| 1. |
|
|
| 2. |
- Ferreira, MA, et al.
(författare)
-
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
-
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.
|
|
| 3. |
|
|
| 4. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
-
Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
-
Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
|
|
| 5. |
|
|
| 6. |
- Ahearn, Thomas U., et al.
(författare)
-
Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
-
Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
|
|
| 7. |
|
|
| 8. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
|
|
| 9. |
- Hagleitner, M M, et al.
(författare)
-
Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
- 2008
-
Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244. ; 45:2, s. 93-9
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients. OBJECTIVE: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients. METHODS: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors. Results and CONCLUSIONS: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.
|
|
| 10. |
- Mavaddat, N, et al.
(författare)
-
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- 2020
-
Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 22:1, s. 8-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
|
|
| 11. |
- Escala-Garcia, M, et al.
(författare)
-
Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19787-
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Park, J, et al.
(författare)
-
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
- 2021
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:10
-
Tidskriftsartikel (refereegranskat)abstract
- In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
|
|
| 16. |
- Kemerink, Martijn, et al.
(författare)
-
Optical properties of a tip-induced quantum dot
- 2001
-
Ingår i: Applied Physics A. - : Springer Verlag (Germany). - 0947-8396 .- 1432-0630. ; 72, s. S239-S242
-
Tidskriftsartikel (refereegranskat)abstract
- We have performed optical spectroscopy measurements on a STM-tip-induced quantum dot in a GaAs layer. The dominant confinement in the (hole) quantum dot is found to be in the direction parallel to the tip axis. Electron confinement is achieved by a sub-surface AlGaAs barrier. Current-dependent measurements indicate that many-body interactions can cause spectral blueshifts up to 75 meV for a tunneling current of 10 nA. Consequently, a full treatment of the many-body problem is required for an accurate description of this type of system.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Kemerink, Martijn, et al.
(författare)
-
Optical detection of ballistically injected electrons in III/V heterostructures
- 2001
-
Ingår i: Applied Physics A. - : Springer Verlag (Germany). - 0947-8396 .- 1432-0630. ; 72, s. S201-S204
-
Tidskriftsartikel (refereegranskat)abstract
- We present a novel spectroscopic technique that is based on the ballistic injection of minority carriers from the tip of a scanning-tunneling microscope into a semiconductor heterostructure. By analyzing the resulting electro-luminescence spectrum as a function of tip-sample bias, both the injection barrier height and the carrier relaxation rate Gamma(s) after injection can be determined. At 4.2 K we found Gamma(s) = 5 x 10(13) s(-1) and at 77 K we found Gamma(s) = 8 x 10(13) s(-1). From current-dependent measurements we find that, at room temperature, a large fraction of the carriers is trapped prior to radiative recombination. At high currents or low temperatures the traps become saturated. We tentatively identify the Be acceptors in the structure as trapping centers.
|
|
| 24. |
- Knoop, J., et al.
(författare)
-
Knee joint stabilization therapy in patients with osteoarthritis of the knee: a randomized, controlled trial
- 2013
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:8, s. 1025-1034
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether an exercise program, initially focusing on knee stabilization and subsequently on muscle strength and performance of daily activities is more effective than an exercise program focusing on muscle strength and performance of daily activities only, in reducing activity limitations in patients with knee osteoarthritis (OA) and instability of the knee joint. Design: A single-blind, randomized, controlled trial involving 159 knee OA patients with self-reported and/or biomechanically assessed knee instability, randomly assigned to two treatment groups. Both groups received a supervised exercise program for 12 weeks, consisting of muscle strengthening exercises and training of daily activities, but only in the experimental group specific knee joint stabilization training was provided. Outcome measures included activity limitations (Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC physical function, primary outcome), pain, global perceived effect and knee stability. Results: Both treatment groups demonstrated large (similar to 20-40%) and clinically relevant reductions in activity limitations, pain and knee instability, which were sustained 6 months post-treatment. No differences in effectiveness between experimental and control treatment were found on WOMAC physical function (B (95% confidence interval - CI) = -0.01 (-2.58 to 2.57)) or secondary outcome measures, except for a higher global perceived effect in the experimental group (P = 0.04). Conclusions: Both exercise programs were highly effective in reducing activity limitations and pain and restoring knee stability in knee OA patients with instability of the knee. In knee OA patients suffering from knee instability, specific knee joint stabilization training, in addition to muscle strengthening and functional exercises, does not seem to have any additional value. Dutch Trial Register (NTR) registration number: NTR1475. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
|
|
| 25. |
- Oprea-Lager, Daniela E, et al.
(författare)
-
Dual-Phase PET-CT to Differentiate [(18)F]Fluoromethylcholine Uptake in Reactive and Malignant Lymph Nodes in Patients with Prostate Cancer
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e48430-
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate whether time-trends of enhanced [(18)F]Fluoromethylcholine ([(18)F]FCH) in lymph nodes (LN) of prostate cancer (PCa) patients can help to discriminate reactive from malignant ones, and whether single time point standardized uptake value (SUV) measurements also suffice.PROCEDURES: 25 PCa patients with inguinal (presumed benign) and enlarged pelvic LN (presumed malignant) showing enhanced [(18)F]FCH uptake at dual-phase PET-CT were analyzed. Associations between LN status (benign versus malignant) and SUV(max) and SUV(meanA50), determined at 2 min (early) and 30 min (late) post injection, were assessed. We considered two time-trends of [(18)F]FCH uptake: type A (SUV early > SUV late) and type B (SUV late ≥ SUV early). Histopathology and/or follow-up were used to confirm the assumption that LN with type A pattern are benign, and LN with type B pattern malignant.RESULTS: Analysis of 54 nodes showed that LN status, time-trends, and 'late' (30 min p.i.) SUV(max) and SUV(meanA50) parameters were strongly associated (P<0.0001). SUV(max) relative difference was the best LN status predictor. All but one inguinal LN showed a decreasing [(18)F]FCH uptake over time (pattern A), while 95% of the pelvic nodes presented a stable or increasing uptake (pattern B) type.CONCLUSIONS: Time-trends of enhanced [(18)F]FCH uptake can help to characterize lymph nodes in prostate cancer patients. Single time-point SUV measurements, 30 min p.i., may be a reasonable alternative for predicting benign versus malignant status of lymph nodes, but this remains to be validated in non-enlarged pelvic lymph nodes.
|
|
| 26. |
- Stuiver, M., et al.
(författare)
-
The Governance of Multi-Use Platforms at Sea for Energy Production and Aquaculture: Challenges for Policy Makers in European Seas
- 2016
-
Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- European seas are encountering an upsurge in competing marine activities and infrastructures. Traditional exploitation such as fisheries, tourism, transportation, and oil production are accompanied by new sustainable economic activities such as offshore windfarms, aquaculture, and tidal and wave energy. One proposed solution to overcome possible competing claims at sea lies in combining these economic activities as part of Multi-Use Platforms at Sea (MUPS). MUPS can be understood as areas at sea, designated for a combination of activities, either completely integrated in a platform or in shared marine space. MUPS can potentially benefit from each other in terms of infrastructure, maintenance, etc. Developing MUPS in the marine environment demands adequate governance. In this article, we investigate four European sites to find out how governance arrangements may facilitate or complicate MUPs. In particular, we apply a framework specifying policy, economic, social, technical, environmental, and legal (PESTEL) factors to explore governance arrangements in four case study sites in different sea basins around Europe ( the Mediterranean Sea, the Atlantic Ocean, the North Sea, and the Baltic Sea). The article concludes with policy recommendations on a governance regime for facilitating the development of MUPS in the future.
|
|
| 27. |
- Agardh, Carl-David, et al.
(författare)
-
The influence of plasma insulin concentrations on tissue insulin levels in rodents: a study of the diabetic Chinese hamster and the ob/ob mouse
- 1986
-
Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 35:3, s. 244-249
-
Tidskriftsartikel (refereegranskat)abstract
- Immunoreactive insulin was measured in acid-ethanol extracts of kidney, brain, liver, and heart from genetically diabetic Chinese hamsters and their nondiabetic controls and from obese (ob/ob) mice and their thin littermates. Selected samples were filtered on Sephadex G-50 columns and the insulin concentration determined. There was a good correlation between the insulin level measured in the acid-ethanol extracts of tissues and the insulin level after gel filtration, suggesting that the concentration measured in the whole extract is representative of the true insulin content. The present data demonstrate that different extrapancreatic organs contain characteristic amounts of insulin that are often (sometimes several-fold) higher than the insulin level of plasma. The tissue insulin concentrations also exhibit a wide range of values, with occasional high values. The data also show a direct correlation between plasma and kidney insulins but no relationship between plasma and brain insulins and a mixed correlation among plasma and liver and heart insulins.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Bocquier, Philipe, et al.
(författare)
-
Ubiquitous burden : The contribution of migration to AIDS and tuberculosis mortality in rural South Africa
- 2014
-
Ingår i: African Population Studies. - : Stellenbosch University. - 0850-5780 .- 2308-7854. ; 28:1, s. 691-701
-
Tidskriftsartikel (refereegranskat)abstract
- The paper aims to estimate the extent to which migrants are contributing to AIDS or tuberculosis (TB) mortality among rural sub-district populations. The Agincourt (South Africa) health and socio-demographic surveillance system provided comprehensive data on vital and migration events between 1994 and 2006. AIDS and TB cause-deleted life expectancy, and crude death rates by gender, migration status and period were computed. The annualised crude death rate almost tripled from 5∙39 [95% CI 5∙13-5∙65] to 15∙10 [95% CI 14∙62-15∙59] per 1000 over the years 1994-2006. The contribution of AIDS and TB in returned migrants to the increase in crude death rate was 78∙7% [95% CI 77∙4-80∙1] for males and 44∙4% [95% CI 43∙2-46∙1] for females. So, in a typical South African setting dependent on labour migration for rural livelihoods, the contribution of returned migrants, many infected with AIDS and TB, to the burden of disease is high.
|
|
| 31. |
|
|
| 32. |
- Cecchi, L, et al.
(författare)
-
Projections of the effects of climate change on allergic asthma : the contribution of aerobiology
- 2010
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:9, s. 1073-1081
-
Tidskriftsartikel (refereegranskat)abstract
- Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Gerritsen, Bart H. M., et al.
(författare)
-
Social Media Coming to the Mall : A Cross-Channel Response
- 2014. - 1
-
Ingår i: <em></em>Product Development in the Socio-sphere. - Cham : Springer. - 9783319074030 - 9783319074047 ; , s. 169-235
-
Bokkapitel (refereegranskat)abstract
- Traditional shopping malls experience the effects of expanding online shopping. In addition, social media grew as a platform for customer orientation and expression. In-mall retail must respond. We take the customer journey as the guiding model for customer experience building and focus on converting cross-channel built customer expectation into enriched customer experiences in in-mall stores. We focus on the in-mall part of the journey but recognize the need to engage with customers in other parts of the journey and on social media. That is where the word-of-mouth spreads nowadays. We develop a ‘u-retail’ process model and a cyber-physical system concept for a mall: we combine a mall website, mobile apps and interactive storefronts containing Facebook processes into an integrating system. Customers can manipulate info and processes displayed on the interactive storefront through touch or mobile devices. The Facebook shopping-with-online-friends process inserts real-time feedback from social media friends in the storefront window. We show how ‘gamification’ and trust and loyalty breeding can be employed. Mall and retailers attract customers in a collective manner, from parking services to package deals. Cross-channel customer tracking is part of the concept, providing a view on both online and offline communities. Ubiquitous tracking of customers foster deep customer relation and experience of data. We implemented a first partly surrogate prototype to validate the concept. This partly empirical, partly designed experimental implementation can itself be a big data tool for scientists and retailers to acquire deeper insights. The concept can be generalized to other social contexts. © Springer International Publishing Switzerland 2014
|
|
| 36. |
|
|
| 37. |
- Hagg, S, et al.
(författare)
-
Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
- 2017
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:4, s. e1100-
-
Tidskriftsartikel (refereegranskat)abstract
- The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−0.699; 95% CI: −1.330, −0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Persborn, Mats, et al.
(författare)
-
The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis
- 2013
-
Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 38:7, s. 772-783
-
Tidskriftsartikel (refereegranskat)abstract
- Background less thanbrgreater than less thanbrgreater thanA total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. less thanbrgreater than less thanbrgreater thanAim less thanbrgreater than less thanbrgreater thanTo examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. less thanbrgreater than less thanbrgreater thanMethods less thanbrgreater than less thanbrgreater thanSixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanPouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P andlt; 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P andlt; 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanProbiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.
|
|
| 43. |
|
|
| 44. |
- Vermeer, Maarten H, et al.
(författare)
-
Novel and highly recurrent chromosomal alterations in Sézary syndrome
- 2008
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 68:8, s. 2689-2698
-
Tidskriftsartikel (refereegranskat)abstract
- This study was designed to identify highly recurrent genetic alterations typical of Sezary syndrome (Sz), an aggressive cutaneous T-cell lymphoma/leukemia, possibly revealing pathogenetic mechanisms and novel therapeutic targets. High-resolution array-based comparative genomic hybridization was done on malignant T cells from 20 patients. Expression levels of selected biologically relevant genes residing within loci with frequent copy number alteration were measured using quantitative PCR. Combined binary ratio labeling-fluorescence in situ hybridization karyotyping was done on malignant cells from five patients. Minimal common regions with copy number alteration occurring in at least 35% of patients harbored 15 bona fide oncogenes and 3 tumor suppressor genes. Based on the function of the identified oncogenes and tumor suppressor genes, at least three molecular mechanisms are relevant in the pathogenesis of Sz. First, gain of cMYC and loss of cMYC antagonists (MXI1 and MNT) were observed in 75% and 40% to 55% of patients, respectively, which were frequently associated with deregulated gene expression. The presence of cMYC/MAX protein heterodimers in Sezary cells was confirmed using a proximity ligation assay. Second, a region containing TP53 and genome maintenance genes (RPA1/HIC1) was lost in the majority of patients. Third, the interleukin 2 (IL-2) pathway was affected by gain of STAT3/STAT5 and IL-2 (receptor) genes in 75% and 30%, respectively, and loss of TCF8 and DUSP5 in at least 45% of patients. In sum, the Sz genome is characterized by gross chromosomal instability with highly recurrent gains and losses. Prominent among deregulated genes are those encoding cMYC, cMYC-regulating proteins, mediators of MYC-induced apoptosis, and IL-2 signaling pathway components.
|
|
| 45. |
|
|
| 46. |
- Yaka, Reyhan, et al.
(författare)
-
Variable kinship patterns in Neolithic Anatolia revealed by ancient genomes
- 2021
-
Ingår i: Current Biology. - : Cell Press. - 0960-9822 .- 1879-0445. ; 31:11, s. 2455-2468.e18
-
Tidskriftsartikel (refereegranskat)abstract
- The social organization of the first fully sedentary societies that emerged during the Neolithic period in Southwest Asia remains enigmatic,(1) mainly because material culture studies provide limited insight into this issue. However, because Neolithic Anatolian communities often buried their dead beneath domestic buildings,(2) household composition and social structure can be studied through these human remains. Here, we describe genetic relatedness among co-burials associated with domestic buildings in Neolithic Anatolia using 59 ancient genomes, including 22 new genomes from Asxikli Hoyuk and Catalhoyuk. We infer pedigree relationships by simultaneously analyzing multiple types of information, including autosomal and X chromosome kinship coefficients, maternal markers, and radiocarbon dating. In two early Neolithic villages dating to the 9th and 8th millennia BCE, Asxikli Hoyuk and Boncuklu, we discover that siblings and parent-offspring pairings were frequent within domestic structures, which provides the first direct indication of close genetic relationships among co-burials. In contrast, in the 7th millennium BCE sites of Catalhoyuk and Barcin, where we study subadults interred within and around houses, we find close genetic relatives to be rare. Hence, genetic relatedness may not have played a major role in the choice of burial location at these latter two sites, at least for subadults. This supports the hypothesis that in Catalhoyuk,(3-5) and possibly in some other Neolithic communities, domestic structures may have served as burial location for social units incorporating biologically unrelated individuals. Our results underscore the diversity of kin structures in Neolithic communities during this important phase of sociocultural development.
|
|
