Harmonizing government responses to the COVID-19 pandemic.

Public health and safety measures (PHSM) made in response to the COVID-19 pandemic have been singular, rapid, and profuse compared to the content, speed, and volume of normal policy-making. Not only can they have a profound effect on the spread of the disease, but they may also have multitudinous secondary effects, in both the social and natural worlds. Unfortunately, despite the best efforts by numerous research groups, existing data on COVID-19 PHSM only partially captures their full geographical scale and policy scope for any significant duration of time. This paper introduces our effort to harmonize data from the eight largest such efforts for policies made before September 21, 2021 into the taxonomy developed by the CoronaNet Research Project in order to respond to the need for comprehensive, high quality COVID-19 data. In doing so, we present a comprehensive comparative analysis of existing data from different COVID-19 PHSM datasets, introduce our novel methodology for harmonizing COVID-19 PHSM data, and provide a clear-eyed assessment of the pros and cons of our efforts.

Newly Synthesized Thymol Derivative and Its Effect on Colorectal Cancer Cells.

Thymol affects various types of tumor cell lines, including colorectal cancer cells. However, the hydrophobic properties of thymol prevent its wider use. Therefore, new derivatives (acetic acid thymol ester, thymol ß-D-glucoside) have been synthesized with respect to hydrophilic properties. The cytotoxic effect of the new derivatives on the colorectal cancer cell lines HT-29 and HCT-116 was assessed via MTT assay. The genotoxic effect was determined by comet assay and micronucleus analysis. ROS production was evaluated using ROS-Glo™ H2O2 Assay. We confirmed that one of the thymol derivatives (acetic acid thymol ester) has the potential to have a cyto/genotoxic effect on colorectal cancer cells, even at much lower (IC50~0.08 µg/mL) concentrations than standard thymol (IC50~60 µg/mL) after 24 h of treatment. On the other side, the genotoxic effect of the second studied derivative-thymol ß-D-glucoside was observed at a concentration of about 1000 µg/mL. The antiproliferative effect of studied derivatives of thymol on the colorectal cancer cell lines was found to be both dose- and time-dependent at 100 h. Moreover, thymol derivative-treated cells did not show any significantly increased rate of micronuclei formation. New derivatives of thymol significantly increased ROS production too. The results confirmed that the effect of the derivative on tumor cells depends on its chemical structure, but further detailed research is needed. However, thymol and its derivatives have great potential in the prevention and treatment of colorectal cancer, which remains one of the most common cancers in the world.

Systematic Study of the Effects of High Shear Granulation Parameters on Process Yield, Granule Size, and Shape by Dynamic Image Analysis.

The aim of the work was to analyze the influence of process parameters of high shear granulation on the process yield and on the morphology of granules on the basis of dynamic image analysis. The amount of added granulation liquid had a significant effect on all monitored granulometric parameters and caused significant changes in the yield of the process. In regard of the shape, the most spherical granules with the smoothest surface were formed at a liquid to solid ratio of ≈1. The smallest granules were formed at an impeller speed of 700 rpm, but the granules formed at 500 rpm showed both the most desirable shape and the highest process yield. Variation in the shape factors relied not only on the process parameters, but also on the area equivalent diameter of the individual granules in the batch. A linear relationship was found between the amount of granulation liquid and the compressibility of the granules. Using response surface methodology, models for predicting the size of granules and process yield related to the amount of added liquid and the impeller speed were generated, on the basis of which the size of granules and yield can be determined with great accuracy.

Politically connected companies are less likely to shutdown due to COVID-19 restrictions.

Objective: While the aim of COVID-19 policies is to suppress the pandemic, many fear that the burden of the restrictions will fall more heavily on less privileged groups. We show one potential mechanism for COVID-19 responses to increase inequality by examining the intersection of business restrictions and business political connections. Methods: We fielded an online survey of 2735 business employees and managers in Ukraine, Egypt, and Venezuela over the summer of 2020 to collect data on companies' closures due to COVID-19 and nuanced information about their political connections. Findings: We show that businesses with political connections to government officials were significantly less likely to shut down as a result of COVID-19 policies. This finding suggests that measures designed to mitigate COVID-19 are ineffective in countries with a weak rule of law if politically connected firms are able to circumvent restrictions by leveraging political connections to receive preferential treatment. In addition, politically connected firms are no more likely-and sometimes even less likely-to engage in social-distancing policies to mitigate the pandemic despite the fact that they are more likely to remain open.

Recombinant Enzymatic Redox Systems for Preparation of Aroma Compounds by Biotransformation.

The aim of this study was to develop immobilized enzyme systems that reduce carbonyl compounds to their corresponding alcohols. The demand for natural aromas and food additives has been constantly growing in recent years. However, it can no longer be met by extraction and isolation from natural materials. One way to increase the availability of natural aromas is to prepare them by the enzymatic transformation of suitable precursors. Recombinant enzymes are currently being used for this purpose. We investigated trans-2-hexenal bioreduction by recombinant Saccharomyces cerevisiae alcohol dehydrogenase (ScADH1) with simultaneous NADH regeneration by recombinant Candida boidinii formate dehydrogenase (FDH). In a laboratory bioreactor with two immobilized enzymes, 88% of the trans-2-hexenal was transformed to trans-2-hexenol. The initial substrate concentration was 3.7 mM. The aldehyde destabilized ScADH1 by eluting Zn2+ ions from the enzyme. A fed-batch operation was used and the trans-2-hexenal concentration was maintained at a low level to limit the negative effect of Zn2+ ion elution from the immobilized ScADH1. Another immobilized two-enzyme system was used to reduce acetophenone to (S)-1-phenylethanol. To this end, the recombinant alcohol dehydrogenase (RrADH) from Rhodococcus ruber was used. This biocatalytic system converted 61% of the acetophenone to (S)-1-phenylethanol. The initial substrate concentration was 8.3 mM. All enzymes were immobilized by poly-His tag to Ni2+, which formed strong but reversible bonds that enabled carrier reuse after the loss of enzyme activity.

The antifungal activity of vapour phase of odourless thymol derivate.

Thymol is a substance with a great therapeutic potential possessing antibacterial and antifungal activity, with a characteristic odour that remains long after application but is not pleasant at higher concentrations. In this study, attention has been focused on describing the chemical and biological properties of the simply prepared trimethylsilyl ether of thymol (kubicin). Interestingly, kubicin has similar volatility as thymol, undergoes hydrolysis in the water (moisture; forming thymol and trimethylsilanol) and can be used at 6,000 times higher concentration than thymol without any negative and irritating odour. Kubicin showed diverse fungistatic and fungicidal activities when tested by direct contact assay, or in vapour phase. The volatile vapour of kubicin was effective on all tested fungal strains. These results suggest that vapours of kubicin might provide an alternative way to fight against fungal contamination.

COVID-19 Government Response Event Dataset (CoronaNet v.1.0).

Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.

Interpretation and identification of within-unit and cross-sectional variation in panel data models.

While fixed effects (FE) models are often employed to address potential omitted variables, we argue that these models' real utility is in isolating a particular dimension of variance from panel data for analysis. In addition, we show through novel mathematical decomposition and simulation that only one-way FE models cleanly capture either the over-time or cross-sectional dimensions in panel data, while the two-way FE model unhelpfully combines within-unit and cross-sectional variation in a way that produces un-interpretable answers. In fact, as we show in this paper, if we begin with the interpretation that many researchers wrongly assign to the two-way FE model-that it represents a single estimate of X on Y while accounting for unit-level heterogeneity and time shocks-the two-way FE specification is statistically unidentified, a fact that statistical software packages like R and Stata obscure through internal matrix processing.

Unusual Chemistry in an Uncatalyzed Bromate-Aniline Oscillator: Ring-Contraction Oxidation of Aniline with Pulsative CO2 Production.

The bromate-aniline oscillatory reaction was discovered 4 decades ago, but neither the detailed mechanism nor the key products or intermediates of the reaction were described. We report herein a detailed study of this reaction, which yielded new insights. We found that oscillatory oxidation of aniline by acidic bromate proceeds, to a significant extent, via a novel reaction pathway with the periodic release of carbon dioxide. Several products were isolated, and their structures, not described so far, were justified on the basis of MS and NMR. One of the main products of the reaction associated with the CO2 release route can be assigned to 2,2-dibromo-5-(phenylimino)cyclopent-3-en-1-one. A number of known compounds produced in the studied reaction, including unexpected brominated 1-phenylpyrroles and 1-phenylmaleimides, were identified by comparison with standards. A mechanism is suggested to explain the appearance of the detected compounds, based on coupling of the anilino radical with the produced 1,4-benzoquinone. We assume that the radical adduct reacts with bromine to form a cyclopropanone intermediate that undergoes a Favorskii-type rearrangement. Further oxidation and bromination steps including decarboxylation lead to the found brominated phenyliminocyclopentenones. The detected derivatives of 1-phenylpyrrole could be produced by a one-electron oxidation of a proposed intermediate 2-phenylamino-5-bromocyclopenta-1,3-dien-1-ol followed by ß-scission with the abstraction of carbon monoxide. Such a mechanism is known from the combustion chemistry of cyclopentadiene. The proposed mechanism of this reaction provides a framework for understanding the observed oscillatory kinetics.

Analysis of volatile organic compounds in the breath of patients with stable or acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. Acute exacerbations COPD (AECOPD), caused by infectious and non-infectious agents, contribute to an increase in mortality. The diagnostic procedure of AECOPD is mainly based on clinical features. The aim of this pilot study was to identify whether volatile organic compounds (VOCs) in breath could be used to discriminate for acute exacerbated COPD. Three patient groups were included in this controlled study: AECOPD patients (n = 14, age mean ± SD: 71.4 ± 7.46), stable COPD patients (n = 16, age mean ± SD: 66.9 ± 9.05) and healthy volunteers (n = 24, age mean ± SD: 28 ± 6.08). Breath samples were collected by optimizing a sampling strategy developed by us. These samples were then analyzed using a thermal desorption-gas chromatography-time of flight-mass spectrometer (TD-GC-ToF-MS). A total of 105 VOCs were identified in the breath samples. Relevant substances were subsequently selected by overall occurrence rate, the frequency of positive alveolar gradient (AG) (i.e. the difference in exhaled and inhaled VOCs concentration), exclusion of 'smoking related' VOCs and significant differences in AGs between the three groups. These steps dramatically reduced the number of relevant analytes and resulted in 12 key VOCs having discriminative values. The performance of patients' classification described by the Receiver Operating Characteristic (ROC) curve using all 12 substances delineates an area under the curve (AUC) of 0.97. A further reduction to four VOCs (AGs only different between AECOPD and COPD) delineates an AUC of 0.92. These results indicate that breath analysis with TD-GC-ToF-MS holds promise for an accurate and easy to perform differential diagnosis between AECOPD and COPD. In this regard, ketones were observed at the highest levels in exhaled breath of AECOPD, some of which are also related to potential bacterial pathogens. Using a set of VOCs that can discriminate for AECOPD, the calculated AUCs in ROC curve analysis show far superior results in comparison to serum AECOPD biomarkers, such as C-reactive protein. The identified VOCs should be further investigated in translational studies addressing their potential for developing highly specific nanosensors for breath gas analysis which would give clinicians a tool for non-invasive diagnosis of AECOPD at the point of care.

Fatty acids in intramuscular fat of Ile de France lambs in two different production systems.

The fatty acid (FA) composition in the intramuscular fat (IMF) of the musculus longissimus dorsi (MLD) of Ile de France purebred lambs in two different production systems in Slovakia was evaluated using gas chromatography. In the first production system, lambs and ewes were assigned to pasture without access to concentrates (P). In the second system, lambs and ewes were confined indoors with hay/silage and access to concentrates (S). An analysis of variance with the following factors was employed: production system, sex, and production system-sex interactions. The proportions of arachidonic, eicosapentaeonic, docosapentaeonic, and docosahexaenoic FAs, i.e. long-chain polyunsaturated FA (PUFA), were significantly higher in P lambs (1.83, 0.82, 0.92, 0.29 g 100 g - 1 FAME, respectively) than in S lambs (0.45, 0.14, 0.30, 0.09 g 100 g - 1 FAME, respectively). The proportions of conjugated linoleic acid (CLA), n-6 PUFA, n-3 PUFA, and essential FA (linoleic and α -linolenic) were also significantly higher in P lambs (2.10, 8.50, 4.55, and 8.80 g 100 g - 1 FAME, respectively) than in S lambs (0.65, 3.27, 1.50, and 3.64 g 100 g - 1 FAME, respectively). The proportions of palmitic acid and myristic acid as important individual saturated FAs (SFA) were significantly higher in S lambs (28.51 and 8.30 g 100 g - 1 FAME, respectively) than in P lambs (21.80 and 5.63 g 100 g - 1 FAME, respectively). The proportion of all SFAs was also significantly higher in S lambs (57.87 g 100 g - 1 FAME) than in P lambs (48.70 g 100 g - 1 FAME). From a nutrition and human health point of view (i.e. higher proportions of PUFA, CLA, and essential FAs and lower proportions of SFAs), meat from P lambs was found to be more favourable and would be more highly recommended for consumption.

Simultaneous analysis of carbohydrates, polyols and amines in urine samples using chemical ionization gas chromatography with tandem mass spectrometry.

A simple method for the simultaneous derivatization of carbohydrates, polyols, amines and amino acids using hexamethyldisilazane and N,O-bis(trimethylsilyl)trifluoroacetamide was developed. This method allows the direct derivatization of urine samples without sample pretreatment before derivatization. The method was successfully used for analysis of the selected metabolites in urine samples of healthy individuals and neonates suffering from galactosemia. The limits of detection by positive chemical ionization gas chromatography with tandem mass spectrometry analysis were in the range of 1.0 mgL-1 for mannitol to 4.7 mg/L for glucose.

Considerations on the determination of the limit of detection and the limit of quantification in one-dimensional and comprehensive two-dimensional gas chromatography.

Methods based on the blank signal as proposed by IUPAC procedure and on the signal to noise ratio (S/N) as listed in the ISO-11843-1 norm for determination of the limit of detection (LOD) and quantitation (LOQ) in one-dimensional capillary gas chromatography (1D-GC) and comprehensive two-dimensional capillary gas chromatography (CG×GC) are described in detail and compared for both techniques. Flame ionization detection was applied and variables were the data acquisition frequency and, for CG×GC, also the modulation time. It has been stated that LOD and LOQ estimated according to IUPAC might be successfully used for 1D-GC-FID method. Moreover, LOD and LOQ decrease with decrease of data acquisition frequency (DAF). For GC×GC-FID, estimation of LOD by IUPAC gave poor reproducibility of results while for LOQ reproducibility was acceptable (within ±10% rel.). The LOD and LOQ determined by the S/N concept both for 1D-GC-FID and GC×GC-FID methods are ca. three times higher than those values estimated by the standard deviation of the blank. Since the distribution pattern of modulated peaks for any analyte separated by GC×GC is random and cannot be predicted, LOQ and LOD may vary within 30% for 3s modulation time. Concerning sensitivity, 1D-GC-FID at 2Hz and of GC×GC-FID at 50Hz shows a ca. 5 times enhancement of sensitivity in the modulated signal output.

Gas chromatography with mass spectrometry analysis of phosphoserine, phosphoethanolamine, phosphoglycerol, and phosphate.

A new, rapid, sensitive, robust, and reliable method has been developed for the qualitative analysis of phosphoserine, phosphoethanolamine, phosphoglycerol, and phosphate using gas chromatography with mass spectrometry and two-step trimethylsilylation. The method employs hexamethyldisilazane for silylation of the phosphate and hydroxyl groups in the first phase and bis(trimethylsilyl)trifluoroacetamide for silylation of the less-reactive amino groups in the second phase. This order is of key importance for the method because of the different reactivities of the two reagents and the mechanism of derivatization of the active groups of the analytes. Trimethylsilylated derivatives of the analytes were identified on the basis of their retention times and mass spectra. The probable structures of the major fragments were identified in the spectra of the trimethylsilylated derivatives and characteristic m/z fragments were selected for each analyte. Fragments with m/z 73 and 299 occurred in the spectra of all the analytes. The characteristic retention data were employed to calculate the retention indices of the individual silylated phosphorylated substances in the hydrocarbon range C12-C19 for the DB-5ms column. The method was employed to measure the polar fraction of the hydrolysate of the cytoplasmic membrane of Bacillus subtilis. The detection limits vary between 5 µg/mL (trimethylsilylated phosphate) and 72 µg/mL (trimethylsilylated phosphoethanolamine).

The analysis of linear and monomethylalkanes in exhaled breath samples by GC×GC-FID and GC-MS/MS.

A new arrangement of the INCAT (inside needle capillary adsorption trap) device with Carbopack X and Carboxen 1000 as sorbent materials was applied for sampling, preconcentration and injection of C6C19n-alkanes and their monomethyl analogs in exhaled breath samples. For the analysis both GC-MS/MS and GC×GC-FID techniques were used. Identification of the analytes was based on standards, measured retention indices and selective SRM transitions of the individual isomers. The GC-MS/MS detection limits were in the range from 2.1 pg for n-tetradecane to 86 pg for 5-methyloctadecane. The GC×GC-FID detection limits ranged from 19 pg for n-dodecane to 110 pg for 3-methyloctane.

Direct silylation of Trypanosoma brucei metabolites in aqueous samples and their GC-MS/MS analysis.

A simple two-step method for the derivatization of polar compounds (lactate, alanine, glycerol, succinate and glucose) using hexamethyldisilazane (HMDS) and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) was developed. This method allows direct derivatization of aqueous samples wihout sample pretreatment. The method was used for the analysis of the metabolites of the unicellular organism Trypanosoma brucei. The limits of detection by GC-MS/MS analysis were in the range of 0.02 mg L(-1) for glucose to 0.85 mg L(-1) for lactate.

Determination of sevoflurane and its metabolite hexafluoroisopropanol by direct injection of human plasma into gas chromatography-tandem mass spectrometry.

The developed method for trace analysis of volatile components in plasma allows direct injection of up to 150 samples to the GC-MS/MS system without injector cleaning. This method requires no modification of plasma and the working environment does not interfere with the determination of these analytes. The method allows simultaneous quantification of non-polar sevoflurane and its polar metabolite hexafluoroisopropanol (free, unconjugated form). It is characterized by high repeatability and sensitivity with the detection limit of 0.009 mg L(-1) for sevoflurane and 0.018 mg L(-1) for hexafluoroisopropanol and the linear range 0.050-150 mg L(-1). The method was used to determine the concentration of sevoflurane and hexafluoroisopropanol in plasma samples of 7 patients undergoing general anesthesia with sevoflurane. The average concentration of sevoflurane and free hexafluoroisopropanol was 57.2 mg L(-1) and 0.39 mg L(-1), respectively. The method can be applied for clinical monitoring, as well as for analytical toxicology.

Equivalent chain lengths of all C4-C23 saturated monomethyl branched fatty acid methyl esters on methylsilicone OV-1 stationary phase.

Isomer mixtures of monomethyl branched saturated C7-C23 fatty acid methyl esters (FAME) were prepared by performing a methylene insertion reaction to the straight chain FAME and this study model was completed by using commercially available standards of C4-C7 FAME. The equivalent chain lengths (ECL) of all 220 C4-C23 monomethyl branched FAME on OV-1 stationary phase were measured, achieving an average repeatability of ±0.0004 ECL units. The monomethyl branched FAME was identified by GC on the basis of regularity of the fractional chain lengths (FCL) dependence on the number of carbon atoms (C(z)) of individual homologous series of methyl 2-, 3-, …, 21-FAME. The prediction of retention of the first homologues, having the new position of methyl group beginning at higher carbon atoms number, and analogously for the second, third, fourth, and other members of the homologous series, allowed the dependence FCL=f(C(z)) for the first and subsequent members of beginning homologous of monomethyl derivatives of FAME. The identification was confirmed by mass spectrometry. All of the methyl isomers of FAME, which could not be completely separated by gas chromatography due to having a methyl group in surroundings of the middle of the carbon chain, were resolved by mass spectrometry using deconvolution in a SIM-mode. Measured gas chromatographic and mass spectrometric data were applied for identification of the monomethyl branched saturated FAME in tongue coating.

Chemometric deconvolution of gas chromatographic unresolved conjugated linoleic acid isomers triplet in milk samples.

A generally known problem of GC separation of trans-7;cis-9; cis-9,trans-11; and trans-8,cis-10 CLA (conjugated linoleic acid) isomers was studied by GC-MS on 100m capillary column coated with cyanopropyl silicone phase at isothermal column temperatures in a range of 140-170 degrees C. The resolution of these CLA isomers obtained at given conditions was not high enough for direct quantitative analysis, but it was, however, sufficient for the determination of their peak areas by commercial deconvolution software. Resolution factors of overlapped CLA isomers determined by the separation of a model CLA mixture prepared by mixing of a commercial CLA mixture and CLA isomer fraction obtained by the HPLC semi-preparative separation of milk fatty acids methyl esters were used to validate the deconvolution procedure. Developed deconvolution procedure allowed the determination of the content of studied CLA isomers in ewes' and cows' milk samples, where dominant isomer cis-9,trans-11 is eluted between two small isomers trans-7,cis-9 and trans-8,cis-10 (in the ratio up to 1:100).