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2. Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

Author

Koenecke, Allison, Powell, Michael, Xiong, Ruoxuan, Shen, Zhu, Fischer, Nicole, Huq, Sakibul, Khalafallah, Adham M., Trevisan, Marco, Sparen, Pär, Carrero, Juan J, Nishimura, Akihiko, Caffo, Brian, Stuart, Elizabeth A., Bai, Renyuan, Staedtke, Verena, Thomas, David L., Papadopoulos, Nickolas, Kinzler, Kenneth W., Vogelstein, Bert, Zhou, Shibin, Bettegowda, Chetan, Konig, Maximilian F., Mensh, Brett, Vogelstein, Joshua T., and Athey, Susan

Subjects
Quantitative Biology - Tissues and Organs, Quantitative Biology - Quantitative Methods
Abstract

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($\alpha_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $\alpha_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $\alpha_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19., Comment: 31 pages, 10 figures

Published
2020
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3. Figure S1 from Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel

Author

Faramand, Rawan, primary, Jain, Michael, primary, Staedtke, Verena, primary, Kotani, Hiroshi, primary, Bai, Renyuan, primary, Reid, Kayla, primary, Lee, Sae Bom, primary, Spitler, Kristen, primary, Wang, Xuefeng, primary, Cao, Biwei, primary, Pinilla, Javier, primary, Lazaryan, Aleksander, primary, Khimani, Farhad, primary, Shah, Bijal, primary, Chavez, Julio C., primary, Nishihori, Taiga, primary, Mishra, Asmita, primary, Mullinax, John, primary, Gonzalez, Ricardo, primary, Hussaini, Mohammad, primary, Dam, Marian, primary, Brandjes, Brigett D., primary, Bachmeier, Christina A., primary, Anasetti, Claudio, primary, Locke, Frederick L., primary, and Davila, Marco L., primary

Published
2023
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4. Tables S1-S4 from Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel

Author

Faramand, Rawan, primary, Jain, Michael, primary, Staedtke, Verena, primary, Kotani, Hiroshi, primary, Bai, Renyuan, primary, Reid, Kayla, primary, Lee, Sae Bom, primary, Spitler, Kristen, primary, Wang, Xuefeng, primary, Cao, Biwei, primary, Pinilla, Javier, primary, Lazaryan, Aleksander, primary, Khimani, Farhad, primary, Shah, Bijal, primary, Chavez, Julio C., primary, Nishihori, Taiga, primary, Mishra, Asmita, primary, Mullinax, John, primary, Gonzalez, Ricardo, primary, Hussaini, Mohammad, primary, Dam, Marian, primary, Brandjes, Brigett D., primary, Bachmeier, Christina A., primary, Anasetti, Claudio, primary, Locke, Frederick L., primary, and Davila, Marco L., primary

Published
2023
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5. Dynamic contrast‐enhanced CEST MRI using a low molecular weight dextran

Author

Han, Zheng, primary, Chen, Chuheng, additional, Xu, Xiang, additional, Bai, Renyuan, additional, Staedtke, Verena, additional, Huang, Jianpan, additional, Chan, Kannie W. Y., additional, Xu, Jiadi, additional, Kamson, David O., additional, Wen, Zhibo, additional, Knutsson, Linda, additional, Zijl, Peter C. M., additional, and Liu, Guanshu, additional

Published
2021
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6. Disulfiram and copper combination therapy targets NPL4, cancer stem cells and extends survival in a medulloblastoma model

Author

Serra, Riccardo, primary, Zhao, Tianna, additional, Huq, Sakibul, additional, Gorelick, Noah Leviton, additional, Casaos, Joshua, additional, Cecia, Arba, additional, Mangraviti, Antonella, additional, Eberhart, Charles, additional, Bai, Renyuan, additional, Olivi, Alessandro, additional, Brem, Henry, additional, Jackson, Eric M., additional, and Tyler, Betty, additional

Published
2021
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7. Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

Author

Koenecke, Allison, primary, Powell, Michael, primary, Xiong, Ruoxuan, additional, Shen, Zhu, additional, Fischer, Nicole, additional, Huq, Sakibul, additional, Khalafallah, Adham M, additional, Trevisan, Marco, additional, Sparen, Pär, additional, Carrero, Juan J, additional, Nishimura, Akihiko, additional, Caffo, Brian, additional, Stuart, Elizabeth A, additional, Bai, Renyuan, additional, Staedtke, Verena, additional, Thomas, David L, additional, Papadopoulos, Nickolas, additional, Kinzler, Ken W, additional, Vogelstein, Bert, additional, Zhou, Shibin, additional, Bettegowda, Chetan, additional, Konig, Maximilian F, additional, Mensh, Brett D, additional, Vogelstein, Joshua T, additional, and Athey, Susan, additional

Published
2021
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8. Author response: Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

Author

Koenecke, Allison, primary, Powell, Michael, additional, Xiong, Ruoxuan, additional, Shen, Zhu, additional, Fischer, Nicole, additional, Huq, Sakibul, additional, Khalafallah, Adham M, additional, Trevisan, Marco, additional, Sparen, Pär, additional, Carrero, Juan J, additional, Nishimura, Akihiko, additional, Caffo, Brian, additional, Stuart, Elizabeth A, additional, Bai, Renyuan, additional, Staedtke, Verena, additional, Thomas, David L, additional, Papadopoulos, Nickolas, additional, Kinzler, Ken W, additional, Vogelstein, Bert, additional, Zhou, Shibin, additional, Bettegowda, Chetan, additional, Konig, Maximilian F, additional, Mensh, Brett D, additional, Vogelstein, Joshua T, additional, and Athey, Susan, additional

Published
2021
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10. The origins of 168, W23, and other Bacillus subtilis legacy strains

Author

Zeigler, Daniel R., Pragai, Zoltan, Rodriguez, Sabrina, Chevreux, Bastien, Muffler, Andrea, Albert, Thomas, Bai, Renyuan, Wyss, Markus, and Perkins, John B.

Subjects
Bacillus subtilis -- Genetic aspects, Bacillus subtilis -- Research, Nucleotide sequence -- Research, Biological sciences
Abstract

Bacillus subtilis is both a model organism for basic research and an industrial workhorse, yet there are major gaps in our understanding of the genomic heritage and provenance of many widely used strains. We analyzed 17 legacy strains dating to the early years of B. subtilis genetics. For three--NCIB [3610.sup.T], PY79, and SMY--we performed comparative genome sequencing. For the remainder, we used conventional sequencing to sample genomic regions expected to show sequence heterogeneity. Sequence comparisons showed that 168, its siblings (122, 160, and 166), and the type strains NCIB 3610 and ATCC 6051 are highly similar and are likely descendants of the original Marburg strain, although the 168 lineage shows genetic evidence of early domestication. Strains 23, W23, and W23SR are identical in sequence to each other but only 94.6% identical to the Marburg group in the sequenced regions. Strain 23, the probable W23 parent, likely arose from a contaminant in the mutagenesis experiments that produced 168. The remaining strains are all genomic hybrids, showing one or more 'W23 islands' in a 168 genomic backbone. Each traces its origin to transformations of 168 derivatives with DNA from 23 or W23. The common prototrophic lab strain PY79 possesses substantial W23 islands at its trp and sac loci, along with large deletions that have reduced its genome 4.3%. SMY, reputed to be the parent of 168, is actually a 168-W23 hybrid that likely shares a recent ancestor with PY79. These data provide greater insight into the genomic history of these B. subtiHs legacy strains.

Published
2008

12. Disulfiram and Copper Combination Therapy Targets NPL4, Cancer Stem Cells and Prolongs Survival in Group 3 Medulloblastoma

Author

Serra, Riccardo, primary, Zhao, Tianna, additional, Huq, Sakibul, additional, Gorelick, Noah L, additional, Casaos, Joshua, additional, Cecia, Arba, additional, Mangraviti, Antonella, additional, Bai, Renyuan, additional, Olivi, Alessandro, additional, Brem, Henry, additional, Jackson, Eric M, additional, and Tyler, Betty, additional

Published
2020
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14. Dynamic contrast‐enhanced CEST MRI using a low molecular weight dextran.

Author

Han, Zheng, Chen, Chuheng, Xu, Xiang, Bai, Renyuan, Staedtke, Verena, Huang, Jianpan, Chan, Kannie W. Y., Xu, Jiadi, Kamson, David O., Wen, Zhibo, Knutsson, Linda, van Zijl, Peter C. M., and Liu, Guanshu

Subjects
CONTRAST-enhanced magnetic resonance imaging, MOLECULAR weights, DEXTRAN, MAGNETIC resonance microscopy, MAGNETIZATION transfer
Abstract

Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady‐state full Z‐spectral images and single offset (1.2 ppm) dynamic dextran‐enhanced (DDE) images were acquired before and after the intravenous injection of Dex1 (2 g/kg). The steady‐state Z‐spectral analysis showed a significantly higher CEST contrast enhancement in the tumor than in contralateral brain (∆MTRasym1.2 ppm = 0.010 ± 0.006 versus 0.002 ± 0.008, P = 0.0069) at 20 min after the injection of Dex1. Pharmacokinetic analyses of DDE were performed using the area under the curve (AUC) in the first 10 min after Dex1 injection, revealing a significantly higher uptake of Dex1 in the tumor than in brain tissue for tumor‐bearing mice (AUC[0‐10 min] = 21.9 ± 4.2 versus 5.3 ± 6.4%·min, P = 0.0294). In contrast, no Dex1 uptake was foundling in the brains of non‐tumor‐bearing mice (AUC[0‐10 min] = −1.59 ± 2.43%·min). Importantly, the CEST MRI findings were consistent with the measurements obtained using DCE MRI and fluorescence microscopy, demonstrating the potential of Dex1 as a highly translatable CEST MRI contrast agent for assessing tumor hemodynamics. [ABSTRACT FROM AUTHOR]

Published
2022
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15. Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel

Author

Faramand, Rawan, primary, Jain, Michael, additional, Staedtke, Verena, additional, Kotani, Hiroshi, additional, Bai, Renyuan, additional, Reid, Kayla, additional, Lee, Sae Bom, additional, Spitler, Kristen, additional, Wang, Xuefeng, additional, Cao, Biwei, additional, Pinilla, Javier, additional, Lazaryan, Aleksander, additional, Khimani, Farhad, additional, Shah, Bijal, additional, Chavez, Julio C., additional, Nishihori, Taiga, additional, Mishra, Asmita, additional, Mullinax, John, additional, Gonzalez, Ricardo, additional, Hussaini, Mohammad, additional, Dam, Marian, additional, Brandjes, Brigett D., additional, Bachmeier, Christina A., additional, Anasetti, Claudio, additional, Locke, Frederick L., additional, and Davila, Marco L., additional

Published
2020
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16. The Lymphoma Tumor Microenvironment Influences Toxicity after CD19 CAR T Cell Therapy

Author

Jain, Michael D., primary, Faramand, Rawan, additional, Staedtke, Verena, additional, Bai, Renyuan, additional, Lee, Sae Bom, additional, Kotani, Hiroshi, additional, Reid, Kayla, additional, Spitler, Kristen, additional, Chavez, Julio, additional, Shah, Bijal, additional, Bachmeier, Christina A, additional, Dam, Marian, additional, Brandjes, Brigett, additional, Gonzalez, Ricardo J, additional, Mullinax, John E, additional, Wang, Xuefeng, additional, Hussaini, Mohammad, additional, Locke, Frederick L., additional, and Davila, Marco L., additional

Published
2019
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20. Non-invasive imaging of infection after treatment with tumor-homing bacteria using chemical exchange saturation transfer (CEST) MRI

Author

Liu, Guanshu, Bettegowda, Chetan, Qiao, Yuan, Staedtke, Verena, Chan, Kannie W.Y., Bai, Renyuan, Li, Yuguo, Riggins, Gregory J., Kinzler, Kenneth W., Bulte, Jeff W.M., McMahon, Michael T., Gilad, Assaf A., Vogelstein, Bert, Zhou, Shibin, and van Zijl, Peter C.M.

Subjects
Clostridium, Mice, Inbred BALB C, Reproducibility of Results, Magnetic Resonance Imaging, Sensitivity and Specificity, Article, Biological Therapy, Mice, Cell Line, Tumor, Image Interpretation, Computer-Assisted, Clostridium Infections, Animals, Humans, Female, Colorectal Neoplasms
Abstract

To develop a noninvasive MRI method for determining the germination and infection of tumor-homing bacteria in bacteriolytic cancer therapy using endogenous CEST contrast.The CEST parameters of the anaerobic gram-positive bacterium Clostridium novyi-NT (C. novyi-NT) were first characterized in vitro, then used to detect C. novyi-NT germination and infection in subcutaneous CT26 colorectal tumor-bearing mice (n = 6) after injection of 300 million bacterial spores. Lipopolysacharide (LPS) injected mice were used to exclude that the changes of CEST MRI were due to inflammation.CEST contrast was observed over a broad frequency range for bacterial suspensions in vitro, with the maximum contrast around 2.6 ppm from the water resonance. No signal could be detected for bacterial spores, demonstrating the specificity for germination. In vivo, a significant elevation of CEST contrast was identified in C. novyi-NT infected tumors as compared to those before bacterial germination and infection (P 0.05; n = 6). No significant change was observed in tumors with LPS-induced sterile inflammation (P 0.05; n = 4).Endogenous bacterial CEST contrast (bacCEST) can be used to monitor the germination and proliferation of the therapeutic bacterium C. novyi-NT without a need for exogenous cell labeling probes.

Published
2013

21. Characterization of tumor vascular permeability using natural dextrans and CEST MRI.

Author

Li, Yuguo, Qiao, Yuan, Chen, Hanwei, Bai, Renyuan, Staedtke, Verena, Han, Zheng, Xu, Jiadi, Chan, Kannie W. Y., Yadav, Nirbhay, Bulte, Jeff W. M., Zhou, Shibin, van Zijl, Peter C. M., and Liu, Guanshu

Abstract

Purpose To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability. Methods Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice ( N = 5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6 nm) and 70 kD (D70, 12 nm) dextran at a dose of 375 mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40 min after each injection using a dynamic CEST imaging scheme. Results All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9 ppm. The detectability and effects of pH and saturation conditions (B1 and Tsat) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant 'dexCEST' enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry. Conclusions As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems. Magn Reson Med 79:1001-1009, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Published
2018
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22. A Robust Approach to Enhance Tumor-selective Accumulation of Nanoparticles

Author

Qiao, Yuan, primary, Huang, Xin, additional, Nimmagadda, Sridhar, additional, Bai, Renyuan, additional, Staedtke, Verena, additional, Foss, Catherine A., additional, Cheong, Ian, additional, Holdhoff, Matthias, additional, Kato, Yoshinori, additional, Pomper, Martin G., additional, Riggins, Gregory J., additional, Kinzler, Kenneth W., additional, Diaz, Luis A., additional, Vogelstein, Bert, additional, and Zhou, Shibin, additional

Published
2011
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26. Profitability and Remuneration in the UK banking industry

Author

Bai, Renyuan and Bai, Renyuan

Abstract

This dissertation tries to examine the determinants of the profitability in the UK banking industry and the pay-performance relationship during the period of 2006-2015. The empirical findings indicate that some variables from common, bank-specific and macroeconomic categories have statistically significant influence on the bank profitability. However, when linking remuneration and bank profitability together, no significant relationship can be found. Later case study on bonuses and bank profitability show a significant relationship exists. The inclusion of diverse variables as well as additional case studies can help us to gain the new insights into what determinants the profitability of the UK banking industry and the pay-performance relationship.

27. Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection.

Author

Koenecke A, Powell M, Xiong R, Shen Z, Fischer N, Huq S, Khalafallah AM, Trevisan M, Sparen P, Carrero JJ, Nishimura A, Caffo B, Stuart EA, Bai R, Staedtke V, Thomas DL, Papadopoulos N, Kinzler KW, Vogelstein B, Zhou S, Bettegowda C, Konig MF, Mensh B, Vogelstein JT, and Athey S

Abstract

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($\alpha_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $\alpha_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $\alpha_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

Published
2021

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