Miracle-dz/UniFAR-FTUs huggingface dataset:
Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.
Economic, Political, Social Factor of Corruption in the Slovak Republic

Abstract Interdisciplinary definitions of corruption perceive corrupt actions as contrary to legal and ethical standards affecting the public interest, perpetrated by a person in public office. The main goal of the study is to identify the factors of corrupt acts in the public sector stemming from the economic, political, cultural and social environments in the Slovak Republic. Through the Delphi method we verify the relevance of economic, political and cultural-social factors of corrupt acts in the public sector defined in the theoretical framework of this issue. The Delphi method was used under the following conditions: the anonymity of experts, feedback control and statistical determination of a consensus of experts. Expert evaluation of the factors underlying corrupt behaviour in the public sector enabled us not only to detect the overall relevance of the factors, but also to identify areas where corruption in the public sector is most widespread, according to experts. We can state that the most problematic areas include the judiciary and the police.
Tankyrase 2 Poly(ADP-Ribose) Polymerase Domain-Deleted Mice Exhibit Growth Defects but Have Normal Telomere Length and Capping

ABSTRACT Regulation of telomere length maintenance and capping are a critical cell functions in both normal and tumor cells. Tankyrase 2 (Tnks2) is a poly(ADP-ribose) polymerase (PARP) that has been shown to modify itself and TRF1, a telomere-binding protein. We show here by overexpression studies that tankyrase 2, like its closely related homolog tankyrase 1, can function as a positive regulator of telomere length in human cells, dependent on its catalytic PARP activity. To study the role of Tnks2 in vivo, we generated mice with the Tnks2 PARP domain deleted. These mice are viable and fertile but display a growth retardation phenotype. Telomere analysis by quantitative fluorescence in situ hybridization (FISH), flow-FISH, and restriction fragment analysis showed no change in telomere length or telomere capping in these mice. To determine the requirement for Tnks2 in long-term maintenance of telomeres, we generated embryonic stem cells with the Tnks2 PARP domain deleted and observed no change, even upon prolonged growth, in telomere length or telomere capping. Together, these results suggest that Tnks2 has a role in normal growth and development but is not essential for telomere length maintenance or telomere capping in mice.
Preparing Future Leaders: An Ethnographic Study Exploring the Culture of Succession Planning and Leader Development in Christian Higher Education

Abstract The purpose of this ethnographic case study was to explore the culture of succession planning and leader development at Lipscomb University, using the 5C’s: Strategies for succession planning in the academy model. In the face of unprecedented disruption and complexity, the review of literature suggested the higher education sector in the United States is largely underprepared for the upcoming exodus and shortage of leaders. With religiously-affiliated institutions accounting for more than one in five colleges and universities in the US, there were no visible studies attending to succession planning and leader development in Christian higher education. Given the important contribution of these faith-based institutions to the educational landscape it is both important and significant to understand the culture of succession planning and leader development in this environment. The study identified nine themes related to the culture of succession planning and leader development at Lipscomb University, a member of the Council for Christian Colleges & Universities. These themes were 1) Developing future leaders is a clear priority of the president, 2) Historic cultural and religious traditional norms are influential, 3) Purpose of the programs are clearly understood by participant, 4) Exposure and interaction with other leaders is highly valued, 5) Participants associate deep value with their engagement in programs, 6) Intentional and ongoing efforts to connect with the Nashville community is important, 7) Clarity around ongoing plans for participants is challenging, 8) Board of trustees prioritize succession planning efforts, and 9) Intentionally developing leaders who understand the changing landscape of higher education is critical. The results of the study have significant implications for presidents and board chairs as they consider the need to identify, develop and prepare the next generation of leaders for their institutions of Christian higher education.
Matrix Gla Protein Inhibition of Tooth Mineralization

Extracellular matrix (ECM) mineralization is regulated by mineral ion availability, proteins, and other molecular determinants. To investigate protein regulation of mineralization in tooth dentin and cementum, and in alveolar bone, we expressed matrix Gla protein (MGP) ectopically in bones and teeth in mice, using an osteoblast/odontoblast-specific 2.3-kb Col1a1 promoter. Mandibles were analyzed by radiography, micro-computed tomography, light microscopy, histomorphometry, and transmission electron microscopy. While bone and tooth ECMs were established in the Col1a1-Mgp mice, extensive hypomineralization was observed, with values of unmineralized ECM from four- to eight-fold higher in dentin and alveolar bone when compared with that in wild-type tissues. Mineralization was virtually absent in tooth root dentin and cellular cementum, while crown dentin showed “breakthrough” areas of mineralization. Acellular cementum was lacking in Col1a1-Mgp teeth, and unmineralized osteodentin formed within the pulp. These results strengthen the view that bone and tooth mineralization is critically regulated by mineralization inhibitors.
Bacterial biliary tract infections in liver transplant recipients

Purpose of reviewThe purpose of this study is to provide an overview of bacterial biliary tract infections in liver transplant recipients with a focus on pathogenesis and conservative treatment strategies. Recent findingsThe development of interventional endoscopic and radiologic interventions has improved the outcome of conservative treatments for bile tract strictures and bilomas. However, recent data show an important rise of infections with multidrug-resistant (MDR) pathogens in liver transplant recipients. SummaryBoth recurrent cholangitis and infected bilomas are bacterial biliary tract infections in liver transplant recipients responsible for significant morbidity and graft loss, which require a multidisciplinary approach. Risk factors for biliary tract strictures and bilomas formation have recently been identified. With the improved outcome of a conservative management including prolonged and/or recurrent antibiotic treatments, the risk of selecting resistant pathogens is increased. There is an urgent need to develop new strategies to reduce the risk of secondary infections by MDR isolates in liver transplant recipients.
A large-scale gastroenteritis outbreak associated with Norovirus in nursing homes

An increase in gastroenteritis outbreaks due to Norovirus has been reported worldwide. We investigated a large-scale outbreak affecting 246 residents and 33 staff members in six nursing homes in the Tel-Aviv district, Israel, during 3 weeks in 2002. Person-to-person spread was noticed in all nursing homes. The spread of disease could not be attributed to social interactions. Among the elderly residents, the hospitalization rate was 10·2% and the case-fatality rate was 2·0%. Bacteriological cultures were negative. Overall, 7 out of 15 stool specimens were positive for Norovirus by RT–PCR. All were sequenced and found to be 90% identical. The characteristics of this outbreak and the RT–PCR results suggest that illness was caused by Norovirus. Due to the high case-fatality rate of Norovirus gastroenteritis, there should be a high index of suspicion when encountering a gastroenteritis outbreak among the elderly. This will enable prompt action to stop the spread of illness.
The Plasma Levels of Homocysteine Are Elevated in Moderate Renal Insufficiency but Do Not Predict the Rate of Progression

Background: Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It is also characterized by elevated plasma levels of total homocysteine (tHcy). Hyperhomocysteinemia has been shown to be a risk factor for atherosclerosis in both the general population and in patients with end-stage renal disease. Aim: To analyze whether elevated tHcy levels also may contribute to a higher rate of progression of renal insufficiency in patients with moderately advanced renal failure. Methods: To investigate whether tHcy concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of tHcy with the progressive decline of renal function in an observational study of human chronic renal disease. Results: Sixty-three nondiabetic patients (49 men, 14 women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.0 years, and the mean rate of decline in glomerular filtration rate (51Cr- EDTA clearance) was –3.2 ± (SD) 3.9 ml/min × 1.73 m2 body surface area. The mean plasma concentration of tHcy at the beginning of the study was 28.3 ± 12.0 µmol/l. Plasma tHcy concentrations correlated significantly with the glomerular filtration rate (r = –0.32, p < 0.01). However, there was no association between the initial plasma level of tHcy and the rate of progression as assessed by linear regression analysis (r = 0.02; NS). In contrast, increased levels of apolipoprotein B, low-density lipoprotein cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Conclusions: Patients with moderately advanced chronic renal insufficiency have elevated plasma levels of homocysteine. The tHcy plasma levels increase in parallel with the degree of reduction in renal function. However, the hyperhomocysteinemia is not prospectively associated with a higher rate of progression of the renal functional impairment. Hence, there is no indication that elevated homocysteine levels play a contributing role for an accelerated glomerulosclerotic process.
Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists

The developmentally important Hedgehog (Hh) signaling pathway has recently been implicated in several forms of solid cancer. Current drug development programs focus on targeting the protooncogene Smoothened, a key transmembrane pathway member. These drug candidates, albeit promising, do not address the scenario in which pathway activation occurs downstream of Smoothened, as observed in cases of medulloblastoma, glioma, pericytoma, breast cancer, and prostate cancer. A cellular screen for small-molecule antagonists of GLI-mediated transcription, which constitutes the final step in the Hh pathway, revealed two molecules that are able to selectively inhibit GLI-mediated gene transactivation. We provide genetic evidence of downstream pathway blockade by these compounds and demonstrate the ineffectiveness of upstream antagonists such as cyclopamine in such situations. Mechanistically, both inhibitors act in the nucleus to block GLI function, and one of them interferes with GLI1 DNA binding in living cells. Importantly, the discovered compounds efficiently inhibited in vitro tumor cell proliferation in a GLI-dependent manner and successfully blocked cell growth in an in vivo xenograft model using human prostate cancer cells harboring downstream activation of the Hh pathway.
Asymmetry effects of exchange rate changes on domestic production in Japan

Abstract Previous studies that assessed the effects of currency depreciation on the domestic production of Japan did not find any significant long-run effects. Using the linear ARDL approach we first confirm previous findings. We then argue and show that failure to find any significant link between the value of the yen and Japanese domestic production is due to assuming a linear adjustment mechanism or symmetric effects of exchange rate changes. Once we use the nonlinear ARDL approach we show that indeed exchange rate changes do have asymmetric effects on domestic production in Japan. Not only we observe adjustment asymmetry, but also short-run asymmetry that lasts into the long run. In the long run while strong yen seems to hurt domestic production in Japan, weak yen seems to have no effect.
The Efficacy of Political Advertising: A Voter Participation Field Experiment with Multiple Robo Calls and Controls for Selection Effects

We document the effectiveness of robo calls for increasing voter participation despite most published research finding little or no effect of automated calls. We establish this finding in a large field experiment in a targeted, partisan get-out-the-vote campaign. Our experimental design includes a follow-up call, which allows us to control for selection effects. We identify subsets of subjects, for whom the treatment effects are substantially larger than those that are found in previous studies. Our findings show that robo calls can cause a one percentage point increase in voter turnout. Additionally, our experimental design allows for testing how the number of calls in a treatment, that is dosage, affects voter turnout. Here, results show that that a few extra calls increase the treatment effect, and that many additional calls decrease that effect.
Secondary use of randomized controlled trials to evaluate drug safety: a review of methodological considerations

Background Randomized clinical trials (RCTs) are often positioned at the top of evidence hierarchies. Meta-analyses of RCTs aim to integrate the state of knowledge on a given scientific question, particularly for rare drug-related outcomes. However, although RCTs are valuable tools in our armamentarium, they are rarely designed to evaluate drug safety and are thus susceptible to limitations that may hamper the ability of both RCTs and meta-analyses to fully characterize the safety profiles of drugs. Their potential limitations might be exacerbated in the study of rare outcomes, often encountered in drug safety assessment, when even minor deviations from the intended randomization could impact the stability of the risk estimates. Purpose This article considers the methodological caveats of both RCTs and meta-analyses of RCTs pertinent to the study of drug-related harms. It is intended to stimulate discussion about the impact of these caveats on interpreting findings of RCTs and meta-analyses for drug safety, which would foster more robust, critical evaluations, and thus enhance clinical and regulatory decision-making. Methods Pertinent issues that can influence the interpretation of drug-related harms discussed in this article were based on authors’ expertise and review of the literature. Results Investigators and clinicians should be cognizant of the potential limitations of the secondary use of RCTs and meta-analyses in the assessment of drug-related harms and, when applicable, should consider potential remedies to overcome these limitations. Limitations Only few practical examples are included in the article due to the fact that many of the discussed caveats are not examined and/or reported in many publications. In addition, the confidential nature of data reviewed at a regulatory agency forestalls an in depth discussion of examples pertaining to specific drugs. Furthermore, our ability to quantify the extent of encountering, or the actual impact of, the caveats addressed in this review on the RCTs findings is limited. It is worth noting that the mere encounter of a given caveat does not mean that it will obviate the utility of drug safety information from a given trial. The extent of its impact is expected to vary based on the specifics of the trial, the drugs studied, the indications, and the nature of the adverse events. Conclusions Although some of the limitations described are inherent in RCTs, some of the sources of bias highlighted in this article could be minimized by careful RCT design, planned follow-up, and improved collection of information on adverse events. As future research sheds more light on pertinent knowledge gaps and issues, the ability to maximize the use of RCTs and meta-analyses of RCTs to address drug safety questions of interest will be greatly enhanced.
The accuracy of the TriTrac-R3D accelerometer to estimate energy expenditure.

PURPOSE This study examined the reliability and validity of the TriTrac-R3D triaxial accelerometer to estimate energy expenditure during various modes of exercise. METHODS Twenty subjects (age = 21.5+/-3.4 yr; body mass index = 23.3+/-3.6 kg x m(-2)) performed five exercises (treadmill walking, treadmill running, stepping, stationary cycling, and slideboard), with each lasting 20-30 min and workload increased at 10-min intervals. To test the inter-TriTrac reliability, two TriTrac-R3D accelerometers were worn during each exercise period, and to examine validity, a simultaneous measurement of energy expenditure was made using indirect calorimetry (SensorMedics 2900 Metabolic Cart). RESULTS Results showed a significant correlation between the two TriTrac-R3D accelerometers during all exercises. The difference in estimated energy expenditure between the two accelerometers during the walking, stepping, and slideboard exercises was less than 1 kcal x min(-1) but statistically significant (P<0.05). There was also a significant correlation between energy expenditure estimated by each of the TriTrac-R3D accelerometers and indirect calorimetry during walking, running, stepping, and slideboard exercise (P<0.05). The interaction of Method x Workload was significant (P<0.05) for each exercise, indicating that the TriTrac-R3D underestimates energy expenditure and that the magnitude of this underestimation increases as workload increases. CONCLUSIONS Therefore, energy expenditure estimated via triaxial accelerometry does not increase with increasing workloads. These results suggest that there are limitations to using triaxial accelerometry to quantify energy expenditure.
Epigenetically regulated clonal heritability of CTA expression profiles in human melanoma

The intratumoral heterogeneity of cancer testis antigens (CTA) expression, which is driven by promoter methylation status, may hamper the effectiveness of CTA‐directed vaccination of melanoma patients. Thus, we investigated whether the intratumoral heterogeneity of CTA expression is inherited at cellular level, or evolves throughout cellular replication, leading to a phenotypically unstable tumor cell population with reduced immunogenicity and/or able to escape immune control. Utilizing a previously characterized ex vivo clonal model of intratumoral heterogeneity of CTA expression in melanoma, Mel 313 MAGE‐A3‐low clone 5 (clone 5M3‐low) and MAGE‐A3‐high clone 14 (clone 14M3‐high) were sub‐cloned and analyzed for CTA profile. Molecular assays demonstrated that levels of MAGE‐A3 expression were highly conserved among generated sub‐clones, as compared to parental clones. A similar behavior was identified for an extensive panel of other CTA investigated. Inherited levels of MAGE‐A3 expression correlated with the extent of promoter methylation among clone 5M3‐low and clone 14M3‐high sub‐clones analyzed. Treatment of clone 5M3‐low with a DNA hypomethylating agent (DHA) resulted in an up‐regulated expression of MAGE‐A3, which was inherited at single cell level, being still detectable at day 60 in its sub‐clones. Bisulfite sequencing demonstrated that also MAGE‐A3 promoter methylation status was inherited among sub‐clones generated from DHA‐treated clone 5M3‐low and strictly correlated with MAGE‐A3 expression levels in investigated sub‐clones. Similar results were obtained for additional CTA studied. Altogether our findings demonstrate that constitutive and DHA‐modified CTA profiles of melanoma cells are clonally inherited throughout cellular replications, thus providing relevant insights to improve the effectiveness of CTA‐based immunotherapy. J. Cell. Physiol. 223: 352–358, 2010. © 2010 Wiley‐Liss, Inc.