The PN-EN 197-1:2012 standard allows the use of additives as the main component above 5.0% by mass, as well as as a secondary component in an amount less than 5.0% by mass of cement. Proper selection of additives positively affects the rheological characteristics and hardened concrete parameters during longer maturity periods. Additives have already become an integral component of concrete mixes. The aim of the research is to confirm the possibility of using the tested additive in the composition of concrete mixes in an amount of 15% relative to the amount of cement, which would solve the problem of storing and utilizing waste generated during the production of broken chalcedonite aggregates. The planned laboratory tests were carried out for concrete of three classes, C30/37, C35/45, C40/50, according to the PN-EN 206+A1:2016-2 standard, with the addition of chalcedonite dust in a constant amount of 15% relative to cement, and three series without additives as control series. The additive used for concrete mixes was chalcedonite dust with a diameter below 72 μm. It is waste from a broken aggregate mine. The research program included rheological tests of fresh concrete mix, i.e., air content, consistency, bulk density, as well as parameters of hardened concrete mix—compressive strength, absorbability, and capillary uptake. Compressive strength was tested after 7, 14, 28, 56, and 90 days. The laboratory tests aimed to verify whether the addition of 15% chalcedonite dust additive would not worsen the predicted hardened concrete parameters resulting from the designed concrete classes. All three tested series, C30/37, C35/45, and C40/50, with the addition of 15% chalcedonite dust relative to the amount of cement, achieved the assumed strength classes after 28 days of maturation. Concrete mix components were correctly designed. The addition of chalcedonite dust to the concrete mix did not cause a decrease in compressive strength to the extent that the analyzed series did not meet the normative requirements for concrete classes according to the PN-EN 206+A1:2014 standard. The results of absorbability testing indicate water absorption below 5%, while the increase in sample mass in the capillary uptake test gained similar values. The PN-EN 206+A2:2021-08 standard “Concrete—Requirements, properties, production and conformity” defines an additive as a component of concrete that is highly fragmented ,4,5. TheType II additives are pozzolanic or weakly hydraulic additives ,12. PozzThe coefficient k concept;The equivalent performance concept;The equivalent performance combination concept.Type II additives can be included in the concrete mixture as part of the cement content and the water/cement ratio. The PN-EN 206 standard specifies three concepts for incorporating Type II additives into the concrete mixture:The principle of using the k-factor concept mainly involves comparing the compressive strength of concrete without additives, i.e., the reference concrete, with the concrete in which part of the cement has been replaced with a selected additive. The comparative criterion is durability and/or compressive strength. The k-factor concept allows for the use of type II additives with aminimal amount of cement in a given exposure class and the replacement of the w/c factor with the water/(cement + k* additive) ratio ,21,22.The concept of equivalent functional properties of concrete is based on the assumption that the properties of the concrete modified with an additive correspond to the properties of the reference concrete. The assumption can be met if we use cement that complies with the requirements of the PN-EN 197-1:2012 standard and also maintains the minimum amount of cement and the maximum w/c ratio in a given exposure class.The concept of combining equivalent functional properties is based on the assumption of the minimum amount of cement and the maximum w/c factor in a given exposure class. The use of type II additives in concrete mixes is possible only for additives with defined suitability whose origin and characteristics are known, ,23,24.Additives used in concrete should meet normative requirements and be used in accordance with the standards. Proper use of additives can improve the rheological properties of the concrete mix and the parameters of the hardened concrete, as well as allow the utilization of waste material heaps ,26,27. OMicronized chalcedonite is a product that contains respirable quartz. It is classified as STOT REI according to the criteria set out in Regulation (EC) No. 1272/2008. Depending on the atmospheric conditions and storage methods, the dust containing free crystalline silica can be suspended in the air. The respirable fraction of chalcedonite dust, when inhaled by humans for a prolonged period, can cause upper respiratory tract inflammation;in a drastic situation of repeated respiratory diseases over several years, it can lead to diffuse nodular fibrosis of lung tissue, commonly called silicosis. The main symptoms of silicosis in humans are persistent coughing, difficulty breathing, pulmonary insufficiency, and worsening apnea. Inhalation of crystalline silica dust should be prohibited. The dust should be handled with extreme caution to avoid inhalation .2, with the EC number 238-878-4. It also contains trace amounts of aluminosilicates and metal compounds, as well as quartz, opal, iron hydroxides, pyrite, manganese compounds, and clay minerals. From a chemical point of view, chalcedonite is a homogeneous material composed of about 94% silica by weight. Utilizing billions of tons of waste material fits into the protection of the natural environment [Therefore, a significant challenge is the problem of utilizing waste materials generated during the production of crushed stone in Poland. This is about chalcedonite dust, whose main component is SiOironment ,29. Usinironment ,31,32.The studies carried out so far indicate that the introduction of 20% of chalcedonite dust into the concrete mix results in a decrease in compressive strength after 28 days by up to 15%. Replacing the cement with a 15% chalcedonite additive reduces the strength after 28 days of curing by 10%. Reducing the addition to 5% in the concrete mix does not reduce the compressive strength.2 after 28 days of curing.The addition of 20% chalcedonite dust in the capillary rise test results in weight gain after 28 days of maturation by up to 54%. In the capillary rise test, it can be seen that the weight gain is comparable for the tested series, in which the additive was used in the amount of 5% and 10% and was about 37 kg/mOn the other hand, water absorption after 90 days of maturation with 20% of chalcedonite dust is lower by about 11% compared to the series of concretes without the addition. Absorption after 28 days of maturation is lower by about 20% for the series with 15% chalcedonite addition in relation to the series of concretes without the addition. The use of chalcedonite powder in concrete mixes seals the cement matrix.It is recommended to extend the curing time of concrete because time has a positive effect on the parameters of compressive strength, capillary rise, and water absorption.The aim of the laboratory research was to determine the influence of chalcedonite dust on the properties of concrete mixtures and the parameters of hardened concrete ,32,33,34Currently, legal regulations and instructions do not provide guidelines on the amount of this additive that can be used. There is also no answer to the question of which rheological characteristics the use of chalcedonite dust in concrete mixtures improves or worsens. The article particularly focused on estimating the compressive strength of concretes with the addition of chalcedonite dust in three classes C30/37, C35/45, and C40/50, compared to concretes without this additive ,37,38. IThe aim of the laboratory research was to determine the parameters of three concrete mixes of class C30/37 (series 1), C35/45 (series 2), C40/50 (series 3) with the addition of chalcedonite dust, as well as three series without the addition of chalcedonite dust, C30/37 (series 1SW), C35/45 (series 2SW), C40/50 (series 3SW). Compressive strength, water absorption, and capillary suction were tested . Mix desThe chalcedonite dust used in laboratory tests is a waste material generated during the crushing of chalcedonite aggregate in the mine. It has the same mineral  composition as the aggregate it comes from. It has a negative impact on human health and can cause respiratory diseases . The dusThe particle size of chalcedonite meal was measured by laser diffractometer.The particle size distribution of the dust was established based on laboratory tests. The share of particles with a size up to 2 µm is 17.5%. In the range of 2 to 10 µm, it constitutes 22.5%. The largest share belongs to particles with a size of 10 to 40 µm, which is 42.5%. Moreover, 99% of the particles do not exceed a size of 72 µm .Laboratory tests were performed in accordance with the composition in Laboratory tests were conducted using Portland cement CEM I 42.5R  and a coDolomite aggregate with fractions of 2/8 and 8/16 was used in the tests. It is a broken aggregate, and its main components are calcium and magnesium carbonate. The aggregate was used in accordance with PN-EN 12,620 “Aggregates for concrete” standard .Tap water was used to prepare the planned concrete mixes in accordance with PN-EN 1008:2004 standard .ISOLA BV plasticizing admixture was used, which is suitable for the production of monolithic, water-resistant, hydrotechnical concrete, as well as concrete exposed to chemical aggression. The action of this admixture improves the workability of the concrete mix at the same w/c ratio, does not affect the cement setting time, reduces water demand, and also increases the early strength of the concrete. The admixture should be used in an amount of 0.2 to 1.4% by weight of cement, depending on the expected plasticizing effect. The admixture was dosed directly into the mixer before adding the mixing water.®-4 WT  Concentrate admixture was used as a sealing admixture. It is an admixture with sealing and hydrophobic properties designed for ordinary and special concrete. It improves workability during compaction, water resistance, absorption, and capillary water absorption. The dosing rate is 0.1%–0.5% by cement mass, depending on the desired effect. In the tests, the admixture was added to the mixing water.SikaControlISOLA LP A.E.A. 2.5 air-entraining admixture was used. It is used for the production of concrete exposed to changing atmospheric conditions and also increases the resistance to frost and de-icing agents. It was dosed into the wet components of the concrete mix ,29.The components of the concrete mix were mixed in the following order: coarse and fine aggregate with sand, then cement with the addition of chalcedonite dust, and finally, water was added. The plasticizing admixture was added to the dry ingredients before adding the mixing water, while the sealing admixture was added to the moist ingredients halfway through the addition of tap water.The compressive strength was tested according to the standard PN-EN 206-1:2014 . Cubic sSamples for testing water absorption were stored for 7 days in water at a temperature of +18 °C and then matured in air at a temperature of +18 °C. The samples were dried to a constant weight for 72 h in a climatic chamber. Then, the samples were placed in water up to half their height for one day. After this time, the water was filled up to +1cm above the sample height. The mass gain of the samples was measured every 24 h until two identical measurements were obtained .The capillary rise was performed on samples with dimensions of 10 × 10 × 10 cm in accordance with standard PN-88/B-06250 . The samRheological tests of the fresh concrete mix were performed. The volumetric density, consistency of the concrete mix using the cone drop method, and the air content in the concrete mixes were examined . The conThe compressive strength gain chart shows that series 3 (C40/50) exhibits the highest compressive strength. Compared to series 1, the strength gain is 33.3% higher after 28 days of maturation and 28.6% higher after 90 days of maturation. From the analysis of All obtained compressive strength results .In After determining the mutual dependencies from any class of concrete C30/35, C35/37, and C40/50, instead of specifying individual parameters, one can determine one characteristic of hardened concrete and estimate the remaining ones based on the equation. This is a faster and less laborious process than conducting individual laboratory tests.The examination of the concrete microstructure for the C35/45 series with chalcedony dust, conducted with a scanning electron microscope, showed that the additive was active in hydration. Confirmation should be sought in the lack of clear boundaries between the dust and the C-S-H fraction . The addAfter laboratory tests of concretes of class C30/37 (series 1), C35/45 (series 2), C40/50 (series 3) with the addition of chalcedonite dust, and three series without the addition of chalcedonite dust C30/37 (series 1SW), C35/45 (2SW series), C40/50 (3SW series) it should be stated that the problem raised in the article—will the compressive strength after 28 days be high enough to qualify the given concretes to the designed classes? The article checks the class of concrete according to PN-EN 206+A1: 2016 for the series with the addition of dust. The conditions were met, despite obtaining a decrease in compressive strength of about 10% on average compared to the series without this additive. In the literature, the researchers published the results of compressive strength after 28 days of maturation, where a decrease in compressive strength was noted, depending on the amount of chalcedonite dust added. For 5% of the added additive, the strength is maintained. The addition of 20% of dust in relation to the mass of cement causes a decrease in compressive strength by 15%, and 15% of dust is a decrease of 10%. When designing the research for this article, we assumed that if we wanted to maintain the assumed classes of concrete, we could not add more than 15% of the dust in relation to cement. After analyzing the literature and carrying out the previous tests, it can be concluded that chalcedonite dust does not have full pozzolanic properties. The additive, which is distinguished by pozzolanic properties, is added in the amount of 20% of the cement mass, and the concrete does not experience a decrease in strength. The second aspect taken into account in the article was the problem of managing heaps of tailings in the mine. The possibility of its use in concrete mixes was checked. The answer is yes, only under the condition of replacing cement up to a maximum amount of 15% of its weight. After exceeding this amount, there will be a decrease in compressive strength even after a long curing time of 56 or 90 days. You can expect a lower strength class and, thus, different use of the designed concrete.The addition of chalcedonite dust reduces the weight gain of samples in contact with water in the water absorption test. A significant decrease in mass gain can be observed in the case of concrete with the addition of 15% chalcedonite dust;this decrease is 21% compared to the reference concrete. Concrete with 10% of chalcedonite dust reduces the weight gain of concrete by about 11%. The use of chalcedonite dust in concrete mixes seals the cement matrix.2 after 28 days of maturation. The differences are not too big;it is due to the fact that dust has a positive effect on concrete, making it more airtight.In the capillary rise test, it can be seen that the weight gain is comparable tothe tested series, in which chalcedonite dust was used in the amount of 15%. From the literature, we learn that by adding dust in the amount of 5%, 10%, and 15%, the weight gain is about 35–40 kg/mConsidering economic and environmental factors, it is advisable to use an additive to concrete in the form of chalcedonite dust in the amount of up to 15%. The use of chalcedonite dust as an additive to concrete could help solve the problem of storage and management of waste from the production of chalcedonite aggregates. This value of 15% is the maximum value that can be added to concrete without impairing its parameters to such an extent that the concrete will then be classified as a class lower than the designed one.Compressive strength: after 28 days of maturation, all three tested series of C30/37 (labeled as 1SW), C35/45 (labeled as 2SW), and C40/50 (labeled as 3SW) with the addition of chalcedonite dust achieved the assumed strength classes. The components of concrete mixtures were correctly designed. The addition of chalcedonite dust to the concrete mixture did not result in a decrease in compressive strength to such an extent that the analyzed series did not meet the normative requirements regarding concrete classes according to PN-EN 206+A1:2014, . CompariWater absorption: the obtained results indicate water absorption below 5%. This means that the concretes made in laboratory conditions  are characterized by water absorption not exceeding 5% for series C30/37 (1SW), C35/45 (2SW), C40/50 (3SW) with the addition of chalcedonite dust.Capillary absorption: the C30/35 (1SW), C35/37 (2SW), and C40/50 (3SW) concrete classes, with the addition of chalcedonite dust, achieved similar values.Dependencies of compressive strength on water absorption or capillary absorption, as well as water absorption on capillary absorption, were developed for the three tested concrete classes C30/37 (1SW), C35/45 (2SW), C40/50 (3SW) with the addition of chalcedonite dust after 28 days of maturation.Based on the obtained laboratory test results, chalcedonite dust can be used as an additive to concrete in an amount of 15% of the cement mass. The use of chalcedonite dust as an additive to concrete could help solve the problem of storing and managing waste from chalcedonite aggregate production in Poland.Consideration should be given to attempting to develop general guidelines for the use of this additive in concrete mixtures in order to manage billions of tons of waste from broken chalcedonite aggregate mines. Disposing of waste in this way could help people protect their health from the adverse effects of inhaling airborne dust.The results of the study provide the basis for the following conclusions:


Based on a series of experiments, this paper systematically studies and compares the workability, mechanical properties, and durability of two kinds of concrete with the river sand in the Santo Tomas River area and natural river sand in Beijing, China as fine aggregates, respectively. In addition, volcanogenic sand in the Philippines is technically optimized for the purpose of in-depth study. After optimization, such sand reaches the standard of Zone II-graded medium sand and is comprehensively improved in performance, which is evidenced by a fineness modulus of 2.4, an apparent density of 2570 kg/m3, a bulk density of 1550 kg/m3, a light-matter content of 6.0%, and a mud content of 6.7%. Study results show that in terms of mechanical properties, the concrete made of the optimized river sand in the Santo Tomas River area is superior to that made from the natural river sand in the Beijing area. In addition, separated light matter can be used as a natural light aggregate, which has a bulk density of 960 kg/m3, a cylindrical compressive strength of 2.5 MPa, and a 1 h water absorption of 8.2%, respectively.The river sand in the Santo Tomas River area of the Philippines is a kind of volcanogenic sand. The sand is fine sand with a fineness modulus of 2.2, an apparent density of 2380 kg/m As raw materials, sand and gravel are most frequently used for global infrastructure construction. At present, 40–50 billion tons of sand and gravel are needed globally . Due to As an important river channel in the Philippines, the Santo Tomas River, which is home to the Pinatubo Volcano, is located in central Luzon and adjoins the South China Sea in the west. In 1991, the Pinatubo Volcano erupted and produced a large amount of lava. The lava covered the original riverbed and was mixed with the river sand, thus making the natural river sand there the riverbed’s unique geographical characteristics ,7. This The cementitious materials used in this paper consist of cement, fly ash, and slag powder with a mass ratio of 3:1:1. P·O 42.5 ordinary Portland cement was used for the test in accordance with GB 175-2007 Common Portland Cement, which has a standard consistency water consumption of 27.8%, an 80 μm sieve residual percentage of 2.8%, a 28 d compressive strength, and a flexural strength of 52.2 MPa and 9.7 MPa, respectively. The chemical composition of cement is shown in The performance indices of coarse aggregates prepared from crushed stones with particle sizes of 5–10 mm and 10–25 mm at a ratio of 1:4 are shown in The polycarboxylic acid water-reducing agent used for testing has a solid content of 10%, and a water reduction rate of 30%. In addition, the water used for the test was drinking water.The concrete mix proportion is shown in Refer to GB/T 14684-2022 Sand for construction, JGJ 52-92 Technical requirements and test methods of sand for ordinary concrete, and the JGJ 52-2006 Standard for technical requirements and test methods of sand and crushed stone (or gravel) for ordinary Concrete tests of the material properties of sand.Refer to GB/T 50080-2016 Standard for test method of performance on ordinary fresh concrete and GB/T 25181-2019 Ready-mixed Mortar to test the concrete mix performance.Refer to GB/T 50081-2016 Standard for test methods of mechanical properties on ordinary concrete, GB/T 50081-2019 Standard for test methods of concrete physical and mechanical properties, and GB/T 50107-2010 Standard for evaluation of concrete compressive strength to test the concrete’s strength. Non-standard specimens of 100 mm × 100 mm × 100 mm were cured under standard curing conditions until the ages of 3 d, 7 d, and 28 d, respectively. Their compressive strengths were determined in the unidirectional pressure loading mode. In addition, the obtained flexural strengths were multiplied by the dimensional conversion factor of 0.95. Non-standard specimens of 100 mm × 100 mm × 400 mm were cured under standard curing conditions until the age of 28 d. The flexural strength was determined by using a three-point bending loading method. The obtained flexural strength values were multiplied by the dimensional conversion factor of 0.85. The standard prismatic specimen of 150 mm × 150 mm × 300 mm was cured until the 28 d age under standard curing conditions, and the axial compressive strength was determined by unidirectional pressure action of loading.Refer to GB/T 50082-2009 Standard for test methods of long-term performance and durability of ordinary concrete, and JGJ/T 193-2009 Standard for inspection and assessment of concrete durability.Refer to GB/T 17431.1-2010 Lightweight Aggregates and its Test Method-Part 1: Lightweight Aggregates, GB/T 17431.2-2010 Lightweight Aggregates and its Test Method-Part 2: Test Methods for Lightweight Aggregates to test the light-matter performance.The geographic location map of the Santo Tomas River and the volcanogenic sand in the Santo Tomas River area are shown in As seen in The workability of C30-C60 concrete with different sand sources is shown in As seen in The compressive strengths of concrete of different strengths prepared with different fine aggregates at various ages are shown in fcp and fcc both range from 0.7 to 0.9, which approximate the generic values of fcp and fcc for light aggregate concrete [As shown in concrete . In addiIn fact, cement is an active component in concrete, and its strength directly affects the strength of the concrete made . ResultsThe elastic modulus of concrete under static pressure is calculated according to the following formula:In the equation:cE—Elastic modulus of concrete under static pressure (Unit: MPa).aF—The stress shall be the load corresponding to one-third of the axial compressive strength (Unit: N).F0—The stress shall be the initial load corresponding to 0.5 MPa (Unit: N).A—The bearing area of the specimen (mm2).L—Measuring range (mm).n—Average value of deformation on both sides of the specimen when loading from F0 to aF for the last time (mm).∆aε—Average value of deformation on both sides of the specimen at aF.ε0—Average value of deformation on both sides of the specimen at F0.1 GPa = 1000 MPa.The elasticity modulus tester is shown in As shown in A horizontal concrete shrinkage meter was used to determine the dry shrinkage deformation at different ages, with pre-embedded copper probes at both ends of the specimens. The experimental results are shown in As shown in In this paper, the NEL method was used to test the chloride ion penetration resistance of concrete. The NEL method assumes that the particle concentration is the chloride ion concentration of concrete hole solution or the used salt solution concentration. On the basis of measuring the conductivity of concrete after salt-filling, the diffusion coefficient of chloride ions in concrete is calculated by using the Nernst–Einstein equation . This meThe evaluation criteria of the NEL method are shown in As shown in During the concrete carbonation test, the cubic specimens were cured for 26 d under standard curing conditions, then dried in a vacuum oven at 60 °C for 2 d, and placed under a rapid carbonation chamber for rapid carbonation immediately after cooling down. The concentration of carbon dioxide in the box is maintained at (20 ± 3) %, the relative humidity is controlled at (70 ± 5) %, and the temperature is controlled at (20 ± 2) °C. Notably, 28 d later, they were split to determine the carbonation depth using phenolphthalein. The results of the concrete carbonation test are shown in 2 gradually diffuses from its surface to the interior of the concrete through the capillary pore channels between cement stones, pores in cement stones and aggregates, as well as microcracks and small pores. In addition, the porous surface of volcanogenic sand also promotes CO2 infiltration. However, water absorption by volcanogenic sand in porous structures reduces the water-to-binder ratio and promotes the formation of a compact “self-vacuum” protective layer at the transition zone of interface with cement stone [2 is hindered, and the early carbonation resistance of PVSC is enhanced. It is also possible that the concrete structure becomes more compact due to the filling effect of stone dust in the volcanogenic sand and the improvement of the interfacial transition zone between the slurry and the aggregates [As shown in nt stone . As a regregates .For the purpose of the test, the average seepage height was determined based on the constant water pressure, which is used to express the concrete seepage resistance. Test results are shown in As shown in 3 and 1550 kg/m3, respectively, while the void ratio decreased to 40%. After optimization, substandard volcanogenic sand became qualified in all three parameters. However, it is still unqualified in light-matter content and belongs to natural volcanogenic light sand, which is different from that specified in GB/T 14684-2022. Without adverse effects on various properties of concrete, the optimized volcanogenic sand can meet the requirements for ordinary engineering.As shown in Due to a high proportion of lightweight large particles, the volcanogenic sand is unqualified in many test indices. In view of this, such lightweight large particles therein were separated out and washed according to Chinese standard GB/T 14684-2022 to obtain the optimized volcanogenic sand and massive light matter containing large particles. Whereas the composition of volcanogenic sand remains unchanged before and after optimization, This paper tests the material properties of the optimized volcanogenic sand, the workability and compressive strength of the new concrete for the unqualified items in volcanogenic sand, so as to eliminate the non-conformity of volcanogenic sand.The proportions of the mix of concrete made from the optimized volcanogenic sand are shown in The workability of C30-C60 concrete with different sand sources is shown in As shown in The chemical composition and material properties of the separated light-matter particles are shown in X-ray fluorescence (XRF) tests were conducted after drying and grinding separated light matter. The test results are shown in As shown in The particle gradation of lightweight large particles and fine aggregates after sieving for the test is shown in 3, which is less than 1200 kg/m3. According to the gradation curves of light matter, the light matter in Philippine volcanogenic sand does not meet the gradation requirements in GBT 14684-2022. In addition, the light matter in Philippine volcanogenic sand fails to meet China’s gradation requirements for light aggregates.The optimized light matter as natural light aggregates of volcanic cinder has a bulk density of 960 kg/mSome mortar with the strength grade M30 made of natural sand from Beijing and volcanogenic sand, respectively, was prepared. Their mix proportion is shown in As shown in The detection age for concrete durability performance indicators specified in the Chinese national standard GB/T 50082-2009 is usually tens of days, while the service life of concrete in practical engineering is a dozen years or even decades. Although the performance of volcanic sand concrete is not much different from that of ordinary concrete in a short term, the long-term durability needs to be further observed. Specific test results show that volcanogenic sand can be used to prepare C30-C60 grade concrete, but it is still uncertain whether it can be used to prepare high-strength concrete or ultra-high-strength concrete. At the same time, although the light substance content is greatly reduced after optimization, it is still higher than the value of not more than 2% specified in the national standard GB/T 14684-2022. If the light substance content can be further reduced to meet the requirement, the utilization rate of volcanogenic sand will be further improved.PVSC is good in workability and resistance to chloride ion penetration and carbonation but is weak in seepage resistance. Additionally, it has a slightly low apparent density and a strength of up to C30-C50. Compared to BSSC, PVSC is similar in overall performance but has a large slump loss.3, a bulk density of 1550 kg/m3, and a light-matter content of 6.0%. Compared with BSSC of the same grade, PVSC, after optimization 1., is basically the same in terms of slump, expansion, and apparent density and has a good slump-retaining capacity and 2. higher compressive strength.Philippine volcanogenic sand contains as much as 12.2% of light matter. The volcanogenic sand optimized through sieving, washing, and drying large particles of more than 4.75 mm reaches the standard of Zone-II medium sand, which obtains a fineness modulus of 2.4, an apparent density of 2570 kg/m3. Under the condition of the same cementitious material and water consumption, the mortar made of Philippine volcanogenic sand, compared to the mortar prepared with natural sand from Beijing, has a low apparent density of 1940 kg/m3 and a water-retention rate of 92%, and the seven-day compressive strength is 30.2 MPa.The separated light matter has a fineness modulus of 4.3, a cylindrical compressive strength of 2.8 MPa, a 1 h water absorption rate of 8.2%, and a bulk density of 960 kg/mThis paper analyzes the material properties of Philippine volcanogenic sand, as well as the workability, mechanical properties, and durability of PVSC. The conclusions are drawn as follows:


The c‐MET protein, encoded by the mesenchymal‐epithelial transition factor (MET) gene, can regulate cell proliferation, migration and invasion. Studies have shown that it is one of the essential driver genes for non‐small cell lung cancer (NSCLC). Currently, several clinical studies have carried out objective assessments on the efficacy and safety of different types of MET tyrosine kinase inhibitors (TKIs). However, direct cross‐sectional comparisons between different agents are still not available.Our study was a single‐center retrospective clinical study, which collected the data from MET positive NSCLC patients treated with MET TKIs at the Lung Cancer Center of Peking Union Medical College Hospital. We explored the efficacy and safety of crizotinib versus savolitinib in patients with METex14 skipping and MET amplification, separately.p > 0.05). In the MET amplification subgroup, savolitinib (median PFS = 7.1 months) demonstrated a better progression‐free survival benefit than crizotinib (median PFS = 1.4 months), p = 0.05. The most common adverse effects of both MET TKIs were peripheral edema (41.2%), gastrointestinal reactions (23.5%), and liver injury (14.7%). The incidence rate of peripheral edema was higher in savolitinib than crizotinib.Patients with METex14 skipping (median PFS = 10.7 months) had a better clinical response to MET TKIs than MET amplification patients (median PFS = 4.1 months). In the METex14 skipping subgroup, savolitinib did not show better survival benefit with significance than crizotinib . In MET amplification subgroup, savolitinib (median PFS = 7.1 months) demonstrated a better progression‐free survival benefit than crizotinib (median PFS = 1.4 months), p = 0.05.Our study was a single‐center retrospective clinical study, which collected the data from MET positive NSCLC patients treated with MET TKIs at the Lung Cancer Center of Peking Union Medical College Hospital. In METex14 skipping subgroup, savolitinib did not show better survival benefit with significance than crizotinib ( Lung cancer is one of the leading causes of mortality, of which non‐small cell lung cancer (NSCLC) accounts for approximately 85%.The MET gene is located in the chromosome 7q21‐31 and encodes c‐MET protein, a tyrosine kinase receptor for hepatocyte growth factor. It is capable of regulating cell proliferation, migration and invasion by activating the downstream MEK–ERK pathway and PI3K pathway.MET TKI can be classified into type Ia, type Ib, type II and type III according to its mechanism.Herein, we conducted a single‐center retrospective observational study to explore the efficacy and safety of two types of MET TKIs available in China (crizotinib vs. savolitinib) in METex14 skipping and MET amplification NSCLC patients. By analyzing data from real‐world applications, we hope to provide a basis for further optimization of clinical decisions in selecting MET TKIs.This was a single‐center retrospective clinical study to explore the difference in efficacy and safety of crizotinib versus savolitinib in NSCLC patients with METex14 skipping and MET amplification. The study design was in accordance with the ethical guidelines of the Declaration of Helsinki and approved by the ethical review committee of Peking Union Medical College Hospital.In this study, we collected and analyzed data from MET positive NSCLC patients treated with crizotinib or savolitinib at Peking Union Medical College Hospital from January 2018 to June 2022. Inclusion criteria was as follows: (1) Diagnosis of NSCLC by histology or cytology; (2) tumor stage IVa or IVb; (3) at least one measurable tumor lesion; (4) presence of METex14 skipping or MET amplification (gene copy number ≥2) identified by next‐generation sequencing (NGS) or fluorescence in situ hybridization (FISH) assay  and (5) received crizotinib or savolitinib treatment and underwent at least one‐time radiographic evaluation.EGFR mutation status, MET mutation status , MET TKI type, treatment lines for MET TKI, baseline tumor dimensions, optimum tumor size change, progression‐free survival, and drug‐related adverse reactions.For each patient, we obtained the following information separately: gender, age, pathology type, disease stage, smoking history, eastern cooperative oncology group (ECOG) score, R2 reflected the fitting degree of the model. A waterfall map was drawn to visually reflect the maximum change value of tumor size in all patients. The survival benefit among different groups was reflected by Kaplan Meier curve. A log‐rank test was used to explore the influence of different MET TKI and other interfering factors on MET positive patients. The hazard ratio (HR) and p‐value from Cox regression were reported. p‐values <0.05 were considered statistically significant.IBM SPSS version 24.0 was used to complete statistical analyses, and graph pad prism version 8.0.1 was used to draw statistical graphs. We analyzed the characteristics of basic information of patients and their treatment strategy with MET TKIs. The patients were grouped according to their MET mutation type. The efficacy of MET TKI was reflected by objective response rate (ORR) and progression‐free survival (PFS), while safety was demonstrated by the incidence of adverse effects. Progression‐free survival was defined as the time from initiation of MET TKI to imaging assessment of lesion progression >20%. Count data was described according to its statistical quantity and percentage, while measurement data was converted into count data by self‐defined stratification. In METex14 skipping and MET amplification subgroups, basic information was further matched according to MET TKI type (crizotinib vs. savolitinib). Correlation between different count data was verified by chi‐square test, while correlation between measurement data was verified by linear regression, and We collected the information of 56 NSCLC patients who were MET positive in the lung cancer center of Peking Union Medical College Hospital from January 2018 to June 2022. Among them, 34 patients who had been treated with MET TKIs and experienced at least one radiographic evaluation, were formally included in our study Table .EGFR mutations, while only three METex14 skipping patients had EGFR mutations. A MET TKI was more commonly used as the first‐line treatment (58.8%) for METex14 skipping due to its independent oncogenic characteristic. In contrast, it was used more frequently for post‐line therapy (88.2%) for MET amplification. In terms of MET TKI selection, 55.9% of patients selected crizotinib while 44.1% chose savolitinib  were male and 13 (38.2%) were female, with no significant differences between METex14 skipping and MET amplification patients. The median age was 62 years old. The METex14 skipping population was dominated by patients over 60 years old (82.4%), whereas more than half of the MET amplification population was made up of young patients (less than 60 years old). The pathological type was mainly adenocarcinoma (94.1%), with only two patients of other types. All patients included in our study had stage IV NSCLC, of which 41.2% were at stage IVa and 58.8% were at stage IVb. Nearly half of the patients had a smoking history (47.1%). At the time of MET TKI initiation, 76.5% of patients were in good general condition (ECOG score 0–1). MET amplification is one of the essential mechanisms of EGFR TKI resistance. All MET amplification patients included in this study had The maximum change in tumor diameter of all patients is shown in Figure p = 0.95)  showed numerically longer median PFS than crizotinib , with no statistical difference  Figure . Furtherp = 0.05  or extension time of PFS (R2 = 0.042).In the MET amplification subgroup, savolitinib  demonstrated better survival benefit than crizotinib , 5 Figure . Matchin5 Figure . FurtherFor the purpose of assessing the safety of medication administration, we estimated the incidence of the three most common adverse reactions . Approximately, 64.7% patients using a MET TKI experienced these drug‐related adverse reactions; the incidence of peripheral edema was 41.2%, gastrointestinal reactions was 23.5% and liver injury was 14.7%. Adverse reactions occurred in 52.6% patients in the crizotinib group, with an incidence of 26.3% for edema, 15.8% for gastrointestinal reactions, and 15.8% for liver injury. Grade 3 or higher adverse reactions occurred in 10.5% patients, mainly consisting of liver injury, while in the savolitinib group, 73.3% of patients experienced MET TKI‐related adverse reactions, with 60.0% edema, 26.7% gastrointestinal reactions and 13.3% liver injury. Among them, the incidence of grade 3 or higher adverse reactions was 26.7%, including two cases of liver injury, one edema and one edema combined with gastrointestinal reaction.EGFR mutations which was significantly higher than the data reported in the previous literature of 0.65%, and may have been due to the bias introduced by the small sample.With an increasing number of MET TKIs approved for marketing, selecting a suitable agent for patients has become an urgent need for clinicians. Currently, the approved MET TKIs include crizotinib, savolitinib, capmatinib, and tepotinib.The PROFILE 1001 study was the first trial to formally evaluate the efficacy of crizotinib in NSCLC patients with METex14 skipping. Of the 65 patients included, the ORR was 32%, the DCR was 77.0%, with a median PFS of 7.3 months.EGFR mutations).In contrast to the strong tumor driving properties of METex14 skipping, MET amplification exhibited weaker oncogenic driving force, which was closely related to gene copy number (GCN).p = 0.05). The ORR of the savolitinib group was 33.3% with a median PFS of 7.1 months, similar to the TATTON Part B1 cohort. In contrast, the crizotinib group had an ORR of 27.3% with a median PFS of only 1.4 months. Notably, 54.5% of patients experienced disease progression at the time of first evaluation. This data is worse than that of the PROFILE 1001 study and the data of Wang et al., which may be due to the difference in the definition of MET amplification.Crizotinib, classified as a type Ia MET TKI, is an ATP‐competitive multitarget inhibitor that inhibits several targets, including MET and ALK, but has a relatively weak inhibitory effect on MET. Savolitinib is a type Ib MET TKI, which can bind to ATP adenine with high specificity. Theoretically, the inhibitory effect of type Ib MET TKI is stronger than that of type Ia. In our MET amplification cohort, real‐world data confirmed this speculation. Both in combination with EGFR TKIs, savolitinib demonstrated a tendency of superior PFS benefit in patients with MET amplification than crizotinib (R2 below 0.1. It also suggested that patients with low MET amplification may possibly benefit from MET TKIs.The standard detection method for MET amplification is MET/CEP7 by FISH, whereas MET gene copy number alone may not be sufficiently accurate.A meta‐analysis showed that the most common adverse reactions to crizotinib included peripheral edema, gastrointestinal reactions, liver injury, and visual impairment,Undeniably, there were some limitations in our study. First, the sample size of our single‐center study was small. In the future, multicenter and large‐scale studies are needed for further demonstration. Second, due to insufficient overall survival data of patients for statistical analysis, we will further extend the follow‐up period. Third, our study was retrospective in character, baseline information could not be matched exactly and thus selective bias was inevitable. The unequal market prices of savolitinib and crizotinib may cause variation in patients' choice. Although we performed matching analysis and found no statistical differences, the degree of matching was still limited. Fourth, some mild adverse reactions that were not recorded in the medical record system may have resulted in missing data.In summary, we conducted a single‐center retrospective clinical study to explore the efficacy and safety of crizotinib and savolitinib in MET positive NSCLC patients. For METex14 skipping, the efficacy of savolitinib and crizotinib did not show significant difference. For MET amplification, savolitinib showed significantly better efficacy than crizotinib. Peripheral edema, gastrointestinal reactions and liver injury were the main adverse effects for both types of MET TKI, but the incidence of peripheral edema was higher in savolitinib than crizotinib.Kang Miao, Xiaotong Zhang: Drafting the manuscript and revising it for important intellectual content. Hanping Wang: Provision of clinical data, article revision and correction. Li Zhang, Xiaoyan Si: Substantial contributions to the conception or design of the work and final approval of the version to be published.No funding was received to assist with the preparation of this manuscript.The authors have no competing interests to declare that are relevant to the content of this article.Table S1. Patient detail information.Click here for additional data file.


Full-thickness ascending aortic wall specimens from TAAD patients (n = 12) and control donors (n = 12) were examined for the expression of TLR4 and its major signalling molecules, in terms of immunity and inflammation. Blood samples from TAAD (n = 49) and control patients (n = 53) were collected to detect the circulating plasma cytokine levels of IL-1β and CCL5. We demonstrated that expression levels of TLR4 and its downstream signalling cascade molecules were significantly elevated. Furthermore, receiver operating characteristic curve analyses showed that elevated IL-1β levels and decreased plasma CCL5 may have diagnostic value for TAAD. In summary, this current study suggests a more generalized pattern of inflammation in TAAD. In addition, TLR4-mediated inflammatory product, such as IL-1β and CCL5, could be novel and promising biomarkers with important diagnostic and predictive value in the identification of sporadic TAAD diseases.Sporadic acute Stanford type A aortic dissection (TAAD) is a serious condition that requires urgent treatment to avoid catastrophic consequences. The purpose of the present study was to explore, firstly, whether TLR4-regulated immune signalling molecules were activated in TAAD patients and, secondly, whether TLR4-regulated inflammatory products interleukin-1 Sporadic acute aortic dissection (AAD) is a catastrophic disease process associated with very high morbidity and mortality. AAD is characterized by medial degeneration with tearing of the intima layer and blood crossing into the artery wall, which leads to the formation of a false lumen within the middle tunica. Depending on the location of the rupture, AAD is classified as acute Stanford type A aortic dissection (TAAD), when the ascending aortic thoracic tract and/or the arch are involved, and Stanford-B aortic dissection, when the descending thoracic aorta and/or aortic abdominal tract are involved . TAAD isIncreasing evidence suggests that the aorta wall of TAAD has inflammatory cell infiltration and enhanced expression of inflammatory mediators . Among tThe procedure used combined previous literature methods with those established in our research group .This study was approved by the Ethics Committee of Union Hospital. All patients provided signed informed consent before participating in the study. This study conforms to the Code of Ethics of the World Medical Association (Declaration of Helsinki), printed in 1975.Appropriate informed written consent was obtained for all procedures. The ascending aortic wall specimens were obtained approximately 3 cm from the aortic annulus of 12 TAAD patients undergoing open surgical treatment. None of the patients had any known genetic syndrome related to aortic disease . Patients with a family history of TAAD or with dissection induced by trauma or cardiovascular operations were excluded. The control group consisted of twelve age- and sex-matched nonaortic dissections of aortic specimens obtained from full-thickness thoracic aortic walls from heart or kidney donors provided by the Union Hospital. These control aortic samples were macroscopically normal and devoid of early atheromatous lesions. Immediately after collection, each (thrombus-free) specimen was divided into 2 equivalent pieces. The first half was divided into small (50 mg) full-wall thickness pieces. The second half was carefully dissected into an outer dissected membrane (DM) and an inner DM. Tissue samples were immediately frozen in liquid nitrogen and then stored at −80°C until processing. Demographic and clinical characteristics of the TAAD and control groups are shown in n = 49) and non-TAAD (n = 53) . Study participants were excluded from the study if they had one or more of the following conditions: (1) onset time >1 day; (2) autoimmune diseases or infectious diseases that can cause changes in the levels of inflammatory factors; (3) iatrogenic aortic injury, traumatic aortic injury, and drug use; (4) various other heart diseases, such as coronary heart disease, viral myocarditis, cardiomyopathy, cardiac insufficiency, and bicuspid aortic valve; (5) certain genetic syndromes, such as Marfan syndrome, Ehlers-Danlos syndrome, and aortitis; (6) inherited tissue connective diseases; (7) intramural haematoma (IMH) and penetrating aortic ulcer (PAU); and (8) disease accompanied by severe liver and kidney damage. The diagnosis was determined based on CTA results and clinical symptoms of patients by doctors with 18 years of clinical experience, and a total of 102 cases were included. They were separated into two groups based on clinical diagnosis: TAAD ((n = 53) . Each paβ (Wanleibio), toll-like receptor-associated activator of interferon , NF-κB p65 (Abcam), CCL5 , and β-actin . The membranes were blocked with 5% fat-free dry milk and then incubated with the appropriate primary antibody for 24 hours at 4°C. The membranes were then treated with a peroxidase-conjugated secondary antibody after three washes . Finally, BeyoECL Plus was used to view the immunological complexes .Briefly, total proteins of each aortic sample were extracted using RIPA lysis buffer  containing a protease inhibitor . Protein concentration was quantified by the BCA protein assay kit , and an equal number of proteins were separated on 12.5% SDS-PAGE gels. After electrophoresis, the proteins were transferred to polyvinylidene fluoride (PVDF) membranes and incubated with antibodies against TLR4 , myeloid differentiation factor 88 , TNF receptor-associated factor 6 , interferon regulatory factor 3 , IL-1β-actin mRNA was measured. β-actin. For relative quantification, the findings were analyzed using the 2-Ct technique. Each experiment was carried out three times.TRIzol was used to extract total RNA from the aortic tissues . Moloney murine leukemia virus reverse transcriptase (M-MLV RT) was used to make cDNA from RNA . 2xPower Taq PCR MasterMix was used for real-time PCR . As an endogenous control, the level of IHC was used to determine the expression levels of CD3+ (T lymphocytes), CD20+ (B lymphocytes), and CD68+ cells (macrophages) in aortic wall tissues. Briefly, 6 m formalin-fixed and paraffin-embedded sections were produced, then incubated overnight at 4°C with primary antibodies against CD3, CD20, and CD68 , followed by diaminobenzidine staining and counterstaining with haematoxylin. Cover slips were used to mount the sections, which were then inspected under a light microscope.IL-1 and CCL5 plasma inflammatory cytokine levels were measured using enzyme-linked immunosorbent assays (ELISAs) as directed by the manufacturer .On the day of the examination, blood was drawn from each patient, and clinical test results were determined on the same day. An Olympus AU640 Autoanalyzer was used to quantify serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) using an automated spectrophotometer and an enzymatic colorimetric technique . On a Hitachi 7600 Autoanalyzer, several biochemical tests were conducted using the Jaffe kinetic technique .t-tests, and Mann–Whitney U-tests were used to assess differences between variables. The correlations between plasma IL-1, CCL5, and plasma D-dimer were determined using Spearman's correlation analysis. The diagnostic effects of serum cytokines were evaluated using receiver operating characteristic (ROC) curves, and the associated cut-off points were determined. Multiple logistic regression models with adjustments for potential confounding factors were used to estimate the predictive value of serum IL-1 and CCL5 in assessing TAAD risk. For regularly distributed variables, all data are provided as medians and interquartile ranges, or means and standard deviations. Statistical analysis was performed using SPSS 16.0 . P < 0.05 was considered significant.ANOVA, independent-sample β-actin, TAAD samples showed significantly increased protein expression levels of TLR4, Myd88, TRAF-6, NF-κB p65, and IL-1β compared with control aorta, especially in the outer DM  × 109/L] and a significantly higher prevalence of hypertension [35 (71.4%)] than the TAAD-free controls [21 (39.6%)]. Furthermore, TAAD patients showed a tendency towards having a higher serum D-dimer than TAAD-free controls [5.41 (3.12 − 8.88) mg/L vs 0.98 (0.52 − 1.26) mg/L]. Moreover, the above indicators were significantly differentially expressed in TAAD patients compared to TAAD-free controls (P < 0.001). The serum level of IL-1β was 3.90 (3.20 − 4.87) pg/mL, which was significantly higher than the reported value of 2.94 (2.05 − 3.77) pg/mL in subjects without TAAD, whereas the serum levels of CCL5 were lower than those in subjects without TAAD (P < 0.001).β and CCL5 levels and D-dimer levels in acute TAAD patients by Spearman's correlation analysis. The results showed that IL-1β levels were positively correlated with D-dimer, whereas the serum levels of CCL5 were negatively correlated with D-dimer , TC, LDL-C, and HDL-C as independent variables, showed that IL-1β, in addition to D-dimer, was a significant and independent factor associated with the presence of TAAD : 1.13–3.71, P=0.019). Model 2, in which IL-1β was replaced with CCL5, demonstrated that CCL5 was significantly associated with the presence of TAAD .Many studies have shown that plasma D-dimer levels have a significant positive correlation with the incidence of TAAD and thus may be an effective predictor of the incidence of TAAD. Therefore, we further analyzed the association between plasma IL-1 Figures . Multipl of TAAD . Model 1β, CCL5 and D-dimer levels in discriminating TAAD diseases is shown in β were 0.939 (95% CI: 0.873–0.977) and 0.779 (95% CI: 0.686–0.855), with corresponding optimal cut-off points of 5.50 (ng/ml) and 3.54 (pg/ml), which were associated with sensitivities of 91.8% and 71.4% and specificities of 86.8% and 69.8%, respectively , whereas fewer reports have investigated the role of TLR4 in TAAD. Although there are still some distinctions in the pathogenesis of the two, TAA and TAAD are both intimately associated to local and systemic immune inflammatory responses. Therefore, the potential role of TLR4 in enhancing the immune inflammation that leads to TAAD needs to be clarified.κB, which controls the production of tumour necrosis factor-a (TNF- a), interleukin-6 (IL-6), and IL-1β [κB is also induced in this pathway [β and CCL5), which play a crucial role in maintaining aortic wall inflammation, leading to matrix degradation [κB, or phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) to mediate cell migration, activation, proliferation, and differentiation [β and CCL5. This hypothesis suggests that the early stages of TAAD are associated with a predominant infiltration of macrophages whose characteristics are induced by TLR4 and that probably enhance vascular inflammation.First, we found that TLR4 was overexpressed in the aortic tissues of TAAD. These observations suggest that increased expression of TLR4 may be related to TAAD. There are two adapter molecules essential for TLR4 signalling: MyD88 and TRIF. MyD88-mediated signalling promotes early-phase activation of NF-nd IL-1β , 13. The pathway , 15. To radation . Furtherntiation –20. Thusβ and CCL5, are potential diagnostic markers and therapeutic targets for TAAD. First, we identified elevated plasma IL-1β and decreased plasma CCL5 as independent risk markers in TAAD. Epidemiologic studies, thus far performed mainly in patients with aortic dissection (AD), have established the notion that serum D-dimer is positively and independently associated with predictors for AD risks [β and CCL5 levels with plasma D-dimer in TAAD patients. Moreover, we evaluated the diagnostic and predictive features of circulating biomarkers for identifying TAAD, which may be helpful for making a reasonable clinical decision in diagnostic and screening procedures. Based on ROC curves, elevated IL-1β and decreased CCL5 levels suggested a high specificity and sensitivity in recognizing TAAD, but it was less than that of D-dimer. Indeed, a significant relationship between the pathogenesis of AAA and serum IL-1β and CCL5 levels has been reported, indicating that aortic aneurysm formation and progression could be blocked by genetic or pharmacological inhibition of IL-1β or CCL5 [β and decreased plasma CCL5 as independent risk markers in TAAD.In light of the above findings, we further investigated whether the TLR4-regulated inflammatory products, IL-1AD risks . Thus, w or CCL5 , 23. HowThe most interesting association observed in this study was CCL5, which showed differential expression in both aortic tissue and plasma. CCL5 is a CC chemokine family T-cell mitogen that exerts a broad spectrum of effects on inflammatory responses. However, CCL5 is also produced by other cells, including macrophages, T-cells, dendritic cells, smooth muscle cells, and platelets (PLTs), and has been shown to be associated with AAA risk . SimilarThis study revealed numerous immune infiltrates composed of macrophages and lymphocytes in the ascending aortic wall in TAAD patients, compared with few infiltrates in control patients. Interestingly, the infiltration of inflammatory cells was particularly high in the outer DM from the TAAD patient samples. Moreover, the activation of the TLR4 signalling pathway was more pronounced in the outer DM. Currently, identifying the initialization and propagation of vascular inflammation has been a controversial focus . The resβ/CCL5. Second, due to the current lack of relevant data, we were unable to accurately account for changes in serum IL-1β and CCL5 levels in 12 patients compared with controls. Moreover, both the aortic sample and blood sample sizes are small, and more patients are needed. Finally, the conclusions were based solely on human aortic wall specimens. Despite these limitations, these preliminary results will provide clues to the molecular mechanisms involved in TAAD, which should be pursued in future investigations.The current study had several limitations that should be mentioned. First, due to the limitations of related experiments, we did not verify the regulatory mode between TLR4 and IL-1β and CCL5 expression that converges on common, pathogenic TLR4 signal transducers and activation of the NF-κB p65 signalling pathway. This pathway stimulates the effector functions of macrophages and enhances inflammatory factor expression, ultimately resulting in deterioration of the vascular wall structural integrity (β and CCL5, may be novel and promising biomarkers with important diagnostic and predictive value in the identification of TAAD diseases.In conclusion, our research results and together with the results from some previous studies, in the specific case of sporadic TAAD, we propose a sequential “two-hit” model of vascular inflammation involving initial vascular injury followed by recruitment of macrophages to injured sites in the aorta. Activated macrophages produce amplification of IL-1ntegrity . Further


Recycled aggregate (RA) made from waste concrete is an environmentally friendly alternative to natural aggregate (NA) for concrete manufacturing. However, compared to NA concrete, concrete produced with recycled aggregates has poor characteristics. Supplementary cementitious materials (SCMs) can be used to enhance the poor properties of recycled aggregate concrete (RAC). Silica fume and fly ash are commonly used SCMs in the World, but their high usage led to a shortage of silica fume and fly ash. Still, the deficiency of these materials in large parts of the world is a challenge that requires exploring alternative feedstock materials for the construction industry in the coming years. Wheat straw ash (WSA) is an agricultural waste product that could be used as an alternative SCM due to its pozzolanic behavior to enhance the properties of RAC. In addition, concrete is brittle and needs reinforcement, for which polypropylene fibers (PPFs) can be used. The current research examines the mechanical characteristics of fiber-reinforced RAC, including compressive strength, splitting tensile strength, and ductility performance. Durability indicators, such as chloride diffusion, chloride penetration, acid resistance, and water absorption test, were also assessed. The results showed that concrete samples with 10% WSA, 50% RA and 1.5% PPFs had the highest compressive and splitting tensile strength, 60.2 MPa and 7.25 MPa, respectively, representing increases of 24.75% and 30.65%, as compared to plain samples at 56 days. In these samples, water absorption was reduced by 13% due to the finer WSA particles resulting in the lowest reduction in strength and mass recorded when exposing concrete samples to acidic media. The statistical analysis also validated that irrespective of WSA and PPFs, the concrete with 0% RA had the highest performance in strength and durability behavior. The study showed that WSA and PPFs might be employed in tandem to offset the poor behavior of RA, enhance the bond between fibers and concrete, and improve the mechanical strength and durability performance of RAC, thus demonstrating its suitability as a sustainable and economical construction material. In addimissions , which itivities ,9. Besidtivities . Alternativities . Recycletivities ,13 and dtivities .2 curing can further improve the ecological profile of recycled concrete aggregates [C–S–H), thereby densifying the structure of RAC [Similar to partially replacing cement with SCMs , using rgregates . Generalgregates . The mecgregates . The durgregates . The higgregates ,24. Anotgregates . Howevergregates . These ae of RAC , ultimate of RAC . Silica e of RAC . Howevere of RAC . The enfe of RAC   to improve the properties and sustainability of fiber-reinforced concrete.22.12.1.1C150 [C311 [°C/min. Wheat straw ash was kept at 600oC–800 °C for 5 h. The particle shape and surface texture of WSA are flat and rough, with porosity values above 45% [C618 [The present research used Type I cement per ASTM C150 . WSA can50 [C311 . The rep50 [C311 . A tradibove 45% . Wheat s5% [C618 . X-ray d2.1.2River sand was used as a fine aggregate with a fineness modulus of 2.7, and crushed stone was utilized as a coarse aggregate. A local crusher plant provided RA. Because of RA's high-water absorption, they were saturated before blending in the concrete mix. Fine and coarse aggregates were used in saturated surface conditions. Natural and recycled aggregate details are presented in 2.1.3Synthetic polypropylene fibers were used as reinforcement material in concrete production. Polypropylene fibers (PPFs) were purchased from Rawalpindi, Pakistan. PPFs are shown in 2.1.4C494 [Third-generation polycarboxylate-based superplasticizer for concrete utilized as a high-range water-reducing admixture as per ASTM C494  to incre2.2Twelve mixes were prepared with gradual increases in recycled aggregate dosage (RA)  in place of natural coarse aggregates (NA). Wheat straw ash (WSA) was used as a cement substitute at a ratio of 10%. The cement replacement level was established based on preliminary laboratory trials and extant literature, which suggest optimal replacement levels in the range of 10% when using recycled aggregates . Moreove2.3C511-13 [Wheat straw ash (WSA), fine aggregate, coarse aggregate (RA and NA), and cement were mixed in dry form using a mechanical mixer at an average mixing speed of 70 rpm for 120 s. Then, 60% of the mixing water was added and blended for 70 s. Afterward, PPFs were introduced to the mixture and blended for three more minutes. The remaining water and admixture were added to the blend later and mixed at a speed of 100 rpm for additional 60 s. The concrete blend was left to rest for 30 s, then blending continued for 60 s before fresh concrete tests. Concrete samples were cast and removed from the mold after 24 h of curing and placed in a water tank at 22 °C until their curing was completed. As per ASTM C511-13 . Calcium2.4C496 [A compression testing machine (CTM) was used for the mechanical testing of cylindrical concrete specimens of 150 mm × 300 mm (diameter x height) as per ASTM C 39 . The comC496  at 28 anC496 . A univeC1556 [x, t) is the concentration of chloride content at the time (sec) and depth (meters), t is time (sec), Ci is the primary chloride, erfn is the error function, and D is the coefficient of chloride diffusion (m2/sec).A chloride bulk diffusion test was performed on samples after 28 days of curing. After chloride exposure, the samples were cut with an electrical saw machine to determine the diffusion of chloride ions. The outer 100 mm portion of the sample was utilized for testing. Concrete specimens were exposed to 17% (by weight) sodium chloride solution for two months. Sodium chloride solution was procured from an Islamabad chemical factory in a ready-to-use form. Sodium chloride was employed as a high concentration of chlorides in chloride diffusion testing . EquatioC1556 .(1)C was employed to evaluate the concrete samples' resistance against acidic media. The test specimens were water cured for 28 days at ambient room temperature, followed by immersion in a 10% solution of HCl acid. To confirm a uniform condition, the specimen's pH was frequently inspected. The test specimens remained in acid for three months and were tested for compression strength afterward. To consider the effect of acid on the concrete's decomposition and strength, loss in mass and reduction in compressive strength of concrete samples were evaluated.For penetration of the chloride test, concrete samples with 100 mm × 50 mm (diameter x thickness) were used. The samples were cured in water for 28 days and placed in a sodium chloride solution, and when the samples were removed from the test setup, they were sprayed with 0.2 N silver nitrate on the cut piece. The silver nitrate chemically reacts with penetrated sodium chloride to create a compound of white color (silver chloride). The test setup for the chloride penetration is presented in 33.1The influence of RA, PPFs and WSA on concrete compressive strength is presented at each curing age in 3.1.1O–Si bond in the concrete because of a large quantity of reactive silica, which WSA adds to concrete [For blends with no WSA, the increase in strength for blends with PPFs is somewhat higher. The difference is considerable for blends having 10% WSA. This is because WSA provides better interaction between PPFs, leading to higher load capacity . Adding concrete . WSA couconcrete . Concretconcrete . The firconcrete , the secconcrete , and theconcrete . The weaconcrete . Overall3.1.2The empirical relationships between tried variable and the value R-square are presented in every statistical analysis Figure. When the value of the R-square is close to unity (1), it signifies an excellent regression response. In most of the statistical analysis, the value of R-square is more than 80%, which indicates that there is a perfect match among the fibers, WSA and recycled aggregates, and the WSA and PPFs are doing their part to mitigate/avert the inferior performance of recycled aggregates. However, in some cases, the R-square value was low, which could be ascribed to the elastic behavior of PPFs. Independently talking about the mixtures, adding wheat straw ash and fibers simultaneously slightly improves the compressive strength in case all mixes. This may be because wheat straw comparatively improves the microstructure , and fib3.2The splitting tensile strength test on representative concrete samples is presented in 3.3A universal testing machine was employed for stress-strain tests, and the experimental stress-strain curves of samples with different dosages of polypropylene fibers, recycled aggregates, and wheat straw ash are shown in 3.43.5Water absorption tests can be used to estimate concrete porosity. Pore connectivity and tortuosity impact the volume of permeable voids in concrete. This testing was conducted on specimens placed in water for 56 days, and the water absorption values of various samples are shown in As RA content is increased from 0% to 100% in fiber and no fiber samples, it enhances water absorption by 44.8% and 33.7%. A rise in water absorption is because of the porous and permeable old mortar present in the recycled concrete aggregate. The cracks inside old mortar allow water to flow in a sample . Adding 3.6Two batches of concrete samples were assembled for the acid test to examine the impact on concrete strength due to acid exposure. One batch of concrete specimens was water-cured, while the second was exposed to acid for 28 days using 5% concentrated hydrochloric acid. Representative images of the sample before and after the acid test are shown in 3.7Resistance to chloride attack is among concrete's most critical durability characteristic due to the corrosion of steel reinforcement bars. Hence its measurement is fundamental for engineers' design of concrete structures, especially for coastal and marine environments. Concrete samples were immersed in sodium chloride (NaCl) solution for 28 days to conduct a chloride penetration test. Values obtained from various mixes of chloride penetration tests are shown in 4The mass production of cement and its usage in concrete leads to the outflow of greenhouse gases with significant environmental harm. In addition, advancing the world's infrastructure causes increasing demolition and construction waste production, and dumping this waste stream causes massive land pollution. So, to avoid or avert the above issues, it is necessary to utilize a material that is not a waste/recycled material but also eco-friendly. Therefore, wheat straw ash is an appropriate substitute material that can partially replace cement in concrete manufacturing. Also, recycled coarse aggregates from demolition and construction waste can effectively replace natural stone aggregate. However, to offset the detrimental impacts of recycled coarse aggregate, it is necessary to use some reinforcement to make concrete more ductile. Using wheat straw ash will reduce clinker consumption and the cost/budget of a construction project. Similarly, coarse recycling aggregate will help save the natural reserves of limestone and other mineral resources used as aggregates and help preserve the environment.51.The substitution of natural aggregates with RA substantially impacts concrete mechanical performance and durability characteristics. As the dosage of RA increases, compressive and split tensile strength reduces, and water absorption and diffusion of chloride ions increase, indicating durability reductions.2.With 10% WSA, 50% RA and 1% PPFs, the compressive strength was increased up to 24% at 90 days of curing relative to reference samples.3.At 50% RA level, splitting tensile strength was increased by 15.3% and 13.4% for non-fibrous and non-WSA concrete at 56 days of curing.4.Including PP fibers improved splitting tensile strength up to 16.6% and 35.6% for 28 and 56 days of curing, respectively.5.Adding 10%, WSA reduced the water absorption of concrete up to 13.0% due to the finer particles of WSA.6.The stress-strain curve confirmed the improved ductility behavior of fiber-reinforced concrete, as the sample with 10% WSA, 1% PP fibers, and 50% RA had the highest ductility.7.With the incorporation of WSA, the durability of RA concrete improves as water absorption is reduced by 13.0%. However, an increasing percentage of RA may lead to less durability because of old mortars present in RA.8.The simple linear statistical analysis showed that the results presented could be recommended for future studies.9.WSA addition mitigated RA's inferior durability performance as the lowest reduction in strength and mass due to acid attack was observed when utilizing WSA, RA, and PPFs , which are acceptable values to use concrete in harsh environments.10.Concrete with 100% RA had high chloride penetration (13 mm), which can lead to detrimental propagation of micro-cracks.11.PPFs can be used to counteract this adverse effect of RA and improve the cohesion of concrete.In this research, the combined effect of wheat straw ash (WSA), polypropylene fibers (PPFs), and recycled aggregate (RA) on the concrete mechanical performance and durability characteristics were examined. Following are the conclusions that are obtained from the trial investigation.In sum, the results showed that WSA is a potentially viable substitute for cement in concrete manufacturing. WSA enhances mechanical strength and durability performance and improves the performance of fiber-reinforced concrete, most likely due to enhancement in bonds between PP fibers and the concrete binders. Considering the above positive outcomes of the current research, the sustainable fiber-reinforced recycled aggregate concrete developed in the present study deserves further examination related to microstructural analysis  as it has demonstrated exciting features to be used in future structural applications.No fundingOsama Zaid, PhD: Performed the experiments; Wrote the paper. Fadi Althoey, PhD; Saleh Alsulamy, PhD: Analyzed and interpreted the data. Rebeca Martínez García, PhD: Conceived and designed the experiments; Wrote the paper. Jesús de Prado-Gil, PhD: Conceived and designed the experiments. Mohammed Awad Abuhussain, PhD: Contributed reagents, materials, analysis tools or data.Data will be made available on request.We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.


OR = 3.442, 95%CI: 1.423–8.327), HI > 1 for preferred veterinary antibiotic use , HQ > 1 for norfloxacin  and HQ > 1 for ciprofloxacin  had a higher risk of developing type 2 diabetes mellitus. Conclusions: Certain antibiotic exposures, mainly those from sources associated with food and drinking water, generate health risks and are associated with type 2 diabetes in middle-aged and older adults. Because of this study’s cross-sectional design, additional prospective studies and experimental studies are needed to validate these findings.Background: Although previous studies have shown an association between clinically used antibiotics and type 2 diabetes, the relationship between antibiotic exposure from food and drinking water and type 2 diabetes in middle-aged and older adults is unclear. ObjectivE: This study was aimed at exploring the relationship between antibiotic exposures from different sources and type 2 diabetes in middle-aged and older people, through urinary antibiotic biomonitoring. MethodS: A total of 525 adults who were 45–75 years of age were recruited from Xinjiang in 2019. The total urinary concentrations of 18 antibiotics in five classes  commonly used in daily life were measured via isotope dilution ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. The antibiotics included four human antibiotics, four veterinary antibiotics and ten preferred veterinary antibiotics. The hazard quotient (HQ) of each antibiotic and the hazard index (HI) based on the mode of antibiotic use and effect endpoint classification were also calculated. Type 2 diabetes was defined on the basis of international levels. Results: The overall detection rate of the 18 antibiotics in middle-aged and older adults was 51.0%. The concentration, daily exposure dose, HQ, and HI were relatively high in participants with type 2 diabetes. After model adjustment for covariates, participants with HI > 1 for microbial effects ( Antibiotics have been widely used for the treatment of bacterial infections in humans and animals and for the growth of animals since Alexander Fleming discovered that penicillin can be used to treat bacterial infections in 1928. Aureomycin was subsequently found to promote growth in animals in the 1940s . The oveThe relationship between antibiotic exposure and type 2 diabetes mellitus (T2DM) has received increasing attention, given the adverse effects of excessive antibiotic use in humans and animals, and the similar effects of antibiotic exposure and use in middle-aged and older adults ,9. Some Many indicators are available for assessing antibiotic exposure, such as the concentration, detection rate, daily exposure dose (DED), hazard quotient (HQ) and hazard index (HI). The HI is an index for the quantitative and systematic evaluation of antibiotic exposure levels, which can provide a comprehensive indication of antibiotic exposure levels . This stParticipants were from the National Key Research and Development Program “Xinjiang Multi-Ethnic Natural Population Cohort Construction and Health Follow-Up Study,” which has been conducted by our group since 2018 . In the For the field investigation, the study participants were instructed to fast before the physical examination. An amount of 12 mL of morning urine was collected from the participants, and the urine samples were stored in the dark and frozen in a −40 °C refrigerator on site after collection. Urine samples (1 mL) were purified with an Oasis HLB 96-well solid phase extraction plate and analyzed via ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry with an isotopic internal standard in 1 mL of urine, hydrolyzed by β-glucuronidase. All antibiotics were analyzed with an HSST3 chromatography column for separation. The three phenols were separated with acetonitrile and an aqueous mobile phase in the negative ionization mode, and the other antibiotics were separated with methanol and an aqueous mobile phase with 0.1% formic acid in the positive ionization mode. Each batch was based on 96-well solid phase extraction plates. A total of 96 samples were analyzed: 92 real urine samples, 2 solvent blank samples and 2 spiked urine samples of 10 ng/mL. The solvent blank samples and the urine samples spiked with the standard were analyzed together with the real urine samples. Solvent blanks were used to monitor background interference, and spiked urine samples were used to monitor precision and accuracy. The limits of detection and limits of quantification were defined as signal-to-noise ratios of 3 and 10, respectively. The limits of detection and limits of quantification for all antibiotics ranged from 0.04 to 1.31 ng/mL and from 0.13 to 4.37 ng/mL, respectively.Physical examinations were performed by trained nurses or physicians. A 20 mL blood sample was collected for each participant with a vacuum blood collection device with an intravenous anticoagulant. Biochemical and routine blood tests were performed with 4 mL blood samples. These tests were performed at the township health center nearest to the survey site. Whole blood samples (3 mL) were transferred to three cryotubes immediately after blood sample collection. The blood samples used to separate plasma and leukocytes were centrifuged  within 2 h after blood sample collection.The questionnaires were administered by medical students who had received professional training. The baseline questionnaire was mainly the China Kadoorie Biobank study baseline questionnaire, with minor modifications based on the comments of experts from Northwestern Medical College, China . The queThe daily exposure dose (DED) is an indicator used to assess the daily antibiotic exposure of an organism according to the following formula for the DED of an environmental contaminant ,19:The acceptable daily intake (ADI) is an indicator of exposure applicable to long-term low doses of antibiotics, rather than the short-term high doses used in clinical settings. The current common standard for the ADI, established by the World Health Organization and the Food and Agriculture Organization of the United Nations in 1957, aims to establish a safe limit value to minimize the hazards threatening population health, which in turn is used to assess the risk of exposure . We quanThe HQ is used to assess the health risk of each antibiotic and is defined as the ratio of daily exposure, i.e., the ratio of DED to the daily available dose ADI : HQ = DEThe HI is used to assess the cumulative health risk of combined antibiotic exposures and is based on a dose-additive concept of similar effects induced by multiple antibiotics, defined as the sum of HQs with similar effect endpoints. It is a new index for the quantitative and systematic evaluation of antibiotic exposure levels that provides a comprehensive indication of the level of antibiotic exposure. The HI is currently applied in evaluating the health risk of the long-term low-dose cumulative intake of antibiotics in humans. Because adults can be exposed to multiple antibiotics simultaneously, the HI was determined for 3 sulfonamides according to toxicological effects, 11 antibiotics according to microbial effects, 4 antibiotics for veterinary use and 10 antibiotics for preferred veterinary use, on the basis of different effect endpoints. An HQ or HI ≥1 indicates the presence of a potential health risk.The 18 antibiotics were grouped according to their antimicrobial mechanism or use, and new variables were generated via the summation of antibiotic mass concentrations in urine. The three new variables were human antibiotics (HAs), veterinary antibiotics (VAs) and preferred veterinary antibiotics (PVAs). The five new variables for antimicrobial mechanisms were tetracyclines, fluoroquinolones, macrolides, sulfonamides and phenicols. The same categories of HI were summed to generate new variables, which were divided into HI for microbiological effects, HI for toxicological effects, HI for veterinary use and HI for preferred veterinary use. Descriptive analysis provided the frequency of antibiotic testing or percentage of selected concentrations . The rank-sum test was used to analyze differences in blood glucose or antibiotic concentrations and other demographic variables, such as sex, age, education, income level, physical activity, diet, smoking and alcohol consumption.p-value for the demographic variable of the total glucose or total antibiotic concentration derived from the t-test, ANOVA or rank test  was <0.05. Model A included the following covariates: age and income level. If the p value of the demographic variables of the total blood glucose or total antibiotic concentration obtained from the t-test, ANOVA or rank test  was <0.2, these variables were included in Model B as covariates. Model B included the variables from Model A as covariates plus sex, education, frequency of eating pork, frequency of eating mutton, frequency of eating fried food, vegetable consumption and smoking. The covariates associated with the relationship between antibiotic use and T2DM that had been studied in previous clinical settings were included in Model C. Model C included the variables in Model B as covariates plus physical activity, frequency of eating beef, fruit consumption and drinking . Finally, the three models were statistically analyzed with binary logistic regression models to assess the relationship between HI and T2DM. All statistical analyses were performed in the statistical software SPSS 26. p-values <0.05 were considered statistically significant.The HI was classified into two groups according to hazard to human health: the HI ≤ 1 group and the HI > 1 group. Participants with fasting blood glucose values ≥7.0 mmol/L and self-reported T2DM were classified as the T2DM group, and those with fasting blood glucose values <7.0 mmol/L were classified as the non-T2DM group . VariablAll 18 antibiotics were detected in urine, with an overall detection rate of 51.0% and detection rates of individual antibiotics ranging from 0.2% to 20.0%. Urinary antibiotic concentrations ranged from below the limit of detection to above 1000 ng/mL . Two or Daily doses of antibiotic exposure were mostly lower in the 95th and 99th percentiles of the non-T2DM population than they were in the T2DM population, except for tetracycline, ofloxacin, sulfamethoxazole and florfenicol .Among 525 middle-aged and older people in Xinjiang, 40 individuals (7.7%) had an HI value ≥ 1 and a health risk. The values of the HQ were mostly higher for the T2DM than they were in the non-T2DM population, except for individual antibiotics such as tetracycline, norfloxacin, ofloxacin, florfenicol and sulfamethoxazole. Notably, the 99th percentile HQ values of oxytetracycline and norfloxacin were relatively high in the T2DM population, at 26.448 and 62.427, respectively, thus indicating that a high oxytetracycline and norfloxacin intake was associated with a high risk of susceptibility to human health effects .CI and an OR of 2.948 (1.287–6.756). The confidence intervals were 3.391 (1.417–8.120) and 3.442 (1.423–8.327) after adjustment for covariates in Model B and Model C, respectively. After adjustment for covariates in Model A, the risk of T2DM was 2.928 times higher in those with an HI > 1 for PVAs than it was in the group with an HI ≤ 1 for PVAs, with a confidence interval of 2.928 (1.279–6.706). After adjustment for covariates in Models B and C, the confidence intervals were 3.271 (1.371–7.802) and 3.348 (1.386–8.083). After adjustment for covariates in Model A, those in the HQ > 1 group for norfloxacin had 10.075 times the T2DM risk of those in the HQ ≤ 1 group for norfloxacin, with a credible interval of 10.075 (1.612–62.952), and they still had a higher risk after adjustment for covariates in Models B and C, with credible intervals of 11.243 (1.728–73.142) and 10.511 (1.571–70.344). The risk of T2DM was 4.789 times greater in the ciprofloxacin HQ > 1 group than it was in the ciprofloxacin HQ ≤ 1 group after adjustment for covariates in Model A, with a confidence interval of 4.789 (1.336–17.175), and also after adjustment for covariates in Model B and Model C, with confidence intervals of 5.241 (1.377–19.946) and 6.565 (1.676–25.715).The binary logistic regression results indicate that, after adjustment for covariates in Model A, the HI for microbiological effects, HI for PVAs, HQ for norfloxacin and HQ for ciprofloxacin were associated with a higher risk of T2DM in participants with higher exposure risk (HI > 1 or HQ > 1), and this association persisted after adjustment for more covariates in Models B and C . SpecifiIn this study, we measured the concentrations of 18 common antibiotics in urine and then calculated the DED, HQ and HI, thus indicating the relationship between T2DM and antibiotic risk in middle-aged and older people. The HI for microbiological effects >1, HI for PVA use >1, HQ for norfloxacin >1 and HQ for ciprofloxacin >1 in middle-aged and older people were positively associated with T2DM. These associations persisted after adjustment for several confounding factors known to be associated with T2DM. To our knowledge, this study is the first to use urinary antibiotic biomonitoring to explore different sources of antibiotic exposure, and to assess the health risks and consequent effects on T2DM.Studies based on the biomonitoring of urinary antibiotic concentrations are lacking. Several studies have been performed in China and Korea ,25,26,27All 17 antibiotics have short half-lives of <15 h, except for azithromycin, which has a half-life of approximately 40 h . PreviouA growing body of evidence from experimental studies suggests a causal relationship between the gut microbiota and diabetes . Age facAlthough clinical studies have reported a relationship between antibiotics and T2DM ,14,55,56This study performed biomonitoring to assess the health risks of middle-aged and older people in Xinjiang. However, it has several limitations. First, this study was a cross-sectional study and thus could not demonstrate a causal relationship between antibiotics and T2DM. Antibiotic exposure might potentially be a proxy for some conditions associated with T2DM. Participants with T2DM might have had different levels of exposure to antibiotics in food or drinking water, and thus different levels of assessed health risks, depending on their dietary structure and intake. Second, because people are intermittently exposed to antibiotics in their daily lives, urinary concentrations in people may vary throughout the day. Antibiotics have short half-lives, and we collected morning urine from participants, thus potentially underestimating the exposure and the health risk assessment after multiple exposures to antibiotics. Single urine samples may not reflect the levels of long-term antibiotic exposure, thus potentially weakening the association between the risk of antibiotic exposure and T2DM in middle-aged and older adults.We used a biomonitoring approach to assess antibiotic exposure and thus the risk of antibiotic exposure, and we found that exposure to antibiotics in daily life (mainly from food or drinking water contaminated with antibiotics), particularly with an HI > 1 for microbiological effects, HI > 1 for PVAs, HQ > 1 for norfloxacin and HQ > 1 for ciprofloxacin, may be risk factors associated with T2DM in middle-aged and older people. Because cross-sectional studies and primary urine sampling reflect long-term antibiotic exposure, more prospective studies and experimental studies are needed to further explore these associations and their underlying mechanisms.


Optimizing antibiotic prescribing is a crucial element of the fight against antibiotic resistance. Antibiotic prescribing patterns in jails have not been studied. We established a baseline of antibiotic prescribing between Massachusetts jails. We detected heterogeneity in quantity and duration of antibiotic prescriptions, revealing an opportunity for improved practice. However, antibiotic prescribing in correctional healthcare settings, including jails and prisons, has gone largely unstudied. Although core elements of antimicrobial stewardship have been recommended by the CDC that include application to low-resource settings, there are no guidelines for antimicrobial stewardship in correctional facilities. Approximately 2 million people are incarcerated each year in the United States, so investment in improving antimicrobial delivery to people who are incarcerated will benefit a sizeable portion of the country. We compared antibiotic use across Massachusetts jails as a first step to improve antibiotic prescribing practices.Antimicrobial resistance is a growing public health emergency that has sparked collaboration and innovation across disciplines. Efforts to improve antibiotic prescribing practices have focused on traditional medical settings, such as hospitals, with an increasing focus on emergency departments, ambulatory clinics, and skilled nursing facilities.We collected deidentified antibiotic prescription data  for all 12 county jails in Massachusetts for the 2021 calendar year. One jail was excluded due to its relatively small size and census. The data set was analyzed across 4 categories of oral and intramuscular antibiotic prescriptions: (1) anti-MRSA agents , (2) fluoroquinolones (ciprofloxacin and levofloxacin), (3) other antibiotics , and (4) all. Due to the limited availability of jail census data, we estimated each jail’s population by converting the average daily population (ADP) to an annual population . The ADP was converted to an average weekly population, then multiplied by the average weekly turnover rate for a jail of that size to account for jail flux, and finally multiplied by 52 weeks.We chose 2 metrics for comparison of antibiotic use between jails: antibiotic days per patient and an estimated defined daily dose (DDD) per 1,000 inhabitants. Antibiotic days per patient was used to model the most prescribed duration of therapy. The DDD methodology is recommended by the WHO and the CDC for monitoring medication use.We detected heterogeneity in antibiotic prescribing practices across the Massachusetts state jail system. Our analysis revealed differences in the quantity of prescriptions and duration of therapy.1). The duration of therapy with anti-MRSA drugs ranged from 7 days in some jail to 10 days in others. Duration of therapy for “other” and “all” antibiotics ranged from 7 to 14 days.The most frequently prescribed duration of therapy with antibiotics varied between jails. For fluoroquinolones, jail 2 had the shortest duration of therapy at 5 days, whereas jail 11 had the longest duration of therapy at 30 days . For uncomplicated skin and soft-tissue infections, a common indication for oral anti-MRSA treatment, shorter courses of therapy (5–7 days) are recommended. Therefore, there may be an opportunity to educate clinicians on the selection of agents within this setting.Variability in prescribing practices reflects an opportunity to optimize antibiotic prescribing.ail Fig. , with 10 Although ASPs may exist at jails or state prisons, we could find no publicly available data about the process or outcomes. Better understanding antibiotic prescribing practices in the carceral healthcare setting comes with an additional urgency owing to the significant health equity and public health concerns associated with the incarcerated population. The carceral system is the primary health provider to a large portion of the United States, with disproportionate incarceration of poor, minoritized, and marginalized communities. Carceral facilities in the United States have high rates of multidrug-resistant infections, and prudent antibiotic use in these settings is highly relevant.Contrary to jails, the federal prison system has developed strategies aimed at improving antibiotic prescribing, including implementation of antimicrobial stewardship programs (ASPs).This study had several limitations. Jail healthcare delivery models vary by county in Massachusetts , and this was not considered in our analysis. Because our data unit was deidentified prescriptions, we could not ascertain nor control for how pre-existing conditions affected antibiotic utilization nor evaluate the appropriateness of antibiotic prescriptions.Despite these limitations, our research is novel as the first publication evaluating variability in prescribing practices among jails within the same state system. Having established this baseline of antibiotic use, our next steps will include analyzing disaggregated data to identify underlying trends and appropriateness of prescriptions. Our goal is to work with key stakeholders in jail and prison healthcare to promote integration of antimicrobial stewardship practices, decrease exposure to unnecessary antibiotics, and decrease the development of resistant bacteria.