Abcg2/Bcrp and Abcb1a/Pgp are xenobiotic efflux transporters limiting substrate permeability in the gastrointestinal system and brain, and increasing renal and hepatic drug clearance. The systemic impact of Bcrp and Pgp ablation on metabolic homeostasis of endogenous substrates is incompletely understood. We performed untargeted metabolomics of cerebrospinal fluid (CSF) and plasma, transcriptomics of brain, liver and kidney from male Sprague Dawley rats (WT) and Bcrp/Pgp double knock-out (dKO) rats, and integrated metabolomic/transcriptomic analysis to identify putative substrates and perturbations in canonical metabolic pathways. A predictive Bayesian machine learning model was used to predict in silico those metabolites with greater substrate-like features for either transporters. The CSF and plasma levels of 169 metabolites, nutrients, signaling molecules, antioxidants and lipids were significantly altered in dKO rats, compared to WT rats. These metabolite changes suggested alterations in histidine, branchetabolism, how transporter inhibition could rewire drug sensitivity indirectly through metabolic changes, and identify functional Bcrp biomarkers. This study aimed to clarify how SARS-CoV-2 RNAemia is related to COVID-19 critical condition development and mortality in comparison with other predictive markers and scoring systems. This is a retrospective cohort study conducted at Yokohama Municipal Citizen's Hospital and National Institute of Infectious Diseases. We recruited adult patients with COVID-19 admitted between March 2020 and January 2021. We compared RNAemia with clinical status on admission including scoring systems such as the 4C Mortality, CURB-65, and A-DROP, as well as the Ct value of the nasopharyngeal PCR, in predicting COVID-19 mortality and critical condition development. Of the 92 recruited patients (median age, 58; interquartile range, 45-71 years), 14 (14.9%) had RNAemia. These patients had an older age (median, 68 years vs. Inflammation inhibitor 55.5 years; p = 0.011), higher values of lactated dehydrogenase (median, 381 U/L vs. 256.5 U/L, p < 0.001), C-reactive protein (median, 10.9 mg/dL vs. 3.8 mg/dL; p < 0.001), D-dimer (median, 2.07 μg/mL vs. 1.28 μg/mL; p = 0.015), lower values of lymphocyte (median, 802/μL vs. 1007/μL, p = 0.025) and Ct of the nasopharyngeal PCR assay (median, 20.59 vs. 25.54; p = 0.021) than those without RNAemia. Univariate analysis showed RNAemia was associated with mortality (odds ratio [OR], 18.75; 95% confidence interval [CI], 3.92-89.76; area under the receiver operating characteristic curve [AUC], 0.7851; p = 0.002) and critical condition (OR, 72.00; 95% CI, 12.98-399.29; AUC, 0.8198; p < 0.001). Plus, multivariate analysis also revealed the association of RNAemia with critical condition (adjusted OR, 125.71; 95% CI, 11.47-1377.32; p < 0.001). On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71.On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71. Many new cancer drugs are being approved by reputed regulatory authorities without evidence of overall survival benefit, quality of life improvement, and often based on clinical trials at high risk of bias. In recent years, most Latin American (LA) countries have reformed their marketing authorization (MA) rules to directly accept or abbreviate the approval process in case of earlier authorization by the European Medicines Agency (EMA) and the US Food and Drug Administration, mainly. This study assessed the potential impact of decisions taken by EMA regarding the approval of new cancer drugs based on no evidence of overall survival or in potentially biased clinical trials in LA countries. Descriptive analysis. Publicly accessible marketing authorization databases from LA regulators, European Public Assessment Report by EMA, and previous studies accessing EMA approvals of new cancer drugs 2009-2016. Number of new cancer drugs approved by LA countries without evidence of overall survival (2009-2013), anperformed clinical trials measuring surrogate endpoints. EMA and other reputed regulators must be aware that their regulatory decisions might directly influence decisions regarding MA, health budgets and patient's care elsewhere.Technological advances in robotics have already produced robots that are indistinguishable from human beings. This technology is overcoming the uncanny valley, which refers to the unpleasant feelings that arise from humanoid robots that are similar in appearance to real humans to some extent. If humanoid robots with the same appearance are mass-produced and become commonplace, we may encounter circumstances in which people or human-like products have faces with the exact same appearance in the future. This leads to the following question what impressions do clones elicit? To respond to this question, we examined what impressions images of people with the same face (clone images) induce. In the six studies we conducted, we consistently reported that clone images elicited higher eeriness than individuals with different faces; we named this new phenomenon the clone devaluation effect. We found that the clone devaluation effect reflected the perceived improbability of facial duplication. Moreover, this phenomenon was related to distinguishableness of each face, the duplication of identity, the background scene in observing clone faces, and avoidance reactions based on disgust sensitivity. These findings suggest that the clone devaluation effect is a product of multiple processes related to memory, emotion, and face recognition systems. COVID-19 pandemic has rapidly required a high demand of hospitalization and an increased number of intensive care units (ICUs) admission. Therefore, it became mandatory to develop prognostic models to evaluate critical COVID-19 patients. We retrospectively evaluate a cohort of consecutive COVID-19 critically ill patients admitted to ICU with a confirmed diagnosis of SARS-CoV-2 pneumonia. A multivariable Cox regression model including demographic, clinical and laboratory findings was developed to assess the predictive value of these variables. Internal validation was performed using the bootstrap resampling technique. The model's discriminatory ability was assessed with Harrell's C-statistic and the goodness-of-fit was evaluated with calibration plot. 242 patients were included [median age, 64 years (56-71 IQR), 196 (81%) males]. Hypertension was the most common comorbidity (46.7%), followed by diabetes (15.3%) and heart disease (14.5%). Eighty-five patients (35.1%) died within 28 days after ICU admission and the median time from ICU admission to death was 11 days (IQR 6-18).