| 1. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
- Tabassum, R, et al.
(author)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Journal article (peer-reviewed)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 3. |
- Kulmala, M., et al.
(author)
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General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
- 2011
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
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Journal article (peer-reviewed)abstract
- In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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| 4. |
- Oksa, L, et al.
(author)
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Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
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Journal article (peer-reviewed)abstract
- T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.
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| 6. |
- Raitio, A, et al.
(author)
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Congenital abdominal wall defects and cryptorchidism: a population-based study
- 2021
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In: Pediatric surgery international. - : Springer Science and Business Media LLC. - 1437-9813 .- 0179-0358. ; 37:7, s. 837-841
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Journal article (peer-reviewed)abstract
- PurposeSeveral studies have reported high prevalence of undescended testis (UDT) among boys with congenital abdominal wall defects (AWD). Due to rarity of AWDs, however, true prevalence of testicular maldescent among these boys is not known. We conducted a national register study to determine the prevalence of UDT among Finnish males with an AWD.MethodsAll male infants with either gastroschisis or omphalocele born between Jan 1, 1998 and Dec 31, 2015 were identified in the Register of Congenital Malformations. The data on all performed operations were acquired from the Care Register for Health Care. The register data were examined for relevant UDT diagnosis and operation codes.ResultsWe identified 99 males with gastroschisis and 89 with omphalocele. UDT was diagnosed in 10 (10.1%) infants with gastroschisis and 22 (24.7%) with omphalocele. Majority of these required an operation; 8/99 (8.1%) gastroschisis and 19/89 (21.3%) omphalocele patients. UDT is more common among AWD patients than general population with the highest prevalence in omphalocele.ConclusionsCryptorchidism is more common among boys with an AWD than general population. Furthermore, omphalocele carries significantly higher risk of UDT and need for orchidopexy than gastroschisis. Due to high prevalence testicular maldescent, careful follow-up for UDT is recommended.
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| 8. |
- Raitio, A, et al.
(author)
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Gastroschisis in Finland 1993 to 2014-Increasing Prevalence, High Rates of Abortion, and Survival: A Population-Based Study
- 2020
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In: European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie. - : Georg Thieme Verlag KG. - 1439-359X. ; 30:066, s. 536-540
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Journal article (peer-reviewed)abstract
- Introduction The study aims to assess the changes in prevalence and mortality of gastroschisis, and to identify associated anomalies.Materials and Methods It is a population-based nationwide study. All gastroschisis cases were identified in the Finnish Register of Congenital Malformations and the Care Register for Health Care from 1993 to 2014 including live births, stillbirths, and terminations of pregnancy due to fetal anomalies. Associated anomalies were recorded, and analyzed, and prevalence and infant mortality were calculated.Results There were 320 cases of gastroschisis; 235 (73%) live births, 16 (5%) stillbirths, and 69 (22%) terminations of pregnancy. Live birth prevalence of gastroschisis in Finland was lower than generally reported (1.73 in 10,000). However, due to relatively high rates of abortion, our total prevalence of 2.57/10,000 was similar with other reports. The most common risk factor was young maternal age. Babies with gastroschisis were born prematurely, on average on the 36th week and most are delivered by caesarean section. There was a significant increasing trend in live birth prevalence (p = 0.0018). Overall infant mortality was 7.7% (18/235), 7.2% (16/222) in simple gastroschisis and 15% (2/13) in complex gastroschisis. Associated anomalies were rare both in aborted fetuses and neonates, and there was only one case with a chromosomal abnormality.Conclusion Gastroschisis is usually an isolated anomaly with increasing birth prevalence and excellent survival rates. Regardless of the good prognosis, the abortion rates in Finland are higher than previously reported, and we hypothesize this to be due to lack of appropriate antenatal counselling.
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| 9. |
- Raitio, A, et al.
(author)
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High incidence of inguinal hernias among patients with congenital abdominal wall defects: a population-based case-control study
- 2021
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In: European journal of pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 180:8, s. 2693-2698
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Journal article (peer-reviewed)abstract
- The aim of this nationwide population-based case–control study was to assess the incidence of inguinal hernia (IH) among patients with congenital abdominal wall defects. All infants born with congenital abdominal wall defects between Jan 1, 1998, and Dec 31, 2014, were identified in the Finnish Register of Congenital Malformations. Six controls matched for gestational age, sex, and year of birth were selected for each case in the Medical Birth Register. The Finnish Hospital Discharge Register was searched for relevant diagnosis codes for IH, and hernia incidence was compared between cases and controls. We identified 178 infants with gastroschisis and 150 with omphalocele and selected randomly 1968 matched, healthy controls for comparison. Incidence of IH was significantly higher in gastroschisis girls than in matched controls, relative risk (RR) 7.20 (95% confidence interval [CI] 2.25–23.07). In boys with gastroschisis, no statistically significant difference was observed, RR 1.60 (95% CI 0.75–3.38). Omphalocele was associated with higher risk of IH compared to matched controls, RR 6.46 (95% CI 3.90–10.71), and the risk was equally elevated in male and female patients.Conclusion: Risk of IH is significantly higher among patients with congenital abdominal wall defects than in healthy controls supporting hypothesis that elevated intra-abdominal pressure could prevent natural closure of processus vaginalis. Parents should be informed of this elevated hernia risk to avoid delays in seeking care. We also recommend careful follow-up during the first months of life as most of these hernias are diagnosed early in life.What is Known:• Inguinal hernia is one of the most common disorders encountered by a pediatric surgeon.• Prematurity increases the risk of inguinal hernia.What is New:• Children with congenital abdominal wall defects have a significantly higher risk of inguinal hernia than general population.• Families should be informed of this elevated hernia risk to avoid delays in seeking care.
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