From observational to actionable: Rethinking omic studies in biopharmaceutical protein production

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Leveraging Mab cell culture platform to predict product quality

Biopharmaceutical therapeutic development timelines can be reduced by quickly generating material to initiate clinical trials and begin the process of drug development in order to improve the lives of patients. One way Biogen has addressed these challenges is the generation of a high productivity host. The high productivity host enables the use of representative cell pools that produce sufficient material for toxicology studies faster than previous workflows which used an individual clone. In general, one caveat of using cell pools is the risk of generating material that may not be fully representative of the commercial process. As product quality may vary from clone to clone, a less productive clone may need to be selected in order to avoid repeating toxicology studies. Biogen has mitigated this risk through changes in the cell culture platform process in order to have more predictable product quality outputs across pools, clones, and products. Cell culture platform modifications to the host cell line, media composition, and process parameters have enabled a predictable quality profile for both clones and pools, thereby enabling a “fast to tox” strategy that is also consistent with generating a commercially desirable proces

As repercussões do processo de Bolonha nas universidades portuguesas: o que dizem os estudos e os professores?

Tendo como referencial teórico os trabalhos que discutem a agenda globalmente estruturada para a Educação (Dale, 2004; Antunes, 2006), a universidade na sociedade e no contexto da economia do conhecimento (Afonso, 2015; Magalhães, 2011), o presente estudo teve como objetivo investigar as repercussões do Processo de Bolonha nos cursos de formação de professores das Instituições de Ensino Superior em Portugal. Foi feito um mapeamento da produção científica a fim de conhecer as mudanças e desafios dos cursos de formação de professores de instituições de ensino superior em Portugal. O corpus de análise inclui periódicos portugueses e estudos do Repositório Aberto de Portugal, além de entrevistas (gravadas e transcritas) realizadas com dois formadores dos ensinos universitário e politécnico, ambos da região norte do país, acerca do processo de reestruturação dos cursos, das mudanças operadas e seus efeitos. O critério de seleção dos professores deve-se à participação destes no processo de reformulação dos planos de ensino de cursos de formação de professores no contexto de Bolonha. O corpus de análise foi submetido à análise de conteúdo, com base em categorias extraídas das entrevistas e da produção mapeada. Os resultados, ainda preliminares, indicam que mudanças pretendidas por Bolonha, como o ensino mais centrado no aluno e consequentemente sua maior autonomia no processo formativo não foram ainda alcançadas e evidenciam tensões na reorganização dos cursos, ao nível da sua concepção e implementação, pois a redução do tempo dedicado às disciplinas de cariz pedagógico é apontada como um retrocesso na formação dos futuros docentes.The theoretical framework of this study is the study of the globally structured agenda for education (Dale, 2004; Antunes, 2006), the university in society and in the context of the knowledge economy (Afonso, 2015; Magalhães, 2011), objective to investigate the repercussions of the Bologna Process on the training courses for teachers of Higher Education Institutions in Portugal. A mapping of the scientific production was made in order to know the changes and challenges of the training courses for teachers of higher education institutions in Portugal. The corpus of analysis includes Portuguese periodicals and studies from the Open Repository of Portugal, as well as interviews (recorded and transcribed) with two university and polytechnic instructors, both from the north of the country, about the process of restructuring courses, changes and their effects. The selection criterion of teachers is due to their participation in the process of reformulation of teaching plans for teacher training courses in the context of Bologna. The corpus of analysis was submitted to content analysis, based on categories extracted from interviews and mapped production. The results, which are still preliminary, indicate that changes intended by Bologna, such as more student-centered teaching and consequently greater autonomy in the training process, have not yet been achieved and show tensions in the reorganization of the courses, at the level of their design and implementation, since the reduction of the time devoted to pedagogical disciplines is pointed out as a setback in the training of future teachers.Este trabalho é apoiado por fundos nacionais através da FCT - Fundação para a Ciência e a Tecnologia, I.P., no âmbito do projeto UID/CED/00167/2013 do Centro de Investigação e Intervenção Educativas (CIIE).info:eu-repo/semantics/publishedVersio

The Use of Supertitles by American Opera Companies.

The main purpose of this monograph was to examine the use of supertitles in foreign language opera by American opera companies. Supertitles are the translation of an opera\u27s text projected simultaneously above the stage during an opera performance. The use of supertitles is one of the most controversial issues in the opera world. Although the primary purpose is to enable the audience to understand a foreign text, there is an ongoing controversy over whether supertitles enhance an opera performance or detract from it. Many opera companies are using supertitles, but there are still those who have not made the investment in equipment or personnel necessary to accomplish this relatively new aspect of opera performance. This research project included the tracing of supertitles from subtitles of silent film to present-day opera, an explanation of the technology involved in supertitle production, an in-depth documentation of the controversial issue of supertitles, and the presentation of data from an original and two previously conducted surveys regarding audience opinion of supertitles. Following these discussions, general recommendations were made on the basis of budget, equipment, and personnel available to various opera companies. Additionally, future technology and other issues related to supertitles were addressed. This research has been compiled as a service to opera companies using supertitles, to those companies who are considering the use of supertitles, and to those audience members curious about the origin and production of supertitles

Monitorización domiciliaria de la presión arterial: actualidades y papel del enfermero

Trata-se de um artigo de revisão sobre o assunto monitorização residencial da pressão arterial (MRPA) com o objetivo de agregar a contribuição científica atual e apresentar a relevância desta abordagem na assistência ao paciente hipertenso em nosso meio. A técnica oferece vantagens em relação à medida casual, pois proporciona um maior número de medidas, melhor relação com lesão de órgãos-alvo, quantifica o efeito do avental branco, possui boa reprodutibilidade, boa aceitabilidade pelos pacientes, proporciona avaliação da pressão sem a influência do observador e do ambiente do consultório, diminui o número de visitas ao consultório e promove maior adesão ao tratamento. A importância da atuação do profissional enfermeiro na MRPA está ligada ao processo de educação, utilizando estratégias de ensino-aprendizagem, implementando a comunicação equipe-paciente e motivando o paciente a realizar o autocuidado.This is a review article on home blood pressure monitoring (HBPM) developed with the purpose to increase the current scientific knowledge and present the importance of this approach in the care to patients with hypertension in our setting. This technique has advantages over the causal measurement, as it provides more measurements, a better relationship with the target-organs injuries, it also quantifies the white-coat effect, has good reproducibility, good acceptability by the patients, assesses blood pressure without the influence from the observer and the environment of the appointment, reduces the number of visits to the doctor and promotes greater adherence to treatment. The importance of nursing practice in HBPM is associated with the education process, using teaching-learning strategies, implementing team-patient communication and encouraging patients towards performing self-care.Se trata de un artículo de revisión sobre el tema de monitorización domiciliaria de la presión arterial (MRPA) con el objetivo de sumar la contribución científica actual y presentar la relevancia de este abordaje en la atención al paciente hipertenso en nuestro medio. La técnica ofrece ventajas en relación a la medida casual, pues proporciona un mayor número de medidas, mejor relación con lesión de órganos-blanco, cuantifica el efecto del delantal blanco, posee buena reproductibilidad, buena aceptación por los pacientes, proporciona evaluación de la presión sin la influencia del observador y del ambiente de consultorio, disminuye el número de visitas al consultorio y promueve mayor adhesión al tratamiento. La importancia de la actuación del personal de enfermería en la MRPA está ligada al proceso de educación, utilizando estrategias de enseñanza-aprendizaje, implementando la comunicación equipo-paciente y motivando al paciente para que realice su autocuidado

O colecionismo: a influência da propaganda e da publicidade no comportamento de consumo feminino

A presente pesquisa monográfica objetiva a identificação da influência da propaganda e da publicidade no processo de consumo feminino, resultando no fenômeno colecionismo. O processo de consumo referido excede a normalidade, pois são abordados os padrões, que se transformam em uma necessidade contínua de adquirir mais itens do mesmo produto, a fim de adquirir satisfação pessoal: as coleções. Por se tratar da atual sociedade de consumo, o trabalho será embasado no livro A Sociedade do Consumo de Baudrillard. Por meio da exibição de três análises de casos ilustrativos e de análises dos resultados de entrevistas, conclui-se que a propaganda e a publicidade influenciam no colecionismo de diversas maneiras através do conjunto aplicado, não contendo uma forma pré-estabelecida

Radiomics in head and neck cancer outcome predictions

The data are publicly available on The Cancer Image Archive (TCIA) [41] website and can be downloaded using the NBIA Data Retriever [42]: https://wiki.cancerimagingarchive.net/display/Public/Head-Neck-PET-CT, accessed on 11 October 2022. The source code is available on GitHub: https://github.com/MariaGoncalves3/Radiomics_for_Head_And_Neck_Cancer, accessed on 11 October 2022.Head and neck cancer has great regional anatomical complexity, as it can develop in different structures, exhibiting diverse tumour manifestations and high intratumoural heterogeneity, which is highly related to resistance to treatment, progression, the appearance of metastases, and tumour recurrences. Radiomics has the potential to address these obstacles by extracting quantitative, measurable, and extractable features from the region of interest in medical images. Medical imaging is a common source of information in clinical practice, presenting a potential alternative to biopsy, as it allows the extraction of a large number of features that, although not visible to the naked eye, may be relevant for tumour characterisation. Taking advantage of machine learning techniques, the set of features extracted when associated with biological parameters can be used for diagnosis, prognosis, and predictive accuracy valuable for clinical decision-making. Therefore, the main goal of this contribution was to determine to what extent the features extracted from Computed Tomography (CT) are related to cancer prognosis, namely Locoregional Recurrences (LRs), the development of Distant Metastases (DMs), and Overall Survival (OS). Through the set of tumour characteristics, predictive models were developed using machine learning techniques. The tumour was described by radiomic features, extracted from images, and by the clinical data of the patient. The performance of the models demonstrated that the most successful algorithm was XGBoost, and the inclusion of the patients’ clinical data was an asset for cancer prognosis. Under these conditions, models were created that can reliably predict the LR, DM, and OS status, with the area under the ROC curve (AUC) values equal to 0.74, 0.84, and 0.91, respectively. In summary, the promising results obtained show the potential of radiomics, once the considered cancer prognosis can, in fact, be expressed through CT scans.This work received funding from the Austrian Science Fund (FWF) KLI 678-B31: “enFaced-Virtual and Augmented Reality Training and Navigation Module for 3D-Printed Facial Defect Reconstructions”,FWF KLI 1044: “enFaced 2.0-Instant AR Tool for Maxillofacial Surgery” (https://enfaced2.ikim.nrw/, accessed on 11 October 2022), “CAMed” (COMET K-Project 871132), which is funded by the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT), the Austrian Federal Ministry for Digital and Economic Affairs (BMDW), the Styrian Business Promotion Agency (SFG), and the FCT-Fundação para a Ciência e a Tecnologia within the R&D Units Project Scope: UIDB/00319/2020. Further, we acknowledge the REACT-EU project KITE (Plattform für KI-Translation Essen, https://kite.ikim.nrw/, accessed on 11 October 2022)

Moving Beyond CHO: Alternative host systems may be the future of biotherapeutics

CHO cells are the primary expression system for recombinant proteins with significant investment over the last three decades resulting in robust cell lines and processes. The flexible nature of CHO has lent itself to multiple process formats, such as fed batch, perfusion and continuous cultures, and advances in omics technology has enabled customization of media formulations and targeted engineering of CHO cells. This knowledge has led to large gains in protein productivity that can be captured with culture duration and/or scale. Despite this, constant pressure exists to reduce cost of manufacturing and improve per batch productivity to meet the needs of increased patient populations and increase accessibility of these therapeutics. Biogen has partnered with MIT to take a holistic view of the potential future of biomanufacturing to identify technologies that can make step changes in productivity and cost reduction. This effort has identified the host system as the most important factor to enabling this vision. Specifically, a non-mammalian host could be the key to realizing the most significant gains in productivity and reduction in cost of manufacturing. Through this initiative, we sought to take a more comprehensive approach to investigate alternative hosts for recombinant antibody production. Eight non-mammalian hosts were selected based on several properties, including proven secretion of recombinant protein products, ability to glycosylate proteins, established genome or molecular biology toolkit, amongst others. The final panel of organisms included yeast, filamentous fungi, a diatom, and a trypanosome. In collaboration with Amyris, we evaluated these eight non-mammalian host cell lines to compare their suitability as a potential primary host for the biotechnology industry. Only non-engineered, wild-type strains were used as a starting point for this evaluation, which assessed the ability of each host to express the same IgG1 model antibody. The outcome of this comparative analysis demonstrated that several of the alternative hosts could express full length antibody with acceptable glycoforms. Additionally, the ease of culture, ability to engineer the genome, and flexibility of carbon source were assessed. As an output of this work, the most productive strains will be made available for use without restrictions to allow others in the community to freely work with these hosts. Based on this initial assessment, a strategy to further investigate the potential of the most promising hosts will be shared

Perspectives on the Lindman Hypothesis and cellulose interactions

In the history of cellulose chemistry, hydrogen bonding has been the predominant explanation when discussing intermolecular interactions between cellulose polymers. This is the general consensus in scholarly textbooks and in many research articles, and it applies to several other biomacromolecules’ interactions as well. This rather unbalanced description of cellulose has likely impacted the development of materials based on the processing of cellulose—for example, via dissolution in various solvent systems and regeneration into solid materials, such as films and fibers, and even traditional wood fiber handling and papermaking. In this review, we take as a starting point the questioning of the general description of the nature of cellulose and cellulose interactions initiated by Professor Björn Lindman, based on generic physicochemical reasoning about surfactants and polymers. This dispute, which became known as “the Lindman hypothesis”, highlights the importance of hydrophobic interactions in cellulose systems and that cellulose is an amphiphilic polymer. This paper elaborates on Björn Lindman’s contribution to the subject, which has caused the scientific community to revisit cellulose and reconsider certain phenomena from other perspectives.info:eu-repo/semantics/publishedVersio

Synthetic skull bone defects for automatic patient-specific craniofacial implant design

Patient-specific craniofacial implants are used to repair skull bone defects after trauma or surgery. Currently, cranial implants are designed and produced by third-party suppliers, which is usually time-consuming and expensive. Recent advances in additive manufacturing made the in-hospital or in-operation-room fabrication of personalized implants feasible. However, the implants are still manufactured by external companies. To facilitate an optimized workflow, fast and automatic implant manufacturing is highly desirable. Data-driven approaches, such as deep learning, show currently great potential towards automatic implant design. However, a considerable amount of data is needed to train such algorithms, which is, especially in the medical domain, often a bottleneck. Therefore, we present CT-imaging data of the craniofacial complex from 24 patients, in which we injected various artificial cranial defects, resulting in 240 data pairs and 240 corresponding implants. Based on this work, automatic implant design and manufacturing processes can be trained. Additionally, the data of this work build a solid base for researchers to work on automatic cranial implant designs. Image Acquisition Matrix Size center dot Image Slice Thickness center dot craniofacial regionimaging technique center dot computed tomography Sample Characteristic - Organism Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13265225This investigation was approved by the internal review board (IRB) of the Medical University of Graz, Austria (IRB: EK-30-340 ex 17/18). This work was supported by CAMed (COMET K-Project 871132), which is funded by the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT) and the Austrian Federal Ministry for Digital and Economic Affairs (BMDW) and the Styrian Business Promotion Agency (SFG). Furthermore, the Austrian Science Fund (FWF) KLI 678-B31: "enFaced: Virtual and Augmented Reality Training and Navigation Module for 3D-Printed Facial Defect Reconstructions" and the TU Graz LEAD Project "Mechanics, Modeling and Simulation of Aortic Dissection". Privatdozent Dr. Dr. Jan Egger was supported as Visiting Professor by the Overseas Visiting Scholars Program from the Shanghai Jiao Tong University (SJTU) in China. Finally, we thank Professor Hannes Deutschmann, MD, from the Department of Radiology - Division of Neuroradiology, Vascular and Interventional Neuroradiology of the Medical University of Graz, for having kindly provided us with the source CT datasets used in this work