However, flexural strength showed a different response, with the highest strength of 5.99 N/mm2 observed at 50% laterite replacement, after which strength declined with further increases in the laterite ratio. For economic and engineering considerations, it is recommended to use 25% laterite replacement with sand to produce grade 30 concrete, while 50% laterite replacement is suitable for grade-25 concrete. Importantly, the study found that a temperature of 250 °C did not significantly affect concrete strength, with changes of no more than 5%, which is consistent with expectations for conventional concrete. Furthermore, this research suggests that an optimal laterite replacement range of 25–50% should be considered when using laterite in concrete production.This study explored the impact of elevated temperatures on the residual structural properties of concrete made with a non-conventional fine aggregate such as laterite and quarry dust. In regions prone to high temperatures, such as tropical climates, the structural integrity of concrete can be compromised when exposed to elevated temperatures. Concrete samples were subjected to high temperatures (250 °C) and compared with control samples tested under normal conditions. In this research, the concrete mix was altered by replacing fine aggregates with different combinations of laterite (Lat) and quarry dust (QD) at varying percentages: 10%Lat:90%QD, 25%Lat:75%QD, 90%Lat:10%QD, 75%Lat:25%QD, and 50%Lat:50%QD. The physical properties of the constituent aggregates, including sand, laterite, quarry dust, and granite, were assessed, and an experimental mix was designed. The concrete samples underwent curing for 3, 7, 14, and 28 days, and their mechanical properties, specifically compression and flexural strength, were analyzed. The results demonstrated that as the percentage of laterite in the concrete matrix increased, there was a linear improvement in performance in terms of density, sorptivity, and strength gain. The maximum compressive strength reached 32.80 N/mm Such exposure to heightened temperatures can have a profound impact on concrete's structural characteristics, resulting in diminished strength, rigidity, and resilience. Often, infrastructures confront elevated temperatures due to fire incidents and other factors, underscoring the importance of considering materials' resistance to high temperatures when designing and implementing such structures2.Concrete serves as a fundamental building material renowned for its adaptability, longevity, and cost efficiency, making it indispensable in various construction applications. Nonetheless, in real-world situations, concrete structures encounter diverse environmental conditions, including exposure to elevated temperatures, which can arise from fires or high-temperature industrial processes4, palm kernel shells5, crushed recycled concrete7, and others. These non-conventional aggregates offer environmental advantages like reduced reliance on natural resources and waste reduction. Nevertheless, their performance under elevated temperature conditions remains a relatively unexplored area of research8.Moreover, with the growing utilization of unconventional materials in construction, there is an increasing need for comprehensive studies to gain deeper insights into how these construction materials perform under varying conditions. Numerous prior investigations have sought to comprehend the behavior of diverse non-traditional concrete materials, including laterites.9, described non-conventional concrete also known as concrete aggregate substitutes as the adding or replacement of some waste materials or fibers in the normal concrete. Also, Limbachiya et al.10 discovered that the compressive strength and modulus of elasticity of concrete made with recycled aggregate is at least two-third that of natural aggregate concrete. Baalbaki et al.11 proved that the volume fraction of aggregates and elastic properties are affected by elastic modulus of concrete. The palm kernel shell which has proven to have properties of a good concrete aggregate according to Abdul and Ganapathy12, is hard and good enough but is not recommendable because of its unavailability, the demand for sand fit for construction works is on the increase daily13.Over time, there has been a notable surge in interest regarding the exploration of alternative materials to replace traditional concrete aggregates. Shanmugavel et al14. Consequently, there is a pressing need to explore alternatives to traditional fine aggregates, such as lateritic sand, to mitigate the environmental impact of sand extraction and reduce the vulnerability of coastal communities to storm damage. This can be achieved by partially replacing sand with laterite15.Moreover, it has been observed that the global extraction of billions of tons of sand and gravel annually to meet the demands of the construction industry is causing significant environmental repercussions. This practice leads to the depletion of beaches and riverbeds, causing damage to public assets and exerting additional stress on industrial, commercial, and residential structures16. Therefore, gaining a comprehensive understanding of how concrete made with non-conventional aggregates behaves under elevated temperature conditions is essential for ensuring the structural integrity and fire resistance of these environmentally sustainable concrete blends. Research conducted by Xie et al.17 evaluated the thermal properties of laterite concrete by conducting thermal conductivity tests. The results indicated that the thermal conductivity of laterite concrete decreased with increasing aggregate size and water-cement ratio.Furthermore, the impact of elevated temperatures on concrete is influenced by various factors, including the properties of the aggregates used in the mix. Non-conventional aggregate-based concrete may exhibit different thermal responses compared to conventional concrete due to variations in mineral composition, porosity, and microstructure18 investigated the compressive strength of laterite concrete specimens subjected to high temperatures. The study revealed a reduction in compressive strength with increasing temperature, highlighting the need to consider the thermal response of laterite concrete in structural design. A study conducted by Wang et al.19 used SEM to analyze the microstructural changes in laterite concrete after exposure to high temperatures. The results showed the formation of micro cracks and the decomposition of hydration products, indicating the deterioration of the concrete's mechanical properties. Additionally, research by Liu et al.20 used FEA to analyze the temperature field and stress distribution in laterite concrete elements subjected to fire. The modeling results provided insights into the thermal response and structural performance of laterite concrete structures. Based on the literature review of previous research in the study area, the following observed research gaps were identified;i.Existing research lacks a comprehensive understanding of how laterized concrete incorporating non-conventional materials reacts to high temperatures.ii.There is limited research examining the thermal stability of laterized concrete in comparison to traditional concrete.iii.The construction sector lacks clear guidelines for the utilization of non-traditional aggregates such as laterite in concrete mixtures.Also, the research by Nguyen et al.This research endeavor aims to bridge these gaps in existing knowledge by exploring the response of laterized concrete to elevated temperatures. It will offer valuable insights and contribute to the establishment of comprehensive guidelines for sustainable construction practices.The primary objective of this research is to investigate how elevated temperatures impact the elastic structural characteristics of concrete that incorporates non-traditional aggregates such as laterite and quarry dust. Additionally, it seeks to assess the mechanical and morphological properties of concrete samples subjected to controlled heating within a high-temperature chamber. The experimental plan will involve the substitution of fine aggregates with various percentages of laterites and quarry dust, ranging from 10 to 90%, to gauge their influence on the concrete's response to elevated temperatures. This study will contribute valuable insights into the fire resistance and thermal stability of sustainable concrete formulations. The outcomes of this research will offer a deeper understanding of how elevated temperatures affect the mechanical attributes of these concrete compositions. This knowledge will empower engineers and designers to make well-informed decisions regarding the utilization of non-traditional aggregates in construction projects located in fire-prone environments. Ultimately, the study's overarching goal is to enhance the resilience and safety of concrete structures exposed to high-temperature conditions, while promoting sustainable construction practices.22.Concrete, though not a refractory material is combustible and has good fire-resistant properties. The ability of the concrete to sustain the effects of heat and the resulting reaction of water without excessively weakening, cracking, or spalling; the concrete's thermal conductivity; and the concrete's coefficient of thermal expansion are the main variables that influence a structure's ability to resist fire. In the case of reinforced concrete, fire resistance depends not only on the kind of concrete but also on the thickness of the cover over the reinforcement. The fire produces huge temperature gradients, and as a consequence, the top layers resist spalling and sputtering off the colder interior. The expansion of the reinforcement bars horizontally and vertically is made worse by heating, which causes the reinforcement to lose its connection and become weaker23.When heated, the aggregates in mortar and concrete expand gradually, whereas the hydrated products in cement once it has expanded to its greatest extent shrinks. The concrete weakens and cracks as a result of these two antagonistic activities. In terms of how they behave when heated, the different aggregates employed differ greatly. Quartz, the main mineral found in sand, gravel, granites, and gravels, grows gradually up to a temperature of around 573 °C. It suddenly expands by 0.85% when this temperature is reached. A descriptive effect of this expansion is seen in concrete's stability. If quartz is the most common mineral in the aggregate, the fire resistance of concrete is at its lowest24. Additionally, fire protection measures, such as the installation of fire-resistant barriers and early detection and suppression systems, are essential for minimizing the impact of fire on concrete structures. Overall, understanding the effects of fire on concrete is vital for designing fire-resistant structures, implementing appropriate safety measures, and ensuring the resilience and structural integrity of concrete buildings and infrastructure in fire situations25. Some of the primary effects of fire on concrete include:i.26.Loss of strength: Elevated temperatures during a fire can cause a reduction in the compressive strength of concrete. This is primarily due to the dehydration of cement paste and the decomposition of calcium hydroxide, which weakens the concrete matrix. The severity of strength loss depends on factors such as the duration and intensity of the fireii.27.Cracking and spalling: Concrete subjected to high temperatures may undergo cracking and spalling. The heat causes moisture trapped within the concrete to turn into steam, resulting in an increase in internal pressure. The buildup of pressure can lead to explosive spalling, where fragments of concrete break off from the surface. Cracking and spalling compromise the structural integrity of the concreteiii.2.Thermal expansion and stress: Fire causes concrete to expand due to thermal effects. The differential expansion of the concrete components, such as the aggregate and cement paste, can induce internal stresses. These stresses may lead to cracking and distortions in the concrete, further weakening its structural performanceiv.28.Loss of durability: The exposure to high temperatures can adversely affect the durability of concrete. The heat can accelerate chemical reactions, such as carbonation and alkali-silica reaction, which can lead to long-term deterioration and reduced service life of the structurev.29.Changes in microstructure: Fire can cause changes in the microstructure of concrete, including the decomposition of hydrated cement compounds and the formation of new phases. These alterations can affect the pore structure, density, and overall mechanical properties of the concreteFire has significant effects on concrete structures, leading to changes in their mechanical, thermal, and chemical properties. To mitigate the effects of fire on concrete, various strategies can be employed, such as the use of fire-resistant additives, fireproofing coatings, and appropriate structural design considerations30. The variation in thermal properties of concrete due to different aggregate types can impact the overall thermal behavior of structures. It can affect the rate of temperature rise or drop within the concrete, as well as the distribution of temperature throughout the structure. This, in turn, can influence factors such as thermal stress development, potential for cracking, and the overall thermal performance of the concrete31. It is important for engineers and designers to consider the thermal properties of concrete and select suitable aggregate types based on the specific requirements of the project. By understanding the effects of aggregate types on the thermal properties of concrete, it becomes possible to optimize the material composition for better thermal performance, energy efficiency, and durability of concrete structures in various temperature conditions17. Howlader et al.32 determined the thermal properties of concrete manufactured with different categories of aggregates. The research focus on the measurement of thermal conductivity of conventional aggregate and brick aggregates respectively. It was concluded that the specific heat of concrete made with bricks is 13% greater than the concrete having stone chips. The research also concluded that thermal conductivity has a linear relationship with thermal diffusivity in both types of aggregates. The duration of fire and the maximum temperature reached vary over a wide range. Temperature of 1000 to 1100 °C in fires lasting from 1 to 2 h have been observed more frequently than 1300 °C.The type of aggregate used in concrete can have significant effects on its thermal properties. The thermal properties of concrete, such as thermal conductivity, thermal diffusivity, and specific heat capacity, play a crucial role in determining how concrete responds to changes in temperature33. Here are some of the effects of aggregate types on the thermal properties of concrete:i.34.Thermal conductivity: The choice of aggregate can influence the thermal conductivity of concrete. Different types of aggregates have varying thermal conductivities, which is a measure of how well heat can transfer through the material. Aggregates with higher thermal conductivity, such as dense and heavy aggregates like granite or basalt, can result in concrete with higher overall thermal conductivityii.35.Thermal diffusivity: Aggregate types also affect the thermal diffusivity of concrete. Thermal diffusivity represents the speed at which heat can travel through the material. Aggregates with higher thermal diffusivity, such as aggregates with good thermal conductivity and low density, can lead to concrete with faster heat transfer propertiesiii.36.Specific heat capacity: The specific heat capacity of concrete is influenced by the type of aggregate used. Specific heat capacity refers to the amount of heat energy required to raise the temperature of a material by a certain amount. Aggregates with higher specific heat capacity, such as aggregates with high density, can contribute to concrete with a higher capacity to absorb and store heatAn accurate estimation of the performance characteristics of structures damaged in a fire helps in taking effective measures of- restoration. The performance characteristics take into account the physio-chemical and mechanical properties of the materials burnt and that of heated concrete. There is an accumulation of irreversible damages of mechanical and physio-chemical factors. Under mechanical factors, creep, cracking, shrinkage and plastic deformations may be classified, while under physio-chemical factors, corrosion, absorption and degradation etc. may be classified37. Neville38 stated that concrete loses it absorbed water in the range of 65 to 80 °C and its interlayer water in the 80 to 100 °C range. The increase in temperature up to 100 °C may supply the un-hydrated cement particle, with needed activation energy to enforce its hydration. This could be beneficial to concrete strength development if the W/C ratio of the gel is correct.It is accepted that in the temperature range of 4 to 80 °C the hydration process of ordinary Portland cement retain chemically stable, except possibly for the slight increase in the C/S ratio, where C and S represent C90 and ST02 respectively39. In this temperature range, dissociation of calcium hydroxides does not occur generally. Actually, the decomposition of calcium hydroxide into lime and water vapour during heating is not critical in terms of strength loss, but it leads to serious damage due to lime expansion during the cooling period. This indicate the harmful effect of cooling the heated concrete by gradual cooling in natural air is also harmful due to the absorption of heated concrete containing lime (CaO) in its cement gel logically, it is concluded that cooling concrete by water  has every harmful effect in reducing concrete compressive strength when compared to the effect of cooling in the natural air 40. In higher temperature ranges 400–600 °C, a series of reaction in hardened cement paste may activate. This reaction starts with the completion of desiccation of the poor water system, followed by (H) and the decomposition of hydration products. Decomposition of C-S-H or C-S-H (H) generally occurs at 600–700 °C. the breakdown of C-S-H may take place at 800 °C and results in slight increase in the residual strength. The chemical decomposition and loss of the chemically bonded water set the stage for melting at temperature above 900 °C41.When temperatures are raised from 100 to 200 °C, the material properties of the cement past raised begins to lose its stability due to a weak physical chemical reaction. In this temperature range, the evaporable moisture plays a dominant role in reducing cohesive forces between C-S-H layers and their gel surface energy. And thus the cement gel shrinks and the strength reduces42. It helps engineers and designers make informed decisions regarding material selection, structural design, and fire-resistant measures to ensure the safety and integrity of concrete structures in such conditions. Additionally, it guides the development of high-temperature resistant cementitious materials and protective measures to mitigate the detrimental effects of high temperatures on cement paste and overall concrete performance43. When cement paste is exposed to elevated temperatures, several changes occur, including:i.44.Dehydration: One of the primary effects of high temperature on cement paste is dehydration. The heat causes the evaporation of water from the cement paste, leading to the loss of moisture. Dehydration can result in a decrease in the volume of the paste and the formation of microcracks, which can weaken the materialii.45.Calcium hydroxide decomposition: Cement paste contains calcium hydroxide (portlandite), which can decompose at high temperatures. The decomposition of calcium hydroxide releases water vapor and leads to a reduction in the pH of the paste. This can affect the chemical stability of the paste and potentially contribute to the deterioration of concreteiii.38.Strength reduction: Elevated temperatures can cause a reduction in the strength of cement paste. Dehydration and the decomposition of calcium hydroxide can weaken the bonding within the paste, leading to a decrease in compressive strength and other mechanical properties. The severity of strength reduction depends on the temperature and duration of exposureiv.46.Microstructural changes: High temperatures can induce significant microstructural changes in cement paste. It can cause the formation of new phases, such as calcium aluminate hydrates and anhydrous phases, which can alter the paste's structure and properties. These changes can impact the paste's density, porosity, and overall durabilityv.39.Cracking: Thermal expansion mismatch between the cement paste and other components, such as aggregates or reinforcement, can lead to the development of cracks in the paste. The differential expansion and contraction can generate internal stresses, resulting in cracking and potential loss of integrityHigh temperatures can have significant effects on cement paste, which is the binding material in concrete. Understanding the effects of high temperature on cement paste is crucial for assessing the performance and durability of concrete structures exposed to fire or other elevated temperature environments47. The importance of lateritic soil in engineering field cannot be over emphasized, Field observation show that the predominant content of the admixture will mainly be sand. However, the sand occurs with different amounts of clay, silt and grave. The sand is expected to influence the engineering behavior of the cohesive soil. Knowledge of the influence of sand on strength and compressibility parameters of the soils is fundamental in the interpretation of their properties for engineering design48.Lateritic soil, also known as laterite, is a type of soil that is commonly found in tropical and subtropical regions. It is formed through weathering processes that occur in hot and humid climates, where intense rainfall and high temperatures promote the decomposition of rocks and minerals2/Fe2O3, in the range of 1.33–2.0. Laterite soil with ratios less than 1.33 are considered indicative of true laterites, while those between 1.33 and 2 indicate laterite soils and those greater than 2 are non-laterite tropically weathered soils. Laterized concrete is defined as the replacement of fine aggregate (sand) with laterite at different proportions in the component of concrete49. The quest of having concrete at a cheaper rate and at varying temperatures has prompted many researchers to work on laterized concrete. Nkanang et al.50 conducted a study on laterized concrete and found that as the percentage of laterite in the mix increased, the compressive strength decreased. They also observed a decrease in flexural strength with higher laterite content. Also, Obilade et al.51 investigated the effect of different laterite particle sizes on the compressive strength of laterized concrete. They reported that smaller particle sizes of laterite resulted in higher compressive strength compared to larger particle sizes.Hence, Laterite can simply be defined chemically as a material having the ratios of silica to sesquioxide represented by molecular silica-alumina ratio: SiOOrdinary Portland Cement (OPC), lateritic sand, river sand and quarry dust were used for all mixes in this research. In obtaining the effect of elevated temperatures, the study considered 0 °C and 250 °C. The concrete strength was studied for 3, 7, 14, and 28 days respectively, the experimental program and concrete mix design for this research study is presented in Tables The Lafarge cement brand of ordinary Portland cement was used for this purpose. This cement sets and hardens when it interacts with water chemically. I ensured that it is kept in a damp-free environment to avoid lump formation. Cement was gotten from Lafarge cement plant at Mfamosing, this is the Ordinary Portland Cement (OPC) which undergoes hydration when it comes in contact with water and conforms to BS EN 197-1:2011. The cement was kept away from wet and extreme cold weather to avoid it from forming lump.Water is what aids the binding of cement; hence, it is importance in this research. It brings about the hydration process of cement and aids the overall reaction between cement and other materials in it. Domestic Portable tap water inside the lab was used throughout the laboratory aspect of this research work and it met the ASTM C1602-12 water specification for concrete works.Aggregates as an important constituent in concrete contributes largely to its economy and also promotes the body building of concrete, while minimizing its shrinkage effect. In this research two different fine aggregates namely laterite and quarry dust were used, while the conventional fine sand obtained in from river bed in Akwa Ibom State, Nigeria with particle size of 6 mm maximum, and 2.4 fineness modulus was used as control.Lateritic sand as one of the fine aggregates used in this work was gotten from a borrowed-pit site at Goodluck Jonathan bypass, Calabar at a depth of 2.5 m. the lateritic soil samples used for the test experiment in this research study is shown in Fig. 1This material was obtained from the rich deposit at Mark Sino quarry site at Akamkpa local government area of Cross River State, and it is a local government located in the Southern part of Cross River State which is approximately 25 min drive from Calabar City.Crushed granite was the coarse aggregate used with maximum and minimum sizes of 20 mm and 5 mm respectively produced at Akamkpa quarry site conformed to BS EN12620.52.The methods involved characterization of the concrete constituent materials, preparation of concrete samples, and testing of hardened concrete samples for different structural properties and water absorption characteristics. Lateritic sand and quarry dust was used to substitute the conventional sand in different proportions from 10 to 90%. In order to develop controls for the experimental works, important related literatures were reviewed and standard/codes of practice were also applied. In the laboratory, experiment was carried out in this work by testing the fresh and hardened concrete53. The specific gravity test by the pycnometer method is a commonly used technique to determine the specific gravity of solid materials. This method involves the use of a pycnometer, which is a glass or metal container with a known volume. To calculate the specific gravity of the test materials, we deploy the formula below using the formula:The specific gravity test is a commonly conducted laboratory test to determine the density or specific gravity of a solid material. It is often performed on construction materials such as aggregates, soils, and cementitious materials, including concrete. The specific gravity of a substance is the ratio of its density to the density of a reference material, typically water. The test helps to assess the quality, composition, and properties of materials, and it can provide valuable information for engineering and construction applications. The specific gravity of a material is a dimensionless value and is typically reported as a ratio or a decimal. A specific gravity greater than 1 indicates that the material is denser than water, while a specific gravity less than 1 indicates it is less denseThe aggregate impact value (AIV) test is a standard test conducted on aggregates to determine their resistance to sudden impact or shock. It provides an indication of the aggregate's toughness and suitability for use in construction applications, particularly in road construction. A representative sample of the aggregate were obtained, usually with a minimum size of 10 mm. Ensure the sample is clean, dry, and free from any contaminants. The test samples were aggregates sized 10.0 mm to 12.5 mm. The aggregates was dried by heating at 100–110 °C in the oven for a period of 4 h and cooled. The test sample is placed in the cylindrical measure and compact it using 25 strokes of the tamping rod. Each layer should be uniformly tamped. The measure with the compacted aggregate is then placed in the impact testing machine. A total of 15 blows evenly distributed on the aggregate is applied, each blow being delivered by a standard hammer weighing between 13.5 to 14 kg. The height of fall for each blow is usually 380 mm. After the impact, remove the aggregate from the measure and sieve it through a 2.36 mm sieve. The aggregate impact value for the test samples is calculated using the formula:54.X-ray fluorescence testing provides valuable information about the elemental composition of a sample, including major, minor, and trace elements. It allows for the identification and quantification of elements ranging from sodium to uranium, depending on the capabilities of the XRF instrument. It is commonly applied in various industries, including mining, geology, environmental analysis, materials science, and archaeology. XRF provides non-destructive and rapid analysis, making it a valuable tool for quality control, research, and exploration purposes. This was done by X-ray fluorescence using an Axios PANAlytical machine with System ID 206104, Type number PW4400/10, S/N DY3222 and MFG date 2015-12 to determine the oxides composition of the samples55. The freshly mixed concrete cubes, cylinders and beams is shown in Fig. The compressive strength test is a standard test conducted on concrete to determine its ability to withstand compressive loads. It is one of the most important tests for evaluating the quality and durability of concrete in various construction applications. The constituent materials used for this research are cement, quarry dust, laterite, crushed granite and water. Lateritic sand and quarry dust were added to the mix to replace conventional fine sand at various percentages of 10–90%. The sample should be taken in accordance with BS EN 12390 standards. Generally, cylindrical or cube-shaped specimens are commonly used for testing. The fresh concrete were filled in the cubic molds of 150 mm × 150 mm × 150 mm. the concrete cubes were removed from the molds after 24 h and immersed into the curing tank for varying curing durations of 3, 7, 14, and 28 days respectively. Place the hydrated specimen centrally on the compression testing machine, ensuring that it sits level and properly aligned with the loading axis. Apply a gradual and continuous load at a specified rate, typically around 0.2 MPa/s, until the concrete specimen fails under compression and record the maximum crushing load applied to the specimen56. The experimental setup for the flexural test is shown in Fig. The flexural strength test, also known as the modulus of rupture test, is conducted on concrete to determine its ability to resist bending or flexural stresses. This test provides valuable information about the concrete's strength and its ability to withstand loads that cause bending or deflection. A concrete beam of 100 mm × 100 mm × 400 mm dimension was cast as sample for flexural test. In casting this beam, a wooden mould of the size above was fabricated in the wood products engineering department of the university, this mould was properly lubricated before the freshly mixed concrete was introduced into it in 3 layers of approximately 30 mm thickness, then vibrated with a vibration table for an average of 15min until all air bobbles/pour spaces are filled. After the last layer which is approximately 40 mm tick the surface was dressed to achieve smooth finishing. The concrete beams were removed from the molded after 24 h and cured for 28 days. The beam specimen are then placed on the supports of the flexural testing machine, ensuring that it rests horizontally and aligns with the loading axis. Apply a gradual and uniform load at the midpoint of the specimen until it fractures or reaches the desired deflection, as per the testing standard BS EN 12390-5. Record the maximum applied load and the corresponding deflection57. The tests were carried out for the sand replaced with quarry dust and laterite in the concrete mix and the control. The sorptivity test is conducted on concrete to measure its ability to absorb and transport water through capillary action. This test provides valuable information about the permeability and durability of concrete in relation to water absorption. Concrete beams of 200 × 100 × 100 mm were cast the same way they were cast for flexural strengths test with a binder to aggregate ratio of 1:2.3:3.2 and w/c ratio of 0.63. Three concrete samples were cast for each percentage replacement . The concrete samples were cured for 28 days, then removed from the curing tank, allowed to drain and sun-dried in a temperature between 28 and 38 °C. The drying took up to 3 days during which the weights of the samples were checked at intervals until the difference in weight remains relatively the same. The samples were then removed from the sun and used for the test. The heated samples were places in a kiln and heated for 250 °C, allowed to cool at room temperature, then removed and used for the test58.Sorptivity is the ability of a materials to absorb water and transmit it through the pours by capillary actiono (g). The concrete sample were placed vertically on the mesh with the 100 mm × 100 mm faced touching the mesh to 5 mm water level and allowed for 4 min timed with a stop watch. After 4 min, each concrete sample was removed and placed on a damp towel to mob-off the excess water on the body. The sample was immediately placed on the digital weighing balance to record the weight at four minutes, taken as W4 (g). The sample was placed back on the mesh and the stop watch placed to continue timing for the process was repeated for 9, 15, 25, 36, 49 and 56min respectively. The weight was recorded as W9, W15, W25, W36, W49 and W64 respectively. For each percentage replacement, the average rate of absorption in (g/mm2) × (10–3) was plotted against the square root of time (√t). The slope of the graph gave the sorptivity of the material59.A steel mesh was placed in a stainless steel tray containing water to a level that reaches 5 mm on the rectangular beam. The initial weight of each concrete sample was taken as WAll authors were highly cooperative and involved in research activities and preparation of this article.60.Concrete is composed of various ingredients that contribute to its physical properties. The physical properties of concrete ingredients can vary depending on factors such as the specific type and source of the ingredient, manufacturing processes, and regional variations. Understanding the physical properties of concrete ingredients is crucial for designing and producing concrete with desired characteristics. These properties influence factors like workability, strength, density, and durability. It is important to consider the specific requirements of each ingredient and their interactions to achieve the desired concrete properties.3 and Ilangovana et al.61The respective specific gravity of constituent aggregate materials: laterite, quarry dust and crushed rocks from the test results are 2.2, 2.6 and 2.9 respectively. The values are in agreement with the research findings of Ukpata et alThe aggregate impact value for the coarse aggregate (crushed granite) was 6.7% thereby making it exceptionally strong, as it is less than 10%. The particle sizes of fine aggregates  ranged from 0.06 to 4.75 mm, while coarse aggregate (crushed granite) ranged from 5 to 20 mm in sizes. With the results above, the aggregate was generally found to be suitable for concrete work, since they meet the BS EN 1097-2:2010 specification.62.The particle size distribution curve for the fine aggregate  and coarse aggregate (granite) is presented in Figs. Concrete is composed of various materials that have distinct chemical properties. Understanding the chemical properties of concrete materials is crucial for assessing compatibility, potential reactions, and long-term performance of concrete structures. It helps in mitigating adverse effects and optimizing the composition and mix design for desired chemical behavior and performance. The oxide composition of the various materials; sharp sand, quarry dust, crushed granite, laterite and cement were obtained from the XRF test results as shown in Table 2 content and very low CaO content. This however satisfied the requirement of Natural Pozzolans, which is that they should have a combined sum of SiO2, Al2O3 and Fe3O2 of at least 70% of the total oxides63. Also, it can be seen that the silica (SiO2) content in sharp sand, quarry dust, crushed granite and laterite falls within the same neighborhood. It is also observed that silica has the highest percentage composition amongst other oxides in all the materials. Silica (SiO2) is important in cement as it imparts strength to the cement due to the formation of di-calcium silicate and tri-calcium silicate. However, excess silica causes slow setting hence should be checked64.From the results of XRF in Table Alumina (Al2O3) On the other hand appears to be second in composition, it is responsible for the setting time of concrete; it imparts quick setting property to the cement. It is also worthy of note that, excess amount of alumina weakens the cement65.Iron oxide (Fe2O3) The next oxide above is Iron oxide (Fe2O3), as can be seen above, the parentage composition of Iron oxide in laterite (1.16), is almost the same with that of conventional sand (1.29). The presence of iron powder in cement improves the compressive strength and porosity but decrease the slump flow. Also, the water adsorption of the concrete increases with increasing amount of Fe in it. However, high amount of iron powder in a cement sample, decreases the workability of the concrete66.Calcium oxide (CaO) This is otherwise known as Lime. This oxide contributes to the mechanical strength of concrete, Attah et al.67, stated that the presence of calcium oxide in concrete gives it a high degree of mechanical strength, hydrates heat, and x-ray diffraction. The results above shows that there is a resemblance between the lime content in sand and that of laterite.Sulphur trioxide (SO3) Some research have implied that increasing Sulphur trioxide can enhance the expansive performance of cement material and prolong the setting time of the cement but the strength of the cement will decrease if the content of the Sulphur trioxide is more than 4%; especially in Portland cement68.Sodium oxide (Na2O) and potassium oxide (K2O) These can be called Alkalis oxide because when they react with water they form alkalis (Mohammed and Ali). The significant proportions of alkalis in cement can cause a quick setting, reduce the ultimate strength of the concrete and increase its expansion under water and shrinkage under drying conditions.3 which indicate concrete for structural and load bearing purposes and showed that the density decreases with increase in lateritic soil percentages in the concrete mix. The declining density of laterite concrete samples as lateritic soil content increases is mainly because of factors like reduced particle density, higher porosity, increased water absorption, variable particle size distribution, aeration, air voids, and chemical interactions. Overall, the unheated specimens possessed higher density properties than the heated samples though some of the results for unheated appear greater than normal weight concrete. This may be due to excess water from curing tank, since the samples were only surface dried before weighing69.Density is an important property of concrete that determines its mass per unit volume. the density of concrete can vary depending on the composition of its constituents and the specific mix design. Understanding the density properties of concrete is essential for various aspects, including structural design, load calculations, and material specifications. It allows engineers and contractors to assess the weight, mass, and performance characteristics of concrete in different applications. The densities of hardened concrete cube samples shown in Fig. 70. The development of compressive strengths for various unheated concrete mixes cured at 3, 7, 14, and 28 days respectively are presented in Fig. 2, 18.1–26.55 N/mm2, 20.20–28.4 N/mm2, 16.33–29.61 N/mm2, 20.91–32.65 N/mm2, and 20.34–32.80 N/mm2 for control, 10% lat., 25% lat., 50% lat., 75% lat. and 90% lat. respectively. The results were generally higher than the control concrete, except for the mix with 10% laterite, which was marginally less than the control. These results appear to contradict earlier findings by Ukpata et al.3, where compressive strengths were found to increase with decrease in laterite contents. This may be attributed to the difference in the quality of lateritic sand used in the study.Compressive strength is a vital property of concrete that measures its ability to withstand compressive forces and is an important parameter for structural design and evaluation. The compressive strength development properties of concrete is essential for designing and assessing the durability performance of concrete structures. It helps in determining the appropriate curing conditions, evaluating the early-age strength gain, and ensuring the long-term durability and structural integrity of concrete elements71, where compressive strengths were found to increase upon heating less than 500 °C temperature.The effects of elevated temperature on the compressive strength of concrete are significant and can have detrimental consequences on the structural performance of concrete. The effects of elevated temperature on the compressive strengths of concrete is vital for assessing the fire resistance and thermal performance of concrete structures. Proper fire protection measures and design considerations are necessary to mitigate the adverse effects and ensure the structural integrity of concrete under high-temperature conditions. The comparison between the compressive strengths of heated and unheated concrete samples cured for 28 days is shown in Fig. 2 for unheated specimens and 5.54 N/mm2 for heated specimens, are achieved at a 50% laterite addition to the mix. However, exposure to elevated temperatures leads to a decrease in flexural strength, and this reduction is more significant when the mix contains lower levels of lateritic soil from 0 to 10%. Interestingly, the flexural strength of the concrete heated with 25% lateritic soil content surpasses that of the unheated concrete sample. As the lateritic soil content exceeds 25%, the differences between the heated and unheated samples become smaller72.Elevated temperatures can have significant effects on the flexural strength of concrete, which is a fundamental property for assessing the structural performance and resistance to bending. The results presented in Fig. The sorptivity of heated and unheated laterized concrete samples refers to the rate at which water is absorbed by the concrete after it has been subjected to heating. Sorptivity is an important property to evaluate the permeability and moisture transport characteristics of concrete. The sorptivity of heated and unheated laterized concrete samples is important for assessing their durability and moisture-related performance. It helps in designing appropriate waterproofing and moisture protection measures for concrete structures to prevent water ingress and potential damage. The graphs of cumulative water absorption were plotted against the square root of time (in minutes) to determine water sorptivities for the concrete samples. The graphs are shown below from Figs. The effects of heating to elevated temperatures on sorptivities of concrete samples is presented in Fig. 73.The microstructure of concrete refers to the arrangement, composition, and characteristics of its constituent materials at the microscopic level. Understanding the microstructure is essential for assessing the properties and performance of concrete. The microstructure of concrete is crucial for optimizing its design, assessing its performance, and developing strategies for improving its properties and durability. Techniques such as microscopy, scanning electron microscopy (SEM), and other imaging methods are commonly used to study the microstructure of concrete samples. Microstructural studies were also employed to understand the behaviors of the various samples concerning mechanical and water transport properties. Hence, scanning electron microscopy (SEM), coupled with energy dispersive x-ray (EDX) spectroscopy were used to study the microstructure of concrete samples. These were supplemented by Fourier Transform Infra-red (FTIR) spectroscopySEM–EDX (Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy) is a powerful technique used to analyze the microstructure and chemical composition of materials, including concrete. By combining SEM imaging with EDX analysis, detailed information about the elemental composition and distribution within concrete samples can be obtained. Figures The elemental EDX spot analysis conducted on the SEM samples has revealed the elements associated with the analyzed points as shown in the EDX spectra in Fig. 74.FTIR (Fourier Transform Infrared) spectroscopy is a technique used to analyze the molecular composition and chemical bonds present in a material. It can also be applied to study concrete and provide valuable information about its composition and chemical characteristics. Fourier Transform Infrared (FTIR) spectra for corresponding samples as for SEM are presented in Figs. This study has investigated the structural properties of concrete containing laterite fine aggregate and the effects of heating to elevated temperature on the residual structural, microstructural and durability properties of concrete samples. It can be seen from the results of this study that the combination of laterite and quarry dust to replace the conventional river sand in the production of concrete for the construction industry in Nigeria and other tropical countries of the world results in structures with reliable structural characteristics and should be encouraged where there is comparative cost advantage. The physical property tests on the aggregates indicated a specific gravity result of 2.6, 2.6, 2.2 and 2.9 for sand, quarry dust, laterite and crushed granite respectively. The aggregate impact value test showed that the coarse aggregate used for the study was exceptionally strong having a value of 6.7% which is less than 10% according to BS EN 1097-2:2010.2 for room temperature, and 23–38.13 N/mm2 for elevated temperatures; flexural strength ranged from 3.88 to 5.98 N/mm2 and 1.43–5.54 N/mm2 for unheated and heated specimens respectively. The above strength properties were found to compared closely with normal concrete, while the proportion of 90% laterite to 10% quarry dust produced higher compressive strength values, 50% laterite to 50% quarry dust however produced better flexural strength.The compressive and flexural strengths of concrete using lateritic sand and quarry dust were measured in the laboratory. Compressive strength of the concrete was found to increase significantly when heated up to 250 °C and also increased with age as it is with conventional concrete. It was discovered that the compressive strength of the concrete at 28days varied with respect to the replacement percentages ranging from 26.55 to 32.8 N/mmThis study has added important contributions to knowledge in numerous ways. This is the first known work to conduct the Fourier Transform Infrared Spectroscopy (FTIR) analysis which provides the chemical properties, and the Scanning Electron Microscopy (SEM), which gives the microstructure of the hardened concrete aggregate constituents with this replacement percentages within the geographical region investigated. The work will trigger further studies into the use of lateritic sand and quarry dust as fine aggregate in the production of structural concrete. This work has also directed interest in new areas for recycling of quarry dusts which solves environmental waste problems.i.The effects of elevated temperatures on the residual elastic modulus properties of concrete produced using laterite and quarry dust as fine aggregateii.Addition of supplementary cementitious materials obtained from waste derivatives in the development of laterized concreteiii.Application of artificial intelligence modelling for the optimization of the effects of elevated temperature on laterized concrete.Further research should be conducted to provide more design data for use. Therefore, the following area is recommended for further studies:


Intranasal delivery of drugs offers several potential benefits related to ease of delivery, rapid onset, and patient experience, which may be of particular relevance to patients with central nervous system (CNS) conditions who experience acute events. Intranasal formulations must be adapted to address anatomical and physiological characteristics of the nasal cavity, including restricted dose volume, limited surface area, and barriers to mucosal absorption, in addition to constraints on the absorption window due to mucociliary clearance. Development of an effective formulation may utilize strategies including the addition of excipients to address the physicochemical properties of the drug within the constraints of nasal delivery. Dodecyl maltoside (DDM) and tetradecyl maltoside are alkylsaccharide permeation enhancers with well-established safety profiles, and studies have demonstrated transiently improved absorption and favorable bioavailability of several compounds in preclinical and clinical trials. Dodecyl maltoside is a component of three US Food and Drug Administration (FDA)–approved intranasal medications: diazepam for the treatment of seizure cluster in epilepsy, nalmefene for the treatment of acute opioid overdose, and sumatriptan for the treatment of migraine. Another drug product with DDM as an excipient is currently under FDA review, and numerous investigational drugs are in early-stage development. Here, we review factors related to the delivery of intranasal drugs and the role of alkylsaccharide permeation enhancers in the context of approved and future intranasal formulations of drugs for CNS conditions. Intranasal drug delivery is a promising option for an increasing number of drugs for systemic absorption and, importantly, for targeting the central nervous system (CNS). Formulating treatments for intranasal delivery must take into account the unique features of nasal anatomy and physiology, which offer potential benefits and present specific challenges to be addressed by a successful formulation. The intranasal route is noninvasive, and prefilled devices can offer the benefits of quick administration for acute events and ease of use by nonmedical caregivers in the community, including the potential for self-administration . SurveysA growing number of intranasal drug formulations for the treatment of neurologic conditions have been developed in recent years. One treatment, esketamine nasal spray, is administered regularly under the supervision of a healthcare provider as an ongoing adjunct treatment for depression . HoweverStructures of the nose heat and humidify air for respiration; clear foreign particles, including pathogens; and facilitate olfaction . The two2, which is available for drug absorption.The central portion of the nasal cavity is covered by the respiratory and olfactory mucosa and represents the area most relevant for drug absorption after intranasal administration. The respiratory mucosa overlays the inferior and middle turbinates, as well as the lower part of the septum . It is tThe olfactory mucosa constitutes ≤10% of the nasal cavity surface area and covers the upper portion of the cavity ,18. ThisAlthough the nasal cavity may effectively capture intranasally delivered medications, it also creates a finite volume for dose delivery. The optimal volume for a dose of intranasal drug is no more than 100 to 150 µL per nostril . Larger Second, mucus coating the epithelium of the nasal cavity acts as a defense against pathogens and particulates. Beating cilia continuously move mucus into the nasopharynx, and it is estimated that the mucus layer in the nasal cavity renews every 10 to 20 min . This maThird, the mucosal lining of the nose is sensitive to irritation by drugs or other compounds, which can lead to inflammation, secretions, itching, sneezing, and pain . This maAn optimal intranasal dose of no more than 100 to 150 µL translates into a requirement for adequate drug solubility in a fixed and relatively small dose volume. Physiochemical properties of a drug, such as its lipophilic-hydrophilic properties, and its molecular weight and size affect how it can be formulated for intranasal delivery and its absorption across nasal mucosa to ensure adequate and consistent bioavailability . In geneExcipients may be used to modify drug solubility, membrane permeation capacity, mucosal tolerability, mucosal adhesion, or formulation stability . These aThe intranasal delivery system must create reproducible parameters of dose delivered, droplet size distribution, and spray pattern and plume geometry to ensure consistent dosing to the intended target tissue . SeveralThe delivery system must provide ease of use for patients who self-administer treatment or for care partners responsible for administration. The device should function reliably in any orientation; have proven biocompatibility so as not to cause irritation to the lining of the nostrils; and, for delivery to incapacitated patients, be able to be used without their active participation ,31. UnidTo overcome the constraints imposed by nasal anatomy and physiology, including small volume, continual mucociliary clearance, and potential low drug permeability through the nasal mucosal membranes, intranasal formulations may use two broad strategies to optimize drug absorption and bioavailability: increase residence time in the nasal cavity or increase the rate of absorption across the mucosal membrane . Both st®  alkylsaccharide absorption enhancers [Alkylsaccharides are a family of sugars characterized by covalent linkages to ≥1 alkyl chain  37], se, se37], nhancers . These enhancers . In the nhancers . DDM is nhancers . DDM is Two possible mechanisms of action have been proposed for Intravail excipients’ effect of increased transmucosal transport. The first involves paracellular transport via transient loosening of tight junctions between epithelial cells by DDM to permit mucosal barrier permeation, which has been demonstrated in several human cell lines and epithelial tissue . A study8 chain length) formulations resulted in little to no absorption of calcitonin, whereas TDM (C14 chain length) formulations (0.125–0.25%) resulted in increased calcitonin plasma levels, peaking 7.5 to 10 min after administration [In animal studies of intranasal absorption, the use of TDM was associated with increased absorption of calcitonin (3.5 kDa), enoxaparin (4.5 kDa), and dalteparin (5 kDa) ,43,44. Tstration . Intranastration . Subsequstration . The stustration . For somstration ,46.To date, three intranasal medications containing DDM have been approved by the US Food and Drug Administration (FDA). They are treatments for migraine, seizure cluster in epilepsy, and opioid overdose. Clinical trials of these treatments support the favorable safety profile of DDM as an excipient. Currently, no intranasal treatments containing DDM are approved by the European Medicines Agency for use in Europe.®, Upsher-Smith Laboratories, Maple Grove, MN, USA) is indicated for the treatment of acute migraine headaches with or without aura in adults [max) for the DDM formulation was 10.2 min, while for sumatriptan 20 mg without DDM, the median time was 2 h. The concentration-time profile of the formulation without DDM registered two peaks. The researchers interpreted the early peak in plasma levels as an indication of nasally absorbed drug, while the second later peak was likely due to most of the dose being swallowed and absorbed through the gastrointestinal tract . Treatment-emergent adverse events (TEAEs) were reported in 9/93 (9.7%) patients, and 7/93 (7.5%) reported a TEAE that was considered to be treatment-related. The most commonly reported TEAEs were dysgeusia (3 patients) and application site pain (2 patients) [The efficacy, safety, and tolerability of sumatriptan plus DDM were assessed in phase 2, a double-blind, 2-period, placebo-controlled study of sumatriptan 10 mg with 0.20% DDM . The stuatients) .max) than subcutaneous dosing , with similar overall exposure, measured as the mean area under the curve (AUC), between intranasal sumatriptan 10 mg with DDM and the 4- mg subcutaneous dose. TEAEs occurring in ≥10% of patients in the trial overall study were dysgeusia , headache , nausea , paresthesia , and dizziness . In an open-label, long-term, repeat-dose safety study of the intranasal formulation of sumatriptan 10 mg with DDM, 51 of 167 (30.5%) patients reported application site pain , usually of mild severity [In the same report, researchers described a 3-way crossover study comparing pharmacokinetic parameters of intranasal sumatriptan plus DDM and 4 or 6 mg sumatriptan administered subcutaneously in 78 healthy volunteers. Intranasal sumatriptan with DDM provided significantly faster time to maximum concentration , which is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity  that are distinct from a patient’s usual seizure pattern in patients with epilepsy 6 years of age and older [Dodecyl maltoside is also a component of diazepam nasal spray  assessed the bioavailability of diazepam nasal spray compared with oral and rectal diazepam . IntranaThe safety of diazepam nasal spray was assessed in a long-term, open-label, repeat-dose phase 3 study of patients aged 6 to 65 years with epilepsy and seizure clusters (n = 163 safety population) . Overallp = 0.012) or the autoinjector  [Finally, surveys of patients with seizure clusters and their caregivers who used intranasal diazepam rescue therapy delivered in unidose pumps reported favorable impressions of the treatment. Patients and caregivers found it comfortable to carry and use outside the home, and they preferred the convenience of the nasal spray over rectal diazepam . Of note< 0.001) .®, Indivior Inc., Chesterfield, VA, USA) received FDA approval for healthcare and community use as an emergency treatment for known or suspected opioid overdose in adults and pediatric patients 12 years of age and older. In a preclinical study assessing three absorption enhancers including DDM in an animal model, absolute nalmefene bioavailability with 0.5% and 0.25% DDM was 76.5% and 71.0%, respectively, a significant increase (p < 0.05) over the bioavailability of nalmefene administered alone (47.7%) [max of intranasal nalmefene 3 mg was 2 h. The addition of DDM reduced tmax to 15 min and more than doubled Cmax . DDM had no apparent effect on nalmefene half-life. The onset of action with nalmefene with DDM was comparable to the intramuscular injection, with a higher Cmax. TEAEs were mild, with no apparent changes in olfaction [In May 2023, nalmefene nasal spray with DDM (Opvee (47.7%) . Nalmefe (47.7%) . A phase (47.7%) . Median lfaction .Three clinical trials  support the safety of nalmefene nasal spray. The most common treatment-related TEAEs (>5%) associated with nalmefene 2.7 mg nasal spray in healthy volunteers (n = 150) were nasal discomfort (28.7%), headache (26.7%), nausea (16.7%), dizziness (9.3%), hot flush (8.0%), and vomiting (6.0%) . These smax that was similar to manually injected epinephrine, with a shorter median tmax. Overall, the nasal spray produced similar or more pronounced pharmacodynamic changes compared with the injected formulations [Intramuscular injection of epinephrine is the standard of care for the treatment of severe allergic reactions, including anaphylaxis. Epinephrine nasal spray  is under development as a noninvasive alternative to injection for use in community settings . Epinephulations . Epinephmax from 30 to 10 min and a ~3-fold increase in Cmax with the addition of DDM to intranasal naltrexone [Naltrexone with DDM  is in development as a nasal spray for the treatment of patients with alcohol use disorder. Based on a pharmacokinetic study in healthy volunteers that showed a decrease in tltrexone , a phaseltrexone ,61. Finaltrexone .Intranasal delivery is becoming an increasingly common route of administration for drugs that treat CNS conditions. As of mid-2023, the FDA has approved ten intranasal formulations of CNS drugs as treatments ,12,13,63Permeation enhancers such as DDM and TDM are valuable excipients in a growing number of FDA-approved intranasal treatments. They have been shown to enhance drug absorption and bioavailability. DDM has a proven record of preclinical and clinical safety as an excipient in intranasal formulations. Moreover, the physicochemical characteristics of alkylsaccharides offer the potential for the development of other intranasal drug therapies for non-CNS and nonemergency conditions, incorporating hydrophilic and hydrophobic formulations of small molecules, peptides, and proteins. In the CNS, in particular, direct nose-to-brain delivery of drugs with intranasal delivery is an important potential benefit for certain molecules. As real-world experience with these newer intranasal formulations grows, additional potential benefits to patients and healthcare utilization may become apparent. Finally, DDM may also have potential applications in buccal, dermal, oral, and other pharmaceutical agents. While approved intranasal formulations have made progress in providing effective and acceptable treatment for patients with some conditions, significant unmet needs remain for many other conditions that range from allergy to psychiatry. Ongoing research and development of intranasal formulations offers future novel and alternative therapies, thereby broadening the choice of treatment options and improving the experience and outcomes for patients living with a number of acute CNS conditions.


Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Several novel therapeutic strategies have been developed to prolong the survival of patients with advanced HCC. However, therapeutic decision-making biomarkers owing to the extensive heterogeneity of HCC. Next-generation sequencing (NGS) is generally used in treatment decisions to help patients benefit from genome-directed targeting.A 56 year-old male with type-B hepatitis for more than 20 years was admitted to our department and underwent laparoscopic left lateral hepatic lobectomy for hepatocellular carcinoma. Unfortunately, the tumor recurred 1 year later. Despite multiple treatments, the tumor continued to progress and invaded the patient’s 5th thoracic vertebras, leading to hypoesthesia and hypokinesia below the nipple line plane 2 years later. NGS revealed MET amplification, and crizotinib, an inhibitor of MET, was recommended. After administration for a month, tumor marker levels decreased, and the tumor shrunk. The patient has remained in remission since that time.We report that a patient with high MET amplification benefited from its inhibitor, which was recommended by NGS. This indicates the potential clinical decision support value of NGS and the satisfactory effect of MET inhibitors. Hepatocellular carcinoma (HCC) is an aggressive malignant tumor that affects more than 600,000 people worldwide . BecauseDue to the genomic instability of carcinoma, it presents genetic and phenotypic variations within and between tumors . CorrespHere, we present a case of HCC that achieved a satisfactory partial response to crizotinib. The fundamental information, process of diagnosis and treatment, genetic test report, and evaluation of the treatment effectiveness of the patient were established in this article. We expect this study to provide new ideas for the diagnosis and treatment of advanced HCC.A 56 year-old male was admitted to our department for liver mass. Because of type B hepatitis for more than 20 years and inappropriate and discontinuous anti-viral therapy, he was diagnosed with slight liver cirrhosis several years before admission. There were few positive findings on physical examination. Based on the elevated serum alpha-fetoprotein level (51 ng/ml) and typical imaging findings, the patient was diagnosed with hepatocellular carcinoma with a history of hepatitis. The patient underwent laparoscopic left lateral hepatic lobectomy on 23 May 2019. Postoperative pathology confirmed moderately to highly differentiated hepatocellular carcinoma Figure 1The therapy was replaced with regorafenib plus sintilimab after the 5th thoracic vertebral metastasis in November. However, in December 2021, the patient experienced hypoesthesia and hypokinesia below the nipple line plane as 5th thoracic vertebras as metastasis progressed with spinal cord compression. Thoracic vertebral lesion resection combined with thoracic laminectomy and decompression was performed to relieve compression. The pathology of the metastasis is also shown in Common therapies for unresectable HCC, including tyrosine kinase inhibitors, checkpoint inhibition immunotherapy, radiotherapy, and interventional treatment, seem to have gradually become invalid. The patient suffered a 5th thoracic vertebra metastasis, ending to paralysis from the waist down. Although lumbar decompression was performed to help regain exercise ability immediately, the tumor showed a rapid progression.Thus, next-generation sequencing (NGS) was used to identify potential molecular-targeted agents. NGS covers all the coding exons, selected introns, and promoters, and analyses all gene mutations, including single-base mutation, DNA intercalation or deletion, gene copy number amplification or loss, and gene fusion or rearrangement. The NGS results of this patient showed MET amplification with copy number variations of 30.2.The patient received crizotinib (200 mg/day) on 24 January 2022 and was continually administered until the last follow-up without any adverse events. The baseline condition and images of the patients are shown in MET is a proto-oncogene encoding the receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF) , and it MET amplification may lead to oncogene addiction and confer poor prognosis . MET ampHGF induced by MET was initially identified as a growth factor for hepatocyte and fibroblast-derived cell motility . As previn situ hybridization (FISH) and NGS were used to evaluate MET amplification. The absolute gene copy number (GCN) or the ratio of MET to CEP 7 (chromosome 7 probe) was reported through FISH, while NGS compared samples to either a paired normal sample or a standardized set across many genes in a particular NGS assay  for the publication of this case report.YG contributed to the study concept and design, collected, and analyzed the data, and participated in drafting the manuscript. MX contributed to data acquisition and assisted in drafting the manuscript. ZC contributed to data acquisition and critically revised the article. QL conceived the study, participated in study design and coordination, and revised the manuscript critically. All authors read and approved the final manuscript


Mesenchymal epithelial transition factor receptor (MET) tyrosine kinase inhibitors (MET‐TKIs) have been approved for the treatment of non‐small cell lung cancers with MET exon 14 skipping mutations. Transient asymptomatic pulmonary opacities (TAPOs) associated with epidermal growth factor receptor (EGFR)‐TKIs have been reported. Here, we report a case wherein ground‐glass opacities (GGOs) appeared during the course of treatment with tepotinib, a MET‐TKI, but spontaneously resolved with drug withdrawal, after which treatment was resumed with a reduced dose. Although there have been no reports of TAPOs with MET‐TKIs, the clinical and imaging findings of this case were consistent with TAPOs. For TAPOs occurring because of MET‐TKI, the drug can be continued under careful observation even if GGOs appear. Mesenchymal epithelial transition factor receptor (MET) tyrosine kinase inhibitors (MET‐TKIs) have been approved for the treatment of non‐small cell lung cancers with MET exon 14 skipping mutations. Here, we report a case wherein TAPOs appeared during the course of treatment with tepotinib, a MET‐TKI. For TAPOs occurring because of MET‐TKI, the drug can be continued under careful observation even if GGOs appear. In recent years, specific gene‐targeting therapies have been developed for the treatment of lung cancer.Here, we present a patient who developed ground‐glass opacities (GGOs) after the initiation of tepotinib and therefore was suspected to have TAPOs.A 57‐year‐old female patient with no history of smoking and unremarkable medical history was admitted to our hospital with complaints of cough, dyspnea, and chest pain for 1 month. Chest X‐ray revealed left pleural effusion. Chest computed tomography (CT) showed a mass in the left lower lobe, mediastinal lymph node metastasis, and right pleural effusion. Pleural fluid cytology led to the diagnosis of adenocarcinoma, and the clinical diagnosis was lung adenocarcinoma with stage T3N2M1a . Three weeks later, the patient complained of worsening dyspnea, and a chest radiograph revealed increased left pleural effusion with a mediastinal shift. Owing to rapid progression, the patient was treated with a combination of cisplatin and pemetrexed as first‐line therapy before the multigene results were available. Subsequently, the patient was switched to oral 500 mg tepotinib (450 mg active moiety) once daily after the multigene test revealed MET exon 14 skipping mutation. A chest CT performed 43 days after the start of tepotinib showed a partial response of lung cancer Figure , but incGround‐glass opacities that manifest during lung cancer treatment are suspected to be indicative of tumor progression or drug‐induced ILD. Although TKI‐induced ILD is rare, it is considered one of the most lethal adverse events, and MET‐TKI‐induced ILDs have also been reported.TAPOs associated with MET‐TKIs have not been previously reported. However, this case was asymptomatic, GGOs were localized, and the tumor did not show any enlargement; rather, it shrunk in line with TAPOs. In addition, the CT images of this case had imaging patterns similar to TAPOs associated with osimertinib treatment, such as GGOs and subpleural nodules.As a limitation, tepotinib‐induced ILD was also suspected owing to the appearance of shadows after initiation of tepotinib in this case. In general, pulmonary toxicity, such as ILD, is not associated with dose intensity,We encountered a case in which TAPOs were suspected, rather than drug‐induced ILD, during MET‐TKI treatment. Readministration of MET‐TKIs at a reduced dosage under close observation was thought to be the appropriate alternative.Writing – Original Draft, S.I.; Writing – Review & Editing, N.Y., Y.S., Y.H., A.S., T.I., T.N.; Supervision, S.I.The authors declare no conflict of interests.


A saturated health care system with a lack of evidence-based antiviral medicine and ignorance of antimicrobial stewardship during pandemics has prompted clinicians to prescribe a broad-spectrum antibiotic more often. A prospective, cross-sectional study of COVID-infected patients was conducted to gain insight into antibiotic prescribing practices and their impact on antimicrobial resistance. The antibiotic susceptibility test was performed using the disc diffusion method. 318 patients met the study’s inclusion criteria, with a mean age of 46 years and 55% (175) of them being males. Antibiotics were prescribed for 93.72% (209) of mild cases, 92.45% (49) of moderate cases, 96.15% (25) of severe cases, and 100% (16) of critical cases of COVID-19. A total of 95 samples were sent in for culture and antibiotic sensitivity testing, with 58.95% (56) confirming growth. The majority of the growth was found to contain E. coli (14). In 54.9% of cases, antibiotics with less than 50% sensitivity to curing bacterial infection were detected. In the study, we found that antibiotics were being used unnecessarily in excessive quantities and that more than half of the antibiotics were less sensitive to isolated bacteria. Antibiotics are being utilized unnecessarily in the treatment of COVID-19. Excessive and needless antibiotic use raises the risk of antimicrobial resistance (AMR) in the future by promoting the emergence of multidrug-resistant (MDR) bacteria , which hCOVID-19 resembles bacterial pneumonia in conjunction with clinical presentation, including fever, cough, and lung infiltrates . It coulHere, the study intends to get insight into antibiotic prescribing practices in COVID-19 treatment and its impact on antibiotic resistance.A prospective, cross-sectional study was conducted in the COVID ward of Adichunchanagiri Hospital & Research Centre (AH & RC) after obtaining approval from the Intuitional Ethical Committee (IEC/AH & RC/AC/002/2021).The study included all patients diagnosed using the diagnostic method reverse transcription- polymerase chain reaction (RT-PCR) and admitted to the COVID wards between August 1st and November 30th, 2021, regardless of gender. The study did not include those diagnosed with other diagnostic methods than RT-PCR.All COVID-19 patients hospitalized in AH & RC’s COVID wards were assessed for inclusion criteria, and those who met them were considered for the study. Although the study was part of a daily medication evaluation by a clinical pharmacist for the patient’s safety, informed consent was obtained from patients who were capable of giving it or from the caretaker for severe and critical patients.mild, moderate, severe, and critical)  8.9% (5), non-fermenting gram-negative bacteria [NFGNB] 7.1% (4), Providencia Stuartii 1.8% (1), Proteus Mirabillis 1.8% (1), and Citrobacter Freundii 1.8% (1) (95 (29.9%) specimens were sent for AST testing out of 318 patients, with 16.59% (37) being mild, 66% (35) being moderate, 80.8% (21) being severe, and 12.5% (2) being critical. 58.9% (56) of them confirmed growth. 1.8% (1) . Regardl1.8% (1)  & Fig 2.There were no statistically significant differences in the antibiotics prescribed between the severity of COVID-19 and the p-value obtained was 0.644. Similarly, the antibiotics prescribed had a p-value of 0.163, indicating that no statistically significant differences existed between the genders. However, statistically significant differences in the severity of diseases were observed in the sample collection for the antibiotic susceptibility test (AST), with a p-value of 0.000.With this study, we intended to get insight into antibiotic prescribing practices in COVID-19 treatment and its impact on antibiotic resistance. In the study, we observed that the antibiotic prescribed was unaffected by the severity of COVID-19. At least 93.7% of the patients were prescribed at least one antibiotic, and azithromycin alone accounted for 73.6%. Similar findings were reported by WHO and Getahun H et al. . AntibacE. coli, K. Pneumoniae, and Pseudomonas spp. were the most commonly isolated bacteria, while Marina G et al. [Pseudomonas aeruginosa and Enterobacterales were the most prevalent in their study. The isolation of organisms is being influenced by the geographical region. 54.5% (12) of the antibiotics used for AST showed more than 50% resistance to the isolated pathogens. Antibiotics such as ampicillin, nalidixic acid, ceftriaxone, ceftazidime, cefotaxime, cefixime, and ciprofloxacin, which are commonly prescribed, were resistant in more than 70% of AST results. The inappropriate and overuse of antibiotics without an indication could be a cause of the issue. It’s also possible that the current pandemic’s focus on minimizing the immediate impact on individuals has obscured the longer-term threat of AMR [Although antibiotics were started before the specimens were collected for AST, the growth was present in 58.9% of the total specimens sent for AST. This shows that antibiotics are being used inappropriately and the process of specimen collection was contrary to the Treatment Guidelines for Antimicrobial Use in Common Syndromes . We founG et al.  reportedt of AMR .Hand sanitizer was used by 92.43% of patients, indicating that it is an important component of COVID-19 transmission prevention awareness campaigns. Ochwoto M et al. reported that half of the hand sanitizers tested have efficacy levels that are lower than the WHO formulation in their study . The panThe findings of the investigation highlight the terrible situation of antibiotics. Its inappropriate and overused nature can be more fatal if a pathogen develops multi-drug resistance. To save antibiotics in the future, no compromises should be made in the implementation of antimicrobial stewardship programs. AMR is caused by a variety of factors, including antibiotic overuse and misuse, as well as exposure to low-quality biocidal agents.Our study’s limitation is that it was a single-center study with a small sample size, and we assessed antibiotic resistance independently of the isolated bacterium. The fact that AH&RC is located in a rural part of the Mandya district may have impacted its decision to ignore coronavirus protective measures such as safe distance and mask use. Further multi-center studies with a large sample size are required to demonstrate the impact of the COVID pandemic on AMR.In the study, we identified that antibiotics were being used unnecessarily in excessive amounts and that more than half of the antibiotics tested were less sensitive to curing bacterial illness, regardless of the isolated bacterium. The current pandemic’s focus on reducing the immediate impact on humans may have hidden the longer-term threat of AMR, overuse of antibiotics, and exposure to inadequate biocidal agents, which might lead to an increase in AMR. To corroborate the findings, a multi-center study with larger sample size is necessary.