| 1. |
- Demichev, Vadim, et al.
(författare)
-
A time-resolved proteomic and prognostic map of COVID-19
- 2021
-
Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
-
Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
|
|
| 2. |
- Huyghe, Jeroen R, et al.
(författare)
-
Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
-
Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
|
|
| 3. |
- Jandrić, Petar, et al.
(författare)
-
Teaching in the Age of Covid-19—1 Year Later
- 2021
-
Ingår i: Postdigital Science and Education. - : Springer. - 2524-485X .- 2524-4868. ; 3:3, s. 1073-1223
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
- Nooijen, Carla F J, et al.
(författare)
-
The relation between sprint power and road time trial performance in elite para-cyclists.
- 2021
-
Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 24:11, s. 1193-1198
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Whilst cycling performance has been studied extensively, very little is known about the performance of para-cyclists. This study assessed the relation between sprint power and road time trial performance in elite para-cyclists, and whether this relation differed based on impairment type and type of bike used.DESIGN: Cross-sectional.METHODS: During international para-cycling events, 168 athletes (88 bicycles, 17 tricycles, 56 recumbent handbikes and 7 kneeling handbikes) performed 20-s sport-specific sprint tests (mean power output (POmean) W), and their road time trial performance (average speed (km/h)) was taken from the official results. Multilevel regression models to assess the relation of sprint with time trial performance were composed for i. leg-cyclists: bicycle and tricycle and ii. arm-cyclists: recumbent- and kneeling handbike, adjusted for identified confounders. Furthermore, impairment type (categorized as i) muscle power/range of motion, ii) limb deficiency/leg length difference, and iii) coordination) and bike type were tested as effect modifiers.RESULTS: POmean ranged from 303 ± 12 W for recumbent handcyclists to 482 ± 156 W for bicyclists. POmean was significantly related to time trial performance, for both leg-cyclists (β = 0.010, SE = 0.003, p < 0.01) and arm-cyclists (β = 0.029; SE = 0.005, p < 0.01), and impairment type and bike type were not found to be effect modifiers.CONCLUSIONS: Sprint power was related to road time trial performance in all para-cyclists, with no differences found in this relation based on impairment type nor bike type. For those competing on a bicycle, tricycle, recumbent- or kneeling handbike, sprint tests might therefore be useful to predict or monitor time trial performance.
|
|
| 5. |
- Tesar, Marek, et al.
(författare)
-
Infanticides : The unspoken side of infantologies
- 2021
-
Ingår i: Educational Philosophy and Theory. - : Routledge. - 0013-1857 .- 1469-5812.
-
Tidskriftsartikel (refereegranskat)abstract
- Infanticides is the third article in a collective writing project that includes ‘Infantologies’ and ‘Infantasies’. It is designed to develop a philosophy of the infant, which is not tied to either developmental psychology or neuroscience but rather links itself to history and philosophy. It looks to develop a perspective on the world, beginning from the infant, that is critical, historical, and from the bottom up, so to speak. At the same time, the series of articles aims to create a thematic philosophical view that does not take for granted the normal set of conventions and assumptions made about the infant and about infancy, an important aspect given that infants and babies have a huge number of experts in medicine, law, education, religion, social work, and baby organizations like Plunket that have developed accepted bodies of knowledge, procedures, and routines about the infant and what is in the infant’s best interests. Historically, we have good reason to doubt this expertise. Also, women who give birth and parents, and other family members, all assume opinions and practices based on actual lived experience. Everyone, it seems, speaks for the infant saving the infant herself who cannot speak or, at least, is not able to articulate verbally their experiences or their expectations or requirements. This series has tried to provide fresh perspectives on these matters through the process of collective writing based on an approach to educational philosophy.
|
|
| 6. |
- Tesar, Marek, et al.
(författare)
-
Infantmethodologies
- 2021
-
Ingår i: Educational Philosophy and Theory. - : Informa UK Limited. - 0013-1857 .- 1469-5812.
-
Tidskriftsartikel (refereegranskat)abstract
- Infantmethodologies is a concept that was playfully invented to gauge philosophical interestin the intersection between infants (or a chid; or infancy; or childhood) and methodologies(and philosophies, theories and concepts). This provocation aims to debate this intersection andweaves thinkers from around the world in order to generate discussion on the question, ‘Howdo we study a child’? Asking this question generates further questions: What processes, methodologies, and methods are in place, and when does such an interface occur? What theories,concepts and philosophies come to mind when such a question is asked?
|
|
| 7. |
- Tesar, Marek, et al.
(författare)
-
Infantographies
- 2021
-
Ingår i: Educational Philosophy and Theory. - : Informa UK Limited. - 0013-1857 .- 1469-5812.
-
Tidskriftsartikel (refereegranskat)
|
|
| 8. |
- Thomas, Minta, et al.
(författare)
-
Response to Li and Hopper
- 2021
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 108:3, s. 527-529
-
Tidskriftsartikel (refereegranskat)
|
|
| 9. |
- Tsilidis, Konstantinos K., et al.
(författare)
-
Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent : a Mendelian randomization study
- 2021
-
Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 113:6, s. 1490-1502
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
|
|
