This article reports the results of a survey of 455 Polish primary school sixth-graders experiencing changes in the education system. The goal of the study was to identify the relationships between the Big Five personality traits, measured with the picture-based personality survey for children (PBPS-C) and locus of control, determined using the locus of control questionnaire (LOCQ). The results lead to the conclusion that primary school students do not have an established locus of control of either success or failure. There are also no significant differences between boys and girls in the way they interpret the causes of situations and events that happen to them. Boys, compared to girls, scored significantly higher on traits related to seeking and enjoying the company of others. On the other hand, girls exhibited significantly higher levels of traits responsible for increased anxiety than boys. The personality traits that correlated the strongest with locus of control were Conscientiousness, Openness to Experience, and Agreeableness. A regression model showed that locus of control of success was significantly affected by two traits: Extraversion and Conscientiousness. Locus of control of failure was significantly predicted by Extraversion, Openness to Experience, Agreeableness (positively), and Neuroticism (negatively). Regression model with gender as a moderator of relationships between personality traits and locus of control turned out to be insignificant. The aim of this study was to analyse personality traits and locus of control of students in the last (sixth) grade of primary school, who were entering adolescence. At the time of the study, the participants were the first generation of students taught in the new education system refashioned by the new education reform in Poland . Before Students in early adolescence are at risk of experiencing impairments in personality development  and showAdolescence is a period of an intensive development of personality, including locus of control, which allows young people to interpret the events in which they participate in their everyday lives and assign meaning to them. Personality traits and locus of control play an important role in predicting successful completion of compulsory education, which, in turn, paves the way for future professional success ,18,19. IBy measuring personality traits and locus of control in students, one can partially estimate the level of their adaptation to the new situation and the way they interpret the events they experience . The litCurrently, one of the most popular personality trait models used in psychological studies of children and adolescents is McCrae’s and Costa ,28,29 BiCosta and McCrae believe that personality traits are biologically determined and are manifested in the ways even very young children respond to various situations. Personality is strongly influenced by the functions of the PFC (Conscientiousness and Openness to Experience)  and by mDespite the fact that personality traits are most often analysed in older adolescents and adults, existing findings show that studies of younger children are also warranted. For middle childhood, personality has been considered a potent predictor of concurrent and later adaptation . AlreadyIn a study by Suldo, Minch, and Hearon , all BigToday, personality psychologists are particularly interested in the developmental changes in the Big Five personality traits occurring during adolescence ,51,52. PResearch also shows that personality traits are associated with intelligence, school achievement, adjustment, coping, willingness to engage in risk-taking behaviours, and social competence. Graziano and Ward , who stuLate childhood and early adolescence are considered to be crucial for the development of action orientations and for conceptualisations of person–environment transactions ,57. For Locus of control may be different for different spheres of human life. For instance, a person who believes that their social success is due to their own mental characteristics may at the same time think that their educational or occupational failures are caused by bad luck or other people’s bad intentions. Research shows that students with an internal locus of control are less likely to perceive negative events in their lives as being due to external factors. They are more likely to take action to remedy the difficult situation, for example, by looking to others for support , which iChubb, Fertmani, and Ross  note thaAlthough personality traits and locus of control are separate theoretical constructs, they share some common features. One of them is that they allow to predict how an individual will behave in an unknown situation. This knowledge can help professionals plan effective teaching and educational activities for young people. While personality traits are biologically based and determined, the locus of control, which is a construct derived from the theory of social learning, is shaped by external experiences and social requirements. Personality traits, being internal dispositions and tendencies to engage in or withdraw from particular activities and to interpret various situations in specific ways, may secondarily lead to the development, in children and adolescents, of a sense of responsibility (or a lack thereof) for various situations they experience directly. Firstly, personality traits may predispose young people to seek activities and ways of spending time that suit their individual preferences. Secondly, they can also influence the mode in which teenagers interpret reward and failure situations as being within or beyond their personal control ,43,75. WPersonality is strongly influenced by motivation systems that organise responses to rewards and punishments and that drive approach and avoidance behaviours . PersonaThese findings are important from the point of view of children and adolescents’ developing sense of influence over various life events. Getting involved in situations that may potentially bring various benefits can be conducive to developing an internal locus of control. Conversely, avoiding uncertain situations and withdrawing from the risk associated with making decisions in new and ambiguous circumstances may result in the perpetuation of a sense of lack of influence on what is happening and may incite young people to attribute the causes of events to factors that are beyond their control, such as bad luck or unfavourable conditions.Limura and Taku  found, i1.What are the differences in personality trait configurations between primary school girls and boys?2.What are the differences in locus of control of success and failure between primary school girls and boys?3.What is the relationship between personality traits and locus of control of success and failure in primary school sixth grade students?The variables analysed in the present article play an important role in the contemporary psychological discussion on the possibility of predicting young people’s educational achievements ,92,93 anIn order to answer these research questions, we formulated three hypotheses:Hypothesis 1 (H1).Girls are more likely than boys to have higher levels of Openness to Experience, Neuroticism, and Conscientiousness.Hypothesis 2 (H2).Girls are more likely than boys to have an external locus of control of success and failure.Hypothesis 3 (H3).In the whole group, Extraversion, Openness to Experience, Conscientiousness, and Agreeableness are associated with internal locus of control of successes and failures. Neuroticism is associated with external locus of control of successes and failures. It was presumed that gender is a moderator of relationships between personality traits and locus of control.Research on differences in personality traits and locus of control between boys and girls is sometimes inconsistent. Given these previous findings, we assumed that the girls and boys participating in the present study would differ in personality traits and locus of control. In light of the research, we also assumed different relationships between personality traits and locus of control as different personality traits may have different influence on the locus of control. Some traits promote internal, while others promote external locus of control in adolescents ,79,96,97The sample consisted of primary school sixth graders from the city of Lublin, Poland. A total of 455 students took part in the study, including 232 girls and 223 boys, min 12 and max 13 years old. The mean age of the respondents was M = 12.43, and standard deviation was SD = 0.50. Surveys were conducted in four primary schools in Lublin with paper–pencil method by authors of this article. Schools were selected randomly from the list of public schools from the website of the Lublin’s Board of Education. Non-public schools were not taken into consideration. Questionnaires were completed in groups during one meeting with each class. In total, students from 29 classes were examined. The study procedure complied with ethical principles regarding confidentiality, anonymity, and voluntary participation. Consent had been obtained from school principals and parents, and school psychologists/counsellors had been consulted before the survey was conducted. The participants were informed about the scientific purpose of the survey and that they had the right to withdraw from participation at any time. The students filled out a personal data sheet, providing their age and gender details, and two self-report questionnaires: the picture-based personality survey for children (PBPS-C) by Maćkiewicz and Cieciuch ,99 and tThe Big Five personality traits were measured using the PBPS-C by Maćkiewicz and Cieciuch . It is wThe locus of control variable was measured using the LOCQ by Krasowicz and Kurzyp-Wojnarska , a PolisThere are two versions of the LOCQ: one for girls and one for boys. They only differ in the grammatical form of the questions (the Polish language has gendered verb and adjective forms); the content of the questions is the same. After reading an item, the respondent chooses one of two alternatives (a or b), the one that best describes his/her own locus of control in the situation depicted by the item. Cronbach’s alpha reliability coefficients for the individual scales are: α = 0.40 (success), α = 0.54 (failure), and α = 0.62 . Despite the low values of the coefficients, we decided to use the LOCQ in the survey because at the time, no other tests for measuring locus of control of success and failure in adolescents aged 12–13 years were available in Polish.The global score is the sum of the scores obtained on the success and failure subscales and is a measure of a generalized locus of control, not differentiated into locus of control in situations of success and failure. It provides information on a person’s generalized tendency to attribute responsibility for various events to internal or external factors. Subscale scores give a more detailed picture of the typical ways a person interprets the causes of events related to successes and failures.t-test of significance of differences was used, and the effect size was measured using Hedge’s g coefficient. Correlation analysis was performed using Pearson’s r, and a regression analysis was carried out in which personality traits were predictors, and locus of control in situations of successes and failures were dependent variables. Moreover, the analysis of interaction effect of gender on relationships between personality traits and locus of control was carried out. Before Student’s t-test was applied, homogeneity of variance of data obtained for the first and second research question had been tested using Levene’s F-test. The F-test was statistically non-significant.The data obtained in the survey were interpreted quantitatively on the basis of raw scores for both the LOCQ and the PBPS-C. Statistical analyses were performed using SPSS v.25. First, normal distribution of the scores was tested using the Kolmogorov–Smirnov test. The distribution of the variables did not deviate from the normal distribution. In further analyses, a parametric Student’s The analyses of the results are presented in the same order as the research questions, i.e., first, the significances of differences are given separately for girls’ and boys’ scores; then, the results of the analysis of correlations between the investigated variables for the entire sample are presented; and finally, the results of the regression analysis, with personality traits as predictors and locus of control as the dependent variable, are shown.The results of comparisons of significance of differences between personality trait scores in the samples of girls and boys are shown in The data indicates that girls differ statistically significantly from boys in terms of Extraversion and Neuroticism, but the effect size for both these personality traits is small. Girls are more prone to anxiety than boys, while boys are more open to making new friends and spending time in the company of other people. There are no statistically significant differences in locus of control of success and failure and the generalized locus of control between the boys and the girls surveyed. Both boys’ and girls’ locus of control scores are in the average range. All the correlations between the participants’ PBPS-C and LOCQ scores are statistically significant. Extraversion correlates moderately positively with locus of control of success, locus of control of failure, and generalized locus of control. Negative weak correlations are observed between Neuroticism and the three types of locus of control. Openness to Experience correlates moderately with locus of control of success and generalized locus control, and there is also a weak relationship between Openness to Experience and locus of control of failure. Conscientiousness correlates moderately with locus of control of success and generalized locus of control, and weakly with locus of control of failure. The last personality trait, Agreeableness, correlates weakly with locus of control of success and locus of control of failure, and moderately with generalized locus of control. F  = 8.78; p < 0.001; however, introduction of gender to the model did not increase percentage of explained variance of locus of control (1%).Data presented in F  = 17.86, p < 0.001) and locus of control of failure  = 17.87, p < 0.001). The regression coefficients show that locus of control of success is associated positively with Extroversion, Openness to Experience, and Conscientiousness. Locus of control of failure, on the other hand, is associated positively with Extroversion, Openness to Experience, and Agreeableness, and negatively with Neuroticism. All the coefficients indicate that there is a significant but weak relationship between personality traits and locus of control of success and failure. The model tested explains a low percentage of variance in each personality trait (R2 = 17%). The values of test of variance inflation factor (VIF) coefficient for all personality traits are less than 2, which means that there is low relationships between personality traits.There are no systematic studies on the associations between personality traits and locus of control in students entering adolescence, especially those who experience changes in educational arrangements, for instance, due to an educational reform ,109. GivIn the first hypothesis (H1), we assumed that girls were more likely than boys to have higher levels of Openness to Experience, Neuroticism, and Conscientiousness. The results partially confirm this hypothesis. Costa and McCrae ,28 have Additional analyses conducted in reference to the second hypothesis, in which we assumed that girls are more likely than boys to have an external locus of control of success and failure, demonstrated that there were no differences between girls and boys in this trait. This observation is inconsistent with the results reported by Kulas  who showIn the third hypothesis, we assumed for the whole group, Extraversion, Openness to Experience, Conscientiousness, and Agreeableness are associated with internal locus of control of successes and failures. Neuroticism is associated with external locus of control of successes and failures. Additionally, we presumed that gender is a moderator of relationships between personality traits and locus of control. The correlation analysis demonstrated that Extraversion was moderately positively correlated with an internal locus of control of successes and failures and generalized control in all the students surveyed, as was expected. Extraverted behaviours associated with the readiness to form interpersonal relationships and derive satisfaction from them contribute to the sense of agency and internal control over the events in which one participates. It has been pointed out that adolescence is a period of intensive development of social relationships , and ExtWe found that Openness to Experience correlated moderately with locus of control of success and generalized locus control, and weakly, but significantly, with locus of control of failure. Openness to Experience has been demonstrated to promote the use of diverse problem-solving strategies and in-depth analysis of complex causes of events, human intentions, and feelings. The ability to change a strategy of action when it turns out to be ineffective increases the likelihood of success and may secondarily contribute to the development of an internal locus of control of success ,124. TheIn our study, Conscientiousness was found to correlate moderately with locus of control of success and generalized locus of control and weakly with locus of control of failure. Conscientiousness, which involves the ability to work hard and continue one’s efforts with patience, has been demonstrated to play an important role in the successful completion of compulsory education ,126. SchIt was expected that Agreeableness would correlate with an internal locus of control. The results indicated that Agreeableness, correlated weakly with locus of control of success and locus of control of failure, and moderately with a generalized locus of control. In light of the research, Agreeableness is broadly considered a key facet of adjustment, motivation to maintain positive interpersonal relations, mental health, and socioemotional competence . In a loThe regression model with personality traits as predictors and locus of control as the explained variable was well fitted to the data and showed that Extraversion and Conscientiousness were important predictors of locus of control of success. On the other hand, locus of control of failure was significantly predicted by Extraversion, Openness to Experience, Agreeableness (a positive predictor), and Neuroticism (a negative predictor). This result is in line with the studies quoted above which indicate that the individual personality traits play a role in the achievement of important educational and non-educational goals, and thus the development of a locus of control in students. Development of an internal locus of control of success is most strongly affected by Extraversion and Conscientiousness. These traits have the greatest impact on the quality of life of young people in two ways: Extraversion is conducive to deriving satisfaction from peer relationships, and Conscientiousness—from educational success. Both these areas are important aspects of young people’s everyday functioning ,131. In The focus of this present study was on the analysis of personality traits and locus of control in students entering the period of early adolescence at a socially important moment of an introduction of a major educational reform in Poland.The present results may be influenced by factors related to the introduction of the education reform of 2016 and the specific character of Polish educational policy and its social reception by young people. Nevertheless, we believe that they provide universal scientific insights into the psychosocial functioning of early adolescents experiencing changes in the education system. The present analyses have practical implications, as they can help specialists in education and psychologists understand the possible causes of young people’s adjustment difficulties or difficulties in meeting school requirements. They can also help students discover new ways of achieving important goals while fully using their personality dispositions and provide support in planning educational programmes aimed at teaching students responsibility and encouraging active participation in everyday educational and non-educational activities. Students who experience stress and are lost in a new educational situation may feel they have no control over what they experience, which may lead to the development of an external locus of control .The present results can be used to plan measures and interventions aimed at supporting their adjustment to the new school environment and requirements. Education reforms are put in place all over Europe with varied success, as described in the literature ,140,141.An important limitation of our study is the fact that the participants were surveyed in only one city in eastern Poland. Therefore, the findings cannot be generalized to the whole population of students experiencing the changes imposed by the education reform in Poland. No detailed information was collected on the socioeconomic status of the students’ families and variables such as parental education or monthly income. These variables should be controlled for in a future study. Likewise, we did not control for parent–children relations, the current students’ achievement level, their sociometric status in the classroom, or their need for psychological support. These factors are important in successful adaptation to new environment and further educational outcomes. Results presented in this study pertain to two variables which are important in predicting academic success but are not the only ones underlying the quality of this process. In addition to taking into account the abovementioned variables in future research, it would also be interesting to examine students’ self-descriptions of their personality traits and compare them with assessments made by their parents and teachers. Studies of this type are very popular because they give a fuller picture of the personality functioning of young people seen from various perspectives ,107. Wit


Orthonairovirus . CCHFV causes a potentially severe, or even fatal, human disease, and it is widely distributed in Africa, Asia, eastern Europe and, more recently, in South-western Europe. Until a few years ago, no cases of Crimean-Congo hemorrhagic fever (CCHF) had been reported in western Europe, with the exception of several travel-associated cases. In 2010, the CCHFV was reported for the first time in South-western Europe when viral RNA was obtained from Hyalomma lusitanicum ticks collected from deer in Cáceres (Spain). Migratory birds from Africa harboring CCHFV-infected ticks and flying to Spain appear to have contributed to the establishment of the virus  in this country. In addition, the recent findings in a patient and in ticks from deer and wild boar of viral sequences similar to those from eastern Europe , raise the possibility of the introduction of CCHFV into Spain through the animal trade, although the arrival by bird routes cannot be ruled out . The seropositive rates of animals detected in regions of South-western Spain suggest an established cycle of tick-host-tick in certain areas, and the segment reassortment detected in the sequenced virus from one patient evidences a high ability to adaptation of the virus. Different ixodid tick genera can be vectors and reservoirs of the virus, although Hyalomma spp. are particularly relevant for its maintenance. This tick genus is common in Mediterranean region but it is currently spreading to new areas, partly due to the climate change and movement of livestock or wild animals. Although to a lesser extent, travels with our pets (and their ticks) may be also a factor to be considered. As a consequence, the virus is expanding from the Balkan region to Central Europe and, more recently, to Western Europe where different genotypes are circulating. Thus, seven human cases confirmed by molecular methods have been reported in Spain from 2016 to August 2020, three of them with a fatal outcome. A One Health approach is essential for the surveillance of fauna and vector populations to assess the risk for humans and animals. We discuss the risk of CCHFV causing epidemic outbreaks in Western Europe.Crimean-Congo hemorrhagic fever virus (CCHFV) is an arthropod-borne virus (arbovirus), mainly transmitted by ticks, belonging to the genus  Crimean Congo Hemorrhagic Fever (CCHF) is the most widely distributed tick-borne viral disease in the world , and the second one (after dengue) among viral hemorrhagic fevers ,2,3,4. TOrthonairovirus , within the realm Riboviria (a new megataxonomic taxon rank), according to the most recent classification based on the advances in viral genomic and metagenomic comparison analysis . Based on these data, the reassortant S segment was similar to genotype IV and related to a Nigeria strain that differed from the Asia strains of this genotype. Other authors [ authors  had alre


The equilibrium adsorption had an alignment with Langmuir isotherms, while the kinetics were most accurately modelled using pseudo- first-order and second order models according to the regression analysis. Thermodynamic parameters such as ΔG°, ΔH° and ΔS° were calculated and the adsorption process was determined to be exothermic and spontaneous.The remarkable adsorption capacity of graphene-derived materials has prompted their examination in composite materials suitable for deployment in treatment of contaminated waters. In this study, crosslinked calcium alginate–graphene oxide beads were prepared and activated by exposure to pH 4 by using 0.1M HCl. The activated beads were investigated as novel adsorbents for the removal of organic pollutants  with a range of physicochemical properties. The effects of initial pollutant concentration, temperature, pH, and adsorbent dose were investigated, and kinetic models were examined for fit to the data. The maximum adsorption capacities q Micropollutants such as pharmaceuticals, personal care products, surfactants and pesticides , as well2-receptor antagonist used for treating gastroesophageal reflux disease and Zollinger–Ellison syndrome [Methylene blue (MB) is a heterocyclic aromatic chemical dye used in textile, paper and cosmetic industries . It is nsyndrome . Famotidsyndrome ,14,15. Dsyndrome ,17. Diclsyndrome . Diclofesyndrome , and it syndrome .The removal of micropollutants and synthetic dyes using membrane-based technologies, ozonation, photolysis, photocatalysis ,22,23, e2+, giving good mechanical properties. Acid-activation of the beads provides an enhancement in the surface, area including micro- and mesopores [Graphene-based materials have received increasing attention as potential candidates for composite preparation due to their high specific surface area and adsorption capacity. Graphene oxide (GO) is a two-dimensional complex of carbon atoms decorated with a multitude of oxygen-containing functional groups densely packed in a honeycomb framework . GO has esopores ,41. In fesopores .In this work, the acid-activated (0.1 M HCl pH 4) adsorption capacity of calcium alginate graphene oxide beads was evaluated as novel adsorbents for MB, FMTD and DFC removal. In addition, the influence of initial pollutant concentration, adsorbent dose, adsorption temperature and pH on adsorption capacity was investigated, along with an examination of the kinetic and thermodynamic modelling of the reactions.2SO4, 95–98%) and hydrogen peroxide  was purchased from Merck Millipore. Hydrochloric acid (37%) was provided by Acros Organics Dublin, Ireland.Graphite flakes (GF) were purchased from Asbury Carbons. Diclofenac sodium , famotidine (FMTC), methylene blue (MB) and alginic acid sodium salt (Na-Alg) were purchased from Sigma Aldrich. The structure of analytes is given in 2SO4 to be mixed with H2O2 in order to produce GO particles. To establish the concentration, 1 g of GO suspension was placed in a dried, weighed beaker, dried overnight at 60 °C and weighed again, and the concentration was then adjusted to 1% GO in DI water on a dry mass basis. The details of the method and Ca-Alg2/GO bead preparation as well as dry and wet images of Ca-Alg and Ca-Alg/GO beads are given in GO was prepared according to a modified version of Hummer’s method . In thisBeads for activation were placed into 600 mL beakers of DI water adjusted to pH 4 using 0.1M HCl, which were agitated for 3 h. Afterwards, the beads were collected, rinsed three times with 300 mL of DI water and stored in a closed bottle at RT.The surface morphological structure of the beads was examined using scanning electron microscopy (SEM) analysis using a Hitachi 3400 SEM, following gold coating. Functional groups of the GO sheets as well as of the Ca-Alg2 and Ca-Alg2/GO beads were identified by Fourier transform infrared spectroscopy . In addi2/GO5, Ca-Alg2/GO10 or Ca-Alg2/GO20 dried beads) over 24 h on a shaker table operating at 125 rpm at room temperature (22 °C), unless otherwise specified. Equilibrium for all pollutants was established by 24 h. In total, 75 mL of pollutant solution at a concentration of 10 mg L−1 was added in each case, with a pH of 7 for MB and FMTD and a pH of 2 for DFC, unless otherwise specified. The pollutant concentration was determined using a UV-VIS spectrophotometer (Varian) at a wavelength of 660, 286 and 274 nm for MB, FMTD and DFC, respectively. Experiments were carried out in triplicate and the average values reported along with the error bars represent the standard deviation.All adsorption measurements were carried out in 250 mL flasks with 0.05 g of adsorbent ) was calculating using Equation (1):0 (mg L−1) is the initial pollutant concentration, Ceq (mg L−1) the equilibrium pollutant concentration, V (L) the solution volume and mads (g) the adsorbent mass.The initial pollutant concentrations tested were 10, 100, 500 and 1000 mgLThe effect of the adsorbent dose was studied using 0.01, 0.025, 0.05 and 0.1 g of Ca-Alg2, Ca-Alg2/GO5, Ca-Alg2/GO10 or Ca-Alg2/GO20 dried beads.The adsorption was performed at pH 7, 9, 10 and 11 for MB and FMTD whereas the adsorption for DFC was at pH 2, 3.5, 5 and 7.The influence of the temperature was studied by performing the adsorption process at 4, 22 and 30 °C.d is calculated using Equation (2):0 (mg L−1) is the initial concentration of the solution and Ceq (mg L−1) the equilibrium concentration in solution. A plot of ln(Kd) versus 1/T gives a straight line where the enthalpy change ΔH° (J·mol−1) and the entropy change ΔS° (J·K−1·mol−1) can be calculated using (Equation (3)):−1·K−1) and T (K) is the temperature of the solution during the adsorption process. The standard Gibbs free energy change can be obtained from Equation (4):The thermodynamic parameters of adsorption were determined at 4, 22 and 30 °C in order to evaluate the feasibility and the spontaneous nature of the adsorption. The adsorption distribution coefficient Kt (mg g−1) at time t was calculated using Equation (5):0 (mgL−1) is the initial concentration, Ct (mgL−1) the concentration at time t, V (L) the volume of pollutant solution and mads (g) the adsorbent mass.Kinetic parameters were studied using 0.05 g of Ca-Alg2, Ca-Alg2/GO5, Ca-Alg2/GO10 or Ca-Alg2/GO20 dried beads. The three most common models were examined as to their fit to the experimental data . The ads1 (min−1) is the Lagergren rate constant, qeq (mg g−1) is the maximum adsorbed amount at equilibrium, and qt (mg g−1) is the amount of adsorption at time t (min). The values of k1 and qeq were determined from the intercept and the slope of a plot of ln(qeq − qt) versus t.The linearized integral form of the pseudo-first-order Lagergren equation is given by Equation (6):2 (g·mg−1·min−1) is the pseudo second-order rate constant of adsorption. The parameters k2 and qeq were determined from the intercept and the slope of a plot of t/qt versus t.The linearized integral form of the pseudo-second-order model is shown in Equation (7):ip (mg g−1·min−0.5) is an intraparticle diffusion rate constant and Cip (mg g−1) is related to the thickness of the diffusion boundary layer. These parameters were obtained from a plot of qt versus t1/2.The intraparticle diffusion model is represented in Equation (8):max (mg g−1) is the maximum adsorption capacity corresponding to complete monolayer coverage, Ceq (mgL−1) is the concentration at equilibrium in the solution and kL (Lg−1) is a constant related to adsorption capacity and the energy of adsorption.The Langmuir model and the Freundlich model were examined for their utility in describing the adsorption process. The Langmuir equation is detailed in Equation (9): (9)qeq= F (L·g−1) and n (-) are the Freundlich constants, indicating the adsorption capacity and the adsorption intensity, respectively. In order to determine the Langmuir and Freundlich constants, Excel Solver was used to fit the adsorption isotherm models with the experimental data. The sum of squared differences between experimental qeq and calculated qeq was minimized by changing the constants of the models with the solver to find the best non-linear regression.The Freundlich equation is an empirical model based on the adsorption on a heterogeneous surface , and is v/v. The desorption process was carried out in 250 mL conical flasks with 75 mL of desorption solution at RT. The conical flasks were agitated for 24 h at 125 rpm. Then, the final concentration in solution was determined using UV-VIS and the percentage desorption was calculated using Equation (11):eq,d (mg g−1) is the adsorbed amount at equilibrium after 24 h of desorption, and qeq,a (mg g−1) is the adsorbed amount at equilibrium after 24 h of adsorption.After the concentration at equilibrium was determined, the beads were removed from the solution and were washed three times with DI water. The desorption of pollutants from the beads was examined using three different desorption systems, 0.1 M HCl, 1 M NaCl and ethanol 1% SEM analysis was carried out in order to characterize the morphological structure of the beads, and the results are given The SEM images show that increased graphene oxide concentration altered the morphological structure of the beads by providing increased porosity and roughness. Due to that increase, the beads had a greater surface available for interactions between adsorbate and adsorbent. The Ca-Alg2/GO20 was typically carbonaceous with similarities to the structure of activated carbon. The FTIR spectrum of GO sheets, Ca-Alg2 and Ca-Alg2/GO beads is given in S4. No significant difference was observed between Ca-Alg2 and Ca-Alg2/GO beads, as the functional groups of the alginate overlap with GO.t was examined by taking samples over 24 h. The average of the results obtained for the adsorption of MB, FMTD and DFC is given in The effect of the contact time on q−1 to 9.18 ± 0.08 and 10.63 ± 0.17 mg g−1, respectively, in comparison to Ca-Alg2 (control), with the p values of 0.034 and 0.023. For the adsorption of FMTD, regardless the level of GO, Ca-Alg2/GO composites showed a significant improvement (p < 0.05) in adsorbate capacity from 2.78 ± 0.34 mg g−1 to a maximum of 7.95 ± 0.54 mg g−1. On the other hand, for the adsorption of DFC, no significant enhancements were seen (high level of error bars), which is attributed to the molecular limitations of DFC.The adsorption gradually increased with the contact time and slowed down progressively to reach an equilibrium after 24 h. An increased adsorbate capacity was achieved with an increased concentration of GO in the composites. Ca-Alg2/GO20 beads were the most efficient for the adsorption of each compound, as expected. For the adsorption of MB, Ca-Alg2/GO10 and Ca-Alg2/GO20 beads caused a significant improvement in the adsorbate capacity by increasing it from 6.91 ± 0.83 mg geq) and the percentage removal are shown in The effects of the different concentrations of methylene blue, famotidine and diclofenac on the adsorption density (qeq) were achieved with an increased GO level in the composites when the initial concentration of the pollutants  was higher. For the highest initial pollutant concentrations, which were 1000, 250 and 20 mgL−1 for MB, FMTD and DFC, respectively, all Ca-Alg2/GO beads (regardless of the GO level) showed a significant increase in qeq value (p < 0.05) for DFC, whereas Ca-Alg2/GO10 and Ca-Alg2/GO20 beads caused a significant improvement in the qeq value of MB and FMTD. The greatest enhancements were achieved with Ca-Alg2/GO20 beads, and were from 856.4 ± 16.8 to 1036.2 ± 30.7mg g−1 (p: 0.022) for MB, from 18.6 ± 1.9 to 32.2 ± 0.8 mg g−1 (p: 0.004) for FMTD and from 14.1 ± 0.329 to 20.4 ± 0.427 mg g−1 (p: 0.0001) for DFC at the highest pollutant concentrations.Higher adsorbed amounts of pollutant at equilibrium  of four different types of beads and the percentages of adsorption of MB, FMTD and DFC on Ca-Alg2/GO20 beads are given in The effects of the adsorbent dose on adsorption density and adsorption percentage were observed by using four different masses of beads varying from 0.01 to 1.0. The adsorption densities (qp < 0.05) when using Ca-Alg2/GO20 beads from 52.9 ± 1.7 to 76 ± 0.4% for MB, from 12.2 ± 0.9 to 58.2 ± 0.5% for FMTD and from 39.7 ± 4.1 to 96.1 ± 1.7% for DFC, due to the increase in adsorbent dose from 0.1 to 1.0. On the contrary, the adsorption density decreased significantly (p < 0.05) from 38.9 ± 1.6 to 5.7 ± 0.1 mg g−1 for MB, from 9.2 ± 1.3 to 4.3 ± 0. mg g−1 for FMTD and from 29.5 ± 2.5 to 7.2 ± 0.1 mg g−1 for DFC due to the increase in adsorbent dose from 0.1 to 1.0. The reduction in the adsorption density was attributed to a lower quantity adsorbed per unit weight of the adsorbent, causing the presence of unsaturated adsorption sites [A decreased adsorption density has been observed with the increased adsorbent dose regardless of the type of beads and of pollutant. On the other hand, adsorption percentage increased significantly . The averages of the results obtained for the adsorption of MB, FMTD and DFC are shown in the figures below A–C.a values of the analytes and Ca-Alg2/GO20 beads. At pH 10, FMTD is in the neutral form, since its pKa value is 6.98 [a = 4.3; 6.6; 9.8 all acid groups and 50% of GO phenolic groups will be ionized) [The adsorption percentage of MB at pH 7 was 62.9 ± 0.75%, which slightly increased up to 68.6 ± 0.7% at pH 10 and attained a maximum value A when Ca is 6.98 , and it ionized) , enhancia = 4.0), alginate (pKa mannuronic = 3.38 and guluronic acid = 3.65 [a 3.65), and that to GO is 200:1  and GO.00:1 see . These rAdsorption studies were performed across three temperatures ranging from 4 to 30 °C . The averages of the results obtained for the adsorption of MB, FMTD and DFC are shown in The coldest temperature (4 °C) showed the highest adsorption percentages of 65.3 ± 0.9% A, 53.3 ±d, enthalpy change ΔH°, entropy change ΔS° and Gibbs free energy change ΔG° were calculated using Equations (2)–(4). The results are given in the Thermodynamic studies were conducted based on the feasibility and the spontaneous nature of adsorption . The disp < 0.05) in the distribution coefficient (Kd) was observed in all cases when the adsorption temperature was increased from 4 to 30 °C, indicating better adsorption at lower temperatures. For example, the Kd value for the adsorption of MB, FMTD and DFC on Ca-Alg2/GO20 beads decreased from 1.88 to 1.60, 1.14 to 0.63 and 6.88 to 0.93, respectively, as a result of increasing the temperature from 4 to 30 °C. Furthermore, negative enthalpy (ΔH°) and entropy (ΔS°) changes were seen in the adsorption of MB, FMTD and DFC on Ca-Alg2 and Ca-Alg2/GO beads , and thermodynamic studies show that the physisorption is spontaneous. The pseudo-second-order model is the best fit for the experimental data concerning the kinetics of adsorption for methylene blue and famotidine; however, the Lagergren pseudo-first order model is better suited to diclofenac. Furthermore, each compound follows the Langmuir model for isotherm adsorption, with a maximum adsorption capacity of 1334, 35.50 and 36.35 mg·g−1 for methylene blue, famotidine and diclofenac, respectively. It should be noted that the adsorption capacity of MB onto calcium alginate graphene oxide beads, particularly Ca-Alg2/GO20 composites, was found to be superior in comparison to other adsorbents, ranging from commercial activated carbon adsorption capacity (980.3 mg·g−1) to bioadsorbents adsorption capacity, such as modified biomass of baker’s yeast (869.6 mg·g−1), and many other natural adsorbents, such as biomass and coal-derived activate carbon, as reviewed in detail by [3O4- graphene at mesoporous SiO2), wherein the adsorption capacity of this graphene-derived nanocomposite was reported to be 178.49 mg·g−1 in terms of MB removal [−1 when GO was incorporated with sodium alginate to produce aero gel beads. Therefore, it can be concluded that graphene oxide calcium alginate composite is a superabsorbent useful for MB removal from water, in addition to being superior to the previously researched compounds [The SEM analysis showed that an increase in graphene oxide modified the morphological structure of the beads. Indeed, they become more porous and rougher with a higher surface available for the interactions between adsorbate and adsorbent. As expected, during the adsorption process, Ca-Alg2/GO20 beads present the best adsorption for each compound. The effect of initial concentration, adsorbent dose, pH and temperature all play an important role in the adsorption. The results show that a higher concentration of pharmaceuticals increases the force of the diffusion of the drug adsorbed by the beads. With a lower concentration of beads, the adsorbed amount at equilibrium qetail by . In addi removal . Furtherompounds ,63. FurtThese beads appear to be an efficient adsorbent for dyes and pharmaceuticals, particularly for methylene blue. This novel technology could be applied as a polishing step in water treatment in order to reduce the concentration of these micropollutants, as well as of the synthetic dyes that negatively impact the environment, human health and aquatic life. Methylene blue is widely used a model pollutant in adsorption studies. It is interesting to note that while the performance of the beads assessed in this study is excellent for MB, it is less than ideal for FMTD and DFC. This calls into question the validity of the common approach of using a single-component pollutant for novel adsorbent testing. However, the treatment of an MB, FMTD and DFC mixture via Alg2/GO beads might have an influence on the adsorption/desorption capacities. Therefore, conducting an experimental study targeting the removal of mixed pollutants via Alg2/GO beads is suggested as a future direction.


Marble is currently a commonly used material in the building industry, and environmental degradation is an inevitable consequence of its use. Marble waste occurs during the exploitation of deposits using shooting technologies. The obtained elements most mainly often have an irregular geometry and small dimensions, which excludes their use in the stone industry. There is no systematic way of disposing of these massive mounds of waste, which results in the occurrence of landfills and environmental pollution. To mitigate this problem, an effort was made to incorporate waste marble powder into clay bricks. Different percentage proportions of marble powder were considered as a partial substitute for clay, i.e., 5–30%. A total of 105 samples were prepared in order to assess the performance of the prepared marble clay bricks, i.e., their water absorption, bulk density, apparent porosity, salt resistance, and compressive strength. The obtained bricks were 1.3–19.9% lighter than conventional bricks. The bricks with the addition of 5–20% of marble powder had an adequate compressive strength with regards to the values required by international standards. Their compressive strength and bulk density decreased, while their water absorption capacity and porosity improved with an increased content of marble powder. The obtained empirical equations showed good agreement with the experimental results. The use of waste marble powder in the construction industry not only lowers project costs, but also reduces the likelihood of soil erosion and water contamination. This can be seen to be a crucial factor for economic growth in agricultural production. In 2019, the global demand for marble was estimated at USD 55,420 million, and it is projected to hit USD 68,790 million by the end of 2026. This is an annual increase of 3.1% [Marble is a crystalline metamorphic rock that can be formed into different shapes and sizes for flooring, monumental and decorative purposes. According to a survey, the demand for marble stone worldwide hit 816 million mMany studies have used various wastes as additives in the manufacturing of clay bricks in order to test their various properties. The use of waste materials for construction purposes can be helpful in reducing the risk of shortages in natural resources and for improving the environment ,9,10. ThFernando P.R. compared the physical and chemical properties of rice husk ash bricks with traditional bricks and found that the addition of 5% of rice husk ash improves the compressive strength and water absorption properties of the bricks . Rao B.JKadir A.A. and Sarani N.A. assessed numerous waste materials, such as fly ash, rubber, limestone, wood dust, and sludge. They noticed that such waste had a beneficial effect on the manufactured lightweight bricks, and also enhanced the thermal conductivity of fired clay bricks . Zhang LOorkalan A. et al. used different proportions of waste products of wood ash, ceramic powder, and marble powder in clay bricks. Compressive strength and water absorption tests were conducted. It was concluded that the raw materials were useful and increased the brick’s compressive strength and durability . NgayakaIncorporating glass waste into fired clay bricks is an excellent way to develop eco-friendly bricks and other enhanced materials for the construction industry. Xin Y. et al. manufactured fired clay bricks with a partial addition of glass waste. They discovered that as the glass content rose and the particle size decreased, the compressive strength of the fired clay bricks improved significantly . Mobili It has been proven that some natural fibers can improve the strength properties of composite materials and also be used to produce cheap bricks from fired clay . Kadir AAn experimental study was conducted on marble waste (in different proportions) as an additive to bricks. It was proven that the marble waste had a good impact on the chemical, physical, and mechanical strength of the resultant bricks ,28,29. CMany researchers have used marble waste and brick waste in different types of concrete and cement mortar. It has been determined that concrete made with the addition of waste marble powder can be ecological. This is consistent with sustainable development strategies, which are now a global trend ,36. AccoThe Earth’s ecosystems are being destroyed, and there is a continuing increase in water pollution, bad air quality, and ground contamination. Pollution is not only a health issue, but also a major obstacle for sustainability. To minimize this challenge, researchers and engineers need to be more focused on the effective use of waste materials in the construction industry. The use of waste materials is one of the most critical steps of sustainability, because it helps to minimize the impact of environmental degradation, save renewable resources, lower the overall cost of building projects, and bring economic value to waste materials. It is more and more clear that advances in the production of waste derived materials benefit society. Marble and granite factories generate a large volume of wastes, including sludge and other residues, which pose a serious threat to the environment by polluting soil and water. In this paper, industrial waste in the form of marble powder was used as the base material for producing bricks. These bricks are inexpensive, offer good compressive strength, and are lightweight. The current research project aims to identify the waste-related commodity arrangements and treatment scenarios that are suitable for the production of marble powder-based slurry for sustainable bricks. This study assesses the properties of the final product after incorporating waste marble powder. As a result of this study, the use of waste marble powder in the construction industry might lead to a sustainable and environmentally friendly material with better properties. The key points of this study were to examine the effects of waste marble powder on the different properties of sustainable marble clay bricks, i.e., water absorption ability, bulk density, apparent porosity, efflorescence, and compressive strength. When optimizing the composition of waste marble bricks, it is possible to minimize the risk of environmental contamination by reducing the amount of marble waste. The use of waste marble powder would be advantageous due to the use of wastes, as well as for obtaining good strength and low-cost bricks beneficial for sustainable construction.The materials used in this research were marble powder, which was collected from a local company in Peshawar, Pakistan, and clay from a kiln in the district of Peshawar, where the bricks were prepared. The type of soil in this region is clay loam containing 30.9% sand, 37.8% silt and 31.3% clay . The res3 for SEM-EDX. X-ray photons were examined spectroscopically in order to obtain basic information about the sample. Various images of regions were taken throughout the course of the EDX test, and the associated peaks for each element are displayed in To check the elements of marble powder, the energy dispersive X-ray test (EDX) was conducted. The contact area from which the X-rays were released was within the spectrum of 1 μmThe water absorption tests were carried out on each of the groups of the analyzed brick samples. Three specimens of bricks from each mix group were tested. The ASTM C67-07 standard, 2007  was follThe efflorescence test was performed on three brick samples taken from each mix proportion group, according to the specifications of the ASTM C67-07 standard, 2007 . Thin fl3).The bulk density test was conducted to find the tapped bulk density or bulk volume of the marble clay bricks according to the ASTM C134-95 standard . The appThis test was performed according to the ASTM C67-07  and ASTM2 per minute until failure occurred. A total of 3 specimens were tested for each proportion group, and the average of the obtained results was taken as the final compressive strength. The compression test was performed in a laboratory at a temperature of 26 ± 1 °C and a humidity of 48 ± 2%.To determine the compressive strength of the marble clay bricks, a compression test was performed according to the ASTM C67/C67M standard  by using2) value is equal to 98%, confirming a good compliance of the obtained empirical results with the experimental data.The results of the water absorption test are given in From the conducted detailed observations and results, a slight efflorescence was seen, i.e., about 10–15% of the exposed areas of the B5 and B6 bricks were covered with a thin deposit of salt, as shown in 2) value is equal to 90%, confirming a good compliance of the obtained empirical results with the experimental data.The results of the bulk density of the clay bricks with the addition of waste marble powder are shown in 2) being released during the calcination process of the calcium carbonate (CaCO3). 2) is equal to 94%, confirming a good compliance of the obtained empirical results with the experimental data.The obtained porosity results (in %) are presented in 2) is equal to 95%, which confirms the good compliance of the obtained empirical results with the experimental data.The results of the compression test indicate that the compressive strength decreased with an increase in the marble powder content in the bricks. The highest compressive strength of 20.4 MPa was obtained by reference sample “A”, which contained a 0% marble powder content. The specimens of group “B1”, with a 5% marble powder content, achieved a compressive strength of 12.2 MPa. In turn, groups B2, B3, B4, B5, and B6, with a 10%, 15%, 20%, 25%, and 30% marble powder content, achieved a compressive strength of 9.6 MPa, 7.8 MPa, 6.5 MPa, 5.9 MPa, and 4.5 MPa, respectively. The compressive strength results are given in To evaluate the characteristics of the marble powder bricks, i.e., water absorption, bulk density, porosity, and compressive strength, the experimental results and empirical results were compared, as shown in Marble clay sustainable bricks can be used both in the exteriors and interiors of buildings. In RCC frame structures, marble powder bricks may be used in partition walls due to the fact that such walls do not need to withstand too excessive loads. Depending on the climatic conditions, in some countries, bricks containing waste marble powder can be used for innovative home flooring and for street surface elements. These bricks are easy to recycle, which means they reduce the cost of making new construction materials for new buildings and leave minimal debris behind, in turn reducing the chance of potential pollution. Such bricks can be used in the construction of pavements for pedestrians. According to the results of this work, adding waste marble powder to bricks reduces their compressive strength, which enables them to be used in emergency situations where high strength is not necessary, e.g., in infrastructure facilities such as shelters and temporary hospitals, rooms for construction site workers, or elements of small architecture. For such purposes, a marble clay sustainable brick with a marble powder content of 5% to 20% is suggested for use as a sustainable building material.The price of the raw materials, such as marble powder and clay soil, was analyzed. The cost of transportation is not included in this cost analysis, since it differs regarding the place of production. It was found that the addition of waste marble powder in the manufacturing of bricks is cost effective. The use of waste marble powder in bricks not only reduces the cost of their production, it also contributes to the obtaining of lighter elements, as well as improving their structural performance. The price of the raw materials was given by the different dealers of constructional materials: the marble powder was about USD 0.06 per kilogram, and the clay was about USD 0.09 per kilogram. Therefore, the marble powder was one third cheaper when compared to the clay that was used for the manufacturing of the bricks. Using waste marble powder as a partial substitute for clay reduces the content of the clay, and thus reduces the cost of the bricks. The price of the bricks was reduced by 1.6%, 3.2%, 4.7%, 6.3%, 7.9% and 9.5% with the addition of marble powder of 5%, 10%, 15%, 20%, 25% and 30%, respectively. The water absorption capacity of the bricks increased with an increase in the content of marble powder.In general, the addition of marble waste to bricks does not significantly affect the amount of salt efflorescence. However, a minor effect of efflorescence was observed when 25% and 30% of marble powder was used in the bricks. The effect of efflorescence was related to the porosity of the bricks, i.e., if the bricks are porous, the effect of efflorescence will be more visible.The bulk density of the bricks declined with a rise in the amount of marble powder, causing the porosity to increase and the weight of the bricks to decrease.The amount of marble powder in clay bricks influences their compressive strength, i.e., as the percentage of marble powder in clay bricks increases, the compressive strength decreases due to increased porosity.The marble powder bricks were lighter in weight than the reference clay bricks. The weight of the bricks decreased as the marble powder content increased. This drop in the weight of the brick samples can result in a large savings for the construction industry, i.e., a higher quantity of bricks and lower structural load.The conducted empirical analysis showed a great compatibility with the laboratory test results regarding the following properties of bricks, i.e., water absorption, bulk density, porosity and compressive strength.Marble clay bricks can be used in emergency situations where high strength is not needed, such as refugee camps, emergency hospitals during flooding and earthquakes, street flooring, and pavements. In such situations, marble clay sustainable bricks with a 5% to 20% marble powder content as are suggested for use as a sustainable construction material.Due to high porosity, the water absorption capacity of marble bricks increased. Therefore, because of this property, it is recommended that marble bricks be used for construction in such areas and countries where the moisture rate in air is relatively low or the bricks are protected against moisture.The use of waste marble powder as a partial replacement for clay in the manufacturing of bricks is cost efficient, as the cost of bricks decreases with the inclusion of marble powder, which has a direct influence on project costs. This study suggests using 5% to 20% waste marble powder as a clay substitute, which reduces the cost of bricks by 1.6% to 6.3%, respectively.Waste materials from marble stone are a major source of concern for stone factories and municipality managements. As a result, the use of waste marble powder as an additive for the production of bricks can improve the natural environment due to the recycling of this waste. For this purpose, the addition of marble powder in different proportions for the manufacturing of bricks was analyzed. The key findings of this study are as follows:


The objective of this critical review is to provide an overview of how emerging bioanalytical techniques are expanding our understanding of the complex physicochemical nature of virus interactions with host cell surfaces. Herein, selected model viruses representing both non-enveloped (simian virus 40 and human norovirus) and enveloped  viruses are highlighted. The technologies covered utilize a wide range of cell membrane mimics, from supported lipid bilayers (SLBs) containing a single purified host membrane component to SLBs derived from the plasma membrane of a target cell, which can be compared with live-cell experiments to better understand the role of individual interaction pairs in virus attachment and entry. These platforms are used to quantify binding strengths, residence times, diffusion characteristics, and binding kinetics down to the single virus particle and single receptor, and even to provide assessments of multivalent interactions. The technologies covered herein are surface plasmon resonance (SPR), quartz crystal microbalance with dissipation (QCM-D), dynamic force spectroscopy (DFS), total internal reflection fluorescence (TIRF) microscopy combined with equilibrium fluctuation analysis (EFA) and single particle tracking (SPT), and finally confocal microscopy using multi-labeling techniques to visualize entry of individual virus particles in live cells. Considering the growing scientific and societal needs for untangling, and interfering with, the complex mechanisms of virus binding and entry, we hope that this review will stimulate the community to implement these emerging tools and strategies in conjunction with more traditional methods. The gained knowledge will not only contribute to a better understanding of the virus biology, but may also facilitate the design of effective inhibitors to block virus entry. Viruses are obligate intracellular parasites requiring access to the intracellular environment in order to replicate. Binding of the virus particle to the plasma membrane of the target cell is an important first step in the viral replication process. It is mediated by specific receptors and attachment factors . While aAlthough the virus uptake mechanisms are principally similar across viral species, the molecular details are specific for each virus/target cell combination. Viruses are not passive cargoes, but trigger internalization by activating endocytic processes. This can be done by activating signaling pathways through direct or indirect contacts with cell-surface molecules and structures, including triggering of clathrin coat formation . DiffereIt is worth noting that individual virus-receptor interactions at the cellular membrane are typically weak and provide only short residence times. Virus binding therefore usually involves the parallel engagement of many such interactions, thereby forming so-called multivalent interactions . Such loDue to the importance of virus-receptor interactions for viral entry, virologists, chemical biologists, biochemists, and biophysicists alike have all shown great interest in untangling the complex mechanisms governing receptor-mediated viral uptake. Such knowledge does not only contribute to a better understanding of infection biology, but may also facilitate the design of effective inhibitors to block viral entry pathway(s). Such insights are urgently needed not only to combat existing viral diseases, but also to rapidly react against emerging viral pathogens, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review focuses on selected key biomolecular processes mediating virus attachment and entry, all relying on the dynamic molecular interactions between viral proteins and cell-surface molecules. In particular, it highlights how recent methodological developments can contribute to a deeper understanding of such dynamic interactions. It further illustrates and discusses how such knowledge can contribute to the development of antiviral drugs targeting viral adhesion proteins, cellular receptors/attachment factors, their interactions, or factors essential in driving such interactions.To reflect the diversity of virus binding and entry as well as the need for different methodological approaches to study such processes, we have selected a few well-characterized non-enveloped (simian virus 40 and norovirus) and enveloped  model viruses. Basic characteristics of these viruses are summarized below and in Table Polyomaviridae and is a non-enveloped DNA virus (Table Simian virus 40 (SV40) belongs to the us Table . The SV4Caliciviridae and is divided into ten genogroups (G), of which GI, GII, and GIV infect humans [Norovirus is a non-enveloped positive-sense single-stranded RNA virus Table . It belot humans . The virt humans . Despitet humans . Most stt humans . In addit humans , to sialt humans  and gangt humans , as wellt humans . Norovirt humans , 23.Orthomyxoviridae family and is a negative-sense RNA virus with the genome divided into eight segments (Table n) protein, which in addition is also responsible for the pH-induced fusion of the viral envelope with the endosomal membrane of the target cell. In addition to the hemagglutinin, the viral membrane also contains a neuraminidase (Nn), which binds to, and cleaves off, sialic acids from the cellular receptors. The balance of these two viral activities is considered critical for the whole infectious process [N-glycans, present in the human lung, which may explain why desialylation with neuraminidase does not block infection [Influenza A virus belongs to the ts Table . The vir process , 31. Recnfection . InfluenHerpesviridae family (Table Herpes simplex virus type 1 (HSV-1) is an enveloped DNA virus belonging to the Retroviridae family (Table Human immunodeficiency virus type 1 (HIV-1) belongs to the Kd, the change in free enthalpy (ΔH), and free energy (ΔG) associated with the binding process [Kd value of the interaction, which is typically determined by non-linear least squares fitting of a Langmuir-type binding isotherm to the data. Such experiments have been done using both isolated viral proteins and entire viruses, but are typically limited to the use of truncated variants of the membrane receptor.As virus-receptor interactions are of paramount importance for virus attachment to target cell membranes and often drive virus internalization, their characteristics have been the subject of intense research. A multitude of methods have been applied in such studies, probing the interactions on different levels of complexity  and providing quantitative insights into the interactions. For example, isothermal titration calorimetry (ITC) has been used to determine the heat released by binding of attachment factors to viral proteins, yielding information on dissociation constant  process , 39. In  process , 41. TheKd) is obtained. The dissociation rate constant (koff), a measure of the bond stability, can be quantified by recording protein detachment upon rinsing. These methods are compatible with the use of receptor/attachment factor-containing supported lipid bilayer (SLB) at an interface for real-time measurements of the binding kinetics of viruses as function of virus concentration [Kd value of the overall interaction (avidity) as well as on- and off-rates (kon and koff) by modelling the data using dedicated binding models. However, due to the often very long residence times associated with multivalent interactions and the notable heterogeneity within virus populations , it is generally very difficult to relate such ensemble-averaged data  to molecular properties of the monovalent interactions (affinity). This challenge can be efficiently tackled using methods that probe interaction kinetics at the single particle level. In contrast to ensemble averaging techniques, single particle techniques are sensitive enough to extract statistics from multiple monovalent binding events, simultaneously also providing information about binding heterogeneity originating from multivalent interactions.In principle, methods such as ITC and NMR can be used to determine the monovalent binding affinity of viral proteins interacting with water-soluble attachment factors. The overall  interaction of a virus with a cell membrane shows, however, a very complex dependence on multiple parameters Fig. , such asntration , 52. Suckon, koff, and hence Kd thanks to a data analysis procedure referred to as equilibrium fluctuation analysis (EFA) [An experimental setup to study the binding of virus particles to cell-surface components on a single particle level takes advantage of total internal reflection fluorescence (TIRF) microscopy Fig. . In thisis (EFA) , 55. AddFurthermore, molecular details of the detachment behavior of individual receptor-bound virus particles can be obtained using dynamic force spectroscopy (DFS). For example, in DFS experiments using atomic force microscopy (AFM), a virus particle is immobilized at the end of a sharp AFM tip and approached to a receptor-presenting surface Fig. . The tipIn addition to the procedures described above to probe virus-membrane interactions on a single particle level, a number of assays have been designed to specifically investigate the different steps leading to virus entry by fusion, and release of the viral content/genome, on a single particle level. In all cases, such assays rely heavily on the use of virus particles labeled with multiple fluorophores. Often, a lipophilic membrane dye is included within the viral lipid membrane at self-quenching concentrations , 58, 59,The kinetic analyses of virus binding and release are simplified if the viruses under investigation share the same well-defined geometry. This condition is fulfilled for many non-enveloped viruses, which are made of a highly regular capsid and whose capsid proteins can adopt only a single or very few geometrical configurations , 74. AccKd << 0.1 μM vs. ~ 5 mM, respectively) [Ralstonia solanacearum  , 76, 77,ctively)  applied rum Fig. . The norrum Fig. . In addirum Fig.  showed tkoff) should be extractable from the measured residence time distributions, which was demonstrated in interaction studies of fixed valency. The corresponding distributions obtained from the norovirus-HBGA interactions were, however, too broad to allow for the extraction of molecular off-rates, which was attributed to a notable variation of the binding valency within the ensemble . A similar experimental approach was used recently by Rimkute et al. [These investigations indicate that receptors/attachment factors engaged in virus binding can participate in a dynamic equilibrium with non-engagedreceptors/attachment factors embedded in lipid membranes. The results also provided estimates for the strength of monovalent interactions between the viral binding protein (VP1) and receptors/attachment factors (HBGA) embedded in a lipid membrane. This estimate, however, relied on assumptions on the maximum valency achievable by the virus on a planar membrane, which was derived in these studies from geometrical considerations. In order to relate the observed virus attachment and release rates with molecular reaction rates, knowledge about the valency distribution of the viruses probed is needed, which requires methods to probe the binding and release of individual virus particles. Such an approach was introduced by Bally et al. , who line et al.  to probeStudies of fluorescently labeled norovirus VLPs have revealed that the VLPs cluster on supported lipid bilayers containing GSLs . Larger As the valency has a strong impact on the virus residence time , informaThe influenza A virus (IAV) which relies on sialic acids for attachment and entry into the host cell has been extensively used to initially demonstrate how off-rates of single viruses interacting with membranes can be extracted , 85. IndThe first demonstration of probing the binding strength of intact influenza viruses by force spectroscopy was done by Sieben et al. , who empThese examples show that both methods, DFS and equilibrium binding probed using TIRF microscopy, are very powerful approaches for characterizing complex interactions on a molecular level. Due to their single-virus/single-molecule resolution, both techniques are able to extract information and identify subpopulations, which are typically lost in the ensemble-averaging process of traditional binding assays. This high resolution requires, however, more sophisticated and time-consuming data analysis schemes, which represents a notable bottleneck in inhibitor screening applications. Hence, ensemble-averaging and single-molecule binding assays complement each other in this respect, as their combinations enable an initial screening of many compounds, followed by an investigation on the binding properties of the most successful candidates using single-molecule binding assays.Together with sialic acid moieties, sulfated glycosaminoglycans (GAGs) are the most common attachment factors for viruses and accordingly, a large variety of human viruses take advantage of these carbohydrates for their initial recruitment to the surface of host cells , includiO-linked glycans, found on viral glycoprotein gC of HSV-1, and of the cellular GAGs have been explored. In a reductionist approach, the binding activity of isolated gC proteins to sensor-immobilized CS chains was investigated using a SPR-based binding assay [koff [O-glycosylated glycoprotein gp150 was found to negatively regulate virus attachment to GAGs by reducing the number of contacts initially formed with GAGs, as revealed by AFM-based DFS performed with GAG-presenting surfaces. This observation was further confirmed by similar experiments on live cells, where the gp150-negative virus mutant was found to adhere with increased frequency to GAG-positive cells but not to GAG-negative ones [In an attempt to elucidate the mechanisms regulating virus-GAG interactions at the cell surface, minimal models of the cellular glycocalyx have been implemented. These typically consist of isolated GAGs, immobilized on a sensor surface in a biomimetic fashion –102. Forng assay . A compang assay , 104, whng assay . In adding assay . These ong assay . Furtheray [koff , once agay [koff . Furtheray [koff , most liive ones . In a diive ones . These rSo far, we have illustrated how minimal cell surface mimics can be used to study virus-GAG interactions, with the example of HSV-1. In such a reductionist approach, only the molecules of interest (GAGs) are taken into consideration, allowing for systematic investigations of how selected components contribute to the overall virus membrane interactions. However, in some cases, a bioanalytical platform presenting the complete repertoire of the plasma membrane components, including lipids, carbohydrates, and proteins, in a native-like environment may be desirable. The use of such a platform may be beneficial for applications requiring a better understanding of the way the virus interacts with the membrane as a whole, i.e., with all receptors, co-receptors, and adhesion factors, both known and unknown. This may be useful for example in the context of efficiently screening for virus binding inhibitors. Additionally, a platform generated from cellular membrane extracts facilitates the study of membrane components difficult to isolate and purify. Along these lines, a number of research groups have proposed approaches to deposit native-membrane material purified from cells at a sensor surface, in the form of supported lipid bilayers of complex composition, i.e., native supported lipid bilayers (nSLBs). The advantage of such nSLB platforms is that they display the full compositional complexity of the cell surface, at a given time, but are decoupled from the physiological processes present in live cells. Accordingly, nSLBs have been implemented to virus research , 105, ilTaken together, this section illustrates the potential of working with bioanalytical platforms relying on cell surface mimics in constant feedback with in vitro cell-based assays to gain a mechanistic understanding, on the molecular level, of how cellular processes are regulated in live cells. It demonstrates how an experimental approach relying on combining various levels of molecular complexity can lead to drastically new insights into cell biology and virology.Currently, there is still an open debate on the relative importance of HIV-1 entry via fusion at the plasma membrane or fusion in the endosomes, and more importantly, about which pathways that lead to productive viral replication in the target cells. This controversy brings up fundamental questions about the individual and/or synergistic roles of the three major factors likely to influence HIV-1 fusion, i.e., interactions with receptors/co-receptors, lipid membrane factors , and pH conditions within the endosomes.Cell membrane mimics of increasing complexity have been used by the Tamm group to elucidate the mechanisms by which nanometer-sized domains rich in cholesterol and sphingomyelin facilitate fusion of HIV-1 with cellular membranes. Such investigations were motivated by reports indicating that the receptor and co-receptor for HIV-1 infection are preferentially enriched in lipid domains , implyin+/CCR5+ membranes [Mechanistic studies of binding and fusion of HIV using reconstituted in vitro systems are complicated by the fact that the process requires two essential cellular transmembrane proteins: the receptor CD4 and a co-receptor, either CCR5 or CXCR4. To include receptors and co-receptors in their bioanalytical assays, the Tamm group used giant unilamellar vesicles and planar supported membranes derived directly from the plasma membranes of cells expressing CD4 and CCR5 , 59. Giaembranes .Fig. 6HIWhile the bioanalytical platforms presented above allowed the examination of virus-membrane interactions at the single virus level and contributed to reveal the molecular mechanism of HIV fusion, they can neither be applied to evaluate the statistical distribution of different fusion or entry pathways nor to comment on whether they lead to cell infection. This can only be achieved by imaging infected cells and by visualizing the binding and entry of individual virus particles in a time-dependent manner and with a high spatial resolution. In the last two decades, a number of research groups have established single virus imaging conditions to study early and late stages of virus replication , 109–113Using several examples of well-characterized enveloped and non-enveloped viruses, this review highlights the nature of the information obtainable through implementation of emerging bioanalytical tools to study virus-membrane interactions. It illustrates the potential of such approaches in the context of studying viral binding kinetics, diffusivity, and fusion at the cell membrane, while emphasizing the importance of multivalency in virus binding and uptake.The appearance of SARS-CoV-2, and the current global pandemic, has reminded us all of the importance of developing new vaccination platforms against viral diseases together with powerful antiviral drugs. In this context, it is our hope to have demonstrated that, beyond providing insights into the molecular mechanisms underpinning viral infection, emerging bioanalytical techniques also represent a solid foundation to the development of antivirals interfering with complex cellular entry pathways. This is exemplified in this review by the capacity to pinpoint how the neuraminidase inhibitor zanamivir affects IAV attachment, as well as the possibility to quantify the extent to which host molecules must be blocked before release of attached virus particles is initiated.A variety of antiviral strategies targeting different aspects of interactions between viruses and cell membranes have already reached clinical trial or even been approved –116. ExaThe current bottleneck to the widespread implementation of the emerging bioanalytical methods described here is that they require advanced instrumentation which is not yet suitable for high-throughput screening. However, optical microscopy in particular is at present witnessing tremendous developmental gains making it very likely that many approaches discussed in this review will soon become broadly available even in the biosafety level 3 and 4 laboratories required to work with highly pathogenic viruses.


The Accreditation Council for Graduate Medical Education milestones and entrustable professional activities (EPAs) are important assessment approaches but may lack specificity for learners seeking improvement through daily feedback. As in other professions, clinicians grow best when they engage in deliberate practice of well-defined skills in familiar contexts. This growth is augmented by specific, actionable coaching from supervisors. This article proposes a new feedback modality called microskills, which are derived from the psychology, negotiation, and business literature, and are unique in their ability to elicit targeted feedback for trainee development. These microskills are grounded in both clinical and situational contexts, thereby mirroring learners’ cognitive schemas and allowing for more natural skill selection and adoption. When taken as a whole, microskills are granular actions that map to larger milestones, competencies, and EPAs. This article outlines the theoretical justification for this new skills-based feedback modality, the methodology behind the creation of clinical microskills, and provides a worked example of microskills for a pediatric resident on a hospital medicine rotation. Ultimately, microskills have the potential to complement milestones and EPAs and inform feedback that is specific, actionable, and relevant to medical learners.The online version of this article (10.1007/s40037-021-00666-9) contains supplementary material, which is available to authorized users. However, a resident may struggle to explicitly apply this EPA to their day-to-day routine in an easily observable way. Distinguishing between respiratory distress and failure requires a specific context in which it can be applied, such as during a bedside presentation on rounds or through written notes that contain contingency planning.As we created microskills based upon our stated criteria, we found that some elements of existing assessment modalities were narrow enough to become microskills without significant adjustments, while others required more modifications. The EPA “another”  served ant care”  was distillness”  containssituational context was also created based on the patient’s hospital experience and intern-patient interactions to demonstrate the possible skills a prototypical intern could employ at various stages of a patient’s hospitalization . A clinical context map was not created, given that this context is already embedded in EPAs and would thus transfer easily onto the relevant microskills.As part of developing microskills mapped to milestones and EPAs, we created a user-centered framework focused on pediatric interns’ hospital medicine workday and the skills they use to navigate that day. User-centered design employs empathy to better understand the needs of the end-user and creates systems that complement the subject’s natural tendencies , 43. By These user-centered maps were then combined with the extracted relevant milestones and EPAs to form situationally anchored microskills umbrellaed under a table of contents . The microskill table of contents mirrors the cognitive schema an intern uses to organize the workday, thereby lending itself to more natural microskill selection and adoption. The table of contents is an amalgamation of both the user-centered maps, incorporating unique aspects of the intern’s workday  as well as skills that surround the patient experience .e.g., PC6: make informed diagnostic and therapeutic decisions that result in optimal clinical judgment) and EPAs [e.g., EPA4: manage patients with acute, common diagnoses in an ambulatory, emergency, or inpatient setting) and naturally align with both user maps. As a result, patient presentations became an independent microskill domain. However, even within patient presentations, an intern must employ different types of skills in various situational and clinical contexts, from integrating pathophysiology into everyday assessments, to creating contingency plans for acutely ill children, to relating to families in easy-to-understand language. Taking this into account, the categories within patient presentations were organized both by the features of presentations that the intern may be working on  as well as the types of patients discussed in the intern’s presentation .Groupings of skills that interns could situationally demonstrate to supervisors were separated into domains in the table of contents. For example, patient presentations are mentioned throughout multiple milestones  , competencies, milestones, and microskills that inform a single EPA can be found in ESM, Fig. S3. , milestones, and microskills).While incorporation of microskills into practice will vary by institution, level of training, and clinical rotation, here we outline how a pediatric intern could use microskills on a hospital medicine rotation. When a new supervisor begins clinical service with the resident team, the intern would select one to three microskills (from the library of previously developed and disseminated microskills) to practice and be observed for the upcoming week. Though the intern will ultimately choose the skills he/she will practice, this should be a collaborative process with input from the supervisor and senior residents, considering skills the intern practiced in previous weeks. Throughout the week, both the intern and the supervisor know which skills are being practiced, thereby allowing the intern to refine the skills, as well as provide an opportunity for the supervisor to give real-time feedback on observations (or take notes to provide feedback at a later time). As one example, supervisors already accompany and observe trainees on clinical rounds, which enables a natural incorporation of the microskills framework. Supervisors can choose to deliver coaching in between trainees’ patient presentations or find time later in the day for more involved feedback. If supervisors find themselves pressed for time during or after rounds, they can consider integrating microskills feedback into their workflow later in the workday, such as by encouraging trainees to practice skills in follow-up conversations with patients.Prior studies demonstrate that unless trainees have an expected forum to ask supervisors for feedback, they will instead forgo asking for feedback altogether . AwareneMicroskills have the potential to fill a current need in the medical training landscape, however, they are not without limitations and will benefit from further testing and refinement. Given the difficulty in demonstrating the effectiveness of randomized educational interventions, meta-analyses of microcounseling skills have come under recent criticism and it is unknown if previously demonstrated effectiveness will translate to medical training . The micThe microskills framework may also become cumbersome if not created and implemented thoughtfully. The number of skills derived from milestones and EPAs can be numerous, and trainees need ways to sort through microskills to select those most relevant for their deliberate practice. Additionally, challenges may develop in standardizing how trainees communicate identified microskills with supervisors and how supervisors track observations and provide timely feedback.Finally, selecting relevant skills requires deft supervisor coaching and a shared understanding that becoming competent in certain skills may not equate to achieving proficiency as a physician. Given their specificity, microskills are not built to offer holistic feedback to a training physician. Programs need a wide array of feedback tools to assist resident progress and microskills can add to, but should not replace, existing assessment methods.Microskills complement milestones and EPAs by making feedback and areas of focus for continued development more specific and actionable in clinical and situational contexts. Building on these strengths, they offer an opportunity to improve day-to-day learner feedback and bring granularity to the personal improvement process, based on deliberate practice and situated learning theory.Future directions for microskills development include eliciting end-user perspectives on microskills compared to currently used assessment and feedback modalities as well as assessing microskill implementation outcomes. Future work should also focus on standardizing microskill implementation, creating microskills for other clinical contexts, specialties, and training levels, and developing the microskills coaching process for senior residents and supervisors. As microskills are created, each set needs to be refined by trainees, supervisors, and rotation directors.Fig. S1 a, b User-centered design maps used to create and organize microskills. Maps depict the skills a prototypical intern might employ throughout the workday as well as how a hospitalized patient might interact with that internFig. S2 Applying user-centered domains to create microskills categories: The microskill table of contents. The organization of the table of contents was created according to a user-centered approach, building off of designed user maps, in order to mirror the cognitive schemas a prototypical intern uses to organize the workdayFig. S3 An example of the connections between EPAs, milestones, and microskills. An example of the many domains of competence (DoC), competencies, milestones, and microskills that compose a single EPA. For a learner to successfully complete the EPA “manage patients with acute, common diagnoses in an inpatient setting”, they need to develop competency in patient care (PC6: make informed diagnostic and therapeutic decisions…) along various milestones. This involves first learning how to successfully navigate a myriad of microskills in different contexts . The microskills in this example are only a few of the many possible options that compose each EPA and the subsequent milestones Fig. S4 An expanded example of the connections between entrustable professional activities (EPAs), milestones, and microskills. Building off of the previous worked example in Fig. S3 , this figure expands the many possible microskills that compose each EPA, competency, and subsequent milestonesTable S1 Comparison of entrustable professional activities (EPAs), milestones, and microskillsTable S2 List of milestones and entrustable professional activities (EPAs) included in microskills development


Stephen Oroszlan received his early education in Hungary, graduating in 1950 from the Technical University in Budapest with a degree in chemical engineering. He worked for several years in Hungary before emigrating, via an arduous journey, to the United States in 1957. With assistance from the American Academy of Sciences, he obtained his Ph.D. in Pharmacology from Georgetown University School of Medicine. His first publications, beginning in 1964, dealt with the purification and properties of  retroviruses, and also other human viruses including adenoviruses and papillomaviruses, reflecting his support from the U.S. National Cancer Institute. After 1970, his research focused exclusively on retroviruses. The story of how he came to be associated with the Cancer Institute is told here [specifically and in as much detail as possible, and to see what can be learned from these descriptions. It is important to realize that sequencing nucleic acids was not routine then, as it is today. Moreover, a great deal of the information he obtained could not have been deduced from nucleic acid sequences. The present volume is a small collection of papers, either by his co-workers or by colleagues whose research was significantly influenced by his work. The breadth and diversity of these papers gives some indication of the remarkable ramifications of Steve’s work. His research in this area was extraordinarily productive, resulting in over 200 publications between 1970 and 2006. It is characterized by a determination to describe the proteins in the viruses Like many viruses, retroviruses synthesize many of their proteins in the form of polyprotein precursors, which are then cleaved to the final products by virus-coded proteases. One of the seminal contributions from Steve’s research is the isolation and characterization of viral proteases. This was, of course, crucial in the development of inhibitors of HIV-1 protease, which are among the principal weapons responsible for the success of highly active antiviral therapy in HIV-1-infected people. The present volume includes a review by Weber et al.  of reseaLike those of many viruses, retroviral proteases are synthesized in ways which deviate from the canonical direct translation of mRNAs into the encoded proteins, and these unexpected mechanisms were obscure until the proteases were isolated and their amino-acid sequences determined. These unusual mechanisms have been collectively termed “recoding”, and the article here by Atkins et al.  is a comMuch of the initial characterization of the proteins of HIV-1 and human T-cell leukemia virus, a retrovirus which induces leukemia, was performed by Steve’s lab in collaborations with that of Robert Gallo (in whose lab the virus was isolated) at the National Cancer Institute. The paper by Zella and Gallo  is a broMy own research career was dramatically influenced by the discoveries in Steve’s lab, as I was repeatedly able to apply genetic and biological tools to further understand the functional significance of the phenomena his lab uncovered. My essay in the present volume tells four stories along these lines .While HIV-1, the cause of the AIDS pandemic, was isolated in 1983 , the lasOne of Steve’s great pleasures in life was considering and discussing data and its implications. I have a vivid memory of him at his desk, poring over newly acquired amino-acid sequences; the sequence Pro-Pro-Pro-Tyr in murine leukemia virus p12 (later shown to be the Late domain of the virus ) elicite