Miracle-dz/UniFAR-FTUs huggingface dataset:
Progress toward the development of a genetically engineered attenuated hepatitis A virus vaccine

Mutations which positively affect growth of hepatitis A virus in cell culture may negatively affect growth in vivo. Therefore, development of an attenuated vaccine for hepatitis A may require a careful balancing of mutations to produce a virus that will grow efficiently in cells suitable for vaccine production and still maintain a satisfactory level of attenuation in vivo. Since such a balance could be achieved most directly by genetic engineering, we are analyzing mutations that accumulated during serial passage of the HM-175 strain of hepatitis A virus in MRC-5 cell cultures in order to determine the relative importance of the mutations for growth in MRC-5 cells and for attenuation in susceptible primates. Chimeric viral genomes of the HM-175 strain were constructed from cDNA clones derived from a virulent virus and from two attenuated viruses adapted to growth in African green monkey kidney (AGMK) and MRC-5 cells, respectively. Viruses encoded by these chimeric genomes were recovered by in vitro or in vivo transfection and assessed for their ability to grow in cultured MRC-5 cells or to cause hepatitis in primates (tamarins). The only MRC-5-specific mutations that substantially increased the efficiency of growth in MRC-5 cells were a group of four mutations in the 5' noncoding (NC) region. These 5' NC mutations and a separate group of 5' NC mutations that accumulated during earlier passages of the HM-175 virus in primary AGMK cells appeared, independently and additively, to result in decreased biochemical evidence of hepatitis in tamarins. However, neither group of 5' NC mutations had a demonstrable effect on the extent of virus excretion or liver pathology in these animals.
Ten‐Year Longitudinal Relationship Between Physical Activity and Lumbar Bone Mass in (Young) Adults

Little is known about the influence of long‐term daily physical activity (PA) on lumbar bone mass after peak bone mass has been reached, that is, during [young] adulthood. The purpose of this study was to investigate the longitudinal relationship between PA and lumbar bone mineral density (LBMD) in healthy subjects over a 10‐year period. The data reported here relate to 225 male and 241 female participants in the Amsterdam Growth and Health Longitudinal Study, who were measured at the mean ages of 27, 32, and/or 36. LBMD, habitual daily PA, total body weight, and calcium intake were assessed at each measurement point. The effects of two aspects of PA were analyzed: the mechanical (MECHPA; sum of all ground reaction forces) and metabolic (METPA; weighted metabolic score of intensity, frequency, and duration) components, each within a separate model. Multilevel analysis was used to investigate the relationship between PA and LBMD over the 10‐year period. Gender, total body weight, and calcium intake were included in the analysis as covariates. The results indicated that MECHPA was a significant positive linear predictor of LBMD for males (r = 0.09; p < 0.001) but not for females. For the METPA, no linear longitudinal relationship with LBMD was found. The results suggest that there is a metabolic threshold at which extra PA becomes “deleterious” and METPA in its totality becomes ineffective for LBMD. It is concluded that during the (young) adult period, between 27 and 36 years of age, PA causing mechanical loading on the skeleton has a small positive influence on LBMD in males.
Effects of atracurium on intraocular pressure, eye position, and blood pressure in eucapnic and hypocapnic isoflurane-anesthetized dogs.

OBJECTIVE To determine effects of atracurium on intraocular pressure (IOP), eye position, and arterial blood pressure in eucapnic and hypocapnic dogs anesthetized with isoflurane. ANIMALS 16 dogs. PROCEDURE Ventilation during anesthesia was controlled to maintain Paco2 at 38 to 44 mm Hg in group- I dogs (n = 8) and 26 to 32 mm Hg in group-II dogs (8). Baseline measurements for IOP, systolic, diastolic, and mean arterial blood pressure, central venous pressure (CVP), and heart rate (HR) were recorded. Responses to peroneal nerve stimulation were monitored by use of a force-displacement transducer. Atracurium (0.2 mg/kg) was administered i.v. and measurements were repeated at 1, 2, 3, and 5 minutes and at 5-minute intervals thereafter for 60 minutes. RESULTS Atracurium did not affect IOP, HR, or CVP Group II had higher CVP than group I, but IOP was not different. There was no immediate effect of atracurium on arterial blood pressure. Arterial blood pressure increased gradually over time in both groups. Thirty seconds after administration of atracurium, the eye rotated from a ventromedial position to a central position and remained centrally positioned until 100% recovery of a train-of-four twitch response. The time to 100% recovery was 53.1 +/- 5.3 minutes for group I and 46.3 +/- 9.2 minutes for group II. CONCLUSIONS AND CLINICAL RELEVANCE Atracurium did not affect IOP or arterial blood pressure in isoflurane-anesthetized dogs. Hyperventilation did not affect IOP or the duration of effect of atracurium.
Low-Frequency-Noise Characteristic of Quasi-Enhancement-Mode HEMT Using a Selectively Hydrogen-Pretreatment

The DC, RF, and low-frequency noise characteristics were investigated for a quasi-enhancement-mode (QE) HEMT using a selective hydrogen pretreatment (SHP). The QE-HEMT with SHP showed a large shift in threshold voltage without severe degradation of RF performances including cut-off frequency and maximum oscillation frequency, compared with those of HEMT without SHP. Moreover, the QE HEMT exhibited a reduction of low-frequency noise bulges compared with those of depletion-mode HEMT without an SHP, leading to an one-order smaller input noise spectral density at 100Hz, and offered a potential for application to a low phase noise oscillator
A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer.

BACKGROUND The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results. METHODS In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation. RESULTS The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors. CONCLUSIONS Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
Paraoxonase (PON 1) as a biomarker of susceptibility for organophosphate toxicity

Paraoxonase (PON1) is an A-esterase capable of hydrolysing the active metabolites (oxons) of a number of organophosphorus (OP) insecticides such as parathion, diazinon and chlorpyrifos. PON1 activity is highest in liver and plasma, and among animal species significant differences exist, with birds and rabbits displaying very low and high activity, respectively. Human PON1 has two polymorphisms in the coding region (Q192R and L55M) and five polymorphisms in the promoter region. The Q192R polymorphism imparts different catalytic activity toward some OP substrates, while the polymorphism at position -108 (C/T) is the major contributor to differences in the level of PON1 expression. Animal studies have shown that PON1 is an important determinant of OP toxicity, with animal species with a low PON1 activity having an increased sensitivity to OPs. Administration of exogenous PON1 to rats or mice protects them from the toxicity of OPs. PON1 knockout mice display a high sensitivity to the toxicity of diazoxon and chlorpyrifos oxon, but not paraoxon. In vitro assayed catalytic efficiencies of purified PON192 isoforms for hydrolysis of specific oxon substrates accurately predict the degree of in vivo protection afforded by each isoform. Low PON1 activity may also contribute to the higher sensitivity of newborns to OP toxicity.
Optimization of the isotope-coded affinity tag-labeling procedure for quantitative proteome analysis.

The combination of isotope coded affinity tag (ICAT) reagents and tandem mass spectrometry constitutes a new method for quantitative proteomics. It involves the site-specific, covalent labeling of proteins with isotopically normal or heavy ICAT reagents, proteolysis of the combined, labeled protein mixture, followed by the isolation and mass spectrometric analysis of the labeled peptides. The method critically depends on labeling protocols that are specific, quantitative, general, robust, and reproducible. Here we describe the systematic evaluation of important parameters of the labeling protocol and describe optimized labeling conditions. The tested factors include the ICAT reagent concentration, the influence of the protein, SDS, and urea concentrations on the labeling reaction, and the reaction time. We demonstrate that using the optimized conditions specific and quantitative labeling was achieved on standard proteins as well as in complex protein mixtures such as a yeast cell lysate.
Risk factors associated with subclinical human infection with avian influenza A (H5N1) virus--Cambodia, 2006.

BACKGROUND We conducted investigations in 2 villages in Cambodia where outbreaks of influenza H5N1 occurred among humans and poultry to determine the frequency of and risk factors for H5N1 virus transmission. METHODS During May 2006, approximately 7 weeks after outbreaks of influenza H5N1 among poultry occurred, villagers living near households of 2 patients with influenza H5N1 were interviewed about potential H5N1 exposures and had blood samples obtained for H5N1 serological testing by microneutralization assay. A seropositive result was defined as an influenza H5N1 neutralizing antibody titer of 1:80, with confirmation by Western blot assay. A case-control study was conducted to identify risk factors for influenza H5N1 virus infection. Control subjects, who had seronegative results of tests, were matched with H5N1-seropositive persons by village residence, households with an influenza H5N1-infected poultry flock, sex, and age. RESULTS Seven (1.0%) of 674 villagers tested seropositive for influenza H5N1 antibodies and did not report severe illness; 6 (85.7%) were male. The 7 H5N1-seropositive persons, all of whom were aged<or=18 years, were younger than participants who tested seronegative for H5N1 antibodies (median age, 12.0 years vs. 27.4 years; P=.03) and were more likely than were the 24 control subjects to report bathing or swimming in household ponds (71.4% vs. 20.8%; matched odds ratio, 11.3; P=.03). CONCLUSIONS Avian-to-human transmission of influenza H5N1 virus remains low, despite extensive poultry contact. Exposure to a potentially contaminated environment was a risk factor for human infection.
Infection, thyroid disease, and autoimmunity.

The etiology of the AITDs remains unclear but it is now generally believed that both genetic and environmental factors contribute to their development. Some recent findings have begun to directly and indirectly implicate the possibility of infectious agents in the pathogenesis of AITD, and these data serve as the basis for this review. Classical AITD (i.e. Graves' disease and Hashimoto's thyroiditis) has been shown to be associated with a variety of infectious agents (e.g. Yersinia enterocolitica, retroviruses) while infections of the thyroid gland (e.g. subacute thyroiditis, congenital rubella) have been shown to be associated with thyroid autoimmune phenomena. However, the causative role of infectious agents in AITD has not been definitively demonstrated in humans although AITD can be induced in experimental animals by certain viral infections. Infectious agents may induce thyroid autoimmunity by a variety of diverse mechanisms, such as inducing modifications of self-antigens, mimicking self-molecules, inducing polyclonal T cell activation (for example by superantigens), altering the idiotypic network, forming immune complexes, and inducing expression of MHC molecules on thyroid epithelial cells. While indirect data suggesting involvement of the infecting organisms in the pathogenesis of human AITD is abundant, only a limited number of studies have employed direct approaches. Such a direct approach would involve isolation or molecular identification of the potentially infecting organisms from the thyroid gland and the subsequent induction of AITD in an experimental model.
Synchronized bursts of miniature inhibitory postsynaptic currents

Spike‐independent miniature postsynaptic currents are generally stochastic and are therefore not thought to mediate information relay in neuronal circuits. However, we recorded endogenous bursts of IPSCs in hypothalamic magnocellular neurones in the presence of TTX, which implicated a coordinated mechanism of spike‐independent GABA release. IPSC bursts were identical in the absence of TTX, although the burst incidence increased 5‐fold, indicating that IPSC bursts were composed of miniature IPSCs (mIPSCs), and that the probability of burst generation increased with action potential activity. IPSC bursts required extracellular calcium, although they were not dependent on calcium influx through voltage‐gated calcium channels or on calcium mobilization from intracellular stores. Current injections simulating IPSC bursts were capable of triggering and terminating action potential trains. In 25% of dual recordings, a subset of IPSC bursts were highly synchronized in onset in pairs of magnocellular neurones. Synchronized IPSC bursts displayed properties that were consistent with simultaneous release at GABA synapses shared between pairs of postsynaptic magnocellular neurones. Synchronized bursts of inhibitory synaptic inputs represent a novel mechanism that may contribute to the action potential burst generation, termination and synchronization responsible for pulsatile hormone release from neuroendocrine cells.
Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years.

OBJECTIVE To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/μL, 19% CD4 < 200/μL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/μL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.
More organic food on the public plate – need for a New Public Governance?: WG 2. Institutional food procurement and school feeding programmes: exploring the benefits, challenges and opportunities

More organic food to public plate can contribute to reaching important goals of the Sustainable Development Goals. Public procurement policies (POPP’s) has proven to be a well suited strategy to increase the uptake of organic produce. Transition of the agricultural system in a more sustainable direction however, cannot be achieved through public policy alone. Instead the concerted action of a long range of stakeholders along the supply chain seems to of importance. The objective of this study was to examine the views and attitudes of important representatives from the three powers of society (civil society, market and public actors) on enabling and disabling factors public procurement policies in order to provide recommendations on governance strategies for sustainable public food consumption. We use Bourdieu' thinking and the ideas of New Public Governance to explain some of the enabling and disabling factors in the dynamics of the organic public plate. The results points to the fact that political decision for supporting and a strong financing from different levels of government and innovative approaches to training of staff focusing on development of craftsmanship and inspiration about organic food in NPG frame were considered by stakeholders to be key enabling factors that opens new possibilities for public organic food services and sustainable development. In contrast to the value conflicts in top managers, were considered to be disabling factors. The findings from our qualitative research suggest that themes rated as important by informants were: leadership and political support, multi-stakeholder engagement, Danish “front running” or “the early moverness” of the Danish organic food and farming case, capacity building strategies, consumer trust in organics products (in general in the DK organic regulation) and “Environmentalisation” (Government 2020 goal: all public kitchens to be organic). However, without being indifferent to issues such as education, model governance, price premiums, timing, ecology, innovation and managers' conflicts. These findings are shown in two categories - as enabling factors that tends to force environmental goals into organic public foodscapes kitchens and as disabling factors that tend to hinder the achievement of POPPs goals. In the following we elaborate on the enabling factors are characterized:
Molecular Cloning of a Novel T Cell-directed CC Chemokine Expressed in Thymus by Signal Sequence Trap Using Epstein-Barr Virus Vector*

Precursors of most secreted and cell surface molecules carry signal sequences at their amino termini. Here we describe an efficient signal sequence trap method and isolation of a novel CC chemokine. An expression library was constructed by inserting 5′ portion-enriched cDNAs from phytohemagglutinin-stimulated peripheral blood mononuclear cells into upstream of signal sequence-deleted CD4 cDNA in an Epstein-Barr virus shuttle vector. After electroporation into Raji cells, CD4 antigen-positive cells were enriched by repeated cell sorting and plasmids were recovered in Escherichia coli. Out of 100 plasmid clones examined, 42 clones directed expression of CD4 antigen on the cell surface. Among them were signal sequences of CD6, β2-microglobulin, MGC-24, and T cell receptor ϵ-chain, and at least four novel potential signal sequences. A cDNA clone encoding a novel CC chemokine was isolated by using one of the trapped fragments. The gene designated as TARC from Thymus and Activation-Regulated Chemokine was expressed transiently in phytohemagglutinin-stimulated peripheral blood mononuclear cells and constitutively in thymus. Radiolabeled recombinant TARC specifically bound to T cell lines and peripheral T cells but not to monocytes or granulocytes. The binding of radiolabeled TARC to the high-affinity receptor (Kd, 2.1 n) on Jurkat was displaced by TARC but not by interleukin-8, MIP-1α, RANTES, or MCP-1. TARC also bound to the promiscuous chemokine receptor on erythrocytes (Kd, 17 n). TARC induced chemotaxis in T cell lines Hut78 and Hut102. Pretreatment of Hut78 with pertussis toxin abolished the TARC-induced cell migration. Collectively, T cells express a highly selective receptor for TARC that is coupled to pertussis toxin-sensitive G-protein. TARC may a factor playing important roles in T cell development in thymus as well as in trafficking and activation of mature T cells.
An Updated Systematic Review and Meta-analysis of the Predictive Value of Serum Biomarkers in the Assessment of Fever During Neutropenia in Children With Cancer

Background: Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. The role of biomarkers in predicting morbidity and mortality associated with FN in children has been explored with varying results. This systematic review identified, critically appraised and synthesized information on the use of biomarkers for the prediction of outcome of FN in children/young adults, updating a review of initial assessment and adding further analysis of their value at reassessment. Methods: This review was conducted in accordance with the Centre for Reviews and Dissemination Methods, using 3 different random effects meta-analysis models. Results: Thirty-seven studies involving over 4689 episodes of FN in children were assessed, including an additional 13 studies investigating 18 biomarkers in 1670 FN episodes since the original review. Meta-analysis was possible for admission C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 and interleukin-8 in their ability to detect significant infection. Marked heterogeneity exists, precluding clear clinical interpretation of the results. Qualitative synthesis of the role of serial biomarkers suggests their predictive ability may be more pronounced at 24 to 48 hours compared with admission. Direct comparisons of the discriminatory power of admission values of PCT and CRP showed PCT generally had a better discriminatory estimate of serious infection than CRP. Conclusions: There remains a paucity of robust and reproducible data on the use of biomarkers in prediction of serious infection in children with FN. Available evidence suggests PCT has better discriminatory ability than CRP and that the role of serial biomarkers warrants further study.