Bmc Med
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Gastrointestinal stromal tumor (GIST) is a rare type of cancer that occurs in the gastrointestinal tract. The majority of GIST cases carry oncogenic forms of KIT, the receptor for stem cell factor (SCF). Small molecule kinase inhibitor imatinib is effective in prolonging the survival of GIST patients by targeting KIT. However, drug resistance often develops during the therapeutic treatment. Here, we produced a SCF-emtansine drug conjugate (SCF-DM1) with favorable drug efficacy towards GIST cells. ⋯ rhSCF is a convenient and effective vector for drug delivery to KIT positive GIST cells. SCF-DM1 is an effective drug candidate to treat imatinib-sensitive and -resistant GIST.
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Significant intertumoral heterogeneity exists as antitumor treatment is introduced. Heterogeneous therapeutic responses are conventionally evaluated by imaging examinations based on Response Evaluation Criteria in Solid Tumors (RECIST); nevertheless, there are increasing recognitions that they do not fully capture patient clinical benefits. Currently, there is a paucity of data regarding the clinical implication of biological responses assessed by liquid biopsy of on-treatment circulating tumor DNA (ctDNA). Here, we investigated whether biological response evaluated by ctDNA kinetics added critical information to the RECIST, and whether integrating on-treatment biological response information refined risk stratification of cancer patients. ⋯ Our study helps advance the implementation of ctDNA-based testing in therapeutic response evaluation for a refined risk stratification. The dynamic and refined risk profiling would tailor future liquid biopsy-based risk-adapted personalized therapy.
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Whether a genetic predisposition to psychiatric disorders is associated with coronavirus disease 2019 (COVID-19) is unknown. ⋯ Our findings suggest a potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19. Our data underscore the need for increased medical surveillance for this vulnerable population during the COVID-19 pandemic.
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The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score. ⋯ Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality.
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The relationship between non-alcoholic fatty liver degree as well as non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) remains poorly understood. We aimed to investigate the prospective association of non-alcoholic fatty liver degree as well as NAFLD with incident IBS in a large-scale population-based cohort. ⋯ High degree of non-alcoholic fatty liver as well as non-alcoholic fatty liver disease is associated with increased risk of incident IBS. Further studies are warranted to confirm the findings and elucidate the underlying biological mechanisms.