Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
In the heavy-fermion metal CePdAl, long-range antiferromagnetic order coexists with geometric frustration of one-third of the Ce moments. At low temperatures, the Kondo effect tends to screen the ...frustrated moments. We use magnetic fields B to suppress the Kondo screening and study the magnetic phase diagram and the evolution of the entropy with B employing thermodynamic probes. We estimate the frustration by introducing a definition of the frustration parameter based on the enhanced entropy, a fundamental feature of frustrated systems. In the field range where the Kondo screening is suppressed, the liberated moments tend to maximize the magnetic entropy and strongly enhance the frustration. Based on our experiments, this field range may be a promising candidate to search for a quantum spin liquid.
The MiniBooNE experiment at Fermilab reports a total excess of 638.0 ± 52.1 (stat .) ± 122.2 (syst.) electronlike events from a data sample corresponding to 18.75 × 10 20 protons-on-target in ...neutrino mode, which is a 46% increase in the data sample with respect to previously published results and 11.27 × 10 20 protons-on-target in antineutrino mode. The overall significance of the excess, 4.8σ, is limited by systematic uncertainties, assumed to be Gaussian, as the statistical significance of the excess is 12.2σ. The additional statistics allow several studies to address questions on the source of the excess. First, we provide two-dimensional plots in visible energy and the cosine of the angle of the outgoing lepton, which can provide valuable input to models for the event excess. Second, we test whether the excess may arise from photons that enter the detector from external events or photons exiting the detector from π 0 decays in two model independent ways. Beam timing information shows that almost all of the excess is in time with neutrinos that interact in the detector. The radius distribution shows that the excess is distributed throughout the volume, while tighter cuts on the fiducial volume increase the significance of the excess. The data likelihood ratio disfavors models that explain the event excess due to entering or exiting photons.
Summary
Background
Hepatitis C virus (HCV) infection has been linked to an increased risk of insulin resistance and carotid atherosclerosis.
Aim
To investigate the association between HCV infection ...and stroke, and the effect of interferon‐based therapy (IBT) on stroke risk in chronic hepatitis C (CHC) patients.
Methods
We conducted a retrospective cohort study that followed up 3113 subjects with a newly detected HCV infection and 12 452 age‐ and gender‐matched subjects without HCV infection selected from a random sample of 106 beneficiaries from the Taiwan National Health Insurance Program up to 5 years. Use of IBT was defined as treatment with interferon alpha, pegylated interferon alpha‐2a or pegylated interferon alpha‐2b for at least 3 months. The hazard ratio (HR) for newly detected stroke was calculated for subjects with HCV compared to those without HCV, and for IBT‐treated HCV patients compared to non‐IBT‐treated HCV patients while adjusting for possible confounding factors.
Results
The overall person‐years of follow‐up were 8624.11 in patients with HCV, 54 533.69 in patients without HCV, 666.65 in IBT‐treated patients, and 7886.49 in nontreated patients. The multivariable‐adjusted hazard ratio (HR) for newly detected stroke was 1.23 for subjects with HCV compared to the age‐ and sex‐matched subjects without HCV (adjusted HR = 1.23, 95% CI = 1.06–1.42, P = 0.008). Moreover, use of IBT significantly reduced the risk of stroke in HCV patients (adjusted HR = 0.39, 95% CI = 0.16–0.95, P = 0.039) after adjusting for known prognostic factors.
Conclusions
Interferon‐based therapy may reduce the long‐term risk of stroke in patients with chronic HCV infection.
Bioconjugation technologies have revolutionized the practice of biology and medicine by allowing access to novel biomolecular scaffolds. New methods for residue-selective bioconjugation are highly ...sought to expand the toolbox for a variety of bioconjugation applications. Herein we report a site-selective methionine bioconjugation protocol that uses photoexcited lumiflavin to generate open-shell intermediates. This reduction-potential-gated strategy enables access to residues unavailable with traditional nucleophilicity-based conjugation methods. To demonstrate the versatility and robustness of this new protocol, we have modified various proteins and further utilized this functional handle to append diverse biological payloads.
This study examined the association of diabetes with the onset of dementia (including Alzheimer's disease (AD), vascular dementia (VD) and any dementia) and mild cognitive impairment (MCI) by using a ...quantitative meta‐analysis of longitudinal studies. EMBASE and MEDLINE were searched for articles published up to December 2010. All studies that examined the relationship between diabetes and the onset of dementia or MCI were included. Pooled relative risks were calculated using fixed and random effects models. Nineteen studies met our inclusion criteria for this meta‐analysis, and 6184 subjects with diabetes and 38 530 subjects without diabetes were included respectively. All subjects were without dementia or MCI at baseline. The quantitative meta‐analysis showed that subjects with diabetes had higher risk for AD (relative risk (RR):1.46, 95% confidence interval (CI): 1.20–1.77), VD (RR: 2.48, 95% CI: 2.08–2.96), any dementia (RR: 1.51, 95% CI: 1.31–1.74) and MCI (RR: 1.21, 95% CI: 1.02–1.45) than those without. The quantitative meta‐analysis showed that diabetes was a risk factor for incident dementia (including AD, VD and any dementia) and MCI.
Aim
To investigate the influence of mineral trioxide aggregate (MTA) on angiogenesis of primary human dental pulp cells (hDPCs) via the MAPK pathway, in particular p38.
Methodology
Human dental pulp ...cells were cultured with MTA to angiogenesis, after which cell viability, ion concentration, osmolality, NO secretion, the von Willebrand factor (vWF) and angiopoietin‐1 (Ang‐1) protein expression were examined. PrestoBlue® was used for evaluating the proliferation of hDPCs. An enzyme‐linked immunosorbent assay was employed to determine vWF and Ang‐1 protein secretion in hDPCs cultured on MTA and the control. Cells cultured on the tissue culture plate without the cement were used as the control. The t‐test was used to evaluate the significance of the differences between the mean values.
Results
Mineral trioxide aggregate elicited a significant (P < 0.05) increased viability compared with the control (15%, 16% and 13% on days 1, 3 and 5 of cell seeding, respectively). MTA consumed calcium and phosphate ions, and released more Si ions in the medium. MTA significantly (P < 0.05) increased the osmolality of the medium to 313, 328 and 341 mOsm kg−1 after 1, 3 and 5 days, respectively. P38 was activated through phosphorylation, and the phosphorylation kinase was investigated in the cell system after being cultured with MTA. Expression levels for Ang‐1 and vWF in hDPCs on MTA were higher than those of the MTA + p38 inhibitor (SB203580) group (P < 0.05) at all of the time‐points.
Conclusions
Mineral trioxide aggregate was able to activate the p38 pathway in hDPCs cultured in vitro. Moreover, Si increased the osmolality required to facilitate the angiogenic differentiation of hDPCs via the p38 signalling pathway. When the p38 pathway was blocked by SB203580, the angiogenic‐dependent protein secretion decreased. These findings verify that the p38 pathway plays a key role in regulating the angiogenic behaviour of hDPCs cultured on MTA.
Background and Objective: Short‐chain fatty acids, such as butyric acid and propionic acid, are metabolic by‐products generated by periodontal microflora such as Porphyromonas gingivalis, and ...contribute to the pathogenesis of periodontitis. However, the effects of butyrate on the biological activities of gingival fibroblasts (GFs) are not well elucidated.
Material and Methods: Human GFs were exposed to various concentrations of butyrate (0.5–16 mm) for 24 h. Viable cells that excluded trypan blue were counted. Cell cycle distribution of GFs was analyzed by propidium iodide‐staining flow cytometry. Cellular reactive oxygen species (ROS) production was measured by flow cytometry using 2’,7’‐dichlorofluorescein (DCF). Total RNA and protein lysates were isolated and subjected to RT‐PCR using specific primers or to western blotting using specific antibodies, respectively.
Results: Butyrate inhibited the growth of GFs, as indicated by a decrease in the number of viable cells. This event was associated with an induction of G0/G1 and G2/M cell cycle arrest by butyrate (4–16 mm) in GFs. However, no marked apoptosis of GFs was noted in this experimental condition. Butyrate (> 2 mm) inhibited the expression of cdc2, cdc25C and cyclinB1 mRNAs and reduced the levels of Cdc2, Cdc25C and cyclinB1 proteins in GFs, as determined using RT‐PCR and western blotting, respectively. This toxic effect of butyrate was associated with the production of ROS.
Conclusion: These results suggest that butyrate generated by periodontal pathogens may be involved in the pathogenesis of periodontal diseases via the induction of ROS production and the impairment of cell growth, cell cycle progression and expression of cell cycle‐related genes in GFs. These events are important in the initiation and prolongation of inflammatory processes in periodontal diseases.
Aim
Food allergy is common in children and adults, and could be potentially fatal in minor groups. It is important for physicians to identify the prevalence of food allergies and to recognise common ...food allergens to make precise diagnosis and choose correct therapeutic approaches.
Methods
We used a nationwide, cross‐sectional, random questionnaire‐based survey to estimate the self‐reported and expert‐screened prevalence of food allergies and to identify the common food allergens in Taiwan. In this study, the perceptional diagnosis of food allergies was screened by physicians according to descriptions of convincing symptoms and medical recordings; in the meantime, non‐allergic adverse reactions to foods, including food intolerance or food avoidance, were clarified.
Results
A total of 30 018 individuals who met the inclusion criteria was evaluated, and 6.95% of them were diagnosed as victims of food allergies. The prevalence was 3.44% in children under 3 years of age, 7.65% in children aged 4–18 years and 6.40% in adults respectively. About 77.33% of the food allergy population had experienced recurrent allergic attacks. Systemic reactions happened about 4.89% in food allergies group. The most commonly reported food allergen in Taiwan is seafood, including shrimp, crab, fish and mollusc. In addition, mango, milk, peanuts and eggs were also important food allergens in the general population; while milk, shellfish, peanuts and eggs were common in children.
Conclusions
Less than 10% of the Taiwan population suffers from food allergy with different allergic symptoms to variable food allergens in different age groups.
A nickel foam-supported Ni(OH)2/NiOOH electrode, synthesized in-situ at a specific electrode overpotential, was used to study the oxidation of ammonia in aqueous solution. Results of voltammetric ...analysis showed the formal potential of Ni(OH)2/NiOOH transition at +0.6 V (vs. Hg/HgO, pH 11) at which the current profile was improved by electron transfers of NH3 in the electrolyte. Selectivity of NH3 conversion to NO3− and N2 was evaluated by batch constant current experiments. Electrochemical parameters, including solution pH (6–12), temperature (20–40 °C), current density (0.2–3 mA cm−2), and initial NH3-N concentration (20–450 mg-L−1), that may affect ammonia oxidation toward nitrogen selectivity were studied. At constant current density of 1.5 mA cm−2A, ammonia removal reached 98.5% and NO3− was the major product at initial NH3-N concentration of 50 mg-L−1 in 7 h. By contrast, N2 evolution dominated at low current density (<1 mA cm−2) and high initial NH3-N concentration (i.e., >100 mg-L−1). A surface steady-state approach, with NH3 deprotonation as the rate-limiting step, provided the reaction pathways of NH3 conversion to molecular nitrogen byproduct.
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•The NiOOH@Ni-electrode was capable of directly oxidizing NH3 to NO3− and N2.•NH3 augmented the anodic current and enhanced the oxidation of Ni(0) to NiOOH.•Increasing initial NH3 concentration improved the transfer coefficient and ammonia oxidation.•Current density and initial ammonia concentration governed nitrogen selectivity.
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