The work reported here focuses on an evaluation of a novel heat stable formulation of a uterotonic peptide drug oxytocin involving stability testing under elevated temperatures and toxicokinetic response generated by sublingual (SL) administration in rabbits. The formulation was thermotolerant, maintaining the potency of oxytocin in the form of a fast-dissolving tablet at the end of 2-year storage at 30 °C/65% relative humidity with less than 5% loss in oxytocin content based on analytical high performance liquid chromatography (HPLC). The toxicokinetic results in rabbits showed that the fast-dissolving tablet was safe without any reactogenicity or toxicity associated with SL administration or the excipients present in the formulation. The SL route elicited rapid absorption of oxytocin in plasma within 5 min of administration although lower than intramuscular (IM) administration. IM resulted in area under the curve (AUC) values approximately 5 times higher than SL oxytocin. However, due to the limitations encountered during SL administration in an anesthetized rabbit model, the relevance of heat stable oxytocin formulation that has the flexibility to be adapted in different formats may warrant a human clinical study to determine whether therapeutically relevant plasma levels for treating postpartum hemorrhage can be generated via alternate non-injectable routes of administration. An estimated 295,000 women die each year in childbirth , with loConsidering the severity of mortality and morbidity caused by PPH in low-resource settings (LRS), it is likely that a dosage form that is safe, easy to administer and provides a rapid and effective response could be more effective in saving lives in these settings. Oral is the most desirable route of administration due to accessibility and simplicity of the dosage form. However, for peptide drugs such as oxytocin, oral delivery displays low systemic availability and diminished efficacy due to the physiology of this route where high proteolytic degradation in the stomach and intestinal region degrades the peptide molecules in addition to the chemical degradation by the harsh pH environment encountered in the stomach region. Furthermore, the characteristics of injectable oxytocin, including its reliance on the cold chain, limit its reach in terms of effective coverage .A heat-stable oxytocin in a fast-dissolving tablet (FDT) format for sublingual (under-the-tongue) delivery, offers easy administration of oxytocin with uncompromised quality (maintaining drug content), eliminating the need for injection and paving the way for community distribution in areas with limited health infrastructure, including potentially at-home births. In addition, heat-stable oxytocin as a SL FDT offers the favorable side effect profile of the WHO uterotonic drug of choice with the added advantage of being indicated potentially for both prevention and management of PPH.The sublingual (SL) route offers a rapid onset of action  and direResults from an initial feasibility study in minipigs reported previously by the authors show successful absorption of oxytocin via the SL route, along with improved thermostability of oxytocin in a fast-dissolving tablet form . ConsideHeat-stable SL oxytocin tablets were produced using the lyophilization cycle used previously  as shownThe toxicokinetic study in rabbits  was condFor SL placement of fast dissolving tablets, the rabbit was anesthetized and positioned on a flat table, with the lower jaw strongly supported in a horizontal level on the table. Using rounded tip stainless tweezers, the rabbit’s tongue was carefully raised, and the sublingual tablet was placed beneath the tongue see . AnestheA “Draize-like” scoring paradigm for injection site monitoring was used to grade the presence of erythema (and/or edema according to the reported method) . In addi2EDTA) tubes for plasma oxytocin determinations. Tubes containing hematology specimens were placed at room temperature on a rocker for at least 30 min prior to shipment. Tubes containing whole blood for serum isolation were maintained for at least 30 min and no more than 4 h at room temperature before being processed to serum. Tubes containing aprotinin-spiked (K2EDTA) specimens for oxytocin determinations were maintained on wet ice or cold packs before use and after collection. They were also maintained on a rocker for at least 30 min prior to processing.Animals were not fasted prior to blood collection. Blood was collected at the time points of 0 min (pre-dose) and 5, 10, 15, 20, 30, 60, 120, and 180 min post-dose and at euthanasia only the first four animals for SL group. All animals were anesthetized pre-dose, prior to dosing. All animals were anesthetized with ketamine (35–50 mg/kg) and xylazine (3–5 mg/kg) via a subcutaneous or intramuscular (IM) route followed by maintenance anesthesia with additional half doses if needed or via inhaled isoflurane. At the selected time points, whole blood was collected aseptically from the auricular artery and dispensed into the appropriate collection tubes in any order: (1) K3 EDTA for hematology determinations; (2) 0.129 M, 3.8% sodium citrate for coagulation analyses (plasma); (3) serum separator tube for serum chemistry and C-reactive protein; and (4) aprotinin-spiked (K2EDTA) vacutainer tubes and processed for collection of plasma. The samples were processed by centrifuging for approximately 15 min at approximately 3000 rpm and approximately 4 °C; they were aliquoted into cryovials without anticoagulant and were immediately placed on dry ice. At termination, blood was collected from the SL group for serum chemistry, C-reactive protein, hematology, and coagulation. Blood collected for coagulation analyses was collected into tubes containing 3.8% sodium citrate and was processed for plasma per the Noble protocol. All serum and plasma samples were processed aseptically.Blood samples for oxytocin determination were collected into the Aprotinin spiked  was validated following the FDA guidelines [The bioanalytical method for quantification of oxytocin in rabbit plasma . The calibration curves for Oxytocin were constructed as a non-linear function of the weighted (1/x2) linear regression of the theoretical concentration versus response  using the following equation:For quantitation, the LC/MS/MS data were acquired using AnalystAccuracy and precision were calculated using the following formulasPrecision:® was used for formatting data tables and computing summary statistics.Accuracy was calculated using theoretical concentrations. Accuracy and precision were reported with one (1) decimal place. All concentration data are reported to two (2) decimal places. Excelmax) and time-to-peak concentration (Tmax) were taken from the plasma concentration time profiles. Plasma concentration (μg) versus time (h) profiles were prepared and peak plasma concentration (Cmax) and time of its occurrence (tmax) were read directly from the respective profiles. The area under the concentration time curve (AUC0→t) was calculated according to linear trapezoidal method using GraphPad Prism version 4.A sublingual FDT containing 400 IU oxytocin was administered in rabbits. A 10 IU dose of oxytocin in the form of IM injection was used as a control. The serum peak concentration  at Histo-Scientific Research Laboratories (HSRL) . The following tissues from the SL group were preserved in 10% neutral buffered formalin.1.Appendix2.Cecum3.Colon4.Duodenum5.Esophagus6.Ileum7.Jejunum8.Rectum9.Sacculus rotundus10.Sublingual tissuePhysical evaluation of the optimized oxytocin in sublingual FDT formulation containing chitosan showed that the tablets were robust with good handling properties for oral disintegration dosage forms based on friability (less than 3 wt%) and hardness (30N) testing using TH3 tablet hardness tester by Copley Scientific  and FT2 friability tester from Sotax Corporation , respectively (data not shown). Overall, the results demonstrate that the FDTs maintained their physico-chemical stability with a disintegration time under 30 s and remained stable, maintaining the oxytocin content within 90–110% for a period of 24 months under 30 °C/65% RH storage with minimal loss due to degradation based on HPLC assay see . At 40 °The mean plasma levels (measured by LC-MS/MS) obtained after SL or IM administration of oxytocin in a rabbit model are shown in Animals that underwent necropsy were within the normal clinical limits of body weight, body temperature, blood pressure, heart rate and food consumption, at the time of gross necropsy. Overall, the tablet administration site  and alimentary tract tissues appeared to be normal and showed no gross observational changes. In all cases, the tongue ventral surfaces appeared normal after administration of the oxytocin in sublingual FDT formulation . There wThere were no findings in erythema or edema scores at either administration site during the study. All animals had 0 scores (no erythema or edema) at the injection site at various time points throughout the study.Our goal was to validate the findings from the previous feasibility study  by usingChitosan, a natural cationic polysaccharide, has received a great deal of attention in the past few years for its mucoadhesive character , permeatmax is obtained quickly, the biological effect of uterus contraction as needed to reduce bleeding (during PPH) would also be obtained quickly. As per the World Health Organization guidelines, oxytocin is administered either via IM or IV, and each route has potential advantages. The IV administration has a clinical advantage, as it leads to a faster response and a higher peak in plasma oxytocin levels; however, IM injection confers practical advantages, requiring fewer skills and less equipment to administer, making it a more serviceable option in a wider array of settings. Considering the rich vasculature in the SL region, where the blood vessels under the tongue drain into the jugular vein, rapid absorption of oxytocin into the blood circulatory system via the SL route is expected and in principle would mimic IV injection by introducing a drug directly into the systemic circulation.It is important to highlight that in the pharmacokinetic study, with SL administration, the absorption of oxytocin was rapid, with a mean absorption time within about 5 min of administration. Rapid absorption is a great advantage for the SL route because it is legitimate to assume that, if Cmax) pg/mL obtained were about 30% to 45% of the oxytocin levels obtained via the IM route (control). In a study conducted in 2004 by Carvalho et al. [The results from the pharmacokinetic study in rabbits showed that, although the SL route appeared to be associated with rapid absorption of oxytocin in plasma, the overall bioavailability was significantly lower with a higher variability among animals within the SL-dosed group as compared to the IM control group. This means that, despite the high sublingual dose of 400 IU, only a fraction of oxytocin was being absorbed via the sublingual route. The maximum concentration of oxytocin obtained via the SL route was 1164 pg/mL; for the control group (IM administration to anesthetized rabbits), the maximum oxytocin concentration was 2662 pg/mL. Specifically, for SL formulations, the plasma levels  of the tablets by the awake animals , indicating the importance of a correct administration approach with the SL route of delivery.Lastly, the optimized formulation containing chitosan was robust, with good handling properties. This formulationmaintained oxytocin drug content in the range of 90–110% drug content as per the USP monograph acceptable potency criteria for oxytocin ,21 underThe present study, as is obvious, has some limitations as correlated with the pharmacokinetic study. First, the rabbits had to be anesthetized for SL administration and therefore, there was limited saliva volume available for tablet disintegration, requiring external administration of fluid 0.25 mL to assist with tablet disintegration. Although the smaller volume had a lower chance of inducing swallowing and/or loss of oxytocin, in an anesthetized animal, it was difficult to “hold” the fluid in place. This may have contributed to involuntary loss in dose, thus contributing to a lower available dose and lower plasma levels of oxytocin, despite the high SL dose in the formulation.In conclusion, the authors have successfully developed a thermo-tolerant form of oxytocin in the form of a fast dissolving tablet for sublingual administration. The sublingual tablet was shown to be safe and demonstrated no reactogenicity or local toxicity in sublingual tissues or other organs in the gastro-intestinal region. The SL route appeared easy to administer and was well tolerated by the animals and characterized by minimal cardiorespiratory and other physiological effects. Due to the lower plasma oxytocin levels, it is unlikely that this administration route will elicit a relevant therapeutic effect as needed for the treatment of PPH. However, the absorption of oxytocin administered via the SL route was rapid, within 5 min of administration. This attribute needs further exploration, which could include an investigational clinical study to assess the potential of sublingual oxytocin for the treatment of mental health conditions such as postpartum depression or generalized anxiety and depression .


Cannabis refers to a plant in the family Cannabaceae, which has been used medically, recreationally, and industrially. The last two decades, in particular, have seen a large increase in the volume of literature on this topic. The present bibliometric analysis aims to capture the characteristics of scholarly journal publications on the topic of cannabis and cannabinoid research.Searches were run on the Scopus database on April 02, 2021, as follows “(TITLE (cannabi* OR hashish OR marijuana OR marihuana)) AND  OR LIMIT-TO  )”. Results were exported on the same day to prevent discrepancies between daily database updates. Only “article” and “review” publication types were included; no further search limits were applied. The “article” publication type includes publications featuring original research, whereas “review” includes reviews and conference papers. The following data were collected: number of publications , authors, and journals; open access status; publications per journal; journals publishing the highest volume of literature and their impact factors, language of publication; document type; publication country; author affiliations; funding sponsors; most highly cited publications; and most highly published authors. Trends in this subset of publications were identified and presented. Bibliometric networks were constructed using the software tool VOSviewer.n = 705). The most productive countries included the USA (n = 12 420), the UK (n = 2236), and Canada (n = 2062); many of the most common institutional affiliations and funding sponsors originated from these countries.A total of 29 802 publications (10 214 open access), published by 65 109 authors, were published in 5474 journals from 1829 to 2021. The greatest number of publications was published over the last 20 years. The journal that published the largest number of publications was Drug and Alcohol Dependence (The number of publications published on the topic of cannabis follows an upward trend. Over the past 20 years, the volume of cannabis research has grown steeply, which can be attributed to a large amount of funding dedicated to researching this topic. Future research should continue to investigate changes in the publication characteristics of emerging research, as the volume of publications on this topic is expected to rapidly grow.The online version contains supplementary material available at 10.1186/s42238-022-00133-0. Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The cannabis plant contains about 540 chemical substances  Cannabis refers to a flowering plant in the family Cannabaceae; while the exact number of species within the genus is disputed, the following three are generally recognized: The effects of cannabis are dependent on strength and quantity, the environment in which it is taken, and the experience of the individual using it. Psychological effects tend to predominate, with the user commonly experiencing mild euphoria. Individuals using cannabis often report distortions in time and space  conducted a bibliometric analysis of cannabis and cannabidiol research published between 1940 and 2019, capturing the characteristics of 1167 publications. They found that the historical development of this research topic could be divided into studies that focused on the following three aspects: chemistry, pharmacology, and molecular biology ) AND  OR LIMIT-TO  )”. Search results were exported in batches due to the download limits imposed by Scopus; all downloads were completed on the same day to prevent discrepancies between daily database updates. Searches were only conducted on Scopus because it is the largest abstract and citation database of scholarly literature Elsevier ; in compCitation analysis uses the number of citations a given research item receives to quantify its relative impact within a field of research , published by 65 109 authors were published in 5474 journals from 1829 to 2021. Since the 1960s, an upward trend with respect to the volume of publication can be observed, with 2020 marking the year with the most publications , followed by Addictive Behaviors (n = 419), and the British Journal of Pharmacology (n = 356) , followed by “pharmacology, toxicology and pharmaceutics” , then “biochemistry, genetics and molecular biology” . Publications were primarily published in English , followed by German , then French . The breakdown by document type was article  and review . The most common publication countries included the USA , the UK , and Canada  , King’s College London , and the National Institutes of Health ; the most common funding sponsors were the National Institutes of Health , the US Department of Health and Human Services , and the National Institute on Drug Abuse  . Between the 1960s and 2010s, a steady increase in the number of publications published in the areas of “immunology and microbiology,” “neuroscience,” “nursing,” “psychology,” and “social sciences” was observed. The subject area that consistently contributed to the highest proportion of cannabis publications was “medicine,” with the 2010s marking the decade with the highest percentage of all cannabis publications . The “biochemistry, genetics and molecular biology” and “pharmacology, toxicology, and pharmaceutics” reflect the subject areas with the second and third highest proportion of publications across the six decades. The number of publications pertaining to the former has ranged from 16.27 to 30.81%, while the latter between 20.93 and 34.67% of the published literature, across these six decades.Since the 1980s, an increase in the volume of open access publications was observed, with the 2010s marking the decade with the highest percentage of open access versus subscription publications  and 1960–1969 . This is supported by the shift in the top 10 funding sponsors of research beginning in the 1970s, where it is observed that an increasing number of publications have been supported by US funders; this includes the National Institutes of Health, the US Department of Human and Health Services, and the National Institute of Drug Abuse from 1970 to 1979  to 1980–1989 . In more recent years, additional US funders have supported cannabis and cannabinoid research, including the National Institute of Mental Health and the National Institute of Alcohol Abuse and Alcoholism.Multiple journals have consistently ranked as a top ten publisher of cannabis and cannabinoid literature across all multiple decades. Examples include the journals “Drug and Alcohol Dependence” (top ten from 1980 to 2019), “Psychopharmacology” (top ten from 1980 to 2019), and the “British Journal of Pharmacology” (top ten from 1990 to 2019). With respect to regional productivity, the USA has consistently generated the highest percentage of publications across each decade, with a notable increase between the decades of 1970-1979 ; other most common languages of publication included German, Spanish, and French, albeit proportionately far less than English.Another country that has consistently remained one of the top ten most productive countries includes the UK, which rose to the top three from the 1970s onwards. This rise to the top three coincides with the Presbyterian Historical Society and UK Research and Innovation, both UK institutions, as tied for the highest-ranking non-US funding sponsors in the 1970s. Similarly, Germany, another country that has remained in the top ten highest producing countries, entered the top three in the 2000s for the first time with Deutsche Forschungsgemeinschaft as the highest-ranking non-US funding sponsor. This is also observed in Canada, which re-entered the top three in 2010s with the Canadian Institutes of Health as the highest-ranking non-US funding sponsor. Despite the top ten funding sponsors across each decade being occupied by institutions from the top producing countries, the top ten affiliations of authors are from a more diverse group of countries. For example, the top author affiliation in the 2000s was the Universidad Complutense de Madrid, an institution in Spain, which was the fifth-highest producing country of the decade. Similarly, the Universidade de São Paulo was ranked fourth in the 2010s, while Brazil was not in the top ten highest producing countries. Lastly, with respect to language, most publications have been written in English across all decades, with the 2010s marking the greatest disparity between publications in English , “depression” (n = 256), “schizophrenia” (n = 529), and “anxiety” (n = 313) (Table n = 178) and cancer (n = 144). Additionally, it was found publications were also written at the intersection of the usage of cannabis/cannabinoids and that of other substances, as shown by the cluster of substance-related keywords  and “tobacco” (n = 327).Cannabis and cannabinoid publications were found to intersect with a wide variety of topics, including mental health disorders, disease, and the usage of other substances. Within the cluster of mental health-related topics, it was found that many publications included the keywords “psychosis” n = 39, “deprescer n = 14. Additin = 12 420) publications, followed by the UK (n = 2236) and Canada (n = 2062), matching the order and approximate proportions as found by the aforementioned analysis. The data also suggests that the presence of funding may contribute to an increase in the productivity of a country, as shown by the first-time appearance of Germany and Canada in the top 3 most productive countries in decades where German and Canadian institutions were included in the top 10 funding sponsors. It is also unsurprising that out of the top 10 institutional affiliations responsible for publishing this cannabis research, five originate from the USA, one from the UK, and one from Canada. Additionally, with respect to funding sponsors, six are based in the USA, two in Canada, and one in the UK (excluding the European Commission). It has also been found that more cannabis research has focused on the harms associated with the substance, as opposed to its medical uses, especially in the USA (Science n = 14) of the 30 journals have published the highest number of cannabis publications containing harm-associated words in their titles such as “dependence,” “addictive/addiction,” “forensic,” “drug,” and “abuse.” In contrast, only a single journal—the Journal of Medicinal Chemistry—exclusively publishes medical cannabis research, while the remaining journals have titles indicating that they publish a mixture of cannabis research relating both to harms and medical properties .The objective of the present bibliometric analysis is to capture the characteristics of scholarly journal publications on the topic of cannabis research. The search conducted on Scopus yielded nearly 30 000 publications, representing the largest bibliometric analysis of cannabis literature to date to the authors’ knowledge. An increase in the volume of literature was observed beginning in the 1960s; however, the most recent 20 years have represented the largest increase in the volume of research published on the topic of cannabis. This can largely be attributed to the fact that more than $1.5 billion in funding has been allocated to cannabis research just between 2000 and 2018 Hellth . One ana Science . This isn = 395), “schizophrenia” (n = 529), and “anxiety” (n = 313) as shown in Fig. Cannabis is a topic of interest when investigating the onset and treatment of mental health conditions, as indicated by the prevalence of the author keywords “psychosis” , cancer (n = 144), and pain (n = 343). One systematic review conducted by Belendiuk et al. (2015) provides a review of the literature exploring the use of cannabis as a treatment for cancer and multiple sclerosis. It was found that there were conflicting results associated with the efficacy of cannabinoids when used to relieve symptoms of cancer treatment  also explored the use of cannabis as a treatment for multiple sclerosis. Studies have reported that cannabis administered orally or sublingually may relieve common symptoms of MS, such as muscle spasticity  and tobacco (n = 327), as evidenced by the author keywords presented in Fig. There is a significant volume of research investigating the intersectionality of cannabis and other substances, particularly alcohol .


The risk of cracking in the early stage is a critical indicator of the performance of concrete structures. Concrete cracked when the tensile stresses caused by deformation under restraint conditions exceeded its tensile strength. This research aims at an accurate prediction of shrinkage cracking of concrete under constraints. Based on the theory of capillary tension under the concrete shrinkage mechanism, the method to test and compute the elastic modulus of a micro-matrix around the capillary,  The cracking of concrete has long been an issue puzzling many scientific researchers and engineering personnel. With the deepening of relevant research and the improvement of concrete mechanical properties, the cracking of concrete has seldom arisen from the impact of the direct load under normal use. Nevertheless, indirect impact, including the impact of temperature on the large-volume concrete as well as the creep and auto-shrinkage of concrete, has gradually played an important role in causing the cracking of concrete . ResearcPrior research into the shrinkage performance of concrete mainly focused on the impact of materials ,5,6, temMany scholars have carried out a series of studies on the elastic modulus of concrete. Several such studies have found that the elastic modulus has a great influence on the properties of concrete materials, such as railway sleepers  and precperties” . The way2) of the specimen; L denotes the measurement gauge length; ∆n indicates the average (mm) of the deformation on two sides of the specimen when the load The standard prism (standard dimensions: 150 × 150 × 300 mm) test specimens are employed to measure the concrete axial compressive strength ; First, the mercury injection apparatus was used to measure the concrete pore structure at the moment of as below :(3)σc(t)t, the concrete shrinkage stress and the concrete-free shrinkage stress at the moment of At the same time, the concrete shrinkage stress and the concrete-free shrinkage stress at the moment of Thereby, as shown in Of special note is that As shown in Then, the restraint stress within the concrete at certain moment, t moment, the concrete cracking will occur.When In order to obtain the concrete elastic modulus of a micro-matrix around the capillary, Portland cement (P.O42.5R) and Bolei Level-I fly ash and additive were adopted as experimental materials. Their chemical components and mechanical properties are demonstrated in The mixing ratio of concrete  at four different strength grades is presented in Concrete shrinkage stress, pore structure and concrete relative elastic modulus under the capillary tension at different strength grades, ages and constraints can be measured and calculated. In this research, two types of specimens were designed. The first type was the concrete cracking specimen constrained by steel plates . The second type was the concrete auto-shrinkage specimen without the constraint of steel plates. The dimensions of these two types of concrete specimens were both 200 mm × 200 mm × 1000 mm. To facilitate the observation of concrete cracking, dry preservation was used. The mold was made up of glass, which was convenient to demolish. The screws and angle steel were used for fixture around the organic glass mold. The upper of the mold is clipped with timbering support to prevent swelling. Concrete shrinkage test usually adopts the commonly used auto-shrinkage test system. Auto-shrinkage test specimens were measured with the linear variable differential transformer (LVDT) installed in the center of the two ends of the test specimens. The measurement precision and scope were set to be 1 μm and 2 mm, respectively. In order to ensure the accuracy of LVDT, two nuts were placed in the center of the two ends of every test specimen. After the initial setting of concrete, the organic glass mold was removed, and the two plastic bolts were both screwed into the two nuts. After that, the LVDT test bar had a direct contact with bolts. The computer was used to automatically measure the records, and the experiment measured the shrinkage of all plain concrete as well as the shrinkage of test specimens inbuilt with the steel plate, whose thickness is 20 mm, 40 mm and 60 mm, respectively. The impact of temperature on concrete could be measured through a preliminary test. Specifically, the temperature and humidity sensor were built into every sample, and all test specimens were placed under the environment at the temperature of 20 ± 1 °C and the relative humidity of 60 ± 5%. There was one specimen per group for the shrinkage test.Similar to the concrete shrinkage strain measurement experiment, concrete test specimens poured in-place by four mixing ratios  were adopted to test the concrete porosity. When the concrete age reached 2, 3, 4, 5, 7, 14 and 28 days, respectively, the core samples were extracted from test specimens to test the concrete porosity. The porosity test had three specimens per group.The concrete core samples thus extracted were first crushed and then screened to have concrete particles collected. The diameter of these concrete particles ranged from 2.5 mm to 5 mm. The acetone was used to prevent the hydration of concrete, and the vacuum dryer was applied to the dry samples. At last, the AutoPoreIV9510 device was employed to test the concrete porosity. The cracking observation experiment was conducted to measure the early cracking of all concrete constrained by steel plates .The reading microscope, which can amplify the target by 40 times , was adopted to observe the concrete surface. The time of the first tensile crack developed on all test specimens constrained by steel plates, together with the follow-up changing the breadth and length of the crack development, was put down.The mechanical properties of all steel plates adopted for this research are presented in As shown in Additionally, the critical capillary diameter of concrete of different grades was compared, revealing that, under the same concrete age, the higher the concrete grade was, the smaller the critical capillary diameter of concrete would be. Take C30, C40, C50 and C60 concrete, whose age was 28 days, for example. Their critical pore diameter was 22.71 nm, 18.64 nm, 17.29 nm and 15.15 nm, respectively. This was because the concrete content was higher in concrete of a higher grade, and the cement hydration effect within the concrete was more complete, thus ensuring a more compact internal structure for the concrete.In this experiment, the porosity and static (static compression) elastic modulus of concrete under different statuses were measured on the 2nd, 3rd, 4th, 5th, 7th, 14th and 28th, respectively. The capillary tension and free shrinkage strain measured at different moments were used to work out the elastic modulus of a micro-matrix around the capillary, As shown in The elastic modulus of a micro-matrix around the capillary, According to Observing the initial cracking time of concrete held vital significance to learn about the concrete cracking development status. In order to study the influence of different constraints on concrete cracking, three kinds of steel plates that had a higher thickness were adopted.In a bid to better display the crack form and position, the concrete actual crack chart was simplified into In terms of crack development, C30 test specimens were found with a steady crack development. After cracks appeared in C30 test specimens, no further cracking was observed, and the maximum crack width was very small, which was 0.08 mm on average. The maximum crack length was 32 mm on average. All this was hard to observe by naked eyes. C40 test specimens, after developing the first crack, was found with other tiny cracks, subsequently. Their maximum crack width was 0.165 mm on average, while their maximum length was 37 mm on average. But the crack development was relatively slow. Multiple cracks were found with C60 test specimens, of which major cracks developed fast, with the maximum crack width reaching 0.28 mm and the maximum crack length reaching 63 mm.The elastic modulus of a micro-matrix around the capillary, According to Based on the theory of capillary tension, the method to work out the elastic modulus of a micro-matrix around the capillary was obtained. Meanwhile, concrete constrained cracking experiments were carried out to verify the accuracy of this method. Through the measurement of the pore structure and porosity as well as the observation of concrete cracks, the impact of different steel plate thicknesses and different mixing ratios on the concrete shrinkage, pore structure, capillary tension and cracking was examined. Below are some deductions of the elastic modulus of a micro-matrix around the capillary of concrete and at different mixing ratios.The free shrinkage of test specimens at different mixing ratios was significantly different. The higher the concrete strength was, the higher the shrinkage. Steel plates had an obviously restraining effect on concrete. The thicker the steel plate was, the stronger the restraining effect.Under the prerequisite that other conditions remained unchanged, the smaller the concrete water-cement ratio was, the faster the crack development was after the concrete cracking, and the longer crack width was thus formed.The positive correlation between the elastic modulus of a micro-matrix around the capillary, The concrete cracking time predicted by Due to the limitation of test conditions and funds for the test, the calculation of the elastic modulus in the article uses data with an interval of 24 h or more. If the sampling interval of porosity and shrinkage values is shortened as much as possible, more accurate relative elastic modulus data can be obtained, and this method can be used to better predict concrete cracking.


To describe patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients at primary and secondary healthcare facilities across Bugisu, Eastern Uganda.We surveyed 37 public and private-not-for-profit healthcare facilities and conducted a retrospective review of antimicrobial prescribing patterns among febrile under-five outpatients (with a focus on antibiotics) in 2019–20, based on outpatient registers. Multilevel logistic regression analysis was used to identify determinants of antibiotic prescribing at patient- and healthcare facility-levels.Antibiotics were prescribed for 62.2% of 3471 febrile under-five outpatients. There were a total of 2478 antibiotic prescriptions of 22 antibiotic types: amoxicillin (52.2%), co-trimoxazole (14.7%), metronidazole (6.9%), gentamicin (5.7%), ceftriaxone (5.3%), ampicillin/cloxacillin (3.6%), penicillin (3.1%), and others (8.6%). Acute upper respiratory tract infection (AURTI) was the commonest single indication for antibiotic prescribing, with 76.3% of children having AURTI as their only documented diagnosis receiving antibiotic prescriptions. Only 9.2% of children aged 2–59 months with non-severe pneumonia received antibiotic prescriptions in line with national guidelines. Higher health centre levels, and private-not-for-profit ownership  were significant contextual determinants of antibiotic prescribing.We demonstrated a high antibiotic prescribing prevalence among febrile under-five outpatients in Bugisu, Eastern Uganda, including prescriptions for co-trimoxazole and ampicillin/cloxacillin (which are not indicated in the management of the common causes of under-five febrile illness in Uganda). Study findings may be linked to limited diagnostic capacity and inadequate antibiotic availability, which require prioritization in interventions aimed at improving rational antibiotic prescribing among febrile under-five outpatients. Hence, understanding antibiotic prescribing practices especially at these levels of healthcare is a prerequisite for optimizing antimicrobial use and improving health outcomes for young children. However, evidence on antibiotic prescribing patterns among paediatric outpatients in primary and secondary healthcare facilities in Uganda remains scarce.9Children under 5 years old are an important group of antibiotic users, one for which antibiotics are often over-prescribed and inappropriately prescribed.10 In Uganda and similar settings, contextual health system factors such as heavy workload for healthcare workers, and limited availability of essential diagnostics and antibiotics may contribute to inappropriate antibiotic prescribing.12 Yet, to our knowledge, little is known about the influence of contextual health system factors on antibiotic prescribing for paediatric outpatients in Uganda. Such evidence could further elucidate modifiable drivers of antibiotic prescribing, which is important for the design of context-appropriate, sustainable antimicrobial stewardship interventions in Ugandan outpatient settings and similar contexts elsewhere. Therefore, this study aimed to describe patterns and contextual determinants of antibiotic prescribing for febrile under-five outpatients at primary and secondary healthcare facilities in Bugisu, Eastern Uganda.Prescribing behaviour is complex, and is influenced not only by the patient–provider interaction, but also by broader healthcare facility and health system factors.13 and has under-five mortality and poverty rates higher than the national average.15This was a cross-sectional study conducted in outpatient settings of 37 primary and secondary healthcare facilities across the six districts of Bugisu . Bugisu, a sub-region in Eastern Uganda, is a malaria-endemic setting, with an estimated population of 1.8 million inhabitants,16 Health Centre level two (HC-II) and HC-III are primary healthcare centres; HC-IV and general hospitals provide secondary healthcare services; and tertiary-level healthcare services are provided at regional- and national referral hospitals.17 The lead role in prescribing is taken by nurses at HC-II, Clinical Officers at HC-III, and Medical Doctors, where available, at higher healthcare levels. Clinical Officers are non-physician clinicians with training in clinical aspects of medicine, and with fewer clinical skills than physicians but more than basic nurses.18Healthcare in Uganda is based on a referral system and a tiered healthcare structure, and is delivered through public and private healthcare facilities. Formal healthcare facilities in Uganda are organized into six levels, according to the services provided and catchment area covered, as described elsewhere.This study included public and private-not-for-profit healthcare facilities at four levels: HC-II, -III, -IV, and general hospital. There were two study components: a healthcare facility survey, and a register-based retrospective review of antimicrobial prescribing patterns among febrile under-five outpatients [children aged under 5 years (including neonates) with febrile illness that were managed as outpatients] at the study healthcare facilities, from January 2019 to December 2020.JAC-AMR Online)Multi-stage and purposive sampling were used in the selection of healthcare facilities for this study, to ensure representation of the six districts, and the multiple levels of healthcare provision in Bugisu. First, two general hospitals and 10 HC-IV facilities in Bugisu were enrolled. Second, 16 HC-III and 11 HC-II were purposively selected, taking into account representation of the districts, health sub-districts, and ownership (public versus private-not-for-profit). One general hospital was excluded because it provided only specialized services, which did not match the aim of the study, and one HC-IV was excluded due to unavailability of the medical records staff on all occasions the facility was visited for data collection. Altogether, 37 healthcare facilities were enrolled, six of which were private-not-for-profit.  fever was not documented as a presenting clinical sign or symptom, or (ii) records had incomplete or illegible entries about the diagnoses and prescriptions.19 where these were available, or by tallying daily attendances from the outpatient registers. This was then divided by the required sample size at that healthcare facility to obtain a sampling interval. Records were then selected by the determined sampling interval, taking the first eligible child attending in January 2019 as the starting point. Whenever an ineligible record was encountered, it was skipped and replaced with the next eligible record without breaking the original sampling interval.Records were selected systematically at the health facilities. To obtain the sampling interval, the total number of under-five children attending the outpatient clinics at each of the facilities within the study period was first obtained. This was determined using health facility monthly reports from the Health Information Management System Form 105,20 using a 5% level of precision and a 95% CI. The proportion of under-five children prescribed an antibiotic was assumed as 84.9%, based on a similar study conducted among paediatric inpatient and outpatients in Tanzania.21 This yielded a sample size of 196, which was adjusted to cater for clustering at the four levels of service delivery , with a 10% allowance for missing data and incomplete records, resulting in an estimated sample size of 2309  group.25 Access antibiotics have the lowest resistance-development potential, and should be widely accessible as first-line antibiotics for most indications; Watch antibiotics are mainly used as second-line treatment; and Reserve antibiotics with the greatest resistance-development potential are last-resort medications.25 Where feasible, prescriptions and their corresponding indications were compared with the UCG,26 to assess degree of congruence. Descriptive statistics were summarized using a bar graph, pie chart and cross-tabulations.Each medication prescribed was considered as one prescription, such that one child could have multiple prescriptions. All prescriptions were assessed to determine the proportion of antimicrobial agents in any form , which were then classified as antibacterials, antimalarials, antifungals, or antiviral agents. Antibiotics were defined as antibacterial medications belonging to the Anatomical Therapeutic Chemical (ATC) J01 , and P01AB (Nitroimidazole derivatives) classes,Multilevel logistic regression was used to investigate the determinants of antibiotic prescribing at patient- (Level-1) and healthcare facility-levels (Level-2), taking the 37 healthcare facilities as clusters. The outcome variable was dichotomous, indicating whether a child had a documented prescription for any oral or parenteral antibiotic (ATC J01/P01AB) or not. Level-1 variables included in the models were: child’s age , child’s sex, date of presentation , child’s malaria test result, and dichotomous variables for the presence or absence of the commonest reported diagnoses. At Level-2, the following variables were included: health centre level , healthcare facility ownership (public or private-not-for-profit), availability of UCG, and a continuous variable representing patient-to-prescriber ratio, obtained by dividing the average outpatient attendance over the 5 working days before the survey, by the total number of prescribers available at the healthcare facility. .The following models were run: Model 1, the null-model containing only the outcome variable and the healthcare facility identifier (cluster) variable; Model 2, which included Level-1 variables with the facility identifier; and Model 3, which included Level-1 and Level-2 variables with the facility identifier. The level of statistical significance was set at 0.05. Variance inflation factor (VIF) was used to assess covariates for multicollinearity. The mean VIF was 1.14 . Data were analysed using Stata 15.1 .Ethics approval was obtained from the Makerere University School of Health Sciences Research and Ethics Committee, reference number MakSHSREC-2020-21. The study was registered and cleared by the Uganda National Council for Science and Technology, reference number HS1155ES.Characteristics of the 37 surveyed healthcare facilities  are shown in Table Records of 3598 febrile under-five outpatients that attended the surveyed healthcare facilities between 1 January 2019 and 31 December 2020 were retrospectively reviewed. The majority, 3583 (99.6%), were reported as first-time presentations, 1774 (49.3%) were male; 1883 (52.3%) were aged 6–23 months, , of the 3598 surveyed febrile under-five outpatients were prescribed at least one medication, resulting in a total of 9745 prescriptions. On average, each febrile under-five outpatient received 2.81 prescriptions per clinical encounter, with 487 (14.0%) receiving at least one injection prescription.Of the total 9745 prescriptions, 4114 (42.2%) were for antimicrobials in any form ], AURTI [1381 (38.4%)], diarrhoea [548 15.2%)], and pneumonia [370 (10.3%)]. Other diagnoses included skin infections in 227 (6.3%), non-specific bacterial infections  in 200 (5.6%), and helminthiasis in 154 (4.3%) children. Diagnostic tests were reportedly performed in 2760 (76.7%) of the 3598 surveyed children  received at least one antimicrobial: 2158 (62.2%) received a prescription of at least one antibiotic, 1327 (38.2%) at least one antimalarial, 95 (2.7%) an antifungal, and 2 (0.06%) an antiviral. 484 (13.9%) received both an antibiotic and an antimalarial. The number of antibiotics prescribed per patient ranged from 0 to 4, with patients receiving on average 0.74 antibiotics prescribed per clinical encounter.AURTI was the commonest single indication for antibiotic prescribing. Of 676 children with AURTI as the only documented diagnosis, 76.3% received at least one antibiotic prescription Table . At leas26 Irrespective of age, amoxicillin for non-severe pneumonia among children aged 2–59 months was mostly prescribed at 250 mg three times daily [104/221 (47.0%)], and for 5 days [184/218 (84.4%)].Of 314 children aged 2–59 months diagnosed with non-severe pneumonia, 303 (96.5%) received at least one antibiotic prescription, with 226 (72.0%) receiving prescriptions for amoxicillin. Only 29 children (9.2%) received a prescription for amoxicillin at the appropriate dose for up to 5 days, in accordance with national guidelines.Of 680 children with malaria as the only documented diagnosis , 103 15.2%) received at least one antibiotic prescription. Similarly, out of 192 children with a single diagnosis of acute watery diarrhoea, 77 (40.1%) received at least one antibiotic prescription  of febrile under-five outpatients in this study, with amoxicillin and co-trimoxazole accounting for two-thirds of all antibiotic prescriptions. AURTI was the commonest single indication for antibiotic prescribing, with a prescribing proportion of 76.3% when AURTI was the only documented diagnosis. Notably, only 9.2% of children aged 2–59 months with non-severe pneumonia received an appropriate antibiotic prescription per the national guidelines. Higher health centre levels (compared with HC-II) and private-not-for-profit ownership were significant contextual determinants of antibiotic prescribing.27 Given the relatively low prevalence of diagnoses necessitating antibiotic prescribing in this study [pneumonia (10.3%) and dysentery (0.39%)], the overall antibiotic prescribing proportion of 62.2% likely indicates over-prescribing. Akin to reports from other LMICs,27–29 we found antibiotic prescriptions for AURTI, acute watery diarrhoea and malaria, which to a large extent may be unnecessary.26 Antibiotic prescribing for other commonly reported conditions, such as skin infections and non-specific bacterial infections was also significant but were less straightforward to appraise. Such generic diagnoses are likely a result of diagnostic uncertainty, considering the limited diagnostic capacity of the study healthcare facilities. Yet, assuming all patients in our study with reported pneumonia, dysentery, skin infections and non-specific bacterial infections required antibiotics for each condition separately, the total prevalence of these conditions (22.6%) would still be well-below the antibiotic prescribing proportion of 62.2%.Antibiotic prescribing proportions of 60.1% and 62.7% have been reported on average for under-five outpatients across LMICs, including Uganda.30 negative malaria tests significantly increased the odds of antibiotic prescribing. Limited diagnostic capacity for non-malarial fevers remains a major driver of inappropriate antibiotic prescribing in malaria-endemic settings such as Uganda.31 Thus, improving the differential diagnostic capacity with microbiology and/or biomarker point-of-care tests for non-malarial fevers at these levels of care could contribute to a reduction in inappropriate antibiotic prescribing.Diagnostic test availability was uneven within and between healthcare facility levels, with mRDTs being most commonly available. Similar to reports from other studies,17 And, while amoxicillin is the first-line treatment recommended for most uncomplicated bacterial infections in Uganda, co-trimoxazole is not indicated in the management of any of the conditions reported in this study (its main indication among under-five children in the UCG is as prophylaxis against opportunistic infections in children with HIV).26 Yet, co-trimoxazole was the second-most-prescribed antibiotic, accounting for 14.7% of all antibiotic prescriptions. Similarly, ampicillin/cloxacillin, the fifth most commonly distributed antibiotic by the NMS in 2019,17 was the most commonly prescribed uncategorized antibiotic in this study, despite having no indication in the national guidelines. The prevalent use of co-trimoxazole and ampicillin/cloxacillin despite their lack of indication is likely a pointer to the inadequate access to effective antibiotics in East-Africa that has been characterized by other authors.32The antibiotic prescribing patterns observed in this study may be more linked to availability than appropriate indication. For example, amoxicillin and co-trimoxazole, the most commonly prescribed antibiotics in the current study were also the top two antibiotics supplied across public secondary and tertiary healthcare facilities nationwide in 2019 by Uganda’s National Medical Stores (NMS).Almost all (96.5%) of the febrile under-five outpatients aged 2–59 months with non-severe pneumonia received an antibiotic prescription. Yet, only 72.0% were prescribed the correct antibiotic (amoxicillin), and more so, only 9.2% received an amoxicillin prescription at the correct dose for the appropriate duration as indicated in the national guidelines. Similarly, although all children with diagnoses of severe pneumonia and dysentery (conditions which necessitate antibiotic treatment) received antibiotics, the choice and combinations of antibiotics prescribed varied—in most cases not in accordance with guidelines. These findings indicate that beyond promoting adequate access to antibiotics where indicated, additional efforts are needed to encourage adherence to national guidelines to ensure their appropriate prescribing.10 We identified that health centre level and ownership were important contextual determinants of antibiotic prescribing. Our finding that antibiotic prescribing was significantly greater at all levels above HC-II is reasonable. HC-II facilities receive fewer antibiotic supplies, since they generally manage less-complicated cases than the higher-level facilities, most of which would not require antibiotics. Finally, in line with our findings, other studies have also shown higher antibiotic prescribing in private facilities,33 where revenue is often directly related to patient volume and medicine sales.We found that 22% of the variation in antibiotic prescribing was attributed to determinants at healthcare facility level, after adjusting for patient-level variables. Our results support findings from qualitative studies indicating that, beyond patient and prescriber characteristics, prescribing behaviour is often shaped by contextual factors.First, this study relied on outpatient registers for data on treatment practices for febrile under-five outpatients. Thus, the study was limited to collected data, and could have been compromised by incomplete or missing data. However, our analysis did not expose any systematic bias attributable to records that were not available at data collection. Second, important data on prescriptions such as dose, interval and duration that were not captured in full for some of the cases made it impossible to determine whether or not patients were prescribed the correct regimen for some of the diagnoses. Third, our determination of patient-to-prescriber ratio was not based on a direct measure of patient load per-prescriber, but represented average patient load at the healthcare facilities and thus could have dampened the effect of this determinant. Future studies could use more direct measures of patient load per shift for each prescriber. Finally, while the analytical statistics took into account the survey and cluster structure of the data by using the mixed-effect approach, the descriptive statistics did not apply weights to account for unequal probabilities of selection due to different client volumes at sampled facilities. Despite the large sample and high response rate, which should reduce the selection bias, we have taken extra caution when interpreting the descriptive findings from this study.We demonstrate a high antibiotic prescribing prevalence among febrile under-five outpatients attending primary and secondary healthcare facilities in Bugisu, Eastern Uganda, including the prescribing of co-trimoxazole and ampicillin/cloxacillin, which are not indicated in the management of the common causes of febrile illness in under-five children in Uganda. These prescribing patterns may be linked to limited diagnostic capacity and antibiotic availability at study facilities. Our study results also provide quantitative evidence that health centre level and ownership are significant contextual determinants of antibiotic prescribing for children in Uganda. There is a need to prioritize access to effective antibiotics and essential diagnostics in interventions aimed at optimizing antibiotic use among febrile under-five outpatients. Future interventions will benefit from qualitative research into coping strategies adopted by care-seekers and healthcare workers in such highly resource-constrained settings.dlac091_Supplementary_DataClick here for additional data file.


The study results show that the usage of 15% CBA and 10% WGS as a cementitious additive and cement replacement has the potential to increase the strength of concrete significantly.Structural materials sustainability is gaining popularity across the globe at present. Reusing natural resources, building, demolition debris, and solid waste are the most apparent tools to make construction more environmentally friendly. Traditional concrete is believed to be less durable, stronger, environmentally friendly, and socially and commercially feasible than industrial waste concrete. The evolution of non-destructive testing (NDT) across time has not been investigated in depth by researchers. An experimental study was carried out to propose the use of non-destructive mechanisms that would enable us to assess concrete’s compressive strength without causing destruction. Varying quantities of industrial waste  and waste glass sludge (WGS)) were incorporated to cast concrete prisms (150 mm × 150 mm × 150 mm). The results obtained helped us to establish relationships between the compressive strength of concrete and the Schmidt hammer rebound value, as well as the ultrasonic pulse velocities. Microstructural analysis showed that incorporating 10% of CBA and WGS improved the porosity of concrete specimens, which shows the applicability of these industrial wastes as partial cement replacements. Scanning electron microscopy (SEM) showed traces of calcium alumino-silicate hydrate (C-A-S-H), portlandite and C-S-H, which indicates the binder characteristics of CBA and WGS. The concept of the response surface approach (RSM) for optimizing cement and industrial waste substitution was validated by the polynomial work expectation. The model was statistically significant when the fluctuation of ANOVA was analyzed using a  CO2 constitutes the majority of the planet-warming greenhouse gases, accounting for 76% of the total [2 emissions. Landfilling with multiple waste products is also causing an increase in ecological contamination [Concrete is one of the most often and extensively employed building materials. Structures are built around it because of its robustness and long-term viability in retaining structures such as walls and channels. Concrete is produced from a variety of materials, including cement. In addition to these fundamentals, additional admixtures are used in the mix to give concrete its diverse qualities. The demand for cement is rising due to a rise in the demand for concrete. The following gases are released as a by-product of the manufacturing process for cement: COhe total . Differemination ,4,5, resmination .2) is released into the atmosphere due to an increase in the demand for cement. Various industrial wastes or by-products are being used in concrete as a partial substitute for cement in order to reduce the CO2 emissions from cement plants. Coal bottom ash and waste glass sludge are two of the world’s most common waste products. Using these waste products in landfills results in serious environmental problems, such as increased soil alkalinity, polluted ground or surface water and negative effects on plants and other living organisms. Aside from helping to reduce CO2 emissions, the use of these waste materials as a cement substitute will also have a positive impact on the environmental hazards posed by landfilling [Carbon dioxide gas , sometimes known as bottom ash. These plants regularly produce a large amount of CBA . The dangerous elements in CBA can travel and contaminate ground or surface water, posing a threat to plants and other living organisms when it is disposed of as landfill. Researchers began working with CBA as a partial substitute for cement, and it was revealed that the construction sector has a great deal of potential to use CBA as a cement replacement material (CRM). In addition to silica, iron and alumina, CBA contains sulfate, magnesium, calcium and other minerals ,19. Rese3 and SiO2 in the admixture all affect the material’s physical qualities. WGS has a high concentration of Al2O3 and SiO2 and large-surface-area particles. As a result, it may be reasonable to use WGS for cement in concrete to improve its mechanical properties. Concrete is subjected to a variety of tests, some destructive, some semi-destructive and some non-destructive [Due to its chemical composition, CBA is a better cement substitute. In the past, researchers have used CBA as a partial substitute for cement and obtained promising results. Waste glass sludge (WGS) is a by-product of the glass cutting and finishing process that is utilized in the industrial sector. Currently, the great majority of WGS is being disposed of in landfill, which is causing a variety of environmental problems. The particle size, surface area and the overall amount of Al2Otructive ,25.Non-destructive testing (NDT) is primarily concerned with determining the quality and long-term performance of a concrete construction. A number of countries have embraced non-destructive testing (NDT)  since itThis method can also be used to identify concrete flaws. The UPV method makes it possible to continuously analyze concrete’s conditions throughout its useful life. Non-destructive testing methods include the rebound hammer test. During the test, the tester’s plunger retracts against a spring, and this spring is mechanically released when it is fully tensioned, which causes the hammer mass to contact the concrete. Members and concrete qualities  all play a role ,32.There are numerous research studies on the relationship between the number of rebounders and the concrete compressive strength. Concrete including industrial waste, on the other hand, displays unity in that there is no clear relationship between the two. According to the findings of this investigation, there are numerous advantages to using non-destructive testing (NDT) methods for concrete structures, such as the fact that no structural component is damaged during NDT, and NDT procedures are less time-consuming than destructive testing techniques . ResearcUnlike previous research, our study adds to the literature by investigating different results using the RSM technique. Different industrial wastes, such as CBA and WGS, which pose a threat to the global environment, are incorporated to minimize the usage of cement. Test results are evaluated using both destructive and non-destructive techniques. Moreover, a microstructural analysis was carried out to study the C-S-H, portlandite and other cementitious properties of CBA and WGS.In order to carry out a series of laboratory tests on a specimen, the tests for determining the physical properties of the aggregates and binders to be employed, the workability of the fresh mixes , compressive tests and non-destructive testing on the hardened mixes (rebound hammer and UPV) are required. Specific gravity and density are also considered in early testing. The current ASTM requirements were followed in the preparation of the concrete mix, preliminary testing of the material and the casting and testing of prism samples. The chemical properties of the cement, CBA and WGS are shown in Ordinary Portland cement was used in this experimental campaign. The chemical composition of cement is shown in Concrete constituents were mixed in a rotating pan-type mixer for approximately ten minutes at an average speed of 32 rpm, until uniformity was attained in the concrete matrix. A steel prism of 150 mm breadth, 150 mm length and 150 mm height, and prisms of 400 mm length and 100 mm cross-section, were filled with fresh concrete in approximately three equal strata and thoroughly compacted through a vibrating table. Mixing and casting were performed in accordance with the recommendations provided in ACI 211.1. Calculation for the concrete mix design was performed, and initially a mix proportion of 1: 1.22: 2.7 was selected by considering the properties of the coarse and fine aggregates. The aggregate was ordered in a large quantity with the factor of safety applied, and the amount calculated from the mix design was well below this limit. The reason for ordering a larger quantity of material initially was that we wished to purchase the material from the same batch so that the properties were consistent. A trial mix was prepared for the slump test (ASTM C 143). The target slump was 75–100 mm, but the trial mix yielded a slump greater than 150 mm. Concrete was produced by combining CBA fume, WGS, cement, water and fine and coarse aggregates along superplasticizer. Cement was tested using 43-grade ordinary Portland cement. With the use of the design of experiments (DOE) methodology and the Design Expert software, the percentage of WGS in the modified high-volume CBA concrete was determined. According to the RSM study, the percentage of CBA varied from 0% to 20%, while the percentage of WGS varied from 0% to 20%. The workability of concrete was assessed using the slump test, while the mechanical properties  were examined using only one test on fresh concrete specimens. These tests were carried out in accordance with ASTM C192/C 192 M-06. The size of the prisms used was 150 mm × 150 mm × 150 mm; in addition to ordinary concrete and CBA and WGS concrete, the samples were cast. The response surface method (RSM) is a quantifiable means of creating mathematical models that show one or more responses within a series of input variables . The RSMUsing both destructive and non-destructive methods, laboratory experiments were conducted on the strength and modulus of elasticity indexes of concrete. NDT and the standard compressive and modulus of elasticity tests on the same concrete specimens must be shown to be related. In the previous section, a detailed explanation of the concrete mix was presented.Concrete containing varied percentages of coal bottom ash and waste glass sludge at different ages is depicted in Using ultrasonic pulse velocity equipment, we also measured the ultrasonic pulse velocity of concrete with different dosages of CBA and WGS. A minimal influence of CBA and WGS may be seen in the UPV results at 28 and 90 days after the casting of all types of concrete. At 90 days, there was a minor increase in UPV due to the addition of coal bottom ash, but at all ages, there was a decrease due to the addition of 15 percent CBA and WGS. The porosity of concrete is a major factor in the development of UPV. UPV increases as the concrete hardens due to the decrease in porosity caused by an increase in density ,38.When CBA and WGS are incorporated into concrete, their smaller particle sizes reduce the porosity, raising the UPV of the final product. Cement content decreases with the addition of CBA and WGS, resulting in less CSH gel and less dense concrete, which is why the UPV decreases with 15% substitution of these components, as shown in The results of the rebound number are represented in The rebound number results are depicted in p values less than 0.05 are considered essential. The effect of three independent variables, a combination of 10% CR (B), 15% SF and 10% FA, on concrete strength was investigated (A). Analysis of variance was used to establish the model’s significance (ANOVA). The coefficient of determination, often known as R-squared (R2), of the model should be near 0.88 to demonstrate its reliability. The adjusted R2 and projected R2 have a variance of less than 0.2. This suggests that the modified R2 and the projected R2 are reasonably consistent. The signal-to-noise ratio measurement is also a minimum requirement for optimal (Adeq) accuracy. All models can navigate the design space, as shown in The impact of the interaction of two factors, silica fume and rubber particles, on the mechanical strength was modeled using the response surface methodology (RSM). When all of the data from the first mixture were effectively acquired, 13 different mixture designs were developed based on the first RSM mixture design and re-entered into the RSM to verify their efficacy, which offered the final model, shown in By examining the WGS SEM images in Traces of needle-like ettringite content can be clearly observed in the SEM images in Porosity analysis can be performed using the Image J software ,40. In tThis investigation included two phases, the first of which involved the use of destructive and non-destructive mechanisms to assess the concrete strength of prisms. Hammer and ultrasonic pulse velocity testing showed validity of the correlations.The following conclusions were made after the experimental and analytical discussions.The maximum increase in compressive strength was observed with 10% CBA and WGS addition after 28 days, and this can be considered the optimum dosage of coal bottom ash for normal-strength concrete.Design Expert software was also used to assess the samples at all ages, and a similar trend was observed as that of compressive strength. RSM was also validated for the prediction of compressive strength at different ages; however, approximately 15% higher experimental values were observed at the age of 90 days.Relationships such as ultrasonic pulse velocity–compressive strength, rebound number–compressive strength and dynamic modulus of elasticity–static modulus of elasticity were proposed in this work for all percentages  of CBA and WGS.The combined use of pundit and rebound hammer as non-destructive test methods for the assessment of both early-age and aging concrete gave more desirable results than each method used in isolation.General relationships were also proposed for CBA- and WGS-incorporated concrete for strengths ranging from 20 MPa to 46 MPa. The coefficients of determination for these relationships were found to be less than 90% , which was due to the larger number of variables used to obtain these relationships.p value less than 0.05. An equation was proposed to relate the compressive strength of CBA and WGS concrete. The RSM model and the equations utilized to calculate CBA and WGS concrete’s compressive strength were accurate. The prediction model results validated the experimental data, revealing a slight variance.To determine whether the predictive models were statistically significant, we utilized a two-way ANOVA with a significance criterion of a Based on the results of this research and previous research, the utilization of coal bottom ash and waste glass sludge as partial substitutions for cement in concrete is highly recommended as they do not only provide improved mechanical properties but also offer suitable solutions to achieve sustainable and environmentally friendly processes.The research findings in this work demonstrate that ultrasonic pulse velocity appears more reliable in predicting the possible compressive strength of concrete, especially for aging concrete, which is the major focus of structural health monitoring in concrete structures. However, the results should be taken with caution and confirmed with proven reliable calibration(s). The results show that pundit values offer higher statistical confidence than the rebound number. Based on the results, one may recommend that coal bottom ash and waste glass sludge can effectively be utilized as partial substitution for cement.


In the present study, we explored computational simulations through bioinformatics analysis and identified the overexpression of c-Met/GSK3β/MYC/CCND1 oncogenic signatures that were associated with cancer progression, drug resistance, metastasis, and poor clinical outcomes in CRC. We further demonstrated the anticancer activities of our newly synthesized quinoline-derived compound, NSC772864, against panels of the National Cancer Institute’s human CRC cell lines. The compound exhibited cytotoxic activities against various CRC cell lines. Using target prediction tools, we found that c-Met/GSK3β/MYC/CCND1 were target genes for the NSC772864 compound. Subsequently, we performed in silico molecular docking to investigate protein–ligand interactions and discovered that NSC772864 exhibited higher binding affinities with these oncogenes compared to FDA-approved drugs. These findings strongly suggest that NSC772864 is a novel and potential antiCRC agent.Colorectal cancer (CRC) is one of the most prevalent malignant tumors, and it contributes to high numbers of deaths globally. Although advances in understanding CRC molecular mechanisms have shed significant light on its pathogenicity, current treatment options, including combined chemotherapy and molecular-targeted agents, are still limited due to resistance, with almost 25% of patients developing distant metastasis. Therefore, identifying novel biomarkers for early diagnosis is crucial, as they will also influence strategies for new targeted therapies. The proto-oncogene,  Althooncogene . The dystastasis ,17,18,19outcomes ,21,22.c-Met promotes resistance to cetuximab [c-Met-dependent and -independent signaling contributes to Met receptor-mediated cell cycle progression [c-MYC, which was shown to be associated with CRC progression through the c-Met signaling pathway [c-MYC proto-oncogene is a transcription factor that modulates the cell cycle, proliferation, and apoptosis. Additionally [c-MYC was shown to enhance the expression of cyclin D1 (CCND1) through activating beta-catenin [CCND1 is a crucial regulator of cell progression through the G1 to S phases of the cell cycle via binding to cyclin-dependent kinase 4 (CDK4) and CDK6 [Moreover, recent reports demonstrated that when activated in CRC patients, etuximab . Therefogression . The c-Mgression ,25. The gression . Severalgression ,28. It hgression ,30. Glycgression , thus magression ,32,33. C pathway . Accumul pathway . The c-Mtionally ,37, whentionally ,42,43,44-catenin , thus pr-catenin . CCND1 iand CDK6 .CCND1 overexpression is linked to poor prognoses in CRC patients [c-Met/GSK3β/MYC/CCND1 were among the top 25 differentially expressed genes (DEGs) in CRC, extracted from the GEO microarray datasets, GSE4107 and GSE41328. MicroRNAs (miRNAs) are noncoding short RNAs (21–25 nucleotides) that negatively regulate gene expression at the translational level by binding to 3′UTR (untranslated region) of their target mRNAs leading to either their degradation or translational inhibition [GSK3β/MYC/CCND1, thus suggesting a close association of Met/GSK3β/MYC/CCND1 and miR-26a promoting cancer proliferation, invasion, migration, drug resistance, and stemness metastasis in CRC patients.Studies showed that patients ,49. Theshibition ,51. The hibition . miR-26ahibition . ThroughThe search for a novel and effective cancer therapy has increased over the years due to resistance to current treatment modalities. Quinoline is a heterocyclic aromatic nitrogen compound commonly used as a parental compound to synthesize various molecules . Numerouhttps://www.ncbi.nlm.nih.gov/ 21 June 2022). We used ULCAN, a web-based tool to analyze The Cancer Genome Atlas (TCGA) level 3 RNA sequencing (RNA-Seq) and clinical data from tumor tissues compared to adjacent normal tissues [p < 0.001) were first selected and represented in a heatmap.The top overexpressed DEGs in colon adenocarcinoma (COAD) samples were retrieved from the following databases: NCBI GEO two datasets, GEO microarray datasets, and GSE4107 and GSE41328 , which compares selected genes from RNA-Seq-based data [p < 0.05 considered statistically significant. Expressions of c-Met/GSK3β/MYC/CCND1 based on individual cancer stages were analyzed by utilizing ULCAN software. Furthermore, we used GECO (https://proteinguru1.shinyapps.io/geco/ 28 June 2022), a gene expression correlation analytical tool, which differentiates two expression profiles into positive and negative correlations [p < 0.05 as statistically significant.To validate expression levels of the identified DEGs, including sed data . A compaelations , with pohttps://string-db.org/ 29 June 2022) [https://david.ncifcrf.gov/ 29 June 2022) functional annotation tool [http://www.funrich.org/ 29 June 2022), to further analyze interactions within the networks, with p < 0.05 considered significant.A protein interaction network (PIN) was analyzed using STRING, a protein–protein interaction (PPI) and functional enrichment analysis web tool (ne 2022) . We furtion tool . Moreovec-Met/GSK3β/MYC/CCND1 mutations and alterations in gene expressions, we utilized the muTarget platform (http://www.mutarget.com 06 August 2022) and web tool that link gene expression alterations and mutation statuses in cancers [http://cbioportal.org 6 August 2022), an online interactive platform for translational research that provides analysis of cancer genomic datasets [p < 0.05.To determine relationships between  cancers . We furtdatasets , to detec-Met/GSK3β/MYC/CCND1 oncogenes and drug sensitivity were determined using the GSCALite database, an online tool for Gene Set Cancer Analysis (GSCA) (http://bioinfo.life.hust.edu.cn/web/GSCALite/ 11 August 2022) [50)) of small molecules. Additionally, correlations considered statistically significant displayed a false discovery rate (F.D.R.) of <0.05.Correlations between expressions of st 2022) . The anahttps://dtp.cancer.gov/ 15 June 2022) is an online pattern recognition algorithm used to predict molecular targets based on ARRAYCGH_GRAY and detect a compound’s similarities to NCI synthetic compounds and standard agents. Herein, we used 50% growth inhibition (GI50), which is an endpoint of the IC50, and the National Safety Code (N.S.C.) number (772864) as delimiters [http://59.78.96.61/pharmmapper 14 August 2022), an integrated pharmacophore mapping platform, to identify potential drug target candidates [The Developmental Therapeutics Program (D.T.P.)-COMPARE online platform, from the NCI (limiters . Further) number 2864 as dhttp://www.swissadme.ch/ 15 June 2022), an online platform used to evaluate PKs, drug-likeness, and the medicinal chemistry friendliness of compounds [Identifying novel and potential drug candidates early in drug discovery and development is crucial, as it reduces time and costs; herein, we applied the drug-likeness concept based on specific criteria ,79. To eompounds . We analompounds . Moreoveompounds . The Abbompounds .https://dtp.cancer.gov/ 30 June 2022). The compound was tested at an initial dose of 10 μM and further tested for dose-dependent treatment. The results show that NSC772864 exhibited antiproliferative activities against several CNS cell lines [NSC772864 was submitted to the NCI Developmental Therapeutics Program (DTP) for screening for potential antiproliferative and cytotoxic effects against a panel of NCI 60 CNS cell lines, in agreement with the protocol outlined by the NCI (ll lines .c-Met (PDB:3VW8), MYC (PDB:6G6K), and cyclin D1 (PDB:2W9Z) proto-oncogenes were retrieved from the Protein Data Bank (PDB) (https://www.rcsb.org/ 26 July 2022). Furthermore, the three-dimensional (3D) structure of NSC772864 was assembled with the Avogadro molecular visualization tool [A docking analysis was performed using AutoDock Vina . Accordingly, crystal structures of the ion tool . Moreoveion tool ,87,88.c-Met/GSK3β/MYC/CCND1 expressions in CRC cancer types.The statistical significance of DEGs was evaluated using the Wilcoxon test. * p < 0.05 was accepted as being statistically significant.Pearson’s correlations were used to assess the correlations of c-Met/GSK3β/MYC/CCND1 in tumor tissues compared to normal colon tissues . A major factor for metastasis is the acquired capacity of the cell to proliferate and invade normal tissues. Herein, we investigated the role of miR-26a in regulating CRC cell proliferation and migration, through the crosstalk with upregulated Met, GSK3β, MYC, CCND1, and oncogenic signatures . We usedc-Met oncogene were first linked to changes in gene expressions in CRC at the genotypic level using the muTarget tool. Herein, high expression levels of MSANTD3 were associated with mutations on the c-Met gene compared to wild-type (WT) c-Met  tissues. Interestingly, the c-Met/GSK3β/MYC/CCND1 oncogenes were shown to be more mutated in CRC  and in microsatellite instability (MSI) and had higher numbers of mutations and amplifications in CRC tissues as shown in the bar graph (c-Met/GSK3β/MYC/CCND1 signatures (c-Met/GSK3β/MYC/CCND1 mutations in CRC across the protein domains (Mutations of the T) c-Met A. MoreovWT group B–D. In ad in CRC E,F. We car graph F. We alsgnatures G and fur domains H–J.9H7N) (and the FDA-approved multitargeted receptor tyrosine kinase (RTK) inhibitor sunitinib[(Z)-N-(2-(diethylamino) ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4 dimethyl-1H-pyrrole-3-carboxamide), which was also demonstrated to inhibit GIST [Computer-based drug discovery tools have been widely used over the years and assist in the processes of discovering novel drugs in various ways by offering many more benefits, such as reducing the screening of multiple compounds experimentally and reducing costs ,92. Thusbit GIST ,101,102,We explored the DTP-COMPARE web server, and the analytical results show that c-Met, MYC, and CCND1 are potential targets of NSC772864. The predictions were based on an ARRAYCGH_GRAY analysis, and we further compared the compound’s similarities to NCI synthetic compounds and standard agents as shown in We explored the GSCA to determine the drug sensitivity profile data of c-Met/GSK3β/MYC/CCND1 against different cancer cell lines. Herein, correlations of c-Met/GSK3β/MYC/CCND1 gene expressions and drug sensitivity were analyzed based on values of the area under the dose–response curve (AUC) for drugs and gene expression profiles for all cell lines. The expression of each gene in the gene set was analyzed using a Spearman correlation analysis of the drug sensitivity (IC50) of the small molecule against various cell lines in the Cancer Therapeutics Response Portal (CTRP) and Genomics of Drug Sensitivity (GDSC) databases. The correlation coefficients indicated that increased gene expression levels were resistant to the drug. Herein, high messenger (m) RNA expression levels of c-Met and CCND1 (as indicated by orange circles) were associated with drug resistance .To evaluate the drug-likeness, PKs, medicinal chemistry, and ADME and toxicity (ADc-Met) properties of NSC772864, we used the swissADME online platform. Accordingly, we analyzed the drug-likeness properties of the compound according to Lipinski (rule of five), Egan, Ghose, and Veber standards. Moreover, we also showed associations of PKs with physiochemical properties. In a further analysis, we used the BBB penetration properties, using the brain or intestinal estimated permeation (BOILED-Egg) model ,103, to The NSC772864 compound was submitted to the NCI DTP for screening for potential in vitro anticancer activities against a panel of NCI CRC cell lines. NSC772864 was first tested at an initial dose of 10 μM. The compound exhibited antiproliferative and cytotoxic activities against CRC cell lines as indicated by the percentage growth altered by treatment. Accordingly, the growth inhibition percentage revealed antiproliferative effects against HCC-2988 cells of 88.65% and cytotoxic activities, showing KM12 to be more sensitive with -53.42% growth inhibition followed by HCT15 (−50 38%), COLO205 (−45.69%), SW620 (−43.72%), HCT116 (−36.96%), and HT29 cells (−9.75%) A-I. BecaTo investigate the potential inhibitory effects of NSC772864, we conducted a molecular docking analysis. The results obtained from ligand–receptor complexes show unique different binding energies of NSC772864 with c-Met (ΔG = −8.0 kcal/mol, In recent years, the survival rates of CRC patients have significantly improved thanks to advancements in novel therapeutics, including surgical resection, chemoradiotherapy, and targeted therapy ,105,106.Accumulating studies have demonstrated that c-Met is a target gene of WNT/β-catenin signaling , which sIn CRC, CCND1 overexpression has yielded conflicting results, as some researchers demonstrated its role in promoting poor clinical outcomes, while others reported it as a good prognostic marker ,119,120.Moreover, we utilized the swissADME web platform and found that NSC772864 passed the drug-likeness, PK, medicinal chemistry, and ADMET criteria, as shown in We identified c-Met/GSK3β/MYC/CCND1 oncogenic signature as major players in CRC progression through the cell cycle. Our bioinformatics analysis demonstrated that these oncogenic signatures are overexpressed in CRC tissues compared to adjacent normal tissues, resulting in tumor progression, metastasis, poor prognoses, and resistance to current chemotherapies and targeted therapies. We further demonstrated the anticancer activities of our newly synthesized quercetin-derived small molecule, NSC772864, against NCI human CRC cell lines and its dose-dependent cytotoxic preference for CRC. Our target prediction analysis showed that c-Met/GSK3β/MYC/CCND1 signatures are target genes for NSC772864, and these findings were validated thought a molecular docking analysis, which showed remarkable binding energies of NSC772864 in a complex with c-Met, GSK3β, c-MYC, and CCND1. These findings create an opportunity for a novel research approach for NSC772864 as a novel and potential antiCRC agent. Further in vitro and in vivo investigations to validate the antiproliferative and cytotoxic activities of NSC772864 are ongoing.


The experimental findings showed that the 7% blended mortars performed better than the reference cement in terms of total and effective porosity, but they absorbed more pressurized water. They also exhibited lower CO2 resistance, particularly in the calcareous blend, likely due to its higher porosity. Including the binary blend of CDW enhanced chloride resistance with diffusion coefficients of 2.9 × 10−11 m2 s−1  and 1.5 × 10−11 m2 s−1  compared to the reference cement’s 4.3 × 10−11 m2 s−1. The siliceous fines-glass blend out-performed the calcareous blend in all the durability tests. As the mortars with and without CDW (construction and demolition waste) performed to similar standards overall, the former were deemed viable for the manufacture of future eco-efficient cements.In recent years, the development of ternary cements has become a priority research line for obtaining cements with a lower carbon footprint, with the goal to contribute to achieve climate neutrality by 2050. This study compared ordinary Portland cement (OPC) durability to the performance of ternary cements bearing OPC plus 7% of a 2:1 binary blend of either calcareous (Hc) or siliceous (Hs) concrete waste fines and shatterproof glass. Durability was measured further to the existing legislation for testing concrete water absorption, effective porosity, pressurized water absorption and resistance to chlorides and CO Given the vast volumes of construction and demolition waste (CDW) generated yearly, it is one of the streams of refuse presently attracting the interest of both the scientific community and the construction industry. The 900 million tonnes of CDW produced in Europe in 2015 . In respAfter processing in management plants, CDW is divided into essentially two types of inorganic waste: concrete and mixed (concrete + masonry), whose deployment has been explored for primarily three applications. These include (a) coarse recycled aggregate for concrete ,6,7, a u4AH13 and C4AcH12 gels [2O = 13%). Such microstructural changes would necessarily have a direct impact on the performance of these new ternary eco-cements.Under the third area, recent research has focused on recycled concrete fines (<5 mm), a material generated during concrete waste crushing and milling. That by-product is subsequently stockpiled in management plants, given its non-reusability due to the possible presence of very fine particles or even deleterious  materials. Preliminary research conducted by the multidisciplinary team of authors of this article showed that these fine concrete fractions have low-to-medium pozzolanicity depending on factors such as the calcareous or siliceous nature of the original aggregate, the formation of C-S-H, CH12 gels  and the H12 gels ,18,19. SH12 gels . ReactioH12 gels . In all The present study therefore proceeded to a first-ever analysis of the durability of ternary cement mortars made with 7% (2:1) concrete waste/glass blends based on their performance in terms of total water absorption, effective porosity, pressurized water penetration and carbonation and chloride resistance. The OPC used in this study, classified in Spanish legislation as CEM I 52.5R , was supThree construction and demolition wastes were analyzed: Two wastes from two fractions of fines (<5 mm) resulting from concrete waste crushing and milling were taken from two Spanish waste management plants that had stockpiled the material in open yards. Depending on the nature of the original aggregate, such fines were divided into calcareous (Hc) and siliceous (Hs). Finally, a shatterproof glass (G) with 100% amorphous material taken from a demolished residential building in northern Spain was selected. All three types of CDW were ground in the laboratory to a particle size of under 63 µm. X-ray diffraction (XRD) patterns and quantitative Rietveld analysis of the raw materials analyzed are included in The ternary eco-cements were prepared by replacing 7% of the OPC with a 2:1 (by weight) binary blend of either Hc-G or Hs-G, found in preliminary research to be the optimal proportion ,20. The 2) at a binder/sand ratio of 1:3 and a water/binder ratio of 0.5 as specified in European standard EN 196-1 [The blended cement mortars were prepared with standardized siliceous sand , as described in the Spanish/European standard UNE EN 14629 [Chloride ion resistance was established further to Spanish/European standard UE EN 12390-11  on unidiEN 14629 .The compressive strength of the mortars was determined on an IBERTEST AUTOTEST 200/20-SW press on 28-day mortar specimens, following the EN 196-1 standard .The chemical composition of the main oxides present was determined on pressed powder wafers using a Philips PW-1404  X-ray fluorescence spectrometer fitted with an Sc-Mo X-ray tube. Mineralogical analysis and crystalline phase quantification were conducted on a Malvern Panalytical X’Pert Pro  X-ray diffractometer bearing a copper anode and a 9.5 mm receiving slit, operating at 40 mA and 45 kV. The measuring range was 5–60°, with rutile as the internal standard. Rietveld quantification was calculated with Match (v.3) and Fullprof software .The dry dispersion D10, D50 and D90 values for the cements were found with a Malvern Panalytical Mastersizer 3000 laser diffraction particle size analyzer.Cement mortar morphology, analyzed after the accelerated carbonation test, was determined under an FE Inspect W-SEM/EDX electron microscope fitted with a DX4i analyzer and a Si/Li detector .The dry and bulk density values for the ternary cement and reference mortars were very similar, although slightly higher in the 7% additioned materials, in all likelihood as a result of their greater fineness, which would induce minor matrix densification . Total post-soaking (TSA) and post-soaking and boiling (TSBA) water absorption values were lower in the mortars bearing 7% CDW-based binary blends than in the reference cement material. At 17%, the reduction in water absorption relative to the reference was greater in siliceous than in calcareous concrete waste, where the decline recorded was 9.2%.−4 K·h−4; Hs: 6.6 × 10−4 K·h−4) and high reactivity glass waste (G: 1.14 × 10−2 K·h−1). The resulting synergies were more intense in the siliceous (Hs) than in the calcareous concrete (Hc) blend. The pozzolanic reaction is widely known to induce additional hydrated phases in cement matrices, substantially modifying microporosity and the paste-aggregate interfacial transition zone (ITZ) [Both blended cement mortars performed well in terms of post-soaking water absorption, with values much lower than the recommended ceiling (<10%) for high-quality cement matrices . The expne (ITZ) ,30. The ne (ITZ) .The standardized effective porosity (EP) test findings followed the same pattern as for TSA and TSBA, i.e., with the inclusion of the binary blend of pozzolans associated with declines in porosity of 5.2% in 7% Hc-G and 8.7% in 7% Hs-G relative to the reference mortar. As with total absorption, higher blended mortar performance in effective porosity was attendant upon the formation of secondary hydrated phases during the pozzolanic reaction. Vigil et al.  reportedIn terms of mechanical properties, the 28-day compressive strength values shown in The penetration depths for the three mortars analyzed are summarized in Further to the provisions of Spain’s Royal Decree on bulk and reinforced concrete  , the mor2) and spraying with phenolphthalein are reproduced in Photographs of the mortar specimens after the accelerated carbonation test  further to the following reaction: Two clearly distinguishable areas were detected: the reddish-purple zone denoted pH values of over 10, an indication that the cement matrix was unaffected by the CO2 and carbonate ion formation; and (c) chemical reaction and carbonate precipitation [However, other calcareous hydrates as well as anhydrous phases may have also been impacted by carbonation . Portlanpitation . The SEMThe mean of the carbonation front depths measured on the two sides of each of the three specimens tested are given in 2 and calcium carbonate solubility due to the rise in the alkali content in the cement matrix prompted by the presence of glass [After a 72-d exposure to 3% accelerated carbonation the mortars prepared with a binary blend of pozzolans exhibited lower carbonation resistance than the reference material, with 37.5% (7% Hc-G) and 15% (7% Hs-G) deeper carbonation fronts. The calcareous blend, in turn (Hc-G), was nearly 20% less resistant than the siliceous material (Hs-G). That may have primarily been the result of the higher effective porosity in the former , which wof glass .2 and thus the progression of the carbonation front to deeper levels. In this study, a third factor may have had a further adverse impact on carbonation rate, attributable to the presence in the bended cements of recycled glass, known to have a high sodium content (recycled glass = 13% Na2O). Some authors have observed that alkalis favor carbonation [Such poorer chemical resistance to carbonation in the blended cements would be associated with their lower portlandite content attributable to dilution (7% less clinker) and the pozzolanic reaction characteristic of CDW ,35. Bothbonation , an advebonation ,37,38,39The effect of the pozzolans on chloride ion transport was quantified by calculating the non-steady state diffusion coefficient (Dnss) for each mortar type. The experimental curves for chloride were subsequently fitted to Equation (2) in keeping with Fick’s law of diffusion as specified in Spanish/European standard UNE EN 12390-11 :(2)Cx=CixC is chloride ion concentration at depth x at time t; iC and sC, respectively, are initial chloride content and the content on the exposed surface; and erf represents the error function. The fitted curves are plotted in In Equation (2), 4Al2(CO3)·11H2O and Ca4Al2(CO3)0.5·12H2O) [4Al2Cl2·10H2O), thereby immobilizing these ions in the outer layers and explaining the behavior of 7% Hc-G mortars in this regard [As noted in 5·12H2O) . Such sus regard ,50,51. Is regard ,52. Thats regard .The conclusions that can be drawn from the present study are set out below.➢When added to OPC at a replacement ratio of 7%, binary CDW mortars bearing a 2:1 (by cement weight) blend of calcareous or siliceous concrete fines and shatterproof glass performed differently relative to the reference cement depending on whether the recycled concrete was calcareous (Hc) or siliceous (Hs).➢The presence of CDW in the blended mortars lowered water absorption by 9.2% to 17%, depending on the nature of the recycled aggregate. ➢The same pattern was observed for effective porosity, which was 5.2% lower than the reference in 7% Hc-G and 8.7% lower in 7% Hs-G.➢Although the maximum and mean penetration depths were greater in the blended cement mortars than in the reference mix, the former were Spanish structural code-compliant.➢2) showed that adding 7% of the binary blend of CDW led to slightly higher (1–3 mm) mean carbonation penetration than in the unadditioned reference. The accelerated carbonation test  samples performed better than their calcareous counterparts. The diffusion coefficients obtained by applying Fick’s law were 2.9 × 10The present findings support the premise that replacing OPC with a 2:1 binary blend of concrete fines (<5 mm) and shatterproof glass at a ratio of 7% does not compromise the durability of the resulting mortar. In fact, for most of the properties analyzed such mortars performed better than the reference material. These recycled products would consequently be usable to prepare future cement matrices with a lower clinker content and smaller carbon footprint. Such a promising future notwithstanding, further research would be recommended, primarily to test performance at higher replacement ratios than explored here.