| 31. |
- Feng, Xiaoshuang, et al.
(författare)
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Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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| 32. |
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| 33. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 34. |
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| 35. |
- Gullberg, Kajsa, et al.
(författare)
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In Scriptura Veritas? : Exploring Measures for Identifying Increased Cognitive Load in Speaking and Writing
- 2024
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Ingår i: Languages. - : MDPI AG. - 2226-471X. ; 9:3, s. 85
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to establish a methodological framework for investigating deception in both spoken and written language production. A foundational premise is that the production of deceitful narratives induces a heightened cognitive load that has a discernable influence on linguistic processes during real-time language production. This study includes meticulous analysis of spoken and written data from two participants who told truthful and deceitful narratives. Spoken processes were captured through audio recordings and subsequently transcribed, while written processes were recorded using keystroke logging, resulting in final texts and corresponding linear representations of the writing activity. By grounding our study in a linguistic approach for understanding cognitive load indicators in language production, we demonstrate how linguistic processes, such as text length, pauses, fluency, revisions, repetitions, and reformulations can be used to capture instances of deception in both speaking and writing. Additionally, our findings underscore that markers of cognitive load are likely to be more discernible and more automatically measured in the written modality. This suggests that the collection and examination of writing processes have substantial potential for forensic applications. By highlighting the efficacy of analyzing both spoken and written modalities, this study provides a versatile methodological framework for studying deception during language production, which significantly enriches the existing forensic toolkit.
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| 36. |
- Gullberg, Kajsa, et al.
(författare)
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In scriptura veritas: ett metodologiskt förslag för att jämföra att skriva och att tala för forensiska ändamål
- 2024
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Can language production processes in writing and speaking facilitate identification of fabrications? If so, are fabrications easier to detect in the written modality compared to the spoken modality? The aim of this study is to examine how language production processes manifest across truthful and fabricated narrative accounts of witnessed events. Specifically, the study asks if and how differences and similarities are manifested across written and spoken modalities, and if/how these differences/similarities can be analyzed within and across modalities. Linguistic processes in written and spoken language production are subject to working memory constraints (Goldman Eisler, 1970; McCutchen, 1996), and this can be seen in for example increased pause duration, frequency, and other disfluencies (Heldner & Edlund, 2010; Matsuhashi, 1981). It has also been found that lying leads to increased cognitive load (Williams, Bott, Patrick, & Lewis, 2013), leading to the hypothesis that fabrication would be visible in the production patterns in both modalities. Due to the synchronous nature of speaking, where the production process is overt, compared to the asynchronous nature of writing, where the process is covert, another hypothesis is that it will be easier to detect fabrication during writing.Two truthful and two fabricated narratives (whereof two spoken and two written) from a corpus of written and spoken narratives were used to qualitatively examine how pauses and disfluencies manifest in the two conditions across modalities. Written data consisted of a keystroke logging file and spoken as an audio file and transcription. Cognitive load was analyzed through text length, pause analyses and revisions (in writing) and reformulations (in speaking). The results show that, taking the difference in production speed across modalities into consideration, cognitive load can meaningfully be operationalized as pause frequency in relation to text length. Further, when measuring text length, the number of written/transcribed charactersis proposed as a way of measuring this while taking repetitions (in speaking) and fragments (in writing) into consideration. In conclusion, the study suggests that comparable results in the modalities can be reached by making informed analytical choices.
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| 37. |
- Gullberg, Kajsa, et al.
(författare)
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Using keystroke logging to explore differences in written language production processes between self-experienced and invented narrative accounts : A forensic linguistic approach
- 2024
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Konferensbidrag (populärvet., debatt m.m.)abstract
- This study aims at investigating if/how writing processes, such as planning and revision, differ between accounts of self-experienced and invented narratives. The underlying assumption is that cognitive load will increase for the writer when s/he is is changing or inventing parts of an otherwise self-experienced series of events. This builds on theories of how limited working memory capacity leads to increased pausing behavior in accordance with increased cognitive demands (Kellogg, 1996; McCutchen 2000), and that the need for revisions will increase when the writer wants to meet the goal of convincing the reader that something is true (cf. the relation between planning, translating and revision described in e.g. the writing model of Hayes and Flower, 1980). This presentation primarily focusses on comparing written accounts, collected with an experimental design. Participants (n=45) were presented with 4 elicitation videos, depicting misdemeanors (e.g., cheating on an exam, stealing a bike). Each participant performed 4 accounts across the 4 films: two written, and two spoken. For one account in each modality the participant is asked to lie and alter “who did it”. Modality, films and invented/self-experienced accounts are balanced for order. The written data was collected online through keystroke logging (ScriptLog). The participants repeated the experiment 4 times with 2 weeks apart, to allow for comparisons of consecutive accounts of both invented and self-experienced narratives. The first results showed no differences between time on task between invented and self-experienced narratives, but the invented narratives required overall more pause time. In addition, time on task and overall pause time decreased over the consecutive accounts, indicating that the retelling task became easier independent of condition. There were no overall differences in the amounts of deleted text between the conditions, but during the writing of the invented narratives, less characters were written between pauses, indicating theneed to pause (and plan?) more often. The general picture is that there are many individual differences, and that individual baselines may need to be established, as well as including comparisons within subjects in the further explorations of the data. Continuing analyses will look more closer at the linguistic contexts where the writers need to pause and revise, and will also compare the written accounts to spoken equivalents. The overall picture is however that using keystroke logging to investigate “true” and “false” narratives may be a rewarding avenue for forensic linguistics, and could be used (in addition to other tools) to identify instances where information needs to be further investigated.
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| 38. |
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| 39. |
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| 40. |
- Henriksson, Roger, et al.
(författare)
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Brain Tumors - Prognostic and Predictive Markers
- 2009
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Ingår i: Histological and Serological Tumor Markers and Gene Expression and Their Clinical Usefulness in Cancers. - Hauppauge : Nova Science Publishers, Inc.. - 9781607413820 ; , s. 53-75
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Bokkapitel (refereegranskat)abstract
- This review summarizes the status of prognostic and predictive markers in brain tumors with a focus on the most frequent tumors, gliomas. Brain tumors are a heterogeneous group of different tumors with a huge variation in outcome. Although the most common tumor, high-grade malignant glioma, still has a dismal prognosis, the last years have seen a significant improvement in the management in this tumor as well as in most other brain tumors. Age, tumor grade and KPS are still the most reliable prognostic and predictive variables available for patients with brain tumors. Although chromosome 1p/19q co-deletion and methylation status of the promoter of the MGMT gene (encoding O6-methylguanine-DNA methyl transferase) have been identified as the most promising potential predictors of response to chemotherapy in malignant gliomas, there are as yet no reliable biomarkers for tumour grading or tumour monitoring in the clinical setting.
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