| 1. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 2. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 3. |
- Sandén, Anna Maria, et al.
(författare)
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Limiting factors in Escherichia coli fed-batch production of recombinant proteins
- 2003
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 81:2, s. 158-166
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Tidskriftsartikel (refereegranskat)abstract
- Fed-batch production of recombinant beta-galactosidase in E. coli was studied with respect to the specific growth rate at induction. The cultivations were designed to induce protein production by IPTG at a glucose feed rate corresponding to high (mu = 0.5 h(-1)) or low (mu = 0.1 h(-1)) specific growth rate. Protein production rate was approximately 100% higher at the higher specific growth rate, resulting in the accumulation of beta-galactosidase up to 30% of the total cell protein. Transcription analysis showed that beta-galactosidase-specific messenger RNA was immediately formed after induction (<5 min), but the amount was the same in both cases and was thus not the initial limiting factor. The content of ribosomes, as represented by rRNA, rapidly decreased with specific growth rate from a relative level of 100%, at the high specific growth rate, to 20% at the low specific growth rate. At high specific growth rate, ribosomes were additionally degraded upon induction due to the high production level. Translation therefore seemed to be the initial limiting factor of the protein synthesis capacity. The alarmone guanosine tetraphosphate increased at both high and low feed level inductions, indicating an induction-forced starvation of charged tRNA and/or glucose. The altered physiological status was also detected by the formation of acetic acid. However, the higher production rate resulted in high-level accumulation of acetic acid, which was absent at low feed rate production. Acetic acid production is thus coupled to the high product formation rate and is proposed to be due either to a precursor drain of Krebs cycle intermediates and a time lag before induction of the glyoxalate shunt, or to single amino acid overflow, since the model product is relatively poor in glycin and alanin. In conclusion, it is proposed that production at high specific growth rate becomes precursor-limited, while production at low specific growth rate is carbon- and/or energy-limited.
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| 4. |
- Sarneel, Judith M., et al.
(författare)
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Reading tea leaves worldwide: Decoupled drivers of initial litter decomposition mass-loss rate and stabilization
- 2024
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Ingår i: ECOLOGY LETTERS. - : John Wiley & Sons. - 1461-023X .- 1461-0248. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.
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| 5. |
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| 6. |
- Börjesson Sandén, Fredrik, 1995, et al.
(författare)
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Effects of boric acid on volatile tellurium in severe accident conditions
- 2024
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Ingår i: Annals of Nuclear Energy. - 0306-4549 .- 1873-2100. ; 200
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Tidskriftsartikel (refereegranskat)abstract
- Boric acid is used in light-water nuclear reactors to control the reactor and is expected to be present as part of the chemistry of a severe accident. Therefore, its influence on other prominent species expected in an accident must be investigated. One such species is tellurium. In the present study, tellurium is volatized, and boric acid is dissolved and injected into the system as a means of studying the interaction between it and tellurium. The experiments were evaluated with ICP-MS and XPS. Results suggest that while there is no direct interaction, boric acid still affects the tendency for tellurium to oxidize. In general, less oxidation was detected in the presence of boric acid than in its absence, especially at high temperatures. The species formed upon oxidation was determined to be TeO2. Since tellurium metal is more volatile than TeO2, this may have implication in a wider severe accident context.
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| 7. |
- Dellborg, M, et al.
(författare)
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Changes in the use of medication after acute myocardial infarction : Possible impact on post-myocardial infarction mortality and long-term outcome
- 2001
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Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 12:1, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the change in the use of medication after acute myocardial infarction (AMI) and discuss its possible impact on risk and risk indicators for death. Patients: All patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital (covering half the community of Goteborg, i.e. 250 000 of 500 000 inhabitants) during 1986-1987 (period I) and at Sahlgrenska Hospital and Ostra Hospital (covering the whole community of Goteborg, 500 000 inhabitants) during 1990-1991 (period II). Methods: Overall mortality was retrospectively evaluated during 5 years of follow-up. Results: In all, 740 patients were included in the study during period I and 1448 during period II. The 5-year mortalities were 44.1% for period I patients and 39.3% for period II patients (P = 0.036). The relative risk of death for period II patients was 0.78 [95% confidence interval (CI) 0.67-0.89, P = 0.0005] after adjustment for differences at baseline. There was a significant interaction with a history of congestive heart failure; improvement in duration of survival was found only for patients without such a history. During period I, only 3% of patients were administered fibrinolytic agents, compared with 33% of patients during period II (P < 0.0001). During period I, aspirin was prescribed for 13% of patients discharged from hospital compared with 79% during period II. Other changes in treatment on going from period I to period II included increases in prescription of [beta]-blockers and angiotensin converting enzyme inhibitors. After adjustment for various risk indicators for death, relative risk of death for those administered fibrinolytic agents was 0.60 (95% CI 0.18-2.02) for patients in the period-I cohort and 0.68% (95% CI 0.51-0.91) for those in the period-II cohort. Adjusted relative risk of death for those prescribed aspirin upon discharge from hospital was 0.81 (95% CI 0.52-1.25) for period-I patients and 0.71 (95% CI 0.56-0.91) for period-II patients. The adjusted relative risk of death for those administered [beta]-blockers was 0.72 (95% CI 0.55-0.96) for period-I patients and 0.70 (95% CI 0.55-0.90) for period-II patients. Conclusion: Increased use of fibrinolytic agents and aspirin for AMI as well as a moderate increase in use of [beta]-blockers and angiotensin converting enzyme inhibitors was associated with a parallel reduction in age-adjusted mortality during the 5 years after discharge from hospital. However, this improvement was seen only for patients without histories of congestive heart failure.
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| 8. |
- Herlitz, Johan, et al.
(författare)
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Determinants of time to discharge following coronary artery bypass grafting
- 1997
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Elsevier BV. - 1010-7940 .- 1873-734X. ; 11:3, s. 533-538
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe clinical factors prior to and at the time of coronary artery bypass grafting (CABG) associated with the number of days until hospital discharge. PATIENTS: All patients from western Sweden in whom during the time period June 1 1988-June 1 1991 CABG was performed without simultaneous valve surgery. METHODS: The time between operation and hospital discharge was calculated for every patient and related to various factors prior to and at the operation. RESULTS: Among 2035 patients the time between operation and discharged alive from hospital varied between 2 and 191 days (median 15 days). When simultaneously considering pre-, per- and postoperative factors the following appeared as independent predictors for a longer hospital time: age (years) (P < 0.0001); female sex, (P < 0.0001); time in respirator (P = 0.0004); previous congestive heart failure (P = 0.0007); reoperation (P = 0.0008); neurological complication (P = 0.001); maximum activity of serum aspartate amino transferase (P = 0.002); pneumo/hydrothorax (P = 0.002), previous cerebrovascular disease (P = 0.004), non-smoker (P = 0.006); supraventricular arrhythmia (0.006); time in intensive care unit (P = 0.007); aortic cross-clamp time (P = 0.009); obesity (P = 0.02). CONCLUSION: A large number of pre- and postoperative factors are associated with an increased time between operation and time to discharge.
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| 9. |
- Herlitz, Johan, et al.
(författare)
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Occurrence, characteristics and outcome of patients hospitalized with diagnosis of acute myocardial infarction who do not fulfil traditional criteria
- 1998
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Ingår i: Clinical Cardiology. - : John Wiley & Sons, Inc.. - 0160-9289 .- 1932-8737. ; 21:6, s. 405-409
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The diagnosis of acute myocardial infarction (AMI) is traditionally based on clinical history, elevation of serum enzyme activity, and typical changes in the electrocardiogram (ECG); however, not all patients who develop AMI fulfill these criteria on discharge from hospital. HYPOTHESIS: The aim of the study was to evaluate (1) the frequency with which the traditional criteria for AMI are not fulfilled among patients diagnosed with AMI on discharge, and (2) whether patients with and without these criteria differ in terms of characteristics, treatment, and outcome. METHODS: All patients aged < 75 years and hospitalized in the municipality of Göteborg with a discharge diagnosis of AMI were included. Fulfillment criteria for AMI were two of the following three points: (1) chest pain, (2) increase in cardiac enzymes, and (3) development of Q waves. RESULTS: In all, 1,188 admitted patients, 27% of whom were women, were included in the analysis. Of these, 193 (16%) did not fulfill the traditional criteria for AMI. These patients had an in-hospital mortality rate of 48%; of these, 59% died a sudden death, and of those who were autopsied (62%), 96% showed signs of a fresh AMI. The most common symptom on admission to hospital in patients who did not fulfill the traditional criteria was chest pain (34%), followed by dyspnea (27%) and fatigue (14%). Of those who died suddenly, fewer than half had been admitted to the coronary care unit. CONCLUSION: Patients diagnosed with AMI who do not fulfill the traditional diagnosis criteria have high mortality. On admission to hospital, the initial suspicion of AMI is often vague. Measures for earlier detection of life-threatening coronary artery disease among these patients are warranted.
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| 10. |
- Herlitz, Johan, et al.
(författare)
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Predictors of hospital readmission two years after coronary artery bypass grafting
- 1997
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Ingår i: Heart. - : BMJ Group. - 1355-6037 .- 1468-201X. ; 77:5, s. 437-442
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the clinical factors before, and in association with, coronary artery bypass grafting (CABG) that increase the risk of readmission to hospital in the first two years after surgery. PATIENTS: All patients in western Sweden who had CABG without simultaneous valve surgery between 1 June 1988 and 1 June 1991. METHODS: All patients who were readmitted to hospital were evaluated by postal inquiry and hospital records. RESULTS: A total of 2121 patients were operated on, of whom 2037 were discharged from hospital. Information regarding readmission was missing in four patients, leaving 2033 patients; 44% were readmitted to hospital. The most common reasons for readmission were angina pectoris and congestive heart failure. There were 12 independent significant predictors for readmission: clinical history (a previous history of either congestive heart failure or myocardial infarction, or CABG); acute operation; postoperative complications (time in intensive care unit greater than two days, neurological complications); clinical findings four to seven days after the operation (arrhythmia, systolic murmur equivalent to mitral regurgitation); medication four to seven days after the operation (antidiabetics, diuretics for heart failure, other antiarrhythmics (other than beta blockers, calcium antagonists, and digitalis), and lack of treatment with aspirin). CONCLUSION: 44% of patients were readmitted to hospital two years after CABG. The most common reasons for readmission were angina pectoris and congestive heart failure. Four clinical markers predicted readmission: clinical history; acute operation status; postoperative complications; and clinical findings and medication four to seven days after operation.
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