Miracle-dz/UniFAR-FTUs huggingface dataset:
MDA5 and MAVS Mediate Type I Interferon Responses to Coxsackie B Virus

ABSTRACT Coxsackie B viruses (CVB) are enteroviruses that have been associated with a variety of human diseases, including myocarditis. In the present study, we found that MDA5 and its adaptor molecule MAVS are critical for type I interferon responses to CVB, since the absence of either MAVS or MDA5 leads to deficient type I interferon production and early mortality in mice infected with CVB. Pancreatic and hepatic necrosis were observed on histopathological examination of MAVS and MDA5 knockout mice infected with CVB. Inflammatory cytokine production in response to systemic CVB infection was independent of MAVS. Surprisingly, virus titers were not elevated in MAVS-deficient mice, despite significant reductions in type I interferon levels. These data highlight the importance of type I interferon in host defense and provide insight on the mechanisms of innate immune responses following coxsackievirus infection.
Economic burden associated with chronic constipation in Sweden: a retrospective cohort study

Background Chronic constipation is a common condition, but few studies have assessed its cost and impact on resource use. The purpose of this cohort study was to assess the health care utilization and costs of chronic constipation in a Swedish population using health care claims data. Methods Data were compiled on health care costs, drug costs, and mortality for Västra Götaland, Sweden (2005–2009). These data were used to identify patients aged 18 years or older with chronic constipation, defined as: at least two health care contacts with a primary diagnosis of constipation within 12 months or at least one care contact with a primary diagnosis of constipation and two dispatches of laxatives 6 months before and 12 months after the index date. Patients with irritable bowel syndrome or taking opioids, both of which can cause constipation, were excluded. Costs, resource use, comorbidities, and laxative use were assessed during a 12-month follow-up period. Results In total, 4,043 patients with chronic constipation were identified. They had a mean (SD) age of 67±18 years. Mortality was 7% during the 12-month follow-up period and the most common comorbidity was hypertension (22%). In the 12-month follow-up period, patients with chronic constipation had a mean (SD) of 2.3±7.5 constipation-related health care contacts and a mean (SD) of 15.2±19.5 other health care contacts. Annual costs, adjusted for sex, age group, mortality, and comorbidities, were €5,388, of which €951 were for constipation-related care. Conclusion Patients with chronic constipation constituted an elderly population with a high disease burden in Sweden between 2005 and 2009. Mean annual constipation-related health care costs, adjusted for potentially confounding factors, were €951 per patient.
Lack of Detectable Alterations in Immune Responses during Sublingual Immunotherapy in Children with Seasonal Allergic Rhinoconjunctivitis to Grass Pollen

Background: Recent work indicates that subcutaneous specific immunotherapy induces specific T-cell anergy, a shift in the TH1/TH2 ratio, and antibody production in favor of IgG4. There are few data on sublingual immunotherapy (SLIT), especially in children. Methods: We assessed the proliferation of peripheral blood mononuclear cells (3H-thymidine incorporation) and secretion of interleukin (IL)-4, interferon (IFN)γ and IL-5 (ELISA) after in vitro stimulation with allergen or phytohemagglutinin (PHA) in 29 children with allergic rhinoconjunctivitis receiving SLIT with grass pollen before, and after 1 and 2 years of treatment in a multicenter placebo-controlled study on the efficacy of the treatment. Further, non-specific intracellular production of IL-4, IL-13, IFNγ, IL-2, IL-10 and IL-5 (FACS) and serum total and specific IgE and IgG4 (ELISA) were analyzed. Results: Proliferation and IL-4 and IL-5 secretion after stimulation with allergen or PHA did not differ between the groups. In addition, we observed no effect of SLIT on intracellular cytokine production. IFNγ secretion after allergen coculture was comparable between the groups. Following PHA stimulation, IFNγ secretion was significantly higher in the SLIT group after 1 year, and a trend was observable already before and after 2 years of treatment, probably due to the inhomogeneity in the groups despite randomization (for age and asthma). No significant changes were observed for sIgE/sIgG4 ratios over time either in or between the groups. Conclusion: During 2 years of SLIT in children with a positive effect on rescue medication use, we observed no significant effects on in vitro T-cell immune responses or immunoglobulins. So far, pediatric studies demonstrating stable effects of SLIT on such reactions are missing, probably due to limited effects of SLIT on systemic immunologic reactions.
Age and aerobic exercise training effects on whole body and muscle protein metabolism

[PDF] [Full Text] [Abstract] , May , 2010; 108 (5): 1410-1416. J Appl Physiol J. M. Dickinson, J. D. Lee, B. E. Sullivan, M. P. Harber, S. W. Trappe and T. A. Trappe initial measurements in humans A new method to study in vivo protein synthesis in slowand fast-twitch muscle fibers and [PDF] [Full Text] [Abstract] , October , 2010; 24 (10): 4117-4127. FASEB J Sheffield-Moore Paddon-Jones, Arthur P. Sanford, Robert C. Hickner, James J. Grady and Melinda William J. Durham, Shanon L. Casperson, Edgar L. Dillon, Michelle A. Keske, Douglas Age-related anabolic resistance after endurance-type exercise in healthy humans [PDF] [Full Text] [Abstract] , November , 2010; 299 (5): R1254-R1262. Am J Physiol Regul Integr Comp Physiol Paul T. Reidy Matthew P. Harber, Adam R. Konopka, Bozena Jemiolo, Scott W. Trappe, Todd A. Trappe and fasted and fed states Muscle protein synthesis and gene expression during recovery from aerobic exercise in the [PDF] [Full Text] [Abstract] , February , 2011; 110 (2): 480-491. J Appl Physiol Gordon I. Smith, Bruce W. Patterson and Bettina Mittendorfer why is it so variable? −− Human muscle protein turnover [PDF] [Full Text] [Abstract] , February , 2011; 93 (2): 322-331. Am J Clin Nutr Loon Bart Pennings, René Koopman, Milou Beelen, Joan MG Senden, Wim HM Saris and Luc JC van acids for de novo muscle protein synthesis in both young and elderly men derived amino − Exercising before protein intake allows for greater use of dietary protein
Early experience with Wide-Platform Mk II implants. Part I: Implant survival. Part II: Evaluation of risk factors involving implant survival.

Part I of this study describes the survival of a wide-platform, wide-diameter implant (Wide-Platform Mk II). Beginning in January 1997, 85 Wide-Platform Mk II implants were placed in the jaws of 63 patients (35 males and 28 females). Male patients experienced 10 implant failures, and female patients lost 9 implants. The mean time of implant follow-up was 286 days (median, 280), with a maximum of 734 days and a minimum of 0 days. Implant loss was 19% in the mandible and 29% in the maxilla. Kaplan-Meier analysis showed a probability of implant failure after 1 year of 0.649 (confidence interval, 0.455 to 0.926) in the maxilla and of 0.751 (confidence interval, 0.616 to 0.915) in the mandible. No apparent relationship was noted between implant survival and implant length. Part II of this study evaluated the association between the survival of a new implant design and a number of potential risk factors. A retrospective chart review was conducted for all patients who received Wide-Platform Mk II implants and who agreed to allow a medical records review for research purposes. Kaplan-Meier survival curves were used to assess the probability of implant survival relative to time. The relationships between implant survival and implant location, history of tobacco use, current tobacco use, sinus grafting, bruxism, and root canal therapy were assessed by Cox proportional hazards modeling. Although the hazard ratio showed an increased risk of implant failure with some factors, particularly a history of root canal therapy in the site of implant placement (hazard ratio 3.2, P = .10), none of the factors were statistically significant. The Wide-Platform Mk II implant used in this population group was associated with a high failure rate, but the failure rate was not related to any specific risk factors reviewed.
Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial.

BACKGROUND Low birth weight infants have been noted to have low zinc concentrations in cord blood, and zinc deficiency in childhood is associated with reduced immunocompetence and increased infectious disease morbidity. This study investigates whether zinc supplementation of infants born full term and small for gestational age affects mortality. METHODS A randomized, double-blind, controlled trial with 2-by-2 factorial design enrolled 1154 full-term small for gestational age infants to receive in syrup 1 of the following: riboflavin; riboflavin and zinc (5 mg as sulfate); riboflavin, calcium, phosphorus, folate, and iron; or riboflavin, zinc, calcium, phosphorus, folate, and iron. A fixed dosage of 5 mL per child was given daily from 30 to 284 days of age. Household visits were made 6 days per week to provide the syrup and conduct surveillance for illness and death. When a child's death was reported, parental reports and medical records were used to ascertain the cause. The effects of zinc and of the combination of iron, folate, calcium, and phosphorus were analyzed by intent to treat. The mortality analysis was performed using a survival analytic approach that models time until death as the dependent variable; all models had 2 terms as independent variables: 1 for the zinc effect and 1 for the vitamin and mineral (calcium and phosphorus, folate and iron) effect. RESULTS Zinc supplementation was associated with significantly lower mortality, with a rate ratio of 0.32 (95% confidence interval: 0.12-0.89). Calcium, phosphorus, folate, and iron supplementation was not associated with a mortality reduction, although a statistically nonsignificant trend toward reduction was observed with a rate ratio of 0.88 (95% confidence interval: 0.36-2.15). CONCLUSIONS Zinc supplementation in small for gestational age infants can result in a substantial reduction in infectious disease mortality.
Channelrhodopsin as a tool to investigate synaptic transmission and plasticity

The light‐gated cation channel channelrhodopsin‐2 (ChR2) has been used in a variety of model systems to investigate the function of complex neuronal networks by stimulation of genetically targeted neurons. In slice physiology, ChR2 opens the door to novel types of experiments and greatly extends the technical possibilities offered by traditional electrophysiology. In this short review, we first consider several technical aspects concerning the use of ChR2 in slice physiology, providing examples from our own work. More specifically, we discuss differences between light‐evoked action potentials and spontaneous or electrically induced action potentials. Our work implies that light‐evoked action potentials are associated with increased calcium influx and a very high probability of neurotransmitter release. Furthermore, we point out the factors limiting the spatial resolution of ChR2 activation. Secondly, we discuss how synaptic transmission and plasticity can be studied using ChR2. Postsynaptic depolarization induced by ChR2 can be combined with two‐photon glutamate uncaging to potentiate visually identified dendritic spines. ChR2‐mediated stimulation of presynaptic axons induces neurotransmitter release and reliably activates postsynaptic spines. In conclusion, ChR2 is a powerful tool to investigate activity‐dependent changes in structure and function of synapses.
Changes from 1986 to 2006 in reasons for liking leisure‐time physical activity among adolescents

Reasons for participating in physical activity (PA) may have changed in accordance with the general modernization of society. The aim is to examine changes in self‐reported reasons for liking leisure‐time physical activity (LTPA) and their association with self‐reported LTPA over a 20‐year period. Data were collected among nationally representative samples of 13‐year‐olds in Finland, Norway, and Wales in 1986 and 2006 (N = 9252) as part of the WHO cross‐national Health Behaviour in School‐aged Children (HBSC) study. Univariate ANOVAs to establish differences according to gender, year, and country were conducted. In all countries, 13‐year‐olds in 2006 tended to report higher importance in terms of achievement and social reasons than their counterparts in 1986, while changes in health reasons were minor. These reasons were associated with LTPA in a similar way at both time points. Health reasons for liking LTPA were considered most important, and were the strongest predictor of LTPA. The findings seem robust as they were consistent across countries and genders. Health education constitutes the most viable strategy for promoting adolescents' motivation for PA, and interventions and educational efforts could be improved by an increased focus on LTPA and sport as a social activity.
Microscopic Evolution of Social Networks by Triad Position Profile

Disentangling the mechanisms underlying the social network evolution is one of social science's unsolved puzzles. Preferential attachment is a powerful mechanism explaining social network dynamics, yet not able to explain all scaling-laws in social networks. Recent advances in understanding social network dynamics demonstrate that several scaling-laws in social networks follow as natural consequences of triadic closure. Macroscopic comparisons between them are discussed empirically in many works. However the network evolution drives not only the emergence of macroscopic scaling but also the microscopic behaviors. Here we exploit two fundamental aspects of the network microscopic evolution: the individual influence evolution and the process of link formation. First we develop a novel framework for the microscopic evolution, where the mechanisms of preferential attachment and triadic closure are well balanced. Then on four real-world datasets we apply our approach for two microscopic problems: node's prominence prediction and link prediction, where our method yields significant predictive improvement over baseline solutions. Finally to be rigorous and comprehensive, we further observe that our framework has a stronger generalization capacity across different kinds of social networks for two microscopic prediction problems. We unveil the significant factors with a greater degree of precision than has heretofore been possible, and shed new light on networks evolution.
Correlation of grade prediction performance and validity of self-evaluation comments

To grasp a student's lesson attitude and learning situation and to give a feed back to each student are educational foundations. Goda et al. proposed the PCN method to estimate a learning situation from a comment freely written by students[6, 7]. The PCN method categorizes comments into three items of P (previous), C(current) and N(next). They pointed out a correlation between the student's final results and the validity of a descriptive content of item C, that is something related to understanding of the lesson and learning attitudes to the lesson. However, a problem left in their work is the badness of performance in prediction for upper grade students. This paper proposes two manners of utilization of PCN scores: the validity level determination for assessment, and for prediction performance of students' final grades. In order to validate the proposed manners of utilization, we conducted two experiments. First, we employed multiple regression analysis to calculate PCN scores that determine the validity level with respect to each viewpoint. Students who wrote comments with a high PCN score are considered as those who describe their learning attitude appropriately. We also applied a machine learning method SVM (support vector machine) to students' comments for predicting their final results in five grades of S, A, B, C and D. Experimental results illustrated that as comments of students get higher PCN scores, the prediction performance of the students' grades becomes higher.
β‐Arrestin2 Regulates RANKL and Ephrins Gene Expression in Response to Bone Remodeling in Mice

PTH‐stimulated intracellular signaling is regulated by the cytoplasmic adaptor molecule β‐arrestin. We reported that the response of cancellous bone to intermittent PTH is reduced in β‐arrestin2−/− mice and suggested that β‐arrestins could influence the bone mineral balance by controlling RANKL and osteoprotegerin (OPG) gene expression. Here, we study the role of β‐arrestin2 on the in vitro development and activity of bone marrow (BM) osteoclasts (OCs) and Ephrins ligand (Efn), and receptor (Eph) mRNA levels in bone in response to PTH and the changes of bone microarchitecture in wildtype (WT) and β‐arrestin2−/− mice in models of bone remodeling: a low calcium diet (LoCa) and ovariectomy (OVX). The number of PTH‐stimulated OCs was higher in BM cultures from β‐arrestin2−/− compared with WT, because of a higher RANKL/OPG mRNA and protein ratio, without directly influencing osteoclast activity. In vivo, high PTH levels induced by LoCa led to greater changes in TRACP5b levels in β‐arrestin2−/− compared with WT. LoCa caused a loss of BMD and bone microarchitecture, which was most prominent in β‐arrestin2−/−. PTH downregulated Efn and Eph genes in β‐arrestin2−/−, but not WT. After OVX, vertebral trabecular bone volume fraction and trabecular number were lower in β‐arrestin2−/− compared with WT. Histomorphometry showed that OC number was higher in OVX‐β‐arrestin2−/− compared with WT. These results indicate that β‐arrestin2 inhibits osteoclastogenesis in vitro, which resulted in decreased bone resorption in vivo by regulating RANKL/OPG production and ephrins mRNAs. As such, β‐arrestins should be considered an important mechanism for the control of bone remodeling in response to PTH and estrogen deprivation.
Value of KRAS as prognostic or predictive marker in NSCLC: results from the TAILOR trial.

BACKGROUND The prognostic and predictive role of KRAS mutations in advanced nonsmall-cell lung cancer (NSCLC) is still unclear. TAILOR prospectively assessed the prognostic and predictive value of KRAS mutations in NSCLC patients treated with erlotinib or docetaxel in second line. PATIENTS AND METHODS NSCLC patients from 52 Italian hospitals were genotyped for KRAS and EGFR mutational status in two independent laboratories. Wild-type EGFR patients (N = 218) received first-line platinum-based chemotherapy and were randomly allocated at progression to erlotinib or docetaxel. Overall survival (OS) according to KRAS mutational status was the primary end point. RESULTS KRAS mutations were present in 23% of TAILOR randomized cases. The presence of a KRAS mutation did not adversely affect progression-free (PFS) or overall (OS) survival [hazard ratio (HR) PFS = 1.01, 95% confidence interval (CI) 0.71-1.41, P = 0.977; OS = 1.24, 95% CI 0.87-1.77, P = 0.233], nor influenced treatment outcome (test for interaction: OS P = 0.965; PFS P = 0.417). Patients randomized to docetaxel treatment experienced longer survival independently from the KRAS mutational status of their tumors (HR: mutated KRAS 0.81, 95% CI 0.45-1.47; wild-type KRAS 0.79, 95% CI 0.57-1.10). CONCLUSION In TAILOR, KRAS was neither prognostic nor predictive of benefit for either docetaxel or erlotinib. Docetaxel remains superior independently from KRAS status for second-line treatment in EGFR wild-type advanced NSCLC patients. CLINICAL TRIAL REGISTRATION NCT00637910.
Title Contact behaviour of children and parental employment behaviour during school closures against the pandemic influenza A ( H 1 N 1-2009 ) in Japan

Objectives: To identify epidemiological determinants of the contact behaviour of children and their impact on parental employment, during school closures that took place over the course of the 2009 pandemic influenza (H1N1-2009) in Japan. Methods: A retrospective survey was conducted in Japanese households between October 2009 and May 2010 by administration of a standardized questionnaire. Demographic and behavioural variables were explored, in association with the frequency with which children left the home and the risk of parents being absent from work during school closures. Results: Data from 882 eligible households were analysed. A total of 181/882 (20.5%) of households reported that children left the home for nonessential reasons during school closures. No impact on parental working hours was reported by 742/882 (84.1%) of households. Univariate analyses showed that the frequency with which children left the home was dependent on age, extent of school closure and requirement for special childcare arrangements. Conclusions: A greater understanding of age-dependent behaviours, during school closures as a consequence of a pandemic, is required. Consideration of a public policy to permit a paid leave of absence from work for parents during school closures may be beneficial; the cost-effectiveness of such a measure should be assessed in future. Journal of International Medical Research
Unsuitability of Quantitative Bacteroidales 16S rRNA Gene Assays for Discerning Fecal Contamination of Drinking Water

ABSTRACT Bacteroidales species were detected in (tap) water samples from treatment plants with three different PCR assays. 16S rRNA gene sequence analysis indicated that the sequences had an environmental rather than fecal origin. We conclude that assays for Bacteroidales 16S rRNA genes are not specific enough to discern fecal contamination of drinking water in the Netherlands.
Physical structure of a native protoplasmic polysaccharide from Escherichia coli.

The physical structure of naturally occurring polysaccharides found in protoplasmic extracts of Escherichia coli was investigated. These materials were found to be linear molecules with particle weights averaging 163,000 and diameters and lenghths of about 16 Å and 1300 Å, respectively. The molecules were not composed of micellar arrays of smaller subunit molecules, as has been shown in endotoxins of E. coli. Therefore, basic structural differences between the endotoxin and NPP molecules have been demonstrated.