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| 2. |
- Bailey-Wilson, Joan E, et al.
(författare)
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Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families
- 2012
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Ingår i: BMC Medical Genetics. - London : BioMed Central. - 1471-2350. ; 13, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
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| 4. |
- Chen, Baoqing, et al.
(författare)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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| 5. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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| 6. |
- Colvin, Christopher J, et al.
(författare)
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Understanding careseeking for child illness in sub-Saharan Africa : a systematic review and conceptual framework based on qualitative research of household recognition and response to child diarrhoea, pneumonia and malaria
- 2013
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 86, s. 66-78
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Tidskriftsartikel (refereegranskat)abstract
- Diarrhoea, pneumonia and malaria are the largest contributors to childhood mortality in sub-Saharan Africa. While supply side efforts to deliver effective and affordable interventions are being scaled up, ensuring timely and appropriate use by caregivers remains a challenge. This systematic review synthesises qualitative evidence on the factors that underpin household recognition and response to child diarrhoea, pneumonia and malaria in sub-Saharan Africa. For this review, we searched six electronic databases, hand searched 12 journals from 1980 to 2010 using key search terms, and solicited expert review. We identified 5104 possible studies and included 112. Study quality was appraised using the Critical Appraisal Skills Program (CASP) tool. We followed a meta-ethnographic approach to synthesise findings according to three main themes: how households understand these illnesses, how social relationships affect recognition and response, and how households act to prevent and treat these illnesses. We synthesise these findings into a conceptual model for understanding household pathways to care and decision making. Factors that influence household careseeking include: cultural beliefs and illness perceptions; perceived illness severity and efficacy of treatment; rural location, gender, household income and cost of treatment. Several studies also emphasise the importance of experimentation, previous experience with health services and habit in shaping household choices. Moving beyond well-known barriers to careseeking and linear models of pathways to care, the review suggests that treatment decision making is a dynamic process characterised by uncertainty and debate, experimentation with multiple and simultaneous treatments, and shifting interpretations of the illness and treatment options, with household decision making hinging on social negotiations with a broad variety of actors and influenced by control over financial resources. The review concludes with research recommendations for tackling remaining gaps in knowledge.
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- Ekirapa-Kiracho, Elizabeth, et al.
(författare)
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Effect of a participatory multisectoral maternal and newborn intervention on maternal health service utilization and newborn care practices : a quasi-experimental study in three rural Ugandan districts
- 2017
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The MANIFEST study in eastern Uganda employed a participatory multisectoral approach to reduce barriers to access to maternal and newborn care services.Objectives: This study analyses the effect of the intervention on the utilization of maternal and newborn services and care practices.Methods: The quasi-experimental pre- and post-comparison design had two main components: community mobilization and empowerment, and health provider capacity building. The primary outcomes were utilization of antenatal care (ANC), delivery and postnatal care, and newborn care practices. Baseline (n = 2237) and endline (n = 1946) data were collected from women of reproductive age. The data was analysed using difference in differences (DiD) analysis and logistic regression.Results: The DiD results revealed an 8% difference in early ANC attendance (p < 0.01) and facility delivery (p < 0.01). Facility delivery increased from 66% to 73% in the intervention area, but remained unchanged in the comparison area (64% vs 63%, p < 0.01). The DiD results also demonstrated a 20% difference in clean cord care (p < 0.001) and an 8% difference in delayed bathing (p < 0.001). The intervention elements that predicted facility delivery were attending ANC four times [adjusted odds ratio (aOR) 1.42, 95% confidence interval (CI) 1.171.74] and saving for maternal health (aOR 2.11, 95% CI 1.39-3.21). Facility delivery and village health team (VHT) home visits were key predictors for clean cord care and skin-to-skin care.Conclusions: The multisectoral approach had positive effects on early ANC attendance, facility deliveries and newborn care practices. Community resources such as VHTs and savings are crucial to maternal and newborn outcomes and should be supported. VHT-led health education should incorporate practical measures that enable families to save and access transport services to enhance adequate preparation for birth.
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| 8. |
- Ekirapa-Kiracho, Elizabeth, et al.
(författare)
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Maternal and neonatal implementation for equitable systems : a study design paper
- 2017
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence on effective ways of improving maternal and neonatal health outcomes is widely available. The challenge that most low-income countries grapple with is implementation at scale and sustainability. Objectives: The study aimed at improving access to quality maternal and neonatal health services in a sustainable manner by using a participatory action research approach.Methods: The study consisted of a quasi-experimental design, with a participatory action research approach to implementation in three rural districts (Pallisa, Kibuku and Kamuli) in Eastern Uganda. The intervention had two main components; namely, community empowerment for comprehensive birth preparedness, and health provider and management capacity-building. We collected data using both quantitative and qualitative methods using household and facility-level structured surveys, record reviews, key informant interviews and focus group discussions. We purposively selected the participants for the qualitative data collection, while for the surveys we interviewed all eligible participants in the sampled households and health facilities. Descriptive statistics were used to describe the data, while the difference in difference analysis was used to measure the effect of the intervention. Qualitative data were analysed using thematic analysis.Conclusions: This study was implemented to generate evidence on how to increase access to quality maternal and newborn health services in a sustainable manner using a multisectoral participatory approach.
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| 9. |
- Ekirapa-Kiracho, Elizabeth, et al.
(författare)
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Unlocking community capabilities for improving maternal and newborn health : participatory action research to improve birth preparedness, health facility access, and newborn care in rural Uganda
- 2016
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Community capacities and resources must be harnessed to complement supply side initiatives addressing high maternal and neonatal mortality rates in Uganda. This paper reflects on gains, challenges and lessons learnt from working with communities to improve maternal and newborn health in rural Uganda. Methods: A participatory action research project was supported from 2012 to 2015 in three eastern districts. This project involved working with households, saving groups, sub county and district leaders, transporters and village health teams in diagnosing causes of maternal and neonatal mortality and morbidity, developing action plans to address these issues, taking action and learning from action in a cyclical manner. This paper draws from project experience and documentation, as well as thematic analysis of 20 interviews with community and district stakeholders and 12 focus group discussions with women who had recently delivered and men whose wives had recently delivered. Results: Women and men reported increased awareness about birth preparedness, improved newborn care practices and more male involvement in maternal and newborn health. However, additional direct communication strategies were required to reach more men beyond the minority who attended community dialogues and home visits. Saving groups and other saving modalities were strengthened, with money saved used to meet transport costs, purchase other items needed for birth and other routine household needs. However saving groups required significant support to improve income generation, management and trust among members. Linkages between savings groups and transport providers improved women's access to health facilities at reduced cost. Although village health teams were a key resource for providing information, their efforts were constrained by low levels of education, inadequate financial compensation and transportation challenges. Ensuring that the village health teams and savings groups functioned required regular supervision, review meetings and payment for supervisors to visit. Conclusions: This participatory program, which focused on building the capacity of community stakeholders, was able to improve local awareness of maternal and newborn health practices and instigate local action to improve access to healthcare. Collaborative problem solving among diverse stakeholders, continuous support and a participatory approach that allowed flexibility were essential project characteristics that enabled overcoming of challenges faced.
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| 10. |
- Kamal-Eldin, Afaf, et al.
(författare)
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Dietary fiber components, microstructure, and texture of date fruits (Phoenix dactylifera, L.)
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Date fruits vary widely in the hardness of their edible parts and they are classified accordingly into soft, semi-dry, and dry varieties. Fruit texture, a significant parameter in determining consumer acceptance, is related to the tissue structure and chemical composition of the fruit, mainly the ratio of sucrose to reducing sugars. This study aimed to understand the relationship between the chemical composition, microstructure, and texture profile of 10 major Emirati date fruits. The soluble sugars, glucose and fructose, represent ca 80 g/100 g of the fruits on the basis of dry weight (DW) while the dietary fiber contents varied 5.2-7.4 g/100 dg D.W. with lignin being the main determinant of the variability. The textures of the samples were studied using instrumental texture profile analysis. While no correlation was found between the soluble sugar and texture parameters in this study, the different fiber constituents correlated variably with the different parameters of date fruit texture. Lignin, arabinoxylan, galactomannan, and pectin were found to correlate significantly with fruit hardness and the related parameters, gumminess and chewiness. Both lignin and arabinoxylan correlated with resilience, and arabinoxylan exhibited a strong correlation with cohesiveness.
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