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- Malm, Gunilla, et al.
(författare)
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Maternal serum vitamin D level in early pregnancy and risk for preeclampsia : A casecontrol study in Southern Sweden
- 2023
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:2 February
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Tidskriftsartikel (refereegranskat)abstract
- Background Preeclampsia is considered a major cause of maternal and fetal morbidity and mortality. The aim of the present case-control study in Sweden was to assess the hypothesized association between low serum vitamin D concentrations in early pregnancy and the risk of developing preeclampsia since vitamin D may play a role in early placental development. Methods The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Serum samples were obtained from a biobank of samples collected in early pregnancy including almost all pregnancies in Southern Sweden. Concentrations of 25-hydroxyvitamin D3 (vitamin D) were analyzed using liquid chromatography-tandemmass- spectrometry (LC/MS/MS). The cases were divided into two categories: i) infants were born before gestational week 34 (early onset) and/or born small-for-gestational age (SGA)(n = 51), ii) and others defined as late onset (n = 245). Vitamin D concentrations were analyzed both as a continuous and a categorized variable. Results When all preeclampsia cases were included in the analyses no consistent patterns were observed. However, the median serum concentrations of vitamin D were significantly lower among the cases who were early onset and/or were born SGA (median 39.2 nmol/L, range 1.2-93.6) as compared to the controls (49.0 nmol/L, 0.1-219; p = 0.01). In addition, high concentrations were statistically significantly associated with a decreased risk of preeclampsia (>66.9 vs ≤30.1 nmol/L; crude OR 0.39, 95% CI 0.16-0.96). When potential confounders were included in the models the associations were even more pronounced. Conclusions Our results support the hypothesis that vitamin D deficiency is a risk factor for preeclampsia, but only in preeclampsia cases who were early-onset and/or were born SGA. Preeclampsia is not a homogenous condition and more studies are needed before vitamin D supplementation during pregnancy can be recommended.
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| 4. |
- Bernstone, Christian, et al.
(författare)
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Verifiering av struktur och fuktmekaniska beräkningsverktyg : Tillämpning på reaktorinneslutningars betongkonstruktioner, Vercors Fas 1
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Électricité de France har utanför Paris byggt en 1/3 skalmodell av en reaktorinneslutning motsvarande en fransk fullskalereaktor modell P4. Anläggningen möjliggör studier av hur åldringsprocesser påverkar förspända reaktorinneslutningar. Syftet är att efter de 7 år som ett övergripande forskningsprojektet vid på anläggningen pågår, uppnå påverkan motsvarande den åldring som en fullskalereaktor har utsatts för efter 6o års drift.Konstruktionen har försetts med ett omfattande instrumenteringsprogram som gör det möjligt att följa konstruktionens beteende i tidigt skede och över tid. Ett av anläggningens forskningsprojekt omfattar en benchmark av olika beräkningsverktygs möjlighet att kunna förutse konstruktionens beteende i tidigt skede och under själva åldrandet, dess täthet till följd av åldrandet och beteende under svåra haveriförhållanden. Denna benchmark har genomförts via en öppen inbjudning till intresserade experter att delta. I projektet, benämnt VeRCoRs , bidrar deltagande organisationer med egna modelleringsarbeten utifrån de tre olika teman. Arbetet med det första temat startade 2015 (tidigt skede), därefter följer den åldrade konstruktionen (2017) och svåra haverisituationer (2021). Denna rapport redovisar det arbete som har gjorts för det första temat (Tema 1) inom ramen för ett Energiforskuppdrag.Modelleringsarbetet har till största delen genomförts av LTH i nära samarbete med KTH och Vattenfall. Simuleringar har gjorts för den unga betongens beteende under den ett år långa byggfasen, med hänsyn tagen till betongens hydratation (temperaturberäkningar/värmeutveckling), uttorkning (självuttorkning och fukttransport) och deformationer (temperatur-, fukt-, kryp-, och spänningsrelaterade deformationer). Resultatet har jämförts mot data från anläggningens instrumentering. Dessutom så har en genomgång gjorts av resultaten från övriga deltagares arbeten i Tema 1.Sammanfattningsvis så visar resultaten på de fördelar som finns med att genom avancerade beräkningar verifiera designparametrar och prognostisering av reaktorinneslutningars funktion, men också på utmaningar. Med hjälp av FEmodellering så kan det tidiga skedet efter färdigställd konstruktion beskrivas både vad gäller temperatur- och deformationer med rimlig tillförlitlighet. Det finns dock potential till förbättringar. Även om betongens temperatur kan predikteras noggrant så kan det skilja kraftigt i uppskattningen av inducerade påkänningar. En viktig orsak till dessa skillnader beror på osäkerheter i bestämning av krypning och krympning i betongen tidiga skede.
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| 5. |
- Berta, Judit, et al.
(författare)
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Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
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- Betancourt, Lazaro Hiram, et al.
(författare)
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Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
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| 7. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.
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| 9. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 10. |
- Brynielsson, Joel, et al.
(författare)
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Using Temporal Analytics for Early Discovery of Upcoming Threats
- 2011
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Ingår i: Proceedings of the National Symposium on Technology and Methodology for Security and Crisis Management 2011 (TAMSEC 2011). ; , s. 16-
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Konferensbidrag (refereegranskat)abstract
- An ocean of data is available on the web. From this ocean of data, information can in theory be extracted and used by analysts for detecting emergent trends. However, to do this manually is a daunting and nearly impossible task. We describe an implemented semi-automatic system in which data is automatically collected from selected sources, and to which linguistic analysis is applied to extract, e.g., entities and events. The extracted information is automatically transformed into OSINT reports which are clustered and visualized. The user can interact with the system in order to obtain a better awareness of historic as well as emergent trends.
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