مستخلص: In recent studies, small cell lung cancer (SCLC) treatment guidelines based on Veterans’ Administration Lung Study Group limited/extensive disease staging and resulted in broad and inseparable prognostic subgroups. Evidence suggests that the eight versions of tumor, node, and metastasis (TNM) staging can play an important role to address this issue. The aim of the present study was to improve the detection of prognostic subgroups from a real-word data (RWD) cohort of patients and analyze their patterns using a development pipeline with thoracic oncologists and machine learning methods. The method detected subgroups of patients informing unsupervised learning (partition around medoids) including the impact of covariates on prognosis (Cox regression and random survival forest). An analysis was carried out using patients with SCLC (n = 636) with stage IIIA–IVB according to TNM classification. The analysis yielded k = 7 compacted and well-separated clusters of patients. Performance status (Eastern Cooperative Oncology Group-Performance Status), lactate dehydrogenase, spreading of metastasis, cancer stage, and CRP were the baselines that characterized the subgroups. The selected clustering method outperformed standard clustering techniques, which were not capable of detecting meaningful subgroups. From the analysis of cluster treatment decisions, we showed the potential of future RWD applications to understand disease, develop individualized therapies, and improve healthcare decision making.
QC 20221115

مصطلحات الفهرس: C reactive protein; carboplatin; cisplatin; etoposide; irinotecan; lactate dehydrogenase; platinum complex, Medical and Health Sciences, Medicin och hälsovetenskap, Cancer and Oncology, Cancer och onkologi, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-321440Test
Clinical and Translational Science, 1752-8054, 2022, 15:10, s. 2437-2447

مستخلص: In recent studies, small cell lung cancer (SCLC) treatment guidelines based on Veterans’ Administration Lung Study Group limited/extensive disease staging and resulted in broad and inseparable prognostic subgroups. Evidence suggests that the eight versions of tumor, node, and metastasis (TNM) staging can play an important role to address this issue. The aim of the present study was to improve the detection of prognostic subgroups from a real-word data (RWD) cohort of patients and analyze their patterns using a development pipeline with thoracic oncologists and machine learning methods. The method detected subgroups of patients informing unsupervised learning (partition around medoids) including the impact of covariates on prognosis (Cox regression and random survival forest). An analysis was carried out using patients with SCLC (n = 636) with stage IIIA–IVB according to TNM classification. The analysis yielded k = 7 compacted and well-separated clusters of patients. Performance status (Eastern Cooperative Oncology Group-Performance Status), lactate dehydrogenase, spreading of metastasis, cancer stage, and CRP were the baselines that characterized the subgroups. The selected clustering method outperformed standard clustering techniques, which were not capable of detecting meaningful subgroups. From the analysis of cluster treatment decisions, we showed the potential of future RWD applications to understand disease, develop individualized therapies, and improve healthcare decision making.
QC 20221115

مصطلحات الفهرس: C reactive protein; carboplatin; cisplatin; etoposide; irinotecan; lactate dehydrogenase; platinum complex, Medical and Health Sciences, Medicin och hälsovetenskap, Cancer and Oncology, Cancer och onkologi, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-321440Test
Clinical and Translational Science, 1752-8054, 2022, 15:10, s. 2437-2447

مستخلص: Key message: Elevated methylglyoxal levels contribute to ammonium-induced growth disorders in Arabidopsis thaliana. Methylglyoxal detoxification pathway limitation, mainly the glyoxalase I activity, leads to enhanced sensitivity of plants to ammonium nutrition. Abstract: Ammonium applied to plants as the exclusive source of nitrogen often triggers multiple phenotypic effects, with severe growth inhibition being the most prominent symptom. Glycolytic flux increase, leading to overproduction of its toxic by-product methylglyoxal (MG), is one of the major metabolic consequences of long-term ammonium nutrition. This study aimed to evaluate the influence of MG metabolism on ammonium-dependent growth restriction in Arabidopsis thaliana plants. As the level of MG in plant cells is maintained by the glyoxalase (GLX) system, we analyzed MG-related metabolism in plants with a dysfunctional glyoxalase pathway. We report that MG detoxification, based on glutathione-dependent glyoxalases, is crucial for plants exposed to ammonium nutrition, and its essential role in ammonium sensitivity relays on glyoxalase I (GLXI) activity. Our results indicated that the accumulation of MG-derived advanced glycation end products significantly contributes to the incidence of ammonium toxicity symptoms. Using A. thaliana frostbite1 as a model plant that overcomes growth repression on ammonium, we have shown that its resistance to enhanced MG levels is based on increased GLXI activity and tolerance to elevated MG-derived advanced glycation end-product (MAGE) levels. Furthermore, our results show that glyoxalase pathway activity strongly affects cellular antioxidative systems. Under stress conditions, the disruption of the MG detoxification pathway limits the functioning of antioxidant defense. However, under optimal growth conditions, a defect in the MG detoxification route results in the activation of antioxidative systems.

مصطلحات الفهرس: Ammonium nutrition, d-Lactate dehydrogenase, Dicarbonyl stress, Glyoxalase, Methylglyoxal, Mitochondrial Complex I mutant, Botany, Botanik, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200516Test
Plant Cell Reports, 0721-7714, 2022, 41, s. 2393-2413

مستخلص: In recent studies, small cell lung cancer (SCLC) treatment guidelines based on Veterans’ Administration Lung Study Group limited/extensive disease staging and resulted in broad and inseparable prognostic subgroups. Evidence suggests that the eight versions of tumor, node, and metastasis (TNM) staging can play an important role to address this issue. The aim of the present study was to improve the detection of prognostic subgroups from a real-word data (RWD) cohort of patients and analyze their patterns using a development pipeline with thoracic oncologists and machine learning methods. The method detected subgroups of patients informing unsupervised learning (partition around medoids) including the impact of covariates on prognosis (Cox regression and random survival forest). An analysis was carried out using patients with SCLC (n = 636) with stage IIIA–IVB according to TNM classification. The analysis yielded k = 7 compacted and well-separated clusters of patients. Performance status (Eastern Cooperative Oncology Group-Performance Status), lactate dehydrogenase, spreading of metastasis, cancer stage, and CRP were the baselines that characterized the subgroups. The selected clustering method outperformed standard clustering techniques, which were not capable of detecting meaningful subgroups. From the analysis of cluster treatment decisions, we showed the potential of future RWD applications to understand disease, develop individualized therapies, and improve healthcare decision making.
QC 20221115

مصطلحات الفهرس: C reactive protein; carboplatin; cisplatin; etoposide; irinotecan; lactate dehydrogenase; platinum complex, Medical and Health Sciences, Medicin och hälsovetenskap, Cancer and Oncology, Cancer och onkologi, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-321440Test
Clinical and Translational Science, 1752-8054, 2022, 15:10, s. 2437-2447

مستخلص: Key message: Elevated methylglyoxal levels contribute to ammonium-induced growth disorders in Arabidopsis thaliana. Methylglyoxal detoxification pathway limitation, mainly the glyoxalase I activity, leads to enhanced sensitivity of plants to ammonium nutrition. Abstract: Ammonium applied to plants as the exclusive source of nitrogen often triggers multiple phenotypic effects, with severe growth inhibition being the most prominent symptom. Glycolytic flux increase, leading to overproduction of its toxic by-product methylglyoxal (MG), is one of the major metabolic consequences of long-term ammonium nutrition. This study aimed to evaluate the influence of MG metabolism on ammonium-dependent growth restriction in Arabidopsis thaliana plants. As the level of MG in plant cells is maintained by the glyoxalase (GLX) system, we analyzed MG-related metabolism in plants with a dysfunctional glyoxalase pathway. We report that MG detoxification, based on glutathione-dependent glyoxalases, is crucial for plants exposed to ammonium nutrition, and its essential role in ammonium sensitivity relays on glyoxalase I (GLXI) activity. Our results indicated that the accumulation of MG-derived advanced glycation end products significantly contributes to the incidence of ammonium toxicity symptoms. Using A. thaliana frostbite1 as a model plant that overcomes growth repression on ammonium, we have shown that its resistance to enhanced MG levels is based on increased GLXI activity and tolerance to elevated MG-derived advanced glycation end-product (MAGE) levels. Furthermore, our results show that glyoxalase pathway activity strongly affects cellular antioxidative systems. Under stress conditions, the disruption of the MG detoxification pathway limits the functioning of antioxidant defense. However, under optimal growth conditions, a defect in the MG detoxification route results in the activation of antioxidative systems.

مصطلحات الفهرس: Ammonium nutrition, d-Lactate dehydrogenase, Dicarbonyl stress, Glyoxalase, Methylglyoxal, Mitochondrial Complex I mutant, Botany, Botanik, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200516Test
Plant Cell Reports, 0721-7714, 2022, 41, s. 2393-2413

مستخلص: In recent studies, small cell lung cancer (SCLC) treatment guidelines based on Veterans’ Administration Lung Study Group limited/extensive disease staging and resulted in broad and inseparable prognostic subgroups. Evidence suggests that the eight versions of tumor, node, and metastasis (TNM) staging can play an important role to address this issue. The aim of the present study was to improve the detection of prognostic subgroups from a real-word data (RWD) cohort of patients and analyze their patterns using a development pipeline with thoracic oncologists and machine learning methods. The method detected subgroups of patients informing unsupervised learning (partition around medoids) including the impact of covariates on prognosis (Cox regression and random survival forest). An analysis was carried out using patients with SCLC (n = 636) with stage IIIA–IVB according to TNM classification. The analysis yielded k = 7 compacted and well-separated clusters of patients. Performance status (Eastern Cooperative Oncology Group-Performance Status), lactate dehydrogenase, spreading of metastasis, cancer stage, and CRP were the baselines that characterized the subgroups. The selected clustering method outperformed standard clustering techniques, which were not capable of detecting meaningful subgroups. From the analysis of cluster treatment decisions, we showed the potential of future RWD applications to understand disease, develop individualized therapies, and improve healthcare decision making.
QC 20221115

مصطلحات الفهرس: C reactive protein; carboplatin; cisplatin; etoposide; irinotecan; lactate dehydrogenase; platinum complex, Medical and Health Sciences, Medicin och hälsovetenskap, Cancer and Oncology, Cancer och onkologi, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-321440Test
Clinical and Translational Science, 1752-8054, 2022, 15:10, s. 2437-2447

مستخلص: In recent studies, small cell lung cancer (SCLC) treatment guidelines based on Veterans’ Administration Lung Study Group limited/extensive disease staging and resulted in broad and inseparable prognostic subgroups. Evidence suggests that the eight versions of tumor, node, and metastasis (TNM) staging can play an important role to address this issue. The aim of the present study was to improve the detection of prognostic subgroups from a real-word data (RWD) cohort of patients and analyze their patterns using a development pipeline with thoracic oncologists and machine learning methods. The method detected subgroups of patients informing unsupervised learning (partition around medoids) including the impact of covariates on prognosis (Cox regression and random survival forest). An analysis was carried out using patients with SCLC (n = 636) with stage IIIA–IVB according to TNM classification. The analysis yielded k = 7 compacted and well-separated clusters of patients. Performance status (Eastern Cooperative Oncology Group-Performance Status), lactate dehydrogenase, spreading of metastasis, cancer stage, and CRP were the baselines that characterized the subgroups. The selected clustering method outperformed standard clustering techniques, which were not capable of detecting meaningful subgroups. From the analysis of cluster treatment decisions, we showed the potential of future RWD applications to understand disease, develop individualized therapies, and improve healthcare decision making.
QC 20221115

مصطلحات الفهرس: C reactive protein; carboplatin; cisplatin; etoposide; irinotecan; lactate dehydrogenase; platinum complex, Medical and Health Sciences, Medicin och hälsovetenskap, Cancer and Oncology, Cancer och onkologi, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-321440Test
Clinical and Translational Science, 1752-8054, 2022, 15:10, s. 2437-2447

مستخلص: Key message: Elevated methylglyoxal levels contribute to ammonium-induced growth disorders in Arabidopsis thaliana. Methylglyoxal detoxification pathway limitation, mainly the glyoxalase I activity, leads to enhanced sensitivity of plants to ammonium nutrition. Abstract: Ammonium applied to plants as the exclusive source of nitrogen often triggers multiple phenotypic effects, with severe growth inhibition being the most prominent symptom. Glycolytic flux increase, leading to overproduction of its toxic by-product methylglyoxal (MG), is one of the major metabolic consequences of long-term ammonium nutrition. This study aimed to evaluate the influence of MG metabolism on ammonium-dependent growth restriction in Arabidopsis thaliana plants. As the level of MG in plant cells is maintained by the glyoxalase (GLX) system, we analyzed MG-related metabolism in plants with a dysfunctional glyoxalase pathway. We report that MG detoxification, based on glutathione-dependent glyoxalases, is crucial for plants exposed to ammonium nutrition, and its essential role in ammonium sensitivity relays on glyoxalase I (GLXI) activity. Our results indicated that the accumulation of MG-derived advanced glycation end products significantly contributes to the incidence of ammonium toxicity symptoms. Using A. thaliana frostbite1 as a model plant that overcomes growth repression on ammonium, we have shown that its resistance to enhanced MG levels is based on increased GLXI activity and tolerance to elevated MG-derived advanced glycation end-product (MAGE) levels. Furthermore, our results show that glyoxalase pathway activity strongly affects cellular antioxidative systems. Under stress conditions, the disruption of the MG detoxification pathway limits the functioning of antioxidant defense. However, under optimal growth conditions, a defect in the MG detoxification route results in the activation of antioxidative systems.

مصطلحات الفهرس: Ammonium nutrition, d-Lactate dehydrogenase, Dicarbonyl stress, Glyoxalase, Methylglyoxal, Mitochondrial Complex I mutant, Botany, Botanik, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200516Test
Plant Cell Reports, 0721-7714, 2022, 41, s. 2393-2413

مستخلص: Key message: Elevated methylglyoxal levels contribute to ammonium-induced growth disorders in Arabidopsis thaliana. Methylglyoxal detoxification pathway limitation, mainly the glyoxalase I activity, leads to enhanced sensitivity of plants to ammonium nutrition. Abstract: Ammonium applied to plants as the exclusive source of nitrogen often triggers multiple phenotypic effects, with severe growth inhibition being the most prominent symptom. Glycolytic flux increase, leading to overproduction of its toxic by-product methylglyoxal (MG), is one of the major metabolic consequences of long-term ammonium nutrition. This study aimed to evaluate the influence of MG metabolism on ammonium-dependent growth restriction in Arabidopsis thaliana plants. As the level of MG in plant cells is maintained by the glyoxalase (GLX) system, we analyzed MG-related metabolism in plants with a dysfunctional glyoxalase pathway. We report that MG detoxification, based on glutathione-dependent glyoxalases, is crucial for plants exposed to ammonium nutrition, and its essential role in ammonium sensitivity relays on glyoxalase I (GLXI) activity. Our results indicated that the accumulation of MG-derived advanced glycation end products significantly contributes to the incidence of ammonium toxicity symptoms. Using A. thaliana frostbite1 as a model plant that overcomes growth repression on ammonium, we have shown that its resistance to enhanced MG levels is based on increased GLXI activity and tolerance to elevated MG-derived advanced glycation end-product (MAGE) levels. Furthermore, our results show that glyoxalase pathway activity strongly affects cellular antioxidative systems. Under stress conditions, the disruption of the MG detoxification pathway limits the functioning of antioxidant defense. However, under optimal growth conditions, a defect in the MG detoxification route results in the activation of antioxidative systems.

مصطلحات الفهرس: Ammonium nutrition, d-Lactate dehydrogenase, Dicarbonyl stress, Glyoxalase, Methylglyoxal, Mitochondrial Complex I mutant, Botany, Botanik, Article in journal, info:eu-repo/semantics/article, text

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200516Test
Plant Cell Reports, 0721-7714, 2022, 41, s. 2393-2413

مصطلحات الفهرس: ACETATE, BOUND L-LACTATE, CYTOKINES, D-LACTATE DEHYDROGENASE, INFECTION, IN-SITU HYBRIDIZATION, Life Sciences & Biomedicine, LIPOOLIGOSACCHARIDE, Microbiology, NEW-GENERATION, Parasitology, PURIFICATION, RESISTANCE, Science & Technology, Virology, Journal Article

URL: http://hdl.handle.net/10536/DRO/DU:30164588Test
http://doi.org/10.1371/journal.ppat.1010209Test
http://elements.deakin.edu.au/viewobject.html?id=299616&cid=1Test
issn: 1553-7366
issn: 1553-7374
http://doi.org/10.1371/journal.ppat.1010209Test
http://elements.deakin.edu.au/viewobject.html?id=299616&cid=1Test
PLoS Pathogens