| 1. |
- Anwar, Mohiemen, et al.
(författare)
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Ixovex-1, a novel oncolytic E1B-mutated adenovirus
- 2022
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Ingår i: Cancer Gene Therapy. - : Springer Nature. - 0929-1903 .- 1476-5500. ; 29:11, s. 1628-1635
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Tidskriftsartikel (refereegranskat)abstract
- There is a great demand for improved oncolytic viruses that selectively replicate within cancer cells while sparing normal cells. Here, we describe a novel oncolytic adenovirus, Ixovex-1, that obtains a cancer-selective replication phenotype by modulating the level of expression of the different, alternatively spliced E1B mRNA isoforms. Ixovex-1 is a recombinant adenovirus that carries a single point mutation in the E1B-93R 3' splice acceptor site that results in overexpression of the E1B-156R splice isoform. In this paper, we studied the characteristics of this novel oncolytic adenovirus by validating its in vitro behaviour in a panel of normal cells and cancer cells. We additionally studied its anti-tumour efficacy in vivo. Ixovex-1 significantly inhibited tumour growth and prolonged survival of mice in an immune-deficient lung carcinoma tumour implantation model. In complementation experiments, overexpression of E1B-156R was shown to increase the oncolytic index of both Ad5wt and ONYX-015. In contrast to prior viruses of similar type, Ixovex-1 includes a functional E3B region for better in vivo efficacy. Throughout this study, the Ixovex-1 virus has been proven to be superior in competency compared to a virus with multiple deletions.
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| 2. |
- Eriksson, Carl, 1981-, et al.
(författare)
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Real-world effectiveness of vedolizumab in inflammatory bowel disease : week 52 results from the Swedish prospective multicentre SVEAH study
- 2021
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Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL).Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52.Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.
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| 3. |
- Nilsson, Daniel P.G., et al.
(författare)
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Physico-chemical characterization of single bacteria and spores using optical tweezers
- 2023
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Ingår i: Research in Microbiology. - : Elsevier. - 0923-2508 .- 1769-7123. ; 174:6
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Tidskriftsartikel (refereegranskat)abstract
- Spore-forming pathogenic bacteria are adapted for adhering to surfaces, and their endospores can tolerate strong chemicals making decontamination difficult. Understanding the physico-chemical properties of bacteria and spores is therefore essential in developing antiadhesive surfaces and disinfection techniques. However, measuring physico-chemical properties in bulk does not show the heterogeneity between cells. Characterizing bacteria on a single-cell level can thereby provide mechanistic clues usually hidden in bulk measurements. This paper shows how optical tweezers can be applied to characterize single bacteria and spores, and how physico-chemical properties related to adhesion, fluid dynamics, biochemistry, and metabolic activity can be assessed.
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| 4. |
- Valijam, Shayan, et al.
(författare)
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A lab-on-a-chip utilizing microwaves for bacterial spore disruption and detection
- 2023
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial spores are problematic in agriculture, the food industry, and healthcare, with the fallout costs from spore-related contamination being very high. Spores are difficult to detect since they are resistant to many of the bacterial disruption techniques used to bring out the biomarkers necessary for detection. Because of this, effective and practical spore disruption methods are desirable. In this study, we demonstrate the efficiency of a compact microfluidic lab-on-chip built around a coplanar waveguide (CPW) operating at 2.45 GHz. We show that the CPW generates an electric field hotspot of ∼10 kV/m, comparable to that of a commercial microwave oven, while using only 1.2 W of input power and thus resulting in negligible sample heating. Spores passing through the microfluidic channel are disrupted by the electric field and release calcium dipicolic acid (CaDPA), a biomarker molecule present alongside DNA in the spore core. We show that it is possible to detect this disruption in a bulk spore suspension using fluorescence spectroscopy. We then use laser tweezers Raman spectroscopy (LTRS) to show the loss of CaDPA on an individual spore level and that the loss increases with irradiation power. Only 22% of the spores contain CaDPA after exposure to 1.2 W input power, compared to 71% of the untreated control spores. Additionally, spores exposed to microwaves appear visibly disrupted when imaged using scanning electron microscopy (SEM). Overall, this study shows the advantages of using a CPW for disrupting spores for biomarker release and detection.
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| 5. |
- Valijam, Shayan, et al.
(författare)
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Fabricating a dielectrophoretic microfluidic device using 3D-printed moulds and silver conductive paint
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Dielectrophoresis is an electric field-based technique for moving neutral particles through a fluid. When used for particle separation, dielectrophoresis has many advantages compared to other methods, like providing label-free operation with greater control of the separation forces. In this paper, we design, build, and test a low-voltage dielectrophoretic device using a 3D printing approach. This lab-on-a-chip device fits on a microscope glass slide and incorporates microfluidic channels for particle separation. First, we use multiphysics simulations to evaluate the separation efficiency of the prospective device and guide the design process. Second, we fabricate the device in PDMS (polydimethylsiloxane) by using 3D-printed moulds that contain patterns of the channels and electrodes. The imprint of the electrodes is then filled with silver conductive paint, making a 9-pole comb electrode. Lastly, we evaluate the separation efficiency of our device by introducing a mixture of 3 μm and 10 μm polystyrene particles and tracking their progression. Our device is able to efficiently separate these particles when the electrodes are energized with ±12 V at 75 kHz. Overall, our method allows the fabrication of cheap and effective dielectrophoretic microfluidic devices using commercial off-the-shelf equipment.
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