Objective To evaluate the rs42524 polymorphism of the procollagen type I alpha (α) 2 (COL1A2) gene as a factor related to the development of pelvic organ prolapse (POP) in Brazilian women.Methods The present study involved 112 women with POP stages III and IV (case group) and 180 women with POP stages zero and I (control group). Other clinical data were obtained by interviewing the patients about their medical history, and blood was also collected from the volunteers for the extraction of genomic DNA. The promoter region of the COL1A2 gene containing the rs42524 polymorphism was amplified, and the discrimination between the G and C variants was performed by digestion of the polymerase chain reaction (PCR) products with the MspA1I enzyme followed by agarose gel electrophoresis analysis.Results A total of 292 women were analyzed. In the case group, 71 had the G/G genotype, 33 had the G/C genotype, and 7 had the C/C genotype. In turn, the ratio in the control group was 117 G/G, 51 G/C, and 11 C/C. There were no significant differences between the groups.Conclusion Our data did not show an association between the COL1A2 polymorphism and the occurrence of POP. Pelvic organ prolapse (POP) is a pathological condition characterized by the displacement of pelvic viscera in the caudal direction, towards the genital hiatus. The standardization of its symptoms was updated in 2016 by the International Continence Society (ICS) and by the International Urogynecology Association (IUGA). They considered the following complaints to be related to POP: vaginal bulging, pelvic or suprapubic pressure, bleeding, discharge and infections related to ulceration, need for manual maneuvers to facilitate defecation or urination, and pain in the sacral spine region.The prevalence of POP varies between 8 and 41%, contributing substantially to the reduction of the quality of life of the patients, as they experience physical symptoms, but also to problems related to general health, personal relationships, and sexual function.The etiology of POP is considered multifactorial, and several risk factors, such as advanced age, pregnancy, obesity, neuropathies, ethnicity, hysterectomy, instrumental delivery, and menopause, have been identified. Recent evidence suggests the existence of a genetic component with a 3.2- to 2.4-fold increased risk for the mothers and sisters of affected women, respectively. The high prevalence of POP in patients with type I and III collagen disorders, such as Ehlers-Danlos and Marfan syndromes, corroborates the importance of studying the genetic background of patients with the disease.Older age and parity are the most significant etiological factors, but they do not fully explain the origin and progression of pelvic floor dysfunction in all women, since POP has been observed in nulliparous women and has been absent in many multiparous women.COL1A1) and procollagen type I alpha (α) 2 (COL1A2) genes, respectively. This protein is physiologically important to support the pelvic floor structures and to confer mechanical stability to the genitourinary tract.The main protein structure of connective tissues is type I collagen, a heterotrimer with two α-1 chains and one α-2 chain encoded by the procollagen type I alpha (α) 1  and in the N-terminus (amino), and a core domain composed of 338 Gly-X-Y repeats, where X and Y exclude cysteine and tryptophan, and are often proline and hydroxyproline, respectively. Glycine, as the smallest amino acid, is the only residue capable of occupying the axial position of the triple helix, so that any change from a glycine residue will entail disruption of the helical structure.Genetic polymorphism is the presence of variation in the DNA sequence found at a frequency of > 1% of the population. A single-nucleotide polymorphism (SNP) is a site in the DNA where a single base pair or nucleotide varies from person to person. As genetic markers, SNPs can be used to track inheritance patterns of chromosomal regions from generation to generation. Although most of the polymorphisms are inactive, some may influence the promoter activity or the conformation of DNA and pre-mRNA, which may result in a change in the amino acid sequence and in the protein function and, therefore, in the phenotypic expression.COL1A2 gene reduce the biosynthesis of type I collagen and, consequently, could be involved in osteogenesis imperfecta.COL1A2 is associated with vascular disease and osteoporotic fractures.COL1A2 rs42524 is a significant risk factor for intracranial aneurysm susceptibility, with an especially strong effect in Asian people.Mutations that affect the Given the aging of the Brazilian population, which is estimated to be predominantly composed of adults and the elderly, according to the Brazilian Institute of Geography and Statistics , and considering the high morbidity of this gynecological condition and the high costs of its treatment, it can be concluded that POP is a highly relevant problem for the global public health.Thus, an important goal on the agenda of the urogynecological scientific community is to develop tools and markers capable of predicting which women will develop POP, so that they receive adequate follow-up, particularly in terms of obstetric care. For this purpose, the identification of genetic polymorphisms, more or less frequent in women with POP compared with the general population, can be the basis for an early disease risk assessment and is therefore extremely important.COL1A2 polymorphisms (rs42524) with POP.Therefore, the objective of the present work is to verify the association between This is a cohort study with a total of 292 postmenopausal women. The patients were treated at the Department of Urogynecology and Vaginal Surgery of the Department of Gynecology and Obstetrics of a School of Medicine. To ensure the rights and duties of the scientific community, of the study population and of the State, the present study complied with the guidelines of Resolution 196/96 of the National Health Council  and, therefore, was previously submitted to evaluation and approval by the Research Ethics Committee of the Faculdade de Medicina do ABC  under the number 554.670/2014. All of the patients were informed about the study and signed a consent form for participation.The inclusion criteria were: (1) diagnosis, by physical examination, of POP stages III and IV in the case group, and of POP stages zero and I in the control group; (2) a history compatible with postmenopause ; and (3) no hormone therapy in the previous 6 months for both groups.The exclusion criteria were: (1) lack of permission from the patient to perform blood collection after having been informed about the study in both groups; and (2) patients who underwent any type of prior vaginal surgery in the control group.In the medical interview, the following data were collected: age, ethnicity, body mass index (BMI), parity, place of birth and delivery route, obstetric interventions , weight of the heaviest newborn, previous diseases , life habits , and previous hysterectomy.All of the women were weighed and measured for the calculation of their BMI, followed by a gynecological examination, in which POP-Q staging was performed for the quantification of genital prolapse.For the extraction of genomic DNA, the illustra blood genomicPrep Mini Spin Kit  was used, following the instructions of the manufacturer. The amplification reaction was performed in 20 μL using an adequately diluted PCR Master Mix reagent  and the primers described by Liu et al (2012): p < 0.05), and the adopted confidence interval (CI) was 95%.The normality of the quantitative data was verified using the Shapiro-Wilk test. The qualitative variables were compared using the chi-squared and the Fisher exact tests. An unpaired t-test was used to compare the quantitative variables. The data were analyzed using GraphPad Prism 6.0  and IBM SPSS Statistics for Windows, Version 23.0 . After the stratification of the groups, the influence of the clinical characteristics on the risk of POP was estimated using odds ratios (ORs) obtained from the binary logistic regression model. The adopted significance level was 5%  and 112 women with stage III or IV (case group) were selected for analysis. The groups were significantly different in terms of age, parity, number of pregnancies, and number of vaginal deliveries and home deliveries .The independent risk factors for the development of POP were determined by calculating the OR using the logistic regression model and are shown in p = 0.046). We did not have DNA amplification in one patient in the case group and in another in the control group, totaling two cases of non-amplified DNA. Conversely, the presence or absence of COL1A2 gene polymorphisms was not associated with the presence of genital prolapse  and compared them with patients without the polymorphic allele (GG). Moreover, the COL1A1 Sp1-binding site was not significantly associated with genital prolapse among our study subjects.COL1A1 gene was found in the control group , suggesting that the GT genotype has a stronger association with POP than the TT genotype.Our results demonstrated a higher, albeit not statistically significant, prevalence of the COL1A2 gene, which replaces alanine for proline at position Y of the helical region of alpha 2 (I) collagen, could be a genetic risk factor for aneurysms.COL1A2 gene polymorphism may be a genetic risk factor related to the development of osteoporosis; and, lastly, Meng et al (2017)COL1A2 gene was associated with a significant increase in the risk of intracranial aneurysms in Japanese patients .It has recently been shown that a common coding polymorphism (rs42524) in the COL1A2 gene with the occurrence of POP. This is a pioneer work in the literature, and it failed to demonstrate the association of this polymorphism with POP.In our study, we investigated the possible association of the rs42524 polymorphism of the We acknowledge that among the limitations of our work is the fact that our samples were not completely homogeneous in terms of some clinical characteristics, likely because advanced degrees of prolapse are more frequent in older women with more gestations and deliveries, who, in this case, correspond to those of the study group. Other limitations of our study are the fact that it only evaluated a single polymorphim and gene, as well as the miscegeneation of the Brazilian population, as well as the lack of equilibrium of Hardy-Weinberg. Regarding the latter, perhaps the small number of patients may be responsible for the absence of the genic equilibrium. In order to ensure that the genotyping was adequate, the PCR was always performed by the same three observers, and their consensus was recorded.We believe that further studies that seek to establish genetic markers for POP are necessary and, therefore, the present study may be useful for future meta-analyses. We also think that we cannot extrapolate the conclusion for other populations based on these results. This study is specially important because the capacity to identify individuals at greater risk of developing POP through genetic screening could be useful in cases such as deciding the most appropriate delivery route for large fetuses.Hopefully, focusing on the genetic susceptibility to POP will allow the stratification of risk for women who develop POP and thus establish strategies for its prevention and lifestyle changes. These interventions could reduce the need for corrective surgery and could improve the quality of life of women with the most severe stages of genital prolapse.COL1A2 polymorphism and the occurrence of POP.In conclusion, our data did not demonstrate an association between the


Papillomaviridae family account for 27.9–30% of all infectious agents associated with human cancer. The aim of our study was to investigate the presence of high-risk HPV (human papilloma virus) genotypes in patients with periodontitis and a pronounced clinical picture. To achieve this goal, after proving the bacterial etiology of periodontitis, the samples positive for bacteria were examined for the presence of HPV. The genotype of HPV is also determined in samples with the presence of the virus proven by PCR (polymerase chain reaction). All positive tests for bacteria associated with the development of periodontitis indicated the presence of HPV. There was a statistically significant difference in HPV positive results between the periodontitis positive target group and the control group. The higher presence of high-risk HPV genotypes in the target group, which was also positive for the presence of periodontitis-causing bacteria, has been proven. A statistically significant relationship was established between the presence of periodontitis-causing bacteria and high-risk strains of HPV. The most common HPV genotype that tests positive for bacteria associated with the development of periodontitis is HPV58.Members of the  Papillomaviridae family make up 27.9–30% of all infectious agents associated with human cancer [Representatives of the n cancer . Althougn cancer ,5. In adn cancer . There in cancer ,9.It is estimated that about 16% of the world’s population is infected with HPV. According to a study by K.J. Syrjanen, nearly 80% of women are at risk for HPV infection. This is not the case with regard to affecting the oral epithelium; for example, in the United States, it has been found that 7% of people aged 14–69 years are infected with HPV, and the infection in men is almost three times more common . The majOncogenic serotypes of human papillomaviruses are used as a tumor marker associated with cervical cancer due to their safe participation in the etiology of this cancer, and in many cases, they are responsible for the development of neoplastic lesions of the penis, tongue, and more rarely of mucosal lesions with other localization. An Italian team of authors conducted a study that reports that women (20.4%) with a diagnosis of cervical-HPV and their male partners (30.7%) are at high risk for subclinical oral HPV infection .The presence of HPV in the oral cavity has been associated with various lesions, but the presence of viruses has also been found without clinical manifestation . The linTwo hundred and thirty samples were used from patients with clinical manifestations of gingivitis and periodontitis without a pronounced clinical picture of oropharyngeal lesions in the oral cavity (target group). The age of the target group patients ranges from 25 to 59 years. All of them required periodontal procedures and placement of implants. There is no evidence in the target group of the presence of immunosuppressed individuals. Samples for the presence of bacteria causing periodontitis were taken only from the gingival margin due to the specificity of the disease. Samples were taken using 0.5 mm dental paper pins using 5 pins per patient. For a control group, 460 buccal mucosa and coronal margin samples from 230 people without clinical signs of periodontitis were used. The representatives of the control group were of a similar age: from 30 to 60 years old. They were screened for high-risk HPV. We used sterile brushes  for the buccal mucosa samples and thin, metallic, sterile swabs  for those from the gingival margin. Various primer systems were used in the present work to detect genomic fragments of HPV. Consensus primers MY09/11 cover a region of the DNA of the virus with a size of 450 nucleotides (nt) encoding the L2 and L1 proteins and the triple primers GPE—the genes encoding proteins E6 and E7  of diffeAn ISOLATE II DNA Mini kit with a silica membrane was used to isolate the DNA . The isolation protocol was according to the manufacturer’s instructions.®plus11 kit . Reactions were performed according to the manufacturer’s instructions using a FluoroCycler® 12 PCR apparatus , and a TwinCubator  was used to perform the hybridization. The pathogenic bacteria associated with periodontitis were detected by micro-IDentAn Amplisens kit  was used to detect HPV types 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, and 66. The protocols were according to the manufacturer’s instructions. GenBank—National Center for Biotechnology Information, USA) were used to perform the reactions. Minor changes were made to the reaction protocols according to the melting temperature of the primers. To determine the temperature range of the primers, a gradient PCR was performed at the following temperatures: 51.0, 52.9, 54.4, 56.2, 58.4, and 60.3 °C. MayTaq HS mix  was used for PCR.The commercial in vitro diagnostic kits and primers described in Primers PC04 and GH20 for the beta globin molecule gene  forming a fragment with a size of 268 base pairs (bp) were used as internal control of the system. Consensus primers MY09-MY11 (10 pmol/µL) adopted as the gold standard were used to detect HPV, yielding a 450 bp fragment .Consensus primers covering E6/E7 genes were also used to detect HPV: GP-E6-3F, GP-E6-5B, and GP-E6-6B primers yielding a 650–700 bp fragment depending on of the genotype.The parameters of the reactions for proving HPV were as follows: initial denaturation—3 min, 40 cycles: denaturation 95 °C—45 s, connection 55 °C—45 s, extension 72 °C—45 s, final extension 72 °C—7 min, and storage 4 °C. Gel electrophoresis was used for qualitative analysis of the extracted DNA and PCR products. Gel electrophoresis was performed with 2% agarose , 10 ng/mL of ethidium bromide , 1 × TAE buffer, 100 bp DNA Ladder , and 1 kb DNA ladder  at 120–150 V and 70–120 mA for 30 min. For statistical processing of the results, chi-square test and McNemar’s test were used to determine the level of significance.DNA obtained from all tested samples had a purity greater than 1000 and an appropriate concentration greater than 20 ng/µL. Evidence of pathogenic bacteria associated with the development of periodontitis.Pm (Peptostreptococcus micros), Fn (Fusobacterium nucleatum/periodo) En (Eubacterium nodatum), and Cr (Campylobacter rectus) was recorded. A total of 230 samples from the coronary margin, isolated from the control group, were examined for the presence of the relevant bacterial pathogens. Samples for the presence of bacteria were taken only from the gingival margin due to the specificity of periodontal disease. After accounting for hybridization, 110 of the samples tested positive for periodontitis-causing bacteria. After DNA preparation, PCR and hybridization were performed to detect 11 pathogens causing periodontitis. The results showed that all examined samples from the target group  showed the presence of periodontitis bacteria. The presence of all tested bacteria was demonstrated, with several types of bacteria present in each sample. In all patients, the presence of After gradient PCR to determine the binding range of the beta globin primers PC04 and GH20, we found that at all temperatures tested (51.0–60.3 °C), there was a product of size 268 nt, and only at temperatures of 51.0 °C were there non-specific bands below 200 and below 100 nt due to the lower annealing temperature of the primers. The periodontitis-positive 230 samples from the target group were also probed with consensus primers GPE6/5B/6B and primers MY09/11. After the PCR, the presence of specific fragments with a size of about 700 bp and 450 bp was confirmed, which proves the presence of HPV. The results of the conducted reaction are presented in Samples from the control group were probed with consensus primers MY09/11 and primers GPE6/5B/6B. Samples were taken from the gingival margin and buccal mucosa. The presence of specific fragments of 450 bp and about 700 bp was detected, which proved the presence of HPV. The number of HPV-positive samples taken from the gingival margin is higher, which is probably due to the structure of the oral epithelium of the gingiva, which allows the development of productive HPV infection with the assembly of functional virions, in contrast to the buccal mucosa. All HPV-positive samples from the target group were tested with an in vitro diagnostic kit for 12 high-risk HPV genotypes. After conducting PCR and visualization by agarose gel electrophoresis, the presence of fragments with a size characteristic of the respective genotypes was reported. The results of the studies are combined and presented in When examining the samples, it was found that in 110 of them, the presence of more than one HPV genotype was reported. High-risk genotypes 66, 31, and 59 were not reported in any of the samples.In a screening of 230 coronal samples taken from the control group, 100 samples tested positive for HPV with the consensus primers. When tested for 12 high-risk HPV genotypes, 9 were positive for type 45 and 9 for type 18. The results are summarized in All HPV-positive samples (100) taken from the gingival margin of patients without clinical signs of periodontitis were also positive for periodontitis bacteria. Of 130 samples negative for HPV, 10 were positive for periodontitis bacteria. The presence of HPV and the absence of periodontitis-causing bacteria were not detected in any of the samples from the gingival margin of the control group.When examining buccal mucosa samples from the control group with the consensus primers, 64 positive samples were found. Genotype 18 was proven in 16 of the samples. The results are presented in In the target group, in 170 patients or 73.9% of them, the presence of high-risk HPV genotypes was demonstrated, and all of them were positive for periodontitis bacteria. The results are presented graphically in 2 = 205; p < 0.001). The number of genotypes is also different when comparing samples taken from the coronal edge of the representatives of the target group and the control group—nine in the target group and only two genotypes in the control group for samples taken from the coronal edge.Eighteen genotypes positive for high-risk HPV, i.e., 7.8%, were found in the coronal margin samples in the control group. A statistically significant difference was found for this indicator . The results are presented in A comparison of the proportion of samples from patients with high-risk HPV genotypes from the target group with the proportion of samples from patients with high-risk HPV genotypes from the control in which bacteria were also isolated from the coronal margin (16.4%) also showed that there was statistical significance  positive for periodontitis-causing bacteria, while in patients without bacteria, there was not a single case with proven presence of HPV. The results were confirmed by the conducted McNemar’s test—χCompared with the coronal margin results in the control buccal mucosa samples, only one high-risk HPV genotype was observed in fewer patients (7%). The observed difference is implausible.From all the research performed and the statistical processing of the results, we can conclude that there is a relationship between the presence of periodontitis-causing bacteria in patients with a pronounced clinical picture and high-risk HPV genotypes.In contrast with colleagues  who founA statistically significant difference was also found between the results obtained when examining the samples from the target group and the samples taken from the gingival margin of the control group in terms of HPV infection. In contrast to previous studies, our genotyping found that the most common genotype in samples positive for periodontitis bacteria was HPV type 58, followed by types 16, 33, and 35. HPV type 58 was found to be dominant in our study and was not associated with the development of papilloma lesions in the maxillofacial area, while the other widely represented genotypes 16, 33, and 35 were associated with the development of various papilloma lesions [In the control group, a preponderance of HPV-positive samples was found in materials from the coronal margin compared to those from the buccal mucosa. This may be due to the fact that, theoretically, the structure of the oral gingival epithelium allows the development of a productive HPV infection with the assembly of functional virions, unlike the buccal mucosa. In relation to the structure of the gum and the pathological processes caused by the bacteria causing periodontitis, it is possible that there is a synergy between the bacteria and HPV. This interaction may be based on the mechanical exposure of the coronal margin (often accompanied by bleeding and pockets), which allows the virus to come into contact with one or both basement membranes as well as the junctional epithelium. We assume this is preparation for an opportunistic infection. Since the gingival mucosa bordering the tooth enamel lacks this differentiation, as does the oral epithelium or skin, i.e., keratinocytes , the absHPV localizes to the inflamed periodontal tissue and is thought to infect the basal keratinocytes in the ulcerated epithelium of the gingival sulcus. Inflammatory periodontal pockets play an important role as a reservoir for HPV. Although interactions between HPV and periodontal bacteria remain unclear, oral HPV infection may be associated with a characteristic oral microbiome. Carcinogenic HPV and periodontitis are likely to contribute to the development of oral cancer. To date, however, oral expression of HPV E6/E7  has not been fully studied in individuals with periodontitis. Overall, the available literature suggests that oral HPV may be associated with periodontitis. To clarify the relationship between oral HPV and periodontitis, the effects of clinical factors contributing to the spread of HPV DNA in the mouth must be considered . Pm (Peptostreptococcus micros), Fn (Fusobacteric nucleatum/periodo), En (Eubacterium nodatum), and Cr (Campylobacter rectus) was recorded in all patients. No statistically significant association was found between well-defined periodontitis-causative agents and well-defined high-risk HPV genotypes. We have reason to believe that it is an opportunistic infection due to the specificity of the disease and the replication cycle of HPV.In our experiments, the presence of all tested bacteria was detected, with several types of bacteria present in each sample. The presence of In the studies we conducted in Bulgaria, we found that for patients with a clinical picture of periodontitis and the presence of bacteria causing the corresponding disease, in the absence of a clinic of oropharyngeal lesions in the oral cavity, the presence of high-risk HPV was proven with a statistically reliable frequency. In control samples from the buccal mucosa and periodontal margin, the presence of high-risk HPV genotypes was significantly less. We can conclude that there is a relationship between the presence of periodontitis bacteria in patients with a pronounced clinical picture and high-risk HPV genotypes as well as a relationship between the presence of these bacteria and the presence of HPV. We could conclude that oral HPV infection is probably an opportunistic infection of the inflamed and bacterially infected gingival tissues. The presence of HPV in patients with periodontitis may influence disease severity and response to treatment. Therefore, the identification of HPV in patients with periodontitis may be essential to determine the appropriate course of treatment.


The sample consisted of 178 typically developing children aged 5 to 7 years. Internal reliability analysis indicated high reliability (from 0.87 to 0.95) for the three composite indices and the Global Executive Composite across all age groups. Confirmatory factor analysis revealed that the dimensional structure of the Russian version of BRIEF2 was different among children aged 5 and 6 years compared to children aged 7 years, which is probably because, in Russia, the transition from kindergarten to school takes place upon reaching the age of 7. The results confirm that the Russian version of the BRIEF2 Teacher Form can be used as a valid tool to assess EF in 5- and 6-year-old children, provided that the three BRIEF2 indices are used for clinical interpretation. For 7-year-old children, the BRIEF2 was found to be an insufficiently valid tool to assess executive function.This study aimed to examine the psychometric properties of the Russian version of the Behavioral Rating Inventory of Executive Function Although the definition of executive functions (EF) has long been debated, it may broadly be viewed as those “cognitive processes that are required for the conscious, top-down control of action, thought, and emotions and that are associated with neural systems involving the prefrontal cortex”  and ages 11–18 years (self-report form)  of the Russian version of BRIEF2 Teacher Forms in a sample of typically developing children aged 5–7 years and investigate its dimensional structure. In addition, this study explores the interrater reliability between children's BRIEF2 results evaluated by two teachers. The study was designed considering the peculiarities of Russia's cultural and educational context. First, due to the multilingual nature of the state, the validity evidence on the applicability of the Russian-language version of BRIEF2 in this study may extend mainly to monolingual regions. Second, the study involved children aged 5–7 years old to assess the applicability of the Russian-language version of BRIEF2 over existing differences in the age period of the transition from ECEC to primary school.The study included 178 typically developing children aged 5–7 years. The participants attended publicly funded kindergartens and schools. Children aged 5 and 6 years attended kindergartens, and children aged 7 years attended the first grade of school. Forms were filled out by 34 kindergarten and 8 primary school teachers .The study was conducted in May–June 2023. In kindergartens, the BRIEF2 was completed by two preschool teachers for each child. In the first grade, the BRIEF2 was completed by a full-time teacher. The teacher was asked to assess 6–10 children who were selected randomly based on their order of appearance on the class list (every third child). This measure of sampling was driven by classroom conditions in Russia, where class sizes are typically ~25–30 students. If teachers completed the form for the whole class, the quality of completion would probably be reduced. The lists given to the teachers were prepared in advance, considering medical and psychological screening information . Another selection condition was that the teacher should have been familiar with the selected children for at least 6 months.A Russian version of the BRIEF2 Teacher Form was derived from the English version of the BRIEF2  internal scale consistency  and (b) interrater reliability between two teachers' reports for a single child, as based on the Cohen's kappa coefficient and a paired samples Given the variation in educational settings for children aged 5, 6, and 7 years, the primary tool's psychometric properties were evaluated separately for each age group. The internal consistency was studied using Cronbach's alpha coefficients as a first metric of reliability, separately, for each age group. Cronbach's alpha reliability coefficient ranges between 0 and 1. George and Mallery  suggest In the sample of 5-year-old children, the results indicate that the internal consistency of all subscales was good or acceptable see . Cronbact-test. This analysis was conducted only for 5- and 6-year-old children because, at these ages in the country of study, children attend kindergarten and have regular contact with two preschool teachers. Cohen's kappa coefficient, ranging from 0 to 1, assesses the measure of consistency between the scores of these two teachers from 0 to 1. According to McHugh .The paired samples p-value of < 0.001  > 0.90, Tucker Lewis Index (TLI) > 0.90, Standardized Root Mean Squared Residual (SRMR) ≤ 0.08, Root Mean Squared Error of Approximation (RMSEA) < 0.08.The underlying factor structure of the Russian version of the BRIEF2 Teacher Forms was explored using a confirmatory factor analysis (CFA) with maximum likelihood estimation. According to Hu and Bentler's , the gooA CFA was conducted for the total sample and separately for three age groups to test the model fit of the BRIEF2 three-factor and nine-factor models. The relevant information on these eight models is presented in The results of the CFA indicate the best model fit for the three-factor model compared to the nine-factor models . FurtherThe objective of this study is to analyze the psychometric properties of the BRIEF2 Russian version in a sample of typically developing children in preschool and primary school settings. Reliability  and validity (the underlying factor structure) of the BRIEF2 Russian version were analyzed as the main psychometric properties.The internal consistency of the subscales of the BRIEF2 Russian questionnaire was heterogeneous among the three age groups. The highest consistency of the scales is observed when completing the BRIEF2 for children aged 5 years. In this age group, the internal consistency of all subscales was good or acceptable. When the form was completed for children aged 6 years, internal consistency was good or acceptable for all subscales except Initiative (0.57). Finally, in the sample of children aged 7 years (the first grade of school in Russia), the internal consistencies were, in general, lower than that in the previous two age groups but still good or acceptable for all subscales except Initiative (0.41). To summarize, the internal consistency of all subscales was adequate for reliability except for the Initiate. Internal consistency of the Initiate subscales was unacceptable among children aged 6 and 7 years and questionably acceptable in the sample of children aged 5 years. Furthermore, the internal consistency results on the three composite indices  and the Global Executive Composite (GEC) have indicated adequate reliability (from 0.87 to 0.95).The interrater reliability analysis results showed that the level of agreement between teachers when evaluating a child decreases slightly as children age. This is observed in the lower levels of agreement when assessing children aged 6 years compared to children aged 5 years. Yet, the two teachers' ratings of most subscales  were sufficiently consistent.The confirmatory factor analysis (CFA) results of a construct validity study indicate the best model fit for the three-factor model compared to the nine-factor models. The underlying factor structure obtained in the present study suggests that the Russian version of the BRIEF2 Teacher Forms reflects three types of difficulties rather than nine. This result coincides with Jacobson et al. , who fouThe sample of this study covered children aged 5 to 7 years to assess the applicability of the Russian-language version of BRIEF2 over existing differences in the age period of the transition from ECEC to primary school in the Russian educational context. It was shown through reliability and CFA analyses that the dimensional structure of the Russian version of BRIEF2 was different for children aged 5, 6, and 7 years. Both internal and interrater reliability and CFA indices of the goodness-of-fit of the a priori model decreased from younger to older children. While the 3-factor model showed a very good fit for the samples at ages 5 and 6 years, the fit indices were poorer at age 7. At the age of 7 in Russia, children enter first grade (see Introduction). This may indicate that the school setting in the Russian education system differs from the preschool setting to such an extent that the children's behavior can no longer be validly assessed using BRIEF2.The results of the present study confirm that the Russian version of the BRIEF2 Teacher Form can be used as a valid tool to assess EF in children aged 5 and 6 years based on observations of their behavior in kindergarten settings. However, three indices  should be used instead of nine BRIEF2 subscales for clinical interpretation. For children aged 7 years, the BRIEF2 was a rather insufficiently valid tool for assessing EF based on CFA results.From a future research perspective, we plan to analyze the external validity of the BRIEF2 using a battery of NEPSY-II tests to individually assess children's main EF skills (Korkman et al., The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving humans were approved by the Ethics Committee of Faculty of Psychology at Lomonosov Moscow State University. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants' legal guardians/next of kin.MG: Formal analysis, Software, Validation, Writing—original draft. MA: Data curation, Formal analysis, Investigation, Writing—review and editing. KT: Data curation, Investigation, Software, Writing—review and editing. YZ: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing—review and editing.


In 1989, the National Asthma Education and Prevention Program (NAEPP) convened an expert panel to develop a report that would provide a general approach to the treatment of asthma. Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma, or EPR-1, was published in 1991 and was subsequently updated with 2 other reports, EPR-2 in 1997 and the EPR update in 2002. Advances in science and a greater understanding of the pathophysiology of asthma prompted the NAEPP to convene a 3rd expert panel in 2004. After nearly 3 years of work, Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma Full Report 2007, or EPR-3, was released on August 29, 2007. EPR-3 update from the NAEPP provides health care professionals with new information to improve the care of patients with asthma, including (1) more comprehensive discussion of asthma severity with expanded descriptions of impairment and risk, (2) increased focus on asthma control as a goal of therapy, and (3) expanded discussion of pharmacologic therapy for asthma with updated treatment algorithms.To (1) extract key educational messages from the EPR-3 update that effectively summarize the appropriate management of the patient with asthma and (2) provide supporting literature to substantiate the development of these educational messages.A consensus meeting of 9 asthma experts (4 pharmacists and 5 physicians) was held to discuss the EPR-3 update and condense its content into a usable format for the health care professional. Experts were selected on the basis of several criteria, including (1) affiliation with the NAEPP, (2) expertise in asthma management, and (3) familiarity with managed care processes. The author served as the 10th member and moderator of the meeting.Thorough review of the EPR-3 update resulted in the development of 7 key educational messages that can assist the health care professional in improving the management of the patient with asthma. Each educational message is presented with supporting literature to substantiate its distinction as a key point to be referenced when developing protocols for asthma management within managed care organizations.The complexity of asthma and its treatment has necessitated the development of several guidelines from the NAEPP, with the most recent EPR-3 update being released in late August 2007. One expert consensus has distilled the EPR-3 document into 7 key educational messages that can assist the health care professional in improving the care of the patient with asthma.


The aim of this report is to evaluate the segmental rib index (RI) from the T1 to T12 spinal levels in mild and moderate idiopathic scoliosis (IS) curves of thoracic, thoracolumbar and lumbar type by gender. The relationship of segmental RI to the frontal plane radiological deformity presented as the Cobb angle and to the posterior truncal surface deformity presented as the scoliometric readings of Angle of Trunk Rotation (ATR) in these patients is also assessed. Any statistically significant relationship between these parameters would be very important for biomechanical relations in rib cage (RC) deformity presented as rib hump deformity (RHD) and deformity in the spine, and would thus provide valuable information about scoliogeny. The segmental rib index (RI) is presented in 83 boys and girls with mild and moderate IS. The measurements include the scoliometric readings for truncal asymmetry (TA), the Cobb angle assessment and the segmental RI from T1-T12. The statistical package SPSS 23 was used for statistical analysis. The TA was documented and the Cobb angle is presented by gender and curve type. The segmental RI of thoracic, thoracolumbar and lumbar curves are presented for the first time. The correlations of the segmental RI to surface deformity presented as rib hump deformity (RHD) in all IS patients, and particularly in thoracic curves, to Cobb angle by gender and age and the comparison of the segmental RI index of asymmetric but not scoliotic children to the scoliotic peers by curve  in boys and girls are presented. The findings emphasize the significant protagonistic role of thoracic asymmetry in relation to the spinal deformity, mainly in girls for the thoracic and in boys for the thoracolumbar curves. The cut-off point of age of the examined scoliotics was 14 years, which is when the RI shows a stronger correlation with spinal deformity, namely when thoracic deformity is decisively effective in the development of thoracic spinal deformity, in terms of Cobb angle. In summary, the results of this study may provide scoliogenic implications for IS, as far as the role of the thorax is concerned.  The existence of truncal asymmetry (TA) presented as rib hump deformity (RHD) in the Adams bending test during the school scoliosis screening (SSS) programs is a finding which defines the number of children who will be referred to the scoliosis outpatient departments of hospitals and is a dominant predictor of scoliosis ,2,3.The rib index (RI) method was introduced as a radiological measurement for the assessment of the RHD, which essentially represents rib cage (RC) deformity in the transverse plane. It was originally presented to assess the RHD of IS at the more prominent point of the double rib contour sign (DRCS) on the lateral standing radiographs (LSR) of their RC .The RI is used for the documentation of initial rib-cage deformity on the transverse plane before any treatment, for the assessment of the benefits of physiotherapeutic scoliosis-specific exercises on RC deformity , for theStudying the lateral spinal profile (LSR) of the IS patients radiographically, we recognized that the thoracic level of the most prominent point of the DRCS differs in the various types of IS curves. This observation motivated us to study the RI segmentally at all the vertebral levels (T1–T12) on the DRC in the radiographs of thoracic, thoracolumbar and lumbar curves. We also investigated whether there was any correlation between segmental RI thoracic levels and the degree of the Cobb angle, respectively, regarding when and how the existing surface deformity correlates to mild and moderate spinal deformity.In idiopathic scoliosis (IS), the word etymology strictly means the factor(s) causing the AIS, pathogenesis means the mode of origin of the morbid process and pathomechanism/pathobiomechanics means the sequence of events in the evolution of its structural and functional changes that result from the pathological process . Prof. RIn summary, the aim of this report was to evaluate the segmental RI from the T1 to T12 spinal levels in mild and moderate IS thoracic, thoracolumbar and lumbar curves by gender and to assess the relationship of segmental RI to the frontal plane radiological deformity and to the scoliometer readings of posterior truncal surface deformity presented by the Angle of Trunk Rotation (ATR). Any significant relationship between these parameters would be very important for the biomechanical relations of the RC (RHD) with spine deformity and may thus provide information about scoliogeny.Study design. This is a retrospective statistical study on cross-sectional data collected in Greece, Bosnia and Herzegovina and Serbia.The examined subjects: Eighty-three children and adolescents, twenty boys and sixty-three girls, with juvenile and adolescent IS were included in the study, with a mean age 12.3 ± 2.7 (range 7 to 17 years) and a mean Cobb angle of 23.8 (15.5–38.7) degrees. Of these, 25 patients  had primary thoracic, 33  thoracolumbar and 25  lumbar curves, respectively. In addition, 27 asymmetric children who were referred for further radiological assessment due to the presence of RHD at the Adams test with a radiological curve less than 10 degrees or with a straight spine were also included. The data of scoliotics were collected before any treatment. Any non-idiopathic scoliotic case was excluded from the study.The measurements. The Cobb angle was assessed according to the classical method described by Cobb, 1948 , showed no significant differences [the correlation was significant at the 0.05 level (2-tailed)] among the three groups.The segmental RI by curve type and gender among all the three curve types—thoracic, thoracolumbar and lumbar—in female and male patients together, using the non-parametric Kruskal–Wallis test [The same analysis for scoliotic female patients only [using the Kruskal–Wallis test and the post hoc Mann–Whitney U-test] showed significant differences between groups at T8, T9 and T12 vertebral levels. The post hoc analysis showed significant differences between thoracic and thoracolumbar at T9 and at T12 between thoracolumbar and lumbar at T12 .The same analysis for scoliotic male patients only showed no significant differences between groups .These findings emphasize the importance of the role of RC asymmetry in relation to spinal deformity, mainly in the girls.Published articles from previous decades sporadically reported that children could have surface deformity in terms of RHD without deformity in their spine ,20. NissThe effect of growth was found to play a key role in the correlation between thoracic and spinal deformity in girls with IS . YoungerThe findings of this study are in line with those reported by Prof. Sevastik’s research work, pertinent to scoliosis aetiology, emphasizing the important role of the rib cage in scoliosis development. Therefore, the benefit of this study is that its findings shed more light on the theory of asymmetric function of the ANS, reported by Prof. Sevastik and his team ,33,34,35Investigating further the effect of growth on the relationship of RC with the spinal deformity in terms of the Cobb angle, we analyzed the segmentally measured RI from T1 to T12. For this purpose, the scoliotics were split into two age cohorts, namely (a) scoliotics less than 13 and more than 13 years of age, and (b) scoliotics less than 14 and more than 14 years of age, as presented in p = 0.462, 0.465, 0.547), respectively; in thoracolumbar curves, it correlated negatively at T4 only (p = 0.031), and in lumbar curves at T9 only (p = 0.046); Before any splitting of the ages, the significant correlation of Cobb angle with the segmental RI  existed After splitting the scoliotic boys and girls in two cohorts by age, namely over and less than 13 years, it was found that, as in p = 0.045, 0.043).In scoliotics over 13 years of age with thoracic curves, the Pearson correlation coefficient was significant at T11 and T12 , and in those over 13 years of age at T6–9 , respectively.In scoliotics less than 13 years of age with thoracolumbar curves, the correlation was significant at T4 .In thoracic curves of patients over 14 years of age, the Pearson correlation coefficient was significant at T8–11 (p = 0.004), and in those over 14 years of age at T1 (p = 0.046), respectively.In thoracolumbar curves of patients less than 14 years of age at T4, the Pearson corr. coeff. was negatively correlated  in boys and girls, interestingly, showed that there was no significant difference between groups . However, considering the fact that a good number of these asymmetric referred children will develop IS ,22, our A limitation of this report is the small number of curve types in the studied scoliotic children and adolescents. However, the results of the analysis are in line with those of a previous publication, see , where tThe benefits of using the RI and segmental RI method are described above. RI can also be used as a surrogate for scoliometry . RI is aOne other benefit of using the RI and segmental RI is that the plain chest radiographs of children and adolescents, being easily available at medical archives, can effectively serve the segmental RI method, without the need for any other special radiographs and exposure to additional radiation. One additional benefit of the segmental RI method is its implementation not only in prospective but also in retrospective studies on non-operative and operative treatment of IS, using the existing initially obtained chest or spinal radiographs of IS patients, provided that the radiography is performed in a standard way.The operation named costoplasty or thoracolpasty or pleuroplasty is the one that has been introduced to correct the deformity of the ribs in the chest, of the AIS patients ,45,46,47In conclusion, this is the first report presenting the segmental rib index according to the location of the curves in thoracic, thoracolumbar and lumbar IS. Additionally, the above study presented results from data collected retrospectively from scoliotics suffering mild and moderate IS. The reported correlations of the surface deformity, in terms of scoliometry, and radiological deformity, in terms of radiography, of the scoliotics in this report show the significant impact of the RC on the spine. The RC seems to play a protagonistic role in the scoliogeny of IS in mild and moderate thoracic and thoracolumbar IS.


The mix design of UHPC has always been based on a large number of experiments; in order to reduce the number of repeated experiments, in this study, silica fume (SF), fly ash (FA), and limestone powder (LP) were used as the raw materials to conduct 15 groups of experiments to determine the particle size distribution (PSD) properties of UHPC. A model of multi-component hydration based on the SF, FA, and LP pozzolanic reactions was devised to quantify the rate and total heat release during the hydration process. Additionally, a microscopic pore development model, which was based on the accumulation of hydration products, was established to measure the effect of these products on the particle-packing properties. Utilizing this model, a UHPC strength prediction technique was formulated to precisely forecast the compressive strength based on a restricted experimental data set. The applicability of this prediction method was verified using 15 sets of existing experimental data along with the data collected from 4 research articles. The results show that the prediction method can predict the strength values of different mix proportions with an accuracy rate of over 80%. Ultra-high-performance concrete (UHPC), a form of concrete designed to maximize the particle size distribution (PSD) of cementitious materials, was founded on the notion of reactive powder concrete (RPC). To increase uniformity and reduce defects, ultrafine reactive powder is added and normally coarse aggregates are not included. To bolster toughness and reduce the water to binder and porosity ratios, steel fibers are also incorporated ,2. UHPC Considering that there are few theoretical bases for UHPC design, further experimental studies are essential for achieving UHPC . A few m3S) [The MAA model, which is essential for gauging dimensional trends, forecasts the strength of concrete based on the initial packing. Nevertheless, the initial packing condition is not able to accurately evaluate the concrete’s strength, as it is constantly influenced by the initial buildup of materials and hydration of the cement. To accurately forecast the strength of concrete, it is necessary to precisely assess the impact of hydration products on the concrete’s stacking properties during hydration. The hydration of cement involves the interaction between cement-based materials, hydration formation, and micro-pores development ,24,25. T3S) ,31,32 as3S)  determin3S)  observed3S) ,36 condu3S)  model, wThe aim of this research was to construct an empirical model for gauging the com-pressive strength of various concrete mix ratios. Experiments of varying mix ratios were conducted to achieve this, and their compressive strength values were gauged. Using the resulting data, an empirical model was developed that could accurately predict the compressive strength of a given mix ratio based on its constituent materials. The model was able to accurately forecast the compressive strength of various mix ratios, thereby demonstrating its wide-ranging applicability and practicality in improving concrete performance. These results have a considerable effect on the design and construction of concrete structures, providing a reliable means for predicting the compressive strength of different mix ratios and ensuring their longevity and dependability.The experimental design is described in this section. First, the initial states and hydration paths of the cement used in this study were obtained. In this study, P.O.52.5 Portland ordinary cement, FA, LP, and SF were used as the raw cementitious materials.2/kg and an apparent density of 2.55 g/cm3 and LP demonstrating a specific surface area and apparent density of 600 m2/kg and 2.84 g/cm3, respectively. SF had an SiO2 content of >95%, a specific surface area of 2000 m2/kg, and an apparent density of 2.25 g/cm3.The chemical and mineralogical makeup of Portland cement is detailed in 3. To enhance the structure’s mechanical properties, straight steel fibers that were 0.2 mm in diameter and 13 mm in length were employed. To adjust the workability of the UHPC, a poly-carboxylic acid-based superplasticizer (SP) was employed with a dosage of 30 kg/m3 for the mix design.Two kinds of sand were used: coarse quartz sand with a size of 0–4.75 mm and fine quartz sand with the size of 0–2 mm. The density of these two kinds of sand was 2.64 g/cmAll mixtures were created and examined at a temperature of 20 ± 2 °C. The lab conditions necessitated us to perform the mixing of dried aggregates and powder materials.The mixing was performed in three steps:(1)Put all dried powder materials and sand in a mixer for 60 s to mix.(2)Add water and SP to 80%, remix the sample for 360 s, and then stop the mixer for 30 s.(3)Mix water, SP, and steel fibers together; add the remaining ingredients, and continue mixing for a further 240 s.Cubes of 100 mm × 100 mm × 100 mm were utilized for the compressive strength testing. After casting, the specimens decomposed approximately 24 h later and were then exposed to customary curing conditions . After 7 and 28 days of curing, the compressive strengths of the specimens were evaluated.The GB/T 31387-2015 test for mechanical properties necessitates a cubic specimen with the dimensions of 100 mm × 100 mm × 100 mm for compressive strength; a loading rate ranging from 1.2 MPa/s to 1.4 MPa/s; and a prism specimen with the dimensions of 100 mm × 100 mm × 400 mm for flexural strength, with a loading rate ranging from 0.08 MPa/s to 0.1 MPa/s.To examine the impact of diverse mineral blends on the compressive strength of UHPC concrete, SF, FA, and LP were chosen for the mix formation.The results are presented in When the content of SF is 10%, its 28-day compressive strength meets the requirement of 100 MPa . From anD (%) is denoted by P(iD); the maximum particle size (μm) is maxD; the minimum particle size is minD; and the distribution modulus, q, is determined by the ratio of large to small particles in the system. The larger the particles, the larger the modulus. Based on the experiments , the MAARSS) was used to further elucidate the divergence between the cumulative distribution curve of the mixture and the model target curve, which is derived from various amounts of raw materials. The RSS was calculated as follows:RSS is the sum of the squares of residuals and Pmix and Ptra are the actual accumulation curve and target curve, respectively.The least square method (LSM) was used to adjust the mass ratio of the raw materials in the dry mixture. The residual sum of squares  was 0.23 to establish the objective function of the MAA model , belite (C2S), aluminate (mainly C3A), and ferrite (C4AF), are powdered cement clinker and gypsum  is the sum of the heat consumption of the component reactions [iP is the weight composition ratio and C3AETHand C4AFETH are the rates of heat generation during the formation of ettringite based on the aluminate and ferrite phases, respectively. After the reaction of calcium hydroxide formation has stopped due to the disappearance of unreacted gypsum, hydration heat is generated in C3A and C4AF . iH is the heat release rate of mineral i per unit weight, as defined in Equation (5):i, which is denoted by iE, is accompanied by the gas constant R, and the reference heat-generation rate of component i at a constant temperature 0T is i,T0H. The coefficient of change when no other effect is present, iγ, is defined as the delaying effect of the chemical admixture and FA in the initial exothermic hydration process; iβ is the decrease in the heat generation rate due to the reduction in the availability of free water. iλ is the coefficient of the heating rate change caused by the absence of Ca(OH)2 in the powder mixture’s liquid phase. A coefficient of heat generation rate alteration, iμ, is the interdependence between alite and belite in Portland cement. (−iE/R) is defined as the thermal activity.An original multi-component cement hydration model was developed by Koichi Maekawa , which ceactions .(3)Qt=∫2 [r and s are the material constants that are common to all minerals. The comparison of the experimental and analytical results show that R = 5.0 and S = 2.4. The coefficient of iβ varies from 0 to 1, and is is a function of the normalized Blaine value, which represents the change in the reference heating rate due to powder fineness. i.FAs are typically regarded as single reaction units that blend cement. However, these components are considered in this model as a single component, and the mixing of cement partially suppresses the generation of heat. The reaction of the powder mixture is determined based on the hydration of cement, which is linked to the amount of Ca(OH)2 .(6)HFA=2 consumed by cement hydration, as other powder mixtures require it. The rate of reduction after mixing is expressed as the ratio of the remaining Ca(OH)2 to the amount required for the active reaction of FA.CHF is the amount of Ca(OH)2, that is produced by the hydration of C3S and C2S but not consumed by the C4AF reaction, and FACHR is the amount of Ca(OH)2 required for the reaction with FA when a sufficient amount of Ca(OH)2 is available. It is essential for the model to calculate the amount of Ca(OH)Because of limited test equipment, this study did not carry out an isothermal exothermic test, but instead used the data obtained from isothermal exothermic tests in other scholars’ articles to verify the model. In the study by He , isotherAs an active admixture, the exothermic process of SF is similar to that of FA; thus, the heat release rate formula of SF is as follows:A comparison of SF concrete’s isothermal heat dissipation test results  with itsTo demonstrate the broad applicability of Kadri’s  isothermIn the multi-component hydration model presented in this study, LP was included as a powder material. LP, although not actively engaged in the hydration process, has a critical role in optimizing the model’s performance. The packing density and porosity are both increased and reduced by its micro-filling effect on other active components ,42, thusFor P2 and P3:For P4 and P5:j is the point number in the reference heat rate function; ijQ and ijHS are the heat rate and accumulated heat of component i, respectively; imaxQ is the maximum heat generation; LPp and Cp are the weight fractions; and LPB and CB are the unit weight surface areas of LP and Portland cement, respectively. The acceleration effect is expressed by the ratio of the surface areas of LP and cement, sr, which is taken as an indicator. The coefficients H1k, H2k, H3k, and Qk are multiplied by sr to represent the degree of contribution of LP.For P6:The results of the isothermal exothermic test for LP concrete, as reported by Moon , were coIn the preceding sections, the hydration of binary powder systems (excluding cement) was analyzed in detail to examine the heat release and chemical reactions that occur during the early stages of hydration. The analysis yielded significant revelations regarding the conduct of these systems, aiding us in constructing a more thorough comprehension of their efficacy. In this section, the analysis was extended to ternary powder systems by using the developed multi-component hydration model to verify the heat release during hydration. Thongsanitgarn  delved iBased on the literature data, the isothermal exothermic test results were compared with the numerical simulation results of the multi-component hydration model in this study . The ovehyd.outD must be taken into account, and the volume of hydrates formed outside the primitive cement particles was used as an index describing strength development [hyd.outD is the ratio of the initial capillary space to the space occupied by a large amount of external hydrates; hyd.outV is the volume of hydrates formed outside the primitive cement particles; hyd.totalV is the total volume of hydration products formed inside the original cement particles; hyd.inV is equivalent to the reaction volume fraction of mineral compounds; and cap.iniV is the volume of the initial capillary space. The volume changes of various hydration inner and outer products are shown in Considering that it is the solid phase rather than the porous phase that sustains strength development, the volume ratio of hydration products to the initial capillary space elopment .(21)Dhycap.iniV is equivalent to the porosity without strength. Although Schiller determined the value by fitting the estimated value with the experimental results, in the model proposed in this study, the volume of the initial capillary space cap.iniV was calculated based on the water to binder ratio of the mixture as follows:W/C is the water to binder ratio and cρ is the cement density.The Schiller model  shows thhyd.outD is the same, due to the smaller spacing between particles in the mixture with a reduced water to binder ratio.The compressive strength is impacted by the magnitude of the hydration products created by cement particles. These particles are shaped like spheres, and the mineral elements of cement clinker react with free water during the hydration process to create products. These spheres are divided into the non-hydration inner core, original boundary, hydrated inner product, and hydrated outer product. As shown in ik of the hydration products’ accumulation state was taken into account by considering two parameters: the alteration in the volume and the gap between cement particles. The ik is calculated as follows:hyd.outD is the ratio of the space occupied by a large amount of external hydrates to the initial capillary space; θ is the gap effect between cement particles; ik is the hydration factor of different powders i, including SF, FA, and LP; iφ is the mass ratio of powders in the mixture; and cm is the mass of different powders i (kg/m3). The change factor The volume of hydration products dynamically changes according to the hydration reaction; thus, the stacking state of the entire structure changes accordingly. An accurate prediction of concrete strength should be quantified by considering the influence of the change in hydration product volume on stacking.∞f is the ultimate strength (N/mm2); α′ and β′ are the material constants; and cP, SFP, FAP, and LPP represent the weight fractions of Portland cement, SF, FA, and LP, respectively. A, B, C, D, and E, are the material constants, indicating the contribution factor of each component on the strength development. This model has A at 120, B at 70, C at 210, D at 240, and E at 180, which represent the critical measure of concrete’s strength and the water to binder ratio while taking into consideration the alterations in hydration products. In this model, the strength prediction of UHPC is limited to 0.14–0.22.A model of strength prediction based on alterations in the porosity and hydration product was proposed in a previous study . The modThe accuracy of the model was verified using 15 sets of strength analysis data, which were obtained through experiments using different mix proportion design combinations .By comparing the measured compressive strength values of different mix designs with the compressive strength values simulated by the empirical model, the experiment proves that the empirical model can successfully quantify the compressive strength values, as shown in To enable an accurate prediction of concrete strength with minimal experimentation, a strength prediction equation was developed based on the changes in the volume and heat rate of water. By establishing a parameter system using only a few experiments, it is possible to use the concrete strength to accurately predict and optimize the mix design process for improved performance. The resulting simplified mix design process, shown in The effectiveness of the simplified mix design process was verified by means of 23 sets of experimental data from various papers ,46,47,48A simulation was conducted to evaluate the efficacy of the simplified mix design process with the aim of ascertaining the ideal mix proportion and forecasting the strength value of concrete. The simulation was designed to demonstrate the dependability and precision of the simplified mix design process in forecasting concrete strength and optimizing mix designs for enhanced performance. The simulation results, as shown in In this study, SF, FA, and LP were used as raw materials to conduct 15 groups of experiments to determine the different original PSD properties of UHPC. A model of multi-component hydration, which was based on the pozzolanic reaction of SF, FA, and LP, was formulated to quantify both the rate and total heat release of the hydration process. Additionally, a microscopic pore development model based on the accumulation of hydration products was created to measure the effect of these products on the particle packing characteristics. A UHPC strength prediction model was designed to measure strength, which was based on the abovementioned model and only used data from a few experiments. The precision of the proposed model was confirmed by contrasting the empirical outcomes with existing experimental outcomes. The conclusions of this study and prospects are as follows:(1) The compressive strength tests using different powders were carried out. The results show that SF can significantly improve the compressive strength of concrete, and FA is better than LP in terms of improving the strength. The MAA model is used to simulate the experimental results of compressive strength with different mix designs, which can predict the trend of compressive strength under different mix designs well.(2) A model of hydration heat release, which was composed of multiple components, was formulated to quantitatively gauge the influence of SF, FA, and LP. Verification through experimentation affirmed that the simulation of the reaction rate and heat release during the hydration process was very accurate. (3) A micro-pore development model was developed based on the accumulation of hydration products. Estimates were made regarding the fluctuation in the volume of distinct hydration products and the dynamic alteration of the cement particle gap. Based on these results, a complete set of formulas was established to create the parameter system.(4) The verification of the proposed strength prediction method was accomplished through the utilization of experimental data obtained from the literature. The results suggest that the proposed method can achieve accurate strength prediction by utilizing data from only a few experiments. (5) In this study, the proposed method could reduce the amount of practical engineering experiments and guide the mix design; however, the UHPC strength model in this paper is only suitable for compressive strength, and the test results of flexural strength have not been further analyzed. It is suggested that in a follow-up study, the prediction model of the bending strength of UHPC with different powders could be considered to better guide the mix design’s mechanical properties in UHPC.


The influences of various factors on blood lead to the formation of extra reactive oxygen species (ROS), resulting in the disruption of morphology and functions of red blood cells (RBCs). This study considers the mechanisms of the mechanochemical synergism of  The most important processes in living organisms are redox processes, which regulate the state and morphology of red blood cell (RBC) membranes. The combination of oxidative and antioxidant processes helps to maintain metabolic processes in RBCs, tissues, and the body as a whole ,2.A wide range of reactive oxygen species (ROS) in aqueous solutions plays a major role in oxidative processes in RBCs. Some examples of active oxygen-containing compounds are and HO2− ,4,5.ROS are formed under the action of various factors in the organism, in particular, in blood, such as toxins, radiation, etc. ,7,8. ROShe blood ,23.The consequence of oxidative stress development is the initiation of lipid peroxidation (LPO), which is a chain process of destructive reactions in RBC membranes. This leads to the formation of LPO products, in particular, hydroperoxides in RBC membrane lipids ,24. The e lipids . This ise lipids . Thus, te lipids . As a ree lipids . Biologi−13 s to several minutes or even years. Other influences in the first stage include a weakening of the immune system during various diseases, resulting in the initiation of other stages of development . T. TH2O2 wemolysis C. As a rSynergism is the interaction or cooperation of two factors to produce a combined effect trait which is greater than the sum of their individual effects.In our experiments, we examined the following possible mechanochemical synergism A in the Suppose the activity of the agent RBCs and their membranes can be considered BOs. The possible effects of two factors, The probability that agent ill be 0 : ResM=0.Res) of the total impact of agents The probability that agent Agent As a result of various factors  on the blood, excited atoms and molecules, radicals, and ions appear. There is a swarm of ROS. The amount of ROS will be increased by the value of ΔROS . ExcitedΔROS C. FigureDepending on the environment, ROS have different spatio-temporal characteristics of interactions with each other. A short lifetime −9−10−6s ,42,43.Therefore, the distances for their diffusion in a biological object are very short. This means that radicals and excited molecules are practically unable to escape from the swarm. That is why the radicals themselves can practically reach the membrane lipids, if the formation of LH, it is able to initiate a chain process of lipid oxidation, leading to the formation of lipid hydroperoxides LOOH. Accordingly, In the ROS series, we distinguish two objects: hydroxyl radical ide H2O2 C. ReactiThe activity of the istances C.(1)Estimates are presented for comparison. The oxidative effect of H•≫AH2O2 ,41.Relative activities with respect to lipids: (2)The characteristic lifetimes of these two ROS differ significantly: −9−10−6s ,43,44. S(3)Correspondingly, the diffusion distances for these particles also vary considerably: Why did we choose reaction C.This raises the question of whether Let us consider the mechanism of mechanochemical synergism according to the scheme shown in As noted above, the free radical e S≫SOH• A. Let usWhat could be the possible delivery route for highly active free radicals Obviously, this is only a schematic mechanistic representation of the mechanochemical synergism of the agents rocesses . At the together C.In solution, the —stage 1 C. This hIn turn, hydroxyl radicals —stage 2 C. Thus, LH at a distance However, if ith them C. This i 2 and 3 C.This is the first level of the mechanochemical synergism of In the work, a kinetic modeling of synergism based on biophysical principles has been proposed. The synergism of free radicals Simultaneously with the first level, the second level of synergism also occurs, namely, free radicals eir loss C. The syLet us consider the mathematical model of the synergism involving The first level of mechanochemical synergism. This synergism delivers The molecule n of OH• :(6)H2O2+As a result of these reactions, Let us designate:In the equations, consider a time A differential equation of the change in  stage 1 C:(7)dydtInitial condition: suppose at some point that Note that in the calculations, all concentrations of chemical components are presented as arbitrary units (A.U.), which are not specified, including in the graphs.Then, we obtain:Suppose that:The graph of The change in the value of into OH• C. Thus, As a result, a positive feedback system between The second level of mechanochemical synergism. There is For different times, the values of For the parameters in Equation (9), the time interval is Let us take the concentration of radicals These radicals will participate in further conversions, causing their reduction (1)Interaction of  stage 2 C: OH•+OH(2)LH, stage Interaction with membrane lipids The interaction of stage 2, C is descInitial condition:x) interacts with lipids LH  A. AdditiIf If The possibility of replenishing the loss of molecules  1 and 2 A, the liAccording to the model, τOH•syn1 A,B. The ROS interaction occurs along their diffusion distances C–F. The S~Dt . For the−5 cm2/s ,46, we wKnowing the dependences The increase in the effective lifetime , respectively. The thickness of the RBC layer, which can be affected by free radicals Under the conditions of ROS synergism, the recovery C,D. TherFricke’s solution was used as the working solution . In the prepared A. In thiTo determine the concentration of FL, USA) A. The exThe maximum characteristic of The working solution B with different concentrations of hydrogen peroxide was designated as To determine the unknown concentration We used software of Origin Pro 2019  for NCF of the experimental data. We used the absorption law function as the theoretical function for NCF:Equation (20) was created based on biophysical principles . The fit data of . Thus, iThe unknown parameters in Equation (20) are the concentrations In Equation (20), instead of the theoretical massive analysis . In our The data were analyzed using software of Origin Pro 2019. Optical spectra were measured five times for a given concentration of Thus, in the study, the fitted value, standard error of the fitting, and the residuals are reported as statistical parameters. The mean, SE, and SD of the sample parameters were also calculated.Mathematical modeling was used to study the kinetics of change in the concentrations of The basic assumptions of the kinetic model are as follows.(1)We consider chemical processes of the conversion of (2)The second assumption is based on the significant difference in the lifetimes of the free radical As a result, the calculated kinetic curves Red blood cells are continuously exposed to both endogenous and exogenous sources of reactive oxygen species in the circulation. To minimize the effects of these ROS, RBCs possess an extensive antioxidant system. An imbalance between excessive ROS production and antioxidant defense results in oxidative stress. The study of the mechanisms of the occurrence of an excess number of ROS and their amplification during the functioning of the circulatory system remains the subject of intensive scientific research. This is due to the fact that oxidative stress plays a significant role in the damage of erythrocyte membranes, cell morphology, and deformability. The mechanisms of the processes involved in the appearance and development of these pathologies are still not fully understood. This is currently the subject of research and scientific discussion. ROS are characterized by a strong interrelation as they undergo chemical transformations. The same ROS can be both a consequence and a cause of chemical transformations of others. Such an overlapping of events between a large number of ROS makes the study and the interpretation of the results very difficult. In this work, based on the biophysical principles, a kinetic model of the mechanochemical synergism of the action of free radicals The effectiveness of the impact of these ROS on RBC membranes under synergistic conditions has been shown to be many times higher than in the case of an exposure to the same factors individually. As a result of this ROS synergism, the efficiency of LPO in RBC membranes is greatly enhanced. A further study of the possible mechanisms of ROS synergism in blood will help to clarify the mechanisms of the destruction of bacteria and viruses in the blood, the damage of RBC membranes during radiotherapy and the long-term storage of packed RBCs, as well as the effects of toxins. This study is also important for the development of new methods to protect RBCs from excessive ROS.


Inconsistencies between a protocol and its umbrella review (UR) may mislead readers about the importance of findings or lead to false-positive results. Furthermore, not documenting and explaining inconsistencies in the UR could reduce its transparency. To our knowledge, no study has examined the methodological consistency of the protocols with their URs and assessed the transparency of the URs when generating evidence.This study aimed to investigate the inconsistency of protocols with their URs in the methodology and assess the transparency of the URs.We searched medical-related electronic databases from their inception to January 1, 2022. We investigated inconsistencies between protocols and their publications and transparencies in the search strategy, inclusion criteria, methods of screening and data extraction, quality assessment, and statistical analysis.We included 31 protocols and 35 publications. For the search strategy, 39 inconsistencies between the protocols and their publications were found in 26 of the 35 (74%) URs, and 16 of these inconsistencies were indicated and explained. There were 84 inconsistencies between the protocols and their URs regarding the inclusion criteria in 31 of the 35 (89%) URs, and 29 of the inconsistencies were indicated and explained. Deviations from their protocols were found in 12 of the 32 (38%) URs reporting the methods of screening, 14 of the 30 (47%) URs reporting the methods of data extraction, and 11 of the 32 (34%) URs reporting the methods for quality assessment. Of the 35 URs, 6 (17%) were inconsistent with their protocols in terms of the tools for quality assessment; one-half  of them indicated and explained the deviations. As for the statistical analysis, 31 of the 35 (89%) URs generated 61 inconsistencies between the publications and their protocols, and 16 inconsistencies were indicated and explained.There was a high prevalence of inconsistencies between protocols and publications of URs, and more than one-half of the inconsistencies were not indicated and explained in the publications. Therefore, how to promote the transparency of URs will be a major part of future work. Umbrella reviews (URs) are clusters that encompass previously published systematic reviews or meta-analyses that consider many comparisons of interventions for the management of the same disease or condition, to provide an overall examination . URs notHowever, since a broad synthesis of data from many systematic reviews requires a high level of subject matter expertise and methodological skills, not all published URs follow clearly described, standardized methodology, which may reduce the credibility of evidence from URs ,4-6. PubInconsistencies may exist because of conscious or subconscious manipulation to reach the desired conclusion, which misleads readers about the importance of findings or causes false-positive results -13. In sThe primary aim of this study was to investigate inconsistencies between a protocol and its publication when developing an UR. The secondary aim was to assess the transparency of the URs when generating evidence.URs that met the following criteria were included: (1) A UR was defined as a quantitative or qualitative synthesis of medical-related systematic reviews, (2) a UR protocol and its publication along with their methodological descriptions were available, (3) URs’ protocols and their publications were published in peer-reviewed journals or preprints, (4) the UR was part of a study, (5) the UR was published in English. There was no restriction on the time frame of the studies. We excluded the following studies: (1) methodological reviews of URs, scoping or rapid reviews, qualitative reviews, integrative reviews, and evidence synthesis and (2) abstracts, conference proceedings, and letters to editors.A comprehensive literature search was performed in 7 medical-related databases, including PubMed, Embase, Web of Science, The Cochrane Library, Joanna Briggs Institute (JBI) Database of Systematic Reviews and Implementation Reports, PROSPERO, and Open Science Framework (OSF), from the inception of these databases to January 1, 2022. The search strategies were developed by an expert in literature searches (JT), and the full search strategies are presented in Table S1 in We managed all records using EndNote  software and removed duplicates using automatic and manual screening. The study selection was divided into 4 steps. First, 2 authors (LZ and ML) independently screened all URs’ protocols and publications using title, abstract, and full text, consecutively. Second, we read the full text of identified publications to find the protocols mentioned in the articles (JZ and LC). Third, for protocols that were not related to included publications in the previous step, the study names or standard abbreviations (where applicable) combined with the term “umbrella” were used to search PubMed, Embase, The Cochrane Library, and Web of Science for their publications . In cases where the same protocol was described in multiple publications, all related publications were included. Finally, the reference lists of included URs were manually searched for additional studies. Any disagreements were resolved through discussion between authors and, if necessary, consultation with senior authors (JZ and JT).We developed the data extraction form and revised it after piloting it on a random sample of 20% of included URs . The extracted data consisted of 2 parts: general characteristics and methodological characteristics. A list of extracted items is given in Table S2 in According to the JBI manual for URs , we asseThe frequency of inconsistencies and transparency were our primary outcomes. Median (IQR) was used for continuous variables, including the number of authors, journal impact factor, total number of studies included, and interval between the protocol and its publication, whereas frequency (%) was used for categorical variables. The statistical analyses were conducted with SPSS Statistics v26.0 (IBM Corp).The database search yielded 2716 records, and an additional 263 records were identified through other sources. Following the removal of duplicates and title and abstract screening, 88 protocols and 684 publications were screened using the full text. In total, we identified 31 protocols and 35 publications . The fulThe included URs were published between 2012 and 2021, and most of them  were published after 2016 . The intAll URs described the search strategy, and 39 inconsistencies between the protocols and their publications were found in 26 of the 35 URs (74%). Of 39 inconsistencies, 16 (41%) were indicated and explained in the publications .Of the 35 publications, 21 (60%) deviated from their protocols in the literature sources: 14 deviations occurred in the databases, and 12 URs generated deviations regarding other literature sources. Of the 21 URs, 3 (14%) indicated inconsistencies in the publications. Compared with the protocols, 1 publication expanded the range of language for included studies, and the other added language restrictions to the included studies. Although 3 publications did not describe language restrictions, their protocols did. In the 5 URs, 4 (80%) inconsistencies were disclosed in the URs. Regarding search times, 13 of the 35 (37%) publications differed from their protocols: 6 because of updates, 3 for other reasons, and the remaining 4 lacked an explanation.All URs described the inclusion criteria, and 31 of the 35 (89%) URs had inconsistencies between the protocols and their publications .For the participants, 13 of the 35 (37%) publications were inconsistent with their protocols. In the 13 URs, 5 described the participants in detail in the protocols but not in the publications. Compared with the protocols, 6 narrowed the inclusion of the participants, and 2 expanded the inclusion of the participants. Of the 13 publications, 5 (38%) indicated and explained the inconsistencies.Of the 35 URs, 16 (46%) generated the following inconsistencies between the protocols and their publications in the interventions: (1) 6 publications narrowed the scope of the interventions compared with the protocols; (2) compared with the protocols, the scope of the interventions was extended in 4 publications; (3) 3 publications were contradictory to the protocols; (4) 3 publications did not describe the interventions, while their protocols did. Of the 16 publications, 6 (38%) pointed out and interpreted the inconsistencies.Regarding the comparators, 10 of the 26 (38%) URs showed deviations between the protocols and their publications: 4 publications increased the number of comparators compared with their protocols, 4 protocols but not their publications described the comparators, and 2 publications removed comparators that were included in the protocols. Of these 10 URs, 4 (40%) publications indicated where the inconsistencies arose.Inconsistencies between the protocols and their publications in the outcomes were found in 19 of the 35 (54%) URs. The most common inconsistency was that the publications reduced the number of outcomes compared with their protocols (8 URs). The second was that the publications added outcomes (4 URs). The third was that the protocols but not the publications described the outcomes (4 URs). Finally, 3 publications changed the outcomes described in the protocols. Inconsistencies were indicated in 7 of the 19 (37%) publications.Inconsistencies between the protocols and their publications regarding the type of studies were found in 13 of the 35 (37%) URs: (1) 6 publications narrowed the inclusion of the study design compared with their protocols; (2) 5 publications expanded the inclusion of the study design, and 1 of them added inclusion of updated randomized controlled trials; (3) 2 protocols but not their publications described the type of included studies. The reasons for deviations were explained by 2 of the 13 (15%) URs.Other inclusion criteria were reported by 24 of the 35 (69%) URs, of which 14 (58%) URs reported the requirements for included studies, 11 (46%) URs reported the quality of included studies, and only 2 (8%) URs reported the requirements of the protocol. In the other inclusion criteria, there were the following inconsistencies between the protocols and their publications in 13 of the 24 (54%) URs: 8 inconsistencies in the requirements for included studies, 5 inconsistencies in the quality of included studies, and 2 inconsistencies in the requirements of the protocol. The inconsistencies were detailed in 5 of the 13 (38%) publications.The following inconsistencies between the protocols and their publications were found in the methods for screening, data extraction, and quality assessment : (1) 14 All URs described tools for quality assessment; the most common  was the JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. The tools used in the protocols were changed in 3 publications, and 3 publications did not depict tools, while their protocols did. The deviations were indicated in 3 of the 6 (50%) publications.We found 62 inconsistencies between the protocols and their publications in 31 of the 35 (89%) URs, and 16 of the 62 (26%) inconsistencies were indicated and explained in the publications .Of the 35 URs, 18 described how to deal with the overlaps of primary studies between included systematic reviews. There were inconsistencies between 3 of the 18 (17%) protocols and their publications. Of them, 2 protocols gave ways to deal with overlaps, while their publications did not implement them; 1 publication added the calculation of the corrected covered area. None of the inconsistencies was indicated in the publications.Tools for assessing the certainty of the evidence were reported by 24 URs, and 20 of these URs used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Inconsistencies existed between 13 of the 24 (54%) URs and their protocols: 10 protocols but not their publications reported assessments of the certainty of the evidence, and 3 publications added tools for assessing the credibility of evidence that were not described in the protocols. Inconsistencies were detailed by 2 of the 13 (15%) URs.What findings to present and how to present them were described in 26 URs: 12 of the 26 (46%) URs generated inconsistencies between the protocols and their publications, and 3 URs indicated and explained inconsistencies in the publications. Compared with the protocols, inconsistencies could be categorized as follows: (1) 5 publications differed on whether to apply the “summary of evidence” table, (2) the forms of evidence presentation were changed in 5 publications, and (3) 2 publications changed the reported elements.All URs depicted the data analysis, and inconsistencies between the protocols and their publications were found in 9 of the 35 (26%) URs. Compared with the protocols, 3 publications removed quantitative analysis, 2 publications added quantitative analysis, 2 publications altered the rules for qualitative synthesis, 1 publication changed the quantitative analysis model, and 1 protocol did not describe the data analysis while the publication did. Of the 9 inconsistencies, 4 (44%) were detailed and explained in the publications.How to standardize the effect sizes was reported in 13 URs, and 11 of these 13 (85%) URs had inconsistencies between the protocols and their publications: 8 URs only reported it in the publications, and 1 UR only reported it in the protocol; regarding the standardization of dichotomous data, 2 publications were inconsistent with their protocols. Of the 11 inconsistencies, 2 (18%) were indicated and explained in the publications.Of the 35 URs, 21 described other statistical analyses, including subgroup analysis , sensitivity analysis , and publication bias or small study effects . Inconsistencies between the protocols and their publications were found in 14 of the 21 (67%) URs. Regarding subgroup analyses, 12 URs had inconsistencies with their protocols. Of the 12 URs, 9 only reported the subgroup analysis in the protocols, 2 only reported it in the publications, and 1 publication changed the subgroup analyses that were described in the protocol. Deviations between the protocols and their publications in publication bias or small study effects and sensitivity analysis were found in 4 URs and 1 UR, respectively. Of the 14 URs with inconsistencies, 5 (36%) detailed the inconsistencies in the publications.We identified 31 protocols and 35 publications of the URs. Inconsistencies between the protocols and their publications were found in all areas, with inconsistencies occurring most frequently in inclusion criteria and statistical analyses. In addition, less than one-half of the inconsistencies were indicated in the publications of URs, and the transparency of URs was inadequate.Our study showed inconsistencies in the search strategy between the protocols and their publications in 74% (26/35) of the URs, which was similar to previous result that indicated 77% of reviews changed the search strategy between the protocols and their publications . ChangesAlthough URs often aim to provide a broad overview of the evidence on a topic, it is still important to be specific about the inclusion criteria . These cIn terms of the statistical analysis, we identified that 89% 31/35) of the URs’ publications deviated from their protocols. This is similar to a finding for systematic reviews , in whic/35 of thOver one-half of the included URs dealt with overlaps of primary studies, which was consistent with the findings by Pieper et al , and 12 As for certainty of evidence, the most common inconsistency was that the GRADE was removed in the publications, which might lead to a diminished certainty of evidence generated by URs ,26. AlthResearch transparency can speed scientific progress, can increase trust in science, and is one of the core values of science ,43. In tPublishing a protocol in a peer-reviewed journal is a crucial way to improve transparency, by comparing the protocol with a completed UR to detect whether unintended and undocumented changes were made . HoweverScience pointed out that systematic reporting standards also contribute to the transparency of research [A study published in the journal research . For exaresearch . It provresearch ,44. TherTo the best of our knowledge, our study was the first study to assess inconsistent reporting between the protocols and the publications of URs in the methodology. Because we comprehensively analyzed each step of the development of an UR, our findings could be considered beneficial to the production of URs. However, there were some limitations in our study. First, only URs published in English were included. Second, our study conducted only an exploratory analysis with a relatively small sample size, so some inconsistencies may be overlooked. Third, some publications depict only part of the methodology of an UR, resulting in incomplete comparisons between protocols and publications. Last, there is no standard protocol to address the analysis of inconsistencies between protocols and their publications; therefore, we created our protocol and analysis process based on previous similar studies. There is potential for bias or that other factors were not included.There are several areas for future development in the methodology of URs, including (1) the specific combination of literature sources that could identify more available evidence, (2) development of a validated reporting quality tool specifically for URs, (3) appropriate and adequate use of statistical analysis in URs, and (4) modification to the GRADE so that it can be applied in URs. It is also beneficial if our study can help medical editors and scientific journals draw attention to whether a UR’s protocol exists and identify any unrecognized or unreasonable changes between the protocols and their publications during the editing process.There was a high prevalence of inconsistencies between protocols and publications of URs, especially in the inclusion criteria and statistical analysis. More worryingly, more than one-half of URs did not indicate and explain the inconsistencies, and the transparency was inadequate. Thus, the authors of URs should be required to describe and explain any deviation from their protocols. Our study provides further evidence that published protocols allow the tracking of any changes that have taken place, to assess the transparency of URs. Therefore, authors of URs are encouraged to publish their protocols, and journals are urged to accept protocols for publication. In addition, editors or peer reviewers could compare publications of URs with their protocols and check back to confirm whether the changes were indicated and explained.