Background:Although the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients. Methods:This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Dia gnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value. Findings:The Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= -0.682). Interpretation:Serum SARS-CoV-2 viral load (RNAaemia) is strongly associated with cytokine storm and can be used to predict the poor prognosis of COVID-19 patients.Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response. All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Highlights d Discovery of prognosis-associated proteins and pathways at early stage of LUAD d Proteomics revealed three subtypes related to clinical and molecular features d Identification of subtype-specific kinases and cancerassociated phosphoproteins d Identification of potential prognostic biomarkers and drug targets in LUAD

SUMMARY For the majority of patients with pancreas cancer, the high metastatic proclivity is life-limiting. Some patients, however, present with and succumb to locally destructive disease. A molecular understanding of these distinct disease manifestations can critically inform patient management. Using genetically engineered mouse models, we show that heterozygous mutation of Dpc4/Smad4 attenuates the metastatic potential of KrasG12D/+;Trp53R172H/+ pancreatic ductal adenocarcinomas while increasing their proliferation. Subsequent loss of heterozygosity of Dpc4 restores metastatic competency while further unleashing proliferation, creating a highly lethal combination. Expression levels of Runx3 respond to and combine with Dpc4 status to coordinately regulate the balance between cancer cell division and dissemination. Runx3 serves as both a tumor suppressor and promoter in slowing proliferation while orchestrating a metastatic program to stimulate cell migration, invasion and secretion of proteins that favor distant colonization. These findings suggest a model to anticipate likely disease behaviors in patients and tailor treatment strategies accordingly.

Quantitative evaluation of liver function by use of gadoxetate disodium (Gd-EOB-DTPA)-enhanced MR Imaging. Manuscript type: Original research Advance in Knowledge:The liver function corresponding to the plasma disappearance rate of indocyanine green (ICG-PDR) can be estimated quantitatively (R = 0.87) from the signal intensities and the volumes of the liver and the spleen on gadoxetate disodium-enhanced MR images. Implications for Patient Care:1. Our study results suggest that (Gd-EOB-DTPA)-enhanced MR imaging of the liver may improve the early detection and treatment of liver diseases by evaluating anatomic and functional information on the liver by one examination.2. Gadoxetate disodium-enhanced MR imaging of the liver may allow quantitative estimation of segmental liver function. Summary statement:The liver function corresponding with ICG-PDR can be estimated quantitatively from the signal intensities and the volumes of the liver and spleen on gadoxetate disodium-enhanced MR images, which may improve the estimation of segmental liver reserve. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Conclusion: The liver function correlating with ICG-PDR can be estimated quantitatively from the signal intensities and the volumes of the liver and spleen on gadoxetate disodiumenhanced MR images, which may improve the estimation of segmental liver function.

[Keywords: Cullin; Dab1; Reelin; cortical development; neuronal migration; ubiquitin] Supplemental material is available at http://www.genesdev.org.