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- Vickman, R. E., et al.
(författare)
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Deconstructing tumor heterogeneity : The stromal perspective
- 2020
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 11:40, s. 3621-3632
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Tidskriftsartikel (refereegranskat)abstract
- Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive versus suppressive stroma and how cellular composition and function may be altered during disease progression. It also highlighted microenvironment-centered mechanisms dictating indolence or aggressiveness of early lesions and how spatial geography impacts stromal attributes and function. The prognostic and therapeutic implications as well as potential vulnerabilities within the heterogeneous tumor microenvironment were also discussed. These broad topics were included in this workshop as an effort to identify current challenges and knowledge gaps in the field. Copyright:
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| 2. |
- Miller, V., et al.
(författare)
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Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study
- 2017
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 390:10107, s. 2037-2049
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Tidskriftsartikel (refereegranskat)abstract
- Background The association between intake of fruits, vegetables, and legumes with cardiovascular disease and deaths has been investigated extensively in Europe, the USA, Japan, and China, but little or no data are available from the Middle East, South America, Africa, or south Asia. Methods We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality. Findings Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3.91 (SD 2.77) servings per day. During a median 7.4 years (5.5-9.3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0.90, 95% CI 0.74-1.10, p(trend) = 0.1301), myocardial infarction (0.99, 0.74-1.31;p(trend) = 0.2033), stroke (0.92, 0.67-1.25;p(trend) = 0.7092), cardiovascular mortality (0.73, 0.53-1.02; p(trend) = 0.0568), non-cardiovascular mortality (0.84, 0.68-1.04; p trend = 0.0038), and total mortality (0.81, 0.68-0.96; p(trend) < 0.0001). The HR for total mortality was lowest for three to four servings per day (0.78, 95% CI 0.69-0.88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality. Interpretation Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day).
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| 3. |
- Attaei, M. W., et al.
(författare)
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Availability and affordability of blood pressure-lowering medicines and the effect on blood pressure control in high-income, middle-income, and low-income countries: an analysis of the PURE study data
- 2017
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Ingår i: Lancet Public Health. - 2468-2667. ; 2:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Hypertension is considered the most important risk factor for cardiovascular diseases, but its control is poor worldwide. We aimed to assess the availability and affordability of blood pressure-lowering medicines, and the association with use of these medicines and blood pressure control in countries at varying levels of economic development. Methods We analysed the availability, costs, and affordability of blood pressure-lowering medicines with data recorded from 626 communities in 20 countries participating in the Prospective Urban Rural Epidemiological (PURE) study. Medicines were considered available if they were present in the local pharmacy when surveyed, and affordable if their combined cost was less than 20% of the households' capacity to pay. We related information about availability and affordability to use of these medicines and blood pressure control with multilevel mixed-effects logistic regression models, and compared results for high-income, upper-middle-income, lower-middle-income, and low-income countries. Data for India are presented separately because it has a large generic pharmaceutical industry and a higher availability of medicines than other countries at the same economic level. Findings The availability of two or more classes of blood pressure-lowering drugs was lower in low-income and middle-income countries (except for India) than in high-income countries. The proportion of communities with four drug classes available was 94% in high-income countries (108 of 115 communities), 76% in India (68 of 90), 71% in upper-middle-income countries (90 of 126), 47% in lower-middle-income countries (107 of 227), and 13% in low-income countries (nine of 68). The proportion of households unable to afford two blood pressure-lowering medicines was 31% in low-income countries (1069 of 3479 households), 9% in middle-income countries (5602 of 65 471), and less than 1% in high-income countries (44 of 10 880). Participants with known hypertension in communities that had all four drug classes available were more likely to use at least one blood pressure-lowering medicine (adjusted odds ratio [OR] 2.23, 95% CI 1.59-3.12); p<0.0001), combination therapy (1.53, 1.13-2.07; p=0.054), and have their blood pressure controlled (2.06, 1.69-2.50; p<0.0001) than were those in communities where blood pressure-lowering medicines were not available. Participants with known hypertension from households able to afford four blood pressure-lowering drug classes were more likely to use at least one blood pressure-lowering medicine (adjusted OR 1.42, 95% CI 1.25-1.62; p<0.0001), combination therapy (1.26, 1.08-1.47; p=0.0038), and have their blood pressure controlled (1.13, 1.00-1.28; p=0.0562) than were those unable to afford the medicines. Interpretation A large proportion of communities in low-income and middle-income countries do not have access to more than one blood pressure-lowering medicine and, when available, they are often not affordable. These factors are associated with poor blood pressure control. Ensuring access to affordable blood pressure-lowering medicines is essential for control of hypertension in low-income and middle-income countries. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.
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| 4. |
- Mohan, D., et al.
(författare)
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Associations of Fish Consumption With Risk of Cardiovascular Disease and Mortality Among Individuals With or Without Vascular Disease From 58 Countries
- 2021
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Ingår i: Jama Internal Medicine. - : American Medical Association (AMA). - 2168-6106. ; 181:5, s. 631-649
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Cohort studies report inconsistent associations between fish consumption, a major source of long-chain omega-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown. OBJECTIVE To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease. DESIGN, SETTING, AND PARTICIPANTS This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies-147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020. EXPOSURES Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish. MAIN OUTCOMES AND MEASURES Mortality and major CVD events (includingmyocardial infarction, stroke, congestive heart failure, or sudden death). RESULTS Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (<= 50 g/mo), an intake of 350 g/wk or morewas not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/moor lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of omega-3 fatty acidswere strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fishwere neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I-2 = 82.6[P =.02]; for death, I-2 = 90.8[P =.001]). CONCLUSIONS AND RELEVANCE Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.
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