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.

Pure and Applied Chemistry
Pure and Applied Chemistry (2021) , Volume 93, Number 2, pp. 253-272

59ce2b8e-afb1-4fce-a948-19e20f456bf6

Good reporting practice for thermophysical and thermochemical property measurements (IUPAC Technical Report)

Abildskov Jens(1); Kontogeorgis Georgios M.(1,2); Soto Ana(2); Anderko Andrzej(3); Baudouin Olivier(4); Chernyak Yury(5); de Hemptinne Jean-Charles(6); Bazyleva Ala(7); Diky Vladimir(7); Dohrn Ralf(8); Elliott J. Richard(9); Jacquemin Johan(10,11); Jaubert Jean-Noel(12); Joback Kevin G.(13); Kattner Ursula R.(14); Loria Herbert(15); Mathias Paul M.(16); O'Connell John P.(17); Schroeer Wolffram(18); Smith G. Jeffrey(19); Wang Shu(20); Weir Ronald D.(21) Correspondence(s): Bazyleva Ala(7)

no abstract available

CHEMICAL ENGINEERING & TECHNOLOGY
2021, Vol. 117, No. 2, pp. 25-29.

3ae30026-c816-42fb-b340-be96d104099d

Ensure Safe Pump Operation

Sharma, Deepak

no abstract available

CHEMICAL ENGINEERING & TECHNOLOGY
2021,

a239bbd0-fda8-494b-889f-8fea6d5ce379

Integrated Reactor-Combustor Recycling System for Safe Operation by Catalytic Removal of Excess O-2

Lu, Mengke; Zeng, Tao; Zhou, Xinggui; Westermann, Thomas; Mleczko, Leslaw

no abstract available

IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2021, Vol. 68, No. 3, pp. 1093-1103. arn. 9119806. Refs: 26

f8908186-257a-43b6-86a3-b854e241ead8

Proactive Air Management in CT Power Injections: A Comprehensive Approach to Reducing Air Embolization.

McDermott, Michael C.; Barone, William R.; Kemper, Corey A. (correspondence)

OBJECTIVE: Venous air embolism as a complication of contrast media administration from power injection systems in CT is found to occur in 7%-55% of patients, impacting patient safety, diagnostic image quality, workflow efficiency, and patient and radiographer satisfaction. This study reviews the challenges associated with reactive air management approaches employed on contemporary systems, proposes a novel air management approach using proactive methods, and compares the impact of reactive and proactive approaches on injected air volumes under simulated clinical use. METHODS: Injected air volumes from three power injection systems were measured under simulated clinical use via custom air trap fixture. Two of the systems employed reactive air management approaches, while a new system implemented the proposed proactive air management approach. RESULTS: The proactive system injected significantly less air (average of 0.005 mL +/- 0.006 mL with a maximum of 0.017 mL) when compared to two systems with reactive approaches (averages of 0.130 mL +/- 0.082 mL and 0.106 mL +/- 0.094 mL with maximums of 0.259 mL and 0.311 mL, respectively) (p < 0.05). CT images were taken of static and dynamic 0.1 mL air bubbles inside of a vascular phantom, both of which were clearly visible. Additionally, the dynamic bubble was shown to introduce image artifacts similar to those observed clinically. CONCLUSION: Comparison of the injected air volumes show that a system with a proactive air management approach injected significantly less air compared to tested systems employing reactive approaches. SIGNIFICANCE: The results indicate that the use of a proactive approach could significantly reduce the prevalence of observable, and potentially artifact-inducing, venous air embolism in contrast-enhanced CT procedures.

INTERNATIONAL JOURNAL OF TOXICOLOGY
2021 Refs: 45

81abe523-b00f-4fa7-a3da-2394c2ef54e1

Nonclinical Development of Biologics: Integrating Safety, Pharmacokinetics, and Pharmacodynamics to Create Smarter and More Flexible Nonclinical Safety Programs Optimizing Animal Use.

Hey, Adam (correspondence); Baumann, Andreas; Kronenberg, Sven; Blaich, Guenter; Mohl, Silke; Fagg, Rajni; Ulrich, Peter; Rattel, Benno; Richter, Wolfgang F.; Kiessling, Andrea; Weir, Lucinda

Safety assessment of biological drugs has its challenges due to the multiple new different modalities, for example, antibody-drug conjugates, bispecifics, nanobodies, fusion proteins and advanced therapy medicinal products (ATMPs), their different pharmacokinetic and pharmacodynamic properties, and their ability to trigger immunogenicity and toxicity. In the public and in the pharmaceutical industry, there is a strong and general desire to reduce the number of animals used in research and development of drugs and in particular reducing the use of nonhuman primates. Important discussions and activities are ongoing investigating the smarter designs of early research and dose range finding studies, reuse of animals, and replacing animal experiments with in vitro studies. Other important challenges include absence of a relevant species and design of studies and developing genetically modified animals for special investigative toxicology studies. Then, the learnings and challenges from the development of the first ATMPs are available providing valuable insights in the development path for these new potentially transformative treatments. Finally, development of strategies for assessment of immunogenicity and prediction of translation of immunogenicity and associated findings to the clinic. On this, the eighth meeting for the European BioSafe members, these challenges served as the basis for the presentations and discussions during the meeting. This article serves as the workshop report reviewing the presentations and discussions at the meeting.

BLOOD ADVANCES
2021, Vol. 5, No. 4, pp. 1081-1091. Refs: 44

c868b935-4b54-4008-bde3-19b3141c56bc

Bleeding and related mortality with NOACs and VKAs in newly diagnosed atrial fibrillation: Results from the GARFIELD-AF registry.

Bassand, Jean-Pierre (correspondence); Virdone, Saverio; Badoz, Marc; Verheugt, Freek W. A.; Camm, A. John; Cools, Frank; Fox, Keith A. A.; Goldhaber, Samuel Z.; Goto, Shinya; Haas, Sylvia; Hacke, Werner; Kayani, Gloria; Misselwitz, Frank; Pieper, Karen S.; Turpie, Alexander G. G.; Eickels, Martin Van; Kakkar, Ajay K.

In atrial fibrillation (AF), lower risks of death and bleeding with non-vitamin-K oral anticoagulants (NOACs) were reported in meta-analyses of controlled trials, but whether these findings hold true in real-world practice remains uncertain. Risks of bleeding and death were assessed in 52 032 patients with newly diagnosed AF enrolled in GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation), a worldwide prospective registry. Baseline treatment was vitamin K antagonists (VKAs) with or without antiplatelet (AP) agents (VKA +/- AP) (20 151; 39.3%), NOACs +/- AP agents (14 103; 27.5%), AP agents only (10 748; 21.0%), or no antithrombotics (6219; 12.1%). One-year follow-up event rates (95% confidence interval [CI]) of minor, clinically relevant nonmajor (CRNM), and major bleedings were 2.29 (2.16-2.43), 1.10 (1.01-1.20), and 1.31 (1.21-1.41) per 100 patient-years, respectively. Bleeding risk was lower with NOACs than VKAs for any bleeding (hazard ratio (HR) [95% CI]), 0.85 [0.73-0.98]) or major bleeding (0.79 [0.60-1.04]). Compared with no bleeding, the risk of death was higher with minor bleeding (adjusted HR [aHR], 1.53 [1.07-2.19]), CRNM bleeding (aHR, 2.59 [1.80-3.73]), and major bleeding (aHR, 8.24 [6.76-10.04]). The all-cause mortality rate was lower with NOACs than with VKAs (aHR, 0.73 [0.62-0.85]). Forty-five percent (114) of all deaths occurred within 30 days, and 40% of these were from intracranial/intraspinal hemorrhage (ICH). The rates of any bleeding and all-cause death were lower with NOACs than with VKAs. Major bleeding was associated with the highest risk of death. CRNM bleeding and minor bleeding were associated with a higher risk of death compared to no bleeding. Death within 30 days after a major bleed was most frequently related to ICH. This trial was registered at www.clinicaltrials.gov as #NCT01090362.

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
2021

303d7e42-60a0-4da2-af2e-3135bff204a4

Editorial special issue on "Quantum Mechanics in Industry

Goeller, Andreas H.

no abstract available

ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
2021

df592009-ff18-458b-bf74-b8a192572062

Guidelines for FAIR sharing of preclinical safety and off-target pharmacology data.

Briggs Katharine; Bosc Nicolas; Camara Tima; Diaz Carlos; Drew Phil; Drewe William C; Kors Jan; Van Mulligen Erik; Pastor Manuel; Pognan Francois; Quintana Jordi Ramon; Sarntivijai Sirarat; Steger-Hartmann Thomas

Pre-competitive data sharing can offer the pharmaceutical industry significant benefits in terms of reducing the time and costs involved in getting a new drug to market through more informed testing strategies and knowledge gained by pooling data. If sufficient data is shared and can be co-analyzed, then it can also offer the potential for reduced animal usage and improvements in the in silico prediction of toxicological effects. Data sharing benefits can be further enhanced by applying the FAIR Guiding Principles, reducing time spent curating, transforming and aggregating datasets and allowing more time for data mining and analysis. We hope to facilitate data sharing by other organizations and initiatives by describing lessons learned as part of the Enhancing TRANslational SAFEty Assessment through Integrative Knowledge Management (eTRANSAFE) project, an Innovative Medicines Initiative (IMI) partnership which aims to integrate publicly available data sources with proprietary preclinical and clinical data donated by pharmaceutical organizations. Methods to foster trust and overcome non-technical barriers to data sharing such as legal and IPR (intellectual property rights) are described, including the security requirements that pharmaceutical organizations generally expect to be met. We share the consensus achieved among pharmaceutical partners on decision criteria to be included in internal clearance procedures used to decide if data can be shared. We also report on the consensus achieved on specific data fields to be excluded from sharing for sensitive preclinical safety and pharmacology data that could otherwise not be shared.

WELLCOME OPEN RESEARCH
2021, Vol. 6, pp. 16.

079c7563-11b3-4d27-837b-1757ff1e0e15

Mendelian randomization for studying the effects of perturbing drug targets.

Gill Dipender; Georgakis Marios K; Walker Venexia M; Schmidt A Floriaan; Gkatzionis Apostolos; Freitag Daniel F; Finan Chris; Hingorani Aroon D; Howson Joanna M M; Burgess Stephen; Swerdlow Daniel I; Davey Smith George; Holmes Michael V; Dichgans Martin; Scott Robert A; Zheng Jie; Psaty Bruce M; Davies Neil M

Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse effects. Large databases of summary level genetic association data are increasingly available and can be leveraged to identify and validate variants that serve as proxies for drug target perturbation. As with all empirical research, Mendelian randomization has limitations including genetic confounding, its consideration of lifelong effects, and issues related to heterogeneity across different tissues and populations. When appropriately applied, Mendelian randomization provides a useful empirical framework for using population level data to improve the success rates of the drug development pipeline.

JOURNAL OF MEDICAL IMAGING
2021, Vol. 8, No.

8c11b3df-86da-4f60-9304-5c2c1224c226

Automated workflow for volumetric assessment of signal intensity ratio on T1-weighted MR images after multiple gadolinium administrations.

Liu Chia-Ying; Ramos Marc; Moreno-Dominguez David; Prckovska Vesna; Rodrigues Paulo; Blank Markus; Moser Franklin G; Agris Jacob

Purpose: Repeated injections of linear gadolinium-based contrast agent (GBCA) have shown correlations with increased signal intensities (SI) on unenhanced T1-weighted (T1w) images. Assessment is usually performed manually on a single slice and the SI as an average of a freehand region-of-interest is reported. We aim to develop a fully automated software that segments and computes SI ratio of dentate nucleus (DN) to pons (DN/P) and globus pallidus (GP) to thalamus (GP/T) for the assessment of gadolinium presence in the brain after a serial GBCA administrations. Approach: All patients ( N = 113 ) underwent at least eight GBCA enhanced scans. The modal SI in the DN, GP, pons, and thalamus were measured volumetrically on unenhanced T1w images and corrected based on the reference protocol (measurement 1) and compared to the SI-uncorrected-modal-volume (measurement 2), SI-corrected-mean-volume (measurement 3), as well as SI-corrected-modal-single slice (measurement 4) approaches. Results: Automatic processing worked on all 2119 studies (1150 at 1.5 T and 969 at 3 T). DN/P were 1.085 +/- 0.048 (1.5 T) and 0.979 +/- 0.061 (3 T). GP/T were 1.084 +/- 0.039 (1.5 T) and 1.069 +/- 0.042 (3 T). Modal DN/P ratios from volumetric assessment at 1.5 T failed to show a statistical difference with or without SI corrections ( p = 0.71 ). All other t -tests demonstrated significant differences (measurement 2, 3, 4 compared to 1, p < 0.001 ). Conclusion: The fully automatic method is an effective powerful tool to streamline the analysis of SI ratios in the deep brain tissues. Divergent SI ratios using different approaches reinforces the need to standardize the measurement for the research in this field.

INVESTIGATIVE RADIOLOGY
2021

a12c0374-b84b-45e4-967b-155607d20ff3

Photon-Counting Multienergy Computed Tomography With Spectrally Optimized Contrast Media for Plaque Removal and Stenosis Assessment.

Sartoretti Thomas; Eberhard Matthias; Nowak Tristan; Gutjahr Ralf; Jost Gregor; Pietsch Hubertus; Schmidt Bernhard; Flohr Thomas; Alkadhi Hatem; Euler Andre

PURPOSE: The aim of this study was to systematically evaluate the potential to combine investigational contrast media with spectrally optimized energy-thresholding of photon-counting detector computed tomography (PCCT) for subtraction of calcified plaques in a coronary artery stenosis phantom. METHODS: A small vessel phantom containing 3 fillable tubes (diameter, 3 mm each) with calcified plaques was placed into an anthropomorphic chest phantom. The plaques had incremental thicknesses ranging from 0.3 to 2.7 mm, simulating vessel stenoses ranging from 10% to 90% of the lumen diameter. The phantom was filled with 5 different investigational contrast media (iodine, bismuth, hafnium, holmium, and tungsten) at equal mass concentrations (15 mg/mL) and was imaged on a prototype PCCT at 140 kVp using optimized, contrast media-dependent energy thresholds. Contrast maps (CMs) were reconstructed for each contrast medium by applying a linear 2-material decomposition algorithm. Image noise magnitude and noise texture of CM were compared among the contrast media using the noise power spectrum. Two blinded readers independently rated the vessel lumen visualization on short-axis and the overall subjective image quality on long-axis CM relative to iodine as the reference standard. Four readers determined the highest degree of stenosis that could be assessed with high diagnostic confidence on long-axis CM. RESULTS: Average image noise on CM was lower for tungsten (49 HU) and hafnium (62 HU) and higher for bismuth (81 HU) and holmium (165 HU) compared with iodine (78 HU). Noise texture of CM was similar among the contrast media. Interreader agreement for vessel lumen visualization on short-axis CM ranged from moderate to excellent (k = 0.567-0.814). Compared with iodine, lumen visualization of each reader was improved using tungsten (P < 0.001 for both readers), similar to improved using hafnium (P = 0.008, P = 0.29), similar using bismuth (P = 0.38, P = 0.69), and decreased using holmium (both, P < 0.001). Overall subjective image quality was similar for holmium and superior for tungsten, hafnium, and bismuth as compared with iodine. Higher-degree stenoses were evaluable with high confidence using tungsten (mean, 70%; interquartile range, 70%-70%), bismuth (70%; 60%-70%), and hafnium (75%; 70%-80%) compared with iodine (50%; 50%-60%) and holmium (50%; 50%-60%). CONCLUSIONS: Spectral optimization in PCCT combined with investigational contrast media can improve calcium subtraction and stenosis assessment in small vessels. Contrast maps of tungsten and, to a lesser extent, hafnium as contrast media yielded superior image noise properties and improved vessel lumen visualization, along with a higher subjective image quality compared with the reference standard iodine.

PHARMACEUTICS
2021, Vol. 13, No. 2.

77155ca1-2ae9-4846-9618-83f0432b259a

The Influence of Equipment Design and Process Parameters on Granule Breakage in a Semi-Continuous Fluid Bed Dryer after Continuous Twin-Screw Wet Granulation.

Ryckaert Alexander; Ghijs Michael; Portier Christoph; Djuric Dejan; Funke Adrian; Vervaet Chris; De Beer Thomas

The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying process is, however, still lacking. A first major goal was to investigate the breakage and attrition phenomena during transport of wet and dry granules, the filling phase, and drying phase on a ConsiGma-25 system (C25). Pneumatic transport of the wet granules after TSG towards the dryer induced extensive breakage, whereas the turbulent filling and drying phase of the drying cells caused rather moderate breakage and attrition. Subsequently, the dry transfer line was responsible for additional extensive breakage and attrition. The second major goal was to compare the influence of drying air temperature and drying time on granule size and moisture content for granules processed with a commercial-scale ConsiGma-25 system and with the R&D-scale ConsiGma-1 (C1) system. Generally, the granule quality obtained after drying with C1 was not predictive for the C25, making it challenging during process development with the C1 to obtain representative granules for the C25.

Agronomy Journal
Agronomy Journal (1 Jan 2021) Volume 113, Number 1, pp. 451-463, 43

30b5367d-c5f1-4001-8460-34d260dd46d6

Biomass and nutrient accumulation and partitioning of fall-winter safflower in a double-cropping system of southeastern Brazil

Guidorizzi, Fernando V. C.; Soratto, Rogerio P.; Silva, Mariana M.; Pinto, Lohan O. G.; Fernandes, Adalton M.; Souza, Emerson F. C.

no abstract available

Applied and Environmental Microbiology
Applied and Environmental Microbiology (1 Mar 2021) Volume 87, Number 5, pp. 1-17

a42d8888-6315-4ede-be07-12d551e2d47f

Cry75Aa (Mpp75Aa) Insecticidal Proteins for Controlling the Western Corn Rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), Isolated from the Insect- Pathogenic Bacterium Brevibacillus laterosporus

Bowen, David; Yin, Yong; Flasinski, Stanislaw; Chay, Catherine; Bean, Gregory; Milligan, Jason; Moar, William; Pan, Aihong; Werner, Brent; Buckman, Karrie; Howe, Arlene; Ciche, Todd; Turner, Keith; Pleau, Michael; Zhang, Jun; Kouadio, Jean Louis; Price, Paula; Roberts, James; Hibbard, Bruce E.

no abstract available

Field Crops Research
Field Crops Research (15 May 2021) Volume 265

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Impacts of vegetative and reproductive plasticity associated with tillering in maize crops in low-yielding environments: A physiological framework

Rotili, Diego Hernan; Abeledo, L. Gabriela; Micheloud, Jose Roberto; Maddonni, Gustavo Angel; Sadras, Victor O.; Ferreyra, Juan Matias; Ermacora, Matias; Duarte, Gustavo; Giron, Paula

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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