The present umbrella review aimed to characterize the type and regimen of antibiotics administered locally and/or systemically, alone or in combination with surgical and nonsurgical treatments, for peri-implantitis and to evaluate and compare the associated clinical, radiographic, and crevicular peri-implant outcomes. The secondary objective was to determine the most effective antibiotic type, route of administration, regimen, and protocols  for treating peri-implantitis. The study protocol, which was developed in advance under the PRISMA statement, was registered at PROSPERO (CRD42022373957). BioMed Central, Scopus, MEDLINE/PubMed, the Cochrane Library databases, and the PROSPERO registry were searched for systematic reviews through 15 November 2022. Of the 708 records found, seven reviews were included; three were judged of a critically low and four of low quality through the AMSTAR 2 tool. Locally administered antibiotics alone or as an adjunct to surgical or nonsurgical treatments for peri-implantitis showed favorable outcomes, albeit with limited evidence. The administration of systemically-delivered antibiotics in combination with nonsurgical or surgical treatments remained questionable. Local plus systemic antibiotics have not been shown to have durable efficacy. Due to the heterogeneity of reported antibiotic types, routes, regimens, and protocols, no definitive conclusions could be drawn regarding the most effective antibiotic use in treating peri-implantitis. Dental implants have become one of the most reliable therapeutic options to replace missing teeth. As a result, a significant increase in the number of dental implants placed annually, on the one hand, and in the number of cases diagnosed with peri-implantitis, on the other hand, has been observed worldwide ,2.The 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions defined peri-implantitis as a pathological condition occurring in the tissues surrounding dental implants characterized by signs of inflammation of the outer tissues and progressive bone loss ,5,6,7,8.A number of therapeutic approaches have been proposed for peri-implantitis management ,17,18,19Abrasive air powder, metallic or non-metallic curettes , with an ultrasonic scaler with a metal or plastic tip ,15 proviAs a counterpart, chemical biofilm control mainly relies on chlorhexidine, along with hydrogen peroxide, cotton pellets soaked in saline solution and citric acid .However, nonsurgical treatment has not yet shown fully predictable results in peri-implantitis treatment ,10, and Moreover, considering that the microbial flora characterizing peri-implantitis has a broader spectrum compared to periodontitis and that the biofilm of peri-implantitis is characterized by higher counts of human cytomegalovirus and Epstein–Barr virus ,8,13, reFurthermore, antibiotics administration as adjuncts to peri-implantitis treatment was first proposed by Mombelli and Lang in 1992 . Since tTherefore, the present umbrella review aimed to characterize the type and regimen of antibiotics administered locally and/or systemically, alone or in combination with surgical and nonsurgical treatments for peri-implantitis, and to evaluate and compare the associated clinical, radiographic, and crevicular peri-implant outcomes. The secondary objective was to determine the most effective antibiotic type, route of administration, regimen, and protocols  for treating peri-implantitis.Prior to the literature search, data extraction, and analysis, the study protocol was defined under the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement , and regThe questions were formulated based on the PICO model ,27, and The research question  focused I-Intervention: locally and/or systemically administered antibiotics alone or ;C-Comparison: no intervention, placebo, between different interventions ;O-Outcome(s): clinical and radiographic and crevicular peri-implant parameters.P-Population: subjects with at least one dental implant and implant-supported restoration(s) with peri-implantitis:Systematic reviews  published in English on local and/or systemic antibiotics in peri-implantitis treatment were searched electronically through the PROSPERO registry and Scopus, MEDLINE/PubMed, BioMed Central, and Cochrane Library databases by three independent reviewers  without date restriction until 15 November 2022, using keywords and Boolean operators as follows:  AND .The following filters were applied: “review (English)” and “refine”: “review (English)” in the Scopus database; “systematic review (English)” in the MEDLINE/PubMed database; “keywords” in the Cochrane Library; no filters were used in the BioMed Central database or the PROSPERO registry.Collected citations were recorded, duplicates were eliminated via the reference management tool EndnoteTM (Clarivate), and the remaining systematic review titles  were screened by the three independent reviewers , who then screened relevant abstracts.The full texts of these potentially eligible title-abstracts were obtained, contacting the study authors if full texts were unavailable, and were independently reviewed by the same authors . Any differences of opinion were clarified by consultation, and in case of doubt, another author (FG) was consulted. No manual search was carried out from the reference lists of included articles.Inclusion criteria: no restrictions were applied on publication date, the number of studies, and study design included in each systematic review; age, gender, and characteristics of the participants; the number of dental implants and type of prosthetic restorations; type and regimen of antibiotics administered locally and/or systemically, alone or in combination with other  peri-implantitis treatment.Exclusion criteria: non-English language studies and self-reported peri-implant status were excluded.Data were extracted independently and in duplicate by two authors  using a standardized data extraction form developed based on the models recommended for intervention reviews of RCTs and non-RCTs  before dOf each systematic review  included in the present umbrella review, data illustrated in A narrative synthesis of the data regarding the population studied, intervention(s), and outcomes was performed.to characterize the type and regimen of antibiotics administered locally and/or systemically alone or in combination with other  peri-implantitis treatments and comparisons;to assess clinical, radiographic, and crevicular peri-implant outcomes according to the type and regimen of locally- and/or systemically-delivered antibiotics administered alone or in combination with other  peri-implantitis provided;to compare clinical, radiographic, and crevicular peri-implant outcomes after administration of locally- and/or systemically-administered antibiotics alone or in combination with other  peri-implantitis vs. placebo and to each other.Data from the included studies were qualitatively synthesized:https://amstar.ca) on 16 November 2022, evaluating for quality the systematic reviews with or without meta-analysis [The quality assessment of the systematic reviews included in this umbrella review was performed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool, accessed online  not relevant; (n = 1) describing antibiotic use combined with antiseptic agents in implant surgery; (n = 1) antibiotics were not used in peri-implantitis treatment; (n = 2) describing prophylactic antibiotic use; (n = 2) reviews were still ongoing .A total of seven systematic reviews ,45,46,47The total number of subjects involved was 1575 with 2262 implants. However, three studies ,46,47 diThe characteristics and outcomes from included studies are synthesized in Locally-delivered antibiotics for treating peri-implantitis were administered alone and in combination with other nonsurgical and surgical interventions and systemic ones.No data were available about the characteristics of systemic antibiotic therapy alone in treating peri-implantitis from included studies. Three systematic reviews ,42,46 deLocal minocycline , doxycycline gel , lincomycin gel, wrythromycin gel, retracycline fibers “Actisite”, and metronidazole gel “Elyzol” proved to reduce PPD and BoP . HoweverFour systematic reviews ,43,46,47Doxycycline hyclate 8.5% + SRP, minocycline 10 mg in 0.5 g of ointment + surgical treatment, and minocycline ointment + nonsurgical treatment improved BoP, GI, PPD, and PI at 4–6 months follow-up .Local tetracycline hydrochloride delivery by monolithic ethylene vinyl acetate fiber (for one time of antibiotic with a duration of 10 days) + rubber cup polishing + SRP, doxycycline “Atridox” subgingivally for one time + SRP and irrigation with 0.2% CHX, and minocycline “Periocline” subgingivally + OFD at 1, 3, and 6 months were found to positively affect PPD and BoP up to 12 months after therapy .Local doxycycline hyclate 8.5% “Atridox” applied through a syringe with a blunt cannula in the peri-implant sulcus + SRP determined a more significant improvement in CAL and PPD values compared to mechanical debridement at 4 months follow-up .Local minocycline gel + ultrasonic periodontal debridement, minocycline hydrochloride microspheres + SRP, and metronidazole (400 mg) + amoxicillin (500 mg) + SRP equally decreased PPD, BoP, and CAL values compared to the baseline .Characteristics of antibiotic administration in peri-implantitis treatment are detailed in Four systematic reviews ,44,45,47Several drug regimens were recorded for amoxicillin , azithromycin , metronidazole , amoxicillin (500 mg/8 h for 7 d) + metronidazole (400 mg/8 h for 7 d) for 5 to 7 days in combination with nonsurgical treatment, open flap debridement and mechanical implant surface debridement, as well as for other antibiotic combinations , overall highlighting that systemic antibiotics should be carefully evaluated in peri-implantitis management considering the risk of antibiotic resistance .Azithromycin , amoxicillin (1.5 g for 3 d preoperatively and 7 d postoperatively + open flap debridement + bone recontouring + rubber cup polishing + chlorhexidine 0.2%), and amoxicillin (500 mg/8 h for 14 d) + metronidazole (400 mg/24 h for 14 d) provided benefits in clinical peri-implant outcomes for up 12 months after therapy . In contThe association of amoxicillin and metronidazole in combination with ultrasonic debridement (500 mg/8 h + 500 mg/24 h for 7 d), scaling and root planing , as well as the administration of clarithromycin in combination with the antimicrobial photodynamic therapy (500 mg/24 h for 3 d) significantly reduced BoP, CAL, and PPD .Two systematic reviews ,43 reporLocal minocycline “Periocline” + amoxicillin (500 mg/8 h for 3 d) in combination with open flap debridement + scaling and root planing at 1, 3, 6 months proved some benefits in BoP and PPD values .Local metronidazole 25% gel “Elyzol” associated with tetracycline hydrochloride “Ambramicine” in combination with apically repositioned flap, as well as amoxicillin (50 mg/kg/d for 8 d) in combination with SRP before surgery did not affect peri-implant outcomes at 2-year follow-up .Three of the studies were judged of critically low ,46,47 anThe treatment of peri-implantitis, which aims to reduce the microbial load, decontaminate the dental implant surface, and eliminate peri-implant mucosal inflammation, thereby preserving the peri-implant bone, can be divided into nonsurgical approaches using mechanical instrumentation, antibiotics, antiseptics, and chemical or laser decontamination of the dental implant surface and surgical approaches such as air powder abrasion, resective, or regenerative procedures ,50,51,52Nonsurgical treatment of peri-implantitis aims to reduce inflammation by controlling biofilm . MechaniSurgical treatment of peri-implantitis is required when PPD and bone resorption have progressed or persist in removing biofilm and creating a surface that allows re-osteointegration through a full-thickness flap . AccordiGiven these considerations and the fact that peri-implantitis is maintained by microorganisms , it is lTherefore, the present umbrella review aimed to characterize the type and regimen of antibiotics administered locally and/or systemically, alone or in combination with surgical and nonsurgical treatments for peri-implantitis, and to evaluate and compare the associated clinical, radiographic, and crevicular peri-implant outcomes. The secondary objective was to determine the most effective antibiotic type, route of administration, regimen, and protocols  for treating peri-implantitis.The efficacy of locally-delivered antibiotics alone on periodontal parameters, especially PPD, BoP, and plaque index (PI), was investigated in three studies ,42,46 wiIndeed, only one study  found anFour studies investigated the efficacy of local antibiotics in combination with nonsurgical and surgical treatment of peri-implantitis. Except for one study in which implant failure was recorded , the varAccordingly, Passarelli et al.  found anTetracyclines were the most commonly administered antibiotics ,42, espeSystemically-delivered antibiotics have always been evaluated in combination with other interventions, likely because antibiotic stewardship advises against prescribing antibiotics unless they are indispensable and their efficacy is supported by evidence to combat antimicrobial resistance ,22.A total of four studies evaluating the efficacy of systemic antibiotics in combination with nonsurgical and surgical treatment for peri-implantitis were presently retrieved.Different associations of amoxicillin and metronidazole at variable doses and durations were administered in combination with nonsurgical  and surgical treatments with implant debridement and showed improvement in PPD and BoP in only two studies ,47. ConvConsequently, combining systemically-administered antibiotics with nonsurgical and surgical treatments for peri-implantitis remains controversial in the current state of knowledge. However, there is some evidence to support their use in recurrent and refractory peri-implantitis cases . The efficacy of locally- plus systemically-delivered antibiotics in combination with nonsurgical and surgical treatment was investigated in two studies ,43.Wang et al.  concludeEsposito et al.  also repNonsurgical treatments such as mechanical debridement and oral hygiene instructions effectively managed peri-implant mucositis and reduced but did not eliminate the inflammatory signs and symptoms of peri-implantitis ,54,55,56Chemical biofilm control and locally- and systemically-delivered antibiotics administration have been proposed to improve nonsurgical and surgical treatment outcomes.In particular, although supported by mild evidence, locally-delivered antibiotics used as an adjunct to nonsurgical mechanical debridement produced favorable results. In addition, local antibiotics, in combination with other surgical interventions, also showed modest clinical improvements in peri-implant parameters. Because adequate drug concentration at the site of infection is required for a sufficient time to eliminate the pathogens , variousConversely, systemically-delivered antibiotics had no significant effect on the treatment of peri-implantitis, either in combination with nonsurgical or surgical treatments ,44,45,47In fact, dentists are responsible for 10% of all antibiotic prescriptions , and antDue to the variability of antibiotic types, routes of administration, dosages, and combinations with other nonsurgical and surgical interventions, the most effective antibiotic type, route of administration, regimen, and protocol  for the management of peri-implantitis could not be determined from the currently retrieved data for either locally- or systemically-delivered antibiotics.Moreover, given the conflicting results and following antibiotic stewardship to combat antimicrobial resistance ,60,61,62Further research on the type of antibiotic, route of administration, therapeutic regimen, and protocols  for managing peri-implantitis is still needed to demonstrate the most effective antibiotic therapy and to limit the risks resulting from inappropriate antibiotic therapy.Given the heterogeneous data on antibiotic type, routes of administrations, therapeutic regimens, duration, and combination with other interventions, the incomplete data on peri-implant outcomes, and those missing on dental implants’ number, location, characteristics, and survival, no meta-analysis could be conducted. Findings from the presently included systematic reviews revealed contrasting and inconclusive results concerning the effectiveness of systemically- and locally-delivered antibiotics in peri-implantitis management. As a result, the ideal antibiotic type, route of administration, regimen, and protocols  in peri-implantitis management could not be determined.In addition, some studies, such as those by Renvert et al. and Cha et al. ,64, wereHowever, the present umbrella review may be the first to collectively evaluate the effectiveness and the proposed regimens and protocols of local and/or systemic antibiotic administration alone and in combination with other nonsurgical or surgical peri-implantitis treatments.Seven systematic reviews were included in the present umbrella review; three were classified as critically low quality and four as low quality using the AMSTAR 2 tool.Locally-delivered antibiotics administered alone or as an adjunct to surgical or nonsurgical treatments for peri-implantitis showed favorable results, albeit with limited evidence. The administration of systemically-delivered antibiotics in combination with nonsurgical or surgical treatments remained questionable. Local plus systemic antibiotics have not been shown to have durable efficacy.Because of the heterogeneity of reported antibiotic types, routes, regimens, and administration protocols, no definitive conclusions could be drawn regarding the most effective antibiotic use in managing peri-implantitis. However, given the phenomenon of antimicrobial resistance, the prescription of systemically-delivered antibiotics should be discouraged, and locally-delivered ones should be used with caution based on a case- and site-specific benefit-risk assessment.Further research is needed on antibiotics’ type, route of administration, therapeutic regimen, and protocols  for managing peri-implantitis, pointing out the case- and site-specific indications and the most effective antibiotic therapy, concurrently limiting the risks of inappropriate antibiotic use.


Stanford type A aortic dissection (TAAD) is one of the lethal macrovascular diseases caused by the invasion of blood into the media layer of ascending aortic wall. Inflammation, smooth muscle dysfunction, and extracellular matrix (ECM) degradation were regarded as the major pathology in affected tissue. However, the expression pattern and its regulation especially through circular RNAs (circRNAs) as an overall characteristic of TAAD molecular pathology remain unclear.We employed CIRCexplorer2 to identify circRNAs based on the RNA sequencing (RNA-seq) data of human ascending aortic tissues to systematically assess the role of circRNA in the massive alterations of gene expression in TAAD aortas. The key circRNAs were determined by LASSO model and functionally annotated by competing endogenous RNAs (ceRNA) network and co-analysis with mRNA profile. The expression level and diagnostic capability of the 4 key circRNAs in peripheral serum were confirmed by real-time polymerase chain reaction (RT-PCR).The 4 key circRNAs, namely circPTGR1 (chr9:114341075-114348445[−]), circNOX4 (chr11:89069012-89106660[−]), circAMN1 (chr12:31854796-31862359[−]) and circUSP3 (chr15:63845913-63855207[+]), demonstrated a high power to discriminate between TAAD and control tissues, suggesting that these molecules stand for a major difference between the tissues at gene regulation level. Functionally, the ceRNA network of circRNA-miRNA-mRNA predicted by the online databases, combining gene set enrichment analysis (GSEA) and cell component prediction, revealed that the identified circRNAs covered all the aspects of primary TAAD pathology, centralized with increasing inflammatory factors and cells, and ECM destruction and loss of vascular inherent cells along with the circRNAs. Importantly, we validated the high concentration and diagnostic capability of the 4 key circRNAs in the peripheral serum in TAAD patients.This study reinforces the vital status of circRNAs in TAAD and the possibility of serving as promising diagnostic biomarkers. Aortic dissection is an acute aortic syndrome clinically characterized by its abrupt onset and high mortality , 2, whicCircular RNAs (circRNAs) are a set of transcriptionally expressed and spliced RNAs composed of an enormous amount of species, each of which covalently forms a closed loop through a cis-linkage between its 5' and 3' ends with the currently unknown biological purpose . HoweverGrowing evidence has implicated circRNAs in various diseases, such as diabetes mellitus, neurological disorders, cardiovascular diseases, and cancers . For exaHowever, few studies have focused on the circRNAs in the pathogenesis of TAAD, with the exception of circMARK3 and hsa_circRNA_101238, which were reported upregulated in TAAD , 16. A sThis study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Nanjing Drum Tower Hospital, the affiliated hospital of Nanjing University Medical School . Written informed consent was collected from all subjects. The venous blood samples of diseased participants, including 8 patients with TAAD, 9 patients with TBAD, and 4 patients with intramural aortic hematoma (IAH), and 10 age-matched normal controls (NC) were obtained from Nanjing Drum Tower Hospital and diagnosed by contrast-enhanced CT. The specimens were immediately processed after collection. Blood samples were centrifuged at 2,000 rpm for 10 min at 4°C, and the supernatant was transferred into RNase-free tubes, which were subsequently stored at −80°C. The baseline information of enrolled samples was listed as follows.−ΔΔCT using β-actin as an internal control  from the respective control serum.Total RNA was isolated from cells using miRNeasy Serum/Plasma Kit  and was reverse transcribed using iScript cDNA Synthesis Kit . RT-PCR was performed with SYBR green PCR Master Mix  using ViiA 7 Real-Time PCR System . The primers used in this work were listed in https://www.ncbi.nlm.nih.gov/geo). The protein-coding genes in transcriptome expression were employed for identifying DEGs by DEseq2 (version 1.34.0) with the threshold of p < 0.05 and |log2 fold change (FC)|>1.In this study, we analyzed RNA-seq data from 20 samples of 10 patients with TAAD and 10 healthy controls produced in a previous study. The dataset GSE153434, including transcriptome expression and sequence read archive (SRA) files, was downloaded from the Gene Expression Omnibus (GEO) database (p < 0.05 and |log2FC|>1) to identify differentially expressed between the different sample groups.After implementing the initial quality assessment, filtered data were mapped to the human reference genome (GRCh37/hg19) with STAR (version 2.7.10a) . CIRCexpA 10-fold cross-validation lasso regression model was implemented in the R package glmnet (version 4.1–4) according to a binomial response type for binary dependent variables . The larCircRNA–miRNA interaction prediction was based on circBank, a comprehensive database of human circRNA which contained over 140,000 human-annotated circRNAs . The infp < 0.05 was identified as a significant outcome.The module gene enrichment analysis was carried out by the R package clusterProfiler (version 4.2.2) . Gene Onhttp://www.gsea-msigdb.org/gsea/index.jsp).For the identification of enriched gene signatures, we applied the gene set enrichment analysis (GSEA) based on R package clusterProfiler . The genGene set enrichment analysis was performed by comparison of gene-expression data obtained from TAAD and NC, as well as Spearman's correlation of circRNAs with gene-expression data. We used 1,000 gene-set permutations for testing of significance. The default parameters were used in this section.t-test after the normal distribution test.We used xCell (version 1.1.0) to calculate the relative proportion of 64 infiltrating cells in each sample based on the gene-expression profile. The different score of infiltrating cells was determined according to Student's T-test was adopted to compare the differences of expression of indicated circRNAs between the TAAD, TBAD and IAH groups and the NC group, respectively. We did the normal distribution test of circRNA relative expression by R function “shapiro.test.” All p-values were considered significant if < 0.05.R (version 4.1.2) was applied to all statistical tests. Spearman's correlation analyses were done by R. The multiple p < 0.05 and |log2FC| > 1, a total of 1,874 DEGs, with 643 upregulated DEGs and 1,231 downregulated DEGs in the aortas of patients with TAAD, were identified  based on all ranked log2FC values, which might benefit the assessment of enriched functions by ranking their expression fold changes. Interestingly, the GSEA revealed a broad and complicated inflammatory response, containing TNF-α, IL-1, 4, 6, 10, and 13 signaling pathways , althougTo explore the regulatory mechanisms of molecular pathology in TAAD, we computed circRNAs by RNA-seq data of TAAD and normal control ascending aortas, which was downloaded from the GEO database. A total of 26,566 kinds of circRNAs were identified by CIRCexplorer2 , while op < 0.05 and |log2 FC|>1. Compared with healthy controls, 78 upregulated and 9 downregulated circRNAs were recognized in TAAD aortas  enriched terms and 89% (16/18) repressed terms (data not shown). Impressively, the function of the key circRNAs was almost identical in three gene sets and was accordant with the target genes enrichment in ceRNA, likely implicating the domination of the circRNA-sponged miRNA function in the TAAD context. The inflammatory response , P53 signaling pathway, and hypoxia were enriched by increasing the key circRNAs, while the ECM components  and cell adhesion  were enriched by decreasing the key circRNAs . As for Notably, the muscle function-related scores, including VSMC contraction and smooth muscle contraction, were enhanced in ceRNA network enrichment, while they were diminished in GSEA analysis in TAAD . Since tCell composition alteration is still the key in tissue pathology. Although immune infiltration and cell apoptosis were reported in TAAD, the analysis of cell proportions and their relationship with circRNAs required more researches. Here, we utilized xCell , a novelWe further applied Spearman's correlation analysis of the key circRNAs and different cell infiltration. Notably, the key circRNAs demonstrated a dual vital role of positive correlation with immune cell scores and negative correlation with stromal cell scores, with circUSP3 showing the highest significance and broader effectiveness on almost all the different cell components, while circPTGR1 tending to be negatively related to the stromal cells . Thus, tFinally, we assessed the diagnostic power of the key circRNAs in the peripheral blood by RT-PCR to evaluate the relative expression level of the circRNAs in the plasma serum in TAAD and healthy controls. As expected, the key circRNAs were all higher expressed in TAAD serum compared to those in the healthy controls, while they varied in TBAD and IAH . As for In conclusion, the results verified that the four key circRNAs were adequate to diagnose TAAD in the peripheral plasma serum. However, determining the early onset of these circRNAs in the risk population is the key.via different mechanisms  of upregulated DEGs in the present dataset and featured the conventional pathological processes of TAAD, such as inflammation, ECM degradation, and aortic wall weakening, which were collaborated in TAAD pathogenesis. MiR-26b was previously reported to suppress TAAD development by directly targeting HMGA2 . Our anaIt is worth noting that, distinguishing from previous studies, we found that the TAAD upstream inflammatory cytokines were focused on IL-6 and IL-33 with massive downstream inflammatory responses linked to IFN-γ, TNF-α, IL-1, IL-2, IL-4, IL-6, IL-10, and IL-13 signaling, suggesting the uniqueness in triggering the inflammation of TAAD. IL-6 is a well-known pan-inflammatory factor coordinating the initiation of tissue inflammation, which is upregulated in various disorder conditions and highly related to TAAD , 70. ImpThe GSEA based on the correlation coefficients of circRNAs and gene expression demonstrated an essentially identical pathological effect of the key circRNAs with the enhancement of inflammation response and P53 signaling pathway, and the alteration and weakening of ECM, which were positively related to the key circRNAs, except the muscle function-related scores, including VSMC contraction and smooth muscle contraction, which were diminished in GSEA analysis in TAAD  while thvia interacting with miRNAs, which accelerated the TAAD development. As discussed earlier, circUSP3 preferred to involve in smooth muscle function and cell adhesion in addition to other classical molecular signatures of TAAD pathology, which was not reflected in cell component analysis, indicating that the dysfunction of intrinsic aorta components was also the key process of TAAD. VSMC was reported as the major source of ECM composition, and impairment of these cells resulted in intolerance of mechanical stress of high blood pressure in large vessels  loss  vessels . As for Our results emphasize the crucial position of circRNAs in TAAD, especially as a superior regulator of pathological molecules, and their potential as diagnostic biomarkers. In the current study, according to the bioinformatic analyses of RNA-seq data, four key DE circRNAs were selected, which were all significantly upregulated in the TAAD dataset and validated in clinical samples. Furthermore, ROC analysis suggested that all four key circRNAs could potentially serve as circulating diagnostic biomarkers of TAAD. Target miRNA prediction analysis demonstrated that these circRNAs contain numerous miRNA-binding sites that may be involved in inflammation, ECM degradation, cell adhesion, and junction. Studies have shown that the alteration of ECM and inflammation cascade were the risk factors of aortic dissection. Furthermore, cell composition analysis found that all four key circRNAs were pervasively correlated to immune cell infiltration and stromal loss. Collectively, these results demonstrated the vital role of the selected circRNAs in the pathogenesis of TAAD. However, the precise mechanism of these circRNAs including the exact ceRNA regulation network and the cell specificity in TAAD is still indistinct. It is necessary to integrate the functional and mechanistic roles of these circRNAs in subsequent studies.https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153434. The generated circRNA expression matrix and code are available by request to the corresponding authors.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School . The patients/participants provided their written informed consent to participate in this study.QL and QG designed the study and wrote the manuscript. QL ran the bioinformatics analyses. ZZ, QT, and YW performed the experiment. HL, AL, JX, YW, HM, LW, SS, and DW provided clinical specimens and data, technical support, and conceptual advice. All authors contributed to the article and approved the submitted version.


Despite their promise as prognostic factors in colorectal cancer, anthropometric data are frequently contradictory or difficult to interpret, with single body-composition parameters often investigated in isolation or heterogeneous clinical cohorts used in analyses. We sought to assess a spectrum of body-composition parameters in a highly selected cohort with locally advanced rectal cancer in a bid to determine those with strongest prognostic potential in this specific setting.Between 2014 and 2020, 78 individuals received neoadjuvant chemotherapy, or chemoradiotherapy, followed by radical surgery in the treatment of locally advanced rectal adenocarcinoma at Oxford University Hospitals Trust. Demographic, treatment-related, perioperative, and short-term outcomes data were assessed. Body-composition parameters included BMI, and those derived from pre-operative computed-tomography imaging: skeletal mass index (SMI), visceral fat area (VFA), subcutaneous fat area (SFA), perinephric fat area (PFA) visceral-to-subcutaneous fat ratio (V/S), sarcopenia, and sarcopenic obesity (SO).p = 0.002), V/S (p = 0.019), SO (p = 0.012), and PFA (p = 0.0016) all associated with an increased length of hospital stay. Univariate and multivariate analyses demonstrated V/S to be the sole independent body-composition risk factor to be associated with an increased risk of developing Clavien–Dindo complications ≥ 2 (p = 0.033) as well as an increased length of stay (p = 0.005).Pre-operative body-composition parameters exhibited particularly strong correlation with post-operative outcomes, with VFA (Among patients with locally advanced rectal cancer, high visceral-to-subcutaneous fat ratio is the body-composition parameter most strongly associated with poor early post-operative outcomes. This should be considered in patient selection and prehabilitation protocols.Our study demonstrates that among body composition parameters, high visceral-to-subcutaneous fat ratio is strongly associated with increased risk of post-operative complications and increased length of stay in patients undergoing surgery for advanced rectal cancer. Colorectal cancer (CRC) is the third most common neoplastic disease and accounts for 10.2% of all new cancer diagnoses. CRC is the second most common cause of death from cancer after lung neoplasms .Rectal cancer surgery is potentially morbid and is associated with prolonged hospital stay in 17.7% of cases and a readmission rate of 14.0% .Neoadjuvant treatment may have a deleterious impact on nutritional state and body composition and may therefore influence post-operative outcomes as well as disease-free survival. Abnormal body composition parameters may enable the detection of high-risk patients allowing them to be targeted for prehabilitation so that they can be optimized prior to surgery. Therefore, the time taken to complete neoadjuvant treatment could potentially be used to optimize a patient’s health prior to surgery.Body composition, defined as the proportions and distribution of adipose tissue and skeletal muscle, is increasingly recognized to impact significantly on disease prognosis and treatment planning . SeveralChanges in patients’ body composition  during oncological treatments have a significant impact on both morbidity and long-term survival of patients affected by hepato-pancreatico-biliary, oesophagogastric, and colorectal malignancies –13. Few Here we look at a highly selected group of patients with locally advanced rectal cancer who have undergone treatment followed by definitive surgery. We examine the following body composition parameters: body mass index (BMI), skeletal muscle index (SMI), visceral fat area (VFA), subcutaneous fat area (SFA), visceral fat area/subcutaneous fat area ratio (V/S ratio), and linear perinephric fat (PNF). In this study, we assess how these parameters are affected by neoadjuvant treatment, and assess their association with early surgical outcomes.In this specific cohort of patients, we demonstrate for the first time that visceral fat area is associated with increased length of hospital stay, and visceral/subcutaneous fat ratio (V/S) is associated with both an increased risk of major complications and increased length of hospital stay.Patients were identified and data were collected in a prospectively maintained database. All patients diagnosed with locally advanced rectal adenocarcinoma  who received neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCHT) combined with chemoradiotherapy (nCRT) followed by radical surgery over a period of six consecutive years (1st of January 2014–31st of January 2020) at Oxford University Hospital NHS Foundation Trust were included. Patients who received only neoadjuvant radiotherapy (nRT) or nCHT, patients who underwent lung or liver resections for metastatic disease before rectal surgery, and patients who had neoadjuvant treatment and had no surgery or had local excision only were excluded. All patients were discussed both at diagnosis and preoperatively at our local colorectal cancer Multidisciplinary Team meeting (MDT). Prospectively collected data included the following: age, gender, American Society of Anesthesiologists (ASA) score, smoking status, physical exercise, site of the malignancy, clinical stage American Joint Committee on Cancer (AJCC), TNM stage, neoadjuvant treatment regimens, surgical procedure, Clavien Dindo score (CD) complication, type of complication, length of stay, 30-day readmission, 30-day mortality, requirement of blood transfusions, haemoglobin (Hb), albumin, and C-reactive protein (CRP).Body mass index (BMI), skeletal muscle index (SMI), visceral fat area (VFA), subcutaneous fat area (SFA), visceral fat area/subcutaneous fat area ratio (V/S ratio), and linear perinephric fat (PNF) were determined for each patient using computed tomography images taken (i) at the time of diagnosis (pre-neoadjuvant therapy) and (ii) prior to their resection procedure (post-neoadjuvant therapy) as described in detail below. Institutional approval was granted and the study was entered into the local audit register (IRID-6388).2.5-mm slice CT scan images at the level of the third lumbar vertebra (L3) including both transverse processes were selected to calculate patients’ skeletal muscle area (SMA), visceral fat area (VFA), and subcutaneous fat area (SFA)11. L3 slices have been demonstrated to accurately estimate the whole-body composition in both healthy  and canc2/m2). The V/S ratio was calculated using the mean VFA and SFA measurements [2/m2 in women and < 52.4 cm2/m2 in men) [2). In addition, linear perinephric fat (PNF) was derived as the shortest distance (mm) between the kidney and the abdominal wall as measured at the level of the renal veins [A number of indices were then derived from the above parameters , 18. Skeurements . Visceraurements . Sarcope in men) –22. BMI al veins , 23.Short-term post-operative outcomes include complications stratified for severity according to the Clavien–Dindo Classification, type of complication, 30 days’ readmission, 30-day mortality, and need for perioperative blood transfusion.t-test for normally distributed data, and the nonparametric Kruskal–Wallis or Mann–Whitney U test for non-normally distributed variables. Bivariate correlation analyses were performed using Pearson’s test. For the test of potential risk factors associated with the outcomes, univariate analyses with clinically relevant parameters were performed. Variables with a value of P < 0.05 in the univariate analyses were included in the subsequent multivariate (logistic regression) analyses. All of the tests were two-sided and considered statistically significant when P values were less than 0.05. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) v26.0 , and GraphPad Prism v8.0.Data are presented as mean ± standard deviation (SD) or median ± interquartile range (IQR) as indicated. Groups were compared using the chi-square test or Fischer’s exact for categorical variables, the two-way analysis of variance (ANOVA) or n = 54), and females 30.8% (n = 24). Forty-four (56.4%) patients underwent abdominoperineal resection of the rectum (APER), 31 (39.7%) underwent low anterior resection, two (2.6%) underwent high anterior resection, and one (1.3%) underwent panproctocolectomy. All patients received neoadjuvant treatment. Fifty-six (71.8%) had chemoradiotherapy and 22 (28.2%) had chemotherapy, followed by chemoradiotherapy.A total of 78 patients were analysed in this study. Patient characteristics are shown in Table The body composition profiles calculated from CT analysis pre- and post-neoadjuvant therapy are shown in Table Body composition parameters pre- and post-neoadjuvant therapy and their relationships with short-term outcomes following rectal cancer surgery are shown in Table p = 0.002), V/S ratio (p = 0.019), sarcopenic obesity (p = 0.012), and perinephric obesity (p = 0.0016) were all associated with an increased length of hospital stay. Among parameters assessed post-neoadjuvant therapy, VFA (p = 0.004) and sarcopenic obesity (p = 0.05) were significantly associated with increased length of hospital stay. Overall, patients that exhibited high VFA pre-neoadjuvant treatment had a mean length of hospital stay of 11.65 days compared to 7.72 days for those patients that exhibited low VFA.For body composition parameters assessed pre-neoadjuvant therapy, VFA (p = 0.033). V/S ratio was also associated with an increased length of stay (p < 0.0001), as were VFA (p < 0.0001) and PNF (p = 0.05). Multivariate analysis incorporating these parameters demonstrated V/S alone to be an independent risk factor for increased length of stay (p = 0.005).To explore the relationship between body parameters pre-neoadjuvant therapy and outcomes, we performed univariate and multivariate regression analyses Table . We founU test and Kruskal–Wallis H test. Group comparisons involving dichotomous or categorical variables were performed using the chi-square test or Fisher’s exact test as appropriate.Analyses of short-term outcomes involving group comparisons of continuous non-parametric variables were performed by Mann–Whitney This study represents the largest single-centre analysis focusing specifically on a cohort of patients with locally advanced rectal cancer who have had neoadjuvant chemoradiotherapy prior to surgery, and which compares a breadth of body composition parameters on specific outcomes following surgery. We find that pre-neoadjuvant visceral-to-subcutaneous fat (V/S) ratio is strongly associated with increased risk of major complications and increased length of hospital stay. We also show that pre-neoadjuvant VFA is also strongly associated with increased length of stay. BMI was not associated with poorer outcomes in our cohort of patients. This is in keeping with other studies, where VFA and V/S ratio have been shown to be a better marker for metabolic X syndrome and poorer surgical outcomes, as opposed to BMI, which is a much cruder index of general adiposity and takes no account of fat distribution, nor ratio of fat to muscle mass.Visceral adiposity is known to be associated with chronic, low-grade inflammation, and a higher risk of cardiovascular outcomes , 25 AnimWe found that body composition parameters pre-neoadjuvant therapy were more strongly associated with increased length of hospital stay than the same body parameters measured post neoadjuvant treatment. At diagnosis, VFA, V/S ratio, sarcopenic obesity, and perinephric obesity were all associated with an increased length of hospital stay. After neoadjuvant treatment, only VFA was associated with increased length of stay. Patients undergoing neoadjuvant treatment are susceptible to body composition changes, as chemoradiotherapy can lead to nausea, loss of appetite, diarrhoea, and subsequent weight loss. We examined the change in body composition parameters between diagnosis and pre-operative state and found that these changes were not associated with increased length of stay or the development of major complications.Whilst other studies have demonstrated an association between sarcopenia and increased complication rates, we did not see this association in our patient population. This might be due to our study involving a highly selected group of patients who have undergone surgery for locally advanced rectal cancer following neoadjuvant chemoradiotherapy. One of the limitations of our study is that we examine short-term outcomes following surgery. Future studies are indicated to examine whether VFA and V/S ratios have a significant effect on long-term disease-free survival.Visceral/subcutaneous (V/S) fat ratio serves as the strongest independent risk factor among body composition parameters for increased length of hospital stay and post-operative complications in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.


Concrete constructions need widespread monitoring for the control of their state of integrity during their service life. In particular, after critical events such as earthquakes, this type of structure may experience the formation and development of cracks and damage. A quick and affordable assessment of structural behavior is indicated to identify conditions of danger for users and the incipient collapse of structural elements. This work presents investigations on multifunctional concretes with self-sensing capabilities to carry out static and dynamic monitoring. The materials were produced by the addition of conductive carbon microfibers to the concrete matrix. Electrical and sensing tests were carried out on samples with small-, medium-, and full-scale dimensions. The tests demonstrated the good electrical and electromechanical properties of the proposed smart concrete sensors, which appear promising for their use in civil elements or structures. In particular, tests on real-scale beams demonstrated the capability of the material to monitor the dynamic behavior of full-scale structural elements. Being a very old material, concrete has been the most used construction material in civil engineering for many years, and its composition is still evolving . It is aIn the last years, SHM has evolved and advanced rapidly . ImproveThis research is a multi-scale investigation of different types of samples made of smart concrete. The components, the electrical setup, and the test instrumentation have been tailored and optimized for the different applications.The sample base material was a concrete designed for a reference characteristic resistance of 30 MPa. The cement was Portland 42.5R; the fine and coarse aggregates were taken from a quarry. The mix design is reported in The aggregates adopted for the small- and real-scale samples possessed tailored characteristics due to the dimensions of the element. The fillers were added to the concrete and then mechanically dispersed in order to obtain a homogeneous material. The quality of the dispersion was examined through microscope investigations at different magnifications using an optical microscope and a scanning emission microscope.The small and medium samples were cured at laboratory conditions, while the full-scale beams were cured at external environmental conditions. The curing time was at least 28 days.The small cubes used for the investigation of the monitoring capabilities of the smart concrete at increasing doping levels had sides of 4 cm. The carbon fillers were added at the percentages of 0.01, 0.025, 0.05, 0.1, 0.25, 0.5, and 1% with respect to the weight of the cement. Before the solidification of the material, two copper wires with a diameter of 0.8 mm were embedded in the central part of each cube at a mutual distance of 2 cm as electrodes for the electrical measurements. A cube sample with sides of 5 cm was then prepared for in depth investigation of the sensing capabilities of the smart concrete. This sample was doped with 0.05% of CMF. For this type of sensor, stainless steel nets were adopted as embedded electrodes in order to evaluate the influence of the type and configuration of the conductive electrodes on the sensitivity of the material. Furthermore, small beams were prepared, with dimensions of 160 × 40 × 40 mmThe middle-scale plate was produced with concrete doped with 0.05% of CMFs a. Its baThe full-scale beam had a cross-section of 200 × 250 mmThe setups used in this study are illustrated in During the electromechanical tests, the sample resistances were calculated through the use of a shunt resistor of known value RThe loads FDuring the tests, the voltage input Ve is the distance between electrodes, and A is the cross-sectional area between the electrodes. Using the notation of e is the distance and The sensitivity of the smart concrete sensors investigated in this study depended on the piezoresistivity of the composite and its electrical setup, which produced electrical signals correlating with the varying strain-states of the sensor. The sensors were assumed to be rectangular solid elements; thus, the resistance of any segment between electrodes could be formulated as follows:R=ρreAwhAfter the substitution of the terms for the cube and small-sized beam sensor element, the following equation can be determined:Equations  and 7)  7) yieldIn the experimental tests, the dynamic characteristics of a real-scale beam equipped with embedded smart concrete cube sensors were evaluated. Analytical characterization of the beam for the dynamical properties was carried out to verify and compare the results attained through the smart sensors.The natural first mode vibration frequency of the beam was calculated by adopting the Euler–Bernoulli beam theory. The boundaries of the beam were assumed to be clamped due to the profile used for the supports of the beam. The exact solution for the first bending mode is shown in Equation .(10)2πfL is the span between supports, equal to 3 m, and I is the moment of inertia of the composite reinforced concrete section. Considering a cover thickness of 25 mm according to the design of the cross-section, the neutral axis occurred at a distance of 127 mm from the top surface. Based on the experimental setup, I was calculated as E, had a value of 22 GPa. With these given parameters, the natural frequency was found to be 88 Hz.Inside Equation , f1 is tThe results of electromechanical tests done on the small cube samples are summarized in The cube sensor with 5 cm sides and 0.05% CMF exhibited good strain sensing performance under cyclic load history. The variations in resistance and strain shown in The linear model of sensing for the beam element, shown in The plate sample was subjected to cyclic surface loads perpendicular to the electrode alignment. The variation in resistance and the strain time histories measured at the location of strain sensor according to the cyclic loading are plotted in The electrical response of the embedded cubes selected from the dynamic tests, and the related frequency analysis are shown in Accordingly, The second sensor appeared to be more sensitive, producing better results in the dynamic analysis of the full-scale beam. This might be related to the location of the second sensor further from the support than the first embedded sensor. Inspecting the resistance time history in Smart concrete, as a strain-sensing multifunctional structural material, shows promising capabilities in terms of widespread SHM of the civil structures. This study inspected the strain-sensing capabilities of CMF-doped concrete with different sensor geometries, doping level, and electrical setups. Small-, medium- and full-scale elements made of smart concrete were tested. The study investigated two types of monitoring, namely sensing at low-varying loads through cyclic loads, and dynamic sensing aimed at detecting the dynamic characteristics of a real-scale beam through embedded sensors placed inside the element excited by hammer hits.The study first investigated the strain sensing potential of smart concrete sensors with different geometries, including the sensing performance and the best amounts of conductive fillers to enhance the sensitivity of ordinary concrete. The results concerning strain-state sensing appeared quite promising; the linear models that correlated strain readings and electrical responses generated by the smart concrete sensors showed high reliability. Accordingly, the small cube and beam sensors appear useful to be employed as embedded strain sensors for SHM purposes, where such smart sensors can be placed on critical structural members to produce a long-lasting and feasible monitoring system.The plate sample of this study had larger dimensions and was loaded on the middle segment of its top surface in order to simulate a bending load for horizontal concrete elements with self-sensing material. The tests demonstrated that signals were highly correlated to the cyclic loads. The plate sample was instrumented by a traditional strain gauge, and the sensing results demonstrated that such a tailored design of electrodes and element characteristics has advantages over traditional strain gauges because the smart sensor used a larger volume for sensing and, as a result, was less affected by limiting factors, such as the placement of the loads on the sensor, local surface conditions, and the local placement of the strain-sensors. In general, the sensors’ responses were found to be scaled to the induced strain and the response time of the material was observed to be short. Moreover, the residual drifts due to material deformations were negligible.The dynamic monitoring tests with embedded concrete sensors generated significant results with important remarks to discuss. The study with full-scale elements demonstrated that dynamic analysis of the structural members and the detection of first modes is feasible with the use of smart multifunctional materials. However, further discussion is necessary to clarify design limits. Instrumentation noise with a constant frequency was present during the tests. Such noise was probably due to the current of the electrical system and the high impedance of the electrical sensing circuit, which affects the readings of the analog-to-digital converter of the data acquisition equipment. To address this issue, the electronic system design could be tailored to reduce the impedance of the sensing circuit, the hardware could be selected to be compatible to high impedance levels, and a post-processing filter could be developed accordingly. Moreover, such a limiting factor could be overcome enhancing the strain sensitivity of the smart material in order to generate signals with great amplitude that will not be affected by the noise. Therefore, the optimization of the multifunctional system design considering all the components is pivotal for the development of advanced applications in the field of engineering. Overall, the obtained results support the possibility of cost-efficient goal-oriented widespread structural health monitoring systems with smart concrete sensors suitable to be applied on structures and infrastructure. Possible applications could be continuous monitoring during the service life of constructions, or the quick assessment of the structural integrity and performance after critical events such as earthquakes.This paper presents the first results of sensing tests carried out on samples made of smart concrete. The monitoring capability was obtained through the addition of carbon microfibers in the construction material. Small-, medium- and full-scale samples with different characteristics and setups were tested by electrical and electromechanical experiments, with various types of applied loads. The aim of the research was to analyze the potential of such a smart concrete to be utilized in real-scale structures. As a matter of fact, the presence of coarse aggregates and the steel rebars in reinforced concrete elements could constitute an issue for the sensing performance of the smart sensors. To this end, the study presents experimental results on full-scale elements towards the use of embedded smart concrete sensors in real constructions, and discusses the strengths and the limitations of such monitoring systems. The electrical and electromechanical tests on small samples with increasing amounts of conductive piezoresistive fibers demonstrated variations in sensitivity and permitted the identification of the most promising filler percentage for monitoring applications. The sensing tests on small samples and on the plate demonstrated the effectiveness of different types of electrical setups and load applications. Finally, the dynamic characterization tests on a full-scale reinforced concrete beam instrumented with embedded smart concrete samples demonstrated the promising sensing capabilities of such novel self-sensing sensors for applications in real structures and infrastructure. Based on the good results obtained by this work, future experimental campaigns can be planned and carried out to examine the statistical dispersion of electromechanical properties over a large number of sensors and to evaluate the performance of full-scale structural elements produced entirely or partially with smart sensing concrete and tailored electrical setups.


In concrete production, the use of high-volume fly ash (FA) as the cement substitute became interesting to achieve more sustainable and eco-friendly construction materials. However, concrete produced using high volumes of FA as cement substitute suffers from various limitations such as low strength at early ages. Considering the engineering solutions and economy of FA-included concrete, it has become vital to address such issues. In this perception, some concrete mixes were designed using more abundant and low-cost local waste materials such as waste glass bottle nanopowders (WGBNPs) and effective microorganisms (EMs) to determine the feasibility of compensating for the strength loss at early ages due to FA inclusion. The proposed mixes contained 10% of EMs as water replacement, 50% of FA, and various percentages of WGBNPs as cement replacement. The effects of EMs and WGBNPs inclusion on the early strength and microstructure properties of the produced FA-based concrete mixes were determined. The results show that the strength indexes of the concrete at all test ages were improved due to WGBNP and EM incorporation. At almost all curing ages, the mechanical performance of the concrete made with 10% EMs and 4% WGBNPs was comparable to that of normal concrete (control mix), wherein the mix containing 6% WGBNPs outperformed the control mix. The microstructure analysis of the studied mixes revealed an increase in the hydration products, structural compactness, and homogeneity due to the synergy of WGBNPs and EMs, especially the specimen made using 10% EMs and 6% WGBNPs. It is established that the proper utilization of EMs and WGBNPs in FA-based concrete can be beneficial for waste recycling and landfill problems, thus lowering environment pollution. The adoption of various industrial by-products (as wastes) in the concrete industry seems to be environmentally and economically beneficial due to their abundance, low carbon footprint, and affordability. This is urgently needed because of the ever-growing environmental concern related to cement uses and various issues concerning landfills because of waste from different industries ,2. The e2) [2 to improve the early strength of high-volume FA-based concrete and, compared with that made without nano-SiO2, as early as after 3 days curing, improvements in the pore size distribution of the suggested concrete were observed. Shaikh and Supit [3) nanoparticles in high-volume FA concrete mixtures significantly improve both early age and later age compressive strength. However, most of the nanomaterials that have been introduced as effective solutions are either rare or too expensive to prepare [Numerous studies have addressed different solutions to surmount the decrease in the early ages strength properties of FA-based concretes, including an increase in the fineness of FA particles ,9,10, in2) ,12, use 2) , inclusi2) , and so 2)  used nannd Supit  reported prepare . Therefo prepare ,19.2 to form extra calcium silicate hydrate gels by avoiding alkali and silica reactions [According to ASTM C618-19 , the gla2 and participate in the production of C–S–H gels. However, all concrete specimens prepared with glass powder showed lower strength performance, where the lower rate in the strength ranged from 1.0–4.2% compared with the one prepared without glass powders [Many investigations ,31,32,33 powders .Clearly, most of the aforementioned previous research has focused on using glass powders as cement substitutes. However, the research related to the utilization of glass as nanomaterial additive to improve the early strength properties of high-volume FA-based concrete is not matured yet. Huseien et al.  demonstrLately, EMs have emerged as innovative bio-concrete components in the concrete industry ,41. TheyA recent study  aimed toIn this view, the present work aimed to make some sustainable concrete mixes for diverse applications for the construction purposes with reduced ecological issues such as carbon dioxide release, energy utilization, and landfill dumping through the replacement of OPC by high volumes of FA (50%) integrated with WGBNPs and EMs. The WGBNPs and EMs were utilized to resolve the problems related to early strength traits and improve the mechanical and microstructural characteristics at both early and late ages. Diverse tests such as CS, FS, TS, WA and X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and thermogravimetric analysis (TGA) were carried out to determine various properties of the proposed concrete mixes.The modified concrete was synthesized using OPC, FA, Ems, and WGBNPs . Herein,2O3, and SiO2 were 89.97% in OPC, 91.17% in FA, and 86.16% in WGBNPs. OPC enclosed a significant quantity of CaO (about 67.84%), while FA contained a relatively small amount (5.16%). The amount of K2O was below 1% in OPC, FA, and WGBNP. Meanwhile, the amount of Fe2O3 was almost the same as OPC (3.35%) and FA (3.67%). Generally, the XRF results indicate that OPC contained a high amount of Ca, and FA and WGBNP enclosed a high amount of aluminum and silicon, respectively. The physical properties of OPC, FA, and WGBNP, such as specific gravity, color, and mean size, are shown in X-ray fluorescence spectroscopy  was used to study the chemical compositions of OPC, FA, and NGBWP . The quaBacillus subtilis and lactic acid bacteria. Generally, these bacteria are considered harmless without any negative effect on humans or environments. In addition, EMs can improve the activity of EMs-AS. To activate these bacteria, a pH of less than 4 was achieved by fermenting them without oxygen supply for about 7 to 10 days. The bacteria were utilized without any protection. The physical characteristics and solubility of water, EMs-AS, and water with 10% EMs were observed to visualize the fresh and solid concrete colors. Consequently, EMs were initially dark brown in color, but the EM solution became dark yellowish after being substituted with 10% water (2)2) into ammonium ions (NH4+) and carbonate radicals (CO32−).The EMs were generated via the usual fermentation process, not genetically engineered or chemically metabolized. The EMs are a mixture made of various advantageous microorganisms that arise naturally or are enclosed in foods. These EMs are not genetically modified organisms. In addition, they are not pathogenic, harmful or chemically synthesized. When EMs are exposed to the natural atmosphere, the influences of individual microorganisms are very much evident. In this study, the EMs of type EMs-1, weighing 5 kg a, were o0% water b. Severa0% water  were perThe XRF study was performed to determine the elemental composition by the mass proportion of EMs. Mg (0.1140%), Al (0.0316%), Si (0.0546%), P (0.0233%), K (0.7670%), Ca (0.981%), Zr (0.0148%), Ru (0.214%), Rh (97.5%), and Pr (97.5%) were found to be the most abundant elements in the EMs (0.0125%). Rhodium had the highest percentage by mass in the EMs (97.5%), which is most commonly found in river sand or agricultural soil. In addition, the soil included various beneficial microorganisms, wherein Rhodium can also be used in the corrosion protection.3 and 2.70. The maximum size and fineness modulus of the fine aggregates were 4.75 mm and 2.3, respectively. The air-dried crushed granite with the highest size of 10 mm, and a specific gravity of 2.7 and 0.5% WA, was used as coarse aggregate in all prepared concrete mixes. Our systematic procedure ensured that the aggregates are devoid of organic matters such as dry muds, leaves, and other harmful components.In this experiment, natural siliceous river sand was used as fine aggregates. First, the collected sand was cleaned following the ASTM C117 to remove silts and impurities. Next, it was dried in an oven at 60 °C for 24 h to control the moisture. The physical characteristics of the fine and coarse aggregates  were recorded using the methods prescribed by ASTM C128. These parameters met all the requirements of normal mortar production, the maximum allowed limit needed by the ASTM C33 standard. The bulk density of the dried fine aggregates and specific gravity on the saturated surface dry (SSD) state were, correspondingly, 1730 kg/m3. Accordingly, the cement content was calculated to be 460 kg/m3. After that, based on the specific gravity of the used coarse aggregates (2.7), the percentage passing of the used fine aggregates on a sieve of 600 µm (40%), and water content of 230 kg/m3, both fine and coarse aggregates were determined to be 880 and 820 kg/m3, respectively. In the case of replacing cement with 50% FA, the DEO method suggested a reduction in the water content by 30 kg/m3. However, for the purpose of comparing the performance of the modified concrete with conventional concrete, the water amount was kept as it is. Then, FA was utilized to substitute 50% OPC by weight, keeping the same other mixing proportions as they are in the control mixture. Similarly, the amount of EMs was used to replace 10% of the mixing water. Then, various levels of WGBNPs  were added. The proportions of the mix were calculated using the Department of the Environment (DOE 1997) method of concrete design following BS 8500-1 and 2 (2002) to classify the class of exposure related to the application of concrete to obtain the mix proportions. In the first round, the water/binder ratio was determined to be 0.56 based on the target strength of 30 MPa at 28 days and crushed coarse aggregates with a maximum size of 10 mm. However, for checking the limitation of water-to-cement ratio (w/c) based on durability considerations for exposed concrete, the approach taken did not allow a w/c ratio of more than 0.50, so the water-to-binder ratio (w/b) was fixed at 0.5. In the second round, based on the desired slump value between (30–60 mm), and the crushed coarse aggregates used with a maximum size of 10 mm, the water content was determined to be 230 kg/mThe workability of the produced concrete mixes was measured by slump to assess an ease of usage of concrete in its fresh state as per ASTM C143  Figure . WithoutThe XRD, SEM, EDS, and TGA data were recorded to determine the microstructure properties of the proposed mixes. The XRD measurement and TGA/differential thermal analysis (DTA) were performed by taking a small part of the interior of the tested specimen. For the CS test, the specimen was ground to pass through a 125 nm sieve. The surface morphology of the mixes was examined by SEM. The specimens tested for strength at 7 and 28 days were taken to prepare the sample for SEM analysis, wherein it was spread onto two cellophane sheets followed by attachment onto a coin. For SEM analysis, each sample was placed in a sample holder (brass-stub-type) and dried for 5 min using ionizing radiation followed by coating with gold via a Blazers sputter coater. The SEM images were recorded at 120 kV with a magnification of 1000×. After choosing a moderately high image magnification, the morphology of the samples was recorded immediately.2 crystals.With regard to the mechanisms that underlay the EMs’ enhancement of concrete properties, previous studies claimed that the addition of EMs can reduce the surface tension of the mixed water, allowing it to create tinier holes when assed to concrete; this condition contributes to the increase in strength values ,70. The 2, generated by cement hydration, leads to the formation of a C-S-H gel, which is the major contributor to gaining strength. However, when the proportion of fly ash in concrete increases, the cement content becomes insufficient to bond the particle aggregates enough, and the calcium hydroxide produced by cement hydration becomes inadequate to activate a large portion of FA content for the pozzolanic reaction. This leaves considerable amount of FA content unreacted in the mix, which increases pore size and overall porosity of the matrix, resulting in a drop in FS. In the case of the EM specimens, the enhancement rate of flexural strength was 46.0, 41.0, and 23.4% at 3, 7, and 28 days, respectively, as compared with NCF. This result can be ascribed to the role of EMs in reducing the mixing water surface tension, enabling some water to escape into the connected pores and accelerate the hydration reaction.2 increases with a slight reduction in the pH value of the solution, which could have a positive effect on the cement hydration process [– contents and pH, thus leading to the formation of more gel products. However, this contrasts with the studies that confirm the Si and Al solubility increase with increased solution alkalinity. Therefore, it is difficult to confirm the effect of a slight decrease in the pH value on the strength indicators of high-volume FA-based concrete at early ages. In accordance with the findings of Rahman et al. [The observed slight reduction in pH could influence the kinetics of hydration in the early stages, where a study mentioned that the solubility of Ca(OH) process . Addition et al.  and Andrn et al. , the addIn the presence of WGBNPs, the findings revealed that the flexural strength of both specimens NS4 and NS6 exceeded that of NC. The FS of NS4 and NS6 were 2.38 and 2.46 MPa at 3 days, as well as 3.16 and 3.41 MPa at 7 days, respectively. Likewise, at 28 days, both samples of NS4 and NS6 achieved an FS of 4.89 and 4.96 MPa, respectively. The increased rates of FS of NS6 were 117.7, 111.8, and 36.6%, while the increment rates of the NS4 specimens were 110.6, 96.3, and 34.7% at 3, 7, and 28 days, respectively.2SiO4, which reacted with Ca2+, forming C-S-H gel [The increase in flexural strength at early ages can be mainly ascribed to the existence of fine WGBNPs particles that served as seeds, providing extra nucleation sites and expediting the hydration process in the mixes . Further-S-H gel . The for2S of cement continues to react, raising Ca(OH)2 concentration, forcing FA to dissolve and react to form further hydrates. The secondary hydration products can fill the pore voids, which are beneficial to the split strength of concrete and contribute to the densification of the transition zone at the interface between the aggregate and the paste, resulting in faster growth of strength at later ages. However, in the case of EM specimens, the enclosing of hydration products around unreacted FA particles at early ages and the increased compactness of samples could limit the ability of some amount of unreacted FA to react at later ages.In the presence of EMs, the tensile strength was significantly improved. The increment rates of EM compared with NCF were 17.0, 21.6, and 9.6% at 3, 7, and 28 days, respectively. This may be due to the role of EMs in lowering the surface tension of mixed water, allowing water to diffuse into the linked pores and speeding up the hydration process and thus allowing more packing, especially at early ages . With thSimilar to CS and FS, specimens containing 4 and 6% WGBNPs showed higher performance regarding split tensile strength. The NS6, which contains 50% FA as cement replacement and 10% EMs as mixing water replacement, recorded higher split strength than the control sample of normal concrete, where the increments were 94.3, 108.6, and 26.4% at 3, 7, and 28 days, respectively. Likewise, the enhancement rate in NS4 was also notable, where it was 67.0, 69.8, and 19.6% at 3, 7, and 28 days, respectively. The main reason for such strength development was the strong pozzolanic reaction of WGBNPs and the decrease in pore size distribution. Similar results show the role of fine glass powder in the development of strength indices to their strong pozzolanic traits and high surface-area-dependent reactivity ,76. Elaq2 crystal growth, thus reducing the possibility of the formation of weak areas within the matrix, improving the modulus of elasticity [asticity ,86.2 and CaCO3 gels’ formulation. With the increase in FA contents, more nonreacted silica was produced, as displayed by XRD peaks. The intense diffraction peaks at 20.1, 39.8, 50, and 60.4° corresponded to the existence of quartz (SiO2), portlandite (Ca(OH)2), calcite (CaCO3), ettringite (Ca6Al2(SO4)3(OH)12.26H2O), and gypsum (CaSiO4) phases originated from OPC and FA blending. The quartz peak intensity was enhanced slightly for the mix made with 50% of FA as OPC substitute due to the presence of more nonreactive quartz than NC, resulting in a decrease in CS from 36.16 to 24.02 MPa at 28 days. The strong reaction of amorphous SiO2 and Al2O3 in FA with highly crystalline C3S, C2S, and C3A in OPC was responsible for such products’ formation. Conversely, the NC specimen displayed portlandite and calcite peaks of about 18–65°. Nonetheless, by substituting OPC with 50% of FA, the portlandite peaks around 18–50° appear weaker, which illustrates the low strength of NCF compared with NC. Unlike with the inclusion of 10% EMs as mixing water replacement and 4 and 6% WGBNPs as nanoadditive, the intensity of the quartz peaks were lowered at the cost of the peak intensity of portlandite because more silica was dissolved, thus formulating the C–(A)–S–H gel via the hydration reaction. With the replacement of mixing water by EMs, a slight increase in the peaks of Ca(OH)2 was noted compared with those in the mixture with only 50% of FA. This indicted the hydration reaction relatively improved, raising compressive strength by 9.5% at 28 days, respectively. This result can be ascribed to the role of EMs in accelerating the hydration process. However, the peaks of Ca(OH)2 increase slightly when WGBNPs were added. This could be attributed to the behavior of WGBNPs as seeds, providing further nucleation sites to precipitate further hydration products. Likewise, an increase in the peak intensities of CaCO3 at 29.32° and 50.22° enhanced strength from 26.31 to 33.42 and 36.34 MPa.2) and C-S-H peaks, which may be ascribed to the deficiency of calcium contents in the proposed mixes, which justifies the reduction in strength in NCF concrete. A relative increase in Ca(OH2) peaks was also observed when mixing water was replaced with 10% EMs, and a similar increase was recorded in calcite intensity peaks in both NS4 and NS6 concrete, which illustrates the increase in strength parameters.The quartz peaks exhibited no uniform trend, and this finding may be related to the possibility of grinding aggregates and the difference in their percentage in the tested powder, leading to the disruption of the uniform trend of quartz peaks. Generally, the substitution of cement by FA produced a considerable decrease in the intensity of Ca(OH2 content due to the acceleration of the OPC reaction. The low percentage of Al content in the EM specimen compared with that in NCF can be attributed to Al being consumed in the formation of C–S–H and C–(A)–S–H chains. Furthermore, the silicon-to-aluminum ratio (Si/Al) was increased from 2.8 to 3.6 with the inclusion of EMs. The observed increase in compressive strength with an increase in Ca(OH2) led to the formation of more gels compared with that of the concrete prepared only with 50% OPC and 50% FA as cement replacement. With the inclusion of WGBNPs, the Si, Al, and sodium (Na) contents increased, whereas Ca percentage decreased. The Ca/Si and Ca/Al also decreased from 2.7 to 0.96 and 0.25 and from 8.1 to 2.73 and 0.89 with the addition of 4 and 6% of WGBNPs, respectively. The reduction in Ca/Si and Ca/Al was ascribed to consumption of Ca content in the formation of complicated chains of C–S–H and C–(A)–S–H gels. Conversely, the inclusion of 10% EMs and WGBNPs increased the Si/Al from 2.8 to 3.5, increasing the compressive strength from 24.02 to 36.34 MPa, respectively. The increase in compressive strength with an increase in Si/Al was ascribed to the consumption of Al in further C–(A)–S–H chains. In general, a decrease in Ca/Si and Ca/Al indicates a consumption of Ca(OH)2 in the pozzolanic reaction and formation of further hydration products, which is reflected in an increase in the strength of specimens with WGBNP. Low Si concentrations (low Si/Al) could be due to the formation of a poly structure, in which silicon is replaced by Al. The trend of compressive strength was observed to increase as the Si/Al ratio increased, while Ca/Si decreased. This finding is compatible with the findings of the researchers in [+4 in the formation of a Si–O–Si structure, which is one of most stable silicate chains.chers in ,91,92,932 and CSH was obtained using the corresponding Equations (1) and (2):2) is the weightloss ascribed to Ca(OH)2 dehydration, MW(Ca(OH)2) is the molecular weight of Ca(OH)2 (74 g.mol−1), and MW(H) is the molecular weight of water (18 g.mol−1).2 in the specimen made with 50% FA (4.81%) compared with the OPC specimen (8.21%). The lower stability of concrete made with 50% FA and the small quantity of C–S–H gel and Ca(OH)2 clearly indicated a negative effect of a low amount of Ca in FA in the formulation of dense gels, leading to the less dense microstructures of the NCF specimen. The low amount of hydration products caused a drop in CS from 36.16 MPa to 24.02 MPa at 28 days with the substitution of OPC by 50% FA. For specimens with EMs, replacing mixing water with 10% EMs led to an increase in C–S–H gel amount from 9.94 to 13.25%, enhancing compressive strength from 24.02 to 26.31 MPa at 28 days, respectively. Similarly, the hydration process was enhanced with the inclusion of WGBNPs, producing more dense gel. Essentially, the addition of 4 and 6% WGBNPs increased the C–S–H gels from 13.25 to 14.17 and 14.92%, increasing compressive strength from 26.31 to 33.42 and 36.34 MPa, respectively. In contrast, the inclusion of 4 and 6% of WGBNPs reduced the Ca(OH)2 from 4.93 to 4.52 and 3.69%, respectively, indicating the role of WGBNPs in the enhancement of the pozzolanic reaction. The better stability of the FA-based concrete with 4 and 6% WGBNPs can be attributed to the formation of the high amount of hydrate gels with a low quantity of Ca(OH)2 [The workability of prepared concrete is significantly influenced by FA, EM, and WGBNP content. The value of the slump was increased with the replacement of 50%OPC and inclusion of 10% EMs as mixing water replacement, while decreasing with the addition of WGBNPs.The strength values were enhanced due to the inclusion of 10% EMs as mixing water replacement and 4 and 6% WGBNPs at early ages.The replacement of 50% OPC with FA enhanced the WA value, while the inclusion of 10% EMs as mixing water replacement and 4 and 6% WGBNPs led to a significant decrease in WA (%).The incorporation of 10% EMs as mixing water replacement and 4 and 6% of WGBNPs boosted the pozzolanic reaction process, thus increasing the formation of hydrate gels and less unreacted cement/FA.The synergy of EMs and WGBNP was found to make the microstructures denser and more homogeneous than the binary mixtures prepared with OPC and FA only, which explained the reason for their higher mechanical performance at early ages.Microstructure results  show that the inclusion of EMs and WGBNPs in concrete increased the content of hydration products, leading to high stability and better mechanical performance.In short, high-volume FA-based concrete containing local waste materials (glass bottles and effective microorganisms) can be beneficial to achieve sustainable construction materials by reducing landfill problems, saving energy consumption, and lowering the demand for natural resources for concrete production, thus diminishing environmental pollution.Although the pH value of effective microorganism solution is lower, which is not a favorable condition for corrosion, effective microorganisms also contain 97.5% rhodium, which has good resistance of corrosion. So, concrete containing effective microorganism solution should be assessed by detailed corrosion investigation.Various contents of WGBNPs and EMs were integrated with a series of high-volume FA-based concretes to boost early strength properties. In these proposed mixes, OPC was replaced with 50% FA by weight of binder, and mixing water was replaced with 10% EMs by weight of water. Then, WGBNPs were added in the proportions of 2, 4, 6, 8, and 10% weight of the binder. The finding indicated a significant and positive effect of EM and WGBNP inclusion on the overall performance and strength properties of the proposed concrete mixes at all studied curing ages. The following conclusions can be drawn based on the main findings:


The use of macro polypropylene fibers increased the post-cracking behavior of concrete. In addition, based on the experimentally obtained results and available literature data, a multivariable equation was developed to predict the concrete toughness as a function of the volume, slenderness, and modulus of elasticity of the fibers. A Pearson’s correlation coefficient, r of 0.90, showed a strong correlation between the developed equation and the experimental data. From this equation, it was possible to determine the participation of the following parameters in calculating toughness. The participation or weight of the fiber’s modulus of elasticity on the concrete’s tenacity is 26%, the volume of the fiber is 39%, the slenderness is 19%, and the reinforcement index is 16%. The construction industry requires concrete with adequate post-cracking behavior for applications such as tunnels, bridges, and pavements. For this reason, polypropylene macrofibers are used, which are synthetic fibers that fulfill the function of providing residual strength to concrete. In this study, an experimental plan is carried out to evaluate the bending behavior of concrete reinforced with polypropylene fibers using the four-point bending test according to ASTM C1609. Three fiber dosages (3.6, 7.2 and 10.8 kg/m Concrete is the most used construction material in the world . NowadaySynthetic fibers are artificial fibers that have resulted from research and development in the petrochemical and textile industries . Carbon PP macrofibers have a low modulus of elasticity, 3–10 GPa, compared to steel, whose modulus of elasticity is between 190–200 Gpa. Bermudez et al.  studied Del Savio et al.  studied Karihaloo and Nallathambi developed an analytical model to determine the toughness of concrete without fibers based on the effective crack model ,30. Yap 3 and three measurements of fiber slenderness . To have a solid statistical study, 8 beams per dosage were tested. The test performed was the 4-point bending test according to ASTM 1609 standard [Although several studies have tested synthetic fibers and their different properties that contribute to concrete, no strong arguments supported by statistical evidence were found about the influence of fibers on the elastic and post-cracking properties of concrete subjected to flexural loads. Mainly because there are more studies about post-cracking properties than the influence of fibers on elastic properties. In addition, it was found that the research that studies post-cracking properties does not develop predictive equations of toughness as a function of the addition of fibers. For this reason, the main contributions of this study are the following: (1) first, a detailed study of the influence of volume and slenderness of PP fibers on the elastic and inelastic properties; and (2) second, a predictive equation of toughness as a function of volume, slenderness, and modulus of elasticity of the fibers is developed, comparing the results of this research with the results of other researchers using synthetic fibers with a different modulus of elasticity and comparing the predictive models using statistical tools. The experimental plan was developed using three fiber dosages . The description of the materials, mix design, specimens, casting process, tests, and hypothesis tests on the results are presented below.3 and a specific area of 336 m2/kg. The amounts of the chemical components are as follows: tricalcium silicate (C3S) at 54.2%, dicalcium silicate (C2S) at 11.9%, tricalcium aluminate (C3A) at 10.1%, and tetracalcium ferroaluminate (C4AF) at 9.7%. The materials used to manufacture the fiber-reinforced concrete were cement, water, coarse aggregate, fine aggregate, superplasticizer, and polypropylene fibers. The cement used was type I Portland cement manufactured according to ASTM C150 . In addiCoarse crushed aggregate classified in HUSO N°56 according to ASTM C33 standard was used . This gr3. They had a straight shape and a knurled texture. Three types of fibers were used  with a common diameter of 0.86 mm. The resulting slenderness (aspect ratios) were 46, 58, and 70, respectively. The fibers used can be seen in The fibers used were PP  with a tensile strength of 540 MPa and a modulus of elasticity of 4.70 GPa. Fiber density was 920 kg/m3, according to the manufacturer’s data. The admixture  used was a high-range water reducer and retarder type G, according to ASTM C494 . The addThe concrete was designed to achieve a compressive strength of 40 MPa at 28 days and a slump of 100 mm. The design method used was the ACI method . The watThe specimens were prepared for the standard test method for the flexural performance of fiber-reinforced concrete (using a beam with four-point loading) according to ASTM C1609 [The freshly mixed concrete was placed in metal molds. The mixture was placed in two layers filling the mold from one direction to the other, T) is calculated as the area under the curve with a deflection up to L/150, which corresponds to 3 mm, see L/150 (resf), calculated through Equation (2). In this study, the residual strength is determined using the second method. In addition to the flexural tests on concrete, the slump test, according to ASM C143 [The test was performed following the ASTM 1609 standard, four-point bending test. This test consisted of supporting a beam at the ends, with a distance between supports of 450 mm, and applying loads with two rollers in the central thirds. The spacing between the rollers applying the load was 150 mm. The load application speed was 0.05 mm/min, controlling the deflection of the beam. A 350 kN capacity compression frame with displacement control was used for the test. The test setup is shown in ASM C143 ; the comASM C143 ; and theASM C143 , were pep-value, significance level, and the r-value, correlation coefficient, are the results of Pearson’s test. The significance level indicates the probability of being wrong. For concrete material with a high coefficient of variation, it is convenient to set this value as 0.100, as performed in previous studies [Pearson’s hypothesis test was performed to verify the statistical validity of the correlations between variables. The  studies ,43.3, the average compressive strength is 41.66 MPa, and the average modulus of elasticity is 30.22 GPa.On the other hand,  shows thTwo failure modes occurred: ductile failures and brittle failures, as shown in p-value) in most cases are greater than 0.100. Therefore, the null hypothesis that establishes no correlation between the variables cannot be discarded. Generally, it is observed that the greater the volume of fibers, the lower the significance level; that is, the lower the probability of error. This behavior is consistent with the research by Del Savio et al. [p value tends to decrease. Although Del Savio et al. concluded that there was an increase of 0.30 MPa for every 0.40% increase in fibers, this increase was residual and less than 20%. Yin et al. [o et al.  since itn et al.  reportedn et al. ,19,54,55n et al.  reportedn et al. . The defn et al.  show as p-value) less than 0.050 in most cases and less than 0.100 for all cases. The correlation coefficients (r) also show very high values. It can be deduced that there is a correlation between fiber volume, toughness, and residual strength. Similarly, there is a correlation between fiber slenderness, toughness, and residual strength. Therefore, there is a correlation between the reinforcement index and both post-cracking properties. These results are evidenced when the concrete reinforced with polypropylene fibers (CRFPP) reaches the maximum cracking load of the specimen, and the material develops a residual strength associated with the ductile behavior of the fibers in the concrete matrix. This is because they begin to resist the tensile forces generated and amplified by the crack opening [ opening ,58. This opening ,60.T), obtained from a linear regression for measurements of fiber slenderness of 47, 58, and 70. The correlation coefficients (r) are 0.99, 0.98, and 1.00, respectively. The three trend lines show higher toughness or energy absorption capacity with increasing fiber dosage. T), which was obtained from a linear regression for fiber volume of 0.4, 0.8, and 1.2%. In addition, the correlation coefficients (r) are 0.99, 0.48, and 0.28, respectively, when the standard concrete is not considered. These same coefficients are 0.98, 0.96, and 0.95 when the standard concrete is considered in the correlation. This means that there is a marked difference between the toughness of the standard concrete and the concrete with fibers. As the fiber slenderness increases, all three trend lines show higher toughness or energy absorption capacity. Also, when the fiber volume is 1.2%, there is no marked difference whether the fibers are 40, 50, or 60 mm long since the toughness is similar. This can be seen in RI), which represents the product of both variables. T). The p-value of this correlation is very close to zero (0.000), so the probability of error is zero. The correlation coefficient (R) was 0.95, classified as strong. The trend line shows that the higher the rate of PP fiber reinforcement, the higher the toughness of the concrete. These results are in accordance with previous research [RI units will produce an increase of 9.2 J in toughness.An important parameter that includes slenderness and fiber volume is the reinforcing index , which was obtained from a linear regression for measurements of fiber slenderness of 47, 58, and 70. These correlations are statistically significant as their p-values are 0.008, 0.009, and 0.024, respectively, all values being less than 0.010. Therefore, the null hypothesis is rejected, and the hypothesis where there is a correlation between the variables is accepted. The correlation coefficient R is 0.99 for all cases. The trend lines show an increase in residual strength. This resistance increases when the volume of the fibers also increases. As with toughness, the increase in residual strength per volume fraction is similar regardless of the fibers’ slenderness. This can be seen in p-value is 0.043, 0.060, and 0.027, respectively, considering the standard mixture. The coefficients of determination (R) are 0.99, 0.34, and 0.93, respectively. The trend line with the greatest slope is presented when a fiber volume dosage of 0.4% decreases as the fiber volume increases. This means that the influence of increasing the slenderness of the fibers is greater when the fiber volume is lower, as shown in p-value of 0.000, less than 0.100. The correlation coefficient (r) was 0.95. The trend line shows that the higher the reinforcement index of the PP fibers, the higher the residual strength of the concrete. The highest experimental residual strength obtained is 2.99 MPa when a reinforcement index of 83.7 is used, and the lowest residual strength obtained is 0.65 MPa for a reinforcement index of 18.6. As a reference, Dopko [RI units will increase 0.4 J in toughness.e, Dopko  presentse, Dopko  presentsRI on the toughness of concrete with synthetic fibers and to compare with the results of the present investigation, (2) to evaluate the influence of fiber stiffness on concrete toughness, and (3) to evaluate the coefficient of variation of toughness tests of other authors.Information on toughness results with synthetic fibers was collected from other authors. This information is shown in RI curve’s slope and the fibers’ modulus of elasticity. The result shows that there is a correlation. In other words, the higher the modulus of elasticity, the higher the increase in toughness per unit RI. Equation (3) shows the result of the linear regression between these variables.Concerning the coefficient of variation, CV, not many authors present this parameter. From the review made, it was found that all the concretes used were made in the laboratory. The coefficient of variation of this study is 21%. For reference, the coefficient of variation published by Conforti et al.  and ManfVf and L/d;) and mechanical strengths . Equations (4) and (5) show the calculation results of (1) toughness as a function of fiber volume and slenderness and (2) residual strength as a function of fiber volume and slenderness. To process the data from this investigation, multiple nonlinear regression was used to obtain relationships between fiber-related variables  is the one with the lowest RMSE. Therefore, it has the best fit. However, the equation that also presents a low RMSE value is Equation (12). The authors believe that this equation is the most convenient because it shows the contribution of each variable separately so that the total result is the sum of all the monomials. The equation has no negative monomials, unlike Equations (7), (8) and (11). In addition, the correlation coefficient of Equation (11) is greater than that of 12. The values are very close, 0.90 for Equation (11) and 0.89 for Equation (12). An experimental plan was executed to investigate the influence of volume and slenderness of PP fibers on the elastic and inelastic properties of fiber-reinforced concrete and to predict the value of toughness as a function of volume, slenderness and modulus of elasticity of synthetic fibers. The experimental plan was developed using three fiber dosages  and three measurements of fiber slenderness .p-values in all correlations between fiber parameters and elastic properties were less than the established significance level of 10%, rejecting the null hypothesis.The results showed a strong correlation between fiber parameters and post-cracking properties. The higher the volume, slenderness, and reinforcement index of PP fibers, the higher the toughness and residual strength of the concrete. Pearson’s hypothesis supports this since the RI is 0.263 units per 10 GPa increase in fiber modulus of elasticity.The modulus of elasticity of the fibers conditions the toughness increase due to the reinforcement index. Investigations using fibers with high values of fiber modulus of elasticity reported greater increases in toughness concerning fibers with low values of modulus of elasticity. The rate of increase in toughness concerning From the data of the present investigation and other investigations, a multivariable nonlinear equation (Equation (12)) has been developed to determine the toughness of concrete according to volume, slenderness, and fiber modulus of elasticity. This equation presents a correlation coefficient of 0.89, which is considered strong. From this equation, it was possible to determine that the participation of the modulus of elasticity on the toughness is 26%, on the fiber volume squared is 39%, on the slenderness is 19% and on the reinforcement index is 16%.