Divergent findings regarding the prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) patients exist in current literature. We aim to review data from published ...studies in order to examine the association between CIMP and CRC prognosis.
A comprehensive search for studies reporting disease-free survival (DFS), overall survival (OS), or cancer-specific mortality of CRC patients stratified by CIMP is carried out. Study findings are summarized descriptively and quantitatively, using adjusted hazard ratios (HRs) as summary statistics.
Thirty-three studies reporting survival in 10 635 patients are included for review. Nineteen studies provide data suitable for meta-analysis. The definition of CIMP regarding gene panel, marker threshold, and laboratory method varies across studies. Pooled analysis shows that CIMP is significantly associated with shorter DFS (pooled HR estimate 1.45; 95% confidence interval (CI) 1.07–1.97, Q = 3.95, I2 = 0%) and OS (pooled HR estimate 1.43; 95% CI 1.18–1.73, Q = 4.03, I2 = 0%) among CRC patients irrespective of microsatellite instability (MSI) status. Subgroup analysis of microsatellite stable (MSS) CRC patients also shows significant association between shorter OS (pooled HR estimate 1.37; 95% CI 1.12–1.68, Q = 4.45, I2 = 33%) and CIMP. Seven studies have explored CIMP's value as a predictive factor on stage II and III CRC patient's DFS after receiving adjuvant 5-fluorouracil (5-FU) therapy: of these, four studies showed that adjuvant chemotherapy conferred a DFS benefit among CIMP(+) patients, one concluded to the contrary, and two found no significant correlation. Insufficient data was present for statistical synthesis of CIMP's predictive value among CRC patients receiving adjuvant 5-FU therapy.
CIMP is independently associated with significantly worse prognosis in CRC patients. However, CIMP's value as a predictive factor in assessing whether adjuvant 5-FU therapy will confer additional survival benefit to CRC patients remained to be determined through future prospective randomized studies.
Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement ...Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes.
This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models.
Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays.
Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure.
International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.
To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for ...major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers.
DyCo2Mnx (x = 0.0, 0.2, 0.4, 0.6, and 1.0) compounds were synthesised and found to all be single-phase, isostructural to DyCo2 (MgCu2 Laves phase cubic structure (Fd-3 m) at room temperature). ...DyCo2Mn exhibits a huge coercivity field HC = 21,170 Oe at 5 K. The magnetic transition at Curie temperature TC, was observed as first order for DyCo2 but second order for the Mn doped compounds. Using Kouvel-Fisher plot, critical isotherm analysis and Arrott-Noaks plot techniques, a detailed critical exponents analysis was carried out on these transitions: critical exponents β ≈ 0.5, γ ≈ 1.0, and δ ≈ 3.0 were derived indicating that all the second-order transitions belong exhibit long-range magnetic interactions during the magnetic transitions. High-resolution synchrotron X-ray measurements confirm that there are crystal structure transformations sychronised with the magnetic transitions from paramagnetism to ferrimagnetism (PM-FM) at TC in the x = 0.0 and 0.2 cases with crystal structure changing from cubic (Fd-3 m) to tetragonal (I41/amd), However structures remain cubic (Fd-3 m) for x = 0.4, 0.6, and 1.0.
•A change of crystal structure from cubic (Fd-3 m) to tetragonal (I41/amd) near Tc occurs in both DyCo2 and DyCo2Mn0.2.•Strong competition between the electronic structure, rare earth molecular field and rR/rCo ratio factors affects the crystal structure type.•An extreme huge coercivity HC = 21,170 Oe at 5 K was found in DyCo2Mn.•TC increases from 141 K for DyCo2 to 295 K for DyCo2Mn0.4.•A broad operating temperature range in DyCo2Mn is found, which is an advantage for the practical magnetic cooling technology application.
This study explored the utility of the impact response surface (IRS) approach for investigating model ensemble crop yield responses under a large range of changes in climate. IRSs of spring and ...winter wheat Triticum aestivum yields were constructed from a 26-member ensemble of process-based crop simulation models for sites in Finland, Germany and Spain across a latitudinal transect. The sensitivity of modelled yield to systematic increments of changes in temperature (−2 to +9°C) and precipitation (−50 to +50%) was tested by modifying values of baseline (1981 to 2010) daily weather, with CO₂ concentration fixed at 360 ppm. The IRS approach offers an effective method of portraying model behaviour under changing climate as well as advantages for analysing, comparing and presenting results from multi-model ensemble simulations. Though individual model behaviour occasionally departed markedly from the average, ensemble median responses across sites and crop varieties indicated that yields decline with higher temperatures and decreased precipitation and increase with higher precipitation. Across the uncertainty ranges defined for the IRSs, yields were more sensitive to temperature than precipitation changes at the Finnish site while sensitivities were mixed at the German and Spanish sites. Precipitation effects diminished under higher temperature changes. While the bivariate and multi-model characteristics of the analysis impose some limits to interpretation, the IRS approach nonetheless provides additional insights into sensitivities to inter-model and inter-annual variability. Taken together, these sensitivities may help to pinpoint processes such as heat stress, vernalisation or drought effects requiring refinement in future model development.
Drylands cover about 40% of the terrestrial land surface and account for approximately 40% of global net primary productivity. Water is fundamental to the biophysical processes that sustain ecosystem ...function and food production, particularly in drylands where a tight coupling exists between ecosystem productivity, surface energy balance, biogeochemical cycles, and water resource availability. Currently, drylands support at least 2 billion people and comprise both natural and managed ecosystems. In this synthesis, we identify some current critical issues in the understanding of dryland systems and discuss how arid and semiarid environments are responding to the changes in climate and land use. The issues range from societal aspects such as rapid population growth, the resulting food and water security, and development issues, to natural aspects such as ecohydrological consequences of bush encroachment and the causes of desertification. To improve current understanding and inform upon the needed research efforts to address these critical issues, we identify some recent technical advances in terms of monitoring dryland water dynamics, water budget and vegetation water use, with a focus on the use of stable isotopes and remote sensing. These technological advances provide new tools that assist in addressing critical issues in dryland ecohydrology under climate change.
The risk of several cancers, including colorectal cancer, is increased in patients with obesity and type 2 diabetes, conditions characterised by hyperinsulinaemia and insulin resistance. Because ...hyperinsulinaemia itself is an independent risk factor for cancer development, we examined tissue-specific insulin action in intestinal tumour formation. In vitro, insulin increased proliferation of intestinal tumour epithelial cells by almost two-fold in primary culture of tumour cells from Apc
mice. Surprisingly, targeted deletion of insulin receptors in intestinal epithelial cells in Apc
mice did not change intestinal tumour number or size distribution on either a low or high-fat diet. We therefore asked whether cells in the tumour stroma might explain the association between tumour formation and insulin resistance. To this end, we generated Apc
mice with loss of insulin receptors in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules and increased the frequency of neutrophils in tumours. We conclude that although insulin is mitogenic for intestinal tumour cells in vitro, impaired insulin action in the tumour microenvironment may be more important in conditions where hyperinsulinaemia is secondary to insulin resistance. Insulin resistance in tumour endothelial cells produces an activated, proinflammatory state that promotes tumorigenesis. Improvement of endothelial dysfunction may reduce colorectal cancer risk in patients with obesity and type 2 diabetes.
The increasing consumption of ultra-processed food (UPF) and the global chain of food production have a negative impact on human health and planetary health. These foods have been replacing the ...consumption of nonprocessed healthy foods. This shift has not only worsened human health by increasing the risk of the development of noncommunicable diseases, but also resulted in environmental perturbations. This review aims to bring awareness of the problems caused by the industrialized food production chain, addressing the negative effects it has on the environment and human health, with special reference to chronic kidney disease (CKD). We discuss possible solutions focusing on the benefits of adopting plant-based diets with low UPF content to promote a sustainable and healthy food production and diet for patients with CKD. For a sustainable future we need to “connect the dots” of planetary health, food production, and nutrition in the context of CKD.
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