Chaos in Opinion-Driven Disease Dynamics.

During the COVID-19 pandemic, it became evident that the effectiveness of applying intervention measures is significantly influenced by societal acceptance, which, in turn, is affected by the processes of opinion formation. This article explores one among the many possibilities of coupled opinion-epidemic systems. The findings reveal either intricate periodic patterns or chaotic dynamics, leading to substantial fluctuations in opinion distribution and, consequently, significant variations in the total number of infections over time. Interestingly, the model exhibits a protective pattern.

Collaboration on Machine-Learned Potentials with IPSuite: A Modular Framework for Learning-on-the-Fly.

The field of machine learning potentials has experienced a rapid surge in progress, thanks to advances in machine learning theory, algorithms, and hardware capabilities. While the underlying methods are continuously evolving, the infrastructure for their deployment has lagged. The community, due to these rapid developments, frequently finds itself split into groups built around different implementations of machine-learned potentials. In this work, we introduce IPSuite, a Python-driven software package designed to connect different methods and algorithms from the comprehensive field of machine-learned potentials into a single platform while also providing a collaborative infrastructure, helping ensure reproducibility. Furthermore, the data management infrastructure of the IPSuite code enables simple model sharing and deployment in simulations. Currently, IPSuite supports six state-of-the-art machine learning approaches for the fitting of interatomic potentials as well as a variety of methods for the selection of training data, running of ab initio calculations, learning-on-the-fly strategies, model evaluation, and simulation deployment.

Determinants of exposure to acrylamide in European children and adults based on urinary biomarkers: results from the "European Human Biomonitoring Initiative" HBM4EU participating studies.

Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014-2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3-18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20-45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (ß coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:ß = - 9.1 µg/g creatinine, 95% CI - 15.8, - 2.4; GAMA: ß = - 3.4 µg/g creatinine, 95% CI - 4.7, - 2.2), living in rural areas (AAMA:ß = - 4.7 µg/g creatinine, 95% CI - 8.6, - 0.8; GAMA:ß = - 1.1 µg/g creatinine, 95% CI - 1.9, - 0.4) and increasing age (AAMA:ß = - 1.9 µg/g creatinine, 95% CI - 2.4, - 1.4; GAMA:ß = - 0.7 µg/g creatinine, 95% CI - 0.8, - 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries.

Modelling the spatial spread of COVID-19 in a German district using a diffusion model.

In this study, we focus on modeling the local spread of COVID-19 infections. As the pandemic continues and new variants or future pandemics can emerge, modelling the early stages of infection spread becomes crucial, especially as limited medical data might be available initially. Therefore, our aim is to gain a better understanding of the diffusion dynamics on smaller scales using partial differential equation (PDE) models. Previous works have already presented various methods to model the spatial spread of diseases, but, due to a lack of data on regional or even local scale, few actually applied their models on real disease courses in order to describe the behaviour of the disease or estimate parameters. We use medical data from both the Robert-Koch-Institute (RKI) and the Birkenfeld district government for parameter estimation within a single German district, Birkenfeld in Rhineland-Palatinate, during the second wave of the pandemic in autumn 2020 and winter 2020-21. This district can be seen as a typical middle-European region, characterized by its (mainly) rural nature and daily commuter movements towards metropolitan areas. A basic reaction-diffusion model used for spatial COVID spread, which includes compartments for susceptibles, exposed, infected, recovered, and the total population, is used to describe the spatio-temporal spread of infections. The transmission rate, recovery rate, initial infected values, detection rate, and diffusivity rate are considered as parameters to be estimated using the reported daily data and least square fit. This work also features an emphasis on numerical methods which will be used to describe the diffusion on arbitrary two-dimensional domains. Two numerical optimization techniques for parameter fitting are used: the Metropolis algorithm and the adjoint method. Two different methods, the Crank-Nicholson method and a finite element method, which are used according to the requirements of the respective optimization method are used to solve the PDE system. This way, the two methods are compared and validated and provide similar results with good approximation of the infected in both the district and the respective sub-districts.

External Quality Assurance Schemes (EQUASs) and Inter-laboratory Comparison Investigations (ICIs) for human biomonitoring of polycyclic aromatic hydrocarbon (PAH) biomarkers in urine as part of the quality assurance programme under HBM4EU.

Polycyclic aromatic hydrocarbons (PAHs) were included as priority substances for human biomonitoring (HBM) in the European Human Biomonitoring Initiative (HBM4EU), which intended to harmonise and advance HBM across Europe. For this project, a specific Quality Assurance and Quality Control (QA/QC) programme applying Inter-laboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs) was developed to ensure the comparability and accuracy of participating analytical laboratories. This paper presents the results of four ICI/EQUAS rounds for the determination of 13 PAH metabolites in urine, i.e. 1-naphthol, 2-naphthol, 1,2-dihydroxynaphthalene, 2-, 3- and 9-hydroxyfluorene, 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene, 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene. However, 4 PAH metabolites could not be evaluated as the analytical capacity of participating laboratories was too low. Across all rounds and biomarkers, 86% of the participants achieved satisfactory results, although low limits of quantification were required to quantify the urinary metabolites at exposure levels of the general population. Using high-performance liquid or gas chromatography coupled with mass spectrometry (HPLC-MS; GC-MS) and isotope dilution for calibration as well as performing an enzymatic deconjugation step proved to be favourable for the accurate determination of PAHs in urine. Finally, the HBM4EU QA/QC programme identified an international network of laboratories providing comparable results in the analysis of urinary PAH biomarkers, although covering all parameters initially selected was still too challenging.

Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000-2021).

Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014-2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000-2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies.

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.

Interlaboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs) for human biomonitoring of perfluoroalkyl substances (PFASs) in serum as part of the quality assurance programme under HBM4EU.

Perfluoroalkyl substances (PFASs) are of very high concern due to their persistence and accumulative behaviour as well as their manifold adverse health effects. Human biomonitoring (HBM) based on the determination of PFASs in serum samples is an adequate and established strategy for exposure and risk assessment of the population. The suspected health risks associated with exposure levels in the general population call for reliable HBM data verified by Quality Assurance and Quality Control (QA/QC) measures. PFASs were among the chemicals selected as priority substances in HBM4EU, a pan-European project to harmonize and advance HBM within 30 European countries. For this purpose, the analytical comparability and accuracy of PFASs-analysing laboratories was assessed in a QA/QC programme comprising Interlaboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs). This paper presents the evaluation process and discusses the results of four ICI/EQUAS rounds for the determination of eight perfluoroalkyl carboxylic acids and four perfluoroalkyl sulfonic acids (PFBS, PFHxS, PFHpS, PFOS) in serum. All 21 participating laboratories achieved satisfactory results for at least six of these biomarkers, although low limits of quantification (of about 0.1 µg/L) were required to quantify serum PFAS levels at general population exposure levels. The mean relative standard deviation of the participants' results (study RSDR) significantly improved from 22 % to 13 % over all PFAS biomarkers in the course of the four rounds. This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of PFASs across 12 European countries.

The impact of travelling on the COVID-19 infection cases in Germany.

BACKGROUND: COVID-19 continues to disrupt social lives and the economy of many countries and challenges their healthcare capacities. Looking back at the situation in Germany in 2020, the number of cases increased exponentially in early March. Social restrictions were imposed by closing e.g. schools, shops, cafés and restaurants, as well as borders for travellers. This reaped success as the infection rate descended significantly in early April. In mid July, however, the numbers started to rise again. Of particular reasons was that from mid June onwards, the travel ban has widely been cancelled or at least loosened. We aim to measure the impact of travellers on the overall infection dynamics for the case of (relatively) few infectives and no vaccinations available. We also want to analyse under which conditions political travelling measures are relevant, in particular in comparison to local measures. By travel restrictions in our model we mean all possible measures that equally reduce the possibility of infected returnees to further spread the disease in Germany, e.g. travel bans, lockdown, post-arrival tests and quarantines. METHODS: To analyse the impact of travellers, we present three variants of an susceptible-exposed-infected-recovered-deceased model to describe disease dynamics in Germany. Epidemiological parameters such as transmission rate, lethality, and detection rate of infected individuals are incorporated. We compare a model without inclusion of travellers and two models with a rate measuring the impact of travellers incorporating incidence data from the Johns Hopkins University. Parameter estimation was performed with the aid of the Monte-Carlo-based Metropolis algorithm. All models are compared in terms of validity and simplicity. Further, we perform sensitivity analyses of the model to observe on which of the model parameters show the largest influence the results. In particular, we compare local and international travelling measures and identify regions in which one of these shows larger relevance than the other. RESULTS: In the comparison of the three models, both models with the traveller impact rate yield significantly better results than the model without this rate. The model including a piecewise constant travel impact rate yields the best results in the sense of maximal likelihood and minimal Bayesian Information Criterion. We synthesize from model simulations and analyses that travellers had a strong impact on the overall infection cases in the considered time interval. By a comparison of the reproductive ratios of the models under traveller/no-traveller scenarios, we found that higher traveller numbers likely induce higher transmission rates and infection cases even in the further course, which is one possible explanation to the start of the second wave in Germany as of autumn 2020. The sensitivity analyses show that the travelling parameter, among others, shows a larger impact on the results. We also found that the relevance of travel measures depends on the value of the transmission parameter: In domains with a lower transmission parameter, caused either by the current variant or local measures, it is found that handling the travel parameters is more relevant than those with lower value of the transmission. CONCLUSIONS: We conclude that travellers is an important factor in controlling infection cases during pandemics. Depending on the current situation, travel restrictions can be part of a policy to reduce infection numbers, especially when case numbers and transmission rate are low. The results of the sensitivity analyses also show that travel measures are more effective when the local transmission is already reduced, so a combination of those two appears to be optimal. In any case, supervision of the influence of travellers should always be undertaken, as another pandemic or wave can happen in the upcoming years and vaccinations and basic hygiene rules alone might not be able to prevent further infection waves.

Adaptive fitting of potential energy surfaces of small to medium-sized molecules in sum-of-product form: Application to vibrational spectroscopy.

A semi-automatic sampling and fitting procedure for generating sum-of-product (Born-Oppenheimer) potential energy surfaces based on a high-dimensional model representation is presented. The adaptive sampling procedure and subsequent fitting rely on energies only and can be used for re-fitting existing analytic potential energy surfaces in the sum-of-product form or for direct fits from ab initio computations. The method is tested by fitting ground electronic state potential energy surfaces for small to medium sized semi-rigid molecules, i.e., HFCO, HONO, and HCOOH, based on ab initio computations at the coupled-cluster single double and perturbative triples-F12/cc-pVTZ-F12 or MP2/aug-cc-pVTZ levels of theory. Vibrational eigenstates are computed using block improved relaxation in the Heidelberg multi-configurational time dependent Hartree package and compared to available experimental and theoretical data. The new potential energy surfaces are compared to the best ones currently available for these molecules in terms of accuracy, including resulting vibrational states, required number of sampling points, and number of fitting parameters. The present procedure leads to compact expansions and scales well with the number of dimensions for simple potentials such as single or double wells.

Long-term monitoring of mercury in young German adults: Time trend analyses from the German Environmental Specimen Bank, 1995-2018.

As highlighted in the Minamata Convention, Mercury (Hg) in its various forms poses a substantial risk to human health and the environment. The health relevance of Hg is also recognized by the European Human Biomonitoring Initiative (HBM4EU), which classifies Hg as a priority substance, since considerable knowledge and data gaps on Hg exposure levels and their changes over time still exist in Europe. The German Environmental Specimen Bank (German ESB) provides valuable policy relevant data and long-term trends of substance exposure on a national level for international comparison and evaluation. In this study we analysed data of the German ESB on Hg exposure of young adults aged 20 to 29 including data on urinary Hg levels from 1995 to 2018 and whole blood Hg levels from 2001 to 2010. Results show a clear decrease in both, about 86% in urine total daily Hg excretion from 1995 (0.76 µg/L) to 2018 (0.11 µg/L) (n = 10,069) and about 57% in blood concentrations of Hg from 2001 (1.76 µg/L) to 2010 (0.77 µg/L) (n = 4085). Over the investigated timeframe only a few values exceeded the toxicologically derived health based guidance value HBM I for blood and urine, with these exceedances decreasing over time in line with the general trend. The factors mostly influencing Hg excretion identified in this study are dental amalgam as well as fish and seafood consumption. Besides other factors (e.g. age and sex), also airborne Hg exposure appears to be a low but evident influencing factor in Germany. Although a considerable decrease in internal Hg exposure is recognized in the last decades, the current low-level exposure may cause adverse health effects especially to vulnerable groups such as pregnant women and children. To further elucidate and evaluate current exposure sources and to reduce human exposure to Hg, continuous environmental and human biomonitoring is needed.

Interlaboratory Comparison Investigations (ICIs) for human biomonitoring of chromium as part of the quality assurance programme under HBM4EU.

BACKGROUND: The pan-European human biomonitoring initiative HBM4EU targets the harmonization of human biomonitoring (HBM) procedures and data for both environmental and occupational exposure, including chromium. The determination of chromium in urine (U-Cr), plasma (P-Cr) and whole blood (WB-Cr) is a common HBM application in employees occupationally exposed to chromium (VI) compounds. METHODS: European laboratories which have registered as candidate laboratories for chromium analysis within HBM4EU were invited to participate in a quality assurance/qualitycontrol (QA/QC) programme comprising interlaboratory comparison investigations (ICI) for the parameters U-Cr, P-Cr and WB-Cr. Participating laboratories received two samples of different concentrations in each of four rounds and were asked to analyse the samples using their standard analytical procedure. The data were evaluated by the Z-score approach and were reported to the participants after each round. RESULTS: The majority of the 29 participating laboratories obtained satisfactory results, although low limits of quantification were required to quantify chromium concentrations in some of the ICI materials. The robust relative standard deviation of the participants' results (study RSDR) obtained from all ICI runs ranged from 6 to 16 % for U-Cr, 7-18 % for P-Cr and 4-47 % for WB-Cr. The application of both inductively coupled plasma mass spectrometry (ICP-MS) and electrothermal atomic absorption spectrometry (EAAS) appeared appropriate for the determination of chromium in urine, plasma and whole blood with regard to occupational exposure levels. CONCLUSION: This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of chromium across Europe.

Lead, cadmium, mercury, and chromium in urine and blood of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Metals reach humans through food and drinking water intake and inhalation of airborne particles and can have detrimental health effects in particular for children. The metals presented here (lead, cadmium, chromium, and mercury) could lead to toxic effects such as neurotoxicity, mutagenicity, and have been classified as (possible) carcinogens. Using population representative data from the German Environmental Survey 2014-2017 (GerES V) from 3- to 17-year-old children on lead and cadmium in blood (n = 720) and on cadmium, chromium, and mercury in urine (n = 2250) we describe current internal exposure levels, and socio-demographic and substance-specific exposure determinants. Average internal exposure (geometric means) in blood was 9.47 µg/L for lead and below 0.06 µg/L (limit of quantification) for cadmium, and in urine 0.072 µg/L for cadmium, 0.067 µg/L for mercury, and 0.393 µg/L for chromium, respectively. Younger children have higher concentrations of lead and chromium compared to 14-17-year-old adolescents, and boys have slightly higher mercury concentrations than girls. With respect to substance specific determinants, higher lead concentrations emerged in participants with domestic fuel and in non-smoking children with smokers in the household, higher levels of cadmium were associated with smoking and vegetarian diet and higher levels of mercury with the consumption of seafood and amalgam teeth fillings. No specific exposure determinants emerged for chromium. The health based guidance value HBM-I was not exceeded for mercury and for cadmium in urine it was exceeded by 0.6% of the study population. None of the exceedances was related to substantial tobacco smoke exposure. Comparisons to previous GerES cycles (GerES II, 1990-1992; GerES IV, 2003-2006) indicate continuously lower levels.

Interlaboratory comparison investigations (ICI) and external quality assurance schemes (EQUAS) for cadmium in urine and blood: Results from the HBM4EU project.

Human biomonitoring (HBM) of cadmium is essential to assess and prevent toxic exposure. Generally, low cadmium levels in urine and blood of the general population place particularly high demands on quality assurance and control measures (QA/QC) for cadmium determination. One of the aims of the HBM4EU project is to harmonize and advance HBM in Europe. Cadmium is one of the chemicals selected as a priority substance for HBM implementation in the 30 European countries under HBM4EU. For this purpose, analytical comparability and accuracy of the analytical laboratories of participating countries was investigated in a QA/QC programme comprising interlaboratory comparison investigations (ICI) and external quality assurance schemes (EQUAS). This paper presents the evaluation process and discusses the results of four ICI/EQUAS rounds for the determination of cadmium in urine and blood. The majority of the 43 participating laboratories achieved satisfactory results, although low limits of quantification were required to quantify Cd concentrations at general population exposure levels. The relative standard deviation of the participants' results obtained from all ICI and EQUAS runs ranged from 8 to 36% for cadmium in urine and 8-28% for cadmium in blood. Applying inductively-coupled plasma mass spectrometry (ICP-MS), using an internal standard, and eliminating molybdenum oxide interferences was favourable for the accurate determination of cadmium in urine and blood. Furthermore, the analysis of cadmium in urine was found to have a critical point at approximately 0.05 µg/l, below which variability increased and laboratory proficiency decreased. This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of cadmium across 20 European countries.

An epidemic model integrating direct and fomite transmission as well as household structure applied to COVID-19.

This paper stresses its base contribution on a new SIR-type model including direct and fomite transmission as well as the effect of distinct household structures. The model derivation is modulated by several mechanistic processes inherent from typical airborne diseases. The notion of minimum contact radius is included in the direct transmission, facilitating the arguments on physical distancing. As fomite transmission heavily relates to former-trace of sneezes, the vector field of the system naturally contains an integral kernel with time delay indicating the contribution of undetected and non-quarantined asymptomatic cases in accumulating the historical contamination of surfaces. We then increase the complexity by including the different transmission routines within and between households. For airborne diseases, within-household interactions play a significant role in the propagation of the disease rendering countrywide effect. Two steps were taken to include the effect of household structure. The first step subdivides the entire compartments (susceptible, exposed, asymptomatic, symptomatic, recovered, death) into the household level and different infection rates for the direct transmission within and between households were distinguished. Under predefined conditions and assumptions, the governing system on household level can be raised to the community level. The second step then raises the governing system to the country level, where the final state variables estimate the total individuals from all compartments in the country. Two key attributes related to the household structure (number of local households and number of household members) effectively classify countries to be of low or high risk in terms of effective disease propagation. The basic reproductive number is calculated and its biological meaning is invoked properly. The numerical methods for solving the DIDE-system and the parameter estimation problem were mentioned. Our optimal model solutions are in quite good agreement with datasets of COVID-19 active cases and related deaths from Germany and Sri Lanka in early infection, allowing us to hypothesize several unobservable situations in the two countries. Focusing on extending minimum contact radius and reducing the intensity of individual activities, we were able to synthesize the key parameters telling what to practice.

Towards Understanding the Reactivity and Optical Properties of Organosilicon Sulfide Clusters.

We report the extension of the class of organotetrel sulfide clusters with further examples of the still rare silicon-based species, synthesized from RSiCl3 with R=phenyl (Ph, I), naphthyl (Np, II), and styryl (Sty, III) with Na2 S. Besides known [(PhSi)4 S6 ] (IV), new compounds [(NpSi)4 S6 ] (1) and [(StySi)4 S6 ] (2) were obtained, the first two of which underwent reactions with [AuCl(PPh3 )] to form ternary complexes. DFT studies of cluster dimers helped us understand the differences between the habit of {Si4 S6 }- and {Sn4 S6 }-based compounds. Crystalline 1 showed a pronounced nonlinear optical response, while for intrinsically amorphous 2, the chemical damage threshold seems to inhibit a corresponding observation. Calculations within the independent particle approximation served to rationalize and compare electronic and optical excitations of [(RSi)4 S6 ] clusters (R=Ph, Np). The calculations reproduced the measured data and allowed for the interpretation of the main spectroscopic features.

Prediction of the miRNA interactome - Established methods and upcoming perspectives.

MicroRNAs (miRNAs) are well-studied small noncoding RNAs involved in post-transcriptional gene regulation in a wide range of organisms, including mammals. Their function is mediated by base pairing with their target RNAs. Although many features required for miRNA-mediated repression have been described, the identification of functional interactions is still challenging. In the last two decades, numerous Machine Learning (ML) models have been developed to predict their putative targets. In this review, we summarize the biological knowledge and the experimental data used to develop these ML models. Recently, Deep Neural Network-based models have also emerged in miRNA interaction modeling. We thus outline established and emerging models to give a perspective on the future developments needed to improve the identification of genes directly regulated by miRNAs.

Effect of gelatin-polysuccinat on cerebral oxygenation and microcirculation in a porcine haemorrhagic shock model.

BACKGROUND: During early treatment of haemorrhagic shock maintenance of cerebral and end-organ oxygen supply by fluid resuscitation is mandatory. Gelatin-polysuccinat (GP) recently regained attention despite a still unclear risk profile and widely unknown effects on cerebral and peripheral microcirculation. This study investigates the effects of GP versus balanced electrolyte solution (BEL) with focus on cerebral regional oxygen saturation and peripheral microcirculation in a porcine haemorrhagic shock model. METHODS: After Animal Care Committee approval haemorrhagic shock was induced by arterial blood withdrawal in 27 anaesthetized pigs. Consequently, the animals received rapid fluid resuscitation by either GP or BEL to replace the removed amount of blood, or remained untreated (n = 3 × 9). Over two hours cerebral regional oxygen saturation by near-infrared spectroscopy and peripheral buccal microcirculation by combined white-light spectrometry and laser-Doppler flowmetry were recorded. Secondary parameters included extended haemodynamics, spirometry, haematological and blood gas parameters. RESULTS: Both fluid resuscitation regimes sufficiently stabilized the macro- and microcirculation in haemorrhagic shock with a more pronounced effect following GP infusion. GP administration led to a persisting, critical impairment of cerebral regional oxygen saturation through considerable haemodilution. Survival rates were 100% in both fluid resuscitation groups, but only 33% in the untreated control. CONCLUSION: Equal amounts of GP and BEL sufficiently stabilize systemic circulation and microcirculatory perfusion. Forced fluid resuscitation by GP should be applied with caution to prevent haemodilution-induced impairment of cerebral oxygen delivery.