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  • 1
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-3-3)
    Abstract: GHB is an endogenous short-chain organic acid presumably also widely applied as a rape and knock out drug in cases of drug-facilitated crimes or sexual assaults (DFSA). Due to the endogenous nature of GHB and its fast metabolism in vivo , the detection window of exogenous GHB is however narrow, making it challenging to prove use of GHB in DFSA cases. Alternative markers of GHB intake have recently appeared though none has hitherto been validated for forensic use. UHPLC-HRMS based screening of blood samples for drugs of abuse is routinely performed in several forensic laboratories which leaves an enormous amount of unexploited data. Recently we devised a novel metabolomics approach to use archived data from such routine screenings for elucidating both direct metabolites from exogenous compounds, but potentially also regulation of endogenous metabolism and metabolites. In this paper we used UHPLC-HRMS data acquired over a 6-year period from whole blood analysis of 51 drivers driving under the influence of GHB as well as a matched control group. The data were analyzed using a metabolomics approach applying a range of advanced analytical methods such as OPLS-DA, LASSO, random forest, and Pearson correlation to examine the data in depth and demonstrate the feasibility and potential power of the approach. This was done by initially detecting a range of potential biomarkers of GHB consumption, some that previously have been found in controlled GHB studies, as well as several new potential markers not hitherto known. Furthermore, we investigate the impact of GHB intake on human metabolism. In aggregate, we demonstrate the feasibility to extract meaningful information from archived data here exemplified using GHB cases. Hereby we hope to pave the way for more general use of the principle to elucidate human metabolites of e.g. new legal or illegal drugs as well as for applications in more global and large scale metabolomics studies in the future.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 7 ( 2016-09-16)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2016
    detail.hit.zdb_id: 2587354-4
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-9-7)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-9-7)
    Abstract: YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein produced by various cell types including stromal, immune, and cancer cells. It contributes to cancer progression through tumor-promoting inflammation and has been shown to inhibit the cytotoxicity of T and NK lymphocytes. In vivo studies have demonstrated synergistic anti-cancer effects of blocking YKL-40 in combination with immune checkpoint inhibitors (ICIs). Biomarkers for the prediction of the response to ICIs are highly needed. We investigated the association between plasma YKL-40 and clinical benefit and survival in patients with metastatic pancreatic cancer (mPC) receiving ICIs and stereotactic body radiotherapy (SBRT). Methods Blood samples were collected from 84 patients with mPC who participated in the randomized phase II CheckPAC study, in which patients received nivolumab with or without ipilimumab combined with a single fraction of SBRT. Plasma YKL-40 was measured using a commercial ELISA kit. Results Elevated baseline plasma YKL-40 was an independent predictor of shorter overall survival (OS) (HR 2.19, 95% CI 1.21–3.95). A ≥ 40% decrease in plasma YKL-40 during treatment was associated with longer progression-free survival ( p = 0.009) and OS ( p = 0.0028). There was no correlation between plasma YKL-40 and the tumor burden marker CA19-9 at baseline or during treatment. Conclusion This study contributes new knowledge regarding YKL-40 as a predictor of clinical benefit from ICIs and radiotherapy. These exploratory results warrant further investigation of YKL-40 as a biomarker for patients treated with immunotherapies. Clinical trial registration Clinicaltrials.gov , identifier NCT02866383.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 4
    In: Frontiers in Ecology and Evolution, Frontiers Media SA, Vol. 10 ( 2022-3-24)
    Abstract: Animals experience climatic variation in their natural habitats, which may lead to variation in phenotypic responses among populations through local adaptation or phenotypic plasticity. In ectotherm arthropods, the expression of thermoprotective metabolites such as free amino acids, sugars, and polyols, in response to temperature stress, may facilitate temperature tolerance by regulating cellular homeostasis. If populations experience differences in temperatures, individuals may exhibit population-specific metabolite profiles through differential accumulation of metabolites that facilitate thermal tolerance. Such thermoprotective metabolites may originate from the animals themselves or from their associated microbiome, and hence microbial symbionts may contribute to shape the thermal niche of their host. The social spider Stegodyphus dumicola has extremely low genetic diversity, yet it occupies a relatively broad temperature range occurring across multiple climate zones in Southern Africa. We investigated whether the metabolome, including thermoprotective metabolites, differs between populations, and whether population genetic structure or the spider microbiome may explain potential differences. To address these questions, we assessed metabolite profiles, phylogenetic relationships, and microbiomes in three natural populations along a temperature gradient. The spider microbiomes in three genetically distinct populations of S. dumicola showed no significant population-specific pattern, and none of its dominating genera ( Borrelia, Diplorickettsia , and Mycoplasma ) are known to facilitate thermal tolerance in hosts. These results do not support a role of the microbiome in shaping the thermal niche of S. dumicola. Metabolite profiles of the three spider populations were significantly different. The variation was driven by multiple metabolites that can be linked to temperature stress (e.g., lactate, succinate, or xanthine) and thermal tolerance (e.g., polyols, trehalose, or glycerol): these metabolites had higher relative abundance in spiders from the hottest geographic region. These distinct metabolite profiles are consistent with a potential role of the metabolome in temperature response.
    Type of Medium: Online Resource
    ISSN: 2296-701X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2745634-1
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Genetics Vol. 11 ( 2020-9-11)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 11 ( 2020-9-11)
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606823-0
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Rehabilitation Sciences Vol. 2 ( 2021-10-26)
    In: Frontiers in Rehabilitation Sciences, Frontiers Media SA, Vol. 2 ( 2021-10-26)
    Abstract: Background: Patient-centred care has received increased attention in recent years. Patient-Reported Outcomes (PROs) and shared decision-making are key components of Patient-Centred care. Low back pain (LBP) is a complex symptom affected by multiple, interacting factors. Therefore, evidence strongly recommend a biopsychosocial and patient-centred approach in the assessment and management. The International Classification of Functioning, Disability and Health (ICF) provide a biopsychosocial model for describing functioning and disability. ICF is widely acknowledged, but implementation into clinical practice is lacking. To support the use of a biopsychosocial and patient-centred approach in daily clinical practice among patients with LBP we developed a practice-friendly tool based on ICF; the LBP assessment tool. Objective: To compare an ICF-based assessment facilitated by the LBP assessment tool with standard care in terms of the use of PROs and shared decision-making in order to promote patient-centred care in patients with LBP. Methods: A non-randomized controlled design was used. Eligible patients were allocated to one of two groups: the ICF group, assessed with the LBP assessment tool or the control group, assessed with a conventional LBP assessment. Primary outcome includes use of PROs. Secondary outcomes include use of a graphical overview displaying the patient profile and shared decision-making. A patient evaluation questionnaire was used to collect data. Results: Seven hundred ten patients were assessed for eligibility of whom 531 were allocated to the ICF group ( n = 299) or the control group ( n = 232). A significantly higher use of PRO data ( p & lt; 0.00) and the patient profile ( p & lt; 0.00) was reported in favor of the ICF group. Patients in the ICF group also experienced being more involved in decision-making ( p = 0.01). Conclusions: This study showed that a functioning assessment, by means of the LBP assessment tool, increased use of PROs and shared decision-making when compared to a conventional LBP assessment. Additionally, this study demonstrated that routine use of ICF-based PRO data and shared decision-making promoted patient-centred care in patients with LBP. The LBP assessment tool may be a strong candidate for a user-friendly ICF-based tool with the potential to support health professionals in a shift toward a biopsychosocial and patient-centred approach to patients with LBP.
    Type of Medium: Online Resource
    ISSN: 2673-6861
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 3091712-8
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