| 1. |
- Öberg, Rasmus, et al.
(författare)
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UV-induced spectral and morphological changes in bacterial spores for inactivation assessment
- 2024
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 128:7, s. 1638-1646
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Tidskriftsartikel (refereegranskat)abstract
- The ability to detect and inactivate spore-forming bacteria is of significance within, for example, industrial, healthcare, and defense sectors. Not only are stringent protocols necessary for the inactivation of spores but robust procedures are also required to detect viable spores after an inactivation assay to evaluate the procedure’s success. UV radiation is a standard procedure to inactivate spores. However, there is limited understanding regarding its impact on spores’ spectral and morphological characteristics. A further insight into these UV-induced changes can significantly improve the design of spore decontamination procedures and verification assays. This work investigates the spectral and morphological changes to Bacillus thuringiensis spores after UV exposure. Using absorbance and fluorescence spectroscopy, we observe an exponential decay in the spectral intensity of amino acids and protein structures, as well as a logistic increase in dimerized DPA with increased UV exposure on bulk spore suspensions. Additionally, using micro-Raman spectroscopy, we observe DPA release and protein degradation with increased UV exposure. More specifically, the protein backbone’s 1600–1700 cm–1 amide I band decays slower than other amino acid-based structures. Last, using electron microscopy and light scattering measurements, we observe shriveling of the spore bodies with increased UV radiation, alongside the leaking of core content and disruption of proteinaceous coat and exosporium layers. Overall, this work utilized spectroscopy and electron microscopy techniques to gain new understanding of UV-induced spore inactivation relating to spore degradation and CaDPA release. The study also identified spectroscopic indicators that can be used to determine spore viability after inactivation. These findings have practical applications in the development of new spore decontamination and inactivation validation methods.
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| 2. |
- Brodin, Daniel, et al.
(författare)
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Inhaled ciclesonide in adults hospitalised with COVID-19 : a randomised controlled open-label trial (HALT COVID-19)
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19.DESIGN: Multicentre, randomised, controlled, open-label trial.SETTING: 9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021.PARTICIPANTS: Adults hospitalised with COVID-19 and receiving oxygen therapy.INTERVENTION: Inhaled ciclesonide 320 µg two times a day for 14 days versus standard care.MAIN OUTCOME MEASURES: Primary outcome was duration of oxygen therapy, an indicator of time to clinical improvement. Key secondary outcome was a composite of invasive mechanical ventilation/death.RESULTS: Data from 98 participants were analysed (48 receiving ciclesonide and 50 receiving standard care; median (IQR) age, 59.5 (49-67) years; 67 (68%) men). Median (IQR) duration of oxygen therapy was 5.5 (3-9) days in the ciclesonide group and 4 (2-7) days in the standard care group (HR for termination of oxygen therapy 0.73 (95% CI 0.47 to 1.11), with the upper 95% CI being compatible with a 10% relative reduction in oxygen therapy duration, corresponding to a <1 day absolute reduction in a post-hoc calculation). Three participants in each group died/received invasive mechanical ventilation (HR 0.90 (95% CI 0.15 to 5.32)). The trial was discontinued early due to slow enrolment.CONCLUSIONS: In patients hospitalised with COVID-19 receiving oxygen therapy, this trial ruled out, with 0.95 confidence, a treatment effect of ciclesonide corresponding to more than a 1 day reduction in duration of oxygen therapy. Ciclesonide is unlikely to improve this outcome meaningfully.TRIAL REGISTRATION NUMBER: NCT04381364.
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| 3. |
- Caldeweyher, Eike, et al.
(författare)
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Hybrid Machine Learning Approach to Predict the Site Selectivity of Iridium-Catalyzed Arene Borylation
- 2023
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 145:31, s. 17367-17376
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Tidskriftsartikel (refereegranskat)abstract
- The borylation of aryl and heteroaryl C–H bonds is valuable for the site-selective functionalization of C–H bonds in complex molecules. Iridium catalysts ligated by bipyridine ligands catalyze the borylation of the C–H bond that is most acidic and least sterically hindered in an arene, but predicting the site of borylation in molecules containing multiple arenes is difficult. To address this challenge, we report a hybrid computational model that predicts the Site of Borylation (SoBo) in complex molecules. The SoBo model combines density functional theory, semiempirical quantum mechanics, cheminformatics, linear regression, and machine learning to predict site selectivity and to extrapolate these predictions to new chemical space. Experimental validation of SoBo showed that the model predicts the major site of borylation of pharmaceutical intermediates with higher accuracy than prior machine-learning models or human experts, demonstrating that SoBo will be useful to guide experiments for the borylation of specific C(sp2)–H bonds during pharmaceutical development.
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| 4. |
- Eriksson, Helen, et al.
(författare)
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Requirements, Development, and Evaluation of A National Building Standard-A Swedish Case Study
- 2020
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Ingår i: ISPRS International Journal of Geo-Information. - : MDPI. - 2220-9964. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to present a proposal for a national building standard in Sweden. We define requirements for the proposed standard, e.g., it should support development of 3D city models, connect to building information models (BIM) and national registers and be based on a national classification system for the urban environment. Based on these requirements we develop an Application Domain Extension (ADE) of the building model in the proposed CityGML 3.0 standard denoted CityGML Sve-Test. CityGML 3.0 includes several new features of interest, e.g., the space concept, enhanced possibilities to convert data, and to link to other standards. In our study we create test data according to CityGML Sve-Test and evaluate it against the requirements. It is shown that BIM models (in Industry Foundation Classes, IFC, format) can be converted to CityGML Sve-Test and that a classification system facilitates this conversion. The CityGML Sve-Test dataset can be used to increase the automation level in building permissions checking and a related study shows that CityGML 3.0 has capabilities to link to legal information and be a base for 3D cadastral index maps. Based on our experience, we suggest that the national building standard should conform to international standards and, if possible, include a classification system. The exchange format (GML, JSON etc.) might change, but to be based on a standardized data model ensures harmonized structures and concepts.
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| 5. |
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| 6. |
- 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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| 7. |
- Johansson, Alexandra C., et al.
(författare)
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Monitoring deactivation processes of bacterial spores using fluorescence spectroscopy
- 2022
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Ingår i: Proceedings Volume 12116, Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XXIII, 2022. - : SPIE - International Society for Optical Engineering.
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Konferensbidrag (refereegranskat)abstract
- There is a need for time efficient evaluation methods to discriminate between viable and dead bacterial spores. In this work, the potential to use the autofluorescence from spore suspensions for evaluation of spore deactivation processes is investigated. Bacillus thuringiensis and Bacillus anthracis ATCC 4229 spores were exposed to UV-radiation for deactivation and the fluorescence response was monitored at different radiation doses and the deactivation was evaluated via traditional bacterial incubation on agar culture plates. For excitation wavelengths of, e.g., 280 m and 330 nm, differences in the fluorescence response could be observed for different live:dead ratios.
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| 8. |
- Lisak, Mikael, et al.
(författare)
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Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200–300µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concentration > 200µg/L (CsAhigh) the first month after HSCT, compared to ≤ 200µg/L (CsAlow), increased the relapse risk of acute myloid leukemia (AML), using unrelated donors (URD) and antithymocyte globulin (ATG). Data was collected from 157 patients with AML, transplanted 2010–2016. The cumulative incidence of relapse (CIR) at 60months was 50% in the CsAhigh versus 32% in the CsAlow group (p = 0.016). In univariate analysis, CsAhigh versus CsAlow (p = 0.028), 10-unit increase of CsA as a continuous variable (p = 0.017) and high risk disease (p = 0.003) were associated with higher CIR. The results remained after adjusting for disease risk. Death following relapse occurred more frequently in the CsAhigh group (p = 0.0076). There were no significant differences in rates of aGvHD, chronic GvHD (cGvHD), EBV/CMV-infections or overall survival (OS) between the two groups. In conclusion, we found that a median CsA concentration > 200µg/L, the first month after HSCT, results in higher CIR of AML when combined with ATG.
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| 9. |
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| 10. |
- Schophuus Jensen, Annette, et al.
(författare)
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Cause-Specific Mortality in Patients During Long-Term Follow-Up After Atrial Switch for Transposition of the Great Arteries
- 2022
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 11:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the cause of death (CoD) in patients with transposition of the great arteries palliated with a Mustard or Senning procedure. The aim was to describe the CoD for patients with the Mustard and Senning procedure during short-(<10 years), mid-(10–20 years), and long-term (>20 years) follow-up after the operation.METHODS AND RESULTS: This is a retrospective, descriptive multicenter cohort study including all Nordic patients (Denmark, Finland, Norway, and Sweden) who underwent a Mustard or Senning procedure between 1967 and 2003. Patients who died within 30 days after the index operation were excluded. Among 968 patients with Mustard/Senning palliated transposition of the great arteries, 814 patients were eligible for the study, with a mean follow-up of 33.6 years. The estimated risk of all-cause mortality reached 36.0% after 43 years of follow-up, and the risk of death was highest among male patients as compared with female patients (P=0.004). The most common CoD was sudden cardiac death (SCD), followed by heart failure/heart transplantation accounting for 29% and 27%, respectively. During short-, mid-, and long-term follow-up, there was a change in CoD with SCD accounting for 23.7%, 46.6%, and 19.0% (P=0.002) and heart failure/heart transplantation 18.6%, 22.4%, and 46.6% (P=0.0005), respectively.CONCLUSIONS: Among patients corrected with Mustard or Senning transposition of the great arteries, the most common CoD is SCD followed by heart failure/heart transplantation. The CoD changes as the patients age, with SCD as the most common cause in adolescence and heart failure as the dominant cause in adulthood. Furthermore, the risk of all-cause mortality, SCD, and death attributable to heart failure or heart transplantation was increased in men >10 years after the Mustard/Senning operation.
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