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Notwithstanding current heavy dependence on gas-fired electricity generation in the Eastern African Power Pool (EAPP), hydropower is expected to play an essential role in improving electricity access in the region. Expansion planning of electricity infrastructure is critical to support investment and maintaining balanced consumer electricity prices. Variations in water availability due to a changing climate could leave hydro infrastructure stranded or result in underutilization of available resources. In this study, we develop a framework consisting of long-term models for electricity supply and water systems management, to assess the vulnerability of potential expansion plans to the effects of climate change. We find that the most resilient EAPP rollout strategy corresponds to a plan optimised for a slightly wetter climate compared to historical trends. This study demonstrates that failing to climate-proof infrastructure investments can result in significant electricity price fluctuations in selected countries (Uganda & Tanzania) while others, such as Egypt, are less vulnerable. Hydropower generation in the Nile River Basin is vulnerable to climatic changes. Here, the authors assess infrastructure resilience of the Eastern African power pool (EAPP) to the effects of a changing climate and suggest that failing to climate-proof infrastructure investments can result in significant electricity price fluctuations.

Marijuana is a widely used psychoactive substance in the US and medical and recreational legalization has risen over the past decade. Despite the growing number of individuals using marijuana, studies investigating the association between epigenetic factors and recent and cumulative marijuana use remain limited. We therefore investigated the association between recent and cumulative marijuana use and DNA methylation levels. Participants from the Coronary Artery Risk Development in Young Adults Study with whole blood collected at examination years (Y) 15 and Y20 were randomly selected to undergo DNA methylation profiling at both timepoints using the Illumina MethylationEPIC BeadChip. Recent use of marijuana was queried at each examination and used to estimate cumulative marijuana use from Y0 to Y15 and Y20. At Y15 ( n  = 1023), we observed 22 and 31 methylation markers associated (FDR P  ≤ 0.05) with recent and cumulative marijuana use and 132 and 16 methylation markers at Y20 ( n  = 883), respectively. We replicated 8 previously reported methylation markers associated with marijuana use. We further identified 640 cis -meQTLs and 198 DMRs associated with recent and cumulative use at Y15 and Y20. Differentially methylated genes were statistically overrepresented in pathways relating to cellular proliferation, hormone signaling, and infections as well as schizophrenia, bipolar disorder, and substance-related disorders. We identified numerous methylation markers, pathways, and diseases associated with recent and cumulative marijuana use in middle-aged adults, providing additional insight into the association between marijuana use and the epigenome. These results provide novel insights into the role marijuana has on the epigenome and related health conditions.

Background High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). Methods This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. Results We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43–58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. Conclusion Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

Adverse childhood experiences (ACEs) are associated with the risk of poorer health, and identifying molecular mechanisms may lay the foundation for health promotion in people with ACEs. To investigate the associations of ACEs with changes in epigenetic age acceleration (EAA), a biomarker associated with various health outcomes in middle-aged adults, in a population with balanced race and sex demographics. Data for this cohort study were from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants in CARDIA underwent 8 follow-up exams from baseline (year 0 [Y0]; 1985-1986) to Y30 (2015-2016), and participant blood DNA methylation information was obtained at Y15 (2000-2001) and Y20 (2005-2006). Individuals from Y15 and Y20 with available DNA methylation data and complete variables for ACEs and covariates were included. Data were analyzed from September 2021 to August 2022. Participant ACEs (general negligence, emotional negligence, physical violence, physical negligence, household substance abuse, verbal and emotional abuse, and household dysfunction) were obtained at Y15. The primary outcome consisted of results from 5 DNA methylation-based EAA measurements known to be associated with biological aging and long-term health: intrinsic EAA (IEAA), extrinsic EAA (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), measured at Y15 and Y20. Linear regression and generalized estimating equations were used to assess associations of the burden of ACEs (≥4 vs <4 ACEs) with EAA adjusting for demographics, health-related behaviors, and early life and adult socioeconomic status. A total of 895 participants for Y15 (mean [SD] age, 40.4 [3.5] years; 450 males [50.3%] and 445 females [49.7%]; 319 Black [35.6%] and 576 White [64.4%]) and 867 participants for Y20 (mean [SD] age, 45.4 [3.5] years; 432 males [49.8%] and 435 females [50.2%]; 306 Black [35.3%] and 561 White [64.7%]) were included after excluding participants with missing data. There were 185 participants with (20.7%) vs 710 participants without (79.3%) 4 or more ACEs at Y15 and 179 participants with (20.6%) vs 688 participants without (79.4%) 4 or more ACEs at Y20. Having 4 or more ACEs was positively associated with EAA in years at Y15 (EEAA: β = 0.60 years; 95% CI, 0.18-1.02 years; PhenoAA: β = 0.62 years; 95% CI = 0.13-1.11 years; GrimAA: β = 0.71 years; 95% CI, 0.42-1.00 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) and Y20 (IEAA: β = 0.41 years; 95% CI, 0.05-0.77 years; EEAA: β = 1.05 years; 95% CI, 0.66-1.44 years; PhenoAA: β = 0.57 years; 95% CI, 0.08-1.05 years; GrimAA: β = 0.57 years; 95% CI, 0.28-0.87 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) after adjusting for demographics, health-related behaviors, and socioeconomic status. In this cohort study, ACEs were associated with EAA among middle-aged adults after controlling for demographics, behavior, and socioeconomic status. These findings of the associations between early life experience and the biological aging process in midlife may contribute to health promotion in a life course perspective.

Background: Methylation of repetitive elements Alu and LINE-1 in humans is considered a surrogate for global DNA methylation. Previous studies of blood-measured Alu/LINE-1 and cancer risk are inconsistent. Methods: We studied 1259 prospective methylation measurements from blood drawn 1–4 times from 583 participants from 1999 to 2012. We used Cox regression to evaluate time-dependent methylation as a biomarker for cancer risk and mortality, and linear regression to compare mean differences in methylation over time by cancer status and analyse associations between rate of methylation change and cancer. Results: Time-dependent LINE-1 methylation was associated with prostate cancer incidence (HR: 1.38, 95% CI: 1.01–1.88) and all-cancer mortality (HR: 1.41, 95% CI: 1.03–1.92). The first measurement of Alu methylation (HR: 1.39, 95% CI: 1.08–1.79) was associated with all-cancer mortality. Participants who ultimately developed cancer had lower mean LINE-1 methylation than cancer-free participants 10+ years pre-diagnosis ( P <0.01). Rate of Alu methylation change was associated with all-cancer incidence (HR: 3.62, 95% CI: 1.09–12.10). Conclusions: Our results add longitudinal data on blood Alu and LINE-1 methylation and cancer, and potentially contribute to their use as early-detection biomarkers. Future larger studies are needed and should account for the interval between blood sample collection and cancer diagnosis.

Background The metabolic syndrome (MetS) is a collection of metabolic disturbances that can lead to various cardiovascular diseases. Previous studies have shown a more adverse metabolic risk profile is associated with more advanced biological aging. The associations between epigenetic biomarkers of age with MetS, however, are not well understood. We therefore investigated the associations between epigenetic age acceleration and MetS severity score and incident MetS. Results A subset of study participants with available whole blood at examination years 15 and 20 from the Coronary Artery Risk Development in Young Adults Study underwent epigenomic profiling using the Illumina MethylationEPIC Beadchip (~ 850,000 sites). Intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA) were calculated from DNA methylation levels. The MetS severity score was positively associated with IEAA at years 15 ( P  = 0.016) and 20 ( P  = 0.016) and EEAA at year 20 ( P  = 0.040) in cross-sectional analysis. IEAA at year 20 was significantly associated with incident MetS at year 30 (OR = 1.05 [95% CI 1.01, 1.10], P  = 0.028). Conclusions To our knowledge, this is the first report of the longitudinal association between epigenetic age acceleration and MetS. These findings suggest that a higher MetS severity score is associated with accelerated epigenetic aging and such aging may play a role in the development of metabolic disorders, potentially serving as a useful biomarker of and early detection tool for future MetS.

Background GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with atherosclerotic cardiovascular disease. However, the associations between early adulthood lipid levels and GAA in midlife are unknown. Also, it is unknown whether GAA mediates the associations between lipid levels in young adults and subclinical atherosclerosis in midlife. Results We estimated measures of epigenetic age acceleration in 1118 White and Black participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at examination years (Y) 15 and 20. We used multivariable regression models to examine associations of Y15 and Y20 GAA estimates with plasma lipid levels measured at prior examination years (Y0, Y5, and Y10) and concurrently: triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. Mediation analysis was used to assess the extent to which GAA may mediate associations between plasma lipids and coronary artery calcification (CAC). In our study each 1-SD higher cumulative TG level was associated with an average 0.73 ± 0.12 years older GAA. Each 1-SD higher cumulative HDL-C level was associated with an average 0.57 ± 0.17 years younger GAA. Stratified analyses showed that the associations between TG and GAA were stronger among female and Black participants and the associations between HDL-C and GAA were stronger among female and White participants. GAA statistically mediated 17.4% of the association of cumulative TG with CAC. Conclusions High TG and low HDL-C in early adulthood are associated with accelerated epigenetic aging by midlife. Increased epigenetic age acceleration may partially mediate the associations between high TG levels and the presence of subclinical atherosclerosis.

This study aimed at supporting robust decision-making for planning and management of water–energy–food Nexus systems in the country of Jordan. Nexus priority challenges in Jordan were identified as (1) water scarcity, (2) agricultural productivity and water quality, and (3) shift to energy independence. We created a water–energy–food Nexus model that integrates three modelling frameworks: (1) the Water Evaluation and Planning system WEAP model to estimate water demands, supplies and allocation; (2) the MABIA model to estimate crop production, and, (3) a GIS-based energy modelling tool to estimate energy requirements of the water system. Through a set of scenario runs, results show how desalination is needed to address water scarcity, but it has to be coupled with low-carbon electricity generation in order to not exacerbate climate change. Improving water productivity in agriculture improves most of the studied dimensions across the water–energy–food security nexus; however, it does little for water scarcity at the municipal level. Reducing non-revenue water can have positive effects on municipal unmet demand and reduction of energy for pumping, but it does not improve agricultural water productivity and may have negative feedback effects on the Jordan Valleys aquifer levels. Energy efficiency can support energy-intensive projects, like desalination, by substantially reducing the load on the energy system, preventing increased emissions and achieving a more resilient water system. Finally, when all interventions are considered together all of the major drawbacks are reduced and the benefits augmented, producing a more holistic solution to the WEF Nexus challenges in Jordan.

Background DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavioral exposures, it is important to identify which of these exposures may have the strongest contributions to differences in GrimAA, to help guide potential intervention strategies. Here, we assessed the relative contributions of lifestyle- and health-related components, as well as their collective association, to GrimAA. Results We included 744 participants (391 men and 353 women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with blood DNA methylation information at CARDIA Exam Year (Y) 20 (2005–2006, mean age 45.9 years). Six cumulative exposures by Y20 were included in the analysis: total packs of cigarettes, total alcohol consumption, education years, healthy diet score, sleep hours, and physical activity. We used quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods to assess the relative contribution of each exposure to a single overall association with GrimAA. We also assessed the collective association of the six components combined with GrimAA. Smoking showed the greatest positive contribution to GrimAA, accounting for 83.5% of overall positive associations of the six exposures with GrimAA (QGC weight = 0.835). The posterior inclusion probability (PIP) of smoking also achieved the highest score of 1.0 from BKMR analysis. Healthy diet and education years showed inverse contributions to GrimAA. We observed a U-shaped pattern in the contribution of alcohol consumption to GrimAA. While smoking was the greatest contributor across sex and race subgroups, the relative contributions of other components varied by subgroups. Conclusions Smoking, alcohol consumption, and education showed the highest contributions to GrimAA in our study. Higher amounts of smoking and alcohol consumption were likely to contribute to greater GrimAA, whereas achieved education was likely to contribute to lower GrimAA. Identifying pertinent lifestyle- and health-related exposures in a context of collective components can provide direction for intervention strategies and suggests which components should be the primary focus for promoting younger GrimAA.

Background The two most common repetitive elements (REs) in humans, long interspersed nuclear element-1 (LINE-1) and Alu element (Alu), have been linked to various cancers. Hepatitis C virus (HCV) may cause hepatocellular carcinoma (HCC) by suppressing host defenses, through DNA methylation that controls the mobilization of REs. We aimed to investigate the role of RE methylation in HCV-induced HCC (HCV-HCC). Results We studied methylation of over 30,000 locus-specific REs across the genome in HCC, cirrhotic, and healthy liver tissues obtained by surgical resection. Relative to normal liver tissue, we observed the largest number of differentially methylated REs in HCV-HCC followed by alcohol-induced HCC (EtOH-HCC). After excluding EtOH-HCC-associated RE methylation (FDR < 0.001) and those unable to be validated in The Cancer Genome Atlas (TCGA), we identified 13 hypomethylated REs (11 LINE-1 and 2 Alu) and 2 hypermethylated REs (1 LINE-1 and 1 Alu) in HCV-HCC (FDR < 0.001). A majority of these REs were located in non-coding regions, preferentially enriched with chromatin repressive marks H3K27me3, and positively associated with gene expression (median correlation r  = 0.32 across REs). We further constructed an HCV-HCC RE methylation score that distinguished HCV-HCC (lowest score), HCV-cirrhosis, and normal liver (highest score) in a dose-responsive manner ( p for trend < 0.001). HCV-cirrhosis had a lower score than EtOH-cirrhosis ( p  = 0.038) and HCV-HCC had a lower score than EtOH-HCC in TCGA ( p  = 0.024). Conclusions Our findings indicate that HCV infection is associated with loss of DNA methylation in specific REs, which could implicate molecular mechanisms in liver cancer development. If our findings are validated in larger sample sizes, methylation of these REs may be useful as an early detection biomarker for HCV-HCC and/or a target for prevention of HCC in HCV-positive individuals.