Polysorbates (PS) are commonly used as stabilizers of biopharmaceuticals such as monoclonal antibodies (mAbs). However, they are prone to chemical and enzymatic degradation. The latter can be caused by residual host cell proteins (HCPs) in the drug substance.
View Article and Find Full Text PDFBackground: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies.
View Article and Find Full Text PDFMultimodal chromatography has emerged as a powerful method for the purification of therapeutic antibodies. However, process development of this separation technique remains challenging because of an intricate and molecule-specific interaction towards multimodal ligands, leading to time-consuming and costly experimental optimization. This study presents a multiscale modeling approach to predict the multimodal chromatographic behavior of therapeutic antibodies based on their sequence information.
View Article and Find Full Text PDFBackground: This study examined age-group differences in the rate, severity, and cost of injuries among construction workers to support evidence-based worker safety and health interventions in the construction industry.
Methods: Ohio workers' compensation claims for construction workers were used to estimate claim rates and costs by age group. We analyzed claims data auto-coded into five event/exposure categories: transportation incidents; slips, trips, and falls (STFs); exposure to harmful substances and environments; contact with objects and equipment (COB); overexertion and bodily reaction.
Since March 2021, Germany has been providing cost-free severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen tests, and many day-to-day activities following the lockdown have required negative test results. Yet it remains unclear how tests have been used and whether there are patterns connected to mitigation measures. We analyzed over 50,000 anonymized records from eight test centers in a typical medium-sized city, with one of them remaining open continuously from March until December 2021.
View Article and Find Full Text PDFMultimodal chromatography has emerged as a promising technique for antibody purification, owing to its capacity to selectively capture and separate target molecules. However, the optimization of chromatography parameters remains a challenge due to the intricate nature of protein-ligand interactions. To tackle this issue, efficient predictive tools are essential for the development and optimization of multimodal chromatography processes.
View Article and Find Full Text PDFAntibody-antigen interaction-at antigenic local environments called B-cell epitopes-is a prominent mechanism for neutralization of infection. Effective mimicry, and display, of B-cell epitopes is key to vaccine design. Here, a physical approach is evaluated for the discovery of epitopes which evolve slowly over closely related pathogens (conserved epitopes).
View Article and Find Full Text PDFMultimodal chromatography offers an increased selectivity compared to unimodal chromatographic methods and is often employed for challenging separation tasks in industrial downstream processing (DSP). Unfortunately, the implementation of multimodal polishing into a generic downstream platform can be hampered by non-robust platform conditions leading to a time and cost intensive process development. Mechanistic modeling can assist experimental process development but readily applicable and easy to calibrate multimodal chromatography models are lacking.
View Article and Find Full Text PDFThe development of biopharmaceutical downstream processes relies on exhaustive experimental studies. The root cause is the poorly understood relationship between the protein structure of monoclonal antibodies (mAbs) and their macroscopic process behavior. Especially the development of preparative chromatography processes is challenged by the increasing structural complexity of novel antibody formats and accelerated development timelines.
View Article and Find Full Text PDFObjective: This study employed analysis of workers' compensation (WC) claims in the landscaping services industry to identify occupational factors associated with claims from workers of different ages.
Methods: Private sector claims for 2005 to 2017 to the Ohio Bureau of Workers' Compensation (OHBWC) and their free-text descriptions were used along with data from the US Census Bureau American Community Survey to examine rates and types of WC claims by worker age.
Results: Although the claim rate for younger workers was higher than that for older workers overall (593 vs 261 per 10,000 full-time equivalent employees, P < 0.
During the third wave of the COVID-19 (coronavirus disease 2019) pandemic in Germany, free SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) point-of-care (PoC) antigen tests were offered to citizens at least once a week to prevent spreading by asymptomatic infected individuals. This study investigated user groups, timing, frequency, and test center locations in a typical medium-sized European city. We analyzed 27,369 pseudonymized datasets from eight centers over 12 weeks.
View Article and Find Full Text PDFAllergy to (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample.
View Article and Find Full Text PDFTGF-β1 is known to have a pro-inflammatory impact by inducing Th9 and Th17 cells, while it also induces anti-inflammatory Treg cells (Tregs). In the context of allergic airway inflammation (AAI) its dual role can be of critical importance in influencing the outcome of the disease. Here we demonstrate that TGF-β is a major player in AAI by driving effector T cells, while Tregs differentiate independently.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2022
Generation of sequence defined antibodies from universal libraries by phage display has been established over the past three decades as a robust method to cope with the increasing market demand in therapy, diagnostics and research. For applications requiring the bivalent antigen binding and an Fc part for detection, phage display generated single chain Fv (scFv) antibody fragments can rapidly be genetically fused to the Fc moiety of an IgG for the production in eukaryotic cells of antibodies with IgG-like properties. In contrast to conversion of scFv into IgG format, the conversion to scFv-Fc requires only a single cloning step, and provides significantly higher yields in transient cell culture production than IgG.
View Article and Find Full Text PDFIn this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil Bee and Wasp.
View Article and Find Full Text PDFDiscriminating and spp. venom allergy is of growing importance worldwide, as systemic reactions to either species' sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients.
View Article and Find Full Text PDFOverexertion is a leading cause of work-related musculoskeletal disorders (WMSDs) among construction workers. Nearly 90% of construction jobs require manual handling of materials for approximately one half of the worker's time (1). In 2015, overexertion from lifting and lowering materials caused 30% of WMSDs among construction workers; overexertion involving pushing, pulling, holding, carrying, and catching materials caused an additional 37% of WMSDs (1).
View Article and Find Full Text PDFWith the technological advances in 3D printing technology, which are associated with ever-increasing printing resolution, additive manufacturing is now increasingly being used for rapid manufacturing of complex devices including microsystems development for laboratory applications. Personalized experimental devices or entire bioreactors of high complexity can be manufactured within few hours from start to finish. This study presents a customized 3D-printed micro bubble column reactor (3D-µBCR), which can be used for the cultivation of microorganisms (e.
View Article and Find Full Text PDFBackground: Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes a subpopulation of glioma cells that becomes highly resistant by integration into tumor microtube (TM)-connected multicellular networks.
Methods: A novel functional approach to detect, isolate, and characterize glioma cell subpopulations with respect to in vivo network integration is established, combining a dye staining method with intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular profiling, and gene reporter studies.
Results: Glioblastoma cells that are part of the TM-connected tumor network show activated neurodevelopmental and glioma progression gene expression pathways.
Clinically relevant brain metastases (BMs) frequently form in cancer patients, with limited options for effective treatment. Circulating cancer cells must first permanently arrest in brain microvessels to colonize the brain, but the critical factors in this process are not well understood. Here, in vivo multiphoton laser-scanning microscopy of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor (VWF) deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice.
View Article and Find Full Text PDFAllergic reactions to stings of Hymenoptera species may be severe and are potentially fatal deviations of the immunological response observed in healthy individuals. However, venom-specific immunotherapy (VIT) is an immunomodulatory approach able to cure venom allergy in the majority of affected patients. An appropriate therapeutic intervention and the efficacy of VIT not only depend on a conclusive diagnosis, but might also be influenced by the patient-specific manifestation of the disease.
View Article and Find Full Text PDFBrain metastases (BM) are an ever-increasing challenge in oncology, threatening quality of life and survival of many cancer patients. The majority of BM originate from lung adenocarcinoma, and stage III patients have a risk of 40-50% to develop BM in the first years of disease onset. As therapeutic options are limited, prevention of their occurrence is an attractive concept.
View Article and Find Full Text PDFIt would be useful for researchers, practitioners, and decision-makers to anticipate the hazards that workers will face in the future. The focus of this study is a systematic review of published information to identify and characterize scenarios and hazards in the future of work. Eleven bibliographic databases were systematically searched for papers and reports published from 1999 to 2019 that described future of work scenarios or identified future work-related hazards.
View Article and Find Full Text PDF