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Sökning: WFRF:(Nilsson Henrik) > (2020-2024)

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1.
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2.
  • Spotorno, Nicola, et al. (författare)
  • Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia
  • 2020
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.
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3.
  • Abarenkov, Kessy, et al. (författare)
  • The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered
  • 2024
  • Ingår i: Nucleic Acids Research. - 0305-1048 .- 1362-4962. ; 52:D1, s. D791-D797
  • Tidskriftsartikel (refereegranskat)abstract
    • UNITE (https://unite.ut.ee) is a web-based database and sequence management environment for molecular identification of eukaryotes. It targets the nuclear ribosomal internal transcribed spacer (ITS) region and offers nearly 10 million such sequences for reference. These are clustered into similar to 2.4M species hypotheses (SHs), each assigned a unique digital object identifier (DOI) to promote unambiguous referencing across studies. UNITE users have contributed over 600 000 third-party sequence annotations, which are shared with a range of databases and other community resources. Recent improvements facilitate the detection of cross-kingdom biological associations and the integration of undescribed groups of organisms into everyday biological pursuits. Serving as a digital twin for eukaryotic biodiversity and communities worldwide, the latest release of UNITE offers improved avenues for biodiversity discovery, precise taxonomic communication and integration of biological knowledge across platforms. Graphical Abstract
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4.
  • Aleksyniene, Ramune, et al. (författare)
  • The Role of Nuclear Medicine Imaging with F-18-FDG PET/CT, Combined In-111-WBC/(99)mTc-Nanocoll, and Tc-99m-HDP SPECT/CT in the Evaluation of Patients with Chronic Problems after TKA or THA in a Prospective Study
  • 2022
  • Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this prospective study was to assess the diagnostic value of nuclear imaging with F-18-FDG PET/CT (FDG PET/CT), combined In-111-WBC/(99)mTc-Nanocoll, and Tc-99m-HDP SPECT/CT (dual-isotope WBC/bone marrow scan) for patients with chronic problems related to knee or hip prostheses (TKA or THA) scheduled by a structured multidisciplinary algorithm.Materials and Methods: Fifty-five patients underwent imaging with Tc-99m-HDP SPECT/CT (bone scan), dual-isotope WBC/bone marrow scan, and FDG PET/CT. The final diagnosis of prosthetic joint infection (PJI) and/or loosening was based on the intraoperative findings and microbiological culture results and the clinical follow-up.Results: The diagnostic performance of dual-isotope WBC/bone marrow SPECT/CT for PJI showed a sensitivity of 100% (CI 0.74-1.00), a specificity of 97% (CI 0.82-1.00), and an accuracy of 98% (CI 0.88-1.00); for PET/CT, the sensitivity, specificity, and accuracy were 100% (CI 0.74-1.00), 71% (CI 0.56-0.90), and 79% (CI 0.68-0.93), respectively.Conclusions: In a standardized prospectively scheduled patient group, the results showed highly specific performance of combined dual-isotope WBC/bone marrow SPECT/CT in confirming chronic PJI. FDG PET/CT has an appropriate accuracy, but the utility of its use in the clinical diagnostic algorithm of suspected PJI needs further evidence.
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5.
  • Bennet, Tova, et al. (författare)
  • Den rättspsykiatriska vården är inte rättssäker – agera nu
  • 2020
  • Ingår i: Göteborgs-Posten. - Göteborg : Göteborgposten. - 1103-9345. ; :Oktober 19
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Det svenska rättssystemet som tillåter att vi dömer psykiskt sjuka för brott och att personer som saknar vårdbehov kan hållas frihetsberövade inom rättspsykiatrin under mycket lång tid med oklart vårdinnehåll, är unikt och har fått rättmätig kritik under lång tid. Ändå händer ingenting. 
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6.
  • Eriksson, Martin, 1970, et al. (författare)
  • Triclosan changes community composition and selects for specific bacterial taxa in marine periphyton biofilms in low nanomolar concentrations
  • 2020
  • Ingår i: Ecotoxicology. - : Springer Science and Business Media LLC. - 0963-9292 .- 1573-3017. ; 29:7, s. 1083-1094
  • Tidskriftsartikel (refereegranskat)abstract
    • The antibacterial agent Triclosan (TCS) is a ubiquitous environmental contaminant due to its widespread use. Sensitivity to TCS varies substantially among eu- and pro-karyotic species and its risk for the marine environment remains to be better elucidated. In particular, the effects that TCS causes on marine microbial communities are largely unknown. In this study we therefore used 16S amplicon rDNA sequencing to investigate TCS effects on the bacterial composition in marine periphyton communities that developed under long-term exposure to different TCS concentrations. Exposure to TCS resulted in clear changes in bacterial composition already at concentrations of 1 to 3.16 nM. We conclude that TCS affects the structure of the bacterial part of periphyton communities at concentrations that actually occur in the marine environment. Sensitive taxa, whose abundance decreased significantly with increasing TCS concentrations, include the Rhodobiaceae and Rhodobacteraceae families of Alphaproteobacteria, and unidentified members of the Candidate division Parcubacteria. Tolerant taxa, whose abundance increased significantly with higher TCS concentrations, include the families Erythrobacteraceae (Alphaproteobacteria), Flavobacteriaceae (Bacteroidetes), Bdellovibrionaceae (Deltaproteobacteria), several families of Gammaproteobacteria, and members of the Candidate phylum Gracilibacteria. Our results demonstrate the variability of TCS sensitivity among bacteria, and that TCS can change marine bacterial composition at concentrations that have been detected in the marine environment.
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7.
  • Forsberg, Elin, et al. (författare)
  • Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs
  • 2023
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.
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8.
  • Gómez-Martínez, Daniela, et al. (författare)
  • Phenotypic and transcriptomic acclimation of the green microalga Raphidocelis subcapitata to high environmental levels of the herbicide diflufenican
  • 2023
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 875
  • Tidskriftsartikel (refereegranskat)abstract
    • Herbicide pollution poses a worldwide threat to plants and freshwater ecosystems. However, the understanding of how organisms develop tolerance to these chemicals and the associated trade-off expenses are largely unknown. This study aims to investigate the physiological and transcriptional mechanisms underlying the acclimation of the green microalgal model species Raphidocelis subcapitata (Selenastraceae) towards the herbicide diflufenican, and the fitness costs associated with tolerance development. Algae were exposed for 12 weeks (corresponding to 100 generations) to diflufenican at the two environmental concentrations 10 and 310 ng/L. The monitoring of growth, pigment composition, and photosynthetic performance throughout the experiment revealed an initial dose-dependent stress phase (week 1) with an EC50 of 397 ng/L, followed by a time-dependent recovery phase during weeks 2 to 4. After week 4, R. subcapitata was acclimated to diflufenican exposure with a similar growth rate, content of carotenoids, and photosynthetic performance as the unexposed control algae. This acclimation state of the algae was explored in terms of tolerance acquisition, changes in the fatty acids composition, diflufenican removal rate, cell size, and changes in mRNA gene expression profile, revealing potential fitness costs associated with acclimation, such as up-regulation of genes related to cell division, structure, morphology, and reduction of cell size. Overall, this study demonstrates that R. subcapitata can quickly acclimate to environmental but toxic levels of diflufenican; however, the acclimation is associated with trade-off expenses that result in smaller cell size.
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9.
  • Hedenström, Per, et al. (författare)
  • Pretreatment Tumor DNA Sequencing of KIT and PDGFRA in Endosonography-Guided Biopsies Optimizes the Preoperative Management of Gastrointestinal Stromal Tumors
  • 2020
  • Ingår i: Molecular Diagnosis & Therapy. - : Springer Science and Business Media LLC. - 1177-1062 .- 1179-2000.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Neoadjuvant tyrosine kinase inhibitor (TKI) therapy increases the chance of organ-preserving, radical resection in selected patients with gastrointestinal stromal tumors (GISTs). We aimed to evaluate systematic, immediate DNA sequencing of KIT and PDGFRA in pretreatment GIST tissue to guide neoadjuvant TKI therapy and optimize preoperative tumor response. Methods All patients who were candidates for neoadjuvant therapy of a suspected GIST [the study cohort (SC)] were prospectively included from January 2014 to March 2018. Patients were subjected to pretreatment endosonography-guided fine-needle biopsy (EUS-FNB) or transabdominal ultrasound-guided needle biopsy (TUS-NB), followed by immediate tumor DNA sequencing (< 2 weeks). A historic (2006-2013) reference cohort (RC) underwent work-up without sequencing before neoadjuvant imatinib (n = 42). The rate of optimal neoadjuvant therapy (Therapy(OPTIMAL)) was calculated, and the induced tumor size reduction (Tumor Regression(MAX), %) was evaluated by computed tomography (CT) scan. Results The success rate of pretreatment tumor DNA sequencing in the SC (n = 81) was 77/81 (95%) [EUS-FNB 71/74 (96%); TUS-NB 6/7 (86%)], with mutations localized in KIT (n = 58), PDGFRA (n = 18), or neither gene, wild type (n = 5). In patients with a final indication for neoadjuvant therapy, the Therapy(OPTIMAL) was higher in the SC compared with the RC [61/63 (97%) versus 33/42 (79%), p = 0.006], leading to a significantly higher Tumor Regression(MAX) in patients treated with TKI (27% vs. 19%, p = 0.015). Conclusions Pretreatment endosonography-guided biopsy sampling followed by immediate tumor DNA sequencing of KIT and PDGFRA is highly accurate and valuable in guiding neoadjuvant TKI therapy in GIST. This approach minimizes maltreatment with inappropriate regimens and leads to improved tumor size reduction before surgery.
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10.
  • Karlsson, Joakim, et al. (författare)
  • Molecular profiling of driver events in metastatic uveal melanoma
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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