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Results for “population attributable fraction”

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PubMed2026

A Common CD36 Variant and the Genetic Landscape of Dilated Cardiomyopathy in Individuals of African Ancestry.

IMPORTANCE: Dilated cardiomyopathy (DCM) is a major cause of heart failure that disproportionately affects individuals of African genetic ancestry (AFR), among whom familial clustering of disease is also more pronounced relative to those of European ancestry (EUR). However, established monogenic DCM genes, identified primarily in EUR populations, explain a smaller proportion of DCM cases in AFR populations. A recent study identified a common AFR-specific nonsense variant in CD36 that accounts for a substantial burden of DCM in AFR. How the risk and population impact of this variant compare with those of established genetic causes of DCM is unknown. OBJECTIVE: To compare the contribution of a CD36 nonsense variant to DCM risk with that of truncating variants in TTN and pathogenic or likely pathogenic (P/LP) variants in other established DCM genes. DESIGN SETTING AND PARTICIPANTS: Multicohort genetic association study including AFR and EUR participants with exome or genome sequence and DCM case status from four datasets: All of Us, Million Veteran Program, Penn Medicine Biobank, and the DCM Precision Medicine Study. EXPOSURE: Carrier status for TTN truncating variants, P/LP variants in 11 high confidence DCM genes, and the CD36 nonsense variant (Y325*; 0, 1, or 2 copies). MAIN OUTCOMES AND MEASURES: Odds of DCM; prevalence of risk-variant carriers among DCM cases; and population attributable fraction (PAF) for DCM. RESULTS: Among 82,623 AFR individuals across four studies, the mean age was 53.4 years and 1,625 had DCM. CD36 Y325* risk-allele homozygotes had 4.8-fold (95% CI, 3.1-7.3) increased odds of DCM, and CD36 Y325* heterozygotes had 1.4-fold (95% CI, 1.2-1.7) increased odds. TTN truncating variants also conferred elevated risk of DCM in AFR participants (OR, 8.46; 95% CI, 5.3-12.3). Among AFR DCM cases, 2.5% were CD36 homozygotes, second only to TTN truncating variants (4.3%) and exceeding all other high-confidence DCM genes combined (1.5%). In population-level analyses incorporating both heterozygous and homozygous CD36 Y325* carriers, the population-attributable fraction for CD36 (9.0%) surpassed that of TTN truncating variants (3.6%). CONCLUSIONS AND RELEVANCE: An ancestry-specific CD36 variant contributes more to DCM burden in AFR ancestry than established DCM genes, including TTN truncating variants, typically considered the most common genetic cause of DCM. These findings reshape the known genetic architecture of DCM in individuals of African ancestry and highlight the importance of representation in genomic research.

Journal Article↗

PubMed2026

Early-onset colorectal cancer burden attributable to early-life obesity from 2000 to 2020 with projections to 2040.

PURPOSE: Early-onset colorectal cancer (age <50 years) incidence has increased globally since the 1990s for unknown reasons. Early-life exposure to established risk factors like adiposity is suspected to play a role, but the contribution to the rising disease burden remains unknown. This study quantified the potential impact of rising early-life obesity on early-onset colorectal cancer in Australia. METHODS: Population attributable fractions for early-onset colorectal cancer were derived from meta-analytic relative risks and obesity prevalence estimates in adolescents (10-19-year-olds), using body mass index data for 1990-2022 from the Noncommunicable Diseases Risk Factor Collaboration. Under age-specific carcinogenesis latency assumptions, we linked adolescent obesity prevalence estimates to colorectal cancer incidence across age groups (20-29, 30-39, and 40-49 years) using observed cancer incidence data from Australian cancer registries covering 2000-2019 and age-period-cohort modelling to generate scenario-based estimates of incidence and obesity-attributable cases through 2040. Trends in obesity-attributable colorectal cancer incidence were quantified using joinpoint regression. RESULTS: The proportion of early-onset colorectal cancers attributable to adolescent obesity across 1990-2022 rose from 2% to 6% in men and 1-3% in women (average annual change: 3-4%). Although absolute attributable incidence rates were low, they increased 2-20% per year, varying by period, age-dependent lag, and sex. Under the projection assumptions applied, scenario estimates suggest that adolescent obesity could account for an estimated 1465 early-onset cases by 2040. CONCLUSION: Early-life obesity is estimated to account for a growing yet minor fraction of early-onset colorectal cancers in Australia and is therefore unlikely to be a major driver of the rising disease incidence. These findings suggest that childhood obesity prevention programs may have only a small public health impact on early-onset colorectal cancer prevention. Therefore, it is imperative that other causal risk factors - especially early-life exposures - are identified to inform prevention strategies that stem the rising disease burden.

Obesity↗

PubMed2026

Sex-stratified mortality trends in preterm birth complications in Sierra Leone: progress, persistence, and equity implications.

BACKGROUND: Preterm birth complications remain a leading cause of neonatal mortality in Sierra Leone, despite recent health system gains. Evidence on long-term sex-specific disparities in mortality due to preterm birth complications is limited, constraining equitable neonatal care planning. OBJECTIVE: To examine two‑decade trends in sex‑stratified mortality from preterm birth complications using standardized equity indicators. METHODS: We conducted a retrospective longitudinal analysis of sex-disaggregated mortality estimates from the World Health Organization (WHO) Global Health Estimates (GHE), accessed through the WHO Health Equity Assessment Toolkit (HEAT), Built-in Database Edition (Version 6.0). Mortality rates per 100,000 population were extracted for 2001, 2006, 2011, 2016, and 2021. Inequality was assessed using absolute difference (D), relative ratio (R), population attributable risk (PAR), and population attributable fraction (PAF). RESULTS: Mortality declined substantially between 2001 and 2021 for both males (85.1-49.3 per 100,000) and females (71.2-39.9 per 100,000). Male mortality remained consistently higher across all years, with relative ratios indicating approximately 20-25% excess mortality among male neonates. Absolute inequalities narrowed modestly over time, whereas relative inequalities remained largely unchanged. PAR and PAF remained close to zero throughout the study period. Wider uncertainty intervals in earlier years reflected limited empirical data availability. CONCLUSION: Although preterm mortality declined over two decades, a persistent male disadvantage remained in Sierra Leone. These findings highlight the importance of integrating sex-disaggregated equity monitoring into neonatal policies and programmes. Future research should evaluate strategies to reduce the persistent excess mortality among male neonates while sustaining overall improvements in neonatal survival and progress toward Sustainable Development Goal 3.2.

Humans↗

PubMed2026

Age-stratified associations of glycemia, blood pressure, and cholesterol with mortality in diabetes: A prospective cohort study.

BACKGROUND: Optimization of HbA1c, blood pressure and cholesterol, referred to as the "ABCs", is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. METHODS: In this prospective cohort study, 43,732 Chinese adults aged ≥ 40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (< 55, 55-<65, 65-<75, ≥ 75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. RESULTS: During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction < 0.05). Among participants aged < 75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged < 65 years and 160 mmHg in those aged 65-<75 years. Among those aged ≥ 75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c ≥ 9%, with a hazard ratio (HR) of 1.51 (95% confidence interval [CI]: 1.19-1.91) for all-cause mortality and a subdistribution hazard ratio (SHR) of 1.70 (95% CI: 1.23-2.36) for cardiovascular mortality, while SBP showed no significant association with any mortality outcome in this age group. Moreover, LDL-C emerged as a significant risk factor for cardiovascular mortality. Compared with participants with LDL-C < 1.8 mmol/L, those with LDL-C of 1.8-<2.6 mmol/L exhibited a significantly higher risk (SHR: 1.86; 95% CI: 1.11-3.11). Additionally, LDL-C had the largest PAF for cardiovascular mortality (9.6%) within this age group. CONCLUSIONS: The impacts of ABC factors on mortality risk vary substantially by age among adults with diabetes. In patients aged ≥ 75 years, less stringent glycemic and blood pressure targets may be appropriate, whereas lipid management remains critically important for reducing cardiovascular mortality.

Humans↗

PubMed2025

Association of alcohol and different types of alcoholic beverages on the risk of buccal mucosa cancer in Indian men: a multicentre case-control study.

INTRODUCTION: While a large proportion of buccal mucosa cancer (BMC) is attributed to tobacco use, the contribution of alcohol is little-known. In India, alcohols include internationally-recognised (IRL) and locally-brewed liquor (LBL) types, which might contribute differently to the risk of BMC. We conducted an observational study to evaluate the association of local and foreign alcoholic beverage use on the risk of developing BMC. METHODS: Data from 1803 BMC cases and 1903 visitor controls from a multicentric case-control study was analysed for 11 IRLs and 30 LBLs. Healthy visitor controls were randomly sampled from the source population of the study centres which enrolled the cases. Quantitative data on the amount, the number of times consumed per day or week, and the lifetime duration of consumption for each of the alcoholic beverages were collected using an interviewer administered standardised questionnaire, which was then used to estimate the grams per day consumption of alcohol. Odds ratios (OR) and 95% CI were estimated after adjustment for potential confounders, including tobacco use. The joint effect of tobacco and alcohol on BMC risk, the attributable fraction (AF) of cases and state-wise population attributable fraction (PAF) were estimated. RESULTS: An increased risk of 1.68 (95% CI=1.44-1.97), 1.72 (95% CI=1.46-2.04), and 1.87 (95% CI=1.46-2.39) was observed for ever-users of any alcohol, IRLs and LBLs, respectively for BMC. The findings show 9 grams/day of alcohol increased the risk of BMC by approximately 50%, and 62% of cases could be attributed to alcohol drinking and chewing tobacco, with an overall PAF of 11.3% for India. CONCLUSION: This study shows that alcohol, even in low quantities, increases the risk for BMC. Prevention of consumption of tobacco and alcohol together could substantially reduce the incidence of BMC.

Humans↗

PubMed2026

Liver Cancer Risk and Incidence Attributable to Human Immunodeficiency Virus: A Meta-Analysis and Population-Attributable Modeling Study of Over 1.2 Million Individuals.

HIV-induced immune suppression and chronic inflammation elevate the risk of cancer progression. We conducted a systematic review and meta-analysis of studies published between January 1, 1984 and October 13, 2023 to assess the association between HIV infection and liver cancer. People living with HIV (PLHIV) had a higher risk (pooled relative risk = 3.36, 95% CI: 2.72-4.15). The global PAF for HIV-attributed liver cancer was 1.43% in 2019, with a three-fold increase over the past 30 years. The Asia-Pacific region recorded the second highest new cases of HIV-attributed liver cancer in 2019, and the highest age-standardized incidence rate (ASIR) in Eastern and Southern Africa. Particularly, the ASIR of HIV-attributed liver cancer increased rapidly in Eastern Europe and Central Asia, with the highest estimated annual percentage change reaching 22.98%. PLHIV have an increased risk and incidence of liver cancer. In regions with high burden of HIV-attributed liver cancer, it is essential to integrate prevention and effective treatment for HIV, viral hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis, and liver cancer.

Humans↗

PubMed1977

[Study of arteriosclerosis in different geographical zones of the Soviet Union. 3. Fatty acid composition of blood serum lipid fractions in Tashkent population].

The composition of fatty acids in triglycerides and cholesterol ethers of blood serum was studied in 90 normal males, Russians and Uzbeks, aged 20 to 50 years, living in the city of Tashkent. The peculiarity of the tryglycerides fraction in indigenous Tashkent inhabitants consists in a high content of linoleic acid. (24.8%). This is attributed to the peculiarities of nutrition of the indigenous Uzbekistan population--a consumption of great amounts of cotton-seed oil rich in linoleic acid. With the growing age, the content of the linoleic acid in the cholesterol ethers decreases, and the portion of palmitic and oleic acids growing. Among indigenous. Tashkent residents, aged 20-29 years, the relative content of the linoleic acid in the cholesterol ether fraction is higher than among the non-indigenous residents of the same age-group.

Adipose Tissue↗

PubMed1977

Differential fluorochromasia of human lymphocytes as measured by flow cytometry.

Peripheral human lymphocytes reacted with fluorescein diacetate and analyzed by flow cytometry produced a bimodal fluorescence distribution that was shown to be attributable to the differential staining of T and B lymphocytes. Lymphocytes were fractionated into rosetting (T cell) and nonrosetting (B cell) populations. Both subfractions were reacted with fluorescein diacetate and analyzed by flow cytometry. The rosetting fraction was more fluorescent than the nonrosetting fraction, and the analysis of an appropriate mixture of the subfractionated populations produced a fluorescence distribution very similar to that obtained with unfractionated lymphocytes.

B-Lymphocytes↗

PubMed1977

Differentiation of functionally active mouse T lymphocytes from functionally inactive bone marrow precursors II. Limited recovery of T-cell responses from mouse bone marrow in tissue culture.

The limited differentiation of mature T cell function from mouse bone marrow in tissue culture is described and compared with similar differentiation occuring in vivo in irradiated bone marrow protected mice. Data are presented to show that a pool of precursors, similar in size to that able to produce early (transient?) regeneration in thymectomized recipients, is responsible for the development of mitogen responsive T cells active in MLC (proliferation) and CML (development of cytotoxic cells) assays. In contrast, a helper cell population which augments antibody formation from T-depleted normal spleen cells derives from a pool of similar precursors yet does not seem to be theta positive. Similarly, larger cells (perhaps typical of those giving rise to suppressor T cells in vivo) give rise to a suppressor cell pool after 4 days of culture, though again only a fraction of this suppressor activity could be attributed to theta positive cells. It is suggested that much of the data for regenration of T lymphocytes in vitro from T-depleted sources needs to be re-interpreted in terms of this evidence for a pool of post-thymic precursors of T cells in such T-deficient cell populations.

Animals↗

PubMed1975

Fractionation of antigen reactive cells from immunized mice on columns coated with antigen or anti-immunoglobulin sera.

Immunocompetent cells obtained from NIP-RGG immunized mice were fractionated on bead columns coated with antigen or anti-immunoglobulin serum. The separated cell fractions were examined for their capacity to be stimulated by the antigen in short term culture, to produce antigen specific antibodies in the plaque assay and to bind radioactive labeled antigen. Cells which produce hapten specific antibodies or bind radioactive labeled hapten are removed from the cell population passed through a hapten-carrier complex coated column. Cells stimulated by the antigen to an increased DNA-synthesis are also retained by columns coated with the hapten-carrier-complex or the carrier alone; the fractionation seems to be carrier specific. The fractionation of cells is blocked by free antigen in the columnar fluid. However, the fractionation patterns of cells passed through anti-Ig-serum coated columns are different when antibody producing cells and cells stimulated by the antigen are compared. Whereas antibody producing cells and antigen binding cells are almost completely retained by anti-Ig-serum coated columns the cells which are stimulated by the hapten carrier complex are not removed from the passed cells. Studies to characterize the fractionated cell populations according to their sensitivity to anti-theta-serum, to the presence of Ig-receptors and to the phytohemagglutinin stimulation indicate that the antibody producing cells and the antigen binding cells have to be attributed to B-cells whereas the question whether the antigen stimulated cells are T- or B-cells cannot be definitely answered.

Animals↗

PubMed1976

A comparative study of extracellular sulfated glycosaminoglycans synthesized by rabbit corneal fibroblasts in organ and confluent cultures.

The extracellular sulfated glycosaminoglycans synthesized by explants of rabbit cornea and sclera, and by confluent cultures of corneal fibroblasts after incubation in medium containing 35S-sulfate were compared. The glycosaminoglycans isolated from corneal explants differed considerably from those obtained from confluent corneal fibroblast cultures and scleral explants. Only the corneal explants secreted into the nutrient medium a population of enzyme-resistant 35S-sulfate-labeled glycosaminoglycan that eluted from Dowex 1-X2 (Cl-) at a 3 M sodium chloride concentration, and which was resistant to testicular hyaluronidase, chondroitinase ABC, and nitrous acid degradation. With time, corneal explants gradually synthesized less of this fraction with these attributes of keratosulfate. If the corneal epithelium and endothelium remained on the corneal explants the total incorporated 35S-sulfate was approximately double that obtained when the cornea was striped of these cells.

Animals↗

PubMed1979

Establishment, characterization and virus expression of cell lines derived from radiation- and virus-induced lymphomas of C57BL/Ka mice.

Permanent cell lines have been established in vitro from lymphoid tumors induced in C57BH/Ka mice by fractionated X-irradiation or by inoculation of the radiation leukemia virus (RadOV). The cultured cells are lymphoblastic, replicate rapidly in vitro, and are tumorigenic in vivo. The cell surface markers Thy 1, Ly 1, Ly 2,3 and GIX are expressed by the lymphoid tumor cells in the mouse and persist in the corresponding cell lines; expression of the H-2 and TL antigens is greatly reduced during in vitro passage, but is restored on in vivo transplantation. The cell lines derived from RadLV-induced tumors (BL/VL lines) produce a virus population (RadLV/LTC) with the thymotropic and leukemogenic attributes of RadLV. Those derived from radiation-induced, virus-negative lymphomas (BL/RL lines) are initially devoid of MuLV expression, but frequently become spontaneous virus producers during in vitro cultivation.

Animals↗

PubMed1975

The extent of the stimulated electrical potential decay under phosphorylating conditions and the H+/ATP ratio in Rhodopseudomonas sphaeroides chromatophores following short flash excitation.

1. In chromatophores from Rps. sphaeroides, the stimulation by ADP and Pi of the electric potential decay indicated by the carotenoid shift is greater than the stimulation of the decay of pH change indicated by the colour change of added cresol red under similar conditions. This difference is attributed to H+ consumption during the synthesis of ATP. The ratio of H+ translocated across the membrane to ATP synthesized was estimated to be approximately 1.7 H+/ATP. 2. The stimulation of the electrical potential decay by ADP and Pi was found to be a constant fraction (10%) of the total decay when the flash intensity was varied. No 'critical' or 'threshold' potential was observed. 3. The stimulated electrical potential decay after a second flash, given within a few seconds of the first, was related to the amplitude of the electrical potential produced by the second flash (10%) but neither to the dark time between the flashes, nor to the total extent of the electrical potential above the dark level. These results are consistent with two hypotheses (a) the chromatophores are a mixed population of vesicles, only a small fraction (10%) of which possess an active ATP synthesizing system (b) the activity of the ATP synthesizing system, though driven by a proton motive force, is controlled by electron transport processess. If alternative (a) is correct then the overall single turnover flash yield of 1 ATP per 1470 bacteriochlorophyll measured in (1) would mean that the yield of the active vesicles is approximately 10 ATP per 1470 bacteriochlorophyll or 30 ATP per vesicle. 4. The stimulation of the electrical potential decay by ADP and Pi is approximately 40% less in antimycin-treated chromatophores. It is shown that this is probably a consequence of antimycin-inhibited H+-release on the inside of the chromatophore vesicles following a flash.

Adenosine Diphosphate↗

PubMed1975

Rsistance to streptomycin in a producing strain of Streptomyces griseus.

Streptomyces griseus S 104 was sensitive to streptomycin during exponential growth in a medium which, in the subsequent stationary phase, supported production of the antibiotic in yields above 200 mug/ml. When antibiotic production began cultures developed a tolerance toward their lethal metabolite. This was not due to an increase in pH associated with antibiotic production, since pH effects on streptomycin sensitivity in S. griseus were in the reverse direction. However, the degree of tolerance was directly related to the amount of cell material present. Streptomycin production caused no change in the proportion of resistant variants in the population, nor did it cause the severe inhibition of protein synthesis observed in non-producing cultures exposed to the antibiotic. The lack of an effect on protein synthesis is attributed to the absence of streptomycin with in the cytoplasm since soluble extracts from mycelium harvested in the production phase were inactive when bioassayed immediately after cell disruption. However, they developed antibacterial activity rapidly when heated, and more slowly when incubated at 25 degrees C. The addition of phosphatase inhibitors during incubation prevented the appearance of antibiotic activity, and it was concluded that a small amount of streptomycin phosphate is present in the mycelium during antibiotic production. Differences in (14C) streptomycin uptake suggested that the mycelium was appreciably less permeable to the antibiotic in the production phase than during exponential growth. However, a small amount was taken up and much of it was in the soluble fraction of disrupted cells. Bioassays showed that this 14C-labeled antibiotic within the cells had been partially inactivated, suggesting that conversion of streptomycin to an inactive derivative is involved in the mechanism which protects the organism from its metabolite.

Alkaline Phosphatase↗