| 1. |
- Assel, Melissa, et al.
(författare)
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A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy : An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer
- 2019
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 5:4, s. 561-567
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Tidskriftsartikel (refereegranskat)abstract
- Background: A panel of four kallikrein markers (total, free, and intact prostate-specific antigen [PSA] and human kallikrein-related peptidase 2 [hK2]) improves predictive accuracy for Gleason score ≥7 (high-grade) prostate cancer among men biopsied for elevated PSA. A four-kallikrein panel model was originally developed and validated by the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as 4Kscore™. Objective: To assess whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC) and whether β-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value. Design, setting, and participants: Among 4861 biopsied screening-positive participants in the first three screening rounds of FinRSPC, a case-control subset was selected that included 1632 biopsy-positive cases matched by age at biopsy to biopsy-negative controls. Outcome measurements and statistical analysis: The predictive accuracy of prespecified prediction models was compared with biopsy outcomes. Results and limitations: Among men with PSA of 4.0-25. ng/ml, 1111 had prostate cancer, 318 of whom had high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve of 0.648 (95% confidence interval [CI] 0.614-0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717-0.774). Adding MSP to the four-kallikrein panel led to a significant (Wald test; p = 0.015) but small increase (0.003) in discrimination. Limitations include a risk of verification bias among men with PSA of 3.0-3.99. ng/ml and the absence of digital rectal examination results. Conclusions: These findings provide additional evidence that kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP. Patient summary: Four kallikrein markers and β-microseminoprotein in blood improve discrimination of high-grade prostate cancer at biopsy in men with elevated prostate-specific antigen. Four kallikrein markers and β-microseminoprotein (MSP) in blood improve discrimination of high-grade cancer at biopsy in men with elevated prostate-specific antigen. These kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP.
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| 2. |
- Ganesan, Harsha, et al.
(författare)
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RNA-Interference-Mediated miR-122-Based Gene Regulation in Colon Cancer, a Structural In Silico Analysis
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:23
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Tidskriftsartikel (refereegranskat)abstract
- The role of microRNA 122 (miR-122) in colorectal cancer (CRC) has not been widely investigated. In the current study, we aimed to identify the prominent gene and protein interactors of miR122 in CRC. Based on their binding affinity, these targets were chosen as candidate genes for the creation of miR122-mRNA duplexes. Following this, we examined the miRNA-mediated silencing mechanism using the gene-silencing complex protein Argonaute (AGO). Public databases, STRING, and GeneMANIA were utilized to identify major proteins and genes interacting with miR-122. DAVID, PANTHER, UniProt, FunRich, miRwalk, and KEGG were used for functional annotation, pathway enrichment, binding affinity analysis, and expression of genes in different stages of cancer. Three-dimensional duplexes of hub genes and miR-122 were created using the RNA composer, followed by molecular interaction analysis using molecular docking with the AGO protein. We analyzed, classified, and scrutinized 93 miR-122 interactors using various bioinformatic approaches. A total of 14 hub genes were categorized as major interactors of miR-122. The study confirmed the role of various experimentally documented miR-122 interactors such as MTDH (Q86UE4), AKT1 (P31749), PTPN1 (P18031), MYC (P01106), GSK3B (P49841), RHOA (P61586), and PIK3CG (P48736) and put forth several novel interactors, with AKT3 (Q9Y243), NCOR2 (Q9Y618), PIK3R2 (O00459), SMAD4 (P61586), and TGFBR1 (P36897). Double-stranded RNA duplexes of the strongest interactors were found to exhibit higher binding affinity with AGO. In conclusions, the study has explored the role of miR-122 in CRC and has identified a closely related group of genes influencing the prognosis of CRC in multiple ways. Further, these genes prove to be targets of gene silencing through RNA interference and might serve as effective therapeutic targets in understanding and treating CRC.
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| 3. |
- Trace, SE, et al.
(författare)
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The genetics of eating disorders
- 2013
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Ingår i: Annual review of clinical psychology. - : Annual Reviews. - 1548-5951 .- 1548-5943. ; 9, s. 589-620
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Tidskriftsartikel (refereegranskat)abstract
- Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.
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| 4. |
- Berndt Rasmussen, Katharina, 1977-, et al.
(författare)
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The Tyranny of Political Correctness? A Game-Theoretic Model of Social Norms and Implicit Bias
- 2023
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Ingår i: Journal of Applied Philosophy. - 0264-3758 .- 1468-5930. ; 41:1, s. 122-144
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Tidskriftsartikel (refereegranskat)abstract
- This article sets out to describe and solve two puzzles that emerge in segregated labour markets (e.g. the USA or Sweden). First, in many hiring contexts people profess to adhere to egalitarian norms, and specifically to a qualification norm according to which job qualification should be the basis of employment. Still there is evidence of frequent norm violations (discrimination). Surprisingly, the norm persists and people do not frequently protest against such norm violations. The second puzzle is that people are suspicious of the hiring of minorities, perceiving such hirings as evidence that a 'political correctness' norm has replaced the qualification norm. The article proposes that both puzzles can be solved within a game-theoretical model of social norm-following, where implicit bias is introduced into an 'employment game'. Within this model, implicit bias plays a double role. First, it interferes with employers' hiring decisions regarding ethnic majority and minority members, respectively. This is the standard way of understanding the effects of implicit bias. Second, implicit bias interferes with bystander evaluations of hired candidates' qualifications. This is a hitherto overlooked effect of implicit bias. The article concludes that once we understand the double role of implicit bias, the two puzzles are resolved.
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| 6. |
- Holmes, Emily A., et al.
(författare)
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Trauma films, information processing, and intrusive memory development
- 2004
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Ingår i: Journal of experimental psychology. General. - : AMER PSYCHOLOGICAL ASSOC. - 0096-3445 .- 1939-2222. ; 133:1, s. 3-22
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Tidskriftsartikel (refereegranskat)abstract
- Three experiments indexed the effect of various concurrent tasks, while watching a traumatic film, on intrusive memory development. Hypotheses were based on the dual-representation theory of Posttraumatic stress disorder (C. R. Brewin, T. Dalgleish, & S. Joseph, 1996). Nonclinical participants viewed a trauma film under various encoding conditions and recorded any spontaneous intrusive memories of the film over the following week in a diary. Changes in state dissociation, heart rate, and mood were also measured. As predicted, performing a visuospatial pattern tapping task at encoding significantly reduced the frequency of later intrusions, whereas a verbal distraction task increased them. Intrusive memories were largely unrelated to recall and recognition measures. Increases in dissociation and decreases in heart rate during the film were also associated with later intrusions.
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| 7. |
- Yang, Junfeng, 1979
(författare)
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Bio-diesel Spray Combustion Modeling Based on a Detailed Chemistry Approach
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The increased use of bio-diesel fuel is expected to reduce emissions of carbon-containing greenhouse gases. To optimize the application of bio-diesel in internal combustion engines, a theoretical model has been developed. The bio-diesel fuels used in the modeling are Palm Methyl Ether (PME, C17H34O2) and Rapeseed Methy Ether (RME, C19H36O2), and blends of these methyl ethers with standard diesel oil. The thermo-physical properties of these bio-diesel fuels have been estimated using empirically determined thermodynamic, gas phase formulae. The description of their combustion processes has been based on the assumption that long chain methyl esters (C17~C19) decompose into short-chain methyl esters (C5}~ C11), for which combustion mechanisms are available. A comprehensive integrated chemical mechanism (with 98 species involving 395 reactions) was constructed to model the combustion of diesel oil surrogate, DOS, PME and RME. The bio-diesel fuels' physical properties and combustion mechanisms were validated using measured auto-ignition delays and laminar flame speeds. The bio-diesels physical properties and combustion mechanism were implemented into KIVA3V, rel.2 code. The KIVA3V fuel model was also extended to include mixing rules approach to calculate properties of blends of the fuel, e.g. RME50.Models of sprays of the fuels were validated against data acquired using observations of sprays in the Chalmers High Pressure /High Temperature (HP/HT) spray chamber. The liquid penetration, and average Sauter Mean Radius, SMR, for sprays of the different fuels were calculated and compared.To study the effect of bio-diesel fuels on the performance of engines, 3D CFD simulations of both a heavy duty engine (Volvo D12C) and a light duty engine (Volvo NED5) were carried our under various operating conditions. The combustion processes of the DOS and PME fuels in the NED5 engine were studied, and those of DOS, RME and RME50 in the Volvo D12C engine. Reasonable agreement between modelled and empirical in-cylinder parameters has been achieved.
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