| 1. |
- Micke, Patrick, et al.
(författare)
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The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
- 2021
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.
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| 2. |
- Hedner, Margareta, et al.
(författare)
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Age-Related Olfactory Decline is Associated with the BDNF Val66met Polymorphism : Evidence from a Population-Based Study
- 2010
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 2:7, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigates the effect of the brain-derived neurotrophic factor (BDNF) val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n = 836). The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70–90years old at baseline) was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45–65years). The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.
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| 3. |
- Hedner, Margareta, et al.
(författare)
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Cognitive factors in odor detection, odor discrimination, and odor identification tasks
- 2010
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Ingår i: Journal of Clinical and Experimental Neuropsychology. - : Informa UK Limited. - 1380-3395 .- 1744-411X. ; 32:10, s. 1062-1067
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to determine cognitive correlates of olfactory performance across three different tasks. A total of 170 men and women (30-87 years of age) were assessed in olfactory sensitivity, discrimination, and identification. Also, participants were tested in a range of cognitive tests covering executive functioning, semantic memory, and episodic memory. Hierarchical regression analyses showed that proficiency in executive functioning and semantic memory contributed significantly to odor discrimination and identification performance, whereas all of the cognitive factors proved unrelated to performance in the odor threshold test. This pattern of outcome suggests that an individual's cognitive profile exerts a reliable influence on performance in higher order olfactory tasks.
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| 4. |
- Hedner, Margareta, 1981-
(författare)
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Olfactory Function : The Influence of Demographic, Cognitive, and Genetic Factors
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Olfactory function is affected by demographic, cognitive, and genetic factors. In the present thesis, three empirical studies investigated individual differences in olfactory ability. Study I explored demographic and cognitive correlates in common olfactory tasks; odor detection, odor discrimination, and odor identification. The results indicated that old age influenced performance negatively in all tasks, and that semantic memory proficiency and executive functioning were related to odor discrimination and odor identification performance. No cognitive influence was observed for measurements of olfactory threshold. Using population-based data, Study II investigated a potential influence of the ApoE gene on olfactory identification after controlling for health status, semantic memory, and preclinical and clinical dementia. The main finding was that the ApoE- ɛ4 allele interacted with age, such that older ɛ4-carriers had an impaired odor identification performance relative to older non-carriers. Importantly, the negative ApoE- ɛ4 effect on olfactory proficiency was independent of clinical dementia conversion within five years. Study III investigated the effects of the BDNF val66met polymorphism on olfactory change over a five-year interval, in a community dwelling sample of young and old age cohorts. The results showed that age-related decline in olfactory identification was influenced by the BDNF val66met. In middle-aged subjects, no effect of BDNF val66met was observed although older val homozygote carriers showed a selectively larger olfactory decline than the older met carriers. Overall, results suggest that the relative influence of demographic and cognitive factors vary across different olfactory tasks and that two genes (ApoE and BDNF) impact age-related deficits in odor identification. Potential theoretical and practical implications of the findings are discussed as well as potential limitations of association studies in genomics research.
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| 5. |
- Jönsson, Fredrik U., et al.
(författare)
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The Testing Effect as a Function of Explicit Testing Instructions and Judgments of Learning
- 2012
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Ingår i: Experimental psychology (Göttingen). - : Hogrefe Publishing Group. - 1618-3169 .- 2190-5142. ; 59:5, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- During study, people monitor their learning; the output of this monitoring is captured in so-called judgments of learning (JOLs). JOLs predict later recall better if they are made after a slight delay, instead of immediately after study (the delayed JOL effect). According to the self-fulfilling prophecy (SFP) hypothesis delayed JOLs are based on covert retrieval attempts from long-term memory, and successful retrieval attempts in themselves enhance learning (the testing effect). We compared memory for 40 Swahili-Swedish paired associates after a week as a function of three different learning conditions, namely study plus (i) explicitly instructed self-testing, (ii) delayed JOLs, or (iii) less self-testing. We showed that repeated delayed JOLs lead to a memory improvement insignificantly different from a comparable condition where the participants are explicitly testing memory, and both the latter groups performed reliably better than a group that self-tested less. The results suggest that delayed JOLs improve long-term retention as efficiently as explicit memory testing and lend support to the SFP hypothesis.
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| 6. |
- Larsson, Maria, et al.
(författare)
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Differential Age and Sex Effects in Semantic Recognition of Odors and Words
- 2009
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Ingår i: Acta Psychologica Sinica. - : Science Press. - 0439-755X. ; 41:11, s. 1049-1053
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the impact of age and sex on olfactory function as determined by a cued odor identification test and on semantic knowledge as indexed by a vocabulary test using a large population-based sample. 1497 healthy adults varying in age from 35 to 95 years were assessed in odor identification and in vocabulary proficiency. The results showed that aging exhibited negative repercussions on performance in both tests, although the age effect was stronger in the olfactory task. Corroborating previous observations, females identified more odors than men irrespective of age. The implications of the findings are discussed.
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| 7. |
- Larsson, Maria, et al.
(författare)
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Olfactory memory in the old and very old : relations to episodic and semantic memory and APOE genotype
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 38, s. 118-126
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Tidskriftsartikel (refereegranskat)abstract
- The neuroanatomical organization that underlies olfactory memory is different from that of other memory types. The present work examines olfactory memory in an elderly population-based sample (Swedish National Study on Aging and Care in Kungsholmen) aged 60-100 years (n = 2280). We used structural equation modeling to investigate whether olfactory memory in old age is best conceptualized as a distinct category, differentiated from episodic and semantic memory. Further, potential olfactory dedifferentiation and genetic associations (APOE) to olfactory function in late senescence were investigated. Results are in support of a 3-factor solution where olfactory memory, as indexed by episodic odor recognition and odor identification, is modeled separately from episodic and semantic memory for visual and verbal information. Increasing age was associated with poorer olfactory memory performance, and observed age-related deficits were further exacerbated for carriers of the APOE epsilon 4 allele; these effects tended to be larger for olfactory memory compared to episodic and semantic memory pertaining to other sensory systems (vision, auditory). Finally, stronger correlations between olfactory and episodic memory, indicating dedifferentiation, were observed in the older age groups.
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| 8. |
- Mezheyeuski, Artur, et al.
(författare)
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An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations.Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy.Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.
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| 9. |
- Olofsson, Jonas K, 1965-, et al.
(författare)
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Odor identification impairment in carriers of ApoE-ε4 is independent of clinical dementia
- 2010
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 31:4, s. 567-577
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Tidskriftsartikel (refereegranskat)abstract
- The ApoE gene is expressed in olfactory brain structures and is believed to play a role in neuronal regenerative processes as well as in development of Alzheimer's disease (AD), the most common form of dementia. The ε4 allele has been reported to be associated with compromised odor identification ability in the elderly, and this deficit has been interpreted as a sign of pre-diagnostic AD. However, because it has not been demonstrated that the relationship between the ε4 allele and odor identification is mediated by dementia, it is possible that the ε4 allele may have an effect on odor identification over and above any effects of dementia. The present study investigated effects of ApoE-status on odor identification in a large, population-based sample (n = 1236) of adults (45–80 years), who were assessed for dementia at time of testing and 5 years later. The results showed that the ε4 allele was associated with an odor identification deficit among elderly participants (75–80). Critically, this effect remained after current and pre-diagnostic dementia, vocabulary, global cognitive status and health variables were partialled out. The present results suggest that the ApoE gene plays a role in olfactory functioning that is independent of dementia conversion within 5 years.
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