| 1. |
- Svensson, Sara, 1981, et al.
(författare)
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Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation
- 2022
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Ingår i: Journal of Materials Science-Materials in Medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 33:1
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Tidskriftsartikel (refereegranskat)abstract
- Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems. Direct exposure to pyrophosphate increased nonadherent monocyte survival (by 120% without LPS and 235% with LPS) and MSC viability (LDH) (by 16-19% with and without LPS). Conditioned media from LPS-primed monocytes significantly upregulated osteogenic genes (ALP and RUNX2) and downregulated adipogenic (PPAR-gamma) and chondrogenic (SOX9) genes in recipient MSCs. Moreover, the inclusion of PPi (250 mu M) resulted in a 1.2- to 2-fold significant downregulation of SOX9 in the recipient MSCs, irrespective of LPS stimulation or culture media type. These results indicate that conditioned media from LPS-stimulated inflammatory monocytes potentiates the early MSCs commitment towards the osteogenic lineage and that direct pyrophosphate exposure to MSCs can promote their viability and reduce their chondrogenic gene expression. These results are the first to show that pyrophosphate can act as a survival factor for both human MSCs and primary monocytes and can influence the early MSC gene expression.
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| 2. |
- Atefyekta, Saba, 1987, et al.
(författare)
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Antimicrobial Peptide-Functionalized Mesoporous Hydrogels
- 2021
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Ingår i: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:4, s. 1693-1702
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10-100x less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.
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| 3. |
- Broom, M., et al.
(författare)
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Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017
- 2023
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Ingår i: Infection. - : Springer Science and Business Media LLC. - 0300-8126 .- 1439-0973. ; 51:2, s. 425-432
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) <= 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. Methods Retrospective study of all culture positive IMD in adult patients (age >= 15 years) in the Auckland region from 2004 to 2017. Results One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. Conclusions This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.
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| 5. |
- Jacobson, Sara, et al.
(författare)
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Hyperglycemia as a risk factor in pancreatic cancer : A nested case-control study using prediagnostic blood glucose levels
- 2021
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:6, s. 1112-1118
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.
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| 6. |
- Mahmoud, Sara, 1988-, et al.
(författare)
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How to train a self-driving vehicle : On the added value (or lack thereof) of curriculum learning and replay buffers
- 2023
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Ingår i: Frontiers in Artificial Intelligence. - : Frontiers Media S.A.. - 2624-8212. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Learning from only real-world collected data can be unrealistic and time consuming in many scenario. One alternative is to use synthetic data as learning environments to learn rare situations and replay buffers to speed up the learning. In this work, we examine the hypothesis of how the creation of the environment affects the training of reinforcement learning agent through auto-generated environment mechanisms. We take the autonomous vehicle as an application. We compare the effect of two approaches to generate training data for artificial cognitive agents. We consider the added value of curriculum learning—just as in human learning—as a way to structure novel training data that the agent has not seen before as well as that of using a replay buffer to train further on data the agent has seen before. In other words, the focus of this paper is on characteristics of the training data rather than on learning algorithms. We therefore use two tasks that are commonly trained early on in autonomous vehicle research: lane keeping and pedestrian avoidance. Our main results show that curriculum learning indeed offers an additional benefit over a vanilla reinforcement learning approach (using Deep-Q Learning), but the replay buffer actually has a detrimental effect in most (but not all) combinations of data generation approaches we considered here. The benefit of curriculum learning does depend on the existence of a well-defined difficulty metric with which various training scenarios can be ordered. In the lane-keeping task, we can define it as a function of the curvature of the road, in which the steeper and more occurring curves on the road, the more difficult it gets. Defining such a difficulty metric in other scenarios is not always trivial. In general, the results of this paper emphasize both the importance of considering data characterization, such as curriculum learning, and the importance of defining an appropriate metric for the task.
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| 7. |
- Mahmoud, Sara, 1988-, et al.
(författare)
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Where to from here? : On the future development of autonomous vehicles from a cognitive systems perspective
- 2022
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Ingår i: Cognitive Systems Research. - : Elsevier. - 2214-4366 .- 1389-0417. ; 76, s. 63-77
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Tidskriftsartikel (refereegranskat)abstract
- Self-driving cars not only solve the problem of navigating safely from location A to location B; they also have to deal with an abundance of (sometimes unpredictable) factors, such as traffic rules, weather conditions, and interactions with humans. Over the last decades, different approaches have been proposed to design intelligent driving systems for self-driving cars that can deal with an uncontrolled environment. Some of them are derived from computationalist paradigms, formulating mathematical models that define the driving agent, while other approaches take inspiration from biological cognition. However, despite the extensive work in the field of self-driving cars, many open questions remain. Here, we discuss the different approaches for implementing driving systems for self-driving cars, as well as the computational paradigms from which they originate. In doing so, we highlight two key messages: First, further progress in the field might depend on adapting new paradigms as opposed to pushing technical innovations in those currently used. Specifically, we discuss how paradigms from cognitive systems research can be a source of inspiration for further development in modeling driving systems, highlighting emergent approaches as a possible starting point. Second, self-driving cars can themselves be considered cognitive systems in a meaningful sense, and are therefore a relevant, yet underutilised resource in the study of cognitive mechanisms. Overall, we argue for a stronger synergy between the fields of cognitive systems and self-driving vehicles.
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