Explainable deep learning enhances robust and reliable real-time monitoring of a chromatographic protein A capture step.

The application of model-based real-time monitoring in biopharmaceutical production is a major step toward quality-by-design and the fundament for model predictive control. Data-driven models have proven to be a viable option to model bioprocesses. In the high stakes setting of biopharmaceutical manufacturing it is essential to ensure high model accuracy, robustness, and reliability.

Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults.

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic.

clusTransition: An R package for monitoring transition in cluster solutions of temporal datasets.

Clustering analysis' primary purpose is to divide a dataset into a finite number of segments based on the similarities between items. In recent years, a significant amount of study has focused on the spatio-temporal aspects of clustering. However, clusters are no longer regarded as static objects since changes influence them in the underlying population.

Against the "one method fits all data sets" philosophy for comparison studies in methodological research.

Many methodological comparison studies aim at identifying a single or a few "best performing" methods over a certain range of data sets. In this paper we take a different viewpoint by asking whether the research question of identifying the best performing method is what we should be striving for in the first place. We will argue that this research question implies assumptions which we do not consider warranted in methodological research, that a different research question would be more informative, and how this research question can be fruitfully investigated.

The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic.

Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed.

Methods: .

Applications of monitoring and tracing the evolution of clustering solutions in dynamic datasets.

The clustering approach is widely accepted as the most prominent unsupervised learning problem in data mining techniques. This procedure deals with the identification of notable structures in unlabeled datasets. In modern days clustering of dynamic data, streams play a vital role in policy-making, and researchers are paying particular attention to monitoring the evolution of clustering solutions over time.

Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A).

Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial.

Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.

Experimental indications of gardeners' anecdotes that snails interfere with invasive slugs.

The invasive Spanish slug () is an important pest species in agriculture and horticulture in Europe. In the last decades it has spread across the continent where it outcompetes native slug and snail species, thus posing a threat for biodiversity. A popular anecdote suggests to promote Roman snails () in gardens because they are able to control .

Temporal patterns of roe deer traffic accidents: Effects of season, daytime and lunar phase.

Wildlife-related accidents, especially deer-vehicle accidents, pose a serious problem for road safety and animal protection in many countries. Knowledge of spatial and temporal patterns of deer-vehicle accidents is inevitable for accident analysis and mitigation efforts with temporal deer-vehicle accident data being much more difficult to obtain in sufficient data quality. We described the temporal patterns of roe deer (Capreolus capreolus) roadkills occurring in the period 2002-2006 in southeastern Austria.

Commercial glyphosate-based herbicides effects on springtails (Collembola) differ from those of their respective active ingredients and vary with soil organic matter content.

Glyphosate-based herbicides (GBH) are currently the most widely used agrochemicals for weed control. Environmental risk assessments (ERA) on nontarget organisms mostly consider the active ingredients (AIs) of these herbicides, while much less is known on effects of commercial GBH formulations that are actually applied in the field. Moreover, it is largely unknown to what extent different soil characteristics alter potential side effects of herbicides.

A subcellular proteome atlas of the yeast Komagataella phaffii.

The compartmentalization of metabolic and regulatory pathways is a common pattern of living organisms. Eukaryotic cells are subdivided into several organelles enclosed by lipid membranes. Organelle proteomes define their functions.

Real-time monitoring and model-based prediction of purity and quantity during a chromatographic capture of fibroblast growth factor 2.

Process analytical technology combines understanding and control of the process with real-time monitoring of critical quality and performance attributes. The goal is to ensure the quality of the final product. Currently, chromatographic processes in biopharmaceutical production are predominantly monitored with UV/Vis absorbance and a direct correlation with purity and quantity is limited.

Changes in Chromosome Counts and Patterns in CHO Cell Lines upon Generation of Recombinant Cell Lines and Subcloning.

Chinese hamster ovary (CHO) cells are the number one production system for therapeutic proteins. A pre-requirement for their use in industrial production of biopharmaceuticals is to be clonal, thus originating from a single cell in order to be phenotypically and genomically identical. In the present study it was evaluated whether standard procedures, such as the generation of a recombinant cell line in combination with selection for a specific and stable phenotype (expression of the recombinant product) or subcloning have any impact on karyotype stability or homogeneity in CHO cells.

Karyotype variation of CHO host cell lines over time in culture characterized by chromosome counting and chromosome painting.

Genomic rearrangements are a common phenomenon in rapidly growing cell lines such as Chinese hamster ovary (CHO) cells, a feature that in the context of production of biologics may lead to cell line and product instability. Few methods exist to assess such genome wide instability. Here, we use the population distribution of chromosome numbers per cell as well as chromosome painting to quantify the karyotypic variation in several CHO host cell lines.

Boosted structured additive regression for Escherichia coli fed-batch fermentation modeling.

The quality of biopharmaceuticals and patients' safety are of highest priority and there are tremendous efforts to replace empirical production process designs by knowledge-based approaches. Main challenge in this context is that real-time access to process variables related to product quality and quantity is severely limited. To date comprehensive on- and offline monitoring platforms are used to generate process data sets that allow for development of mechanistic and/or data driven models for real-time prediction of these important quantities.

Associations of growth patterns and islet autoimmunity in children with increased risk for type 1 diabetes: a functional analysis approach.

Background: Several studies indicate associations between early growth and type 1 diabetes (T1D). However, it remains an open question whether these findings can be translated to typical growth patterns associated with increased risk for T1D-associated islet autoimmunity.

Methods: We analyzed pooled data from 2236 children followed up in two large prospective German birth cohorts with a genetically increased risk for T1D including 18 564 measurements of height and weight, which were transformed to sex- and age-specific standard deviation scores (SDS).

The potential of random forest and neural networks for biomass and recombinant protein modeling in Escherichia coli fed-batch fermentations.

Product quality assurance strategies in production of biopharmaceuticals currently undergo a transformation from empirical "quality by testing" to rational, knowledge-based "quality by design" approaches. The major challenges in this context are the fragmentary understanding of bioprocesses and the severely limited real-time access to process variables related to product quality and quantity. Data driven modeling of process variables in combination with model predictive process control concepts represent a potential solution to these problems.

A review on the temporal pattern of deer-vehicle accidents: impact of seasonal, diurnal and lunar effects in cervids.

The increasing number of deer-vehicle-accidents (DVAs) and the resulting economic costs have promoted numerous studies on behavioural and environmental factors which may contribute to the quantity, spatiotemporal distribution and characteristics of DVAs. Contrary to the spatial pattern of DVAs, data of their temporal pattern is scarce and difficult to obtain because of insufficient accuracy in available datasets, missing standardization in data aquisition, legal terms and low reporting rates to authorities. Literature of deer-traffic collisions on roads and railways is reviewed to examine current understanding of DVA temporal trends.

Clinical study results from a randomized controlled trial of cognitive behavioural guided self-help in patients with partially remitted depressive disorder.

Objectives: Cognitive behavioural guided self-help has been shown to be effective in mild and moderate depressive disorder. It is not known, however, if it is effective in individuals with partially remitted depressive disorder, which is a serious clinical problem in up to 50-60% of treated patients. This study is the first one to examine the clinical benefit of this intervention in this patient population.

A new way of identifying biomarkers in biomedical basic-research studies.

A simple, nonparametric and distribution free method was developed for quick identification of the most meaningful biomarkers among a number of candidates in complex biological phenomena, especially in relatively small samples. This method is independent of rigid model forms or other link functions. It may be applied both to metric and non-metric data as well as to independent or matched parallel samples.

Modelling time course gene expression data with finite mixtures of linear additive models.

Unlabelled: A model class of finite mixtures of linear additive models is presented. The component-specific parameters in the regression models are estimated using regularized likelihood methods. The advantages of the regularization are that (i) the pre-specified maximum degrees of freedom for the splines is less crucial than for unregularized estimation and that (ii) for each component individually a suitable degree of freedom is selected in an automatic way.

Instability of the cellular lipidome with age.

The human lens nucleus is formed in utero, and from birth onwards, there appears to be no significant turnover of intracellular proteins or membrane components. Since, in adults, this region also lacks active enzymes, it offers the opportunity to examine the intrinsic stability of macromolecules under physiological conditions. Fifty seven human lenses, ranging in age from 12 to 82 years, were dissected into nucleus and cortex, and the nuclear lipids analyzed by electrospray ionization tandem mass spectrometry.

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation.

Background: Several DNA microarray based expression signatures for the different clinically relevant thyroid tumor entities have been described over the past few years. However, reproducibility of these signatures is generally low, mainly due to study biases, small sample sizes and the highly multivariate nature of microarrays. While there are new technologies available for a more accurate high throughput expression analysis, we show that there is still a lot of information to be gained from data deposited in public microarray databases.