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  • 1
    In: Forests, MDPI AG, Vol. 13, No. 11 ( 2022-11-16), p. 1932-
    Abstract: Plant endophyte and epiphyte communities cooperatively interact with their host plants and play crucial roles in sustaining plant fitness. In Korea, a variety of studies have been conducted to elucidate the reasons for the declining population of the endangered Korean fir (Abies koreana), but the relationship between microbiota and the healthy condition of trees remains unclear. Here, we conducted bacterial 16S rRNA gene and fungal ITS sequence analyses to dissect the composition of endophytic and epiphytic microbiota in both live and dead trees located in the same Mt. Jiri habitat. In the live trees, the bacterial class Armatimonadia and the lichenized fungi groups were significantly dominant, whereas many bacterial and fungal taxa mainly found in rotten wood were enriched in the dead trees. Functional prediction of the microbial communities in live trees suggested the possibility that bacterial endophytes and epiphytes play a role in inorganic nutrient metabolism and fungal endophytes and epiphytes produce biologically active secondary metabolites, thereby contributing to the healthy condition of Korean fir trees. The ecological function of endophytes and epiphytes in dead trees was predicted to be involved in the decomposition of wood for nutrient recycling. Our analyses revealed a distinct difference in microbial communities depending on the health condition of Korean fir trees. The results from this study would be useful for understanding the ecological function of endophytic and epiphytic microorganisms to conserve and manage this endangered species from ecologically vulnerable environments.
    Type of Medium: Online Resource
    ISSN: 1999-4907
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527081-3
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e21217-e21217
    Abstract: e21217 Background: Radiomics can predict diagnosis, metastasis, actionable mutations and treatment response in NSCLC patients by analyzing the heterogeneity of tumors and its surrounding tissues from medical images. In this abstract, machine-learning models based on radiomic features, in patients with NSCLC, were established and evaluated. Methods: Patients with NSCLC and treated with ICIs were selected. Main tumor and peri-tumoral space were segmented on chest CT scans with contrast at the start of immunotherapy by four clinicians. Among 255 radiomic features were extracted using LIFEx software (IMIV/CEA, Orsay, France), the top 30 features with the highest Fleiss’ kappa coefficient were chosen. The Random Forest (RF) algorithm with mixed effects was utilized to develop models. We divided data into two groups as a training set (70%) and a validation set (30%) and conducted bootstrapping to evaluate the efficiency of the models. The performance of the models was determined by calculating the sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). Durable disease control, progression, clinical progression, EGFR mutations, bone metastasis was evaluated by each model. Durable disease control was defined as no progression of diseases for 24 weeks or more after initiation of ICIs according to RECIST 1.1. Progression was defined by RECIST 1.1 on the first follow-up CT. Clinical progression was defined when treatment was discontinued due to disease progression. Results: Total 102 patients were analyzed; 55 (53.9%) were female and 47 (46.1%) were male. The mean age at the start of ICI treatment was 65.6 [range: 22-89] . The multi-reader radiomics-based models predicts durable disease control, progression, clinical progression, EGFR mutation, and bone metastasis with a sensitivity of 0.700, 0.714, 0.286, 0.909, and 0.810, and specificity of 0.417, 0.444, 0.778, 0.200, and 0.222 respectively. The statistical values of the models are shown in the Table. Conclusions: The machine-learning models grounded on radiomics features has limited accuracy to prognosticate ICIs treatment outcome, EGFR mutations, and distant bone metastasis. Further studies with larger sample sizes are warranted. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21025-e21025
    Abstract: e21025 Background: HPD is an unexpected and rapid acceleration of tumor growth in patients following treatment with ICI. The definition of HPD is not fully established and risk factors are uncertain. Our aim in this study was to find the incidence of HPD as well as its significant clinicopathological and genetic predictive factors. Methods: A total of 203 patients with NSCLC treated with ICI at Northwestern Memorial Hospital during 2015-2020 were included. Clinicopathological data were retrospectively gathered and analyzed. Tumor growth kinetics (TGK) of pre-immunotherapy and post-immunotherapy were collected and TGK ratio (TGKr) was calculated. HPD was defined as TGKr≥2. Results: HPD was observed in 16% (33/203) of patients. There was a statistically significant difference in overall survival(OS) between the two groups (non-HPD vs. HPD) [OR = 2.39, P 〈 0.01]. The progression-free survival(PFS) also showed a statistically significant difference in patients (non-HPD vs HPD) [OR = 3.4, P 〈 0.01]. The median OS and PFS of patients with HPD were 13.57 months and 2.2 months respectively. The median OS and PFS of patients without HPD were 30.67 months and 7.3 months respectively. HPD was significantly associated with performance status (3-4 vs. 1-2) [OR = 4.52, P = 0.01] , presence of bone metastasis [OR = 2.51, P = 0.01], neutrophils/lymphocyte ratio(NLR) ≥5 [OR = 2.68, P = 0.01] , thrombocytosis (platelet count 〉 450k) [OR = 5.31, P 〈 0.01], and treatment with PD-L1 inhibitor vs. PD-1 inhibitor [OR = 2.14, P = 0.06] . HPD was inversely associated with positive PD-L1 expression [OR = 0.34, P = 0.01], ICI combined with chemotherapy vs. ICI monotherapy [OR = 0.24, P = 0.04] , and positive TTF-1 expression [OR = 0.46, P = 0.06]. HPD was not associated with histological subtypes of NSCLC, age( 〈 70, ≥70), sex, smoking history, number of metastatic lesions ( 〈 3, ≥3), brain metastasis, liver metastasis, brain metastasis before treatment initiation, EGFR mutation, TP53 mutation, BRAF mutation, TNM staging, tumor mutational burden (TMB) ( 〈 10, ≥10), microsatellite stability index (MSI), human leukocyte antigen-1 (HLA-1) heterozygosity, hemoglobin(≤12, 〉 12), albumin(≤3.5, 〉 3.5), and LDH(≤240, 〉 240). Conclusions: The incidence of HPD, 16%, was consistent with current literature. NLR ≥5, platelet count 〉 450k, poor performance status, presence of bone metastasis, treatment with PD-L1 inhibitor, negative PD-L1 expression, negative TTF-1 expression, and ICI monotherapy were predictors of HPD. To our knowledge, this is the first study to report an inverse correlation of TTF-1 expression, and non correlation of HLA-1 heterozygosity with HPD. The strength of our study is that we analyzed recently emerging next-generation sequencing (NGS) data to find novel predictors of HPD. Further studies on validating risk factors of HPD and exploring their associated mechanisms are warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Controlled Release, Elsevier BV, Vol. 133, No. 1 ( 2009-1), p. 60-67
    Type of Medium: Online Resource
    ISSN: 0168-3659
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 1482453-X
    SSG: 15,3
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5200-5200
    Abstract: Background: HPD is an unexpected rapid acceleration of tumor growth reported for patients treated with ICI. The definition of HPD is not fully established and risk factors are uncertain. Our aim in this study was to find the incidence of HPD as well as its significant clinical and genetic risk factors. Method: A total of 203 patients with NSCLC who received ICI at Northwestern Memorial Hospital during 2008-2020 were included. Tumor growth kinetics (TGK) on immunotherapy and TGK pre-immunotherapy were collected and TGK ratio (TGKR) was calculated. HPD was defined as TGKR≥2. Result: HPD was observed in 16% (n=33) of patients. HPD was significantly associated with high ECOG (3-4 vs 1-2) [OR = 4.52, 95% CI = 1.31 to 16.29, P = 0.01], presence of bone metastasis [OR = 2.51, 95% CI = 1.10 to 5.28, P = 0.01] , neutrophils/lymphocyte ratio(NLR) ≥5 [OR = 2.68, 95% CI = 1.24 to 5.81 P = 0.01], thrombocytosis (platelet count & gt;450k) [OR = 5.31, 95% CI = 2.07 to 14.70, P=0.0003], and treatment with PD-L1 inhibitor vs PD-1 inhibitor [OR = 2.14, 95% CI= 0.97 to 4.68, P= 0.068] . HPD was inversely associated with positive PD-L1 expression [OR = 0.34, 95% CI = 0.13 to 0.86, P = 0.01], ICI combined with chemotherapy vs ICI monotherapy [OR = 0.24, 95% CI = 0.055 to 0.97, P=0.04] , and positive TTF-1 expression [OR = 0.46, 95% CI = 0.21 to 1.02, P=0.057]. HPD was not associated with histology of NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and large cell neuroendocrine carcinoma), age( & lt;70, ≥70), sex, smoking history, number of metastatic lesions ( & lt;3, ≥3), brain metastasis, liver metastasis, brain metastasis before treatment initiation, EGFR mutation, TP53 mutation, BRAF mutation, and TNM staging. Conclusion: The incidence of HPD in NSCLC treated with ICI was consistent with current literature. High NLR and platelet count are suggestive of an immunosuppressive environment that could contribute to the rapid growth of tumors. To our knowledge, this is the first study to report an inverse correlation of PD-L1 expression and TTF-1 expression with HPD. The strength of our study lies in a large number of patients. Further studies on validating risk factors of HPD and exploring their associated mechanisms are warranted. Citation Format: Hyeonseon Kim, Yeun Ho Lee, Chiwoo Song, Leeseul Kim, Min Jeong Kim, Horyun Choi, Jinah Kim, Young Kwang Chae. The incidence and risk factors of hyperprogressive disease(HPD) in non-small cell lung cancer(NSCLC) treated with immune checkpoint inhibitors(ICI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5200.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2012
    In:  Acta Neurochirurgica Vol. 154, No. 1 ( 2012-1), p. 75-77
    In: Acta Neurochirurgica, Springer Science and Business Media LLC, Vol. 154, No. 1 ( 2012-1), p. 75-77
    Type of Medium: Online Resource
    ISSN: 0001-6268 , 0942-0940
    RVK:
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 1464215-3
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5619-5619
    Abstract: Background: Radiomics is an emerging tool that involves the extraction of high-throughput features from medical images. These quantitative values can be used to develop predictive models for clinical characteristics and treatment outcomes. We evaluated radiomic features-based models as imaging biomarkers in NSCLC patients. Methods: 71 patients with NSCLC treated with immunotherapy who had pretreatment CT chest with contrast were retrospectively evaluated. The main tumor and 1cm-thick peritumoral space surrounding the tumor were manually segmented using LIFEx software (IMIV/CEA, Orsay, France) by four physicians. Of 255 radiomic features collected, those with & gt;0.4 of Fleiss’ kappa coefficient were selected. The Random Forest (RF) algorithm with mixed effects was used to develop multi-reader models and assess feature importance. The dataset was divided into a training set (75%) and a test set (25%). Bootstrapping with 1,000 iterations was conducted to estimate the model performance. Durable disease control was defined as having no progression of diseases per RECIST 1.1 up to 24 weeks from starting immunotherapy. Results: Among 71 patients, 35 (49.3%) are female and 36 (50.7%) are male. The median age was 66. 48 (67.6%) adenocarcinoma, 13 (18.3%) squamous cell carcinoma, and 10 (14.1%) other histologic types were included. 22 radiomic features were included based on importance in the prediction models from both the tumor and peritumoral space. Each model is trained to predict patients’ durable disease control, TTF1 expression, PD-L1 expression, histology (adenocarcinoma or not), and Neutrophils Lymphocyte Ratio (NLR; greater than 5 or not) status. The statistical results from the models to predict clinical outcomes are shown in Table. Conclusion: The radiomic features-based models lack accuracy in predicting clinical characteristics and outcomes. Further validation with larger cohorts is warranted. Statistics of radiomics-based models in predicting clinical characteristics and treatment outcomes Durable Disease Control(Yes/No)(n=64) TTF1 expression(Yes/No)(n=62) Histology(Adeno/Other)(n=71) NLR( & gt;=5/ & lt;5)(n=71) PD-L1 expression(Yes/No)(n=52) Patient Number(%) 33 (51.56%)/31 (48.44%) 37 (59.68%)/25 (40.32%) 48 (67.61%)/23 (32.39%) 28 (39.44%)/43 (60.56%) 35 (67.31%)/17 (32.69%) Sensitivity (95% CI) 0.63 (0.58, 0.72) 0.62 (0.56, 0.74) 0.69 (0.56, 0.82) 0.55 (0.47, 0.61) 0.57 (0.48, 0.65) Specificity (95% CI) 0.46 (0.37, 0.52) 0.68 (0.58, 0.76) 0.22 (0.12, 0.34) 0.60 (0.56, 0.68) 0.36 (0.30, 0.45) Positive Predictive Value(95% CI) 0.52 (0.49, 0.57) 0.44(0.37, 0.60) 0.62 (0.59, 0.64) 0.69 (0.67, 0.74) 0.72 (0.68, 0.77) Negative Predictive Value(95% CI) 0.58 (0.54, 0.63) 0.79 (0.74, 0.88) 0.28 (0.22, 0.32) 0.46 (0.39, 0.51) 0.25 (0.21, 0.28) Citation Format: Jisang Yu, Yury Velichko, Hyeonseon Kim, Moataz Soliman, Nicolo Gennnaro, Leeseul Kim, Youjin Oh, Trie Arni Djunadi, Jeeyeon Lee, Liam Il-Young Chung, Sungmi Yoon, Zunairah Shah, Soowon Lee, Cecilia Nam, Timothy Hong, Rishi Agrawal, Pascale Aouad, Young Kwang Chae. Radiomics-based machine learning models to predict progression and biomarker status in non-small cell lung cancer (NSCLC) patients treated with immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5619.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    Online Resource
    Online Resource
    Radiological Society of North America (RSNA) ; 2023
    In:  Radiology Vol. 308, No. 3 ( 2023-09-01)
    In: Radiology, Radiological Society of North America (RSNA), Vol. 308, No. 3 ( 2023-09-01)
    Type of Medium: Online Resource
    ISSN: 0033-8419 , 1527-1315
    RVK:
    Language: English
    Publisher: Radiological Society of North America (RSNA)
    Publication Date: 2023
    detail.hit.zdb_id: 80324-8
    detail.hit.zdb_id: 2010588-5
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  • 9
    In: Journal of Controlled Release, Elsevier BV, Vol. 220 ( 2015-12), p. 119-129
    Type of Medium: Online Resource
    ISSN: 0168-3659
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 1482453-X
    SSG: 15,3
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  • 10
    In: Journal of Neurosurgery: Spine, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 18, No. 1 ( 2013-01), p. 69-75
    Abstract: The aim in this study was to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) leads to sensory improvement in rat spinal cord injury (SCI) models. Methods Thirty male Sprague-Dawley rats were included in this study: 10 in the sham group (laminectomy alone without SCI), 10 in the SCI group (SCI treated with phosphate-buffered saline), and 10 in the GM-CSF treatment group (SCI treated with GM-CSF). A locomotor function test and pain sensitivity test were conducted weekly for 9 weeks after SCI or sham injury. Spinal tissue samples from all rats were immunohistochemically examined for the expression of calcitonin gene-related peptide (CGRP) and abnormal sprouting at Week 9 post-SCI. Results Granulocyte-macrophage colony-stimulating factor treatment improves functional recovery after SCI. In the tactile withdrawal threshold and frequency of the hindlimb paw, the GM-CSF group always responded with a statistically significant lower threshold than the SCI group 9 weeks after SCI (p 〈 0.05). The response of the forelimb and hindlimb paws to cold in the GM-CSF group always reflected a statistically significant lower threshold than in the SCI group 9 weeks after injury (p 〈 0.05). Decreased CGRP expression, observed by density and distribution area, was noted in the GM-CSF group (optical density 113.5 ± 20.4) compared with the SCI group (optical density 143.1 ± 18.7; p 〈 0.05). Conclusions Treatment with GM-CSF results in functional recovery, improving tactile and cold sense recovery in a rat SCI model. Granulocyte-macrophage colony-stimulating factor also minimizes abnormal sprouting of sensory nerves after SCI.
    Type of Medium: Online Resource
    ISSN: 1547-5654
    RVK:
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2013
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