Miracle-dz/UniFAR-FTUs huggingface dataset:
Construct and criterion validity of the SF-12 health questionnaire in patients with acute myocardial infarction and unstable angina.

BACKGROUND The aim of the study was to determine the construct and criterion validity of the 12-item short-form questionnaire (SF-12) in coronary patients with either acute myocardial infarction or unstable angina in Spain. METHOD A total of 186 patients hospitalized with coronary heart disease have been studied. The construct validity has been analysed by means of the association between the SF-12v.1 and sociodemographic and clinical variables; and the criterion validity was tested by the correlations between 36-item short-form question (SF-36) and SF-12 summary scores. The equivalence between both health questionnaires was examined by means of the proportion of variance in the SF-36 physical and mental component summary (PCS-36 and MCS-36) scores explained by the 12 items adjusted by age and sex. RESULTS The validation result was as expected: female patients and those with poor education level, worse mental health, unstable angina, cardiovascular risk factor and co-morbidity obtained a lower score in the SF-12. The correlations between SF-36 and SF-12 summary scores were high. The equivalence between the SF-12 and SF-36 was good, because the models explained 87% of the variation in PCS-36 score and 93% of the variation in MCS-36. CONCLUSION The SF-12 is a valid tool in studies assessing health-related quality of life in coronary patients. The use of the SF-12 may be especially useful in patients where the clinical situation make difficult the application of the longer instrument.
Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability

Background: The effect of HDAC inhibitor kinetic properties on biological function is currently unknown. Results: The kinetic rate constants of HDAC inhibitors differentially affect histone acetylation, cell viability, and gene expression. Conclusion: Evaluating HDAC inhibitor properties using histone acetylation is not predictive of their function on cellular activity. Significance: Characterizing the biological effect of different HDAC inhibitors will help to evaluate their clinical utility. Histone deacetylases (HDACs) are critical in the control of gene expression, and dysregulation of their activity has been implicated in a broad range of diseases, including cancer, cardiovascular, and neurological diseases. HDAC inhibitors (HDACi) employing different zinc chelating functionalities such as hydroxamic acids and benzamides have shown promising results in cancer therapy. Although it has also been suggested that HDACi with increased isozyme selectivity and potency may broaden their clinical utility and minimize side effects, the translation of this idea to the clinic remains to be investigated. Moreover, a detailed understanding of how HDACi with different pharmacological properties affect biological functions in vitro and in vivo is still missing. Here, we show that a panel of benzamide-containing HDACi are slow tight-binding inhibitors with long residence times unlike the hydroxamate-containing HDACi vorinostat and trichostatin-A. Characterization of changes in H2BK5 and H4K14 acetylation following HDACi treatment in the neuroblastoma cell line SH-SY5Y revealed that the timing and magnitude of histone acetylation mirrored both the association and dissociation kinetic rates of the inhibitors. In contrast, cell viability and microarray gene expression analysis indicated that cell death induction and changes in transcriptional regulation do not correlate with the dissociation kinetic rates of the HDACi. Therefore, our study suggests that determining how the selective and kinetic inhibition properties of HDACi affect cell function will help to evaluate their therapeutic utility.
The Role of Web Interviews as Part of a National Travel Survey

Abstract Purpose — The paper is analysing the effect of adding a web survey to a traditional telephone-based national travel survey by asking the respondents to check in on the web and answer the questions there (Computer Assisted Web Interview, CAWI). If they are not participating by web they are as usual called by telephone (Computer Assisted Telephone Interview, CATI). Design/methodology/approach — Multivariate regression analyses are used to analyse the difference in response rates by the two media and to analyse if respondents' answering by the two media have different travel patterns. Findings — The analyses show that web interviews are saving money, even though a more intensive post-processing is necessary. The analyses seem to show that the CAWI is resulting in a more careful answering which results in more trips reported. A CAWI is increasing the participation of children in the survey and of highly educated. And it is offering a higher flexibility to answer after a couple of days off. The CATI is on the other hand more useful for the elderly. In addition, the CATI survey proved to be more useful for busy people and people not willing to participate in a survey at all. Young people and people with low resources who are difficult to reach by telephone are neither met on the web. Most of the differences in the response shares can be compensated by a weighting procedure. However, not all seems to be possible to compensate for. An effort to increase the number participating in the CAWI survey might increase the quality of the survey in general. Originality/value of paper — In many countries authorities are considering how to reduce the cost of their national travel surveys. The value of the paper is to show that a combination of a CAWI and a CATI could be a good solution. Furthermore, it shows that the mixed mode could improve a CATI and therefore be the reason in itself to change methodology.
Brief interventions targeting personality risk factors for adolescent substance misuse reduce depression, panic and risk-taking behaviours

Background: Personality-targeted cognitive-behavioural interventions have been proven to be effective in reducing alcohol-related behaviours in adolescents. Aims: As these interventions target personality traits linked to risk for non-addictive psychopathology, the aim of this study is to examine the extent to which this approach can also prevent the onset or reduce relevant psychological problems in youth. Method: Participants aged 13 – 16 years (n = 423) were randomly assigned to either a personality matched cognitive-behavioural intervention or a no-intervention control. The personality matched interventions targeted four personality risk factors: negative thinking (NT), anxiety sensitivity (AS), impulsivity (IMP), and sensation seeking (SS). Results: Baseline and follow-up data were obtained on depression scores, panic attacks, and reckless behaviour. Results showed a moderate effect of the NT intervention on depression scores, and a similar effect of the AS intervention on panic attack and truancy (i.e., school avoidance). A small but significant intervention effect was found for shoplifting for the entire sample, as well as a moderate intervention effect on this outcome for the IMP intervention group. Conclusions: These intervention effects indicate that personality-targeted interventions designed to prevent alcohol misuse, can concurrently reduce other relevant psychological problems in youth.
Control of Voltage-gated Potassium Channel Kv2.2 Expression by Pyruvate-Isocitrate Cycling Regulates Glucose-stimulated Insulin Secretion*

Background: Pyruvate-isocitrate cycling is involved in control of glucose-stimulated insulin secretion (GSIS), but the underlying mechanisms are unknown. Results: Pyruvate-isocitrate cycling controls expression of the voltage-gated potassium channel family member Kv2.2 in islet cells. Conclusion: Pyruvate-isocitrate cycling maintains Kv2.2 expression, allowing it to serve as a negative regulator of Kv channel activity. Significance: Kv2.2 is a potential new target for reversing β-cell dysfunction of type 2 diabetes. Recent studies have shown that the pyruvate-isocitrate cycling pathway, involving the mitochondrial citrate/isocitrate carrier and the cytosolic NADP-dependent isocitrate dehydrogenase (ICDc), is involved in control of glucose-stimulated insulin secretion (GSIS). Here we demonstrate that pyruvate-isocitrate cycling regulates expression of the voltage-gated potassium channel family member Kv2.2 in islet β-cells. siRNA-mediated suppression of ICDc, citrate/isocitrate carrier, or Kv2.2 expression impaired GSIS, and the effect of ICDc knockdown was rescued by re-expression of Kv2.2. Moreover, chronic exposure of β-cells to elevated fatty acids, which impairs GSIS, resulted in decreased expression of Kv2.2. Surprisingly, knockdown of ICDc or Kv2.2 increased rather than decreased outward K+ current in the 832/13 β-cell line. Immunoprecipitation studies demonstrated interaction of Kv2.1 and Kv2.2, and co-overexpression of the two channels reduced outward K+ current compared with overexpression of Kv2.1 alone. Also, siRNA-mediated knockdown of ICDc enhanced the suppressive effect of the Kv2.1-selective inhibitor stromatoxin1 on K+ currents. Our data support a model in which a key function of the pyruvate-isocitrate cycle is to maintain levels of Kv2.2 expression sufficient to allow it to serve as a negative regulator of Kv channel activity.
Variations in bulk leaf carbon isotope discrimination, growth and related leaf traits among three Populus nigra L. populations.

The ongoing global change could be an additional threat to the establishment and the long-term survival of Populus nigra L. , an emblematic European riparian species. With the general aim of gaining insights into the adaptive potential of this species, we (i) quantified variations within and among three French P. nigra populations for key physiological attributes, i.e., water-use efficiency (assessed from bulk leaf carbon isotope discrimination, Δ(13)C), growth performance and related leaf traits, (ii) examined genotype and population by environment interactions, and (iii) explored the relationship between Δ(13)C and growth. Thirty genotypes were sampled in each of three naturally established populations and grown in two different sites, Orléans (ORL) and Guémené-Penfao (GMN). In ORL, two similar plots were established and different watering regimes were applied in order to test for the drought response. Significant variations were observed for all traits within and among populations irrespective of site and watering. Trait variation was larger within than among populations. The effect of drought was neither genotype- nor population-dependent, contrary to the effect of site. The population ranking was maintained in all sites and watering regimes for the two most complex traits: Δ(13)C and growth. Moreover, these two traits were unrelated, which indicates that (i) water-use efficiency and growth are largely uncoupled in this species, and (ii) the environmental factors driving genetic structuration for Δ(13)C and growth act independently. The large variations found within populations combined with the consistent differences among populations suggest a large adaptive potential for P. nigra.
Two Distinct Determinants of Ligand Specificity in T1R1/T1R3 (the Umami Taste Receptor)

Background: T1R1/T1R3 exhibits species-dependent differences in ligand specificity. Results: The ligand specificity is dependent on a combination of amino acid selectivity at the orthosteric site and receptor activity modulation at the non-orthosteric site. Conclusion: The molecular mechanism underlying the amino acid recognition of T1R1/T1R3 has been elucidated. Significance: This study provides new insights into the molecular mechanisms of the l-Glu-specific response in human T1R1/T1R3. Umami taste perception in mammals is mediated by a heteromeric complex of two G-protein-coupled receptors, T1R1 and T1R3. T1R1/T1R3 exhibits species-dependent differences in ligand specificity; human T1R1/T1R3 specifically responds to l-Glu, whereas mouse T1R1/T1R3 responds more strongly to other l-amino acids than to l-Glu. The mechanism underlying this species difference remains unknown. In this study we analyzed chimeric human-mouse receptors and point mutants of T1R1/T1R3 and identified 12 key residues that modulate amino acid recognition in the human- and mouse-type responses in the extracellular Venus flytrap domain of T1R1. Molecular modeling revealed that the residues critical for human-type acidic amino acid recognition were located at the orthosteric ligand binding site. In contrast, all of the key residues for the mouse-type broad response were located at regions outside of both the orthosteric ligand binding site and the allosteric binding site for inosine-5′-monophosphate (IMP), a known natural umami taste enhancer. Site-directed mutagenesis demonstrated that the newly identified key residues for the mouse-type responses modulated receptor activity in a manner distinct from that of the allosteric modulation via IMP. Analyses of multiple point mutants suggested that the combination of two distinct determinants, amino acid selectivity at the orthosteric site and receptor activity modulation at the non-orthosteric sites, may mediate the ligand specificity of T1R1/T1R3. This hypothesis was supported by the results of studies using nonhuman primate T1R1 receptors. A complex molecular mechanism involving changes in the properties of both the orthosteric and non-orthosteric sites of T1R1 underlies the determination of ligand specificity in mammalian T1R1/T1R3.
Uremic Pruritus; Its Prevalence, Pathophysiology and Management

Pruritus is a nociceptive sensation transmitted centrally from the periphery by the unmyeli‐ nated, large, slowly conductive C fibers [1]. Pruritus is the dominant symptom of skin disease and a frequent manifestation of systemic disease. Of all of the systemic disorders, uremia is certainly the most important cause of pruritus [2]. The association between uremia and pruritus was first reported more than a century ago. Patients with severe chronic renal failure may be predisposed to the development of xerosis, hyperpigmentation, uremic roseola, calcinosis cutis, acquired perforating dermatosis, bullous dermatosis of hemodialysis, half and half nails and pruritus [3,4]. However, pruritus is often the most difficult to manage [5] and also related to mortality of end-stage renal disease (ESRD) patients. Aside from kidney transplantation, which is the only definitive treatment, therapeutic approaches for the treatment of pruritus have largely been empirical. The main goal of therapy remains to minimize the severity of pruritus and improve the quality of life, especially among those who are not transplantation candidates or are waiting for surgery.
Interacting effects of elevated CO2 and weather variability on photosynthesis of mature boreal Norway spruce agree with biochemical model predictions.

According to well-known biochemical and biophysical mechanisms, the stimulation of C(3) photosynthesis by elevated atmospheric CO(2) concentration ([CO(2)]) is strongly modified by changes in temperature and radiation. In order to investigate whether a static parameterization of the commonly used Farquhar et al. model of photosynthesis (i.e., without CO(2)-induced seasonal or thermal acclimation of photosynthetic capacity) can accurately predict these interactions in mature boreal Norway spruce (Picea abies (L.) Karst. ) during the frost-free part of the growing season, shoot gas exchange was continuously measured on trees during their second/third year of exposure to ambient or doubled [CO(2)] inside whole-tree chambers. The relative CO(2)-induced enhancement of net photosynthesis (A(n)) at a given temperature remained stable over the study period, but increased strongly with temperature and radiation, in agreement with predictions by the model. Light-saturated A(n) (+67% at 20 °C), dark respiration (+36%) and intercellular to ambient [CO(2)] ratio (c(i)/c(a); +27%) were significantly increased by CO(2) treatment. Stomatal conductance (g(s)) was not significantly affected. Our results demonstrate that the Farquhar et al. model of photosynthesis has the capability to predict interactions between [CO(2)] and seasonal weather variability on A(n) in Norway spruce during the non-frost growing season without accounting for CO(2)-induced seasonal and/or thermal photosynthetic acclimation. However, stomatal model assumptions of reduced g(s) and constant c(i)/c(a) under rising atmospheric [CO(2)] did not hold.
C-reactive protein point of care testing and physician communication skills training for lower respiratory tract infections in general practice: economic evaluation of a cluster randomized trial.

RATIONALE, AIMS AND OBJECTIVES An economic evaluation of general practitioner (GP) use of C-reactive protein (CRP) point of care test, GP communication skills training, and both GP use of CRP and communication skills training on antibiotic use for lower respiratory tract infections (LRTIs) in general practice. METHODS Cost-effectiveness analysis with a time horizon of 28 days alongside a factorial, cluster randomized trial in 431 patients with LRTIs recruited by 40 GPs. INTERVENTIONS usual care (control group), GP use of CRP point of care test, GP communication skills training, and both CRP use and communication skills training. MAIN OUTCOME MEASURE health care costs. Cost-effectiveness, using the primary outcome measure antibiotic prescribing at index consultation, was assessed by incremental cost-effectiveness ratios (ICER). To adjust for skewed data and clustering, we used non-parametric bootstrapping re-sampling to derive percentile intervals for the mean difference in total costs and the mean difference in effectiveness between the groups. Various implementation scenarios according to GP preference were modelled with corresponding net monetary benefit (NMB) curves based on a given willingness-to-pay (λ) for a 1% lower antibiotic prescribing rate. RESULTS The total mean cost per patient in the usual care group was €35.96 with antibiotic prescribing of 68%, €37.58 per patient managed by GPs using CRP tests (antibiotic prescribing 39%, ICER €5.79), €25.61 per patient managed by GPs trained in enhanced communication skills (antibiotic prescribing 33%, dominant) and €37.78 per patient managed by GPs using both interventions (antibiotic prescribing 23%, ICER €4.15). The interventions are cost-effective in any combination (yielding NMB at no willingness-to-pay), taking into account GPs' preferences where at least 15% of GPs chose to implement the communication skills training. CONCLUSIONS The two strategies, both singly and combined, are cost-effective interventions to reduce antibiotic prescribing for LRTI, at no, or low willingness-to-pay. Taking GP preferences into account will optimize investment in strategies to reduce antibiotic prescribing for LRTI.
The RNA-binding Protein Fused in Sarcoma (FUS) Functions Downstream of Poly(ADP-ribose) Polymerase (PARP) in Response to DNA Damage*

Background: FUS has been implicated in the DNA damage response; however, the mechanisms are unknown. Results: FUS recruitment to DNA lesions is PARP-dependent. Depletion of FUS disrupts DNA repair. Conclusion: FUS functions downstream of PARP and promotes double-strand break repair. Significance: This work identifies FUS as a novel factor at DNA lesions and furthers our understanding of RNA-binding proteins in maintaining genomic stability. The list of factors that participate in the DNA damage response to maintain genomic stability has expanded significantly to include a role for proteins involved in RNA processing. Here, we provide evidence that the RNA-binding protein fused in sarcoma/translocated in liposarcoma (FUS) is a novel component of the DNA damage response. We demonstrate that FUS is rapidly recruited to sites of laser-induced DNA double-strand breaks (DSBs) in a manner that requires poly(ADP-ribose) (PAR) polymerase activity, but is independent of ataxia-telangiectasia mutated kinase function. FUS recruitment is mediated by the arginine/glycine-rich domains, which interact directly with PAR. In addition, we identify a role for the prion-like domain in promoting accumulation of FUS at sites of DNA damage. Finally, depletion of FUS diminished DSB repair through both homologous recombination and nonhomologous end-joining, implicating FUS as an upstream participant in both pathways. These results identify FUS as a new factor in the immediate response to DSBs that functions downstream of PAR polymerase to preserve genomic integrity.
Elevated Protein Kinase D3 (PKD3) Expression Supports Proliferation of Triple-negative Breast Cancer Cells and Contributes to mTORC1-S6K1 Pathway Activation*

Background: TNBC is an aggressive breast cancer subtype for which effective targeted therapies are still lacking. Results: PKD3 is increased in TNBC tissues and cells and contributes to mTORC1-S6K1 activation at endolysosomal membranes. Conclusion: PKD3 in TNBC cells is required for endolysosomal homeostasis and cell proliferation. Significance: PKD3 may represent a potential drug target in TNBC. Here, we show that the expression of the Golgi-localized serine-threonine kinase protein kinase D3 (PKD3) is elevated in triple-negative breast cancer (TNBC). Using an antibody array, we identified PKD3 to trigger the activation of S6 kinase 1 (S6K1), a main downstream target of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Accordingly, PKD3 knockdown in TNBC cells led to reduced S6K1 phosphorylation, which was associated with impaired activation of mTORC1 at endolysosomal membranes, the accumulation of the mannose 6-phosphate receptor in and the recruitment of the autophagy marker light chain 3 to enlarged acidic vesicles. We further show that PKD3 depletion strongly inhibited cell spreading and proliferation of TNBC cells, identifying this kinase as a potential novel molecular therapeutic target in TNBC. Together, our data suggest that PKD3 in TNBC cells provides a molecular connection between the Golgi and endolysosomal compartments to enhance proliferative mTORC1-S6K1 signaling.
Perceived risk of using novel psychoactive substances in school students: lower in users compared to non-users

Abstract Background: There has been an increase in the availability of novel psychoactive substances (NPS) over the last decade. The 2013 US Monitoring the Future study suggested that the perceived risk of NPS use in US students was greater than for classical recreational drugs. This survey was undertaken to determine the perceived risk of NPS in adolescents in UK education. Methods: Questionnaire survey of 917 students (15–18 years) collected the details of whether: (i) they had heard of NPS; (ii) they had taken an NPS; and (iii) their perceived risk of NPS use. Results: Five-hundred and fifty-four (57.9%) had heard of NPS and 75 (8.2%) had previously used an NPS. The mean ± standard deviation perceived risk of using an NPS was 7.32 ± 2.07 (95% CI 7.18–7.46), where 1 is “completely safe” and 10 is “not safe at all”; those who had previously used an NPS had a lower perceived risk [6.11 ± 2.17 (95% CI 5.60–6.62)] compared to those who had not previously used an NPS [7.46 ± 2.00 (95% CI 7.31–7.61) (p < 0.0001)]. Discussion: Further work is needed to determine whether the lower perceived risk relates to having previously used NPS or whether those who perceive them as low risk are more likely to use NPS. It is important to determine whether this perceived risk is same across all NPS to inform the development of harm minimisation educational strategies.