Publications by authors named "Cairns J"

Article Synopsis
  • - Long-range regulatory elements like enhancers interact with gene promoters to control cell-specific gene expression through DNA looping during development.
  • - The study uses Promoter Capture Hi-C to map chromosomal interactions involving about 22,000 gene promoters in both pluripotent and lineage-committed human cells, identifying potential target genes for known and predicted enhancers.
  • - The research reveals significant changes in regulatory contacts as cells commit to specific lineages, including the gaining and losing of promoter interactions, which correlate with shifts in the activity of regulatory elements and affect gene expression.
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  • - Metformin shows potential as an anticancer agent beyond its role as an anti-diabetic drug, prompting a pharmacogenomic study with 266 lymphoblastoid cell lines (LCLs) to assess individual responses to the drug.
  • - Researchers used extensive genetic analyses (including SNPs and DNA methylation) to identify candidate genes linked to metformin's effectiveness, finding 198 mRNA probes and several specific genetic loci that impact drug sensitivity.
  • - The study highlighted STUB1 as a key gene influencing metformin response by promoting the degradation of cyclin A, suggesting new genetic and epigenetic biomarkers for optimizing metformin therapy in cancer treatment.
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Interactions between nitrogen-fixing (i.e. diazotrophic) cyanobacteria and their viruses, cyanophages, can have large-scale ecosystem effects.

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Background: Policymakers in high-, low-, and middle-income countries alike face challenging choices about resource allocation in health. Economic evaluation can be useful in providing decision makers with the best evidence of the anticipated benefits of new investments, as well as their expected opportunity costs-the benefits forgone of the options not chosen. To guide the decisions of health systems effectively, it is important that the methods of economic evaluation are founded on clear principles, are applied systematically, and are appropriate to the decision problems they seek to inform.

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Bacteria live in dynamic systems where selection pressures can alter rapidly, forcing adaptation to the prevailing conditions. In particular, bacteriophages and antibiotics of anthropogenic origin are major bacterial stressors in many environments. We previously observed that populations of the bacterium Pseudomonas fluorescens SBW25 exposed to the lytic bacteriophage SBW25Φ2 and a noninhibitive concentration of the antibiotic streptomycin (coselection) achieved higher levels of phage resistance compared to populations exposed to the phage alone.

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Background: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction.

Methods: Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction.

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Sub-minimum inhibiting concentrations (sub-MICs) of antibiotics frequently occur in natural environments owing to wide-spread antibiotic leakage by human action. Even though the concentrations are very low, these sub-MICs have recently been shown to alter bacterial populations by selecting for antibiotic resistance and increasing the rate of adaptive evolution. However, studies are lacking on how these effects reverberate into key ecological interactions, such as bacteria-phage interactions.

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Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types.

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Article Synopsis
  • Researchers developed a method called P-Map to identify genes that can change how cancer cells respond to chemotherapy drugs, aiming to combat drug resistance.
  • They used gene expression data from human cells to create networks that show how cells react to two common cancer drugs: anthracycline and taxane.
  • The findings suggest that by manipulating certain genes, it's possible to shift cancer cells from being resistant to sensitive to these drugs, paving the way for new therapeutic strategies that target both the disease and the underlying gene networks.
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Background: The objective of this study was to assess the efficacy of sealing intermediate nonobstructive coronary saphenous vein graft (SVG) lesions with drug-eluting stents (DES; paclitaxel- or everolimus-eluting stents) for reducing major adverse cardiac events (MACE).

Methods And Results: This was a randomized controlled multicenter clinical trial that enrolled patients with a previous coronary artery bypass graft who had developed at least 1 intermediate nonobstructive SVG lesion (30%-60% diameter stenosis by visual estimation). Patients were randomized (1:1) to DES implantation (SVG-DES) or medical treatment (SVG-MT) of the target SVG lesion.

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Whilst contingent valuation is increasingly used in economics to value benefits, questions remain concerning its external validity that is do hypothetical responses match actual responses? We present results from the first within sample field test. Whilst Hypothetical No is always an Actual No, Hypothetical Yes exceed Actual Yes responses. A constant rate of response reversals across bids/prices could suggest theoretically consistent option value responses.

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The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates.

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Cost-utility analyses undertaken to inform decision making regarding colorectal cancer (CRC) require a set of health state utility values (HSUVs) so that the time CRC patients spend in different health states can be aggregated into quality-adjusted life-years (QALY). This study reviews CRC-related HSUVs that could be used in economic evaluation and assesses their advantages and disadvantages with respect to valuation methods used and CRC clinical pathways. Fifty-seven potentially relevant studies were identified which collectively report 321 CRC-related HSUVs.

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Background: The prevalence of diabetes among adults in Mexico has increased markedly from 6.7 % in 1994 to 14.7 % in 2015.

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Providing a healthy school environment is a priority for child health. The aim of this study is to develop a methodology that allows quantification of the potential economic benefit of reducing indoor exposure to nitrogen dioxide (NO2) in children attending primary schools. Using environmental and health data collected in primary schools in London, this study estimates that, on average, 82 asthma exacerbations per school can be averted each year by reducing outdoor NO2 concentrations.

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Capture Hi-C (CHi-C) is a method for profiling chromosomal interactions involving targeted regions of interest, such as gene promoters, globally and at high resolution. Signal detection in CHi-C data involves a number of statistical challenges that are not observed when using other Hi-C-like techniques. We present a background model and algorithms for normalisation and multiple testing that are specifically adapted to CHi-C experiments.

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Introduction: Type 1 diabetes (T1D) in children and adolescents is increasing worldwide with a particular increase in children <5 years. Fewer than 1 in 6 children and adolescents achieve recommended glycated hemoglobin (HbA1c) values.

Methods: A pragmatic, cluster-randomized controlled trial assessed the efficacy of a clinic-based structured educational group incorporating psychological approaches to improve long-term glycemic control, quality of life and psychosocial functioning in children and adolescents with T1D.

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Maize crop production is constrained worldwide by nitrogen (N) availability and particularly in poor tropical and subtropical soils. The development of affordable high-throughput crop monitoring and phenotyping techniques is key to improving maize cultivation under low-N fertilization. In this study several vegetation indices (VIs) derived from Red-Green-Blue (RGB) digital images at the leaf and canopy levels are proposed as low-cost tools for plant breeding and fertilization management.

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Background: The influence of donor and recipient factors on outcomes following kidney transplantation is commonly analysed using Cox regression models, but this approach is not useful for predicting long-term survival beyond observed data. We demonstrate the application of a flexible parametric approach to fit a model that can be extrapolated for the purpose of predicting mean patient survival. The primary motivation for this analysis is to develop a predictive model to estimate post-transplant survival based on individual patient characteristics to inform the design of alternative approaches to allocating deceased donor kidneys to those on the transplant waiting list in the United Kingdom.

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Background: To determine whether treatment with ritonavir-boosted protease inhibitor (PI) monotherapy is associated with detrimental effects on neurocognitive function or brain imaging markers compared to standard antiretroviral therapy (ART).

Methods: Neuropsychological assessment and brain magnetic resonance imaging were performed at the last study visit in a subset of participants randomized to PI monotherapy (PI-mono group) or ongoing triple ART (OT group) in the PIVOT trial. We calculated a global z-score (NPZ-7) from the average of the individual test z-scores and the proportion of participants with symptomatic neurocognitive impairment (score >1 standard deviation below normative means in ≥2 cognitive domains and neurocognitive symptoms).

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Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceramidases may affect Gaucher disease. Here, we report the first three-dimensional structure for any GH116 enzyme, Thermoanaerobacterium xylanolyticum TxGH116 β-glucosidase, alone and in complex with diverse ligands.

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Purpose: Mid Upper Arm Circumference (MUAC) measurement is proposed as an adjunctive measure of re-nutrition progress in youth with eating disorders. We propose that MUAC is a clinically-useful measurement that can be used to inform clinicians about treatment progress. The aims of this study were twofold: 1) to test whether assessments of MUAC can track weight restoration in a similar pattern to direct measures of weight and 2) to examine adolescents' self-reported feelings in response to assessments of MUAC, weighing, and skinfolds (SF).

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