board of our center approved this treatment and an informed consent was signed by patient’s parents. We assessed the efficacy of this combination therapy by measuring alanine aminotransferase concentration and by performing both qualitative and quantitative HCV RNA RT-PCR using the Cobas Amplicor HCV Monitor assay (Roche Diagnostics-LA Roche, Ltd., Basel, Switzerland). We evaluated therapy response after 1, 4, 8, 12, 24, and 48 weeks, respectively. We noted a dramatic decrease of serum alanine aminotransferase concentration (from 350 to 35 U/L), correlated with a significant decrement in viral load (from>5,000,000 to 50 IU/L). Although we used an adult dosage, no side effects related to the combination therapy have occurred. Three consecutive qualitative HCV-RNA RT-PCR assays have been performed at 3 and 6 months and 1 year from therapy withdrawal, each demonstrating an undetectable level of viral RNA. Although the implementation of blood donor screening, the prevalence of anti-HCV seropositivity among leukemia survivors is still high [3]. Evidence of progression to liver failure in survivors of pediatric malignancies has been reported [3]. Because their previously immunocompromized status might have promoted more rapid viral replication, increasing the risk for a rapid disease progression, amore aggressive approach regarding the use of antiviral therapy in this population with chronic HCV is needed. Based on our experience, we suggest that administration of PEG-IFN in association with ribavirin should be considered as first line treatment in childrenwith chronic HCV hepatitis who have been previously cured of malignancies.
A study on the of effects of social media on young consumers ' buying behaviors

Consumers started to use Internet and web tools more today thanks to the rapid development of technology and communication channels. The most important one of these tools is social media. Consumers access to information that they need about goods and services to be purchased by means of social media to a great extent. It is clear that today especially the popular social networks of social media elements such as Facebook and Twitter have been great consumer markets. Therefore, this study aims to know about social media which affects our live in recent years and brings a new dimension to Internet and to determine the effects of social media networks on purchasing behaviors of consumers. The study group consisted of a total of 688 young consumers between the age group of 18-24 years who use social media platforms and have an account in any of the social networks. Random sampling method was used to determine the study group. Face-to-face interview technique was used to obtain the data of the study; the questionnaire form and the scale developed by the researcher were taken into account. The first chapter of the questionnaire form consists of questions to determine demographic information of young people and the second chapter consists of questions to determine the duration and aim of young people to use Internet and social media. In the last chapter of the form, 5-point likert attitude scale was used to determine the relationship between purchasing behaviors of young people and social media. The reliability and validity studies of the scale were performed. The Cronbach Alpha reliability coefficient of the scale which was prepared to determine the relationship between purchasing behaviors of consumers and social media was . 965. SPSS 16.0 package program and suitable statistical techniques were used to analyze the data obtained from the answers of social media users. The study results indicate that social media tools create a statistically significant difference on purchasing behaviors of consumers according to age groups and educational status of them (p<.01). © 2013 European Journal of Research on Education by IASSR.
Molecular and epidemiological investigations of cryptosporidiosis in Cuban children

Abstract Molecular and epidemiological studies of Cryptosporidium infections amongst 28 Cuban children (aged 2–8 years) with diarrhoea are described. As few of the younger infected children but most of the older infected children had been breastfed, short-term protection from maternal antibodies passed to infants during breastfeeding may result in a lack of cryptosporidial infection in infancy. This protection of breastfeeding children may, however, result in such children developing less anti-Cryptosporidium immunity of their own (than their bottle-fed counterparts), so that, by school age, the children who had been breastfed are those most likely to be found infected. In the present study, in contrast with the observations made during a previous study of cryptosporidiosis in Cuban children, vomiting was rare (7%) whereas abdominal pain was common (57%). These differences in expression of symptoms between studies may be age-related. As seen in other studies from similar countries, including those of the Caribbean and Latin America, C. hominis was found to predominate, the results of the successful molecular analyses revealing 10 C. hominis infections but no C. parvum. Subgenotyping (at the gp60 locus) indicated that the C. hominis infections included a wide range of subtypes, with isolates from three subtype families (Ia, Ib and Id) being detected.
Molecular Pathogenesis of H5N1 Influenza Virus Infections

Highly pathogenic H5N1 influenza viruses have become endemic in poultry populations throughout Southeast Asia and continue to infect humans with a greater than 50% case fatality rate. So far, human-to-human transmission of these viruses has been limited. Here, we discuss the molecular features of H5N1 influenza viruses that might affect their pathogenicity, and explain the current lack of efficient human-to-human transmission. Such knowledge is critical in evaluating the pandemic risk these viruses pose.
Do activated human dendritic cells diminish the suppressive functions of CD4+,CD25+ regulatory T cells? Comment on the article by van Amelsfort et al.

To the Editor: We agree with many of the points made by Brandt and colleagues in their letter responding to our special article, “The futility of current approaches to chondroprotection. ” Most intriguingly, these senior authorities on OA appear to agree fully that current approaches to developing chondroprotective agents are futile, especially if they are unaccompanied by corrections of the mechanical abnormalities that, as they wrote, “got the joint into trouble in the first place. ” While we concur with Brandt et al that the pathophysiology of Heberden’s nodes also has a mechanical element, high rates of heritability of disease in DIP joints and in the adjacent proximal interphalangeal joints (1), as well as suggestions that hand OA may be associated with vitamin K deficiency (2) and may be related to metabolic factors associated with adiposity (3), all suggest that metabolic manipulations may affect hand OA. In contrast, knee OA has low heritability and is unrelated to vitamin K deficiency. Its association with obesity can be understood entirely through effects of loading (4). While we may be incorrect, we suggest that hand OA may be more amenable than knee OA to structural effects of drugs, and certainly, given the number of joints one can follow, treatment efficacy may be easier to detect in hand OA. Like Brandt et al, we are mindful of the low rate of disease progression in knee OA, which has been a barrier to drug development. However, in our view, these are consequences of technical and measurement limitations that new approaches may overcome. We provided some examples (e.g., delayed gadolinium-enhanced MRI of cartilage and other MRI approaches; using the number of hand joints affected) in our special article, and, for knee radiographs, we suggest that limiting the focus (as in traditional trials) to the medial joint space on only the anteroposterior view cuts progression rates by 50% compared with an approach using other views and other compartments. While future imaging technologies may permit us to overcome the slow disease progression problem, drugs that attempt to reverse structural disease will fail without correcting pathomechanics. We stated strongly in our special article that there needs to be an increasing focus on treating bone or synovitis in OA, if only because these structures are likely sources of pain. We agree with Brandt and colleagues that, for knees, restoring meniscal function could be of value (assuming other structures in the knee are not already failing). Ultimately, focusing only on cartilage as a treatment target in human OA is likely to remain a fruitless endeavor.
The c-FLIPL Cleavage Product p43FLIP Promotes Activation of Extracellular Signal-regulated Kinase (ERK), Nuclear Factor κB (NF-κB), and Caspase-8 and T Cell Survival*

Background: c-FLIPL is a regulator of caspase-8 activity in T lymphocytes. Results: Caspase-8 activity is lost upon deletion of c-FLIPL. p43FLIP rescues caspase-8 activity through Raf1, TRAF2, and RIPK1 association, augmenting ERK and NF-κB pathways. Conclusion: The FLIPL cleavage product p43FLIP promotes activation of pathways involved with T cell growth. Significance: This study provides new insight into the regulation of caspase-8 activity by c-FLIP. Caspase-8 is now appreciated to govern both apoptosis following death receptor ligation and cell survival and growth via inhibition of the Ripoptosome. Cells must therefore carefully regulate the high level of caspase-8 activity during apoptosis versus the modest levels observed during cell growth. The caspase-8 paralogue c-FLIP is a good candidate for a molecular rheostat of caspase-8 activity. c-FLIP can inhibit death receptor-mediated apoptosis by competing with caspase-8 for recruitment to FADD. However, full-length c-FLIPL can also heterodimerize with caspase-8 independent of death receptor ligation and activate caspase-8 via an activation loop in the C terminus of c-FLIPL. This triggers cleavage of c-FLIPL at Asp-376 by caspase-8 to produce p43FLIP. The continued function of p43FLIP has, however, not been determined. We demonstrate that acute deletion of endogenous c-FLIP in murine effector T cells results in loss of caspase-8 activity and cell death. The lethality and caspase-8 activity can both be rescued by the transgenic expression of p43FLIP. Furthermore, p43FLIP associates with Raf1, TRAF2, and RIPK1, which augments ERK and NF-κB activation, IL-2 production, and T cell proliferation. Thus, not only is c-FLIP the initiator of caspase-8 activity during T cell activation, it is also an initial caspase-8 substrate, with cleaved p43FLIP serving to both stabilize caspase-8 activity and promote activation of pathways involved with T cell growth.
Dopamine D1 receptors mediate CREB phosphorylation via phosphorylation of the NMDA receptor at Ser897–NR1

Addictive drugs such as amphetamine and cocaine stimulate the dopaminergic system, activate dopamine receptors and induce gene expression throughout the striatum. The signal transduction pathway leading from dopamine receptor stimulation at the synapse to gene expression in the nucleus has not been fully elucidated. Here, we present evidence that D1 receptor stimulation leads to phosphorylation of the transcription factor Ca2+ and cyclic AMP response element binding protein (CREB) in the nucleus by means of NMDA receptor‐mediated Ca2+ signaling. Stimulation of D1 receptors induces the phosphorylation of Ser897 on the NR1 subunit by protein kinase A (PKA). This phosphorylation event is crucial for D1 receptor‐mediated CREB phosphorylation. Dopamine cannot induce CRE‐mediated gene expression in neurons transfected with a phosphorylation‐deficient NR1 construct. Moreover, stimulation of D1 receptors or increase in cyclic AMP levels leads to an increase in cytosolic Ca2+ in the presence of glutamate, but not in the absence of glutamate, indicating the ability of dopamine and cyclic AMP to facilitate NMDA channel activity. The recruitment of the NMDA receptor signal transduction pathway by D1 receptors may provide a general mechanism for gene regulation that is fundamental for mechanisms of drug addiction and long‐term memory.
Price and Probability: Decomposing the Takeover Effects of Anti-Takeover Provisions

We study the causal effects of anti-takeover provisions on takeovers. We decompose their effect on prices, takeover likelihood and target selection and explore the channels through which they change shareholders' value. We provide causal estimates based on shareholder proposals and deal with the endogenous selection of targets through bounding techniques. Voting to remove an anti-takeover provision increases the annual takeover probability by 0.9% and increases premiums by 2.8%. The premium effect is driven by more related acquisitions, better matching and higher synergies when targets are less protected. We do not find evidence of a trade-off between premiums and takeover probabilities.
WHAT HELPS MIDDLE-AGED WIDOWS WITH THEIR PSYCHOLOGICAL AND SOCIAL ADAPTATION SEVERAL YEARS AFTER THEIR LOSS?

This study examines the factors contributing to middle-aged widows' adaptation to their husbands' death due to physical illness, 1 to 5 years after the initial loss. Ninety-three widows and 93 married women, who served as controls, filled out questionnaires assessing their experience of stress and strain, their Sense of Coherence level, the social support they received, as well as measures of psychological and social adaptation. Results show that several years after their husbands' death, many widows still perceive life events and hassles as significantly more intense experiences than do their married counterparts. Moreover, they report a significantly lower Sense of Coherence, diminished social support and a lower level of mental health, as compared with married women. Multiple regression revealed that Sense of Coherence was the most significant contributor to adaptation variables, especially to mental health. Social support contributed significantly to the 2 social adaptation subscales. The discussion emphasizes the importance of Sense of Coherence to adaptation.
In Vitro Antibacterial Activity and Synergistic Antibiotic Effects of Phlorotannins Isolated from Eisenia bicyclis Against Methicillin‐Resistant Staphylococcus aureus

Six phlorotannins, isolated from Eisenia bicyclis, were evaluated for antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentrations (MIC) of the compounds were in the range 32 to 64 µg/mL. Phlorofucofuroeckol‐A (PFF) exhibited the highest anti‐MRSA activity, with an MIC of 32 µg/mL. An investigation of the interaction between these compounds and the β‐lactam antibiotics ampicillin, penicillin, and oxacillin revealed synergistic action against MRSA in combination with compound PFF. To our knowledge, this is the first report on the anti‐MRSA activity of phlorotannins from E. bicyclis. The results obtained in this study suggest that the compounds derived from E. bicyclis can be a good source of natural antibacterial agents against MRSA. Copyright © 2012 John Wiley & Sons, Ltd.
Design of a poly silicon MEMS microphone for high signal-to-noise ratio

This paper reports on the state of the art silicon micromachined microphone utilizing a dual poly silicon membrane system. MEMS chips from 1.4mm down to 1.0mm side length are applied for mobile communication. Design aspects related with key performance parameters such as sensitivity, signal to noise ration and distortion are discussed. Sensitivity of - 38BV/Pa is achieved for different microphone membrane diameters. A maximum signal to noise ration of 66dB(A) for the largest system could be achieved. The perfect fit of simulation versus measurements enables deeper analysis and balancing of noise contributors. Environmental noise suppression of 5dB by acoustical high pass design is demonstrated.
The Impact of Strategic Trajectory Optimization on Illusory Target Biases During Goal-Directed Aiming

ABSTRACT During rapid aiming, movements are planned and executed to avoid worst-case outcomes that require time and energy to correct. As such, downward movements initially undershoot the target to avoid corrections against gravity. Illusory target context can also impact aiming bias. Here, the authors sought to determine how strategic biases mediate illusory biases. Participants aimed to Müller-Lyer figures in different directions (forward, backward, up, down). Downward biases emerged late in the movement and illusory biases emerged from peak velocity. The illusory effects were greater for downward movements at terminal endpoint. These results indicate that strategic biases interact with the limb-target control processes associated with illusory biases. Thus, multiple control processes during rapid aiming may combine and later affect endpoint accuracy (D. Elliott et al., 2010).
Q fever

One hundred and eleven cases of Q fever which were referred over a 20‐year period are described, including description of the clinical illness, epidemiology, serological findings and management. Unusual features reported here are a long incubation period, rash, haemolysis and abnormal findings in cerebrospinal fluid. Special emphasis is given to the course of the disease, treatment, and serological follow‐up investigations.
Bioactive acylphloroglucinols from Hypericum densiflorum

Three acylphloroglucinol derivatives have been isolated from the hexane and acetone extracts of the aerial parts of Hypericum densiflorum Pursch. The compounds were characterized by NMR spectroscopy and mass spectrometry and identified as 4‐geranyloxy‐2,6‐dihydroxybenzophenone (1), 4‐geranyloxy‐1‐(2‐methylpropanoyl)‐ phloroglucinol (2) and 4‐geranyloxy‐1‐(2‐methylbutanoyl)‐phloroglucinol (3). Compounds 1–3 were evaluated for in vitro cell proliferation inhibitory activity against human breast (MCF‐7), lung (NCI H460), CNS (SF‐268), stomach (AGS) and colon (HCT‐116) tumor cell lines; antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA); inhibition of cyclooxygenase (COX‐1 and ‐2) enzymes; and antioxidant activity in the lipid peroxidation (LPO) assay. All three compounds showed moderate to strong antitumor, antibacterial, antioxidant and inhibition of COX‐2 activities. Also, this is the first reported occurrence of compound 3 in the Hypericum genus. Copyright © 2009 John Wiley & Sons, Ltd.
Diagnosis and management of femoroacetabular impingement.

Femoroacetabular impingement (FAI) is a pathological hip condition characterised by abnormal contact between the acetabulum and femoral head–neck junction.1 This can occur within the normal physiological range of motion as a result of osseous abnormalities described as either cam or pincer deformities. Cam deformities describe an abnormal anterosuperior femoral head–neck junction, whereas pincer deformities describe abnormalities in the shape or orientation of the acetabulum (Figure 1). Some patients have both deformities, designated mixed pathology.2 Impingement can also occur in a morphologically normal hip as a result of extreme range of motion activities, such as in ballet dancers or gymnasts. Figure 1 Illustrative lateral view of a hip showing a) cam deformity with additional bone at the anterior femoral headneck junction (shown in red) b) normal hip c) pincer deformity with additional bone at the anterior acetabular rim (shown in red). The deformities in a) and c) cause the femoral neck to impact against the labrum and acetabular rim on flexion and internal rotation. Repeated abutment of the femoral neck against the acetabular rim can result in injury to the labrum and adjacent cartilage.3 Over time these focal lesions may progress to more extensive degenerative disease. There is increasing evidence implicating FAI in the development of osteoarthritis (OA). 1,4 In a large population study, cam …
Lipases and lecithin: cholesterol acyltransferase in the control of lipoprotein metabolism

Lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase have coordinated enzymatic roles in lipoprotein metabolism. New evidence suggests that the lipases are multifunctional proteins that are able to mediate lipoprotein binding and uptake. The importance of all three enzymes in the control of lipoprotein metabolism can be explored in the future by using the newly generated transgenic animals
A comparison of the metabolic cost of protein synthesis in stenothermal and eurythermal isopod crustaceans.

To examine the presence of metabolic cold adaptation in Antarctic isopods, whole animal rates of oxygen uptake (MVo2) and protein synthesis were measured in Glyptonotus antarcticus at 0 degree C and compared with the temperature isopod Idotea rescata at 4 and 14 degrees C. The specific relationship between rates of metabolism and protein synthesis was investigated by injecting animals with cycloheximide, a protein synthesis inhibitor. In G. antarcticus, routine MVo2 was 11.10 +/- 0.89 mumol.kg-1.min-1 (n = 19 animals), and ks was 0.24 +/- 0.04% protein synthesized/day (n = 8 animals). Comparison with I. rescata showed that standardized whole animal MVo2 decreased with temperature (temperature quotient = 1.99), but whole animal ks was considerably lower in the Antarctic isopod; 66 and 22% of total MVo2 was attributable to protein synthesis in G. antarcticus at 0 degree C and I. rescata at 4 degrees C, respectively. The energetic cost of protein synthesis was four times higher in G. antarcticus at 885 +/- 141 mmol ATP/g protein (n = 5 animals) compared with 237 +/- 76 mmol ATP/g protein (n = 6) in I. rescata. G. antarcticus does not show metabolic rate compensation and maintains extremely low ks levels because of the relatively high energetic cost of protein synthesis.