Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclosporine A: impact on mitochondrial function in endothelial cells

Illsinger S, Janzen N, Lücke T, Bednarczyk J, Schmidt K‐H, Hoy L, Sander J, Das AM. Cyclosporine A: impact on mitochondrial function in endothelial cells. Clin Transplant 2011: 25: 584–593. © 2010 John Wiley & Sons A/S.
The Economic Impact of Methicillin-Resistant Staphylococcus aureus in Canadian Hospitals

Abstract Objectives: To determine the costs associated with the management of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA), and to estimate the economic burden associated with MRSA in Canadian hospitals. Design: Patient-specific costs were used to determine the attributable cost of MRSA associated with excess hospitalization and concurrent treatment. Excess hospitalization for infected patients was identified using the Appropriateness Evaluation Protocol, a criterion-based chart review process to determine the need for each day of hospitalization. Concurrent treatment costs were identified through chart review for days in isolation, antimicrobial therapy, and MRSA screening tests. The economic burden to Canadian hospitals was estimated based on 3,167,521 hospital discharges for 1996 and 1997 and an incidence of 4.12 MRSA cases per 1,000 admissions. Setting: A tertiary-care, university-affiliated teaching hospital in Toronto, Ontario, Canada. Patients: Inpatients with at least one culture yielding MRSA between April 1996 and March 1998. Results: A total of 20 patients with MRSA infections and 79 colonized patients (with 94 admissions) were identified. This represented a rate of 2.9 MRSA cases per 1,000 admissions. The mean number of additional hospital days attributable to MRSA infection was 14, with 11 admissions having at least 1 attributable day. The total attributable cost to treat MRSA infections was $287,200, or $14,360 per patient. The cost for isolation and management of colonized patients was $128,095, or $1,363 per admission. Costs for MRSA screening in the hospital were $109,813. Assuming an infection rate of 10% to 20%, we determined the costs associated with MRSA in Canadian hospitals to be $42 million to $59 million annually. Conclusions: These results indicate that there is a substantial economic burden associated with MRSA in Canadian hospitals. These costs will continue to rise if the incidence of MRSA increases further.
Binary differential evolution strategies

Differential evolution has shown to be a very powerful, yet simple, population-based optimization approach. The nature of its reproduction operator limits its application to continuous-valued search spaces. However, a simple discretization procedure can be used to convert floating-point solution vectors into discrete-valued vectors. This paper considers three approaches in which differential evolution can be used to solve problems with binary-valued parameters. The first approach is based on a homomorphous mapping, while the second approach interprets the floating-point solution vector as a vector of probabilities, used to decide on the appropriate binary value. The third approach normalizes solution vectors and then discretize these normalized vectors to form a bitstring. Empirical results are provided to illustrate the efficiency of both methods in comparison with particle swarm optimizers.
Circadian regulation gene polymorphisms are associated with sleep disruption and duration, and circadian phase and rhythm in adults with HIV

Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep–wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72 h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep–wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep–wake behavior patterns.
Meta-analysis of micrornas expression in head and neck cancer: uncovering association with outcome and mechanisms.

Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at advanced stages, incurring significant high mortality and morbidity. This review explored the risk stratification of miRNAs, and investigated the impact of miRNA networking in HNSCC prognostication. We performed a meta-analysis and a systematic literature search on online databases for papers published prior to December 1, 2016. The list of miRNAs was uploaded to MetacoreTM to construct a protein-protein interaction network, which was used to identify targets of the miRNAs and potential drugs. In addition, a representative network was further validated by immunohistochemistry in a cohort of 100 patients. We found 116 studies that included 8,194 subjects, in which the relationship between miRNA expression and prognosis of HNSCC were analyzed. Significant elevated expressions of 27 miRNAs and decreased expression of 26 miRNAs were associated with poor outcome. After excluding the studies causing heterogeneity, a fixed model was applied, which showed a statistically significant association between increased expression of miR-21 and poor survival (Pooled HR = 1.81,95% CI = 0.66-2.95, P < 0.005). We identified four networks affected by the miRNAs expression and enriched in genes related to metabolic processes and regulation of cell mitogenesis in response to extracellular stimuli. One network point out to 16 miRNAs directly or indirectly involved in the regulation of androgen-receptor (AR). Evaluation of AR protein expression in our cohort revealed that patients with upregulation of AR had poor survival rates (log-rank test, P < 0.005). This study showed that miRNAs have potential prognostic value to serve as screening tool for HNSCC during the follow-up. In addition, the implementation of a network-based analysis may reveal proteins with potential to be used as a biomarker.
Global overview of injecting drug use and HIV infection among injecting drug users

Objective: To provide global estimates of the prevalence of injecting drug use (IDU) and HIV prevalence among IDU, in particular to provide estimates for developing and transitional countries. Methods: Collation and review of existing estimates of IDU prevalence and HIV prevalence from published and unpublished documents for the period 1998–2003. The strength of evidence for the information was assessed based on the source and type of study. Results: Estimates of IDU prevalence were available for 130 countries. The number of IDU worldwide was estimated as approximately 13.2 million. Over ten million (78%) live in developing and transitional countries (Eastern Europe and Central Asia, 3.1 million; South and South-east Asia, 3.3 million; East-Asia and Pacific, 2.3 million). Estimates of HIV prevalence were available for 78 countries. HIV prevalence among IDU of over 20% was reported for at least one site in 25 countries and territories: Belarus, Estonia, Kazakhstan, Russia, Ukraine, Italy, Netherlands, Portugal, Serbia and Montenegro, Spain, Libya, India, Indonesia, Malaysia, Myanmar, Nepal, Thailand, Viet Nam, China, Argentina, Brazil, Uruguay, Puerto Rico, USA and Canada. Conclusions: These findings update previous assessments of the number of countries with IDU and HIV-infected IDU, and the previous quantitative global estimates of the prevalence of IDU. However, gaps remain in the information and the strength of the evidence often was weak.
The role of growth factors in gastrointestinal cell proliferation.

The epithelial lining of the gastrointestinal (GI) tract is in a state of continuous cell renewal, and the proliferating and differentiating/differentiated cell populations are spatially clearly demarcated. Members of the epidermal growth factor (EGF) family of peptides, the trefoil peptides and enteroglucagon appear to be the most important enterotrophic molecules for both normal cell renewal and healing after cell damage. Transforming growth factor‐a (TGF‐a) appears to be the primary physiological ligand for the EGF receptor (EGFR), promoting normal cell renewal, and TGF‐a/EGFR are part of an autocrine loop in many intestinal cancers. In response to damage, a differentiating cell lineage arises from adjacent epithelium secreting EGF, TGF‐a and trefoil peptides; this may be viewed as part of a ‘repair kit’ in damaged endodermally‐derived tissue.
SRCS: Statistical Ranking Color Scheme for Visualizing Parameterized Multiple Pairwise Comparisons with R

The problem of comparing a new solution method against existing ones to find statistically significant differences arises very often in sciences and engineering. When the problem instance being solved is defined by several parameters, assessing a number of methods with respect to many problem configurations simultaneously becomes a hard task. Some visualization technique is required for presenting a large number of statistical significance results in an easily interpretable way. Here we review an existing color-based approach called Statistical Ranking Color Scheme (SRCS) for displaying the results of multiple pairwise statistical comparisons between several methods assessed separately on a number of problem configurations. We introduce an R package implementing SRCS, which performs all the pairwise statistical tests from user data and generates customizable plots. We demonstrate its applicability on two examples from the areas of dynamic optimization and machine learning, in which several algorithms are compared on many problem instances, each defined by a combination of parameters.
Public Education and Income Distribution: A Dynamic Quantitative Evaluation of Education-Finance Reform

Many states are implementing school-finance reforms which will have complex effects on income distribution, intergenerational income mobility, and welfare. This paper analyzes the static and dynamic effects of such reforms by constructing a dynamic general equilibrium model of public-education provision and calibrating it using U.S. data. The authors examine the consequences of a reform of a locally financed system to a state-financed system which equalizes expenditures per student across districts. They find that this policy increases both average income and the share of income spent on education. Steady-state welfare increases by 3.2 percent of steady-state income. Copyright 1998 by American Economic Association.
Wireless Competition Under Spectrum Exhaust

There is a growing concern that the present inventory of commercial spectrum — an essential input for providers of mobile wireless services — represents just a fraction of the amount necessary to match growing demand for mobile data services. At the same time, there has been mounting anxiety among policymakers about the number of competitors in the mobile wireless industry. What is lacking from the policy debate today is an economic theory of market performance that integrates these two key issues — spectrum exhaust and industry structure. In this paper, we provide such a theory, and our findings are significant. The addition of a spectrum constraint to the traditional model of competition turns the conventional view that high industry concentration is a bellwether of poor economic performance on its head. Indeed, under a binding spectrum constraint, a market characterized by few firms (rather than a large number of firms) is more likely to produce lower prices and possibly increase sector investment and employment. Given the FCC’s stated position on spectrum exhaust, the agency needs to re-orientate the way it thinks about spectrum policy. Policies that impede incumbent carriers from acquiring more spectrum — via either auction or acquisition — may do harm rather than good.
Synergistic dopaminergic neurotoxicity of manganese and lipopolysaccharide: differential involvement of microglia and astroglia

Overexposure to manganese is known to cause damage to basal ganglial neurons and the development of movement abnormalities. Activation of microglia and astrocytes has increasingly been associated with the pathogenesis of a variety of neurological disorders. We have recently shown that microglial activation facilitates manganese chloride (MnCl2, 10–300 μM)‐induced preferential degeneration of dopamine (DA) neurons. In this study, we report that combinations of MnCl2 (1–30 μM) and endotoxin lipopolysaccharide (LPS, 0.5–2 ng/mL), at minimally effective concentrations when used alone, induced synergistic and preferential damage to DA neurons in rat primary neuron‐glia cultures. Mechanistically, MnCl2 significantly potentiated LPS‐induced release of tumor necrosis factor‐alpha and interleukin‐1 beta in microglia, but not in astroglia. MnCl2 and LPS were more effective in inducing the formation of reactive oxygen species and nitric oxide in microglia than in astroglia. Furthermore, MnCl2 and LPS‐induced free radical generation, cytokine release, and DA neurotoxicity was significantly attenuated by pre‐treatment with potential anti‐inflammatory agents minocycline and naloxone. These results demonstrate that the combination of manganese overexposure and neuroinflammation is preferentially deleterious to DA neurons. Moreover, these findings not only shed light on the understanding of manganese neurotoxicity but may also bear relevance to the potentially multifactorial etiology of Parkinson’s disease.
Overweight and Obese Adolescent Girls: The Importance of Promoting Sensible Eating and Activity Behaviors from the Start of the Adolescent Period

The adolescent period is associated with changes in eating and activity behaviors in girls. Less reliance on parental provision and choice of food, coupled with a decrease in participation in physical activity and sport, can create an energy imbalance, predisposing to weight gain. Physiological alterations to body composition, reduction in insulin sensitivity, and psychological adjustments may further amplify the risk of becoming overweight and maintaining an unhealthy level of body fat into childbearing years. During pregnancy excess body fat is a risk factor for poor pregnancy outcomes and may predispose an infant to a lifelong heightened risk of being overweight and developing chronic disease. Interventions aimed at preventing the accumulation of body fat in adolescent girls and young women may have far reaching impact and be critically important in reducing intergenerational weight gain. Lifestyle interventions in adolescence have the potential to modify adult obesity risk by switching at-risk individuals from a high to lower obesity risk trajectory. This paper discusses multiple approaches to assist at-risk individuals reduce obesity risk. A key focus is placed on engagement in food preparation and choice, and opportunities for physical activity and sport. Support, education, and opportunity at home and at school, are often associated with the success of lifestyle interventions, and may enable adolescents to make positive choices, and engage in health promoting behaviors during adolescence and childbearing years.
Overproduction of fatty acids in engineered Saccharomyces cerevisiae

The long hydrocarbon fatty acyl chain is energy rich, making it an ideal precursor for liquid transportation fuels and high‐value oleo chemicals. As Saccharomyces cerevisiae has many advantages for industrial production compared to Escherichia coli. Here, we attempted to engineer Saccharomyces cerevisiae for overproduction of fatty acids. First, disruption of the beta‐oxidation pathway, elimination of the acyl‐CoA synthetases, overexpression of different thioesterases and acetyl‐CoA carboxylase ACC1, and engineering the supply of precursor acetyl‐CoA. The engineered strain XL122 produced more than 120 mg/L of fatty acids. In parallel, we inactivated ADH1, the dominant gene for ethanol production, to redirect the metabolic flux to fatty acids synthesis. The engineered strain DG005 produced about 140 mg/L fatty acids. Additionally, Acetyl‐CoA carboxylase was identified as a critical bottleneck of fatty acids synthesis in S. cerevisiae with a cell‐free system. However, overexpression of ACC1 has little effect on fatty acids biosynthesis. As it has been reported that phosphorylation of ACC1 may influent its activity, so phosphorylation sites of ACC1 were further identified. Although the regulatory mechanisms remain unclear, our results provide rationale for future studies to target this critical step. All these efforts, particularly the discovery of the limiting step are critical for developing a “cell factory” for the overproduction of fatty acids by using type I fatty acids synthase in yeast or other fungi. Biotechnol. Bioeng. 2014;111: 1841–1852. © 2014 Wiley Periodicals, Inc.
Beyond File Sharing–Commerce in Peer-to-Peer Networks: Surveying the Landscape

ABSTRACT Peer-to-peer (P2P) networks have become ubiquitous due to their synonymous association with illicit file sharing. Although P2P networks offer the unique ability for users to work and share data directly with each other, they also have become a harbor for those illegally trading copyright-protected material. These concerns have led to a variety of court actions that have taken P2P technology itself to the verge of being declared illegal. This paper explores the developments in the P2P marketplace and investigates the hypothesis that commercial opportunities exist for this unique medium. Through a review of past and current research, legal issues, and existing and developing applications, the researcher explores the potential for P2P networks to facilitate legitimate, e-commerce-based applications.
Annual report IC disclosures in The Netherlands, France and Germany

Purpose – This paper replicates and extends the Bontis research on intellectual capital (IC) disclosures in Canadian companies and also elaborates on the Beaulieu et al. research on disclosures by Swedish firms.Design/methodology/approach – The paper studies IC disclosures by French CAC‐40, Dutch AEX and German XETRA‐DAX publicly‐listed companies for the years 2000 and 2001. The paper also discusses country‐specific arguments in favour of and against voluntary disclosure by such companies and searches both the annual reports and financial statements for IC hits.Findings – Applying the Gray‐scale to categorise countries, the paper finds not only that voluntary IC disclosure significantly differs between these countries, but also that this difference can be explained by country‐specific regulation and auditor conservatism.Research limitations/implications – The paper only studies Dutch, French and German IC disclosures in annual reports and financial statements. These three countries are European Union memb.
Simplifying ARM concurrency: multicopy-atomic axiomatic and operational models for ARMv8

ARM has a relaxed memory model, previously specified in informal prose for ARMv7 and ARMv8. Over time, and partly due to work building formal semantics for ARM concurrency, it has become clear that some of the complexity of the model is not justified by the potential benefits. In particular, the model was originally non-multicopy-atomic: writes could become visible to some other threads before becoming visible to all — but this has not been exploited in production implementations, the corresponding potential hardware optimisations are thought to have insufficient benefits in the ARM context, and it gives rise to subtle complications when combined with other ARMv8 features. The ARMv8 architecture has therefore been revised: it now has a multicopy-atomic model. It has also been simplified in other respects, including more straightforward notions of dependency, and the architecture now includes a formal concurrency model. In this paper we detail these changes and discuss their motivation. We define two formal concurrency models: an operational one, simplifying the Flowing model of Flur et al., and the axiomatic model of the revised ARMv8 specification. The models were developed by an academic group and by ARM staff, respectively, and this extended collaboration partly motivated the above changes. We prove the equivalence of the two models. The operational model is integrated into an executable exploration tool with new web interface, demonstrated by exhaustively checking the possible behaviours of a loop-unrolled version of a Linux kernel lock implementation, a previously known bug due to unprevented speculation, and a fixed version.
Long-term Recall of Time to Pregnancy

Background: Despite the widespread use of retrospectively reported time to pregnancy to evaluate fertility either as an outcome or as a risk factor for chronic disease, only two small studies have directly compared prospective data with later recall. Methods: The North Carolina Early Pregnancy Study (1982–1986) collected prospective time-to-pregnancy data from the beginning of participants’ pregnancy attempt. In 2010, (24–28 years later) women were sent a questionnaire including lifetime reproductive history that asked about all prior times to pregnancy. Of the 202 women with prospective time-to-pregnancy data, 76% provided recalled time to pregnancy. Results: A lower proportion of women with times to pregnancy ≥3 cycles provided a recalled time to pregnancy than women with times to pregnancy <3 cycles. Also, high gravidity or parity was associated with a lower likelihood of providing a recalled time to pregnancy. Women with very short or very long times to pregnancy (1 cycle or ≥13 cycles) had good recall of time to pregnancy. Positive predictive values of 1 or ≥13 cycles were 73% and 68%, respectively, while positive predictive values for other categories of time to pregnancy ranged from 38% to 58%. The weighted kappa statistic for recalled versus prospective time to pregnancy was 0.72 (95% confidence interval: 0.65, 0.79). Conclusions: Recalled time to pregnancy showed good agreement with prospective time to pregnancy. Informative missingness must be considered when imputing recalled time to pregnancy. Associations observed in future studies can be corrected for misclassification.