One of the processes that may play a key role in plant species coexistence and ecosystem functioning is plant–soil feedback, the effect of plants on associated soil communities and the resulting ...feedback on plant performance. Plant–soil feedback at the interspecific level (comparing growth on own soil with growth on soil from different species) has been studied extensively, while plant–soil feedback at the intraspecific level (comparing growth on own soil with growth on soil from different accessions within a species) has only recently gained attention. Very few studies have investigated the direction and strength of feedback among different taxonomic levels, and initial results have been inconclusive, discussing phylogeny, and morphology as possible determinants. To test our hypotheses that the strength of negative feedback on plant performance increases with increasing taxonomic level and that this relationship is explained by morphological similarities, we conducted a greenhouse experiment using species assigned to three taxonomic levels (intraspecific, interspecific, and functional group level). We measured certain fitness‐related aboveground traits and used them along literature‐derived traits to determine the influence of morphological similarities on the strength and direction of the feedback. We found that the average strength of negative feedback increased from the intraspecific over the interspecific to the functional group level. However, individual accessions and species differed in the direction and strength of the feedback. None of our results could be explained by morphological dissimilarities or individual traits. Synthesis. Our results indicate that negative plant–soil feedback is stronger if the involved plants belong to more distantly related species. We conclude that the taxonomic level is an important factor in the maintenance of plant coexistence with plant–soil feedback as a potential stabilizing mechanism and should be addressed explicitly in coexistence research, while the traits considered here seem to play a minor role.
We tested plant–soil feedback, a suggested mechanism of plant coexistence, at three taxonomic levels within the same experiment. We found that its strength increased from the intraspecific over the interspecific to the functional group level indicating a role in diversity maintenance within and between species.
The interactions between pregnancy and breast cancer (BC) are complex. Overall, parity is associated with long-term protective effects against BC, however in a small group of susceptible patients, ...pregnancy can lead to the development of a form of BC with a particularly poor prognosis. Pregnancy-associated breast cancer (PABC) remains an under-studied but important and growing clinical problem worldwide. Several aspects of PABC, including risk factors and mechanisms involved in its occurrence and aggressiveness, are incompletely understood. This review aims to summarize the epidemiology, biology, patho-physiology and clinical characteristics of PABC. We emphasize that age at first pregnancy, absence of breastfeeding and family history stand out as possible risk factors for developing PABC that ought to be incorporated into clinical tools for assessing a woman's risk of developing PABC. Also, improved methods for identifying women at risk of developing PABC in the general population are needed.
•Pregnancy exerts a dual effect on the subsequent risk of developing breast cancer (BC).•Pregnancy-associated breast cancer (PABC) is a BC case that occurs during pregnancy or within 1 year following birth.•Mechanisms causing PABC are unclear due to hormonal and immune changes that occur during pregnancy and breast involution.•Older age- first pregnancy, no breastfeeding, and family history of BC are possible clinical biomarkers for developing PABC.•A higher awareness and improved methods for identifying women at risk in the general population are needed.
Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG ...methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test.
A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05.
At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP.
Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs.
Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Understanding the mechanisms of community coexistence and ecosystem functioning may help to counteract the current biodiversity loss and its potentially harmful consequences. In recent years, ...plant–soil feedback that can, for example, be caused by below‐ground microorganisms has been suggested to play a role in maintaining plant coexistence and to be a potential driver of the positive relationship between plant diversity and ecosystem functioning. Most of the studies addressing these topics have focused on the species level. However, in addition to interspecific interactions, intraspecific interactions might be important for the structure of natural communities. Here, we examine intraspecific coexistence and intraspecific diversity effects using 10 natural accessions of the model species Arabidopsis thaliana (L.) Heynh. We assessed morphological intraspecific diversity by measuring several above‐ and below‐ground traits. We performed a plant–soil feedback experiment that was based on these trait differences between the accessions in order to determine whether A. thaliana experiences feedback at intraspecific level as a result of trait differences. We also experimentally tested the diversity–productivity relationship at intraspecific level. We found strong differences in above‐ and below‐ground traits between the A. thaliana accessions. Overall, plant–soil feedback occurred at intraspecific level. However, accessions differed in the direction and strength of this feedback: Some accessions grew better on their own soils, some on soils from other accessions. Furthermore, we found positive diversity effects within A. thaliana: Accession mixtures produced a higher total above‐ground biomass than accession monocultures. Differences between accessions in their feedback response could not be explained by morphological traits. Therefore, we suggest that they might have been caused by accession‐specific accumulated soil communities, by root exudates, or by accession‐specific resource use based on genetic differences that are not expressed in morphological traits. Synthesis. Our results provide some of the first evidence for intraspecific plant–soil feedback and intraspecific overyielding. These findings may have wider implications for the maintenance of variation within species and the importance of this variation for ecosystem functioning. Our results highlight the need for an increased focus on intraspecific processes in plant diversity research to fully understand the mechanisms of coexistence and ecosystem functioning.
We investigate intraspecific trait variation, as well as intraspecific plant–soil feedback as a potential coexistence mechanism and ecosystem functioning in Arabidopsis thaliana. We demonstrate that plant–soil feedback indeed operates at intraspecific level, with accessions showing strong trait‐independent differences in feedback strength and direction. Furthermore, positive intraspecific diversity effects emerged.
The World Health Organization (WHO) early warning indicators (EWIs) of HIV drug resistance (HIVDR) assess factors at individual ART sites that are known to create situations favourable to the ...emergence of HIVDR.
In 2014, the Namibia HIV care and treatment program abstracted the following adult and pediatric EWIs from all public ART sites (50 main sites and 143 outreach sites): On-time pill pick-up, Retention in care, Pharmacy stock-outs, Dispensing practices, and Viral load suppression. Comparisons were made between main and outreach sites and between 2014 and 2012 using the Wilcoxon signed-rank test in a matched analysis.
The national estimates were: On-time pill pick-up 81.9% (95% CI 81.1-82.8) for adults and 82.4% (81.3-83.4) for pediatrics, Retention in care 79% retained on ART after 12 months for adults and 82% for pediatrics, Pharmacy stock-outs 94% of months without a stock-out for adults and 88% for pediatrics, and Dispensing practices 0.01% (0.001-0.056) dispensed mono- or dual-therapy for adults and 0.01% (0.001-0.069) for pediatrics. Viral load suppression was significantly affected by low rates of Viral load completion. Main sites had higher On-time pill pick-up than outreach sites for adults (p<0.001) and pediatrics (p<0.001), and no difference between main and outreach sites for Retention in care for adults (p = 0.761) or pediatrics (p = 0.214). From 2012 to 2014 in adult sites, On-time pill pick-up (p = 0.001), Retention in care (p<0.001), and Pharmacy stock-outs (p = 0.002) worsened. In pediatric sites, On-time pill pick-up (p<0.001) and Pharmacy stock-outs (p = 0.012) worsened.
Results of EWIs monitoring in Namibia provide evidence about ART programmatic functioning and contextualize results from national surveys of HIVDR. These results are worrisome as they show a decline in program performance over time. The national ART program is taking steps to minimize the emergence of HIVDR by strengthening adherence and retention of patients on ART, reducing stock-outs, and strengthening ART data quality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Early detection and treatment of precancerous cervical lesions through population-based screening has significantly reduced cervical cancer morbidity and mortality. In the United States (US), the ...addition of high-risk human papillomavirus co-testing to traditional Papanicolaou testing has improved the identification of cervical abnormalities and refined management guidelines. However, millions of abnormalities still necessitate follow-up to confirm the presence of high-grade cervical intraepithelial neoplasia (CIN2+) versus low-grade (≤CIN1) histology, which determines subsequent management.DNA methylation patterns at cytosine-phosphate-guanine (CpG) sites in cervical samples are promising biomarkers to improve detection and risk stratification of screening-detected abnormalities. Epigenome-wide methylation studies are needed in the US—particularly prospective studies of low-grade lesions in diverse populations—to optimally inform national guidelines. We utilized data from the Cervical Intraepithelial Neoplasia Cohort Study (CINCS), a prospective clinical cohort of patients presenting to colposcopy following an abnormal screening test in North Carolina, to examine 1) CpG differential methylation (DM) and differential variability (DV) in baseline CIN2+ vs. ≤CIN1 (cross-sectional), and 2) associations between methylation and five-year progression to incident CIN2+ among those with ≤CIN1 (prospective). We conducted targeted analyses of pre-selected genes with known roles in cervical cancer and exploratory epigenome-wide association studies (EWAS) to identify novel methylation biomarkers.We confirmed previously observed cross-sectional patterns of DM at CCNA1, CDH1, and RARB CpGs in CIN2+, and we detected DV among CDH1 and FHIT CpGs. The EWAS detected 3,534 CpGs exhibiting DM in CIN2+ and 270 CpGs with DV; 202 CpGs exhibited both DM and DV. We identified 44 gene ontology terms enriched among DM CpGs and 5 among DV CpGs, including terms related to DNA transcription, neuronal structures, cell structure, and developmental processes. Prospectively, we confirmed associations between CADM1 and RARB CpGs and time-to-progression to CIN2+, with trends supporting associations among DAPK1 and PAX1 CpGs. We detected 336 novel CpGs in the time-to-progression EWAS.Methylation biomarkers may help distinguish lesions with differential risks of CIN2+ and improve risk-based stratification of screening-detected cervical abnormalities. This study contributes to the growing literature assessing the utility of methylation biomarkers to inform management of millions of cervical precancerous lesions detected annually in the US.
CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential ...variability (DV) in high-grade (CIN2+) vs. low-grade (≤CIN1) lesions. In ≤CIN1 (n=117) and CIN2+ (n=31) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M values among nine cervical cancer-associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDR). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR<0.05) and Gene Ontology (GO) term enrichment. Compared to ≤CIN1, CIN2+ exhibited greater methylation at CCNA1 Cluster 1 (M value difference 0.24; 95% CI 0.04, 0.43) and RARB Cluster 2 (0.16; 95% CI 0.05, 0.28), and lower methylation at CDH1 Cluster 1 (-0.15; 95% CI -0.26, -0.04). CIN2+ exhibited lower variability at CDH1 Cluster 2 (variation difference -0.24; 95% CI -0.41, -0.05) and FHIT Cluster 1 (-0.30; 95% CI -0.50, -0.09). EWAS detected 3,534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms.CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential variability (DV) in high-grade (CIN2+) vs. low-grade (≤CIN1) lesions. In ≤CIN1 (n=117) and CIN2+ (n=31) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M values among nine cervical cancer-associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDR). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR<0.05) and Gene Ontology (GO) term enrichment. Compared to ≤CIN1, CIN2+ exhibited greater methylation at CCNA1 Cluster 1 (M value difference 0.24; 95% CI 0.04, 0.43) and RARB Cluster 2 (0.16; 95% CI 0.05, 0.28), and lower methylation at CDH1 Cluster 1 (-0.15; 95% CI -0.26, -0.04). CIN2+ exhibited lower variability at CDH1 Cluster 2 (variation difference -0.24; 95% CI -0.41, -0.05) and FHIT Cluster 1 (-0.30; 95% CI -0.50, -0.09). EWAS detected 3,534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms.
Background Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of ...CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. Methods A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. Results At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. Conclusions Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. Impact Methylation levels at novel CpG sites may help identify individuals with less than or equal toCIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines. Keywords: Cervical cancer, Cancer surveillance and screening, DNA methylation, Epigenomics, Epigenetics, Cancer risk, Pre-neoplasia
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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