| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Nemlander, E., et al.
(författare)
-
A machine learning tool for identifying non-metastatic colorectal cancer in primary care
- 2023
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 182, s. 100-106
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Primary health care (PHC) is often the first point of contact when diagnosing colorectal cancer (CRC). Human limitations in processing large amounts of information warrant the use of machine learning as a diagnostic prediction tool for CRC. Aim: To develop a predictive model for identifying non-metastatic CRC (NMCRC) among PHC patients using diagnostic data analysed with machine learning. Design and setting: A case-control study containing data on PHC visits for 542 patients >18 years old diagnosed with NMCRC in the Vastra Gotaland Region, Sweden, during 2011, and 2,139 matched controls. Method: Stochastic gradient boosting (SGB) was used to construct a model for predicting the presence of NMCRC based on diagnostic codes from PHC consultations during the year before the date of cancer diagnosis and the total number of consultations. Variables with a normalised relative influence (NRI) >1% were considered having an important contribution to the model. Risks of having NMCRC were calculated using odds ratios of marginal effects. Results: Of the 361 variables used as predictors in the stochastic gradient boosting model, 184 had non-zero influence, with 16 variables having NRI >1% and a combined NRI of 63.3%. Variables representing anaemia and bleeding had a combined NRI of 27.6%. The model had a sensitivity of 73.3% and a specificity of 83.5%. Change in bowel habit had the highest odds ratios of marginal effects at 28.8. Conclusion: Machine learning is useful for identifying variables of importance for predicting NMCRC in PHC. Malignant diagnoses may be hidden behind benign symptoms such as haemorrhoids. 2023 The Author(s). Published by Elsevier Ltd.
|
|
| 5. |
|
|
| 6. |
- Becquart, Cécile, et al.
(författare)
-
Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS
- 2022
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:29, s. 10549-10556
-
Tidskriftsartikel (refereegranskat)abstract
- Antisense oligonucleotide (ASO)-based therapeutics hold great potential for the treatment of a variety of diseases. Therefore, a better understanding of cellular delivery, uptake, and trafficking mechanisms of ASOs is highly important for early-stage drug discovery. In particular, understanding the biodistribution and quantifying the abundance of ASOs at the subcellular level are needed to fully characterize their activity. Here, we used a combination of electron microscopy and NanoSIMS to assess the subcellular concentrations of a 34S-labeled GalNAc-ASO and a naked ASO in the organelles of primary human hepatocytes. We first cross-validated the method by including a 127I-labeled ASO, finding that the absolute concentration of the lysosomal ASO using two independent labeling strategies gave matching results, demonstrating the strength of our approach. This work also describes the preparation of external standards for absolute quantification by NanoSIMS. For both the 34S and 127I approaches used for our quantification methodology, we established the limit of detection (5 and 2 μM, respectively) and the lower limit of quantification (14 and 5 μM, respectively).
|
|
| 7. |
- Carlstrom, KE, et al.
(författare)
-
Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4071-
-
Tidskriftsartikel (refereegranskat)abstract
- Arrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in multiple sclerosis (MS) is associated with neurodegeneration and clinical worsening. We show that Glutathione S-transferase 4α (Gsta4) is highly expressed during adult OL differentiation and that Gsta4 loss impairs differentiation into myelinating OLs in vitro. In addition, we identify Gsta4 as a target of both dimethyl fumarate, an existing MS therapy, and clemastine fumarate, a candidate remyelinating agent in MS. Overexpression of Gsta4 reduces expression of Fas and activity of the mitochondria-associated Casp8-Bid-axis in adult oligodendrocyte precursor cells, leading to improved OL survival during differentiation. The Gsta4 effect on apoptosis during adult OL differentiation was corroborated in vivo in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis models, where Casp8 activity was reduced in Gsta4-overexpressing OLs. Our results identify Gsta4 as an intrinsic regulator of OL differentiation, survival and remyelination, as well as a potential target for future reparative MS therapies.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Hatamie, Amir, et al.
(författare)
-
Advances in nano/microscale electrochemical sensors and biosensors for analysis of single vesicles, a key nanoscale organelle in cellular communication
- 2023
-
Ingår i: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663. ; 220
-
Tidskriftsartikel (refereegranskat)abstract
- The study of subcellular targets and biochemical processes within a living cell is valuable for biological and medical research. Secretory vesicles, one such important intracellular target, are nanoscale lipid structures that are capable of storage, transport, and secretion of, for example, neurotransmitters, hormones, proteins or waste products. Vesicles play an essential role in intercellular communication systems, as they facilitate the release of chemical messaging agents. If deregulated, these communication processes can be a central part in the pathogenesis of some neurodegenerative diseases or diabetes. Generally, due to their nanometer size and intracellular location, the analysis of single vesicles and their content is a great challenge. It requires sensitive techniques, micro/nanoscale tools and sensitive instruments with extreme spatio-temporal resolution. This review focuses on electrochemical sensors to study the biochemistry and quantification of messenger molecules and other species (e.g., reactive oxygen and nitrogen species) stored in organelles, providing new trends and developments in this field. Furthermore, we review the effect of the chemical environment of single cells (e.g., treatment with chemicals, drugs, lipids, and ions) on regulation of the physical and chemical properties of vesicles. Finally, unsolved challenges of and perspectives on vesicle electroanalysis are discussed.
|
|
