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Sökning: WFRF:(Gutierrez A.) > Linköpings universitet

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  • Attia, Zachi I., et al. (författare)
  • Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram
  • 2021
  • Ingår i: Mayo Clinic proceedings. - : ELSEVIER SCIENCE INC. - 0025-6196 .- 1942-5546. ; 96:8, s. 2081-2094
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). Methods: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. Results: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. Conclusion: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control. (C) 2021 Mayo Foundation Medical Education and Research
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  • Oakman, C, et al. (författare)
  • Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the Breast International Group 02-98 phase III trial
  • 2013
  • Ingår i: Annals of Oncology. - : Oxford University Press (OUP): Policy A1. - 0923-7534 .- 1569-8041. ; 24:5, s. 1203-1211
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. less thanbrgreater than less thanbrgreater thanMethods: Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) x 4 -andgt; classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) x 4 -andgt; CMF; (iii) sequential docetaxel: A (75 mg/m(2)) x3 -andgt; docetaxel (T) (100 mg/m(2)) x3. CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) x 4 -andgt; CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. less thanbrgreater than less thanbrgreater thanResults: Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. less thanbrgreater than less thanbrgreater thanConclusion: With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.
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  • Palasz, A.T., et al. (författare)
  • Effects of hyaluronan, BSA, and serum on bovine embryo in vitro development, ultrastructure, and gene expression patterns
  • 2006
  • Ingår i: Molecular Reproduction and Development. - : Wiley-Blackwell. - 1040-452X .- 1098-2795. ; 73:12, s. 1503-1511
  • Tidskriftsartikel (refereegranskat)abstract
    • Effects of hyaluronan (HA), BSA, and FCS on in vitro development, ultrastructure, and mRNA transcription of four developmentally important genes: apoptosis (Bax), oxidative stress (SOX), growth factor (IGF-II), and cell-to-cell adhesion (Ecad) were examined. Two biological origin HA, Hylartil and Hyonate and one produced by fermentation (f-HA) MAP-5 were tested. Embryos were cultured in SOF medium with 0.4% BSA or with 0.4% BSA and 10% FCS. HA was added 96 hr post insemination (pi) to half of the embryos from each culture group. Embryo development was not affected by either HA preparation, however, hatching rates were higher in Hyalartil and MAP-5 than in control and Hyonate (P less than 0.05). There was no effect of HA on number of blastocysts developed in SOF + BSA. However, more blastocysts developed in SOF + BSA + f-HA than in SOF + BSA + FCS or with BSA + FCS + f-HA. HA added to SOF + BSA, increased level of expression of epidermal growth factor (EGF)-II and decreased the levels of expression of BAX, SOX, and Ecad (P less than 0.05). Presence of FCS increased the levels of SOX and decreased the level of IGF-II (P less than 0.05) and the addition of f-HA to SOF containing FCS showed no effect on the level of transcription of any analyzed genes. The fine structure of embryos cultured with f-HA irrespective of protein sources used was clearly improved. In summary, f-HA added 96 hr pi to SOF supplemented with BSA but not FCS improved development, molecular composition and fine structure of bovine embryos.
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  • Pestalozzi, B. C., et al. (författare)
  • Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup phase III BIG 02-98 trial
  • 2008
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:11, s. 1837-1841
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. Patients and methods: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG 02-98 trial comparing anthracycline-based adjuvant chemotherapy (control arms) to anthracycline-docetaxel-based sequential or concurrent chemotherapy (experimental arms). After a median follow-up of 5 years, 403 patients had died and detailed information on CNS relapse was collected for these patients. Results: CNS relapse occurred in 4.0% of control patients and3.7% of docetaxel-treated patients. CNS relapse occurred in 27% of deceased patients in both treatment groups. CNS relapse was usually accompanied by neurologic symptoms (90%), and 25% of patients with CNS relapse died without evidence of extra-CNS relapse. Only 20% of patients survived 1 year from the diagnosis of CNS relapse. Prognosis of CNS relapse was worse for patients with meningeal carcinomatosis when compared with brain metastases. Unexpected findings included a higher rate of positive cerebrospinal fluid cytology (8% versus 3%) and more frequent use of magnetic resonance imaging for diagnosis (47% versus 30%) in the docetaxel-treated patients. Conclusion: There is no evidence that adjuvant docetaxel treatment is associated with an increased frequency of CNS relapse. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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  • Romanos, Jihane, et al. (författare)
  • Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants
  • 2014
  • Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 63:3, s. 415-422
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. OBJECTIVE: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. DESIGN: We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case-control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. RESULTS: Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. CONCLUSIONS: Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.
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  • Vazquez-Sanchez, Ernesto A., et al. (författare)
  • Heptapeptide HP3 acts as a potent inhibitor of experimental imiquimod-induced murine psoriasis and impedes the trans-endothelial migration of mononuclear cells
  • 2020
  • Ingår i: Molecular Medicine Reports. - : SPANDIDOS PUBL LTD. - 1791-2997 .- 1791-3004. ; 22:1, s. 507-515
  • Tidskriftsartikel (refereegranskat)abstract
    • During the progression of psoriatic lesions, abundant cellular infiltration of myeloid cells, such as macrophages and activated dendritic cells, occurs in the skin and the infiltrating cells interact with naive lymphoid cells to generate a T helper (Th)1 and Th17 environment. Therapies to treat psoriasis include phototherapy, non-steroidal and steroidal drugs, as well as antibodies to block tumor necrosis factor-alpha, interleukin (IL)-17-A and IL-12/IL-23, which all focus on decreasing the proinflammatory hallmark of psoriasis. The present study obtained the heptapeptide HP3 derived from phage display technology that blocks mononuclear cell adhesion to endothelial cells and inhibits trans-endothelial migrationin vitro. The activity of the heptapeptide in a murine model of psoriasis was also assessed, which indicated that early administration inhibited the development of psoriatic lesions. Therefore, the results suggested that HP3 may serve as a potential therapeutic target for psoriasis.
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