Retroperitoneal fibrosis (RPF) is an uncommon condition characterized by inflammation and fibrosis in the retroperitoneal space. More than two-thirds of RPF are idiopathic, with the remaining stemed from a variety of secondary causes. It was suggested that IgG4-related RPF is a secondary form of RPF. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-related RPF and IRPF in a large Chinese cohort. We retrospectively reviewed the medical records of 132 RPF patients diagnosed at Peking University People’s Hospital between March 2010 and March 2018. Among the 132 patients, the mean age at disease onset was 54.8 years. IgG4-related RPF group showed greater male predominance compared to IRPF group. IgG4-related RPF patients showed a longer interval between symptom onset and diagnosis, and allergic diseases were more common in this group. Sixty-four patients (48.4%) had lower back pain, which was more common in IRPF group than that in IgG4-related RPF patients. In terms of organ involvement, although 42 of 47 patients (89.3%) with IgG4-related RPF had other organ involvement, there were no patients in the IRPF group with other organ involvement. In addition, the serum IgG4 level, elevated eosinophils counts and IgE level were significantly higher in IgG4-related RPF patients. We described the demographic, clinical and laboratory differences between IgG4-related RPF and IRPF patients, indicating their potential differences in pathogenesis, which was of great importance to diagnose and manage the two phenotypes. Retroperitoneal fibrosis (RPF) is a rare disorder characterized by the presence of chronic inflammation and fibrosis in the retroperitoneal space . It usua+ plasma cells and irregular and distinct fibrosis [Last decade, the concept of IgG4-related disease (IgG4-RD) emerged. IgG4-RD consists of fibro-inflammatory diseases that affect a variety of structures . It is featured with lympho-plasmacytic inflammation, infiltration by IgG4fibrosis , 6. It wfibrosis –10.Researchers have proposed that the pathogenesis of IgG4-related RPF may be different with that of idiopathic retroperitoneal fibrosis (IRPF) –13. HoweWe retrospectively reviewed the medical records of RPF patients at Peking University People’s Hospital, from March 2010 to March 2018. A total of 132 cases were diagnosed with RPF, and RPF from other secondary causes were excluded, such as malignancy, infection, drugs, surgical injury, and radiation therapy. Patients who did not receive serum IgG4 detection were also excluded. The diagnosis of RPF was based on the reports of Computed tomography (CT) or magnetic resonance imaging (MRI) from radiologists. Well-delimited but irregular soft-tissue mass surrounding the aorta, which extends from the renal arteries to the iliac vessels was deemed as typical manifestation of image of RPF . RetropePatients were divided into two groups, IgG4-related RPF and IRPF, based on the comprehensive diagnostic criteria published by Umehara et al  in 2011.A standardized case report form was used for data collection. Age at disease onset, age at diagnosis, gender, follow up time, clinical symptoms, smoking history, biopsy status, complication of allergic disease were included in the forms. The location of the retroperitoneal fibrotic mass was classified as periaorta, renal pelvis and ureter by image. For patients who had undergone biopsy, the pathology reports were reviewed.Laboratory index comprised hemoglobin, eosinophil count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatinine before the initial treatment, complement 3 (C3), C4, immunoglobulin E (IgE), immunoglobulin G4 (IgG4) and autoantibodies.According to literature, the treatment response of IgG4-related RPF was defined as improvement in symptoms attributed to RPF or the dimensions of the imaging finding –18. And t-test was used to analyze differences for continuous, normally distributed data; and continuous, non-normally distributed data were analyzed with the Mann–Whitney test. Chi-square or Fisher’s exact tests, as appropriate, was used to process categorical variables. It was considered statistically significant when a P-value was less than 0.05.All statistical analyses were performed by SPSS 24.0. Data were analyzed using descriptive methods, including mean ± SD, median, interquartile range (IQR) and proportions. The Student’s A total of 132 patients diagnosed as RPF were enrolled in this study. Among the 132 cases in our cohort, 47 patients (35.6%) were classified as having IgG4-related RPF , and 85 patients were classified as having IRPF. The demographic features of all cases are shown in P = 0.012). The time from disease onset to diagnosis was 26 months in IgG4-related group, which was significantly longer than that in IRPF group (12 months) (P = 0.001). The mean follow-up time of IgG4-related RPF group and IRPF patients was 20 months and 24months, respectively. In terms of allergic disorders, IgG4-RD RPF patients (21.2%) had a higher frequency of allergic diseases  than that in IRPF patients (4.7%) (P = 0.006).We compared the demographic features of patients with IgG4-related RPF against cases of IRPF in P = 0.035). Thirty-five patients (26.5%) had flank pain and twenty-seven (20.4%) had abdominal pain, respectively. Hydronephrosis occurred in 85 of 132 patients (64.3%), with 35 bilateral and 50 unilateral involvement, however, there was no statistical difference between this two groups. Other constitutional symptoms were fever, weight loss, lower limb edema, venous thrombus, and anorexia (P<0.001). The other organ involvement was shown in P = 0.482).Clinical symptoms varied from patient to patient. Pain was the most common presenting symptom. Sixty-four patients (48.4%) had lower back pain, which was more common in IRPF group (anorexia . Organ iP = 0.04). Hypocomplementemia was a common finding in both IgG4-related RPF (29.8%) and IRPF group (22.4%) (P = 0.345), and the number of patients with low serum C4 was significantly higher in IgG4-related RPF group (P = 0.024). The serum IgG4 level and IgE level were significantly higher in IgG4-related RPF group. IgG4-related RPF patients were more commonly associated with elevated eosinophils counts .We further compared the laboratory tests between these two groups . The levTreatment strategies are reported in With regard to surgical interventions, 55 patients (41.6%) had ureteral stents to help alleviate the symptoms. Ureterolysis was carried out in 18 of 132 patients. Fourteen patients (10.6%) underwent percutaneous nephrostomy.P = 0.868). And the median serum IgG4 level of relapse and no relapse group were 581.5 (243–959) mg/dl and 244 (162–669) mg/dl, respectively (P = 0.082).We further examine the role of serum IgG4 level in treatment among IgG4-related RPF. Among 47 patients with IgG4-related RPF, 34 cases (72.3%) achieved treatment response and 10 patients (21.3%) showed relapse during the follow-up period. The median serum IgG4 level of response and no response group were 252 (171–877) mg/dl and 403 (210–669) mg/dl, respectively , which is consistent with previous studies , 29. TheSteroid therapy is the main treatment option for IgG4-related and IRPF patients. Although there are currently no standard treatment regimens, moderate to high dose of steroids with slow tapering are recommended , 32. In To our knowledge, this is the first study to compare the differences between the two groups in such large sample size. However, this study also has some limitations. This observational study was limited by its retrospective nature with inherent biases, some potential confounding factors could not be well ruled out. And the retroperitoneal biopsies were not conducted for every patient, partly resulting from the fact that retroperitoneal biopsy is a high-risk and invasive procedure.In conclusion, we have analyzed demographic, clinical and laboratory differences between IgG4-RD RPF and IRPF patients. IgG4-RD RPF patients were associated with longer time from onset to diagnosis and showed greater male predominance compared to IRPF patients. Allergic diseases and multi-organ involvement were more commonly observed in IgG4-RD RPF group. IgG4-RD RPF phenotype showed higher level of IgG4 and IgE. These findings indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.S1 File(XLS)Click here for additional data file.S1 Checklist(DOCX)Click here for additional data file.


Inefficiency of medical therapies used in order to cure patients with bacterial infections requires not only to actively look for new therapeutic strategies but also to carefully select antibiotics based on variety of parameters, including microbiological. Minimal inhibitory concentration (MIC) defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotic. Reliable assessment of MIC has a significant impact on the choice of a therapeutic strategy, which affects efficiency of an infection therapy. In order to obtain credible MIC, many elements must be considered, such as proper method choice, adherence to labeling rules, and competent interpretation of the results. In this paper, two methods have been discussed: dilution and gradient used for MIC estimation. Factors which affect MIC results along with the interpretation guidelines have been described. Furthermore, opportunities to utilize MIC in clinical practice, with pharmacokinetic /pharmacodynamic parameters taken into consideration, have been investigated. Due to problems related to PK determination in individual patients, statistical estimation of the possibility of achievement of the PK/PD index, based on the Monte Carlo, was discussed. In order to provide comprehensive insights, the possible limitations of MIC, which scientists are aware of, have been outlined. The increasing resistance of bacteria to antibiotics and more and more common failed infection treatments call for identification of the underlying causes of this problem and, further, for searching the ways to reduce it and to improve the effectiveness of infection therapies. One of the recognized reasons behind failed therapies is the drug selection pressure, especially when they are ill-chosen and administered in doses too small, which leads to the survival of a resistant bacterial population or induces antibiotic resistance mechanisms . TherefoMIC is the lowest concentration of an antibacterial agent expressed in mg/L (μg/mL) which, under strictly controlled in vitro conditions, completely prevents visible growth of the test strain of an organism .in agar○micromethod/ microdilution○macromethod/ macrodilutionin a liquid mediumDilution methodsstrips impregnated with a predefined concentration gradient of antibioticGradient methodsThe following methods are used:H. influenzae strains and antibiotics colistin and daptomycin for which MIC can be determined only by broth dilution and fosfomycin for which, like in EUCAST guidance documents, MIC can be measured using the agar dilution method. In addition, CLSI recommends HTM medium for H. influenzae instead of the MH–F broth medium recommended by EUCAST.EUCAST  mostly rTo determine MIC values, all quantitative methods use Mueller–Hinton (MH) medium either in the form of agar (MHA) or broth (MHB), in some cases additionally supplemented with, for example, 5% lysed horse blood or other compounds depending on bacteria or antibiotic type . Only foTo determine MIC by dilution methods, antibiotics are also needed in a substance that require preliminary dissolution to obtain a stock solution and then dilution to obtain an appropriate starting concentration. For most antibiotics, water is both a solvent and a diluter, including for most beta-lactams, fluoroquinolones and aminoglycosides. Some require alcohol as a solvent, especially macrolides, chloramphenicol and rifampicin, while others require a phosphate buffer or dimethyl sulfoxide DMSO . DissolvWorking solutions should contain double dilutions of antibiotics, with the range of concentrations used for testing depending on the medication concerned and should take into account the MIC breakpoints for reference strains . SubsequIn the broth microdilution method, the prepared working solutions with double dilutions of antibiotics are distributed into appropriate wells of microtiter plates, and in this form they can be either used directly for MIC determinations or can be stored in plastic bags for up to three months at a temperature ≤ −60 °C ,4,6,9.In the agar dilution method, each of the obtained antibiotic concentrations at a volume of 1 mL is added to 19 mL of still liquid MHA medium at a temperature of 45–50 °C and is poured on Petri dishes with a diameter of 9 cm .5 CFU (colony forming units) /mL . R,4. R3,4]akpoints ,42,43. Wakpoints .Salmonella enterica serovar Typhi (S. Typhi). Strains with MIC ≤ 0.06 mg/L had a point mutation associated with the gyrA gene, which further led to the development of resistance of this strain to fluoroquinolones [S. aureus infections. According to literature data [In addition, contrary to qualitative methods, the MIC value allows to assess the degree of susceptibility or resistance to the antibiotic. Information on the degree of susceptibility carries great epidemiological and clinical value, but it must be properly interpreted. The differences in the degree of a strain’s susceptibility to antibiotics cannot be assessed by making a direct comparison of the MIC values obtained for such antibiotics, which, unfortunately, is sometimes done. Such an interpretation leads to the erroneous belief that the strain is most sensitive to the antibiotic for which the MIC is the lowest. EUCAST has greatly facilitated the assessment of susceptibility degree of micro-organisms to antibiotics by introducing new criteria for result interpretation. These criteria distinguish between two levels of susceptibility of strains. The first level concerns standard dosing whereas the second level is referred to higher MIC values and requires increased exposure to the antibiotic. Of course, the magnitude of the MIC value will have an impact on the probability of the pharmacokinetic/pharmacodynamic indexes which are crucial for therapy efficacy. It must not be forgotten that in some cases higher levels of antibiotic MIC close to breakpoints may indicate therapy failure, although the strain might be considered as sensitive at standard doses. This may be the first signal of resistance to the medicine. Such a phenomenon was found, for example, in inolones ,45. The ure data  and EUCAure data , a MIC o90) is close to the breakpoint could be transferred to a group of medications with a limited access to empirical therapy, unless of course there are other factors in favor of using such an antibiotic. Doing so could contribute to reducing the selection of antibiotic-resistant strains, although this would need to be confirmed in the results of studies which are difficult to perform. It is virtually impossible to obtain data about the distribution of MIC values of antibiotics in most hospitals, because the actual values of MIC  are not routinely determined and if they are, they are performed for selected antibiotics only. Thus, there is usually no cumulative data on the distribution of MIC values for dominant pathogens in specific infections. However, this does not mean that the antibiotic stewardship team cannot introduce, in consultation with the microbiological laboratory, a program to monitor the degree of susceptibility to certain antibiotics in a given hospital, especially in those units where, despite the strain’s antibiotic susceptibility, therapeutic failures are more common. The obtained data could be used as a basis for assessing whether the list of antibiotics dedicated for empirical therapy and the dosage regimens adopted are appropriate for the degree of susceptibility of the strains. Based on such cumulative data, Kuti et al. introduced prolonged infusions of meropenem and continuous infusions of cefepime in an intensive care unit to achieve effectiveness given the high MIC values of these antibiotics [Why does the degree of susceptibility matter? The more susceptible the strain to the antibiotic, the greater the likelihood that its MIC is below the ECOFF and therefore the strain does not develop any drug-resistant subpopulation, so there is no increased risk of bacterial survival during treatment. In addition, high susceptibility of the strain increases the chance for reaching the therapeutic concentration of the antibiotic and for effective eradication of the pathogen using the standard dosage even in patients with significant changes in pharmacokinetic parameters. The knowledge of the degree of susceptibility of strains to various antibiotics used in the hospital may also be a tool used in antibiotic stewardship ,48,49,50ibiotics . In addiibiotics . The intS. aureus, Klebsiella claceae (formerly Enterobacter cloacee), Klebsiella pneumoniae, E. coli, P. aeruginosa, Accinetobacter spp., and in many antibiotics, especially colistin, fosfomycin or even carbapenemes. Difficult detection of heteroresistance to colistin, one of the last active antibiotic against resistant Gram-negative bacteria, has led to recommendations update. It is advised to administer properly It is advised to administer properly adjusted first loading dose of colistin and frequently use it in combination with other antibiotics [The use of low MIC values antibiotics during infections treatment may improve therapy efficacy. However, it should be taken into consideration that in some cases, even when correct dosing is applied, pathogen eradication will not be achieved. There may be various reasons of such a condition including heterogeneous antibiotic resistance (heteroresistance), tolerance or persistence of micro-organisms in the environment of certain antibiotics. Each of these phenomena is different from commonly described antibiotic resistance. Typical bacterial resistance is displayed in many mechanisms originated from stable genetic mutation or as a result of expression of acquired, by entire cell population, resistance genes. Heteroresistance means the resistance of a very small subpopulation of cells, which begins to grow rapidly in the presence of an antibiotic while the vulnerable population is killed. Antibiotic discontinuation reduces replication of a resistant subpopulation . The detibiotics . Moreoveibiotics . This isibiotics . Anotheribiotics ,54. Persibiotics ,54. Thos1/2), clearance (CL), maximal concentration (Cmax), minimal concentration (Cmin), and area under curve (AUC). The value of these parameters depends on many factors, such as the patient’s weight or age and on the degree of organ dysfunction, the supply of fluids, but it also varies in different groups of patients. In addition, PK parameters change with time. In the case of antibiotic-resistant strains, identification of the mechanism of bacterial resistance, may have an additional impact on the significance of the MIC value. This topic is particularly discussed in case of Gram-negative bacteria producing carbapenemases. It is widely known that carbapenemases may possess a different spectrum and strength of hydrolytic activity against particular beta-lactams, including carbapenems. According to both EUCAST and CLSI, the detection of the resistance mechanism does not eliminate the possibility of carbapenems use in the treatment of infections caused by carbapenemase-producing bacteria. Regardless of the type of carbapenemase or extended spectrum beta-lactamases (ESBL) produced, clinical interpretation and S, I or R classification of the strain should be based on the obtained MIC value. Currently, meropenem is considered the most important carbapenem, active against Gram-negative Enterobacterales. It is listed among antibiotics recommended for the treatment of infections caused by CPE strains, especially when the strain is defined as S ). Usually, elicitation of full susceptibility indicates effective therapy with the use of standard doses of a drug, but in this case, due to detection of carbapenemase production, meropenem should be used in high doses, i.e., 2 g every 8 h in prolonged infusions. In a range of values 2 mg/L < MIC ≤ 8 mg/L (Susceptible (I), increased exposure, according to EUCAST v.11.0), meropenem should be used in not only in high doses and with prolonged infusion but additionally in combination with such antibiotics as colistin, tigecycline or amikacin, depending on susceptibility of the pathogen. If the MIC value does not exceed 32 mg/L, it is also allowed to use meropenem in case of resistance to carbapenem [The MIC value is regarded to have the greatest importance in the optimization of targeted antibiotic therapy. For this purpose however, it must be analyzed together with pharmacokinetic (PK) parameters that describe the fate of the drug in the host organism. The most important PK parameters are: volume of distribution (Vd), elimination half-life  T > MIC, a parameter reflecting the percentage (%) of time between consecutive administrations of an antibiotic in which the drug’s concentration remains above the MIC. The closer the T > MIC parameter is to 100% the greater the likelihood of efficacy. The achievement of this value is especially important in immunosuppressed patients and in the case of Gram-negative infections ,65,66. F1/2—serum half-life (hours), elimination rate constant (h-), DI = dosing interval (hours).It becomes easier to capture the relationship between the MIC and the achievement of the PK/PD index when the interaction is presented in a graphic form  and also(2) Cmax/MIC is a parameter characteristic for antibiotics whose effectiveness depends on maximum concentration which is many times greater than the MIC (min. 8–10×) and not on the time it is kept above the MIC ,64,73. H(3) AUC/MIC (∫AUC/MIC): characterizes time- and concentration-dependent antibiotics ,74,75,761/2—serum half-life (hours), DI—dosing interval (hours).The formula for the calculation of the AUC/MIC index taking into account the MIC value  is as foThe distribution of antibiotics according to PK/PD parameters is given in When using PK parameters in predicting the clinical efficacy of antibiotics, it is necessary to choose those that are used for specific groups of patients  or to rely on those individually determined for a given patient. However, the latter option is much more difficult . Automat90 value, obtained on the basis of cumulative epidemiological analyses, may be applied. Due to problems related to PK determination in individual patient, statistical estimation of the possibility of achieving the PK/PD index based on the Monte Carlo method has gained recognition. The simulation uses population pharmacokinetic (PK) parameters specific to the patient groups concerned and the individual MIC values of antibiotics. The Monte Carlo method allows to approximate the relationship between the antibiotic MIC and the possibility of obtaining an optimal PK/PD index taking into account the specific dose of the medicine. It is also a useful tool that can be used to check if changing the dosage at the same MIC value will have a positive effect on the PK/PD index.Currently, in anticipation of an individually determined MIC value, the MICSuch ready-made simulations are included among others in EUCAST recommendations in the Rationale documents . HoweverStaphylococcus aureus. According to many studies, the effectiveness of Staphylococcus spp. eradication under the influence of this glycopeptide decreases significantly at MIC ≥ 1 mg/L [Drug sensitivity tests, including quantitative MIC tests, are based on the direct interaction of the pathogen isolated from the patient with a chemical (such as the antibiotic). The result obtained in such test does not take into account the factors affecting the antibiotic in the patient’s body. Factors such as volume of distribution, albumin levels or organ failures  and also the activity of the immune system and its various components, other therapeutic procedures such as nutrition, blood transfusion, or additional drugs can significantly affect the final effect of treatment involving an antibiotic to which the micro-organism is susceptible ,84,85,86≥ 1 mg/L ,88,89,90≥ 1 mg/L . It may Another problem is the time required to obtain the result of drug sensitivity determination which is usually 3–5 days. Thus, the time at which the result is obtained is not the same as the time at which the test was ordered. As highlighted by Doern et al. , while wThe MIC value is currently the best available parameter to reflect the effectiveness of an antibiotic against bacterial strains. Despite standardization of approved methods, it should be taken into consideration that the actual MIC value may differ ± double dilution from the one obtained in investigation. This difference usually does not affect clinical interpretation; although, with MIC value equal to breakpoint, it may be of high significance—firstly, to assess whether the strain is resistant or susceptible, and secondly, to use this value to optimal treatment selection involving PK/PD parameters.The use of MIC value in treatment, based on individually defined PK parameters can significantly improve the effectiveness of antibiotic therapy. Although, the methodology for the determination of these parameters is very difficult and not even accessible to doctors, the PK/PD parameters can be estimated using the Monte Carlo method. Such a solution was proposed by EUCAST, to evaluate the achievement of PK/PD index depending on the MIC and antibiotic dose of known PK. In addition, recently, EUCAST, by introducing two susceptibility categories, has clearly made dose volume and road of administration depend on MIC values. The possibility to use the MIC values to increase the probability of therapeutic success can therefore be easier to implement. However, this does not change the fact that the attempt of determining this value in a microbiological laboratory is difficult due to methodology recommended by EUCAST and CLSI. According to these institutions, the most reliable is the broth microdilution method, a manual, demanding and time-consuming procedure. It should also be underlined that sometimes the information about susceptible strain, which is a result of even as precise value as the MIC, does not necessarily have to be true. It is known that bacteria have mechanisms that are impossible to detect in laboratory routine such as heterogeneous resistance, tolerance or persistence. Unfortunately, this feature of micro-organisms can contribute to the treatment failure, despite the optimal choice of antibiotic therapy.


Background: In recent years, due to its complexity and relevance, academic performance has become a controversial research topic within the health and educational field. The main purposes of this study were to analyze the links between publications and authors via citation networks, to identify the different research areas and to determine the most cited publications. Methods: The publication search was performed through the Web of Science database, using the term “Academic Performance” for a time interval from 1952 to 2019. The software used to analyze the publications was the Citation Network Explorer. Results: We found a total of 16,157 publications with 35,213 citations generated in the network, and 2018 had the highest number of publications of any year. The most cited publication was published in 2012 by Richardson et al. with a citation index score of 352. By using the clustering function, we found nine groups related to different areas of research in this field: health, psychology, psychosociology, demography, physical activity, sleep patterns, vision, economy, and delinquency. Conclusions: The citation network showed the main publications dealing with the different factors that affect academic performance, and it was determined that psychological and psychosocial factors were the most relevant. Academic performance is frequently associated with a country’s social and economic development . NumerouMotivation is an internal condition that influences behavior, i.e., mental power that helps people to meet their goals and achieve academic success ,6,7. To Scientific literature supports that cognitive abilities and self-efficacy can predict academic performance outcomes ,9. In 19Furthermore, psychosocial wellbeing is strongly related to thoughts, motivation, and decision-making relating to academic effort ,12. AccoOther factors related to good performance at school include a healthy diet (rich in fiber and nutrients); practicing physical activity ; sleeping well  and good vision  ,15,16,17Citation network analysis is used to search for a specific topic within the scientific literature. By analyzing one publication, it is possible to find other relevant additional publications, to demonstrate, qualitatively, and quantitatively, the connections between articles and authors by creating groups . FurtherGiven the numerous factors that affect academic performance, this study aimed to identify the different areas of research and to discover the most cited publications. The connection between publications and research groups was also analysed using CitNetExplorer, software which enables the study of how the scientific literature in a particular field of has evolved.The search was performed using the Web of Science (WOS) database, by entering the main descriptor: “Academic performance”, as this is the most commonly used expression in both fields, education and health. The search was limited to a topical search (TS) on article, keywords, and abstract, linked with the OR Table. Time was limited to the interval 1952–2019. Likewise, the Web of Science database allows the adding of references to its library when performing bibliographical searches directly in external databases or library catalogues.With regards to the citation indices, the Social Sciences Citation Index, Science Citation Index Expanded and Emerging Sources Citation Index were used.On the other hand, and due to the differences in citation styles among authors and institutions, CiteSpace software was used with a view to standardizing the data. The search and download date of the publications was the 25 April 2020.All the publications were analyzed using the Citation Network Explorer software. This software is used for analyzing and visualizing the citation networks of scientific publications. It allows the researcher to download citation networks directly from Web of Science. Likewise, it makes it possible to manage citation networks which include millions of publications and related citations. In this way, a citation network comprising millions of publications can be initiated so a deeper analysis can then be performed in order to obtain a smaller subnetwork of 100 publications on the same topic. By using the citation score as an attribute, a quantitative analysis of the most cited publications within a specific time interval was performed. Through this, internal connections within the WOS database were quantified. By considering other databases, included in the WOS, the external connections were also quantified .CitNetExplorer offers a number of techniques to analyze the citation networks of publications. The clustering function is achieved using the formula developed by Van Eck in 2012 [The clustering function was used to establish a group for each publication. This function grouped those publications with a greater level of association according to the citation networks .Finally, the central publications were analyzed using the Identifying Core Publications function. The role of this function was to identify the publications that were considered as the core of the citation network and eliminate those which were considered insignificant. The number of connections was established by the researchers, meaning therefore that the greater this parameter was, the lower the number of central publications would be . Thus, tOn the other hand, the drilling down function was used, as it allows deep analysis to be carried out at different levels for each of the groups.The first articles on academic performance were published in 1952, so therefore it was decided that the selected time interval would be from 1952 to 2019. 16,157 publications and 35,213 citations inside the WOS were found. Out of all the publications, 77.62% were articles, 13.5% proceedings papers, 3.75% reviews, 2.16% meeting abstracts, 1.61% book chapters and the remaining 1.01% was comprised of editorial materials, letters, notes, book reviews, corrections, books, data papers, news items, reprints, amendments, additions and retracted publications.The number of publications on this topic has increased significantly since 2015 . 2018 was the year with the highest number of publications, with 1889 publications and 120 citations on the network .Out of the 20 most-cited articles, 11 dealt with the psychological factors that affect academic performance ,32,36,37Academic performance is a multidisciplinary research field and the areas of education (36%) and psychology (28.24%)  are partThe countries with the highest number of publications are the United States (39.10%), Spain (8.51%) and England (5.54%) .23 groups were found using the clustering function, with 9 of these groups containing a significant number of publications; however, the remaining 14 groups only reached 1.5% .With regards to clustering parameters, a resolution value of 1.0  was considered, and the minimal publication size for each group was 500.In group 1, 3223 articles and 11,097 citations were found across the network. The most cited publication was the article by Richardson et al. , which wIn group 2, 1095 publications and 4407 citations were found across the network. The most cited publication in this group was the article by Hillman et al. , which wIn group 3, 971 publications and 2638 citations were found across the network. The most cited publication was the article by Ferguson et al. , which wIn group 4, 776 publications and 1354 citations were found throughout the network. The most cited publication was the article by Fuligni et al. , which wIn group 5, 734 publications and 1567 citations were found throughout the network. The most cited publication was the article by Crede et al. , which wIn group 6, 665 publications and 1107 citations were found throughout the network. The most cited publication was an article by Duncan et al. , which wIn group 7, 640 publications and 2407 citations were found throughout the network. The most cited publication was an article by Curcio et al. , which wIn group 8, 619 publications and 1587 citations were found throughout the network. The most cited publication was an article by Dupaul et al. , which wIn group 9, 591 publications and 1772 citations were found throughout the network. The most cited publication was an article by Kirschner et al. , which w10 subclusters have been found , five of10 subclusters have been found , three o4660 publications with four or more citations  and a citation network of 23,747 were found .The main databases, such as WOS and Scopus, allow for the exploration of citation networks. However, these databases do not offer a general overview of the connection between citations from a group of publications. Thus, their usefulness is limited to carrying out a systematic review of all existing literature. This is the reason why we used CitNetExplorer software to visualize, analyze, and explore citation networks of scientific publications. CitNetExplorer offers a more detailed analysis of the citation networks in comparison with other databases such as WOS or Scopus .As our main objective was to analyze all the existing literature on the different factors that influence academic performance, we used the WOS database to perform our bibliographic search, given that it is the only database for which the search range begins in 1900. However, it is important to point out that WOS only accepts journals with an international presence, and these are only admitted following a rigorous selection process. In this way, the CitNetExplorer software allowed us to gather and analyze all of the literature available on academic performance up to the present date. Furthermore, the connection between the fields of study and the different research groups was also found by using citation network analysis.In order to obtain the results, the following functionalities were used: the clustering functionality, as it allows the publications to be grouped by citation relationship; the drilling down functionality, which provides a deeper analysis of the existing bibliography for each of the groups; and the core publications functionality, which shows the most relevant publications, i.e., those which have a minimum citation number. Therefore, these functionalities enable the researcher to conduct a complete analysis of the studies published on a particular subject. In recent years, the number of publications on academic performance has significantly increased. In the past, research carried out on this topic focused predominantly on the influence of psychological factors on academic performance ,81. FromSince 2015, the number of publications on psychological and psychosocial factors has increased by 52.83% and they have taken a multidisciplinary turn. As such, multiple factors that affect academic performance, such as demographic, psychosocial, psychological, lifestyle, and mental and physical health factors, have been analysed. ,83,84,85With regards to the authors, Kirk is worth mentioning in the early years, for having published over 70 papers on academic performance between 1952 and 1982. Currently, Rozelle and Salamonson are considered as two of the most prominent authors in this field of study, as they have published 40 and 33 papers respectively in the period between the years 2005 and 2010 and up to date.2018 has been identified as a “key year”, given the large number of publications and the content of the documents, in which the main topic of study was the importance of mental and physical health on academic performance ,87. In tThe countries with a greater number of publications are the United States, Spain and Britain. The educational systems of these countries are intense, which places students at a higher risk of anxiety and stress. Furthermore, and with regards to psychosocial factors, the students are more competitive. Consequently, many studies have focused on analyzing risk factors for academic performance in these countries. Nevertheless, it must be taken into consideration that, in the case of China, students are showing symptoms of anxiety and depression more often, and therefore the number of publications is expected to increase over the coming years. In the United States, the number of publications is significantly higher than in other countries. This is due to increased interest in the topics related to student learning. Likewise, the trend for the number of publications to increase in the field of education in countries like the United States or Britain has been associated with a combination of factors, such as being English-speaking countries and the possible connections among the various research groups in the scientific community ,89.With regards to the journals with the larger numbers of publications, it is worth mentioning that they are mainly Psychology and Educational Science journals, as psychological and psychosocial factors are those with the greatest influence. Moreover, the majority of the journals are from the United States and Britain.Nowadays, students are more competitive and are therefore at a greater risk of suffering from stress. Several authors have defined stress as “an adverse reaction that people have to excessive pressures and demands placed on them. In other words, stress arises when people find themselves in an overwhelming situation and believe they are unable to cope with it” ,91. The Health professionals recommend physical exercise and a balanced diet to prevent stress. Several studies have shown that people who exercise are less likely to suffer from anxiety and depression, and that stress symptoms can be improved by doing exercise ,94. AnotIn the future, health and welfare programs must be established in schools to reduce the incidence of behaviors that could have a detrimental effect on the physical and mental health of young people, as this could result in improved academic performance. In the study by Van Loon et al. , publishThis study provides a brand new approach which can guide researchers in the revision of the wealth of literature that exists on academic performance. Over the coming years, research in this field will continue to focus mainly on the impact of psychological factors on academic performance as a consequence of the constant increase in competitiveness among students. In this way, research questions based on this data posed by future studies will focus mainly on how psychological and psychosocial factors could be improved in order to increase academic performance.Likewise, the number of studies on the impact of the use of devices on academic performance is also likely to increase, given that constant changes in lifestyle are becoming more and more frequent. With regards to citation network studies, they are also likely to become more numerous as it is the only method of analysis which provides a global overview of the different research fields within a particular subject. Moreover, the CitNetExplorer software facilitates the analysis of all existing studies on a given topic, thus allowing for detailed research to be conducted, which might change the way in which research is carried out in different fields of study.In this study, 16,157 publications on academic performance were analysed, which were obtained from the Web of Science (WOS) database between 1952 and 2019. All of the publications were analysed using the Citation Network Explorer software, which makes it possible to visualize, analyze and explore the citation networks of scientific publications.Academic performance may be influenced by various factors, including psychological, psychosocial, economic, environmental or personal factors. Self-sufficient students present learning and self-control skills which facilitate studying, and as a consequence increase their motivation. This means that they have the skills and willingness to learn. Likewise, the personality of the students with psychosocial wellbeing is often characterized by determination and pragmatism in academic effort, which enables them to set high-level goals for themselves, which they successfully pursue. On the other hand, scientific evidence suggests a significant relationship between academic performance and health, meaning that vision problems, nutrition, stress, obesity, anxiety, behavioral disorders or aggression are associated with poor academic performance. This is why it is necessary to establish health and wellbeing programs in schools, which are aimed at preventing behaviors that put the mental and physical health of young people at risk, and at improving their academic performance.The citation network showed the main publications on the different factors that affect academic performance, and it was determined that psychological and psychosocial factors were the most relevant. This study offers a global overview of the number of publications for each of the years and field of study, as well as a general description of the 20 most-cited publications.


Antibiotics are notable weapons in fighting bacteria. Nowadays, however, the effectiveness of antibiotics is severely hindered by the increasing levels of antibiotic resistances in pathogenic bacterial populations, which can persist due to the selective pressure caused by antibiotic exposure. Arguably, the main cause of antibiotic resistances endurance in nature is antibiotic misuse, such as via overusing, inappropriate prescribing as well as the uncontrolled use in agriculture and livestock. There is also a lack of knowledge on appropriate antibiotic usage by the general public. Public scientific literacy and more research on therapeutic practices are fundamental to tackle this problem. Here, we present SimulATe a software which allows the simulation of the effects of antibiotic therapies on bacterial populations during human infections. This software can be used to develop students’ scientific literacy, using infections and antibiotic treatments as context to engage students in scientific practices, and discussions on antibiotic treatment onset and duration or on its use in immunosuppressed or critically ill individuals. SimulATe’s features also allow it to be used for research purposes allowing the simulation of real scenarios and exploration of their outcomes across the parameters’ landscape. Antibiotics can be crucial for the survival of severe bacterial infections, and its introduction into medical practice led to a decrease in the rate of human death due to infection . In the http://forio.com/simulate/busekirmaz92/antibiotic-resistance ); ‘Stochastic Simulation of E. coli Antibiotic Resistance’ ); ‘Antibiotic Resistance Evolution Simulator’ ); or ‘Superbugs’ ). These applications have one feature in common: the simulation of the effects of antibiotic resistance, in general. Some were aimed at being used to teach the concept of antibiotic resistance, but none allows for a great customization of the simulation, thus limiting the possibilities of engaging students in scientific practices.Some applications have been developed with the aim of simulating the effect of antibiotic administration, although not completely customizable in terms of parameters: ‘Antibiotic Resistance Game’  user-friendliness; (2) allow manipulation of several variables and parameters; (3) allow the testing of hypotheses and predictions and (4) adapt to different scenarios. These features make this software interesting from an educational point of view, providing teachers with a resource, which can help to foster their students’ scientific literacy and also make it an interesting tool with which to perform scientific research about antibiotic resistance evolution and its impact on bacterial communities.SimulATe was written using the Python 2.7.13  programmSimulATe makes use of several mathematical equations which, together, govern the interaction between antibiotic, bacteria and immune system. All equations were based on a study by Gjini and Brito . Their dB)Bacteria density , (d) indicates the presence of antibiotic, and This equation yields a new bacterial density for a given time step, where N)Naïve precursor cells density Effector cells density Memory cells density Antibiotic uptake omega is the defined bacteria density threshold. Both these equations yield the state of the antibiotic administration at each time step as a Boolean value, either 0 (antibiotic is being administered) or 1 (no antibiotic is being administered).Antibiotic uptake  activities which can be explored using SimulATe as an educational resource see  1. The fGiven the impacts of personal and medical decisions on the use of antibiotics, while using SimulATe as an educational resource, teachers should explore the importance, applications, and limitations of models in science. It should also be discussed under which circumstances these kinds of models can be used to inform public and private decisions. In agreement with NRC  recommendelta parameter], we assume that, in a bacterial population, some individuals will be able to persist in the presence of an antibiotic. In this scenario, we have considered antibiotic-sensitive bacteria as 10 times more abundant than resistant bacteria although growing at the same rate. These are the default parameters in SimulATe and will, from this point forwards, be considered as the standard condition. Given that bacteria reproduce by duplication, bacterial load will increase exponentially with time. In the human body, in an auto-limited bacterial infection, this growth will stimulate a pathogen-tailored immune response, proportional to the density of the pathogenic bacteria, which eventually clears the infection  be used for educational purposes; (2) be user-friendly, enabling the manipulation of several variables and parameters; (3) allow students to engage in several scientific practices required to become scientific proficient , 18; andOur results suggest that SimulATe cannot only model scenarios that support ECDC’s recommendations but also provide the required conditions for students to analyse the outcomes in distinct situation scenarios.This also highlights the potential of using SimulATe for research projects that study the effects of antibiotics on bacterial population dynamics and to model realistic scenarios of treatment and its expected outcomes by varying different parameters of infectious processes. Nonetheless, a real parameterization could be difficult to achieve, which leads us to emphasize that the simulations should be assessed with caution and in its proper context.One important limitation of the SimulATe software is that it does not take in account horizontal gene transfer of antibiotic resistance coding elements that shape population dynamics by changing the frequency of resistant bacteria in a population.https://github.com/Kronopt/SimulATe.The SimulATe software is available, under the GPL-3.0 license, at bpz004_Supplementary_DataClick here for additional data file.


Antibiotic resistance is a major public health concern. It has been associated with factors such as uncontrolled consumption, lack of knowledge, beliefs, and sociodemographic characteristics. Lebanon is characterized by high levels of antibiotic misuse, as almost half of the population self-medicates with antibiotics and over 30% of the antibiotics are dispensed without prescription. To-date, no studies determined adequately the association between knowledge, beliefs and antibiotic misuse in Lebanon.To assess the association between level of knowledge and beliefs about antibiotics, and antibiotic misuse in Lebanon.We conducted a cross-sectional study among 1,421 parents of schoolchildren using an anonymous self-administered Knowledge, Attitude and Practices questionnaire. The participants´ level of agreement with each item of knowledge and beliefs was measured using a Likert-type (0–10) scale. Misuse practices in the last month were detected through a series of questions aimed at determining the level of compliance with physicians´ instructions in terms of dosage and duration. Data were analyzed using logistic regression.277 participants (16%) acknowledged using antibiotics in the previous month, 41% of whom showed at least one misuse behavior. Misconceptions and beliefs about antibiotics substantially increased the odds of their misuse. For instance, participants who believed that antibiotics were effective in treating viruses, cold, or sore throat infections were twice as likely to misuse antibiotics . Parents who usually keep antibiotics at home antibiotics for future use were more likely to misuse antibiotics [aIqOR: 2.44 ].Our findings indicate that the low level of knowledge and the existence of erroneous beliefs about antibiotics are associated with increased odds of antibiotic misuse. Key elements including rationale prescription and control of dispensing should be addressed when designing educational campaigns against antibiotic misuse. Antibiotic resistance is a growing global public health concern, with heavy economic and social burdens. Antibiotic-resistant bacteria cause 700,000 deaths per year worldwide, and it is predicted that resistance will be more lethal than cancer by 2050.  The misuPopulation mobility is another important factor contributing to the globalization of the antibiotic resistance threat, as international travelers disseminate resistant bacteria across geographical boundaries. , 9–10 InA complete list of all private and public schools in the Beirut area was compiled and an invitation to participate in our study was sent to each school’s administration. 11 schools accepted our invitation and the parents of schoolchildren attending those schools were enrolled in this study and were provided with a printed copy of the questionnaire.Our study was authorized by the Lebanese Ministry of Education and Higher Education and approved by the Institutional Review Board at the American University of Science and Technology (AUST-IRB-20180202-01).We calculated the sample size based on the following assumptions: alpha = 0.05, power: 0.8, ratio exposed/non exposed: 2, Odds Ratio to be detected: 2. With these assumptions, the needed number of respondents was 1052 subjects.Schools were contacted by telephone or electronic mail, or were visited, in order to explain the study purpose and obtain the approval of schools’ directors to circulate the questionnaire among the community of parents. Before delivering it to parents, the questionnaire was reviewed by the board at every school, and parents were informed about the study objectives and the expected delivery date of the questionnaire by the director’s office.As the questionnaire was anonymous, a written informed consent was neither necessary nor reasonable as it would have defeated the objective of anonymity. We therefore placed the following statement in the first page of the questionnaire : “By senThe questionnaire was then delivered to the parents in the main two languages of instruction used at the school . A questionnaire was delivered to every household in a sealed envelope given to only one child of the family attending the school. Only one of the parents (either the mother or the father) was requested to answer the questionnaire. The parents were also notified about the questionnaire delivery in the same day in order to assure that they received the questionnaire. An extensive follow up was conducted to maximize the response rate. Questionnaires were collected five days after they were provided to parents.https://doi.org/10.6084/m9.figshare.9929897.v1Data were collected at different time points: November 2018 and January 2019. The corresponding dataset is available in the data repository FigShare We selected relevant items from published questionnaires that preferably underwent a validation process previously. , 16–19 IUsing antibiotics without medical prescription, shortening the duration of treatment with antibiotics, saving or sharing leftover antibiotics, skipping a dose of antibiotics or changing the prescribed dose were considered as practices of antibiotic misuse.The level of agreement with the knowledge and beliefs statements was measured using a scale of zero  to 10 . For the items assessing attitude to antibiotics and demographic characteristics, respondents were given a set of possible answers to choose from. The questionnaire was initially written in English then translated forward and backward by bilingual researchers into Arabic and French languages. The questionnaire was designed using Remark Office OMR software  to allow for automated optical reading of the data, thereby minimizing errors during data entry. The English version of the questionnaire is available as an online supplement . SubsequTo assess the reproducibility of the instrument, the questionnaire was administered to 60 subjects on two occasions, with a four-week interval. The intraclass correlation coefficients (ICCs) with their 95% CI and the weighted kappa indexes were calculated for variables with 0–10 scale outcomes and for nominal variables, respectively. Items showing an ICC value or weighted kappa index ≥ 0.4 were considered acceptable and retained in the final questionnaire.In this study, six different outcomes were used to assess the misuse of antibiotics. The first outcome assessed antibiotic use without medical prescription and was determined by asking the following question “Q20. Who prescribed or recommended the use of antibiotics to you?”. The second outcome addressed the shortening of antibiotic therapy and was assessed through the question “Q21. The last time you had to take antibiotics; did you complete the course of treatment?”. The third outcome assessed whether unused antibiotics were saved or shared, using the question “Q22. What did you do with the antibiotics that were left unused?”. The fourth outcome assessed whether in case of a missed dose, the subsequent one was doubled or taken when remembered. The question used was “Q24. What did you do when you skipped a dose of your antibiotics?”. The fifth outcome assessed whether the parent modified the dose without medical advice and whether it was an increase or a decrease in the dose. We used two questions: “Q25. The last time you had to take antibiotics, did you change the dose on your own ” and “Q26. What did you do when you changed your dose of antibiotics on your own ?”. In the sixth outcome, the occurrence of any of the previously mentioned five misuse behaviors was evaluated.The independent variables consisted of each item of knowledge, attitude or behavior included in the questionnaire. Covariates included age, sex, financial status, educational level, area of residence, alcohol consumption, access to medical care facilities, and frequency of telephone medical consultation.Associations between independent variables and misuse of antibiotics were modeled using multiple logistic regression. Potential confounders were introduced consecutively into the model, and those that modified the value of the adjusted odds ratio by at least 10% were retained in the final model. Only individuals with complete data on the variables included in the model were analyzed. Finally, the adjusted interquartile odds ratio (aIqOR) were calculated to measure the effect of the exposure change from the 25th to the 75th percentile.Out of 4,460 questionnaires distributed, a total of 1,460 (32.7%) were answered by the parents. 39 questionnaires were excluded as they were incompletely answered. We observed that these 39 excluded subjects had very low educational level (unschooled or primary education). The demographic characteristics of the parents included in the analysis are indicated in In our study population, 64.1% of the participants did not always consult the doctor when they were sick; 8.9% of them due to financial reasons and 34.3% because of a lack of time. More than 60% of the respondents tended to consult the doctor over the phone and 27% believed that there was no need for always visiting the doctor.In the month preceding the study, 277 (16%) parents had used antibiotics and 94 (41.4%) of them had shown at least one misuse behavior. The most frequent misuse behaviors consisted in using antibiotics without medical prescription (22.5%), keeping antibiotic leftovers for future use or sharing them with other individuals (22%), and doubling the dose of antibiotics or taking it when remembered, in case a dose was skipped (10.6%). The associations between the items of knowledge and beliefs with each pattern of misuse of antibiotics were calculated after adjusting for gender and age. These variables were kept in the final model due to their biologic relevance and their known potential for confounding in epidemiologic studies. These associations are presented below.Parents who thought that antibiotics were effective against viruses were twice as likely to present any of the antibiotic misuse behaviors [aIqOR: 2.08 ] . This miParents who thought antibiotics treat colds were at substantially higher odds of any misuse behavior [aIqOR: 1.81 ] . SpecifiThe odds of misusing antibiotics were more than twice higher among parents who usually take antibiotics when they suffer from a sore throat [aIqOR: 2.19 ] . These pParticipants who usually keep antibiotics at home for future use were more than twice as likely to misuse antibiotics [aIqOR: 2.44 ] . They weSimilar results were obtained for subjects who tends to buy antibiotics without medical prescription when they believe that they need a drug-based treatment that the physician did not prescribe Tables  and 3.Parents who believed that the physician explained clearly the motives for prescribing or not prescribing antibiotics were less likely to use antibiotics without medical prescription [aIqOR: 0.63 ] . The patThis study is the first to quantitatively assess the relation between the level of knowledge and beliefs, and the misuse of antibiotics in Lebanon, using measures of association. We showed that the misuse of antibiotics in Lebanon is strongly associated with the level of knowledge and the beliefs of the population. Furthermore, preference for storing antibiotic leftovers was identified as an attitude leading to antibiotic misuse. In contrast, trusting the physician´s decision, believing that the physician explained clearly the motives for prescribing or not prescribing antibiotics, and believing that the pharmacist explained clearly the instructions of use of antibiotics and their correct therapeutic compliance, were associated with a lower frequency of misuse.Our findings have important implications. They confirm that the prevalence of antibiotic misuse remains high in the country, since 41% of the participants who took antibiotics in the month prior to the survey showed at least one misuse practice. Previous studies had shown that 22% to 51% of the Lebanese self-medicated themselves with antibiotics. , 13 FurtTo date, the determinants of inappropriate antibiotic prescription have not been evaluated in Lebanon specifically. However, inappropriate antibiotic prescription practices have been widely reported, including in developed countries. , 22 In gThe present study has its strengths and limitations. To our knowledge, it is the largest study that was ever conducted in the country on this topic though we cannot disregard the fact that only one-third of the parents answered the questionnaire, which may have increased the possibility of response bias. However, as observed in some studies, non-respondents are more likely to have poorer socio-economical levels and health profiles than the respondents. , 30 TherPrevious studies in similar settings in Lebanon have mainly relied on convenience sampling. , 13 Our Another potential limitation of our study is its cross-sectional design. Theoretically, this design does not allow inferring causal effects as the outcome (misuse of antibiotics) may have preceded the exposure (knowledge on antibiotics). However, in KAP studies, this is unlikely to occur as knowledge and beliefs, in general, are formed long before the misuse practices. Finally, we cannot ignore the possibility of overestimating the statistical significance due to multiple comparisons.Since patients´ demands and perceptions strongly contribute to inappropriate prescription and use, as well as to antibiotic dispensing without medical prescription, we believe that interventions aiming at promoting proper use of antibiotics should include public awareness, implementation of regulations regarding the sale of antibiotics without medical prescription, the dispensing of exact quantities as indicated in the medical prescription, as well as enforcing laws for antibiotic prescription according to international clinical guidelines. In this regard, it has been shown that modern communication methods such as social media platforms and web-based initiatives proved useful in improving the knowledge of the population on antibiotic medication. In the present study we identified the factors (knowledge and beliefs of the population) that are associated with the behavior towards antibiotics. Our results could prove useful for countries that share a similar situation of antibiotics´ improper use. We showed that there is a need for educational campaigns that improve the awareness of the population towards the proper use of antibiotics and the consequences of their misuse. Future studies assessing country-specific determinants of antibiotic misuse, such as country wealth and healthcare system factors would be useful for the implementation of comprehensive multilevel interventional programs aimed at limiting the spread of antibiotic resistance.S1 File(PDF)Click here for additional data file.


The paper presented aimed at examining the effect of a fiber-reinforced concrete layer in the compressed zone on the mechanical properties of composite fiber-reinforced concrete slabs. Steel fibers (SF) and polypropylene fibers (PP) in the amount of 1% in relation to the weight of the concrete mix were used as reinforcement fibers. The mixture compositions were developed for the reference concrete, steel fiber concrete and polypropylene fiber concrete. The mechanical properties of the concrete obtained from the designed mixes such as compressive strength, bending strength, modulus of elasticity and frost resistance were tested. The main research elements, i.e., slabs with a reinforced compression zone in the form of a 30 mm layer of concrete with PP or SF were made and tested. The results obtained were compared with a plate made without a strengthening layer. The bending resistance, load capacity and deflection tests were performed on the slabs. A scheme of crack development during the test and a numerical model for the slab element were also devised. The study showed that the composite slabs with fiber-reinforced concrete with PP in the upper layer achieved 12% higher load capacity, with respect to the reference slabs. The requirements for the load-bearing capacity and serviceability of structures are becoming more and more stringent under various conditions of operation, and meeting them is becoming problematic in the case of ordinary concrete. The reason for the formation and propagation of cracks in concrete structures is their brittleness, which causes the use of normal concrete as a material transmitting tensile stresses independently to be limited . ShrinkaAccording to the literature review, the use of different fibers in the concrete technology has become very popular in recent decades. This type of concrete is called fiber reinforced concrete (FRC) and can be defined as a material consisting of Portland cement, fine and coarse aggregates as well as short, irregular fibers. By using FRC, architects and designers have greater architectural freedom in designing the shapes and forms of structural elements because the use of steel reinforcement bars can be almost eliminated. Many factors influence the mechanical properties of the fiber-reinforced concrete ,27,28,29Usually, PP ,9,12 andDesigners quite often use one of the most innovative structural solutions, namely composite structures. These are structures combined of two materials, e.g., steel–concrete, wood–concrete and concrete–concrete. The combination of two materials is used in the construction of such structural systems as plates, columns, beams and spandrel beam ,40. The In this research, the influence of fibers on the mechanical properties of steel or polypropylene FRC composite panels was considered. The lower layer of the slab (5 cm thick) was ordinary concrete, while the upper layer (3 cm thick) was fiber concrete—one with SF and one with PP fibers. Two concretes of different classes and structures were wet-bonded. The purpose of using steel and polypropylene fibers is to control cracks at different curing periods of concrete slabs and different crack widths. In addition, the polypropylene fiber is a rather cheap polymer and can be an effective approach to increase the possibility of plastic shrinkage cracking, impact resistance and hardness of a reinforced concrete fiber slab.The experimental study consisted of tests on cubes, beams, cylinders and prismatic samples made of ordinary concrete and SF or PP reinforced concrete. Compressive and flexural strength, static modulus of elasticity, frost resistance and tensile flexural behavior, as well as bending resistance test of a complex concrete slab were determined and analyzed. A comparative analysis of the experimental results and results from numerical simulations in terms of deflections was also performed.Two types of fibers were used in the research carried out: straight steel fibers  and polypropylene fibers . The appearance of the fibers applied is shown in Three concrete compositions for testing were established on the basis of EN 206–1  standardThe fine and coarse aggregates used in the concrete mixtures met the provisions of the EN 12620 standard .A very important stage in the production of samples and test elements was the proper design of the concrete mix as well as its preparation. The mixture using steel and polypropylene fiber required proper dosing of ingredients in the right order and mixing time. Weighted components were added in the following order: concrete with dispersed fiber initially dry components were mixed for about 7 min , then the fiber was added and mixing continued for another 10 min. After that time, a superplasticizer with 1/3 of the water volume was added to the previously mixed ingredients. After 3–4 min of further mixing the remaining water was added. Then, in order to prepare the samples and elements for testing, the concrete mixture was laid to the previously prepared forms.As mentioned above, different plasticizers were added to particular concrete mixes. Their characteristics are shown in According to EN 1008 , the wat3 of the batch of concrete. The use of reactive powder may increase the water content without reducing the strength characteristics of the concrete. This material is a highly reactive pozzolanic additive, which contains the active forms of aluminum and silicon oxides. Its use improves workability, plasticity and consistency of the mix. It is a factor responsible for lowering the temperature dynamics of concrete and increasing the resistance to negative environmental effects. The application of the powder eliminates the sulfate corrosion. In turn, silica dust is a powdered mineral additive with highly pozzolanic properties. Its use reduces lime hydroxide, increases watertightness and improves the workability of the concrete mix.Moreover, reactive powder and silica ash were added to the F-RCS and F-RCP concretes. Their properties are presented in Four types of samples were prepared for the tests. For the determination of the compressive strength, 18 cubic samples (6 per concrete) with an edge length of 100 mm were made. Cylindrical specimens with a height of 300 mm and a diameter of 150 mm, in the amount of 3 samples for each concrete, were made to test the static modulus of elasticity . The flexural strength test was carried out on 400 mm high prism-shaped samples with the base dimensions of 100 mm × 100 mm . The dimensions of the above-mentioned samples were in accordance with the EN 12390-1 standard . Their mThe first stage of sample making was to measure the weight of individual components with the accuracy of 0.1 g, according to the recipes given in The main research elements were reinforced concrete slabs made from reference concrete and reference concrete combined with fiber-reinforced concrete. They were used to demonstrate the influence of the application of a layer of fiber concrete in the compression zone on deflections, the nature of crack development and the load-bearing capacity of the slabs. The slabs were marked as follows: C-REF—reference concrete; C-REF + F-RCS—reference concrete combined with the fiber-reinforced concrete with steel fibers and C-REF + F-RCP—reference concrete combined with the fiber-reinforced concrete with polypropylene fibers. For the above-mentioned types of slabs, 3 slabs for each were made . The slabs had dimensions of 1200 mm × 600 mm × 80 mm. In the C-REF + F-RCS and C-REF + F-RCP slabs, the lower layer of 5 cm thick was the reference concrete, the upper layer (3 cm thick) was fiber concrete, while the C-REF slabs were made entirely of the reference concrete. In the C-REF + F-RCS and C-REF + F-RCP slabs, two different types of concrete were “wet combined”. The molds for slabs were made of plywood. The reinforcement of the slabs was a reinforcement net, formed from 8 mm (in diameter) ribbed steel bars of the BS500SP steel grade. The reinforcement was designed in accordance with EN 1992-1-1 . The lonThe molds for the slabs were precoated with an antiadhesive agent. After the concrete mix for the molds had been laid, the lower layer of the test element made of reference concrete was compacted on a vibrating table. The upper layer of the slab, fiber concrete, was also laid and compacted on a vibrating table. Next, the surface of the slabs was leveled. After concreting the slabs, they were left for 24 h at 20 °C. Following their removal from the molds, the main research elements were covered with PVC foil and cured until the strength tests were carried out.The compressive strength test was carried out on the cubic samples on the basis of standard EN 12390-3  on a tesThe cylindrical samples were tested for the static modulus of elasticity, according to the standard EN 12390-13 . Figure The bending tensile strength test was carried out on the basis of the EN 12390-5 standard . The samAfter the samples were saturated with water, they were tested for frost resistance. The samples were frozen for 4 h at −20 °C and subsequently thawed in water at +20 °C. The samples were evaluated in terms of mass loss and reduction in compressive strength, in comparison to the reference concrete, which was submerged in water +20 ± 2 °C throughout the test. The test was carried out in line with the PN-B-06250 standard .The beam specimens were placed in the testing machine and then subjected to a central force load. The essence of the research was to determine the stresses in the tensile zone that caused damage to the specimen. The flexural strength was considered to be the moment when an increase in the loading force did not increase the load-bearing capacity of the element.The bending strength test of the plate elements was carried out on the slabs with reinforced fiber concrete compression zone and the slabs made entirely of the reference concrete. The reinforced concrete slabs were placed in the CONTROLS  testing machine, where they were loaded locally with axial force through a centrally positioned steel plate .Inductive sensors were also set up to measure the displacement during the tests. Sensors no. 1 and no. 2 were located in the center of the longer edges of the slab . Figure The induction sensors recorded the actual deflections of the composite and control slabs. The readout was performed at the initial phase, and then each time the applied force increased by 5 kN. The force that destroyed the tested element was assumed as the bearing capacity of the slab. Each tested slab element was destroyed.In order to compare the results of deflections obtained from experimental studies, a model of the research element was designed in the Autodesk Robot Structural Analysis numerical program, which is based on the finite element method. In the calculating program, a slab made of the reference concrete with the parameters obtained from the experimental research was modeled (the length of the slab between supports amounted to 1000 mm). Then, the modeled slab was divided into finite elements with a mesh size of 10 cm . AfterwaThe results of strength tests are summarized in The studies on the fiber-reinforced samples showed that the use of fibers noticeably improved the mechanical properties of concrete compared to the concrete without them.As it can be seen in While analyzing the results only for the fiber-reinforced concretes, which had the same percentage of fibers added, it can be seen that the compressive strength of the F-RCS concrete was approximately 1.2 times higher than the F-RCP concrete. After the analysis of the results, it can be concluded that this value was influenced to a greater extent by steel fibers. The effectiveness of steel fibers lies in their dimensions. Shorter fibers, as is the case here, are more effective in preventing the growth and spread of microcracks. The longer fibers, with higher aspect ratio, are more effective for macrocracks and, as a result, in improving the compressive strength.3 amounted to 22.17 dm3 while steel fibers −2.94 dm3·m−3. Air voids can be formed by long fibers with a relatively high fiber content, which can also reduce the compressive strength. The volume and distribution of the fibers used could also reduce the compressive strength of the F-RCP samples. Although in both concretes the fibers were added in the same amount by weight, there were much more polypropylene fibers by volume. The polypropylene fibers per m3·m−3), the PP could carry macrocracks as can be seen in Concerning the flexural strength, a different situation occurred. In this case, the higher flexural strength was achieved by the specimens made of the polypropylene fiber-reinforced concrete. Despite the lower strength parameters of PP compared to SF, the F-RCP sample achieved 8.4% higher strength value, compared to F-RCS . Under l3.The value of the modulus of elasticity was strongly linked to the compressive strength. The F-RCS samples reached a higher value in the case of the elastic modulus. The value of the module for them was 1.01 times higher than in the case of F-RCP . AggregaThe correlation between the compressive strength and flexural strength as well as the correlation between compressive strength and modulus of elasticity is shown in Additionally, the splitting tensile strength against the compressive strength and elastic modulus is shown in In their work, Afroughsabet and Ozbakkaloglu  analyzedIn our tests , the fibyk = 500 MPa; diameter of reinforcing bars 8 mm; fck = 36.3 MPa; modulus of elasticity of concrete 30.06 GPa; Poisson’s coefficient 0.2 and specific gravity 24.53 kN·m−3. Next, the slab was loaded with its weight and a centric axial force of 10 kN, 15 kN, 20 kN and 25 kN, and deflections were verified , in the fourth type, the core and the compressive layer was concrete with a density of 700 kg·m−3. The reinforcement was in different fiber and bar configurations. On the basis of their tests, it turned out that the highest force was carried by the slab B2—59 kN, achieving a deflection under its influence of 38 mm. The first cracks appeared under 20 kN and the final deflection was 51 mm. The B2 slab was composed of 48 kg of steel (0.46% on the tensile side) and the compressive and tensile layers were reinforced with steel rods. Mansour et al. [Wang et al.  analyzedr et al.  divided r et al.  made 14 r et al.  was sand3. Additionally, they show the tendency towards clustering, which hinders their distribution in the concrete mix [The study was conducted using the fibers produced by a service company; however, they differ from typical short fibers most often used in the concrete technology, which have the length of 12 mm, diameter of 25 µm and density of 0.9 g/cmrete mix . The fibThe compressive strength tests of the cubic samples made of fiber-reinforced concrete with SF and PP fibers of the same content showed that the average compressive strength of F-RCS was higher than that of F-RCP by 23%. The reduction in the average compressive strength of F-RCP concrete was caused by excessive fiber volume. Higher compressive strength of the reference concrete could also be achieved by changing the water–cement ratio.The flexural strength tests showed that the average strength of the samples made of the C-REF concrete reached a lower value in relation to the average strength of the samples made of the F-RCS and F-RCP fiber-reinforced concrete by 15% and 27%, respectively. Under the maximum loading force, the destruction of the beam made of the C-REF concrete took on the character of a sudden brittle crack. In the case of the beams made of the fiber-reinforced concrete with the addition of steel and polypropylene fibers, a crack was formed at a certain value of force, which did not cause a loss of strength. Under the increasing force, the beam bent, showing a further load-bearing capacity.The bending resistance tests of the testing elements were carried out on the reinforced concrete slabs with a strengthened compression zone made of the fiber-reinforced and reinforced concrete slab made of normal concrete. In the scope of these tests, it was found that composite slabs achieved a higher load-bearing capacity, with respect to the slabs without a strengthened compression zone. It was noted that the composite slabs with fiber-reinforced concrete with polypropylene fibers in the upper layer achieved a load capacity 12% higher with respect to the reference slabs. In the case of the fiber-reinforced concrete slabs with steel fibers, the strength increased by 9% compared to the C-REF slabs.In the composite slabs, the development of cracks was all over their width, while only the first crack tended to increase in width along with the loads applied. In the case of the reference plates, the development and width of cracks were more expressive. Several cracks increased in width along with the load. It was observed that more force was needed to destroy a slab with a strengthened compression zone.The analysis of the results obtained from the experimental studies showed that the application of the fiber-reinforced concrete layer in the compression zone of the bending slabs allowed increasing their load capacity and stiffness. This confirmed the effectiveness of using of fiber-reinforced concrete to improve the strength characteristics of bending slab elements.This work aimed to demonstrate the effect of combining a fiber concrete layer with ordinary concrete on improving the strength characteristics of the composite slab structural elements in relation to the slab elements made entirely of the non-fiber concrete. The research program and the analysis of the obtained results allow drawing the following conclusions:


IgG4-related disease (IgG4-RD) is a newly classified but poorly understood immune-medicated systemic disease. It causes potential fibroinflammation in one or more organs, characterized by tumescent organs and marked IgG4-positive plasma cells infiltration in the affected tissues. There have been a few cases revealing close relationship between IgG4-RD and formation of B cell lymphoma. Diffuse large B cell lymphoma (DLBCL) and extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue are the most common sub-types ever described, whereas the exact mechanism remain unclear.18F-FDG-PET/CT. Prednisone combined with oral cyclophosphamide helped the patient to get a partial remission of renal function and an obvious decrease of IgG4 level. However, he developed DLBCL 16 months after IgG4-RD diagnosis. The DLBCL is speculated to transform from a pre-existing but possible missed diagnosed EMZL.We report a 64-year old Chinese male who presented chronic kidney disease and was initially diagnosed typical IgG4-RD. Pathological findings revealed there was restricted expression of lambda light chain in the kidney. There was also elevated uptake abnormality observed in Concurrent IgG4-RD with kidney-origin EMZL developing DLBCL has never been reported in the literature. Clinicians should keep in mind that lymphoma may occur in IgG4-RD. The mechanism of lymphomagenesis potential in IgG4-RD needs further study. IgG4-related disease (IgG4-RD) is a newly classified but poorly understood immune-medicated systemic disease. It causes potential fibroinflammation in one or more organs, characterized by tumescent organs and marked IgG4-positive plasma cells infiltration in the affected tissues. This chronic inflammatory state is thought to be associated with a high incidence of lymphoma during the course of the disease. There have been a few case reports revealing concurrence of IgG4-RD and B cell lymphoma. But the exact pathogenesis remain unclear.18F-FDG-PET/CT. The patient developed DLBCL 16 months after IgG4-RD diagnosis. The DLBCL is speculated to transform from a pre-existing but possible missed diagnosed EMZL.We describe a 64-year old Chinese male who presented chronic kidney disease and was firstly diagnosed typical IgG4-RD and IgG4-related tubulointerstitial nephritis. There was also restricted expression of lambda light chain in the kidney and extremely elevated uptake observed in A 64-year old Chinese male was admitted to hospital for investigation of renal dysfunction. He was asymptomatic when his serum creatinine was found to be 143.9 μmol/L in routine medical examination 1 year ago. Subsequent laboratory testing showed marked hypergammaglobulinema along with slight hypocomplementemia . The patient complained loss of appetite for the recent 2 months before hospital admission. As a retired sewing worker and also a heavy smoker, he was diagnosed interstitial lung disease by CT for 6 years.18F-FDG-PET/CT scan showed diffuse high uptakes in bilateral submaxillary glands (SUVmax 4.3), kidneys (SUVmax 4.6) and interlobular septa (SUVmax 5.1). There was extremely elevated uptake in a local region of the right kidney , the SUVmax was 11.1  with small molecular weight proteins accounting for 62.1% of the total. There was a polyclonal hypergammaglobulinemia  because M-protein was negative both in serum and urine. The level of complement C3 was obviously decreased to 0.405 g/L, C4 was 0.031 g/L. The antinuclear antibody was negative. Doppler ultrasonography and abdominal CT revealed enlarged kidneys. There was no evidence of masses in kidneys and other organs or signs of retroperitoneal fibrosis in CT image. The patient underwent routine ultrasonic guided right kidney biopsy. By light microscopy, there were 16 glomeruli in biopsied samples, 9 glomeruli were ischemic sclerosis. Pathological findings revealed a diffuse lymphoplasmacytic interstitial infiltrate that included lymphocytes, macrophages, plasma cells and eosinophils. The hallmark storiform fibrosis could be seen Fig. a. Electr18F-FDG-PET/CT showed remarkably high uptake of multiple lymph nodes in cervical, supraclavicular, submaxillary and peri-abdominal aorta areas. The SUVmax value was 15.1–22.3. However, The previous high uptakes of kidneys had completed disappeared. The patient received periodical chemotherapy of R-DA-EPOCH strategy. His serum creatinine fluctuated within a short time and eventually was stable at 125 μmol/L in a recent follow-up.The patient was mobilized for bone marrow biopsy, but unfortunately the patient refused at that time. He was finally diagnosed IgG4-RD, multiple organs involved of kidneys, bilateral submaxillary glands and interlobular septa. He was prescribed oral prednisolone at an initiated dose of 40 mg/day for 6 weeks then tapered. Symptoms relieved soon and serum creatinine declined gradually to 149 μmol/L at the 12-week after prednisolone initiation. With combination of oral cyclophosphamide , the IgG4 concentration was reduced to 1.27 g/L and maintained at 1.56 g/L with a daily dose of prednisolone 5 mg  is a newly classified but poorly understood immune-medicated systemic disease. It causes potential fibroinflammation in one or more organs, characterized by tumescent organs and marked IgG4-positive plasma cells infiltration in the affected tissues, often with elevated serum IgG4 level . The IgGThe underlying pathophysiologic mechanisms that may potentially contribute to lymphomagenesis in IgG4-RD are poorly defined. Chronic inflammation is a known predisposing factor for increased risk of malignant lymphoma including DLBCL. It could establish an environment fertile to lymphoma development in both nodal and extranodal sites especially EMZL , 18. TheIn the present case, DLBCL developed 16 months after the first diagnosis of IgG4-RD. The occurrence of DLBCL is related either to the development of DLBCL de novo or to the transformation from EMZL. According to the literature, the rate of histological transformation to a DLBCL has been reported to be in the range of 2–5% for EMZL, with the median time for transformation being 11–48 months –30. InteIn summary, this case was confirmed to have a IgG4-RD with kidney involvement as tubulointerstitial nephritis. It is noteworthy that this case also showed lambda light chain restriction, indicating the probable existence of oligoclonal expansion of IgG4 positive circulating plasmablasts at initiation. An EMZL might exist on the background of IgG4-related disease, and histological transformation to aggressive B-cell lymphoma may be possible. Concurrent IgG4-RD with kidney-origin EMZL developing DLBCL has never been reported in the literature. This case further expanded the pool of potential sites of tumourigenesis in the entity of IgG4-RD. Most important, clinicians should keep in mind that lymphoma may occur in IgG4-RD. Researches focusing on disease pathogenesis and malignant potential are necessary in the future.