ScienceInSpotlight

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Science in Spotlight is an internet platform listing scientific publications authored by Bayer employees to increase transparency and visibility of Bayer’s innovative research activities to the external scientific community.

The platform, focusing on Bayer’s Pharmaceuticals & Crop Science Divisions, allows keyword search and provides links to the published manuscripts.

ONCOIMMUNOLOGY
2022 , Vol. 11, No. 1. arn. 2008110. Refs: 53

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T cell-mediated elimination of cancer cells by blocking CEACAM6-CEACAM1 interaction.

Pinkert, Jessica; Boehm, Hans-Henning; Trautwein, Mark; Doecke, Wolf-Dietrich; Wessel, Florian; Ge, Yingzi; Gutierrez, Eva Maria; Carretero, Rafael; Freiberg, Christoph; Gritzan, Uwe; Luetke-Eversloh, Merlin; Golfier, Sven; Von Ahsen, Oliver; Volpin, Valentina; Sorrentino, Antonio; Rathinasamy, Anchana; Xydia, Maria; Lohmayer, Robert; Sax, Julian; Nur-Menevse, Ayse; Hussein, Abir; Stamova, Slava; Beckmann, Georg; Glueck, Julian Marius; Schoenfeld, Dorian; Weiske, Joerg; Zopf, Dieter; Offringa, Rienk; Kreft, Bertolt; Beckhove, Philipp; Willuda, Joerg (correspondence)

no abstract available

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2022 Jan 12, Vol. 144, No. 1, pp. 349-357.

47434394-a068-4d11-b413-59b5dd634100

Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β-N-Acetylglucosamine Strategy.

Shi Wei-Wei; Shi Chaowei; Wang Tong-Yue; Li Yu-Lei; Zhou Yong-Kang; Zhang Xu-Han; Bierer Donald; Zheng Ji-Shen; Liu Lei

Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. Our strategy comprises the introduction of simple O-linked beta-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. After folding, the O-GlcNAc groups can be efficiently removed using O-GlcNAcase (OGA) to afford the correctly folded proteins. Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation.

LIVER INTERNATIONAL
2022 Jan 10 Electronic Publication Date: 10 Jan 2022 Journal code: 101160857. E-

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Early prediction of decompensation (EPOD) Score - non-invasive determination of liver cirrhosis decompensation risk.

Schneider Annika R P; Schneider Carolin V; Schneider Kai Markus; Baier Vanessa; Schaper Steffen; Diedrich Christian; Coboeken Katrin; Mayer Hannah; Gu Wenyi; Trebicka Jonel; Blank Lars M; Burghaus Rolf; Lippert Joerg; Rader Daniel J; Thaiss Christoph A; Schlender Jan-Frederik; Trautwein Christian; Kuepfer Lars

BACKGROUND & AIMS: Decompensation is a hallmark of disease progression in cirrhotic patients. Early detection of a phase transition from compensated cirrhosis to decompensation would enable targeted therapeutic interventions potentially extending life expectancy. This study aims to (1) identify predictors of decompensation in a large, multicentric cohort of patients with compensated cirrhosis, (2) to build a reliable prognostic score for decompensation, and (3) to evaluate the score in independent cohorts. METHODS: Decompensation was identified in electronic health records data from 6049 cirrhosis patients in the IBM Explorys database training cohort by diagnostic codes for variceal bleeding, encephalopathy, ascites, hepato-renal syndrome and/or jaundice. We identified predictors of clinical decompensation and developed a prognostic score using Cox regression analysis. The score was evaluated using the IBM Explorys database validation cohort (N = 17662), the Penn Medicine BioBank (N=1326) and the UK Biobank (N=317). RESULTS: The new Early Prediction Of Decompensation (EPOD) score uses platelet count, albumin, and bilirubin concentration. It predicts decompensation during a 3-year follow-up in three validation cohorts with AUROCs of 0.69, 0.69 and 0.77, respectively, and outperforms the well-known MELD and Child-Pugh score in predicting decompensation. Furthermore, the EPOD score predicted the three-year probability of decompensation. CONCLUSIONS: The EPOD score provides a prediction tool for the risk of decompensation in patients with cirrhosis that outperforms well-known liver cirrhosis scores. Since EPOD is based on three blood parameters, only, it provides maximal clinical feasibility at minimal costs.

NATURE COMMUNICATIONS
2022 Jan 10, Vol. 13, No. 1, pp. 182.

d1f4e56c-c6d3-4ba2-b16b-decb4cfe831b

Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatment.

Qi Zhi; Xu Zihan; Zhang Liuzhen; Zou Yongkang; Li Jinping; Yan Wenyu; Li Cheng; Liu Ningshu; Wu Hong

Combining immune checkpoint therapy (ICT) and targeted therapy holds great promises for broad and long-lasting anti-cancer therapies. However, combining ICT with anti-PI3K inhibitors have been challenging because the multifaceted effects of PI3K on both cancer cells and immune cells within the tumor microenvironment. Here we find that intermittent but not daily dosing of a PI3Kalpha/beta/delta inhibitor, BAY1082439, on Pten-null prostate cancer models could overcome ICT resistance and unleash CD8(+) T cell-dependent anti-tumor immunity in vivo. Mechanistically, BAY1082439 converts cancer cell-intrinsic immune-suppression to immune-stimulation by promoting IFNalpha/IFNgamma pathway activation, beta2-microglubin expression and CXCL10/CCL5 secretion. With its preferential regulatory T cell inhibition activity, BAY1082439 promotes clonal expansion of tumor-associated CD8(+) T cells, most likely via tertiary lymphoid structures. Once primed, tumors remain T cell-inflamed, become responsive to anti-PD-1 therapy and have durable therapeutic effect. Our data suggest that intermittent PI3K inhibition can alleviate Pten-null cancer cell-intrinsic immunosuppressive activity and turn "cold" tumors into T cell-inflamed ones, paving the way for successful ICT.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
2022 Jan 10 Electronic Publication Date: 10 Jan 2022 Journal code: 7503323. E-

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Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study.

Kubitza Dagmar; Heckmann Michael; Distler Jana; Koechel Annemone; Schwers Stephan; Kanefendt Friederike

AIM: To evaluate BAY 2433334, an oral activated factor XI (FXIa) inhibitor, in volunteers. METHODS: Phase 1 study of healthy men at a German centre. Part A: randomized, single-blind, multiple dose-escalation study of BAY 2433334 (25/50/100 mg once daily [OD]) versus placebo. Part B: similar design to Part A; evaluated BAY 2433334 25 mg twice daily. Part C: non-randomized, open-label study; evaluated potential interactions between BAY 2433334 (25/75 mg OD) and midazolam (7.5 mg), a CYP3A4 index substrate. Primary variables: treatment-emergent adverse events (TEAEs; Parts A and B); AUC and Cmax of midazolam and alpha-hydroxymidazolam (Part C). STUDY PERIOD: 18 days plus follow-up visit. RESULTS: Parts A and B: 36 participants randomized to BAY 2433334; 12 to placebo. Part C: 48 participants assigned to BAY 2433334 plus midazolam. BAY 2433334 was well tolerated in all study parts. AUC and Cmax of BAY 2433334 in plasma appeared dose proportional over 25-100 mg OD, with low-to-moderate variability in pharmacokinetic parameters. Multiple dosing caused minor-to-moderate accumulation and a mean terminal half-life (15.8-17.8 hours) supporting once-daily dosing. Dose-dependent FXIa activity inhibition and activated partial thromboplastin time prolongation were observed. BAY 2433334 appeared to have a minor effect on area under the plasma concentration-time curve for midazolam (ratio [90% CI]: 1.1736 [1.0963-1.2564]) and alpha-hydroxymidazolam (0.9864 [0.9169-1.0612]) only for BAY 2433334 75 mg OD on day 10. CONCLUSION: Multiple dosing of BAY 2433334 in healthy volunteers was well tolerated, with a predictable pharmacokinetic/pharmacodynamic profile and no clinically relevant CYP3A4 induction or inhibition.

FUTURE ONCOLOGY
2022 Jan 13 Electronic Publication Date: 13 Jan 2022 Journal code: 101256629. E-

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Outcomes of sorafenib treatment of advanced renal cell carcinoma according to International Metastatic Renal Cell Carcinoma Data Consortium risk criteria: analysis of Japanese real-world data from postmarketing all-patient surveillance of sorafenib.

Inamoto Teruo; Azuma Haruhito; Adachi Masatoshi; Okayama Yutaka; Sunaya Toshiyuki; Oya Mototsugu

Aim: To assess sorafenib survival outcomes in renal cell carcinoma patients using standard International Metastatic Renal Cell Carcinoma Data Consortium (IMDC) risk criteria. Patients & methods: The authors restratified a real-world cohort of 3255 advanced renal cell carcinoma patients, obtained from Japanese sorafenib postmarketing surveillance, to assess survival outcomes using IMDC criteria; intermediate risk was subdivided into Int-1 and Int-2 (one and two risk factors, respectively). Results: Overall, 2225 (68%) IMDC-evaluable patients were reclassified as favorable (17%), intermediate (62%) and poor (21%) risk, with median progression-free survival of 10.4, 8.1 and 3.4 months, respectively. Int-1 (36%) and Int-2 (26%) subgroups had median progression-free survival of 10.1 and 6.0 months, respectively. Sorafenib had acceptable safety/tolerability. Conclusion: Sorafenib effectiveness was promising for IMDC intermediate risk, particularly Int-1, warranting further investigation.

Toxicology Letters
September 2021 , Vol. 350, Supp. Supplement, pp. S88. ISSN: 0378-4274; E-ISSN: 1879-3169

2cee5fd6-4ae5-40f9-af14-d615ba91f7ae

P04-01 In vitroskin sensitization test methods: applicability to plant protection products.

Grivel, A.; Pecoraro-Mercier, C.; Tinwell, H.

no abstract available

Toxicology Letters
September 2021 , Vol. 350, Supp. Supplement, pp. S215. ISSN: 0378-4274; E-ISSN: 1879-3169

69488ca0-dcb7-49b5-9221-457fc353deee

P23-04 Rethinking carcinogenicity assessment for agrochemicals.

Hilton, G.M.; Akerman, G.; Baldassari, J.; Battalora, M.; Buesen, R.; Clippinger, A.; Lowit, A.; Melching-Kollmuss, S.; Kormos, T.; Papineni, S.; Peffer, R.; Riffle, B. Williamson; Ryan, N.; da Rocha, M. Sanches; Visconti, N.; Wolf, D.

no abstract available

Toxicology Letters
September 2021 , Vol. 350, Supp. Supplement, pp. S144. ISSN: 0378-4274; E-ISSN: 1879-3169

087b8e88-9050-4bdb-82b0-0f6a92a6c8ba

P11-08 Transcriptomic and morphological study of the influence of all-trans retinoic acid's duration exposure on the zebrafish developmental mechanisms..

Samrani, L.M.-E.M.; Pennings, J.; Zwart, E.; Hallmark, N.; Bars, R.; Pallardy, M.; Tinwell, H.; Piersma, A.

no abstract available

Toxicology Letters
September 2021 , Vol. 350, Supp. Supplement, pp. S45. ISSN: 0378-4274; E-ISSN: 1879-3169

35400cb6-6724-405f-b789-6f260b9df9a1

S23-02 A microfluidic two-organ chip to investigate species specific differences of thyroid-liver crosstalk in human and rats.

Karwelat, D.; Kuhnlenz, J.; Raschke, M.; Bauer, S.; Tinwell, H.; Bars, R.; Marx, U.; Steger-Hartmann, T.

no abstract available

Toxicology Letters
September 2021 , Vol. 350, Supp. Supplement, pp. S116-S117. ISSN: 0378-4274; E-ISSN: 1879-3169

d04b702f-1602-491b-9d90-d06b841749bb

P06-08 A microfluidic thyroid-liver platform to evaluate species-specific dysregulations of the thyroid hormone axis.

Kuhnlenz, J.; Karwelat, D.; Steger-Hartmann, T.; Bauer, S.; Raschke, M.; Tinwell, H.; Bars, R.

no abstract available

Toxicology Letters
September 2021 , Vol. 350, Supp. Supplement, pp. S137-S138. ISSN: 0378-4274; E-ISSN: 1879-3169

8002f1f6-5851-4950-8b73-9b190b9e3703

P10-04 Rodent thyroid toxicity and potential child neurodevelopmental impairment.

Hannas, B.R.; Asiimwe, A.; Botham, P.A.; Charlton, A.; Guignard, D.; Hallmark, N.; Jacobi, S.; Marty, S.; Melching-Kollmuss, S.; Sauer, U.G.; Schneider, S.; Strauss, V.; van Ravenzwaay, B.

no abstract available

PHYSIOLOGICAL AND MOLECULAR PLANT PATHOLOGY
2021 DEC 2021 , Vol. 116. ISSN: 0885-5765.

f7b3a7cf-3c8d-4ad0-9b88-320ee444ba95

Utilizing Tajima's D to identify potential microbe-associated molecular patterns in Xanthomonas euvesicatoria and X. perforans

Pasion, Julius; Hind, Sarah R.

no abstract available

Weed Technology
21 2021 JUN 2021 ISSN: 0890-037X.

0021bd5e-4d0e-4a0a-b3d1-37dca89d36d8

Strategies for increased yellow nutsedge (Cyperus esculentus) control in turfgrass with halosulfuron, sulfentrazone, and physical removal

Li, Luqi; Sousek, Matthew; Reicher, Zachary; Gaussoin, Roch

no abstract available

JOURNAL OF ANIMAL SCIENCE
2021 NOV 2021 , Vol. 99, pp. 74-74. ISSN: 0021-8812.

deb97260-049a-4784-9d65-90f4aeeff61c

Disinformation and Scientific Integrity: The Bad Stuff Is Easier to Believe

Ryan, Camille D.

no abstract available

Disclaimer:

The Science in Spotlight platform retrieves publications based on the affiliation of the author with Bayer (Pharmaceuticals, Crop Science, Engineering & Technology). This may sporadically lead to cases where

publications of authors who recently joined Bayer are referenced in Science in Spotlight although the research work was conducted at the author´s previous institution or organization.
publications that are supported or sponsored by Bayer, but that are independently developed/written and/or do not include a Bayer author may not be referenced in Science in Spotlight.

Due to copyright reasons access to the full text of the publications depends on individual or journal access rights. Currently, Science in Spotlight references publications dating back to 2016.

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