Zagreb Group Research Articles

Damir Bartol Indoš and Tanja Vrvilo — House of Extreme Music Theatre: Performative Translation of Croatian Neo/Avant-garde

DB Indoš and Tanja Vrvilo — House of Extreme Music Theater work with material from the Croatian historical avant-garde scene in all their performances of exhausting, physical theater, which they approached through the Zagreb circle of zenithists, “through Kamov and Čerina as predecessors of the Futurists (but not the Marinettists), and their influence on the literary-revolutionary circle of rebellious youth. Some of them included August Cesarec, Đuka Cvijić, Zora Ruklić and members of their ‘Republic of Stenjevac’, members of the Zagreb group Zenit, the lyrics of a visionary film through the books of Ivan Martinac, concrete poetry by Josip Stošić and the silent art that we ‘shachtophonize’ for our parallel performance canon” (Vrvilo 2020). Their systematic work on the performance and reactualization of the neo/avant-garde can be defined, by using Roman Jakobson’s definition, by intersemiotic translations (cf. Munday, Ramos Pinto, Blakesley 2022: 9) into musical theater which, in their example, is based on manipulating sound objects/installations/sculptures with the cut-up technique of original texts into schachtophone scores (moving away from music notation to graphic notation) for schachtophone music, all through the vision of the performance of exhausting (physical) theater with Indoš’s constant dedication to Artaud’s theater of cruelty, the alchemical theater of pre-logic and pre-rationality, a theater that, as a magical ritual, can lead to the healing of society.

Compound Prioritization through Meta-Analysis Enhances the Discovery of Antimicrobial Hits against Bacterial Pathogens.

The development of informatic tools to improve the identification of novel antimicrobials would significantly reduce the cost and time of drug discovery. We previously screened several plant (Xanthomonas sp., Clavibacter sp., Acidovorax sp., and Erwinia sp.), animal (Avian pathogenic Escherichia coli and Mycoplasma sp.), and human (Salmonella sp. and Campylobacter sp.) pathogens against a pre-selected small molecule library (n = 4182 SM) to identify novel SM (hits) that completely inhibited the bacterial growth or attenuated at least 75% of the virulence (quorum sensing or biofilm). Our meta-analysis of the primary screens (n = 11) using the pre-selected library (approx. 10.2 ± 9.3% hit rate per screen) demonstrated that the antimicrobial activity and spectrum of activity, and type of inhibition (growth versus virulence inhibitors) correlated with several physico-chemical properties (PCP; e.g., molecular weight, molar refraction, Zagreb group indexes, Kiers shape, lipophilicity, and hydrogen bond donors and acceptors). Based on these correlations, we build an in silico model that accurately classified 80.8% of the hits (n = 1676/2073). Therefore, the pre-selected SM library of 4182 SM was narrowed down to 1676 active SM with predictable PCP. Further, 926 hits affected only one species and 1254 hits were active against specific type of pathogens; however, no correlation was detected between PCP and the type of pathogen (29%, 34%, and 46% were specific for animal, human foodborne and plant pathogens, respectively). In conclusion, our in silico model allowed rational identification of SM with potential antimicrobial activity against bacterial pathogens. Therefore, the model developed in this study may facilitate future drug discovery efforts by accelerating the identification of uncharacterized antimicrobial molecules and predict their spectrum of activity.

Safety, immunogenicity of lyophilized purified vero cell cultured rabies vaccine administered in Zagreb and Essen regimen in post-exposure subjects: A post-marketing, parallel control clinical trial

ABSTRACT To compare the safety and immunogenicity of lyophilized PVRV under Zagreb and Essen regimen. A post-marketing parallel control clinical trial was conducted. Totally 240 subjects were assigned to two groups randomly, immunized with lyophilized PVRV under Zagreb and Essen schedule. Solicited adverse events were observed after each dose and unsolicited adverse events were collected. Serum samples were collected on days 0, 7, 14, 42, 180 and 365 to be used to determine immunogenicity level. No severe adverse events (SAE) were observed. The incidence of adverse events under Zagreb and Essen were similar and there was no significant difference between the two groups and within all age groups. Fever and pain were the most frequently reported systemic and local adverse events (AEs) respectively. There were no differences in the GMT and the positive seroconversion rate between these two groups. All participants in the Zagreb group obtained protective effect on day 14, while 99.16% of the subjects obtained in the Essen group. Both groups showed similar enduring immunity. Immunizations under Zagreb and Essen regimens showed similar safety and immunogenicity. For lyophilized PVRV, Zagreb was non-inferior to Essen to patients of all age groups.

Immunogenicity and safety of purified vero cell-cultured rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in the healthy Chinese subjects: a randomized, double-blind, positive controlled phase 3 clinical trial

ABSTRACT Aim: The aims of the study were to evaluate the non-inferiority of the safety and immunogenicity of a new trial purified vero cell-cultured rabies vaccine (trial vaccine) in healthy subjects comparing with the control purified vero cell-cultured rabies vaccine (control vaccine) following Essen regimen and to evaluate the non-inferiority of the safety and immunogenicity of the trial vaccine following two intramuscular regimens, between Zagreb and Essen regimen. Methods: Serum samples were collected before vaccination and on d 7, 14, 35/42 post vaccination. Adverse events (AEs) were recorded for 30 d following each vaccination. This study was registered in the Chinese Clinical Trial Registry (ChiCTR-PPR-15007057). Results: There was no significant difference in the incidence of AEs, local and systemic reactions, among Zagreb group, Essen group, and control group. But the incidence of solicited AEs was a significant difference among the three groups (p = 0.0498). The incidence of solicited AEs was higher in Essen group than that in control group and Zagreb group (p = 0.0278, p = 0.0248). In the subjects whose antibodies were seronegative before vaccination, the seroconversion rates of antibodies among three groups were all 100.0% on d 14 and d 35/42. The Essen group was not inferior to the control group, and the Zagreb group was not inferior to the Essen group on d 14. On d 14 and d 35/42, the geometric mean concentration of the three groups was much higher than the immune protection level of 0.5 IU/ml. Conclusions: The trial vaccine had good safety and immunogenicity, and the trial vaccine is not inferior to the control vaccine. Abbreviations: PVRV: purified vero cell-cultured rabies vaccine; AE: adverse event; CI: confidence interval; GMC: geometric mean concentration; IM: intramuscular; NIFDC: National Institutes for Food and Drug Control; PPS: per-protocol set; SS: safety set; REFIT: Rapid Fluorescent Focus Inhibition Test; RVNA: rabies virus neutralizing antibody; WHO: World Health Organization.

Meta-analysis of immunogenicity and safety of human rabies vaccination under Zagreb and Essen regimens.

Aim: To assess the immunogenicity and safety of rabies vaccination under the Zagreb and Essen regimens by performing a meta-analysis. Methods: Electronic databases were searched for eligible studies. Risk ratios and weighted mean differences with 95% CIs were used to calculate estimates. Results:A total of18 studies were included. Rabies virus neutralizing antibody concentration was comparable between the two regimens at D7 and 14. No significant differences were observed in seroconversion rates from D14 and 42. Incidence of fever was higher in Zagreb group (risk ratio: 1.55 [1.37-1.76]); but no significant differences were present for other common adverse events. Conclusion: Rabies vaccination under the Zagreb regimen was noninferior to the Essen regimen in immunogenicity and had an acceptable safety profile.

A new approach in topological descriptors usage. Iterated line graphs in the theoretical prediction of physico-chemical properties of saturated hydrocarbons

A new look on the problem of the molecular systems index description is presented. The capabilities of iterated line (edge) graphs in characterization of saturated hydrocarbons properties were investigated. It was demonstrated that single selected molecular (graph-theoretical (topological) or informational) descriptor calculated for the sequence of nested line graphs provides quite reliable progressive set of regression equations. Hence, the problem of descriptor set reduction is solved in the presented approach at list partially. Corresponding program complex (QUASAR) has been implemented with Python 3 program language. As the test example physico-chemical properties of octane isomers have been chosen. Among the properties under investigation there are boiling point, critical temperature, critical pressure, enthalpy of vaporization, enthalpy of formation, surface tension and viscosity. The corresponding rather simple linear regression equations which include one, two or three parameters correspondingly have been obtained. The predictive ability of the equations has been investigated using internal validation tests. The test by leave-one-out (LOO) validation and Y‑scrambling evaluate the obtained equations as adequate. For instance, for the regression model for boiling point the best equation characterizes by determination coefficients R2 = 0.943, with LOO procedure – Q2 = 0.918, while for the Y-scrambling test Q2y-scr<0.3 basically. It is shown that all the abovementioned molecular properties in iterated line graph approach can be effectively described by commonly used topological indices. Namely almost every randomly selected topological index can give adequate equation. Effectiveness is demonstrated on the example of Zagreb group indices. Also essential effectiveness and rather universal applicability of the so-called “forgotten” index (ZM3) was demonstrated.

Immunogenicity and safety of purified vero cell rabies vaccine (PVRV) produced by Liaoning Cheng Da Co. under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese adults aged 50 and above

ABSTRACTBackground: Two kinds of regimens (2-1-1 and 1-1-1-1-1) can be selected after Zagreb regimen(2-1-1)of PVRV was officially approved in Beijing in January 2015. Up to now, the subjects for most studies about the comparison between Zagreb and Essen regimen are under 50 y old, rarely at and above. Aging of the immune system may result in decreasing efficacy of vaccination, especially for adults aged above 65–70 y. This study compared the safety and immunogenicity of the Zagreb and Essen regimen in Chinese adults aged 50 and above with the goal to provide a supplemental data for this age group. Methods: A total of 114 cases were divided into 2 groups randomly, received PVRV under the Zagreb and Essen regimens respectively. Serum samples were collected at D0, D7, D14, D42, D180 and D365 to determine the rabies serum neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT). Safety analyses were made by comparing the AEs in day-3, day-7, and day-(7 + 21) in Zagreb or day-(7 + 28) in Essen by gender and age cohorts. Results: 617 blood samples were obtained. Two groups showed similar immunogenicity, the neutralizing antibody titer of all subjects at D14 and D42 showed >0.5 IU/ml. Under the same regimen, Subjects ≥65 y had lower GMC than those who <65 years from D7 to D365 within 2 groups. This difference was significantly shown on D7, D14, D180 in Zagreb group, and on D180 in Essen group (t = 2.38, p = 0.02; t = 3.78, p < 0.001; t = 2.30, p = 0.03; t = 4.42, p < 0.001). Subjects<65 years had higher seroconversion rate compared to ≥65 y on D7, D180 and D365 in both 2 groups, this difference was also significantly shown on D180, D365 in Zagreb group and on D180 in Essen group (χ2 = 20.66, p < 0.001; χ2 = 6.56, p = 0.02; χ2 = 10.96, p = 0.002). Two regimens all showed favorable performances with mildly or common adverse events (AEs). The incidence of local AEs after 3 d in Essen group was higher than Zagreb group (χ2 = 9.69, p = 0.002). The most common local AE was pain, the incidences (8.8%) in Zagreb group was higher than Essen group (8.4%, χ2 = 5.12, p = 0.02). All AEs for Zagreb group and 52.3% of AEs for Essen group occurred during the first 72 hours. During the first 72 hours, subjects aged <65 in Zagreb group (16.26%) had higher incidences of AEs than Essen group (8.57%, χ2 = 4.54, p = 0.03), males in Zagreb group (16.05%) had higher incidence of AEs than Essen group (5.71%, χ2 = 5.34, p = 0.02). The incidences of AEs close in during the first 7 d. Conclusion: The Zagreb and Essen regimens demonstrated the similar safety and efficacy of PVRV in Chinese adults aged 50 and above. People ≥65 y showed reduced immune response to both regimens. More AEs for the Zagreb regimen were observed within the first 72 hours, especially for male and people < 65 y.

Comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vaccine (PCECV) administered according to two different simulated post exposure intramuscular regimens (Zagreb versus Essen)

Despite availability of effective rabies vaccines, India has the highest global mortality rate for rabies. Low socio-economic communities are most affected due to lack of awareness of the disease and poor compliance to post-exposure prophylactic regimens. Currently, the only approved intramuscular regimen for post-exposure prophylaxis (PEP) against rabies in India is the Essen regimen, which consists of 5 injections administered over 5 separate days in a period of one month. The high number of doses and clinical visits, however, are major reasons for non-compliance, and thus a shorter regimen would be beneficial. In a simulated PEP trial in healthy, adult subjects, this study evaluated whether purified chick embryo cell vaccine (PCECV), administered according to the WHO-recommended 4-dose/3 visit Zagreb vaccination regimen is of equal immunogenicity and safety as the standard Essen regimen in Indian subjects. Two hundred and 50 healthy adults were enrolled and randomized into a Zagreb or Essen group, each receiving PCECV according to their respective regimen. Blood samples were collected on Days 0, 7, 14 and 42 and analyzed using the rapid fluorescent focus inhibition test (RFFIT). By Day 14, all subjects across both groups attained rabies virus neutralizing antibody (RVNA) concentrations of ≥ 0.5IU/ml. The Zagreb regimen was then demonstrated to be immunologically non-inferior to the Essen regimen by Day 14, which was the primary endpoint of the study. No safety issues were noted and the occurrence of adverse events was similar in both groups (17% and 15%, respectively). NCT01365494. CTRI No.: CTRI/2011/07/001857

A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults

The Zagreb regimen has been used for 20 years in various countries. In China, until 2010, the Zagreb schedule was only approved for purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies vaccines (PVRV). In this phase III clinical trial, we aimed to demonstrate the safety and immunogenic non-inferiority of the Zagreb regimen compared with the Essen regimen in healthy adult Chinese immunized with PCECV (Rabipur®). The study enrolled 825 subjects aged 18 to 50 years; serum samples were collected on Days 0, 7, 14, 42, and at 13 months to assess rabies virus neutralizing antibody (RVNA) concentrations. Solicited and unsolicited local and systemic reactions were recorded for 6 days following the day of vaccination, and collected throughout the entire study period (Day 1 until Month 13). The Zagreb regimen was non-inferior to the Essen regimen with regard to RVNA concentrations after 7, 14, and 42 days, and 13 months of immunization. The non-inferiority of seroconversion was established at Days 14 and 42. The incidence of local and systemic reactions was similar between groups, and mostly of mild or moderate severity. Vaccine-related adverse events occurred more frequently in the Essen group than in the Zagreb group. Vaccination with PCECV under a 2-1-1 regimen is as safe and immunogenic as under the traditional 5-dose Essen regimen for rabies post-exposure prophylaxis, and is a more cost-effective option, has a more practical vaccination schedule, and can potentially increase compliance.

Materials modification using ions with energies below 1 MeV/u

Materials modifications using swift heavy ion beams provided by large scale accelerators have been used for many years in a wide variety of ways, e.g. to produce ion tracks or to modify the shape of nanoparticles. In all those applications the most relevant parameter for the materials modification is the electronic stopping power and not the ion kinetic energy. For many materials, ions with energies below 1MeV/u delivered from medium and small size accelerators have already sufficiently high electronic stopping power to modify materials in different ways. Also, in this energy range the nuclear stopping power can be large enough to provide additional opportunities for materials modifications. In the present paper, we review recent experimental activities of the Zagreb group where ion beams with energies below 1MeV/u, obtained from a 6MV EN Tandem Van de Graaff accelerator have been used. Additionally, we present several novel examples of materials modifications and their analysis with such ion beams.

KANET Test: Experience of Zagreb Group

ABSTRACT A new scoring system for the assessment of fetal neurological status, Kurjak antenatal neurodevelopmental test (KANET), has been recently published in several journals. Test is based on prenatal assessment of fetal behavior by three-dimensional/fourdimensional (3D/4D) sonography. Assessment of fetal behavior gave a promising opportunity to understand the hidden function of the developmental pathway of the fetal central nervous system. This new test has been proposed by the Zagreb group based on the several years of research. In this review we present the most significant results of the Zagreb group which led to construction of KANET test, basic presumptions of the KANET, and our published results on KANET. How to cite this article Miskovic B, Predojevic M, Stanojevic M, Tikvica A, Kurjak A, Ivankovic D, Vasilj O. KANET Test: Experience of Zagreb Group. Donald School J Ultrasound Obstet Gynecol 2012;6(2):166-170.

The use of 4D imaging in the behavioral assessment of high-risk fetuses

Fetal behavioral patterns have been considered as indicators of fetal brain development. Numerous studies employing conventional 2D ultrasound have shown that normally developing fetuses and fetuses at risk exhibit different patterns of behavior. With the appearance and development of 4D ultrasound, fetal behavioral movements, and the full range of facial expressions can be observed. After standardization of valid reference ranges of movements appropriate for the gestational age, the Zagreb group published a new scoring system for fetal neurobehavior based on prenatal assessment by 4D sonography, the Kurjak Antenatal Neurological Test. The aims and objectives of this article were to describe the latest 4D sonographic studies on fetal behavior and to present results of behavioral assessment by KANET in high-risk pregnancies.

Some Topological Indices of Tetrameric 1,3-Adamantane

Topological indices are numerical parameters of a graph which characterize its topology. In this paper the PI, Szeged and Zagreb group indices of the tetrameric 1,3–adamantane are computed.

Prediction of the agonist allosteric enhancer activity of thiophenes with respect to human A1 adenosine receptors using topological indices

Relationships between Wiener’s index W (a distance based topological descriptor), the Zagreb group parameter M 1 (an adjacency based topological descriptor), and the eccentric connectivity index ξc (an adjacency-cum-distance based topological descriptor) of thiophenes, on the one hand, and their agonist allosteric enhancer activity with respect to human A1 adenosine receptors, on the other hand, have been studied. A training set comprising 59 analogs of substituted thiophenes was selected and the corresponding values of Wiener’s index, the Zagreb group parameter, and the eccentric connectivity index for each compound were calculated. The results were analyzed and suitable models were developed after determination of the activity ranges. Subsequently, the biological activity was assigned using these models to each compound involved in the data set, and the results were compared to the reported agonist allosteric enhancer activity. The overall accuracy of prediction was found to vary from a minimum of 84% for a model based on the eccentric connectivity index to a maximum of 91% for a model based on the Zagreb group parameter.

Application of graph theory: Models for prediction of carbonic anhydrase inhibitory activity of sulfonamides

The relationship of Wiener’s index–a distance-based topological descriptor, Zagreb group parameter – M1, an adjacency-based topological descriptor and eccentric connectivity index–an adjacency-cum-distance based topological descriptor with the carbonic anhydrase (CA) isozyme-II inhibitory activity of sulfonamides has been investigated. A training set comprising of 34 analogues of substituted sulfonamides was selected for the present investigations. The values of the Wiener’s index, Zagreb group parameter, and eccentric connectivity index for each of 34 analogues comprising the data set were computed. Resulting data was analyzed and suitable models were developed after identification of active ranges. Subsequently, a biological activity was assigned to each analogue involved in the data set using these models, which was then compared with the reported CA isozyme-II inhibitory activity. Accuracy of prediction was found to vary from a minimum of 82% for model based on Wiener’s index to a maximum of 88% for the model based on Zagreb group parameter. Moreover, highly active range of the proposed models also exhibited appreciable inhibitory activity against CA isozyme-I and CA isozyme-IV.

Application of Graph Theory: Prediction of Cytosolic Phospholipase A2 Inhibitory Activity of Propan-2-ones

The relationship of Wiener’s index – a distance-based topological descriptor, Zagreb group parameter–M 1, an adjacency-based topological descriptor and eccentric connectivity index– an adjacency-cum-distance based topological descriptor with the cytosolic phospholipase A2 inhibitory activity of propan-2-ones has been investigated. A training set comprising 44 analogues of substituted propan-2-ones was selected for the present investigations. The values of the Wiener’s index, Zagreb group parameter and eccentric connectivity index for each of 44 analogues comprising the data set were computed. Resultant data was analyzed and suitable models were developed after identification of active ranges. Subsequently, biological activity was predicted for each analogue involved in the data set using these models, which was then compared with the reported cytosolic phospholipase A2 inhibitory activity. Accuracy of prediction was found to vary from a minimum of ∼84% for model based on Zagreb group parameter to a maximum of 88% for model based on eccentric connectivity index.

Predicting carbonic anhydrase inhibitory activity of sulfonamides: computational approach using topological descriptors

The relationship of Wiener's index—a distance-based topological descriptor, Zagreb group parameter— M 1, an adjacency-based topological descriptor and eccentric connectivity index—an adjacency-cum-distance-based topological descriptor with the carbonic anhydrase inhibitory activity of sulfonamides has been investigated. A training set comprising of 34 analogues of substituted sulfonamides was selected for the present investigations. The values of the Wiener's index, Zagreb group parameter and eccentric connectivity index for each of 34 analogues comprising the data set were computed. Resulting data was analyzed and suitable models developed after identification of active ranges. Subsequently, a biological activity was assigned to each analogue involved in the data set using these models, which was then compared with the reported carbonic anhydrase inhibitory activity. Accuracy of prediction was found to vary from a minimum of 85% for model based on Wiener's index to a maximum of 91% for the model based on Zagreb group parameter.

Impersonality of the Connectivity Index and Recomposition of Topological Indices According to Different Properties

The connectivity index chi can be regarded as the sum of bond contributions. In this article, boiling point (bp)-oriented contributions for each kind of bond are obtained by decomposing the connectivity indices into ten connectivity character bases and then doing a linear regression between bps and the bases. From the comparison of bp-oriented contributions with the contributions assigned by chi, it can be found that they are very similar in percentage, i.e. the relative importance of each particular kind of bond is nearly the same in the two forms of combinations (one is obtained from the regression with boiling point, and the other is decided by the constructor of the chi index). This coincidence shows an impersonality of chi on bond weighting and may provide us another interpretation of the efficiency of the connectivity index on many quantitative structure-activity/property relationship (QSAR or QSPR) results. However, we also found that chi's weighting formula may not be appropriate for some other properties. In fact, there is no universal weighting formula appropriate for all properties/activities. Recomposition of some topological indices by adjusting the weights upon character bases according to different properties/activities is suggested. This idea of recomposition is applied to the first Zagreb group index M(1) and a large improvement has been achieved.

Application of graph theory: prediction of glycogen synthase kinase-3 β inhibitory activity of thiadiazolidinones as potential drugs for the treatment of Alzheimer's disease

The relationship of Wiener's index, a distance-based topological descriptor; Zagreb group parameter, M 1, an adjacency-based topological descriptor and eccentric connectivity index,an adjacency-cum-distance based topological descriptor with the glycogen synthase kinase-3 β inhibitory activity of thiadiazolidinones has been investigated. A training set comprising 28 analogues of substituted thiadiazolidinones was selected for the present investigations. The values of the Wiener's index, Zagreb group parameter, and eccentric connectivity index for each of 28 analogues comprising the data set were computed. Resulting data was analyzed and suitable models developed after identification of active ranges. Subsequently, biological activity was predicted for each analogue involved in the data set using these models, which was then compared with the reported glycogen synthase kinase-3 β inhibitory activities. Accuracy of prediction was found to vary from a minimum of ∼83% for model based on Zagreb group parameter to a maximum of ∼87% for model based on Wiener's index.

Topological models for the prediction of HIV-protease inhibitory activity of tetrahydropyrimidin-2-ones

Relationship between the topological indices and HIV-protease inhibitory activity of tetrahydropyrimidine-2-ones has been investigated. Three topological indices, Wiener's index—a distance based topological descriptor, Zagreb group parameter—an adjacency based topological descriptor and eccentric connectivity index—an adjacency-cum-distance based topological descriptor were used for the present investigations. A dataset comprising of 80 substituted tetrahydropyrimidine-2-one analogues was selected for the present studies. The values of the Wiener' s index, Zagreb group parameter and eccentric connectivity index for each of the 80 compounds comprising the dataset were computed using an in-house computer program. The dataset was divided randomly into training and test sets. Resultant data was analyzed and suitable models were developed after identifying the active ranges in the training set. Subsequently, a biological activity was assigned to each of the compound involved in the test set using these models, which was then compared with the reported HIV-protease inhibitory activity. Accuracy of prediction using these models was found to vary from a minimum of ∼86% to a maximum of ∼88%.