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- Weinstock, Joshua S, et al.
(författare)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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- Broomé, Sara, et al.
(författare)
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Going Deeper than Tracking : A Survey of Computer-Vision Based Recognition of Animal Pain and Emotions
- 2023
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Ingår i: International Journal of Computer Vision. - : Springer Nature. - 0920-5691 .- 1573-1405. ; 131:2, s. 572-590
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Tidskriftsartikel (refereegranskat)abstract
- Advances in animal motion tracking and pose recognition have been a game changer in the study of animal behavior. Recently, an increasing number of works go ‘deeper’ than tracking, and address automated recognition of animals’ internal states such as emotions and pain with the aim of improving animal welfare, making this a timely moment for a systematization of the field. This paper provides a comprehensive survey of computer vision-based research on recognition of pain and emotional states in animals, addressing both facial and bodily behavior analysis. We summarize the efforts that have been presented so far within this topic—classifying them across different dimensions, highlight challenges and research gaps, and provide best practice recommendations for advancing the field, and some future directions for research.
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- Barkholt, L M, et al.
(författare)
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Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis
- 1997
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 10:6, s. 432-438
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial infections, especially cholangitis, are still common complications after liver transplantation (LTx). During recent years, multiresistant enterococci have become a nosocomial problem in transplant units. The present prospective study on 26 patients, including 24 patients with chronic liver disease, demonstrated that enterococci were the predominant micro-organism involved in post-LTx bacterial infections. They were cultured in the feces and in other sites of 10 out of 13 (77%) patients who underwent extensive examinations. Ampicillin-resistant Enterococcus faecium strains were isolated in urine or feces of 2 of the 13 patients prior to LTx. Similarly, resistance to ampicillin and gentamicin, the empirically used antibiotics for patients with fever of unknown origin, was found in E. faecium strains in 3 and 2 patients, respectively. Moreover, multiresistant E. faecium and E. faecalis strains were demonstrated in 46% of the patients in the postoperative period (3 months). However, no vancomycin-resistant enterococci were isolated. The use of antibiotics within 4 months prior to LTx significantly increased the risk of developing ampicillin-resistant bacteria at the time of LTx and of infections with bacteria of enteric origin after LTx (P = 0.03 and 0.01, respectively). We conclude that stool and urine cultures performed prior to LTX may be useful for selecting prophylactic antibiotic regimens.
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