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- Dareng, EO, et al.
(författare)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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- Morales Salinas, Alberto, et al.
(författare)
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Clinical Perspective on Antihypertensive Drug Treatment in Adults With Grade 1 Hypertension and Low-to-Moderate Cardiovascular Risk : An International Expert Consultation
- 2017
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Ingår i: Current problems in cardiology. - : Elsevier. - 0146-2806 .- 1535-6280. ; 42:7, s. 198-225
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Forskningsöversikt (refereegranskat)abstract
- Hypertension is a leading risk factor for disease burden globally. An unresolved question is whether grade 1 hypertension (140-159/90-99 mm Hg) with low (cardiovascular mortality < 1% at 10 years) to moderate (cardiovascular mortality ≥ 1% and <5% at 10 years) absolute total cardiovascular risk (CVR) should be treated with antihypertensive agents. A virtual international consultation process was undertaken to summarize the opinions of select experts. After holistic analysis of all epidemiological, clinical, psychosocial, and public health elements, this consultation process reached the following consensus in hypertensive adults aged < 80 years: (1) The question of whether drug treatment in grade 1 should be preceded by a period of some weeks or months during which only lifestyle measures are recommended cannot be evidence based, but the consensus opinion is to have a period of lifestyle alone reserved only to patients with grade 1 "isolated" hypertension (grade 1 uncomplicated hypertension with low absolute total CVR, and without other major CVR factors and risk modifiers). (2) The initiation of antihypertensive drug therapy in grade 1 hypertension with moderate absolute total CVR should not be delayed. (3) Men ≥ 55 years and women ≥ 60 years with uncomplicated grade 1 hypertension should automatically be classified within the moderate absolute total CVR category, even in the absence of other major CVR factors and risk modifiers. (4) Statins should be considered along with blood-pressure lowering therapy, irrespective of cholesterol levels, in patients with grade 1 hypertensive with moderate CVR.
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- Bernson, Elin, 1987, et al.
(författare)
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Identification of Tissue-Resident Natural Killer and T Lymphocytes with Anti-Tumor Properties in Ascites of Ovarian Cancer Patients
- 2023
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Ingår i: Cancers. - 2072-6694. ; 15:13
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Ovarian cancer is the deadliest among gynecological cancers, and there is a huge demand for new treatments for these patients. Immunotherapy holds great potential in cancer treatment, but has not yet proven successful for the majority of ovarian cancer patients. To better understand the immunological landscape of the disease, we have characterized lymphocytes in patients with high-grade serous ovarian cancer. Natural killer cells and T cells are present in both primary tumors and in the metastasizing environment of ascites, a fluid in the abdominal cavity that is developed in many patients with ovarian cancer. Our data reveal that a large fraction of these natural killer cells and T cells express tissue-resident markers and the inhibitory receptor, NKG2A, and are able to kill ovarian cancer cells. In summary, we report a functional subset of lymphocytes that may be targeted in future immunotherapeutic approaches. Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ascites production. The ascites represents a unique peritoneal liquid tumor microenvironment with the presence of both tumor and immune cells, including cytotoxic lymphocytes. We characterized lymphocytes in ascites from patients with high-grade serous ovarian cancer. Our data reveal the presence of NK and CD8(+) T lymphocytes expressing CD103 and CD49a, which are markers of tissue residency. Moreover, these cells express high levels of the inhibitory NKG2A receptor, with the highest expression level detected on tissue-resident NK cells. Lymphocytes with these features were also present at the primary tumor site. Functional assays showed that tissue-resident NK cells in ascites are highly responsive towards ovarian tumor cells. Similar results were observed in an in vivo mouse model, in which tissue-resident NK and CD8(+) T cells were detected in the peritoneal fluid upon tumor growth. Together, our data reveal the presence of highly functional lymphocyte populations that may be targeted to improve immunotherapy for patients with ovarian cancer.
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- Ghadami Yazdi, M., et al.
(författare)
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Naphthalene on Ni(111) : Experimental and Theoretical Insights into Adsorption, Dehydrogenation, and Carbon Passivation
- 2017
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 121:40, s. 22199-22207
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Tidskriftsartikel (refereegranskat)abstract
- An attractive solution to mitigate tars and also to decompose lighter hydrocarbons in biomass gasification is secondary catalytic reforming, converting hydrocarbons to useful permanent gases. Albeit that it has been in use for a long time in fossil feedstock catalytic steam reforming, understanding of the catalytic processes is still limited. Naphthalene is typically present in the biomass gasification gas and to further understand the elementary steps of naphthalene transformation, we investigated the temperature dependent naphthalene adsorption, dehydrogenation and passivation on Ni(111). TPD (temperature-programmed desorption) and STM (scanning tunneling microscopy) in ultrahigh vacuum environment from 110 K up to 780 K, combined with DFT (density functional theory) were used in the study. Room temperature adsorption results in a flat naphthalene monolayer. DFT favors the dibridge[7] geometry but the potential energy surface is rather smooth and other adsorption geometries may coexist. DFT also reveals a pronounced dearomatization and charge transfer from the adsorbed molecule into the nickel surface. Dehydrogenation occurs in two steps, with two desorption peaks at approximately 450 and 600 K. The first step is due to partial dehydrogenation generating active hydrocarbon species that at higher temperatures migrates over the surface forming graphene. The graphene formation is accompanied by desorption of hydrogen in the high temperature TPD peak. The formation of graphene effectively passivates the surface both for hydrogen adsorption and naphthalene dissociation. In conclusion, the obtained results on the model naphthalene and Ni(111) system, provides insight into elementary steps of naphthalene adsorption, dehydrogenation, and carbon passivation, which may serve as a good starting point for rational design, development and optimization of the Ni catalyst surface, as well as process conditions, for the aromatic hydrocarbon reforming process.
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- Tomsic, A, et al.
(författare)
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Molecular-dynamics simulations of cluster-surface collisions: Emission of large fragments
- 2001
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 1089-7690 .- 0021-9606. ; 115:22, s. 10509-10517
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale classical molecular-dynamics simulations of (H2O)n (n = 1032,4094) collisions with graphite have been carried out. The clusters have an initial internal temperature of 180 K and collide with an incident velocity in the normal direction between 200 and 1000 m/s. The 1032-clusters are trapped on the surface and completely disintegrate by evaporation. The 4094-clusters are found to partly survive the surface impact provided that the surface is sufficiently hot. These clusters are trapped on the surface for up to 50 ps before leaving the surface under strong evaporation of small fragments. The time spent on the surface is too short for full equilibration to occur, which limits the fragmentation of the clusters. The size of the emitted fragment is roughly 30% of the incident cluster size. The cluster emission mechanism is found to be very sensitive to the rate of the surface-induced heating and thus to the surface temperature. The incident cluster velocity is less critical for the outcome of the collision process but influences the time spent on the surface. The trends seen in the simulations agree well with recent experimental data for collisions of large water clusters with graphite [Chem. Phys. Lett. 329, 200 (2000)].
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