Using heterogeneous sources of data and interpretability of prediction models to explain the characteristics of careless respondents in survey data

Abstract Prior to further processing, completed questionnaires must be screened for the presence of careless respondents. Different people will respond to surveys in different ways. Some take the easy path and fill out the survey carelessly. The proportion of careless respondents determines the survey’s quality. As a result, identifying careless respondents is critical for the quality of obtained results. This study aims to explore the characteristics of careless respondents in survey data and evaluate the predictive power and interpretability of different types of data and indices of careless responding. The research question focuses on understanding the behavior of careless respondents and determining the effectiveness of various data sources in predicting their responses. Data from a three-month web-based survey on participants’ personality traits such as honesty-humility, emotionality, extraversion, agreeableness, conscientiousness and openness to experience was used in this study. Data for this study was taken from Schroeders et al.. The gradient boosting machine-based prediction model uses data from the answers, time spent for answering, demographic information on the respondents as well as some indices of careless responding from all three types of data. Prediction models were evaluated with tenfold cross-validation repeated a hundred times. Prediction models were compared based on balanced accuracy. Models’ explanations were provided with Shapley values. Compared with existing work, data fusion from multiple types of information had no noticeable effect on the performance of the gradient boosting machine model. Variables such as “I would never take a bribe, even if it was a lot”, average longstring, and total intra-individual response variability were found to be useful in distinguishing careless respondents. However, variables like “I would be tempted to use counterfeit money if I could get away with it” and intra-individual response variability of the first section of a survey showed limited effectiveness. Additionally, this study indicated that, whereas the psychometric synonym score has an immediate effect and is designed with the goal of identifying careless respondents when combined with other variables, it is not necessarily the optimal choice for fitting a gradient boosting machine model

Neural differentiation of canine mesenchymal stem cells/multipotent mesenchymal stromal cells

Background: The ability of adipose tissue-derived multipotent mesenchymal stromal cells/mesenchymal stem cells (ASCs) to differentiate in neural lineages promises progress in the field of regenerative medicine, especially for replacing neuronal tissue damaged by different neurological disorders. Reprogramming of ASCs can be induced by the growth medium with neurogenic inductors and specific growth factors. We investigated the neural differentiation potential of canine ASCs using several growth media (KEM, NIMa, NIMb, NIMc) containing various combinations of neurogenic inductors: B27 supplement, valproic acid, forskolin, N2-supplement, and retinoic acid. Cells were first preconditioned in the pre-differentiation neural induction medium (mitogenically stimulatedSTIM1), followed by the induction of neuronal differentiation. Results: After 3, 6, and 9 days of neural induction, elongated neural-like cells with bipolar elongations were observed, and some oval cells with light nuclei appeared. The expression of neuronal markers tubulin beta III (TUBB3), neurofilament H (NF-H), microtubule-associated protein-2 (MAP2), and glial fibrillary acidic protein (GFAP) was observed using immunocytochemistry, which confirmed the differentiation into neurons and glial cells. Flow cytometry analysis showed high GFAP expression (between 70 and 90% of all cells) after cells had been growing three days in the neural induction medium a (NIMa). Around 25% of all cells also expressed adult neuronal markers NF-H and MAP2. After nine days of ASCs differentiation, the expression of all neural markers was reduced. There were no differences between the neural differentiation of ASCs isolated from female or male dogs. Conclusions: The differentiation repertoire of canine ASCs extends beyond mesodermal lineages. Using a defined neural induction medium, the canine ASCs differentiated into neural lineages and expressed markers of neuronal and glial cells, and also displayed the typical neuronal morphology. Differentiated ASCs can thus be a source of neural cellular lineages for the regenerative therapy of nerve damage and could be useful in the future for therapy or the modelling of neurodegenerative diseases

A Highly Productive, Whole-Cell DERA Chemoenzymatic Process for Production of Key Lactonized Side-Chain Intermediates in Statin Synthesis

<div><p>Employing DERA (2-deoxyribose-5-phosphate aldolase), we developed the first whole-cell biotransformation process for production of chiral lactol intermediates useful for synthesis of optically pure super-statins such as rosuvastatin and pitavastatin. Herein, we report the development of a fed-batch, high-density fermentation with <i>Escherichia coli</i> BL21 (DE3) overexpressing the native <i>E. coli deoC</i> gene. High activity of this biomass allows direct utilization of the fermentation broth as a whole-cell DERA biocatalyst. We further show a highly productive bioconversion processes with this biocatalyst for conversion of 2-substituted acetaldehydes to the corresponding lactols. The process is evaluated in detail for conversion of acetyloxy-acetaldehyde with the first insight into the dynamics of reaction intermediates, side products and enzyme activity, allowing optimization of the feeding strategy of the aldehyde substrates for improved productivities, yields and purities. The resulting process for production of ((2<i>S</i>,4<i>R</i>)-4,6-dihydroxytetrahydro-2<i>H</i>-pyran-2-yl)methyl acetate (acetyloxymethylene-lactol) has a volumetric productivity exceeding 40 g L⁻¹ h⁻¹ (up to 50 g L⁻¹ h⁻¹) with >80% yield and >80% chromatographic purity with titers reaching 100 g L⁻¹. Stereochemical selectivity of DERA allows excellent enantiomeric purities (<i>ee</i> >99.9%), which were demonstrated on downstream advanced intermediates. The presented process is highly cost effective and environmentally friendly. To our knowledge, this is the first asymmetric aldol condensation process achieved with whole-cell DERA catalysis and it simplifies and extends previously developed DERA-catalyzed approaches based on the isolated enzyme. Finally, applicability of the presented process is demonstrated by efficient preparation of a key lactol precursor, which fits directly into the lactone pathway to optically pure super-statins.</p></div

Time course of whole-cell, DERA-catalyzed batch reactions.

<p>Reactions were performed using <i>E. coli</i> BL21 (DE3) pET30/<i>deoC</i> fermentation cultures directly (DERA specific activity = 232 kRFU s⁻¹ g⁻¹, WCW = 207 g L⁻¹). Results are given as mass concentrations obtained from GC-FID analysis. The measured quantity of a particular compound, with the exception of the stable 6-ring hemiacetals (<b>3</b>), represents the sum of the corresponding equilibrium forms (hydrate, aldehyde and acetal/hemiacetal), which exist under the reaction conditions. <b>A:</b> Reaction species data from reactions using 400 mmol L⁻¹ of <b>2g</b> and 840 mmol L⁻¹ of <b>1</b> are shown. <b>1</b> (▪, black), <b>3a</b> (▴, blue) <b>3g</b> (♦, green), <b>8g</b> (•, red), <b>10g</b> (Δ, orange) and <b>2g</b> (◊, brown). <b>B:</b> Reaction species data from reactions using 400 mmol L⁻¹ of <b>2b</b> and 840 mmol L⁻¹ of <b>1</b> are shown. <b>1</b> (▪, black), <b>3a</b> (▴, blue) <b>3b</b> (♦, green), <b>8b</b> (•, red), <b>10b</b> (Δ, orange), <b>2b</b> (◊, brown), 2,6-chloro-2,4-dideoxyhexose (□, grey). Concentration of the latter (Information S8) is evaluated based on the assumption, that the GC-FID response factor is similar to that of <b>3b</b>.</p

Current art in the direct synthesis of optically pure super-statins from the lactol precursors.

<p>Current art in the direct synthesis of optically pure super-statins from the lactol precursors.</p

Inactivation of DERA whole-cell catalyst and DERA cell-free lysate with various aldehydes.

<p>Samples were treated with 75 mM, 150 mM and 225 mM substrate aldehydes for 15 minutes prior to the activity assay. The specific DERA activity was 226.8 kRFU s⁻¹ g⁻¹ and 226.6 kRFU s⁻¹ g⁻¹ for the whole-cell catalyst and for the cell-free lysate, respectively. Residual activities are given relative to non-treated whole-cell catalyst. Aldehydes used were acetaldehyde (A), <b>2b</b> (B) and <b>2g</b> (C).</p

DERA activity measurements of the whole-cell catalyst.

<p><b>A.</b> Fluorescence raw data for a DERA activity assay (dotted lines). Velocities for triplicate samples of the whole-cell catalyst were measured for 7 different loads (<i>b–h,</i> 3.16 µg–26.9 µg in 3.96 µg increments) of biomass. After normalization with the blank (<i>a</i>), maximum slopes were determined for each sample and averaged (solid lines) to yield velocity for a given biomass load. <b>B.</b> Velocity vs. biomass load plot. The first 5 points are taken for the specific activity calculation. Linear regression: y = 0.2366x+0.2073 R² = 0.9936 <b>C.</b> Comparison of velocities measured for cell-free lysate spiked with increasing loads of biomass. <b>D.</b> Validation of linearity of the activity assay within samples with constant biomass. The whole-cell catalyst <i>E. coli</i> BL21 (DE3) pET30/<i>deoC</i> was mixed with w.t. <i>E. coli</i> BL21 (DE3) biomass (•). Linear regression: y = 248.94x+1.3840, R² = 0.9995. In parallel, sonicated and cleared samples were measured (□). Linear regression: y = 235.00x+2.6433, R² = 0.9989.</p

Time course of whole-cell, DERA-catalyzed, fed-batch reactions yielding 3g.

<p>Reaction species data from three independent experiments using (in total) 550 mmol L⁻¹ of <b>2g</b> and 1200 mmol L⁻¹ of <b>1</b> are shown. Whole-cell catalyst (<i>E. coli</i> BL21 (DE3) pET30/<i>deoC</i> high-density culture) with 217 kRFU s⁻¹ g⁻¹ DERA specific activity and 182 g L⁻¹ WCW was used. Results are given as molar concentrations obtained from GC-FID analysis. The measured quantity of a particular compound, with the exception of the stable 6-ring hemiacetals (<b>3</b>), represents the sum of the corresponding equilibrium forms (hydrate, aldehyde and acetal/hemiacetal) which exist under the reaction conditions. <b>1</b> (<b>▪</b>, black), <b>3a</b> (▴, blue) <b>3g</b> (♦, green), <b>8g</b> (•, red), <b>10g</b> (Δ, orange), <b>2g</b> (◊, brown), cumulative molarity of reaction species originating from <b>2g</b> (□, grey; sum of <b>2g</b>, <b>8g</b>, <b>10g</b> and <b>3g</b> ). Secondary vertical axis shows in %: residual DERA activity (□, violet), cumulative feed of <b>2g</b> (dotted line), cumulative feed of <b>1</b> (dashed line).</p

The optimization of lactol (<b>3g</b>) oxidation yielding lactone <b>15</b>.

<p>The optimization of lactol (<b>3g</b>) oxidation yielding lactone <b>15</b>.</p