| 1. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 2. |
- Gracias, J., et al.
(författare)
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Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia. Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
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| 3. |
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| 4. |
- Lindgren Belal, Sarah, et al.
(författare)
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Automated quantification of PET/CT skeletal tumor burden in prostate cancer using artificial intelligence: The PET index
- 2023
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 50:5, s. 1510-1520
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Consistent assessment of bone metastases is crucial for patient management and clinical trials in prostate cancer (PCa). We aimed to develop a fully automated convolutional neural network (CNN)-based model for calculating PET/CT skeletal tumor burden in patients with PCa. Methods A total of 168 patients from three centers were divided into training, validation, and test groups. Manual annotations of skeletal lesions in -[F-18]fluoride PET/CT scans were used to train a CNN. The AI model was evaluated in 26 patients and compared to segmentations by physicians and to a SUV 15 threshold. PET index representing the percentage of skeletal volume taken up by lesions was estimated. Results There was no case in which all readers agreed on prevalence of lesions that the AI model failed to detect. PET index by the AI model correlated moderately strong to physician PET index (mean r = 0.69). Threshold PET index correlated fairly with physician PET index (mean r = 0.49). The sensitivity for lesion detection was 65-76% for AI, 68-91% for physicians, and 44-51% for threshold depending on which physician was considered reference. Conclusion It was possible to develop an AI-based model for automated assessment of PET/CT skeletal tumor burden. The model's performance was superior to using a threshold and provides fully automated calculation of whole-body skeletal tumor burden. It could be further developed to apply to different radiotracers. Objective scan evaluation is a first step toward developing a PET/CT imaging biomarker for PCa skeletal metastases.
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| 5. |
- Tran, Dien M., et al.
(författare)
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High prevalence of colonisation with carbapenem-resistant Enterobacteriaceae among patients admitted to Vietnamese hospitals : Risk factors and burden of disease
- 2019
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Ingår i: Journal of Infection. - : Saunders Elsevier. - 0163-4453 .- 1532-2742. ; 79:2, s. 115-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC).MethodsA point prevalence survey (PPS) with screening for colonisation with CRE was conducted on 2233 patients admitted to neonatal, paediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of faecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome.ResultsA total of 1165 (52%) patients were colonised with CRE, most commonly Klebsiella pneumoniae (n=805), Escherichia coli (n=682) and Enterobacter spp. (n=61). Duration of hospital stay, HAI and treatment with a carbapenem were independent risk factors for CRE colonisation. The PPS showed that the prevalence of CRE colonisation increased on average 4.2 % per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5•5, P < 0•01) with CRE colonisation and HAI on admission.ConclusionThese data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalised patients.
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| 6. |
- Vinblad, Elin, et al.
(författare)
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Children and young people’s experiences of participation in pediatric rehabilitation : a qualitative study
- 2019
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Ingår i: Developmental Medicine & Child Neurology. - Chichester : Wiley-Blackwell. - 0012-1622 .- 1469-8749. ; 61:S2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Creating a healthcare system of justice requires a child-centered care where children and young people, regardless of disability, are allowed to participate in their own rehabilitation. The aim of this study was to explore children and young people’s experiences of participation in pediatric rehabilitation.Patients and methods: The study had a descriptive design with a qualitative content analysis approach. Interviews were conducted with 20 children (6-17 years old, 9 girls and 11 boys) and 8 young people (18-30 years old, 6 women and 2 men) with intellectual disabilities, physical disabilities or autism spectrum disorders.Results: Three categories emerged that reflected children and young people’s experiences of participation in pediatric rehabilitation: to be included; to be empowered; and to feel supported. To be included meant that children and young people are respected, listened to and involved in shared decision-making. To be empowered comprised autonomy, responsibility and understanding as essential aspects for participation. To feel supported meant that children and young people described their parents as facilitators for enabling participation by supporting communication and being a bridge between child and professionals.Conclusion: To increase participation, children need support in communication with the healthcare professionals in a way that they feel respected, empowered and able to be included in decisions concerning their own pediatric rehabilitation. This result constitutes an important step in the development of a forthcoming digital communication and decision tool, with the main objective to increase participation, for children with disabilities.
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| 8. |
- Benavidez, A. D., et al.
(författare)
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Environmental Transmission Electron Microscopy Study of the Origins of Anomalous Particle Size Distributions in Supported Metal Catalysts
- 2012
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 2:11, s. 2349-2356
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Tidskriftsartikel (refereegranskat)abstract
- In this Environmental Transmission Electron Microscopy (ETEM) study we examined the growth patterns' of uniform distributions of nanoparticles (NPs) using model catalysts. Pt/SiO2 was heated at 550 degrees C in 560 Pa of O-2 while Pd/carbon was heated in vacuum at 500 degrees C and in 300 Pa of 5%H-2 in Argon at temperatures up to 600 degrees C. Individual NPs of Pd were tracked to determine the operative sintering mechanisms. We found anomalous growth Of NPs occurred during the early stages of catalyst sintering wherein some particles started to grow significantly larger than the mean, resulting in a broadening of the particle size distribution (PSD). The abundance of the larger particles did not fit the log normal distribution. We can rule out sample nonuniformity as a cause for the growth of these large particles, since images were recorded prior to heat treatments. The anomalous growth of these particles may help explain PSDs in heterogeneous catalysts which often show particles that are significantly larger than the mean, resulting in a long tail to the right. It has been suggested previously that particle migration and coalescence could be the likely cause for such broad size distributions. We did not detect any random migration of the NPs leading to coalescence. A directed migration process was seen to occur at elevated temperatures for Pd/carbon under H-2. This study shows that anomalous growth of NPs can occur under conditions where Ostwald ripening is the primary sintering mechanism.
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| 9. |
- Birgegard, Andreas, et al.
(författare)
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Validity of eating disorder diagnoses in the Swedish national patient register
- 2022
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Ingår i: Journal of Psychiatric Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0022-3956 .- 1879-1379. ; 150, s. 227-230
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish National Patient Register (NPR) includes population-level longitudinal data, and determining the validity of NPR diagnoses is critical to undergirding the research and policy recommendations they inform. Sweden also has the integrated "Riksa & BULL;t " and "Stepwise " National Quality Registers (QR), with data from specialized eating disorder (ED) treatment based on structured, valid assessment methods. To validate NPR ED diagnoses, we compared ICD-10-based anorexia nervosa (AN), bulimia nervosa (BN), and unspecified ED in NPR to DSM-IV-based AN, BN, and ED not otherwise specified category (EDNOS) in QR. Patients' first diagnoses registered in QR between February 2008 and August 2013 were compared with NPR diagnoses entered within & PLUSMN;1 month (N = 2074). QR registration includes the semi-structured DSM-IV-based Structured ED Interview. Each ED diagnosis was analyzed separately for degree of match using several indices: overall agreement, sensitivity, positive predictive value, specificity, negative predictive value, area under the curve, and Cohen's kappa. Results showed moderate to excellent agreement depending on estimate (e.g. positive predictive values AN: 0.747; BN:.836; EDNOS: 0.761), except for a somewhat low sensitivity for BN, and EDNOS agreement was overall the lowest. Case prevalence in the NPR and QR was highly similar for AN, and within five percentage points for BN and EDNOS. Generalizability is hampered by limited age range and diagnostic resolution as well as few males. Available data precluded study of presence/absence of ED, and complementary approaches are considered for future research. We conclude that NPR ED diagnoses have acceptable validity and are appropriate for use in research.
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| 10. |
- Brink, Daniel P., et al.
(författare)
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Draft Genome Assembly of Stutzerimonas sp. Strain S1 and Achromobacter spanius Strain S4, Two Syringol-Metabolizing Bacteria Isolated from Compost Soil
- 2023
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Ingår i: Microbiology Resource Announcements. - : American Society for Microbiology. - 2576-098X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Two bacterial strains able to use syringol as a sole carbon source were isolated from compost. The isolates, named S1 and S4, were sequenced using the Illumina platform. The final assemblies contained 4.2 Mbp, 63% GC, and 3,912 genes for S1 and 6.2 Mbp, 64% GC, and 5,503 genes for S4.
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