Miracle-dz/UniFAR-FTUs huggingface dataset:
Sensitivity of FRAMINGHAM, PROCAM and SCORE models in Turkish people with Type 2 diabetes: comparison of three cardiovascular risk calculations

Purpose: To determine the cardiovascular risk factors according to the Framingham, PROCAM and SCORE models, to evaluate the 10-year cardiovascular disease (CVD) risk factors, and to compare the suitability of different models in Turkish Type 2 diabetes patients. Methods: Risk factors and the 10-year CVD risk in 265 patients were evaluated using three risk models. Measurements included blood pressure, weight, height, waist and hip circumferences. Cholesterol, triglycerides, fasting and postprandial plasma glucose and HbA1c were measured. Low-, moderate- and high-risk groups were determined according to the three risk calculations. Results: Hypertension, obesity and no exercise, dyslipidemia and high HbA1c in women, and excessive cigarette/alcohol consumption, increased weight, dyslipidemia and high HbA1c in men were crucial. Men were in the moderate-risk group according to three risk models. Women were in the medium-risk group according to the Framingham and PROCAM risks and in the low-risk group according to the SCORE. Conclusion: Results estimating the 10-year CVD according to the three risk models were inconsistent. More sensitive CVD risk calculators are needed. Discussion and practice implications: Our results could guide diabetes specialists in identifying gender-specific risks and designing preventive interventions.
Clinical features and prognostic factors in adults with bacterial meningitis.

BACKGROUND We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis. METHODS From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively evaluated. All patients underwent a neurologic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable outcome were identified through logistic-regression analysis. RESULTS We evaluated 696 episodes of community-acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in mental status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. The mortality rate was higher among patients with pneumococcal meningitis than among those with meningococcal meningitis (30 percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count. CONCLUSIONS In adults presenting with community-acquired acute bacterial meningitis, the sensitivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae.
Membrane-anchored proteases in endothelial cell biology

Purpose of reviewThe endothelial cell plasma membrane is a metabolically active, dynamic, and fluid microenvironment where pericellular proteolysis plays a critical role. Membrane-anchored proteases may be expressed by endothelial cells as well as mural cells and leukocytes with distribution both inside and outside of the vascular system. Here, we will review the recent advances in our understanding of the direct and indirect roles of membrane-anchored proteases in vascular biology and the possible conservation of their extravascular functions in endothelial cell biology. Recent findingsMembrane-anchored proteases belonging to the serine or metalloprotease families contain amino-terminal or carboxy-terminal domains, which serve to tether their extracellular protease domains directly at the plasma membrane. This architecture enables protease function and substrate repertoire to be regulated through dynamic localization in distinct areas of the cell membrane. These proteases are proving to be key components of the cell machinery for regulating vascular permeability, generation of vasoactive peptides, receptor tyrosine kinase transactivation, extracellular matrix proteolysis, and angiogenesis. SummaryA complex picture of the interdependence between membrane-anchored protease localization and function is emerging that may provide a mechanism for precise coordination of extracellular signals and intracellular responses through communication with the cytoskeleton and with cellular signaling molecules.
A family-based genome-wide association study of chronic rhinosinusitis with nasal polyps implicates several genes in the disease pathogenesis

Background The pathogenesis of chronic rhinosinusitis with nasal polyps is largely unknown. Previous studies have given valuable information about genetic variants associated with this disease but much is still unexplained. Our goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study. Methods 427 patients (293 males and 134 females) with CRSwNP and 393 controls (175 males and 218 females) were recruited from several Swedish hospitals. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX). Analyses of pathway enrichment, gene expression levels and expression quantitative trait loci were then performed in turn. Results None of the analysed SNPs reached genome wide significant association of 5.0 x 10−8. Pathway analyses using our top 1000 markers with the most significant association p-values resulted in 138 target genes. A comparison between our target genes and gene expression data from the NCBI Gene Expression Omnibus database showed significant overlap for 36 of these genes. Comparisons with data from expression quantitative trait loci showed the most skewed allelic distributions in cases with chronic rhinosinusitis with nasal polyps compared with controls for the genes HLCS, HLA-DRA, BICD2, VSIR and SLC5A1. Conclusion Our study indicates that HLCS, HLA-DRA, BICD2, VSIR and SLC5A1 could be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. HLA-DRA has been associated with chronic rhinosinusitis with nasal polyps in previous studies and HLCS, BICD2, VSIR and SLC5A1 may be new targets for future research.
Optimal therapy of genotype‐2 chronic hepatitis C: what's new?

The standard of care (SOC) for the treatment of HCV genotype 2 (HCV‐2) was pegylated interferon alpha plus ribavirin (PEG‐IFN/RBV) at weight‐based doses for a response‐guided duration. The launches of sofosbuvir and daclatasvir in 2014 have resulted in new, better tolerated and shorter treatment. The combination of sofosbuvir and RBV for 12 weeks appears to be the new SOC in both European and American guidelines. The cost and therefore the access to this treatment remains a problem in many countries because of major economic constraints. For the few more difficult‐to‐treat patients, a combination of direct acting antivirals may be suitable and is being studied in ongoing trials. Because of rapidly changing treatment recommendations, the decision to treat HCV‐2 patients with currently approved drugs or to wait until a better option is available in the future, must be made according to the stage of fibrosis.
Minimizing the vulnerabilities of supply chain: A new framework for enhancing the resilience

Today's globalized, leaner and just-in-time supply chains are more vulnerable to natural and man-made disasters. The business environment is continuously varying which produces risk and to manage this risk, it requires resilience. This paper proposes a new framework for supply chain resilience that leverages existing knowledge and offers a better understanding of the available notion in literature. It incorporates flexibility, adaptability, collaboration, visibility and sustainability as the major pillars for resilient supply chains. This framework provides a new means to evaluate ‘supply chain fitness’ and also provides critical insights for decision making by minimizing the negative impact of unavoidable risk events. Thus it incorporates event readiness and provides an efficient response.
Fetal DNA hypermethylation in tight junction pathway is associated with neural tube defects: A genome-wide DNA methylation analysis

ABSTRACT Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2). Correlation analysis of differentially methylated CpG sites in fetal neural tissues and polycyclic aromatic hydrocarbons concentrations in fetal neural tissues and maternal serum was conducted. Differentially methylated CpG sites of neural tissues were further validated in fetal mice with NTDs induced by benzo(a)pyrene given to pregnant mice. Differentially hypermethylated CpG sites in neural tissues from 17 genes and 6 pathways were identified in stage 1. Subsequently, differentially hypermethylated CpG sites in neural tissues from 6 genes (BDKRB2, CTNNA1, CYFIP2, MMP7, MYH2, and TIAM2) were confirmed in stage 2. Correlation analysis showed that methylated CpG sites in CTNNA1 and MYH2 from NTD cases were positively correlated to polycyclic aromatic hydrocarbon level in fetal neural tissues and maternal serum. The correlation was confirmed in NTD-affected fetal mice that were exposed to benzo(a)pyrene in utero. In conclusion, hypermethylation of the CTNNA1 and MYH2 genes in tight junction pathway is associated with the risk for NTDs, and the DNA methylation aberration may be caused by exposure to benzo(a)pyrene.
Do We Need to Recover T + 0 Trading? Evidence from the Chinese Stock Market

ABSTRACT In this study, we examine the effects of a change in the day trading rule from T + 0 to T + 1 for B-shares in Chinese stock market. We remove the influence of adjusting stamp taxes, which happened around the change in the day trading rule. We also apply the difference-in-difference method to remove the effects of other factors that may influence the market quality during the same period. The results show that a change in the day trading rule from T + 0 to T + 1 will increase price volatility, raise bid-ask spread, reduce the trading activity, and lower the price efficiency.
Clinical, laboratory and molecular characteristics of children with Familial Mediterranean Fever‐associated vasculitis

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurrent self‐limited attacks of fever accompanied by peritonitis, pleuritis and arthritis. Approximately 5% of individuals with FMF have been reported to have Henoch‐Schonlein purpura (HSP) and about 1% have polyarteritis nodosa (PAN). Protracted febrile myalgia is another vasculitis‐associated clinical entity among patients with FMF. Recently, the gene responsible for FMF, MEFV, has been cloned and four missense mutations (M680I, M694V, V726A and M694I) have been described. In this report, we present clinical and laboratory findings and mutation results of 23 children with FMF‐associated vasculitis. HSP, PAN and protracted febrile attacks have been diagnosed in 11, 2 and 10 children, respectively. Mutation analysis shows that 3 children are homozygotes for the M694V mutation and 11 are compound heterozygotes for 2 of the studied mutations. M694V/V726A mutations were identified in 8, M694V/M694I in 2 and M680I/M694V in 1 of these children. In six children only one mutation was found and in three none of the studied mutations were identified. This study confirms that most children with FMF‐associated vasculitis have identifiable mutations in the MEFV gene. Environmental and/or other genetic factors are possibly involved in the pathogenesis of vasculitis in FMF; elucidation of these mechanisms will help to understand pathogenesis of childhood vasculitides. Children, Familial Mediterranean Fever, MEFV mutations, vasculitis
Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes

Abstract. Fyhrquist F, Tiitu A, Saijonmaa O, Forsblom C, Groop P‐H, on behalf of the FinnDiane Study Group (Minerva Institute for Medical Research; Helsinki University Central Hospital; and Folkhälsan Institute of Genetics; Helsinki, Finland). Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes. J Intern Med 2010; 267: 278–286.
Spontaneous mutation rate is a plastic trait associated with population density across domains of life

Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life.
Docking of combinatorial peptide libraries into a broadly cross‐reactive human IgM

A monoclonal IgM cryoglobulin with diverse binding behavior was isolated from a patient (Mez) with Waldenström's macroglobulinemia. It gave very high titers in the binding of combinatorially synthesized libraries of peptides ranging in size from two to eight residues. The crystal structure of Mez Fv revealed that the binding site was divided into two cavities of unequal volumes with dimensions and chemical properties that were compatible with the binding of peptides. Access to this unique combination of structural information and peptide binding data led us to carry out Mez‐peptide docking simulations to gain insight into the Mez binding propensities. In the present article, the results for docking of five peptide libraries are combined with discussions of the methods and approximations involved in the docking process. We analyze the origins of peptide binding affinity for Mez IgM in terms of its cross‐reactivity and its structural preferences. Copyright © 2001 John Wiley & Sons, Ltd.
The Incidence of Injury in Texas High School Basketball

Recent publications have reported differences in the incidence, rate, risk, and type of sports injury among men and women. We undertook a prospective study to determine the incidence of injury among high school basketball players and to examine the differences in injury type, incidence, rate, and risk between male and female athletes. During a single basketball season, an injury survey of girls' varsity teams at 100 class 4A and 5A high schools in Texas was conducted. These data were previously reported. We surveyed the same 100 high schools during a subsequent season to gather injury data from the boys' varsity teams. The athletic trainer collected data on each reportable injury and reported the data weekly to the University Interscholastic League. A reportable injury was defined as one that occurred during a practice or a game, resulted in missed practice or game time, required physician consultation, or involved the head or the face. The boys' and girls' data were compared and statistically analyzed. The rate of injury was 0.56 among the boys and 0.49 among the girls. The risk of injury per hour of exposure was not significantly different between the two groups. In both groups, the most common injuries were sprains, and the most commonly injured area was the ankle, followed by the knee. Female athletes had a significantly higher rate of knee injuries including a 3.79 times greater risk of anterior cruciate ligament injuries. For both sexes, the risk of injury during a game was significantly higher than during practice.
Gametocyte maturation, exflagellation and fertilization in Parahaemoproteus (=Haemoproteus) velans (Coatney & Roudabush) (Haemosporidia: Haemoproteidae): an ultrastructural study.

SYNOPSIS. The structural changes in macro and microgametocytes of Parahaemoproteus velans following removal of infected blood from the avian host were studied in the light and electron microscope. Gametocytes of both sexes round up and soon escape from their host cells. Shortly thereafter they assume a dumbbell shape. The microgametocyte undergoes exflagellation forming 8 slender microgametes. During fertilization the entire microgamete appears to enter the female. The most striking ultrastructural change in the formation of the macrogamete is the condensation and enclosure by a membrane of abundant amophorus dense material seen in the cytoplasm of the immature gametocyte. Maturation of the microgametocyte begins prior to its escape from the host cell. Axonemes are present in the cytoplasm and nuclear reorganization occurs while the parasite is intracellular. Bundles of microtubules associated with condensed chromatin are found in the peripheral cytoplasm of maturing forms and apparently participate in the formation of small compact microgamete nuclei. Each of these filiform structures consists of a dense, centrally located nucleus and a single axoneme lying in flocculent cytoplasm. The nucleus and axoneme of the microgamete are seen free in the cytoplasm of a fertilized macrogamete.
Development of real time PCR to detect Toxoplasma gondii and Borrelia burgdorferi infections in postal samples

Background: Most of the samples sent to reference laboratories are delivered by post. Thus, diagnostic PCR tests on blood samples have to be performed using methods which are optimised and validated for such conditions. There is a low probability that the organisms Toxoplasma gondii and Borrelia burgdorferi will be present. Aim: To confirm that robotic extraction methods followed by real time PCR will detect as little as one organism/test sample in postal specimens. Methods: Human blood samples spiked with decreasing numbers of each organism (range 105–1/per extract) were extracted using two commercial kits on a Qiagen BioRobot EZ1 Workstation. Extracts of whole blood and blood fractions were tested by real time PCR. The effect of storage of blood for 1–6 days at room temperature was also investigated. Results: Maximum sensitivity (1 organism/test sample) was achieved for T gondii with either extraction method; the sensitivity for B burgdorferi was between 1 and 10 organisms/test. Whole blood was the most suitable sample to extract, as both organisms were as likely to be detectable in the red cell as the white cell fraction. Sensitivity was not reduced by storing spiked samples at room temperature for up to 6 days. Inhibitory effects on PCR were not a significant problem provided that samples were extracted using the blood extraction kit. Conclusions: Using appropriate robotic extraction methods, both T gondii and B burgdorferi can be detected by real time PCR with near maximum possible sensitivity in whole blood samples. Blood samples can be transferred to reference laboratories by post without loss of sensitivity over the likely transit period.
Substate variations in political values in Canada

ABSTRACT The article aims to make three methodological and substantive contributions to the literature on substate cleavages in political values. Considerable controversy characterizes this literature. The paper argues that this controversy is due to how indicators representing political values are chosen and constructed. The paper proposes to use factor analysis to select and construct indicators of political values. The analysis identifies five dimensions, which collectively account for 57% of Canadians’ political values. They include support for moral traditionalism, egalitarianism, pluralism, openness to immigration and personal responsibility. Second, the paper shows that there is only limited variation across provinces in political values. Third, the paper shows that this result holds when considering regional variations rather than provincial variations.
Problem solving by patients with multiple sclerosis Comparison of performance on the Wisconsin and California Card Sorting Tests

Abstract Problem solving by patients with clinically definite multiple sclerosis (MS) was examined using the Wisconsin and California Card Sorting Tests (WCST and CCST). On the WCST, the MS patients achieved fewer categories and made more perseverative responses and errors than controls, confirming results of several previous studies. On the CCST, the MS patients generated and identified fewer concepts, but they performed normally when sorting was cued by the experimenter and they made no more persevcrations than controls. Although findings from the WCST indicate that the problem solving deficits by MS patients closely resemble those exhibited by patients with various conditions that produce frontal lobe dysfunction, results from the CCST indicate that the problem solving difficulties exhibited by patients with MS arc distinct and probably represent a primary deficit in concept formation. (JINS, 1996, 2, 134–140.)