One of the reasons is the wide range of densities and properties of lightweight aggregates available on the market. As a part of the research, properties of concrete based on sintered fly ash were determined. The ash, due to its relatively high density is suitable to be used as a filler for structural concretes. Concrete was based on a mixture of sintered fly ash and exfoliated vermiculite aggregate also tested. The purpose of the research was to determine the possibility of using sintered fly ash as alternative aggregate in structural concrete and the impact of sintered fly ash lightweight aggregate on its physical, mechanical and durability properties. Conducted tests were executed according to European and Polish standards. Created concretes were characterized by compressive strength and tensile strength ranging from 20.3 MPa to 54.2 MPa and from 2.4 MPa to 3.8 MPa, respectively. The lightest of created concretes reached the apparent density of 1378 kg/m Concrete structures are ubiquitous in today’s world. At the moment, concrete, as the structural material, does not have a worthy replacement. Due to large-scale production of concrete, the construction industry significantly impoverishes the deposits of natural raw materials, including aggregates which constitute majority of concrete volume. Moreover, in an increasingly environmentally conscious world, concrete production is blamed for a negative impact on the environment and subsequently climate change ,2. The 2There are many reasons to increase the amount of Coal Combustion Products development. Firstly, the landfill area can be used differently. Secondly, selling the by-products as raw material can generate financial gains, or at least offset processing and storage costs. Thirdly, it should be remembered that ash is a waste and if not properly disposed it may pose a threat in the form of possible contamination of soil, air and water. It also carries significant risk of spontaneous combustion . The proSFA is classified as lightweight aggregate. Concrete based on SFA, in addition to being a pro-ecological material, is characterized by reduced weight and higher thermal, acoustic and fire resistance in comparison to ordinary concrete. The specific properties of lightweight concretes are utilized in the construction of tall buildings, long span bridges, buildings erected in seismic zones  and in a3) and strength [3 [3) is vermiculite. This is also the aggregate which can be used only for production of insulation concrete [While the use of lightweight concrete is constantly increasing due to its practical, economic and environmental advantages, it is still a contentious technological and designing challenge for many engineers, architects and contractors. The majority of this “reserved” attitude is caused by bad experiences with low-quality lightweight aggregates for less demanding applications  in the past decades. Light aggregates, unlike natural aggregates, have a very wide range of density  sintering in the rotary kiln. Fly ash does not swell during sintering. The result of this process is a coating that is much less porous than the internal structure of the aggregate. The achieved material is less absorbent, has higher mechanical strength but is much heavier than other light aggregates, such as pumice or vermiculite ,12.00 °C sinIn experimental studies, three fractions of aggregates 0/2 mm; 1/4 mm (achieved by crushing larger particles) and 4/8 mm (as crushed aggregate in about 90% ), were uExfoliated vermiculite (EV) was used as the second light aggregate. Vermiculite is a naturally occurring mineral from the group of hydrous layer aluminosilicates. It is widespread around the world together with other clay minerals. Significant deposits of raw vermiculite are located in Australia, China, the USA and South Africa ,20,21. TParticle size analysis of EV  indicate3). This phenomenon is caused by significant porosity of particles (from 40% to 80%). The porosity of lightweight aggregates usually increases with the size of the aggregate; therefore, coarse fractions are characterized by lower apparent density than fine fractions. SFA is characterized by high density as for light aggregate. However, its density is still within the limits of lightweight aggregate characteristics. It constitutes around 65% of the density of ordinary aggregates (2400–2600 kg/m3). In case of EV the apparent density was not determined. The bulk density of EV was more than five times lower than bulk density of SFA of similar diameter (1/4 mm).The apparent density of lightweight aggregates varies greatly  particles. Water absorption of crushed and non-crushed particles of the same light aggregate was determined by Zhang and Gjørv . Their sA mix of Portland cement 42.5 R  and an active additive of type II zeolite  was used as a binder ,26. ZeolFirstly, the good aggregate grading  was achieved using three fractions of SFA. The process is based on mixing different aggregate fractions until the maximum compacted bulk density is achieved. The tests showed that the proportions (by volume) for the optimal grading are as follows: SFA 0/2 mm—20.51%; SFA 1/4 mm—26.23%; SFA 4/8 mm—53.25%. This was the first aggregate mix used in the research program. In the second aggregate mix, the SFA 1/4 mm was replaced by EV 2/4 mm. The changes were made by volume. The apparent density of EV is unknown. Therefore, the mass demand for new aggregate was estimated on the basis of the results of the research on the bulk density and the percentage content of the SFA 1/4 mm fraction of SFA in the first aggregate mix. For both SFA and SFA + EV aggregate mixes, sieve analysis was conducted. Grading curves are shown in The concrete mix was designed using the iteration method. The desired consistency of the fresh mix was S2 . Porous The mix of cement and zeolite (in proportion 85% and 15%) was used as a binder. A pan type concrete mixer was utilized for the creation of the concrete mixes. The procedure of concrete mix preparation was as follows. Firstly, aggregate and water for aggregate were placed in the mixer. Secondly, the water and aggregate were pre-mixed and left for 15 min. Thirdly, cement, zeolite and 2/3 of mixing water were added to the mixer. During mixing the superplasticizer with the last part of mixing water was slowly added to the mixer. The recipes of both SFA and SFA + EV are given in 3 and 1738 kg/m3, respectively. It can be observed that density decreased by about 50 kg/m3 due to the use of vermiculite. The volume of the components in their initial state (before combining) was the same. During mixing, the brittle grains of vermiculite crumbled, resulting in the reduction of the volume of the created fresh SFA + EV concrete mix (by about 7% in comparison to SFA fresh concrete mix).The density of fresh SFA and SFA + EV fresh concrete mixes was equal to 1790 kg/mThe 100 mm cube specimens were prepared for water absorption, freeze-thaw resistance , compressive  and tensile strength tests . The 150 mm cube specimens were used to determine water permeability . Both types of cubes were utilized to establish density of hardened concrete at various levels of water absorption. The specimens were cast in three layers in plastic molds and compacted on a vibration table. After casting and vibrating the molds were cover with plastic foil to prevent water evaporation. Specimens were demolded after 48 h of curing. Earlier demolding causes defects, cracks and other damages to the concretes in question. Specimens were kept in a curing tank with a relative humidity of 95% until the specified age of testing. All tests were conducted using minimum three specimens.Density of SFA and SFA + EV concretes was determined in different saturation states. The following saturation states were considered: wet, moist (relative humidity ±95%) and after 3, 6, 9 and 12 days of drying at 105 °C. Density in the different saturation states is presented in 3 [The density of lightweight concrete is its key property in combination with the strength class. It is thanks to the reduced density that the weight of a structure with the same load-bearing capacity can be reduced by 20 or even 40%. The density of the concrete mix depends on the density and proportion of its components, the air content and (in the case of lightweight concrete), on the initial moisture level of porous aggregates. The change in the density of the built-in concrete is caused by a change in the internal saturation, which results from the prevailing climatic conditions and the internal structure. This means that the concrete in the structure is not dry, but is in equilibrium with the relative humidity of the environment, which will vary depending on the exposure, geographic location and season of the year. Therefore, the properties of concrete should be related to the actual state, taking into account the influence of humidity, which, as a rule, can increase the density of concrete by 50–200 kg/m3 .3. The vermiculite aggregate absorbs and stores more water than SFA. The difference in density between SFA and SFA + EV concretes in the wet state is around 40 kg/m3 and in the dry state it is around 80 kg/m3.In the case of lightweight concrete, the loss of moisture through drying is a longer process in comparison to an ordinary concrete. It is related to the water in the aggregate pores. The oven-dry state of the specimens (drying to a constant mass) was achieved after 12 days of keeping specimens in the temperature of ±105 °C. The greatest dynamics of weight loss occurs during the first three days of drying and then the process slows down significantly. The study showed that even concretes saturated with water can be classified as lightweight concretes with density below 2000 kg/mSuch properties of concrete as water absorption and watertightness largely depend on the humidity of the specimens ,36. TherDynamic increase in water absorption of the specimens was observed during the first 24 h. The next days are a period of stabilization, during which the increase of water absorption is within the limits of less from 0.01% to 0.39% per day. The 24 h water absorption constitutes 91% and 87% of full water absorption of SFA and SFA + EV concretes respectively.Lightweight structural concrete is characterized by water absorption from 5 to 25%. This considerable variation is caused by properties of used lightweight aggregates. Domagała  demonstrSFA + EV concrete achieved slightly higher (by 0.74%) final water absorption than SFA concrete. SFA + EV concrete absorbed more water than SFA concrete in the first hour of the test. This phenomenon is caused by the presence of the vermiculite material in the cement matrix which is characterized by high sorptivity. The porosity of the cement matrix and pores between the layers of vermiculite were confirmed by numerous researchers to influence the water absorption ,23,38. FThe test method and the water absorption limits are not specified in the concrete standard EN 206 . TherefoThat is a satisfying result which was obtained thanks to complete initial saturation of the aggregate. As a consequence of water absorption by the aggregate during curing, the w/c ratio decreased and the aggregate particle structure was sealed with cement paste.As proved by many researchers ,37,41, tIn previous tests conducted by other research teams ,37 attenDuring the current research program concrete was made using aggregate in a pre-wetted state. The depth of penetration of water under pressure was determined with apparatus generating water pressure from the bottom of specimens. The testing procedure consisted of water pressure from 0.4 to 0.8 MPa which was kept for 100 h. Cement paste was removed (by grinding) from the surface of a specimen which was going to be exposed to water pressure (a circular area with the diameter of 10 cm). After the test, specimens were split and the cross-section was examined and the penetration range was measured . The ave−Depth ≤50 mm—high resistance against weak chemical substances.−Depth ≤30 mm—high resistance against strong chemical substances.The current European standard  does notBased on the above conditions, the SFA concrete showed adequate resistance to exposure to weak chemicals substances. Concrete SFA + EV did not meet any of the requirements. The research did not confirm the effect of vermiculite presented by Azad et al. . VermicuCompressive strength of hardened concrete specimens was determined by the destructive method in accordance with EN 12390-3 . The speEV as a partial replacement for aggregate caused a reduction in compressive strength in comparison to SFA. This phenomenon is caused by the properties of the vermiculite itself which in turn results in decrease in concrete density and an increase in porosity ,46. CompThe concretes showed high early strength. The 2-day compressive strength, which was determined on the day of demolding of the specimens, constituted around 59 and 48% of the maximum strength achieved by SFA and SFA + EV concretes respectively. In both cases, after 28 days of curing the dynamic development of endurance ends. However, in the case of SFA + EV, the increase in the following days is much lower but is still gradually progressing. SFA strength results after 56 and 91 days of curing are inconclusive. The decrease of average strength of SFA concrete after 56 days is caused by significant dispersion of single results.The tensile strength was tested with the help of the splitting method according to EN 12390-6 . ConstanSFA concrete test results until the 28th day of curing increase. The 2-day strength reached 87% of the 28-day strength. After 28 days of curing, results start to be scattered; thus, the average value decreases. The 91-day strength is almost equal to 2-day strength.The strength of SFA + EV concrete increased less dynamically than SFA concrete during early days of curing. Despite lower early strength (after 2 and 7 days) and lower strength after 28 days of curing, the strength in late age was higher than that of SFA concrete. The results of SFA + EV concrete show a continuous increase in strength over time. SFA + EV concrete demonstrates an increase in late strength in comparison to SFA concrete.The freeze/thaw resistance of lightweight concrete is a very complicated and multifaceted issue. It depends largely on material factors, but in structural lightweight concrete even more on technological factors. The most important of them is process of pre-wetting of aggregates. The influence of each degree of saturation  was tested by other researchers ,48. The During the current research program the used aggregate was pre-wetted at the level of 13% and 16% for fine and coarse aggregate, respectively. The freezing/thawing cycles test was performed in a climatic chamber. 150 freezing/thawing cycles were executed. One cycle consisted of 4 h of freezing in the air at −15 °C and 4 h of thawing in water at +15 °C. Four specimens were used for each test. As control specimens, 3 cubes kept in water and 3 cubes kept in relative humidity of ±95% were prepared. The strength of specimens after freeze/thaw cycles and strength of control specimens are shown in The European standard EN 206  does notThe recorded weight losses for single specimens were very diversified. In this case, the SFA + EV concrete showed a significant dispersion of the results. The average level of mass loss was 0.24 and 0.89% for SFA concrete and SFA + EV concrete, respectively. Freezing/thawing cycles influenced the loss of strength to a greater extent than the loss of mass. Surface flaking of specimens was also observed as shown in the The microstructural characteristics of concretes in question were analysed using a Nikon SMZ 1500 stereoscopic microscope. No segregation of the components was observed. Despite the large differences in density between the materials used, they were homogenously distributed in the concrete volume. The microscopic photos  also conThe analysis of the photos taken showed that:A clear sinter line is visible in the aggregates of the largest fraction. The microstructure of the interior is full of pores of various sizes and shapes. The coating produced by sintering is an element of very different thickness and due to the fact that it is less porous; it can limit the penetration of water into the aggregates, if the aggregate particles are intact.The surface of the lightweight aggregate is rough, which increases the aggregate/ slurry interface. The interfacial contact zone shows no delamination or damage, it is continuous, tight and without large pores. It indicates a strong bond between the matrix and the aggregate.Cement hydration products penetrate the structure of the open porosity of the aggregate particles. Closed pores remain without hydration products.The conducted research program is limited by the types of tested mixes and utilized technological approaches. The research should be continued taking into account the significant material and technological influence on the properties of lightweight concretes in question. Special interest should be focused on variability of the results which was noticed during current research program. Very large population of specimens would be desired enabling full statistical analysis. Both used lightweight aggregates were sourced from one region. The same tests should be repeated using SFA and EV aggregates provided by other producers from other geographic regions. Possible further research programs should include tests of thermal, fire-retardant and acoustic properties of the concretes in question. Concrete mixes with different volumes of SFA and EV aggregates should be also tested.SFA aggregate is a good alternative to ordinary aggregates. Concrete based on SFA can be successfully used in elements with load-bearing functions. It is a pro-ecological product that perfectly fits the idea of sustainable development. After the aggregate with insulating properties is incorporated into the crumb pile, the concrete can still perform the load-bearing functions. After the tests of both types of concrete, the following conclusions can be drawn:The term "fraction" in reference to vermiculite aggregate is unreliable. Fine grains of vermiculite disintegrate  during sieve analysis, mixing, etc., which is a problem when trying to determine the grain size and select a tight aggregate composition.Despite significant differences in the density of components in the concrete based SFA + EV aggregate, no segregation was observed. The fresh mix showed adequate homogeneity and viscosity.3.Partial replacement of the SFA aggregate by much lighter EV aggregate reduced the density of the mixture by about 50 kg/mAdding vermiculite aggregate to the concrete mix resulted in obtaining a greater water demand. Consequently, with the same amount of water, a lower consistency class of the concrete mix was obtained.3 of concrete is higher.After combining the components of the mixture, the vermiculite is crushed and partially compressed, so despite the use of the same volume of individual components, the volume of the finished mixture is reduced by about 7% compared to the mixture based on SFA aggregate only. As a result, the consumption of other ingredients per 1 mThe curing conditions of lightweight concretes have a huge impact on their mechanical and durability properties. Keeping the specimens in 95% relative humidity is preferable.The maximum water absorption of the specimens was 15%.With SFA aggregates, without any special technological measures, it is possible to achieve concrete of the LC 40/44 class and higher from mixed aggregates SFA + EV concrete of the LC 30/33 class and higher.The addition of vermiculite may increase the tensile strength in later maturation periods (>28 days). It affects the plastic behaviour of concrete. This should be confirmed in further studies.The most important disadvantage of using vermiculite is the reduction of compressive strength.The presence of vermiculite makes the concrete more homogeneous in most cases.Taking into account the large material and technological influence on the properties of lightweight concretes, a significant variability of the results was observed in the tests, even in a batch of samples made of the same mix. Therefore, the tests should be carried out on a larger population of samples , trying to make the technological process of making subsequent samples as regular as possible.The further part of the research should include thermal, fire-retardant and acoustic properties, as well as the next higher and lower volume of vermiculite content. One should also focus on the influence of technological conditions of execution and preparation.The future application of the concretes in question covers a wide range of construction industry areas from thermal insulating panels, light secondary structural elements and acoustic insulation elements. Elements resistant to vibrations and absorbing energy of impacts are also possible to achieve after additional research.


Concrete and cement-based materials inherently possess an autogenous self-healing capacity. Despite the huge amount of literature on the topic, self-healing concepts still fail to consistently enter design strategies able to effectively quantify their benefits on structural performance. This study aims to develop quantitative relationships through statistical models and artificial neural network (ANN) by establishing a correlation between the mix proportions, exposure type and time, and width of the initial crack against suitably defined self-healing indices (SHI), quantifying the recovery of material performance. Furthermore, it is intended to pave the way towards consistent incorporation of self-healing concepts into durability-based design approaches for reinforced concrete structures, aimed at quantifying, with reliable confidence, the benefits in terms of slower degradation of the structural performance and extension of the service lifespan. It has been observed that the exposure type, crack width and presence of healing stimulators such as crystalline admixtures has the most significant effect on enhancing SHI and hence self-healing efficiency. However, other parameters, such as the amount of fibers and Supplementary Cementitious Materials have less impact on the autogenous self-healing. The study proposes, through suitably built design charts and ANN analysis, a straightforward input–output model to quickly predict and evaluate, and hence “design”, the self-healing efficiency of cement-based materials. Cementitious materials undergo the natural process of autogenous healing that is total or partial self-closure of cracks. The closure of these cracks subsequently results in partial regaining of concrete initial strength as well as improving the durability performance. In 1973, tests were performed on cement mortars used for the lining of iron water pipes, to study the autogenous self-healing under the pipe service water as well as non-service water conditions ,3. This 2) in healed cracks [Several self-healing mechanisms and their efficacy have been investigated to promote the self-healing properties of concrete. These mechanisms include are continuing hydration, dissolution and crystallization, particle clogging, and carbonation . The prod cracks . Based od cracks .The autogenous healing is more effective when the cracks are smaller. As a result, the autogenous, inherent healing capability of cement-based materials may be significantly enhanced by restricting and regulating the fracture width. In this respect, many studies have been done to determine the relationship between performance recovery rate and initial crack width for different types of concrete. For high performance concrete (HPC) with fly ash, micro-silica, and water-reducing agent, a logarithmic relation was obtained between the normalized flow rate recovery and time of exposure. It was observed that for larger cracks, the permeability was increasing at a higher rate. The experimental results were also in close agreement with the law of Hagen–Poiseuille . FurtherThe addition of supplementary cementitious materials (SCM) and crystalline admixture (CA) can additionally improve the rate and efficiency of self-healing as a “stimulated-autogenous healing” approach. The partial substitution of cement with fly ash along with the addition of crystalline admixture can lead to a recovery of both compressive strength and electrical resistivity of concrete up to 94% . It was Polymers are widely used to enhance the self-healing of concrete either by encapsulation method, vascular method, or by directly injecting the polymers into the crack. Some of these polymers are polyurethane, superabsorbent polymers (SAP), acrylamide, acrylate, epoxy, poly styrene-divinylbenzene, styrene-butadiene rubber, etc. The inclusion of these polymers improves the regain ratio of mechanical properties and increases the surface crack healing .Numerous experiments, as well as studies, have also been conducted on the concrete reinforced with synthetic fibers and steel fibers. The fibers control the opening of the cracks that make self-healing products to easily attach to the surface of the cracks and fill them. Permeability tests and microstructural characterization of the engineered cementitious composite (ECC) containing different synthetic fibers, like polypropylene (PP), ethylene vinyl alcohol (EVA), and poly-vinyl acrylate (PVA), have been performed. The study concluded that the precipitation of calcium carbonate potentially increases with the inclusion of synthetic fibers , fibers The environment and the time of exposure have been varied by different researchers to either optimize the treatment condition for concrete under investigation or to investigate the effect of the intended field of investigation. Some of these treatment conditions are tap/distilled water curing at a different temperature, air chambers with controlled relative humidity (RH) and temperature, wet/dry cycle, freeze/thaw cycles, etc. . In the Similarly, ultra high-performance (or fiber-reinforced) concretes (UHPC/UHPFRC) materials, due to their mix composition, featuring a high binder content and a low water/binder ratio ,18,19, hIt is evident from the literature that several factors influence the efficiency of self-healing, which makes the systematic review of research the best supporting evidence. However, this form of review must be supported by statistical mathematical tools like meta-data analysis. This form of analysis is quite common in evidence-based healthcare research. Multiple clinical trials are performed by different labs, and the results are publicly filed. The systematic reviews summarize the results of different labs with several statistical parameters. The first systematic review was performed in 1747 by James Lind to find the optimum treatment of scurvy .In the field of cement-based construction materials, a few systematic reviews have been performed. Moreover, meta-data analyses are rarer in the same field. A recent systematic review has been done to study the effect of fly-ash replacement in high volume fly-ash concrete (HVFAC) . In thisA meta-analysis study has been done, where the parameters of mix-design of self-consolidating concrete have been related to fresh state parameters of concrete . In thisOn a separate note, new predictive models are being developed to determine the properties of concrete in the rapidly evolving concrete industry. The existing models for predicting the durability and mechanical properties of different types of concrete are usually based on empirical formulations. These formulations are obtained through linear or nonlinear best fitting models developed from the experimental data. In recent studies, neural networks have been used extensively for predicting the durability and mechanical parameters of the cement-based systems, also exploiting the extensive datasets created by researchers, based on the experimental data or the existing literature review. For instance, the durability of RC concrete was predicted using ANN models by analyzing the deterioration of the concrete samples using accelerated chloride tests. The researchers used around 250 points to analyze the influence of cement type, period of exposure, amount of SCM, and the w/b ratio on the chloride penetration in the concrete specimens .In a separate study, the compressive strength of geopolymer concrete has been predicted based on the mix design and the age of specimen. The 70:15:15 ratio of total data has been used for training, validation, and testing of the model. The total number of data points considered in the study were 117. The correlation coefficient, R, was lying in the range of 0.95–0.96. The results were also compared with the Gene Expression Programming (GEP) model, another type of computational model. It was shown that ANN model performed better than the classic regression model .A substantial study and review have been carried out on autogenous healing of different cement-based materials. The construction industry is interested in concrete that does not decay; however, further research is needed to perform the standardization and codification of the existing findings. The contractors and owners globally, depend on the local national codes for infrastructure construction. With the present-day understanding of the self-healing of concrete, a huge proportion of these contractors may not take the risk of promising repair-free concrete. Therefore, more quantitative proofs, depending on multiple studies, correlating the several involved factors to the self-healing of concrete must be provided.One way of supporting this activity is to carry out a state-of-the-art quantitative study that unifies the observations of numerous studies on an individual scale through data-mining and statistical models. This study will lay down a comparison and present in a quantitative way the effect of numerous parameters on the autogenous self-healing of cementitious material. The first objective is to determine the factors affecting the autogenous self-healing of concrete by analyzing multiple existing literatures. It is then followed by developing a meta-data statistical model determining the impact as well as the reliability of these factors on the self-healing property. Finally, an ANN model is to develop to present a robust simulation model to predict the self-healing capacity of different cementitious materials on a uniform scale. The relevant data has been collected from numerous peer-reviewed articles. “ScienceDirect” was a major scientific database to collect the relevant articles, journals, and book chapters. In the initial survey, 236 papers related to the self-healing capacity of concrete were analyzed. However, based on the required data, several papers were later removed because of the inadequacy or incompleteness of the data provided. The total number of relevant papers collected for both meta-analysis is 100. The distribution of the timeline of publications is presented in 3) and of supplementary cementitious materials (SCM) (kg/m3), fiber type and content (%vol), water/cement ratio, crack width (μm), age of treatment (days), and self-healing environment. The parameters collected as output are relevant results of the self-healing characterization test and geometrical closure of cracks. The relevant results are then converted into “Self-Healing Indices” (SHI) to maintain the consistency of results. These parameters for different tests are determined according to the experiment and the initial data. The values are being normalized to 1.0 by simple mathematical manipulations. The formulas of self-healing indices for several experiments are presented in The input parameters collected from each of these studies are the dosage of cement , and its width represents the 95% confidence interval (CI). The mean and standard deviations of SHI values are used to calculate the margin of error (MoE) (Equation (1)) and Cohen’s d-value (Equations (2) and (3)) [d-value is used to represent the magnitude of the effect of the certain parameter under analysis. The meta-analysis results of the various comparison will be shown in terms of Cohen’s d-value and MoE.z is Z-value , and N is the sample size.d, The self-healing indices have then been used to develop forest plots. A forest plot is a graph that displays results from several studies. The inference of the forest plot is a diamond that represents the result of a meta-analysis of the considered studies. The position of the diamond represents Cohen’s and (3)) . The Cohw/c, and total cementitious material (kg/m3) (TCM). The relative importance analysis was carried out against the output of SHI. The relative importance analysis has been carried out from the collected dataset to calculate the importance percentage of total cementitious material, water to cement content, crack width, age of healing, and fiber content in determining the self-healing index of concrete. Tonidandel and LeBreton’s method has been used to calculate the relative weight percentage . The tecFurthermore, based on the collected data, optimization charts have been developed for optimized design concerning the self-healing capacity of cementitious material. The Delaunay triangulation has been implemented to evaluate the interpolated values of SHI to generate the contour lines. Delaunay triangulation is used as an optimal method to generate a linear interpolation function that can be used to reconstruct the functional approximation in three-dimensional space. The Delaunay triangulation is applied to the pair of chosen parameters  and linear interpolation functions are constructed based on the value of response (SHI) . The chaFor ANN analysis, a back-propagation network has been developed in this study. A single-layer feed-forward neural network has been developed. In this network, the output and hidden layers are associated with biases. The training of data is performed by the method of supervised learning in this algorithm. The predicted output values are compared with the provided outputs and the associated error is calculated. The weights and biases of each neural network are adjusted based on this error. This process is iteratively carried out until the error is below the desired value or the maximum number of iterations is reached. 3), SCM dosage (kg/m3), fiber content (%vol), w/c ratio, crack width (μm), and age of treatment (days). The output variable is SHI. The ANN architecture is presented in In this ANN model, six input variables have been taken into consideration, i.e., cement dosage  weight and bias learning function while “learngdm” is the gradient descent with momentum (GDM) weight and bias learning function. As the study is preliminary, the number of hidden layers is kept at 1.0 and the number of neurons is varied from 1.0 to 30. The hyperbolic tangent and log-sigmoid functions are used as two activation functions in the neural network model as the only choices provided in MATLAB.Based on the literature review, most of the researchers have investigated the effects of different parameters on the self-healing efficiency and since the data mining analysis is based on the accumulations of the existing study parameters and their effects, the focus has been kept on the effect of the most common studied parameters including crack size, healing time and environment, presence of admixture, and presence of fibers. The meta-data analysis presents the effect of each parameter on the SHI as well as yields confidence on the effect of the parameter on the analyzed SHI.d-value” on scale presents “less than equal to ‘X’ μm” and “positive d-value” represents “greater than ‘X’ μm” case. The total number of relevant studies considered are 16, 13, and 11, for the ‘X’ value of 75 μm, 150 μm, and 225 μm, respectively. It is visually clear from the forest plots that the self-healing efficiency of smaller cracks is better than the bigger cracks. The average “d-value” is −0.2203, which shows the faster rate of healing for the smaller crack in all the cases. It is also evident that the absolute value of Cohen’s d is increasing with the increase in the value of ‘X’. The d-coefficient, as defined earlier, is proportional to the difference in mean values from two opposing arguments.A multitude of research has been carried out on the effect of crack size on the self-healing efficiency of concrete. Following the gathering of relevant data and preliminary inspection, the whole range of crack sizes is distributed in a certain range. The argument in this study is the self-healing efficiency of cracks “less than equal to ‘X’ μm” and “greater than ‘X’ μm”. ACI 224R-01 suggests the maximum allowable crack in the range of 100–250 micron for a different type of environment . Hence, d-value is also increasing with the crack size. Therefore, this result quantitatively infers that the SHI value decreases at a faster rate with the increase in crack size.Therefore, it is evident that the difference between SHI increases with the increase in crack size with the difference between average SHI for cracks “less than equal to 225 μm” and “greater than 225 μm” being largest. Furthermore, it can be noticed that the difference in The MoE values are of the same order for all three studies showing the equal similar variance in data for three analyses. The average value of the diamond ratio is calculated as 2.61, which shows the presence of heterogeneity in data collected from different studies. This can be attributed to the variation of other parameters, that aspect of the self-healing efficiency of concrete, among multiple studies.d-value” on the scale presents “less than equal to ‘X’ days” and “positive d-value” represents “greater than ‘X’ days” case. The total number of relevant studies considered are 28, 25, and 18, for ‘X’ value of 7 days, 28 days, and 56 days, respectively.The effect of the healing period on self-healing is the most researched parameter on the self-healing efficiency of cement-based materials. The self-healing time has been varied from few hours to 1 year and even more depending on the employed healing technology. However, most studies focus on the healing period of 3 days to 90 days. Imitating the same steps as in the case of cracks, the overall range of healing time has been divided by three values based on the observations from multiple studies. The opposing arguments will be the self-healing capacity of concrete treated for “less than or equal to ‘X’ days” and “greater than ‘X’ days”. The three values of ‘X’ chosen are 7 days, 28 days, and 56 days. The meta-analyses of three different arguments are shown in d-value” is 0.2068, which shows the faster rate of healing for a longer amount of treatment time. It is also evident that the d-value is decreasing with the increase in the value of ‘X’. It is inferred that the difference between SHI decreases with the increase in the healing period with the difference between average SHI for the period of “less than equal to 7 days” and “greater than 7 days” being largest. Furthermore, it can be noticed that the difference in d-value is also increasing with the healing period. Therefore, this result quantitatively suggests that the rate of healing decreases with an increase in the healing period. The healing rate is higher in the early stage, as autogenous healing happens predominantly in the first 28 days.It can be observed in the forest plots that the self-healing efficiency for a longer healing time is better than for shorter periods. The average “d-value” that the significance of the effect of crack size is like the effect of the healing period on the self-healing capacity of concrete.The average value of the diamond ratio is calculated as 3.11, which shows the presence of heterogeneity in data collected from different studies. The reasons have been explained in the previous section. It is also evident from the average “d-value” on scale represents “without admixture” and positive “d-value” represents the “with admixture” case. The total number of relevant studies considered are 14 and 15, for mineral and chemical admixture, respectively. In this study, the effect of SCM and the effect of crystalline admixtures (CA) have been studied separately. In both the studies, the opposing arguments are the self-healing capacity of concrete “without admixture” and “with admixture”. The meta-analysis of two different admixtures are shown in d-value for analysis with SCM and CA are 0.0811 and 0.2275, respectively. This striking difference between these two values shows the upper hand of crystalline admixtures on improving the self-healing capacity of concrete. The presence of CA in the concrete mix design is a significant factor equivalent to, if not more than, the crack size and healing period. A very low d-value infers the improvement of SHI with the inclusion of SCM; however, its effect is not as significant compared to the presence of CA. The average value of the diamond ratio is calculated as 2.22, which shows the presence of heterogeneity in data collected from different studies. The reasons have been explained in the previous sections.The forest plots show that the self-healing efficiency of concrete containing the admixtures is higher than for concrete without the presence of admixtures. The The healing environment significantly influences the self-healing efficiency of concrete. The studies have been carried out with different treatment conditions, such as complete water immersion, wet/dry cycles, sea-water exposure, humid chamber, air curing, natural weathering, etc. However, two of the most common methods are water immersion and wet/dry cycles. The analyses of all the treatment conditions have not been possible due to the lack of multiple studies. Therefore, the meta-data analysis has been carried out to compare the effect of water curing with the effect of the wet/dry cycle on the self-healing capacity of concrete.d-value supports the wet/dry cycles, and the negative value supports the complete water immersion. The total number of studies considered is limited to 8. The forest plots show that the self-healing efficiency of concrete incomplete water immersion is far greater than the wet/dry cycles. The d-value for analysis is −0.2736, quite relevant if compared to all the other values obtained in the analysis. This shows the high significance of the healing environment on the self-healing capacity of the cementitious system, more importantly, the time of exposure to water.The two arguments in this study are “Water immersion” and “Wet/Dry cycle”. The meta-analysis has been presented in The MoE value is 0.1234, which shows a high variance in the errors, mainly due to a smaller number of relevant studies on the same topics. The average value of the diamond ratio is calculated as 2.91, which shows the presence of heterogeneity in data collected from different studies. The reasons have been explained in the previous sections.The effect of the presence of fibers on autogenous self-healing of concrete has been explored by several researchers. The type of fibers has been varied, including PVA fibers, PP fibers, steel fibers of different shapes, acrylic fibers, etc. However, there are not a significant number of studies with the variation of fiber content and type. Therefore, all the types of fiber have been grouped in a single category of fiber. The meta-analysis has been carried out to study the effect of the presence of any fiber on the SHI of concrete.d-value supports the presence of fiber and the negative value supports the absence of fibers. The total number of studies considered is limited to 5. The two arguments in this study are “Without fiber” and “With fiber”. The meta-analysis is presented in d-value for analysis is 0.1185. This is a small value compared to all the other values obtained in the analysis, highlighting the low significance of fiber on the self-healing capacity of the cementitious system. The MoE value is 0.0957, which shows a high variance in the errors. This is mainly because of a smaller number of relevant studies on the same topics. The average value of the diamond ratio is calculated as 2.02, which shows the presence of heterogeneity in data collected from different studies. The reasons have been explained in the previous sections.The forest plots show that the self-healing efficiency of concrete with the presence of fiber is slightly better than the concrete without fiber. The d-value shows the effect of parameter on design and MoE yields the confidence on the effect of parameter on SHI. Forest plots take consideration of numerous studies to show the effect of each parameter on the SHI at a general scale. Cohen’s It is noted that the meta-data analysis portrays that the SCM content does not impact the SHI significantly; however, the meta-analysis only considers the presence or the absence of SCM in the mix design. In most of the studies, cement has been replaced by a certain percentage of SCM. Hence, the conclusion of meta-analysis is not dependable as the amount of cement is variable during the comparison of data. Therefore, a relative importance analysis has been carried out keeping the total cementitious material (TCM) as a parameter to provide a better picture.The relative weight analysis is an effective method to evaluate the relative importance of correlated parameters. d-value result from the meta-analysis hence the low influence of the fiber content on the self-healing capacity of concrete.The age of healing and water to cement content has also a significant effect on determining the SHI with an importance percentage of around 20% and 13%, respectively. The results validate the statements made based on the meta-analysis regarding the healing period in the previous sections of the study. Similarly, the relative importance percentage of fiber content is lowest with a percentage of 4.1%, confirming the low The optimization charts of some of the design parameters are shown in w/c ratio and the dosage of cement (kg/m3) in concrete are presented in w/c ratio for low-cement concrete  and vice versa (high-performance concrete). The SHI also gets significantly influenced by other factors like the period of healing and width of cracks. It is noticeable from the chart that SHI increases with cement content even with low w/c ratios, which is reasonable because this will correspond to the higher availability of un-hydrated cement for further hydration reactions. However, the rate of increase in SHI decreases slightly with the increase in cement content in concrete.The SHI contours for the The effect of supplementary cementitious material on the SHI is presented in The influence of crack width on self-healing efficiency is presented in The contour graph of SHI mapping the effect of the period of healing as well as cement content is presented in The influence of fiber content with cement on the self-healing capacity of concrete is shown in It has any way to be remarked that, since the optimization charts are based on the available reliable literature, they only cover a specific range of parameters. Therefore, more range of parameters should be included and an effort from the scientific community being implemented in documenting in the papers, as many of them as possible to enable meta-analysis to cover a wider range of applicability, thus also paving the way for the construction of a vigorous database that could foster standardization of healing test methods and design-oriented healing efficacy assessment procedures. Furthermore, besides estimating SHI using the Delaunay triangulation, a multi-input and output neural network model is being developed and optimized using the collected data. The development of the model and inferences are discussed in the following section.The step-wise optimization of the ANN model has been performed in the following steps. Firstly, the Root Means Square Error (RMSE) values were calculated for the optimization of the number of neurons. The optimization corresponding to adaptation learning functions and activation functions were also performed concerning correlation coefficient, R. The two adaptation learning functions were gradient descent (learngd) and gradient descent with momentum (learngdm), while two activation functions were hyperbolic tangent sigmoid (tansig) and hyperbolic tangent (tanh) function. The four combinations based on two parameters were hence learngd-tansig, learngd-tanh, learngdm-tansig, and learngdm-tanh. The best regression model was obtained for the learngdm-tansig combination . The desw/c ratio in The SHI contour plot based on crack size and cement content  is in goR-value) of the model. Hence, it is necessary to improve the ANN model by improving it as a multi-layer deep neural network model to provide better approximation of SHI value.In the case of healing period and fiber volume, the performance trends from the chart obtained  from ANNThe statistical analysis has been carried out using statistical tools, like effect size, the margin of error, and the diamond ratio. The meta-analysis shows that crack size, healing period and environment, as well as the presence of CA has the highest effect on the self-healing efficiency. On the other hand, presence of fibers and SCM improves the self-healing capacity in cementitious materials; however, the effect is not as significant as other parameters.w/c ratio, and fiber content in determining the SHI are 32.7%, 30.5%, 20%,13%, and 4.1%, respectively. The results validate the conclusions made based on the meta-analysis. The relative importance percentage of total cementitious material, crack width, period of healing, The analysis suggests that the crack greater than 300 microns have much less healing efficiency, even for longer times of treatment, whereas cracks smaller than 100 microns can heal completely within a shorter rime, down to one week. Furthermore, it is observed that the rate of healing decreases notably after a period of 14 to 28 days of treatment depending on the crack size, hence corroborating with the reaction mechanism of autogenous self-healing in concrete.w/c ratio and cement content shows that SHI increases with cement content even with low w/c ratios. This is because the hydration reactions augment with the availability of un-hydrated cement. However, more data is required for low-cement concrete with high w/c ratio to obtain better trends in optimization charts.The design chart of The analysis of supplementary cementitious material shows that there is a peak range for SCM content, around 40–60% of total cementitious materials, for optimum SHI. This is because the hydration reaction of fly-ash utilizes the hydration products of cement. The low amount of cement produces less hydration energy for the activation of the hydration reaction of fly-ash.The design chart investigating the effect of the period of healing shows rapid recovery at the beginning of the treatment process. For a longer period of healing, the effect of cement becomes more pronounced on healing capacity. It is suggested to treat concrete for the period of around 28 days as the hydration mechanism is almost complete in this period.The increase in the volume of fibers from 1% to 2.5% causes a slight improvement in the SHI of concrete. It has been shown that for low-cement concrete, the increase in SHI due to the addition of fibers is slightly more pronounced than high-cement concrete.The results obtained were in good agreement with the existing literature. However, more range of parameters should be included, and more relevant papers should be documented to enable meta-analysis to cover a wider range of applicability. Based on the optimization charts, this study can suggest some recommendations and highlight the expected research works that would contribute to fill the gap and provide more data to strengthen the confidence relating to self-healing/sealing parameters. A brief analysis is drawn below.w/c ratio are in good agreement with the theoretical interpolation charts, whereas a moderate error has been observed in the charts of the healing period and fiber volume. This can be attributed to the lack of demarcation of data points based on more parameters.The SHI contour plots based on crack size, total cementitious material, It is evident that optimized single-layer feed forward neural network provides a low correlation value. Hence, multilayered deep model must be developed in future study to improve the accuracy of the machine learning model. The results of neural network modeling are presented as follows.A systematic review of 100 papers has been carried out to study the effect of several factors on the self-healing capacity of cementitious systems. Primarily, a preliminary literature review has been carried out to investigate the factors that influence the autogenous self-healing efficiency of concrete. The numerical values of these factors and corresponding self-healing indices  are obtained to carry on quantitative analysis. The summary of important finding corresponding to meta-analysis, design charts, and neural network model is presented below:The approach herein employed, together with the produced design charts can pave the way toward codification and standardization of the composition of cementitious materials to exploit its best self-healing capacity.


In order to study the durability behavior of CFRP (carbon fiber reinforced polymer) reinforced concrete, three category specimens  were selected to investigate its performance variation concerning chlorine salt and salt-freeze coupled environment, which included the microscopic examination, the distribution of chloride ion concentration, and the compressive properties. By observing the microscopic of the specimens, the surface and cross-section corrosion deterioration was examined with increasing exposure time, and the physical behavior of CFRP and core concrete were discussed. The chloride ion diffusion test exerted that the chloride ion concentration in plain specimens is at least 200 times higher than that of fully reinforced specimens. Therefore, the effectiveness of CFRP reinforcement will be proved to effectively hinder the penetration of chloride ions into the core section. The formula of the time-dependent effect of concrete diffusivity with salt-freeze coupling effect was presented and its accuracy verified. A time-varying finite element model of chloride ion distribution was established by using ABAQUS software. It can be seen from the axial compression test that the strength loss rate of three categories of specimens was varied when subjected to the corrosion environment. Therefore, it is proved that CFRP reinforcement can effectively reduce the deterioration of the specimen’s mechanical properties caused by the exposure environment. The research results can provide technical reference for applying the CFRP strengthened concrete in a severe salt-freeze environment. In cold coastal areas, many concrete buildings are subjected to the coupling effect of the freeze–thaw cycle and chlorine salt immersion . The salt-freeze effect environment accelerates the deterioration process of a concrete structure and dramatically reduces the bearing capacity and durability of concrete structure . CFRP reSome scholars have studied the durability of bonding strength between CFRP and concrete under chloride salt immersion. It was found that failure modes of unsoaked specimens included cohesion, shear, and bonding failure. The failure mode of the soaked specimens is the failure of the bonding surface between CFRP and concrete. It shows that the bonding performance between CFRP and concrete decreases after being soaked in chloride salt. Finally, the reduction factor of bond strength between CFRP and concrete under a chloride salt immersion environment is proposed ,5,6,7,8.Other scholars have studied the diffusion law of chloride ions in concrete. It is found that the permeability of chloride ions in reinforced concrete beams increases with the increase in crack width. Reducing the water–cement ratio can inhibit the permeability of chloride ions in reinforced concrete beams ,10. Liu 4 solution immersion environment [4 solution will improve the compressive properties of epoxy resin. Few researchers studied the durability of CFRP composites in a chloride environment. It is found that the tensile properties of CFRP composites decrease slightly in a chloride environment. The damage of CFRP composites in a seawater immersion environment is more severe than that in a distilled water immersion environment because the thermal expansion coefficient of carbon fibers is different from that of epoxy resin. In addition, the hydrolysis of an epoxy matrix can also lead to contact surface damage [Some research focuses on the tensile durability of epoxy adhesives in aqueous solution and chloride solution, respectively. The tensile properties of the two epoxy adhesives are better evaluated by the method based on the flexibility beam. It is found that the degradation of tensile properties of specimens in chloride solution is more severe than that in tap water solution ,15. Rudaironment . It is fe damage . Hong ete damage . It is fIn this study, three category specimens  were selected to investigate its performance variation concerning chlorine salt and salt-freeze coupled environment. Firstly, during the exposure process, the mass of the concrete specimen and the pH value of the immersion solution is measured. Secondly, the surface and cross-section of the specimen are observed with a microscope. Then, powder samples are taken at different locations to measure the chloride concentration, and a time-varying formula for chloride concentration is proposed. An ABAQUS diffusion model is established based on the presented equation. Thirdly, the axial compression test is carried out to discuss the influence of exposure environment on the mechanical properties of the specimens, and the stress characteristics of three types of specimens are studied by combining the ABAQUS compression model. Finally, the durability behavior of the CFRP strengthened concrete in a chlorine salt and salt-freeze coupled environment is discussed.CFRP composite consists of a layer of carbon fiber woven fabric and epoxy adhesive on both sides in this test. Generally, there are one-way carbon fiber woven fabric and two-way carbon fiber woven fabric. The one-way carbon fiber woven fabric was used in this test, consisting of 12 K pure carbon fiber filaments. The single-layer thickness of carbon fiber woven fabric is 0.167 mm. The epoxy adhesive includes A and B two-component, in which component A is epoxy resin and B is the curing agent. The mixing mass ratio of A and B is 2:1. Therefore, the CFRP composite is a single-layer one-way plate. In order to obtain the tensile properties of CFRP composite and epoxy adhesive, the sheet specimens of epoxy adhesive and CFRP composite were prepared according to ASTM D3039. The sheet specimens of CFRP composite is a single-layer unidirectional plate, and the tensile test results are shown in The plain, partially reinforced, and fully reinforced specimens were selected to discuss the effect of CFRP reinforcement area ratio on the specimen’s mechanical performance. The shape of the specimens is a cylinder with a diameter of 100 mm and a height of 200 mm. The CFRP bonding area ratios on the side of the specimen are 0%, 50%, and 100%, respectively. Two widths of CFRP composite are used, which includes 200 mm and 20 mm, respectively. The plain specimens are not reinforced. Instead, the partially reinforced specimen are reinforced with 5 CFRP composites with a width of 20 mm, and the CFRP composites are evenly spaced 25 mm along with the height of the concrete specimens. Similarly, fully reinforced specimens are reinforced with 1 CFRP composites with a width of 200 mm, which equals the same specimens’ height. Generally, there are two failure modes of CFRP composites on the specimen surface, namely material fracture and bonding failure at the interface. The former can give full play to the mechanical properties of CFRP composites. In order to ensure the reinforcement effect, the adhesive force at the interface must be strengthened, so the two ends of the CFRP composite need to be overlapped. According to relevant research, the overlap length is about 1/4 of the circumference of the specimen circular section to prevent debonding at the interface section. Firstly, polish the reinforced part of the concrete specimen to make it rough. Secondly, epoxy adhesive is applied on both sides of the carbon fiber woven fabric to prepare a CFRP composite. Then paste the CFRP composite on the reinforced part of the concrete specimen. Finally, leave the concrete specimens at room temperature for seven days until the epoxy adhesive solidifies. In addition, epoxy adhesive is applied on the top and bottom surfaces to retard the chloride penetration path for partially and fully reinforced specimens. The specimen size and reinforcement location are shown in The chlorine salt freeze–thaw environment is set according to “The Standard of Testing Methods for Long-Term Performance and Durability of Common Concrete” (GB/T 50082-2009). A freeze–thaw cycle lasts for 4 h. The upper and lower limits of the center temperature of concrete specimens are 8 ± 2 °C and −17 ± 2 °C, respectively. The freeze–thaw medium is NaCl solution with a mass concentration of 3.5%, as shown in The specimens were divided into 15 groups according to the difference of reinforcement type and exposure environment. There are six specimens in each group, a total of 90 specimens. Firstly, take out one of each group of specimens for cutting, then observe its micro morpHology with a microscope, and finally, measure the chloride ion concentration at different positions. Then, another five specimens in each group shall be subjected to an axial compression test. The specimens’ grouping and label information are shown in The change of pH value of NaCl solution and the change of specimen mass are used to characterize the damage degree of the exposed environment to the specimen. For the specimen in the chlorine salt immersion environment, the NaCl solution’s pH value and the specimen’s mass shall be measured every 100 h. In addition, the NaCl solution’s pH value and the specimen’s mass shall be measured every 25 cycles for the specimen in a chlorine salt freeze–thaw environment. The measurement process is shown in In order to visually reflect the degree of damage to the concrete specimen by the exposure environment, an electron microscope  was used to observe the cross-section and surface of the concrete specimen. Firstly, cut a cross-section at half the height of the concrete specimen. Secondly, rinse the concrete specimen with clean water and silence it until the concrete specimen is dry. Finally, adjust the microscope scope, and the optimal magnification factor of 500 times is selected to observe the apparent property of the specimen, as shown in The chloride ion concentration at different positions was measured to study the diffusion law in the concrete specimen. Firstly, grind the sample powder every 10 mm along the radius of the cross-section. Six sampling points are selected, including point A, point B, point C, point D, and E and point F, as shown in The loading process of the axial compression test consists of a mechanical control system and strain acquisition system. The former is responsible for controlling the loading rate and collecting load data. YAM-5000F electro-hydraulic servo hydraulic pressure testing machine  is used to conduct an axial pressure test on the specimen, and the loading speed is 0.5 MPa/s. The latter is responsible for collecting strain gauges data. A strain gauge is bonded at 1/2 height of the specimen to obtain the axial strain of the specimen. The loading process and acquisition process is shown in According to 3, which is the salt of strong alkali weak acid. On the one hand, SiO32− reacts with H+ to produce HSiO3−, as chemical formula (1). On the other hand, HSiO3− reacts with H+ to produce H2SiO3, as chemical formula (2). During the immersion or freeze–thaw of a concrete specimen, OH− will dissociate into the NaCl solution, resulting in its alkalinity. The contact area between NaCl solution and concrete determines the change rate of pH value. To a certain extent, the change in pH value can represent the damage of the exposed environment to concrete. The greater the pH value variation, the more severe damage of concrete is observed. The change rate in pH value from large to small is plain specimens, partially reinforced specimens, and fully reinforced specimens. It can be explained that CFRP composites effectively prevent NaCl solution from directly contacting the concrete and weaken the damage of the exposed environment to the concrete. In addition, the change rate of pH in the salt-freeze environment is more significant than that in the chlorine salt immersion environment for the specimens with the same reinforcement type. The micro-cracks are generated on the surface and core concrete, and the structure becomes loose. It can be proved that the NaCl solution is easier to penetrate the specimen and increase the contact area with concrete. It shows that the deterioration of the salt-freeze environment to the specimen is more severe than that of the chlorine salt immersion environment.The main component of concrete is CaSiOAccording to According to In the chlorine salt immersion environment, the growth rate of specimen mass from large to small is plain specimens, partially reinforced specimens, and fully reinforced specimens. The NaCl solution will slowly penetrate the specimen, increasing the mass of the specimen, and the CFRP composite can effectively hinder the penetration of the NaCl solution into the specimen. After drying, the final value of the specimen mass is slightly higher than the initial value. It is because a small amount of NaCl crystals remain after the evaporation of water in the specimen.In the chlorine salt freeze–thaw environment, the mass of plain specimens and partially reinforced specimens decreases, and the mass of plain specimens decreases faster. In contrast, the mass of fully reinforced specimens increases slowly. In the chlorine salt freeze–thaw environment, a large matrix falls off the concrete surface of plain specimens and partially reinforced specimens. The mass of dropped matrix is greater than that of the NaCl solution absorption, resulting in the decline in the mass of the specimen. The matrix at the CFRP composite position of partially reinforced specimens does not fall off, so the mass decline rate of partially reinforced specimens is smaller than that of plain specimens. Due to the wrapping of CFRP composite, the matrix of fully reinforced specimens did not fall off. As a result, a small amount of NaCl solution penetrated the interior, increasing the mass of fully reinforced specimens.According to The micro-cracks appear in the cross-section of plain specimens, and there are no micro-cracks in the cross-section of partially reinforced specimens and fully reinforced specimens after immersion for 200 h, as shown in Similarly, after immersion for 400 h, the micro-cracks in the cross-section of plain specimens further expand and extend. The micro-cracks appear in the cross-section of partially reinforced specimens, as shown in According to Similarly, According to According to According to According to According to After immersion in NaCl solution and drying, the crystallization pressure is generated due to the precipitation of NaCl crystals, resulting in micro-cracks in the specimen. From the appearance and development of microcracks, the damage of specimens from large to small is plain, partially reinforced, and fully reinforced specimen. CFRP composites hinder the penetration of NaCl solution into concrete, and its radial binding force inhibits the emergence and development of microcracks. It shows that the CFRP reinforcement method can effectively improve the durability of concrete in a chloride immersion environment. The more the amount of CFRP is, the stronger the protection effect on concrete specimens is.2SO4 solution [2SO4 solution. Therefore, it can be explained that the CFRP partially retard the penetration of the H2SO4 solution into the core concrete, which is consistent with this study.During the freeze–thaw cycle, the frost heaving force caused by pore water crystallization leads to micro cracks. From the appearance and development of microcracks, the damage of specimens from large to small is plain, partially reinforced, and fully reinforced specimen. This is because the radial binding force of CFRP composites counteracts the frost heaving force to a certain extent and inhibits the emergence and development of microcracks. It shows that the CFRP reinforcement method can effectively improve the durability of concrete in a chlorine salt freeze–thaw environment. The more the amount of CFRP used, the more protection effect on concrete specimens observed. In addition, from the shape and development of microcracks, the damage of chlorine salt freeze–thaw is more severe than chlorine salt immersion. Related research discusses the durability of CFRP reinforced concrete specimens in an Hsolution . The micD28 is 36.2 × 10−12 m2·s−1, and the value of m is 0.052.tD is chloride ion diffusion coefficient after t days (m2·s−1); D28 is chloride ion diffusion coefficient after 28 days (m2·s−1); t is immersion period (days); m is attenuation index of diffusion coefficient.Many studies show that the diffusion characteristics of chloride ions in concrete comply with Fick’s second law. Furthermore, relevant studies show that the chloride ion diffusion coefficient decreases exponentially during the period of chloride salt . Based oD0 is 36.2 × 10−12 m2·s−1, and the value of β is 7.25 × 10−13.NFTD is chloride ion diffusion coefficient after N freeze–thaw cycle (m2·s−1); D0 is chloride ion initial diffusion coefficient (m2·s−1); β is increase coefficient of diffusion coefficient; N is the number of freeze–thaw cycles.Relevant studies show that the chloride ion diffusion coefficient increases linearly with the number of freeze–thaw cycles . Therefoerf(u) is Gauss’s error function. C is chloride mass concentration in concrete (kg/m3); SC is chloride mass concentration of immersion solution (kg/m3); x is the diffusion depth (m); t is the exposure period (s); and D is the chloride ion diffusion coefficient (m2·s−1).Combined with Fick’s second law, Formulas (3) and (4), a time-varying model of chloride ion concentration is proposed, which can be expressed by Formula (5).In order to explore the time-varying effect of chloride ion diffusion coefficient of concrete in an exposure environment, a time-varying model of chloride ion distribution in concrete specimens was established based on Formula (5) and ABAQUS software. The mesh division of the model is shown in According to the finite element model, the chloride ion concentration distribution nepHogram of PSSI-200, PSSI-400, PSSF-50, PSSF-100, FRSSI-200, FRSSI-400, FRSSF50, and FRSSF-100 is obtained, as shown in The test and simulation values of chloride ion concentration of plain specimens in chlorine salt immersion and freeze–thaw environments are shown in According to All these observations can be explained by the many micro-cracks that occur on the surface and inside the specimen. As a result, the structure becomes loose, which accelerates the penetration rate of chloride ions to the specimen in the salt-freeze environment. However, concrete undergoes continuous hydration and its internal structure becomes compact, which hinders the penetration of chloride ions into concrete in the chlorine salt immersion environment. Related studies have established the chloride ion diffusion model of plain concrete specimens in the chloride salt immersion environment and the chloride salt freeze–thaw environment and discussed the diffusion law of chloride ions in the concrete . TherefoThe failure modes of plain specimens under different exposure environments are the same. The specimen has no noticeable damage at the initial stage of loading. However, tiny cracks appear on the surface of the specimen with the progress of loading. Then small cracks begin to increase, expand, extend and cross each other, and finally develop into multiple discontinuous longitudinal cracks. The failure mode of the specimen is shown in The failure modes of partially reinforced specimens under different exposure environments are the same. At the initial stage of loading, the specimen has no noticeable damage. With the progress of loading, small cracks appear in the unreinforced part of the specimen, and the crack development is relatively slow. The reason is that CFRP composites inhibit the development of cracks. When the load reaches 80% of the ultimate bearing capacity of the specimen, the specimen makes a “crackling” sound, and partially epoxy adhesives crack. When the load reaches the ultimate bearing capacity of the specimen, the specimen will make a large “pop” sound. Three CFRP composites in the middle of the specimen broke instantaneously, accompanied by fragments of concrete splashing. The specimen shows apparent brittle failure, and the failure mode of the specimen is shown in The failure modes of fully reinforced specimens under different exposure environments are the same. The specimen has no noticeable damage at the initial stage of loading. The specimen makes a “crackling” sound and partially epoxy adhesives crack as the load reaches 85% of the ultimate bearing capacity of the specimen. The specimen will make a large “pop” sound when the load reaches the ultimate bearing capacity of the specimen. The middle part of the CFRP composite broke instantaneously, accompanied by the splashing of concrete fragments. The specimen shows apparent brittle failure, and the failure mode of the specimen is shown in The axial compression process of PSND, PRSND, and FRSND was simulated by the finite element software ABAQUS. Material properties of concrete are obtained from the tests, as shown in The stress nepHogram of PSND is shown in The stress nepHogram of PRSND is shown in The stress nepHogram of FRSND is shown in According to Similarly, −6. After 400 h chlorine salt immersion, the ultimate compressive strength decreases by 5.03%, the ultimate strain decreases by 16.69%, and the initial slope of stress–strain curves increase slightly. The ultimate compressive strength of PRSND is 45.2 MPa, and the ultimate strain is 10,422.5 × 10−6. After 400 h chlorine salt immersion, the ultimate compressive strength decreases by 3.94%, the ultimate strain decreases by 12.68%, and the initial slope of stress–strain curves increases slightly. The ultimate compressive strength of FRSND is 71 MPa, and the ultimate strain is 24,866 × 10−6. After 400 h chlorine salt immersion, the ultimate compressive strength decreases by 2.65%, the ultimate strain decreases by 4.31%, and the initial slope of the stress–strain curves is almost unchanged.2SO4 solution is obtained [It is concluded that after chloride salt immersion, the ultimate compressive strength, ductility, and elastic modulus of plain specimens and partially reinforced specimens decrease slightly. NaCl crystals fill the pore in the specimen after chloride salt immersion, the overall structure is compact, and the elastic modulus increases slightly. During the process of chloride salt immersion, micro-cracks appear successively on the surface and in the interior. The micro-cracks of the specimens extend continuously during the compression process, which leads to the early destruction of the concrete structure and reduction of the bearing capacity of the specimens. After chloride salt immersion, the ultimate compressive strength and ductility of fully reinforced concrete specimens are reduced slightly, the modulus of elasticity is almost unchanged. This is because the CFRP composite prevents most NaCl solutions from penetrating the inside of the specimens during chloride salt immersion. Only a small amount of NaCl solution penetrates the inside of the specimens, which results in little change in the mechanical properties of fully reinforced concrete specimens. The mechanical properties of specimens change from large to small in order: plain specimens, partially reinforced specimens, and fully reinforced specimens. The larger the area of CFRP reinforcement, the smaller the influence of chloride salt immersion environment on the mechanical properties of specimens. A similar conclusion for the durability of CFRP reinforced concrete specimens in Naobtained . The res−6. After 100 freeze–thaw cycles, the ultimate compressive strength decreases by 50.56%, the ultimate strain increases by 20.96%, and the initial slope of stress–strain curves decrease significantly. The ultimate compressive strength of PRSND is 45.2 MPa, and the ultimate strain is 10,422.5 × 10−6. After 100 freeze–thaw cycles, the ultimate compressive strength decreases by 16.12%, the ultimate strain increases by 12.63%, and the initial slope of stress–strain decreases significantly. The ultimate compressive strength of FRSND is 71 MPa, and the ultimate strain is 24,866 × 10−6. After 100 freeze–thaw cycles, the ultimate compressive strength decreases by 10.47%, the ultimate strain increases by 4.72%, and the initial slope of stress–strain decreases significantly.The ultimate compressive strength of PSND is 28.6 MPa, and the ultimate strain is 4276.3 × 10Related studies discussed the durability of plain concrete in a chlorine salt freeze–thaw environment . HoweverThis paper discusses the influence of CFRP reinforcement on the durability of concrete specimens from three aspects: micromorphology, chloride ion distribution characteristics, and mechanical properties. The specific conclusions are as follows.From the microscopic observation results, the damage degree of the specimens is plain specimens, partially reinforced specimens, and fully reinforced specimens from large to small. It shows that the CFRP reinforcement method can effectively improve the durability of concrete in chlorine salt immersion or chlorine salt freeze–thaw environment. The more CFRP is used, the higher the durability of concrete specimens. In addition, from the development of microcracks and matrix falling state, the damage of chlorine salt freeze–thaw is more severe than chlorine salt immersion.Under the same exposure period, the chloride ion concentration in plain specimens is at least 200 times higher than that of fully reinforced specimens. It indicates that CFRP reinforcement can effectively hinder chloride ion diffusion to the specimen. Under the same exposure period, the chloride ion concentration of the specimen in the chlorine salt freeze–thaw environment is more significant than that in the chlorine salt immersion environment. It indicates that the freeze–thaw cycle can promote the diffusion of chloride ions to the specimen. In addition, a time-varying formula for chloride ion concentration was proposed, and an ABAQUS model was established based on the formula.According to the axial compression test, after 100 freeze–thaw cycles, the strength reduction rate of plain specimens is 50.56%, and that of fully reinforced specimens is 10.47%. It proves that CFRP reinforcement can effectively reduce the influence of exposure environment on the mechanical properties of specimens. In addition, compared with the chlorine salt immersion environment, the strength reduction rate of the specimen in the chloride freeze–thaw environment is greater.


Hospitalized patients requiring intravenous antibiotics frequently undergo surgical intervention. These surgeries involve multiple transitions of care that may lead to antibiotic delay, additional unnecessary doses, omission, or substitution. While many studies examine the use of antibiotics for surgical site infection prophylaxis, there are no studies investigating antibiotic use in the perioperative period for inpatients already on an IV antibiotic regimen. This study examined the incidence and nature of antibiotic misadministration in the perioperative period among inpatients. We conducted a retrospective cross-sectional study at a Veterans Affairs Medical Center involving all inpatients who underwent surgery in 2019. Patients 18 years or older who were on an IV antibacterial regimen prior to surgery were included. Patients undergoing cardiac surgery and patients only receiving surgical infection prophylaxis were excluded. Through manual chart review, we collected information on the prescribed IV antibiotic regimen and timing of antibiotic doses in the perioperative period. Errors were classified as administration of additional unnecessary IV antibiotics and missed, delayed, and additional doses of prescribed IV antibiotics. There were 168 inpatients on an IV antibiotic regimen who underwent surgery in 2019. Complete data was available for 158 patients. Errors in antibiotic administration in the perioperative period were identified in 64 (41%) patients. Missed, delayed, additional unnecessary antibiotics, and additional doses of prescribed IV antibiotics were identified in 21 patients (13%), 14 patients (9%), 13 patients (8%), and 7 patients (4%), respectively . We found errors in antibiotic administration for inpatients undergoing surgery to be common, with the most frequent error being a missed dose of a prescribed IV antibiotic. This illustrates an area for quality improvement in inpatient antibiotic stewardship in our hospital and we suspect in other hospitals as well. Future work will incorporate more centers and examine how these errors affect outcomes for inpatients undergoing surgery, particularly in patients with sepsis or those requiring surgery for infection source control. All Authors: No reported disclosures


Organ-specific autoimmunity is often characterized by autoantibodies targeting proteins expressed in the affected tissue. A subgroup of autoimmunopathies has recently emerged that is characterized by predominant autoantibodies of the IgG4 subclass . This group includes pemphigus vulgaris, thrombotic thrombocytopenic purpura, subtypes of autoimmune encephalitis, inflammatory neuropathies, myasthenia gravis and membranous nephropathy. Although the associated autoantibodies target specific antigens in different organs and thus cause diverse syndromes and diseases, they share surprising similarities in genetic predisposition, disease mechanisms, clinical course and response to therapies. IgG4-AID appear to be distinct from another group of rare immune diseases associated with IgG4, which are the IgG4-related diseases (IgG4-RLD), such as IgG4-related which have distinct clinical and serological properties and are not characterized by antigen-specific IgG4. Importantly, IgG4-AID differ significantly from diseases associated with IgG1 autoantibodies targeting the same organ. This may be due to the unique functional characteristics of IgG4 autoantibodies  that affect how the antibodies cause disease, and the differential response to immunotherapies of the IgG4 producing B cells/plasmablasts. These clinical and pathophysiological clues give important insight in the immunopathogenesis of IgG4-AID. Understanding IgG4 immunobiology is a key step towards the development of novel, IgG4 specific treatments. In this review we therefore summarize current knowledge on IgG4 regulation, the relevance of class switching in the context of health and disease, describe the cellular mechanisms involved in IgG4 production and provide an overview of treatment responses in IgG4-AID. IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases caused by IgG4 subclass autoantibodies , 2. AutoAntibodies involved in IgG4-AID, known to date, target antigens in mainly four organ systems: 1) the central and peripheral nervous system with diseases such as MuSK myasthenia gravis (MG), anti-LGI1 and anti-Caspr2 encephalitis, anti-IgLON5 disease or chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against NF155/contactin-1/CASPR1, 2) the skin and mucosa with skin blistering diseases such as pemphigus vulgaris (PV) and pemphigus foliaceus (PF), 3) the kidneys with PLA2R- and THSD7A- antibody positive membranous glomerulonephritis and 4) the haematological system with diseases such as thrombotic thrombocytopenic purpura  or GPIHBP1 autoantibody syndrome. Other unifying features of IgG4-AID are their low prevalence , their eHow can the disease-overarching association of these common features be explained and which commonalities can we identify in the immune cells involved in the production of pathogenic IgG4 autoantibodies , 20?IgG is the main antibody class in the human body, with serum concentrations of 7-15g/L. However, the four IgG subclasses are numbered in descending order of their frequency, making IgG4 with an average of 5% (0.35-0.51g/L) of total IgG the rarest IgG subclass –23. NotaNormally IgG4 is produced after chronic exposure to antigen –31 or a The four IgG subclasses share over 90% sequence homology, but single amino acid differences in IgG4 affect its structure and function substantially. IgG4 has anti-inflammatory properties Figure 1Therefore, IgG4 autoantibodies do not hold classical effector functions such as complement- or immune cell- mediated tissue damage. Rather they exert their effects by direct steric interference with their target antigens. Since they are unable to form immune complexes, this interaction would be beneficial in situation where non pathogenic antigen needs to be cleared and eliminated without causing overt inflammation. However, in the setting of autoimmunity, this mechanism has the potential to act as pharmacological antagonism at its target antigen. Increasing antibody concentrations will increasingly compete with physiological interaction of the targeted protein with its partners. And indeed, this has been found to be the main effect in many IgG4-AID such as MuSK-MG, pemphigus vulgaris or anti-LGI1 encephalitis –67. For The autoantibody isotype and subclass is thus a critical factor in the pathomechanism of antibody-mediated autoimmunity. Yet it remains a crucial question, why IgG4 subclass autoantibodies are produced in the first place. What causes B-cells to undergo class-switching towards IgG4 and which cells are involved in its production?in vivo  have now been identified to modulate the polarization of CD4+ T cell responses in vivo , 74.During isotype switching, which is required for the formation of immunoglobulin subtypes, T helper cells stimulate the progeny of IgM– and IgD–expressing B lymphocytes to produce antibodies of different heavy-chain isotypes. Heavy chain isotype switching is induced by a combination of CD40L-mediated signals and cytokines. These signals act on antigen stimulated B cells and induce switching in some of the progeny of these cells. In the absence of CD40 or CD40L, B cells secrete only IgM and fail to switch to other isotypes, indicating the essential role of this ligand-receptor pair in isotype switching. Activated B cells in germinal centers may differentiate into long-lived plasma cells or memory cells. The antibody-secreting cells, called plasmablasts, enter the circulation and migrate to the bone marrow or mucosal tissues, where they may survive for years as plasma cells and continue to produce high-affinity antibodies, even after the antigen is eliminated , 76. In Considering the substantial progress in B cell targeting therapy approaches in recent years, understanding the role of effector B cells and B cell dysregulation in subgroup specific differences of IgG4-AID is crucial. Although the proportion of B cells in the peripheral blood is not altered, memory B cells are increased in both AChR- and MuSK-MG patients . NotablyThe importance of B cells has been shown in other IgG4-AID as well. In great likeness to MuSK-MG, PV patients show increased memory B cell pools and impaired regulatory B cell functions. Treatment induced amelioration of PV symptoms is associated with reduction of memory B cells and enhancement of IL-10 producing regulatory B cells –94. MemoIn brief, the dysbalance between memory/regulatory B cell activities appears to be a determining factor in IgG4-AID. Treatment response appears to be more closely associated with those targeting the aforementioned B cell subsets than other cell types of adaptive and innate immunity. However, what makes antigen-secreting B cells undergo class switch to IgG4? Does IgG4 have a physiological role and which cytokine factors are inductors of IgG4?via glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) and GITR- ligand (GITR-L)  . Regulatin vitro –104. A cin vitro , even plin vitro . In one in vitro . How exain vitro . In the in vitro .via regulatory T and B cells via cytokines like IL-10 . Since Intravenous immunoglobulins (IVIGs) are pooled human IgG from many healthy donors, and as such comprised of a highly diverse antibody repertoire of human IgG1,2,3 and 4. IVIGs have a range of proposed mechanisms, of which some may be relevant and others irrelevant for IgG4-AID .Possible mechanisms: A key mechanism of action of IVIGs may be the blocking of the neonatal Fc receptor (FcRn), which contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation to 3-4 weeks . IVIGs bIn the highly diverse antibody repertoire of IVIGs, it is possible that antibodies against distinct autoantibodies, particularly against the antigen-binding part, termed anti-idiotype antibodies, can be present, and could neutralize the effects of autoantibodies –174. IVILess likely mechanisms: Effect on proinflammatory cytokines: IVIGs may reduce the levels of proinflammatory cytokines that do not play a major role for IgG4-AID and induce anti-inflammatory cytokines –177. EffEffect on complement: An important mechanism of IVIGs that is not relevant for IgG4 is the inhibition of complement activation, which is a main effector mechanism of IgG3 and IgG1, but not of IgG4 autoantibodies . PerhapsWhile IVIGs are considered as short-term treatment for most IgG4-AID, it is also used as a long-term treatment in certain disorders such as inflammatory neuropathies . The undTaken together, IVIGs have several potential mechanisms of action targeting different parts of the immune system, and depending on their respective role for disease, IVIGs may be more or less efficient. The effects on complement, cytokine production and cellular immunity may not have a major impact of IVIGs in most IgG4-AIDs. These anti-inflammatory actions may in theory also backfire in IgG4-AID: IVIGs upregulate regulatory T-cells , 192, whTargeting B-cells, which are the cells producing autoantibodies, is a main focus of therapy for IgG4-AID. CD20 is a marker that is expressed on B-cells throughout development, but not on the antibody-secreting cells, short-lived plasmablasts or long-lived plasma cells. Rituximab is an anti-CD20 monoclonal antibody and as such depletes B-cells expressing CD20, therefore the treatment efficacy of rituximab depends directly on the type of B-cells involved in the production of autoantibodies which also appears to be linked to the IgG subclass.For example, in refractory AChR-MG, rituximab is usually the preferred treatment , but itsIt has well been established that CIDP patients with neurofascin antibodies do not respond to steroid and IVIG treatment but to rituximab, which was found to enhance regulatory B cell responses and inhibit memory B cell and plasmablast populations . More imHowever, because of its potential side effects and its high cost, in several countries rituximab is mostly used for the treatment of steroid-refractory MuSK-MG. In several cases, rituximab treatment was sufficient by itself, eliminating the need for other treatments or even leading to long term remission , and aggIn vitro treatment of thymocytes from AChR-MG patients with bortezomib resulted in marked depletion of long-lived plasma cells and inhibition of autoantibody production  and depletion of antibodies or B cell antigen-specific, which are non-specific. Therefore, they can be associated with side-effects, raising the need for novel, more targeted therapies.in vitro experiments, where immunoadsorption resulted in almost complete removal of the autoantibodies from all the patients’ sera tested  initial disease includes antigen-specific IgG1-3 antibodies with low pathogenicity (e.g. via complement activation) or at low concentration, but chronic antigen exposure and influence from regulatory T cells induces class switch to IgG4, which then- either by increased dosis or pathogenicity- cause disease by steric hindrance. 2) Genetic predisposition, e.g. via distinct MHCII-antigen-T-cell receptor combinations may lead to a “skewed” isotype profile towards IgG4, or 3) aberrant B cell development in IgG4-AID may lead to individuals being more inclined to develop an IgG4 response. Further studies are necessary to investigate these different possibilities. Clinically, therapies targeting B cells have led to better clinical outcomes than general immunosuppression with corticosteroids in MuSK-MG and anti-LGI1 encephalitis, therefore we conclude that IgG4-AID may require different treatment strategies than classical antibody-mediated autoimmunity. We also discuss IgG4- or antigen-specific -apheresis and IL-4 receptor blockade as potential new treatment strategies for IgG4-AID. Finally, we think that the key to a better therapy lies in understanding the underlying immunopathogenesis and better diagnostics that also include the analysis of IgG subclasses to improve our assessment of treatment outcomes.IgG4-AID affect different organs, are characterized by IgG4 autoantibodies targeting specific antigens and mostly display a strong genetic predisposition mediated by HLA-genes. IgG4-AID are distinct from IgG4-RLD which are characterized by fibrosis, elevated serum IgG4 concentrations and IgG4 positive plasma cell infiltrates in the affected tissue, but mostly lack antigen-specific IgG4. Hallmarks of IgG4 are the absence of complement activation, lack of bispecificity due to Fab arm exchange and inability to activate cells IK conceived the idea, wrote the manuscript, and provided figures. MM-D wrote the manuscript and provided a figure. VY, JT, KL, ST, ET and MH wrote the manuscript. IK, FL, RH, PM-M, and ET revised the final manuscript. All authors contributed to the article and approved the submitted version.IK was funded by a Hertha Firnberg Fellowship by the Austrian Science Fund, Austria, project number: T996-B30. FL is supported by German Ministry of Education and Research (01GM1908A) and E-Rare Joint Transnationalresearch support . JT and ST were cofinanced by the EU and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation . MM-D was funded by a Kootstra Talent Fellowship awarded by the Maastricht University Medical Center+. PM-M was funded by NIH 18-003826 and NIH 4224868 grants. MH receives financial support from the LUMC (Gisela Thier Fellowship 2021), Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen via the Target to B! Consortium (LSHM18055-SGF), PPS-Match call LUMC – Topsector LSH 2021, Prinses Beatrix Spierfonds (W.OR-19.13), and the Dutch Science Organization NWO (VENI 0915016181 0040).JT and ST have shares in the research and diagnostic laboratory Tzartos NeuroDiagnostics, Athens. FL discloses having received speaker honoraria from Grifols, Teva, Biogen, Bayer, Roche, Novartis, Fresenius, travel funding from Merck, Grifols and Bayer and serving on advisory boards for Roche, Biogen and Alexion. MH Is a member of the European Reference Network for Rare Neuromuscular Diseases and The Netherlands Neuromuscular Center. MH is a co-inventor on two patent applications on MuSK-related research. LUMC and MH receive license income from these patents. LUMC receives royalties on a MuSK ELISA.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.