Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonadherence with mood stabilizers: prevalence and predictors.

BACKGROUND The prevalence of nonadherence with mood stabilizers ranges from about 18% to 52%. Only 1% of publications on mood stabilizers address this issue. This study aimed to explore the prevalence and predictors of nonadherence in a cohort of individuals with affective disorders receiving long-term treatment with mood stabilizers. METHOD Subjects receiving lithium, carbamazepine, and/or valproate were identified from biochemistry laboratory data. Ninety-eight of these subjects had major depressive disorder (N = 20) or bipolar disorder (N = 78) (DSM-IV) and gave informed consent to participate in a structured clinical interview to assess their medication adherence and the factors that influenced it. RESULTS Just under 50% of subjects (46/98) acknowledged some degree of medication nonadherence in the previous 2 years, and 32% (29/92) reported only partial adherence in the last month (missing 30% or more of their prescribed medication). Backward stepwise logistic regression demonstrated that partially adherent subjects were best distinguished from adherent subjects by a more frequent past history of nonadherence, denial of severity of illness, and greater duration of being prescribed a mood stabilizer. CONCLUSION Rates of mood stabilizer nonadherence are high. Attitudes and behaviors are better predictors of nonadherence than side effects from medication. Clinicians need to inquire routinely about problems with adherence.
Impact of a cleaners' strike on compensation claims for asthma among teachers in Ontario.

BACKGROUND A review of Workplace Safety and Insurance Board (WSIB) claims in Ontario from 1998 to 2002 showed an unusual spike in the number of claims accepted for work-exacerbated asthma (WEA) in April 2001. OBJECTIVE To identify the cause for the spike in the number of WSIB claims for WEA in April 2001. METHODS File reviews were performed to identify the occupations of workers with claims accepted for WEA in April 2001 compared with claims during March and May 2001, and during the same months in 2000 and 2002. RESULTS In April 2001, there were 61 accepted WEA claims; the most common occupation was 'teacher'. In contrast, among educational workers, there was only one WEA claim in the previous month and one in the following month. From March to May in the preceding and following years, there were only four and two claims, respectively. The most frequently implicated causative agents were dust and dirt exposure, which were responsible for 98% of claims; the mean (± SD) number of lost workdays was 6.5±10. The only identified environmental change associated with this spike was a cleaners' strike at all elementary and high schools in the Toronto District School Board in Ontario, which started on March 31, 2001 and ended on May 1, 2001. CONCLUSION [corrected] The spike in accepted WEA claims in Ontario in April 2001 was temporally associated with a strike by Toronto District School Board cleaners, suggesting acute symptomatic effects of poor workplace (school) maintenance on asthmatic employees. The WSIB database was sufficiently sensitive to capture this phenomenon.
Labour Market Resilience- Comparative Evidence From Romanian Counties

In economics, the concept of resilience illustrates the adaptability capacity of a system after an external shock. The goal of the empirical analysis presented in this paper is to investigate the labor market resilience of Romanian Counties relative to the economic crisis whose negative effects occurred since 2009. The counties are compared in terms of resistance or sensitivity to the shock, speed of recovery after the shock. These dimensions were assessed by means of statistical analysis of employment and unemployment rate evolution. With respect to the factors that could influence the trajectory of the system after a recessionary shock, this study discusses the correlation between different types of resilience and economic diversification.
Myristoylation of cGMP-dependent Protein Kinase Dictates Isoform Specificity for Serotonin Transporter Regulation*

By transporting serotonin (5-HT) into neurons and other cells, serotonin transporter (SERT) modulates the action of 5-HT at cell surface receptors. SERT itself is modulated by several processes, including the cGMP signaling pathway. Activation of SERT by cGMP requires the cGMP-dependent protein kinase (PKG). Here we show that in HeLa cells lacking endogenous PKG, expression of PKGIα or PKGIβ was required for 8-bromoguanosine-3′,5′-cyclic monophosphate (8-Br-cGMP) to stimulate SERT phosphorylation and 5-HT influx. Catalytically inactive PKG mutants and wild-type PKGII did not support this stimulation. However, a mutant PKGII (G2A) that was not myristoylated substituted for functional PKGI, suggesting that myristoylation and subsequent membrane association blocked productive interaction with SERT. PKG also influenced SERT expression and localization. PKGI isoforms increased total and cell surface SERT levels, and PKGII decreased cell surface SERT without altering total expression. Remarkably, these changes did not require 8-Br-cGMP or functional kinase activity and were also observed with a SERT mutant resistant to activation by PKG. Both PKGIα and PKGIβ formed detergent-stable complexes with SERT, and this association did not require catalytic activity. The nonmyristoylated PKGII G2A mutant stimulated SERT expression similar to PKGI isoforms. These results suggest multiple mechanisms by which PKG can modulate SERT and demonstrate that the functional difference between PKG isoforms results from myristoylation of PKGII.
Quantitative analysis of tumor vascular structure after drug treatment

This paper reports a method that aims to quantify the changes of tumour vascular structure as a result of drug treatment. The measures we have investigated to date include: vessel radii, inter-branch lengths, tortuosity and branch angles. We show that the distribution of vessel radii is better modelled as a gamma distribution as opposed to the log-normal distribution asserted by other researchers. We propose a new metric based on multiple linear regression to measure vascular tortuosity. We report statistical analyses which confirm that (as expected), at different significance levels, all the drugs we have tested (FTI, Iressa, Nelfinavir and PI-103) have positive effects in improving a tumour's vascular network. In each case, the changes are quantified.
Differential inactivation of Escherichia coli membrane dehydrogenases by a myeloperoxidase-mediated antimicrobial system.

Neutrophil myeloperoxidase, hydrogen peroxide, and chloride constitute a potent antimicrobial system with multiple effects on microbial cytoplasmic membranes. Among these is inhibition of succinate-dependent respiration mediated, principally, through inactivation of succinate dehydrogenase. Succinate-dependent respiration is inhibited at rates that correlate with loss of microbial viability, suggesting that loss of respiration might contribute to the microbicidal event. Because respiration in Escherichia coli can be mediated by dehydrogenases other than succinate dehydrogenase, the effects of the myeloperoxidase system on other membrane dehydrogenases were evaluated by histochemical activity stains of electrophoretically separated membrane proteins. Two bands of succinate dehydrogenase activity proved the most susceptible to inactivation with complete loss of staining activity within 20 min, under the conditions employed. A group with intermediate susceptibility, consisting of lactate, malate, glycerol-3-phosphate, and dihydroorotate dehydrogenases as well as three bands of glucose-6-phosphate dehydrogenase, was almost completely inactivated within 30 min. The relatively resistant group, including the dehydrogenases for glutamate, NADH, and NADPH and the remaining bands of glucose-6-phosphate dehydrogenase, retained substantial amounts of diaphorase activity for up to 60 min of incubation with the myeloperoxidase system. The differential effects of myeloperoxidase on dehydrogenase inactivation could not be correlated with published enzyme contents of flavin or iron-sulfur centers, potential targets of myeloperoxidase-derived oxidants. Despite the relative resistance of NADH dehydrogenase/diaphorase activity to myeloperoxidase-mediated inactivation, electron transport particles prepared from E. coli incubated for 20 min with the myeloperoxidase system lost 55% of their NADH oxidase activity. (ABSTRACT TRUNCATED AT 250 WORDS)
Are European Stock Markets Influencing Latin American Stock Markets

In this study, we examine the response of Latin American stock markets to movements in European stock markets. Our results vary depending on the openness of the country in terms of international trade. We find evidence that Latin American stock markets are affected by Spanish stock market. Additionally, during the second and third-periods (1995 to 1998 and 1999 to 2004) Spain appears to have much stronger ties (such as more trade) with Brazil and Chile, and this might explain why Brazil and Chile are affected from Spain and not from the other European markets. This study uncovers two important findings. First, Spain has an effect on Latin American markets but these responses are not homogeneous across markets. Second, the magnitude of Spain's influence is different in each of the three sub-periods under study.
A new algorithm for haplotype‐based association analysis: the Stochastic‐EM algorithm

It is now widely accepted that haplotypic information can be of great interest for investigating the role of a candidate gene in the etiology of complex diseases. In the absence of family data, haplotypes cannot be deduced from genotypes, except for individuals who are homozygous at all loci or heterozygous at only one site. Statistical methodologies are therefore required for inferring haplotypes from genotypic data and testing their association with a phenotype of interest. Two maximum likelihood algorithms are often used in the context of haplotype‐based association studies, the Newton‐Raphson (NR) and the Expectation‐Maximisation (EM) algorithms. In order to circumvent the limitations of both algorithms, including convergence to local minima and saddle points, we here described how a stochastic version of the EM algorithm, referred to as SEM, could be used for testing haplotype‐phenotype association. Statistical properties of the SEM algorithm were investigated through a simulation study for a large range of practical situations, including small/large samples and rare/frequent haplotypes, and results were compared to those obtained by use of the standard NR algorithm. Our simulation study indicated that the SEM algorithm provides results similar to those of the NR algorithm, making the SEM algorithm of great interest for haplotype‐based association analysis, especially when the number of polymorphisms is quite large.
MR imaging of postischemic neuronal death in the substantia nigra and thalamus following middle cerebral artery occlusion in rats

The goal of this study was to investigate apparent diffusion coefficient (ADC) and T2 relaxation time (T2) in the substantia nigra and thalamus after middle cerebral artery occlusion in rats. In the substantia nigra ipsilateral to infarct, ADC was significantly lower and T2 was significantly higher on the third and fourth days, but they did not change significantly on the first, second, eighth and 15th days. In the ipsilateral thalamus, ADC and T2 did not change significantly between the first and fourth days, but were significantly lower on the eighth and 15th days. This combination of MR findings suggested that secondary degeneration in the thalamus was different from that in the substantia nigra. Copyright © 2003 John Wiley & Sons, Ltd.
The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype.

BACKGROUND Most of the previous studies that explored the molecular basis of raltegravir resistance were conducted studying the HIV-1 B subtype. It has been shown that the CRF02_AG subtype in relation to its natural integrase (IN) sequence could develop different genetic pathways associated with raltegravir resistance. The aim of this study was to explore resistance pathways preferably used by CRF02_AG viruses compared with subtype B. METHODS Twenty-five HIV-1 CRF02_AG-infected patients failing a raltegravir-containing regimen were studied. IN gene sequences were examined for the presence of previously described IN inhibitor (raltegravir, elvitegravir, dolutegravir and MK-2048) resistance mutations at 20 amino acid positions. RESULTS Among the 25 studied patients, 7 showed viruses harbouring major raltegravir resistance mutations mainly associated with the 155 genetic pathways and 18 showed viruses harbouring none of them; however, for 1 patient, we found a 118R mutation, associated with MK-2048 in vitro resistance, in a 74M background. For this patient, the phenotypic analysis showed that addition of only the G118R mutation conferred a high level of resistance to raltegravir (fold change = 25.5) and elvitegravir (fold change = 9.2). CONCLUSIONS This study confirmed that mutation pathways for raltegravir resistance could be different between the two subtypes CRF02_AG and B with a preferential use of the 155 mutation in non-B subtypes. A new genetic pathway associated with raltegravir resistance, including the 118R mutation, has also been identified. This new genetic pathway, never described in subtype B, should be further evaluated for phenotypic susceptibility to dolutegravir and MK-2048.
Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease

Background: Little is known about Alzheimer disease at advanced ages, although its incidence continues to increase at least through the ninth decade of life. Objective: To examine the effects of age on the relationship between clinical dementia severity and neuropathologic hallmarks in a large sample spanning the full age range. Methods: The authors assessed 81 subjects during life for dementia severity, and examined their brains. They analyzed plaque and tangle burden, as well as the activities of the cholinergic marker enzymes acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), in relation to age at death and the clinical severity of dementia. Results: Dementia severity was strongly related to plaque and tangle burden in relatively young patients (aged <75 years), but this correlation diminished with age and disappeared in the ninth decade of life. Among the oldest patients studied, there was no difference in plaque and tangle load between the mild and severe dementia cases. This interaction (p < 0.0001 for plaque density) was not observed for the cholinergic markers ChAT and AChE. Conclusion: The nature or expression of Alzheimer disease may be different in severely demented older patients, who have equal cholinergic deficits but significantly lower plaque and tangle burden. If confirmed in a prospective study, these findings have diagnostic and therapeutic implications.
An immunotoxin with increased activity and homogeneity produced by reducing the number of lysine residues in recombinant Pseudomonas exotoxin.

Pseudomonas exotoxin A (PE) is a protein composed of 613 amino acids arranged into three major, and one minor, domains. Immunotoxins (ITs) containing PE38, a mutant form of PE which lacks the cell binding domain (Ia, amino acids 1-252) and 16 amino acids from domain Ib (amino acids 365-380), are extremely potent cytotoxic agents which can cause a complete regression of various human carcinomas grown in nude mice. However, these ITs are a mixture of several different chemical forms since the coupling between the antibody and the toxin may occur between either the light or heavy chain of the antibody and one of the four primary amino groups present on the truncated toxin. To modify the toxin with heterobifunctional crosslinking reagents only at specific sites, we replaced lysines 590 and 606 with glutamines and lysine 613 with arginine (PE38QQR). We also added two different peptide sequences, each containing a lysine residue, at the N-terminus of PE38. In one of these the sequence is ANLAEEAFK ("Lys" peptide), and in the other, the sequence is LQGTKLMAEE ("NLys" peptide). The mutant toxins were coupled using a thioether linkage to monoclonal antibody B3 which recognizes an antigen present in large amounts on many human cancers. PE38QQR-containing recombinant toxins can only be linked to an antibody through the N-terminal methionine or the lysine within the peptide. (ABSTRACT TRUNCATED AT 250 WORDS)
Asymmetric technological distance measure based on language model

ABSTRACT This article introduces a novel technological distance measure between companies based on their patent portfolios. We describe the technological position or characteristics of companies by applying the framework of language modelling technique in information retrieval on their patent portfolios. The proposed novel approach is an asymmetric measure and better captures the technological characteristic of a company and hence is a more accurate distance measure.
Additive and non-additive genetic architecture of two different-sized populations of Scabiosa canescens

Future adaptation to changes in the environment depends on the existence of additive genetic variances within populations. Recently, considerable attention has also been given to the non-additive component, which plays an important role in inbreeding depression and bottleneck situations. In this study, I used data from a North Carolina II crossing experiment, analysed with restricted maximum-likelihood methods, to estimate the additive and dominance genetic (co)variances for eight quantitative characters in two different-sized populations of Scabiosa canescens, a rare and threatened plant in Sweden. There was no evidence for genetic erosion in the small Hällestad population (≈25 individuals) relative to the large Åhus population (≈5000 individuals). In fact, slightly higher heritabilities were found in the Hällestad population. The additive genetic variance was statistically significant for all traits in both populations, but only a few additive covariances reached significance. The Hällestad population also had higher mean levels and more traits with significant dominance variance than the Åhus population. The variance attributable to maternal effects was too low to be considered significant. There was only a weak correspondence between heritabilities for each trait in the present study and previous estimates based on open-pollinated families of the same populations, but the mean heritability (over characters) was consistent between the studies.
A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease

The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC) to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors. Binding of an active-site inhibitor to the protease resulted in a conformational change of NS2B and led to significant SLC enhancement. Mutagenesis of key residues at an allosteric site abolished this induced conformational change and SLC enhancement. We also performed a virtual screen of NCI library compounds to identify allosteric inhibitors, followed by in vitro biochemical screening of the resultant candidates. Only three of these compounds, NSC135618, 260594, and 146771, significantly inhibited the protease of Dengue virus 2 (DENV2) in vitro, with IC50 values of 1.8 μM, 11.4 μM, and 4.8 μM, respectively. Among the three compounds, only NSC135618 significantly suppressed the SLC enhancement triggered by binding of active-site inhibitor in a dose-dependent manner, indicating that it inhibits the conformational change of NS2B. Results from virus titer reduction assays revealed that NSC135618 is a broad spectrum flavivirus protease inhibitor, and can significantly reduce titers of DENV2, Zika virus (ZIKV), West Nile virus (WNV), and Yellow fever virus (YFV) on A549 cells in vivo, with EC50 values in low micromolar range. In contrast, the cytotoxicity of NSC135618 is only moderate with CC50 of 48.8 μM on A549 cells. Moreover, NSC135618 inhibited ZIKV in human placental and neural progenitor cells relevant to ZIKV pathogenesis. Results from binding, kinetics, Western blot, mass spectrometry and mutagenesis experiments unambiguously demonstrated an allosteric mechanism for inhibition of the viral protease by NSC135618.
Relationship Between the Risk of Suffering a First-Time Noncontact ACL Injury and Geometry of the Femoral Notch and ACL

Background: The morphometric characteristics of the anterior cruciate ligament (ACL) and the femoral intercondylar notch within which it resides have been implicated as risk factors for injuries to this important stabilizer of the knee. Prior research has produced equivocal results with differing methodologies, and consequently, it is unclear how these characteristics affect the injury risk in male and female patients. Hypothesis: The morphometric characteristics of the ACL and femoral intercondylar notch are individually and independently associated with the risk of suffering a noncontact ACL injury, and these relationships are different in male and female patients. Study Design: Case-control study; Level of evidence, 3. Methods: Magnetic resonance imaging scans of the bilateral knees were obtained on 88 case-control pairs (27 male, 61 female) matched for age, sex, and participation on the same sports team. Patients had suffered a grade III, first-time, noncontact ACL tear. The femoral notch width at 4 locations, the thickness of the bony ridge at the anteromedial outlet of the femoral notch, the femoral notch volume, ACL volume, and ACL cross-sectional area were measured. Results: Multivariate analysis of combined data from male and female patients revealed that decreased ACL volume (odds ratio [OR], 0.829), decreased femoral notch width (OR, 0.700), and increased bony ridge thickness at the anteromedial outlet of the femoral notch (OR, 1.614) were significant independent predictors of an ACL injury. Separate analyses of male and female patients indicated that the femoral notch ridge may be more strongly associated with a risk in female patients, while ACL volume is more strongly associated with a risk in male patients. However, statistical analysis performed with an adjustment for body weight strengthened the association between ACL volume and the risk of injuries in female patients. Conclusion: Morphometric features of both the ACL and femoral notch combine to influence the risk of suffering a noncontact ACL injury. When included together in a multivariate model that adjusts for body weight, the effects of the morphometric measurements are similar in male and female patients. If body weight is not taken into consideration, ACL volume is not associated with a risk in female patients.