Bmc Med
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Pancreatic ductal adenocarcinoma (PDAC) has the lowest overall survival rate primarily due to the late onset of symptoms and rapid progression. Reliable and accurate tests for early detection are lacking. We aimed to develop a noninvasive test for early PDAC detection by capturing the circulating tumour DNA (ctDNA) methylation signature in blood. ⋯ The PDACatch assay demonstrated high sensitivity for early PDAC plasma, providing potential utility for noninvasive detection of early PDAC and indicating the effectiveness of methylation haplotype analyses in discovering robust cancer markers.
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Multicenter Study
Conteltinib (CT-707) in patients with advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, first-in-human phase 1 study.
Conteltinib (CT-707) is a potent second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) showing promising anti-tumor activities in preclinical studies. This study aimed to assess the safety, pharmacokinetic (PK), and efficacy of conteltinib in patients with ALK-positive non-small cell lung cancer (NSCLC). ⋯ In this study, conteltinib showed manageable safety profile, favorable PK properties, and anti-tumor activity in advanced ALK-positive NSCLC patients. The recommended phase 2 dose was determined to be 600 mg QD for ALK TKI-naïve patients and 300 mg bis in die (BID) for patients who received crizotinib previously.
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Supporting decisions for patients who present to the emergency department (ED) with COVID-19 requires accurate prognostication. We aimed to evaluate prognostic models for predicting outcomes in hospitalized patients with COVID-19, in different locations and across time. ⋯ NOCOS performed moderately worse than COPE, probably reflecting unique aspects of the early pandemic in NYC. Frequent updating of prognostic models is likely to be required for transportability over time and space during a dynamic pandemic.
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We performed phenome-wide Mendelian randomization analysis (MR-PheWAS), two-sample MR analysis, and systemic review to comprehensively explore the health effects of milk consumption in the European population. ⋯ This study suggests several health effects of milk consumption in the European population.
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Meta Analysis
Identifying and ranking causal biochemical biomarkers for breast cancer: a Mendelian randomisation study.
Only a few of the 34 biochemical biomarkers measured in the UK Biobank (UKB) have been associated with breast cancer, with many associations suffering from possible confounding and reverse causation. This study aimed to screen and rank all UKB biochemical biomarkers for possible causal relationships with breast cancer. ⋯ Our findings support a likely causal role of genetically predicted levels of testosterone, HDL cholesterol, and IGF-1, as well as a novel potential role of ALP in breast cancer aetiology. Further studies are needed to understand full disease pathways that may inform breast cancer prevention.