[Predicting the Incidence of Venous Thromboembolism Using the Khorana Score: A Literature Review].

Venous thromboembolism (VTE) is the second most common cause of cancer-related deaths globally. The Khorana score, a VTE prediction model, is calculated using the site of cancer, white blood cell count, hemoglobin level, platelet count, and body mass index. This study aimed to investigate the usefulness of the Khorana score, using data available in the literature. On July 28, 2020, we collected papers using the following keywords: "cancer", "venous thromboembolism", "deep vein thrombosis", "pulmonary embolism", and "Khorana score" on PubMed. Papers published after 2016 were eligible. The selection criteria were as follows: "English or Japanese", "original paper", "abstract and full text", and "comply with the clinical question". There were 131 papers that matched the keywords, and 15 of them complied with the selection criteria. In 15 papers, Khorana score was calculated in 8047 patients. In the low- and intermediate-risk groups, 532 of 6812 patients developed VTE [7.8%, 95%confidence intervals (CI) 7.2-8.5], whereas in the high-risk group, 127 of 1235 patients developed VTE (10.3%, 95% CI 8.7-12.1) [odds ratio (OR) 1.3, 95% CI 1.0-1.6] (I2=0%, τ2=0, p=0.50). Venous thromboembolism prediction using the Khorana score might be useful. However, most of the number of VTE patients are in the low- and intermediate-risk groups. Therefore, a comprehensive evaluation according to clinical conditions is required, regardless of the risk classification using the Khorana score.

The Use of Chemical Compounds to Identify the Regulatory Mechanisms of Vertebrate Circadian Clocks.

Circadian clocks are intrinsic, time-tracking processes that confer a survival advantage on an organism. Under natural conditions, they follow approximately a 24-h day, modulated by environmental time cues, such as light, to maximize an organism's physiological efficiency. The exact timing of this rhythm is established by cell-autonomous oscillators called cellular clocks, which are controlled by transcription-translation negative feedback loops. Studies of cell-based systems and wholeanimal models have utilized a pharmacological approach in which chemical compounds are used to identify molecular mechanisms capable of establishing and maintaining cellular clocks, such as posttranslational modifications of cellular clock regulators, chromatin remodeling of cellular clock target genes' promoters, and stability control of cellular clock components. In addition, studies with chemical compounds have contributed to the characterization of light-signaling pathways and their impact on the cellular clock. Here, the use of chemical compounds to study the molecular, cellular, and behavioral aspects of the vertebrate circadian clock system is described.

Post-translational Modifications are Required for Circadian Clock Regulation in Vertebrates.

Circadian clocks are intrinsic, time-tracking systems that bestow upon organisms a survival advantage. Under natural conditions, organisms are trained to follow a 24-h cycle under environmental time cues such as light to maximize their physiological efficiency. The exact timing of this rhythm is established via cell-autonomous oscillators called cellular clocks, which are controlled by transcription/translation-based negative feedback loops. Studies using cell-based systems and genetic techniques have identified the molecular mechanisms that establish and maintain cellular clocks. One such mechanism, known as post-translational modification, regulates several aspects of these cellular clock components, including their stability, subcellular localization, transcriptional activity, and interaction with other proteins and signaling pathways. In addition, these mechanisms contribute to the integration of external signals into the cellular clock machinery. Here, we describe the post-translational modifications of cellular clock regulators that regulate circadian clocks in vertebrates.