To describe the evolution of COVID-19 related publications in the field of ophthalmology.  All articles published in the field of ophthalmology and relevant to COVID-19 were identified by conducting a search on PubMed and Scopus databases using the string  OR (eye) OR (ocular)) AND ((corona) OR (COVID-19) OR (pandemic)). Search was conducted on September 30, 2020. Each eligible publication was independently graded by two experienced ophthalmologists based on the level of evidence-based medicine (EBM), with scores ranging from 1 (the highest level of EBM) to 5 (the lowest level). The average level of EBM was also evaluated for each month from February through September. Finally, we analyzed the interval (in days) between submission and acceptance for publication as well as the percentage of manuscripts that required revision before being accepted. p=0.024). Moreover, the number of citations per article was significantly correlated with the level of EBM ; however, we found no correlation between the number of citations and either the month of publication or the ranking of the journal in which the article was published. The mean interval between submission and acceptance for publication was 20.4 days (SD: 20.2 days), and 48.2% of submitted manuscripts were accepted without revision. From February through September, the interval between submission and acceptance increased significantly ; however, we found no significant change in the percentage of publications that were accepted without revision over this same time period.  Our search yielded a total of 425 relevant publications. Of these publications, 359 (84.5%), 59 (13.9%), and 7 (1.6%) were rated as level 5, 4, and 3, respectively; none of the publications was rated as level 1 or 2. From February 2020 through September 2020, we found a significant increase in the relative proportion of level 3 and 4 publications compared to level 5 publications (rho = 0.108,  In the early months of the COVID-19 pandemic, primarily lower-level EBM articles were published, and these publications were accepted relatively quickly. However, this effect was temporary, and over time the EBM levels improved and the interval between submission and acceptance increased, indicating an increase in publication standards. Evidence-based medicine (EBM) is a well-accepted approach used to address the plethora of information in the field of medicine . In thisAn inherent feature of EBM is that much like a pyramid, higher levels of EBM rely on the lower levels; thus, higher quality EBM is not available in the early stages of an outbreak or pandemic such as the global COVID-19 pandemic .Consistent with reports in other fields of medicine –6, we prWe found no publications addressing the change in the quality of EBM in the ophthalmology literature during the COVID-19 outbreak. In our work, we examined the temporal evolution of EBM quality and standards for publishing in the field of ophthalmology during the COVID-19 pandemic in early 2020.The COVID-19 pandemic erupted in late 2019, and by the end of September 2020, the vast majority of places globally have removed lockdown measures and adapted a pandemic routine . We thusThe remaining publications were included in our analysis and were graded using a commonly accepted categorization system developed by the Centre for Evidence-Based Medicine (CEBM) . In brieEach publication was graded as level 1 through 5 by two independent experienced ophthalmologists . The coefficient of agreement between the two graders was calculated, and disagreement between graders was discussed until consensus was reached.For each publication, we documented the principal country of origin, journal, month of publication, number of citations, interval in days between submission and acceptance for publication, and whether the authors were required to revise the original manuscript. If more than one date relating to publication was available, we used the date of publication provided on PubMed as the date of acceptance. For each journal, we also obtained the 2019 impact factor and quartile from Web of Science .p < 0.05.Analyses were performed using SPSS, version 25.0 . Frequency counts and percentages generated were appropriate. After testing for normality, groups were compared using a paired Student correlations and analyzed using Pearson's correlation coefficient. Statistical significance was defined as p < 0.0005). Of the publications for which the data were available, nearly half (48.2%) were accepted for publication without revision, and this did not change significantly from February through September (p=0.104).Our search yielded 425 unique articles that met the inclusion criteria and were published between February 2020 and September 2020. These 425 articles originated from 35 countries, with the most articles originating from the US (15.5%), followed by India (13%), the UK (8.7%), China (6.8%), Italy (6.4%), and Hong Kong (4.5%). These 425 articles were published in 115 journals, with the most articles published in the Indian Journal of Ophthalmology, Eye, Ophthalmology, Graefe's Archives of Ophthalmology, and Acta Ophthalmologica. The mean (±SD) impact factor of these 115 journals was 2.24 ± 3.46 (range: 0.18–60.39). The interval between the first submission and acceptance for publication as well as information regarding whether revisions were required was available for 245 publications (57.6%). The mean interval between submission and acceptance was 20.4 ± 20.2 days, with 83 articles (19.5%) accepted within 7 days of submission. From February 2020 through September 2020, this interval increased significantly (p < 0.0005). The majority of publications  were rated the lowest at level 5, while 59 publication (13.9%) were rated as level 3, and 7 (1.6%) of publications were rated as level 3. None of the publications was rated at either level 2 or level 1, and no level 3 publications were accepted in February, March, or April 2020 .We then examined the percentage of publications that were either level 4 or level 3 out of all publications accepted in a given month and found that this percentage increased significantly from February to September . In contrast, we found no significant correlation between the average number of citations per publication and the month of publication  in ophthalmology regarding COVID-19 were published in the first 8 months of the pandemic. This is not surprising, given that properly conducted prospective cohort studies and RCTs require both time to conduct and a foundation of knowledge on which to expand.At the start of the pandemic, ophthalmologists needed to make countless clinical decisions, with implications for both their own well-being and their patients' outcome. However, these clinicians were largely baffled by the hastily published information—some of it conflicting—regarding questions such as, is it possible to contract the virus by contact with the patient's tears? How safe is it safe to perform nonurgent ocular surgery? Do we need to wear a facemask in public places? Indeed, one of the most famous victims of the pandemic was Chinese physician Dr. Li Wenliang, an ophthalmologist, who was among the first to report the outbreak of this new disease entity in Wuhan, China, later contracting the disease and subsequently dying from it .The trend we found to rush and publish data applying lower publication standards is in no way unique to Ophthalmology and has also been noted in publications in other fields of medicine as well. Palayew et al. have found a significantly shorter latency between submission and acceptance of publications on the topic of COVID-19 when compared to prepandemic publications on other topics . This emAs mentioned above, the approach to treating patients with hydroxychloroquine highlights the need to properly weigh the available evidence. Hydroxychloroquine was first regarded as a potentially lifesaving medicine for treating and/or preventing COVID-19; however, its use outside of controlled clinical trials was later discouraged with leading medical journals having to retract previously published articles . MoreoveUnfortunately, our modern world and global lifestyle increases the likelihood of future pandemics. Therefore, the medical community should learn from our experiences with the COVID-19 pandemic, for example, by avoiding rushing to publish relatively low-quality articles, despite the temptation to fill the urgent need for information. Even in the face of a pandemic, standards must be maintained, and adhering to these standards will ultimately save more lives compared to the rapid dissemination of low-quality information. Unfortunately, however, maintaining these standards is increasingly difficult in our modern fast-paced Internet age.The main strengths of our study are that it analyzes the quality of publications in the field of ophthalmology during the early stage of the COVID-19 pandemic. No results were excluded, and we used two independent graders to assess the EBM level of each publication.Our study has several limitations that warrant discussion. First, our analysis was limited to publications written in English; therefore, including non-English publications may have provided a more accurate picture of the articles available to clinicians in non-English-speaking countries. Second, other methods are available for categorizing EBM , and theIn conclusion, our findings indicate that in the field of ophthalmology, the desire to quickly disseminate knowledge regarding COVID-19 inevitably resulted in the publication of a high percentage of papers with lower levels of EBM, with relatively lower publication standards; however, as time passed, these standards increased, resulting in the publication of articles with higher levels of EBM.


Hybrid slabs made of carbon-fiber-reinforced polymer (CFRP) and concrete provide a solution that takes advantage of the strength properties of both materials. The performance of the system strongly depends on the CFRP–concrete interaction. This study investigates the shear behavior in the interface of the two materials. Eight full-scale experiments were carried out to characterize the interface shear response of these hybrid elements using different connection solutions. An untreated surface is compared to a surface with aggregates, with a novel system comprising a flexible, straight glass fiber mesh and an inclined glass fiber mesh. The experimental results show that the fabric connection improves the friction between materials and is responsible for the pseudo-plastic performance of the specimens. The inclined mesh produces a more uniform tightening effect compared to the straight mesh. In simulations via the finite element method, we used an adjusted frictional model to reproduce the experiments. Within the last six decades, many reinforced concrete structural elements have been developed under different design code regulations and using different construction techniques. They require maintenance, retrofitting, or even strengthening; see, for example, Colajanni et al. . In addiRegarding hybrid beams, they are mainly used for bridge applications; see Zou et al. . Hulatt Given that most of the FRP–concrete hybrid structures use FRP pultruded beams, it is important to highlight the work by Bank , who invFam and Skutezky  investigAl-Amery and Roberts  introducHence, there is much research interest on hybrid FRP–concrete structures, but previous studies mainly addressed bridges or cross sections composed of pultruded beams and concrete. There are few studies specifically conducted on hybrid slabs of thin CFRP laminates and even fewer on the mechanical connection between the materials.In this paper, we aim to investigate the interface shear mechanical response of hybrid CFRP sheet–concrete slabs characterized by the use of connectors such as bonded particles or a high-strength glass fiber mesh. Experimental and numerical analyses of these elements are included and compared in order to validate and analyze the performance. The connection of hybrid CFRP–concrete using a flexible material is a novel idea that is compared to the traditional roughening method using aggregates. Moreover, it has the advantage of connecting materials without the use of any steel bolts, avoiding the problem of corrosion. Finally, the manufacture of these slabs seems to be very simple and competitive in the construction market.3 of Portland cement with continuous 0 to 12 mm limestone aggregates and plasticizer. It was mixed with a water/cement ratio of 0.6, reaching a compressive strength below 25 MPa.All specimens were cast using commercial (FIASA HS-25) dry concrete  distributed in 25 kg bags. It was composed of 300 kg/mThe strength of the concrete was estimated using a non-destructive Schmidt impact hammer . Six repetitions were conducted on each specimen to estimate the average value of the compressive strength according to the ASTM method . Table 1CFRP sheets were manufactured using the traditional hand layout process on a mold of a thin steel sheet with a top-hat shape. The material was unidirectional carbon fiber Masterbrace FIB 300/50 . Each CFRP sheet had three plies with orientation [0°/90°/0°]. Epoxy resin Resoltech 1204  was brushed over every ply using a fiber/resin ratio (by weight) of 1. After impregnating the fibers, a counter mold was placed over them, and some weight was applied to it for a 48 h period to guarantee uniform impregnation. Tensile tests were conducted on eight samples extracted from the manufactured CFRP sheets according to the ASTM test  with a s2 and an average tensile strength of 45 kN/m. The mesh had a grid distribution of 25 × 25 mm, leaving empty spaces to mechanically lock the poured concrete. The grid was bonded to the CFRP sheet on the flat upper surfaces using a carbon fiber strip and the same resin (Resoltech 1024). The mesh was placed aligning the grid with the nerves of the slab in some specimens (straight specimens), while in others, the relative orientation between the grid and the nerves was 45° (inclined specimens).For some connections between the CFRP sheet and concrete, we used a flexible mesh made of MapeGrid (G220) glass fiber  with a weight of 225 g/mSolid particles of different sizes were used to increase the friction interface between the CFRP sheet and concrete. The dimension of those aggregates depended on the size of the specimen to ensure reliable manufacturing and presented a diameter between 0 and 4 mm for sand and between 5 and 12 mm for gravels. The amount of aggregates was measured by weight using 300 g of gravel and 150 g of sand, and aggregates were randomly distributed on the surface of the CFRP sheet. The aggregates were bonded by brushing the surface of CFRP with Resoltech 1024 and dropping them on.Eight hybrid specimens designed for direct shear testing were manufactured. The specimen geometry consisted of two parts with different lengths, as shown in A hydraulic jack with manual control  was placed between the two blocks of the specimen. One of the concrete blocks acted as a reaction wall while the other failed under a pushing force. The stability of the system relied on the shear stresses between the two materials. The shear test setup is shown in Force was uniformly applied through a steel loading tool (U80 steel profile)  that increased the contact area between the jack and the tested block in order to avoid local concrete damage. The applied force was increased gradually, and it was continuously measured with a 10 kN UC9 load cell . Two LVDT sensors with a range of 20 mm and 0.02% linearity were placed on each side to measure the relative displacement between the smaller block and the CFRP sheet. A data acquisition system recorded all data simultaneously.All specimens failed at the surface contact of the CFRP and concrete. The smallest block resisted up to a maximum value of force and then physically separated from the CFRP sheet. In the case of samples N and A, the failure was sudden and the load dropped instantaneously. Minor friction due to the roughness of the surfaces remained, but only for very low load values. For samples A-SM and A-IM, the failure was progressive. The load reached a maximum and the connection started to separate, but friction related to the existence of the glass fiber mesh maintained the load value. The ultimate failure occurred with a mixed mode, combining breakage of the fibers and debonding of the mesh see .The values of failure were pretty different from those of other types of connection based on bolts. Zou et al.  observed2. Moreover, the calculation of tangential strain was performed simply by dividing the average displacement measured with LVDTs (in millimeters) by the length of the small block, which was 200 mm.The force–displacement plots are shown in From the plots in From analysis of the stress variation, it is clear that the untreated surface showed an irregular response; therefore, this technique is not recommended for practitioners. It may produce non-conformities in the execution that are more severe than those that occur with hand manufacturing. The surface treatment improved the homogeneity of the results. The mean average stresses presented two groups: Case A (aggregate connections) with a level of 15.75 kPa and Cases A-SM and A-IM (mesh connections) with levels of 44.93 kPa and 34.88 kPa, respectively. This result indicates that the loads that the connections with the meshes could withstand were larger than those in other cases. Therefore, the mechanical performance of the flexible material is more competitive than that achieved by traditional roughening with aggregates.Another significant difference could be found in the shape of the plots presented in For both samples with mesh connections, the material had a positive effect. During the loading process, after the peak load, several complex types of damage took place: cracking of the concrete, debonding of the tows and the concrete, mechanical locking of the concrete in the mesh gaps, and the breakage of threads. Nevertheless, for the A-SM, damage continued to grow, and the system was unable to withstand the applied load, losing stiffness and producing a softening effect. On the contrary, the A-IM was capable of maintaining the same load level. The reason for this pseudo-plasticity lies in the mesh position.The inclined mesh has several advantages compared to the straight mesh. Firstly, the contribution of fibers to the strength comes from a tightening effect. The strength of fibers is very high compared to the levels of load, so its contribution to the load-bearing is negligible. Hence, the placement in a non-optimal direction (in terms of only the stress response) is not a limitation. Secondly, straight fibers are distributed discontinuously; there are strands only every 25 mm and, hence, there are important gaps with no fibers. Moreover, the flexibility of the perpendicular fibers cannot produce an effective locking mechanism in the gaps. On the contrary, the inclined mesh covers the whole width with its strands and does not leave any empty spaces without fibers. Moreover, the inclined threads can produce a more effective locking mechanism in the gaps. Hence, the inclined mesh provides a uniform response that helps to maintain a high level of friction.Compared to push-out tests by other authors like Zou et al. , Gong etIn order to better understand the performance of the mesh connections, some finite element simulations were performed in order to clarify the locking mechanism and the shear response of the interface between the concrete and the CFRP sheet. Both the A-SM and A-IM cases were modeled using a general-purpose finite element software program, ABAQUS  . In the The general geometry of all numerical models was the same, and it corresponded to the shortest concrete block. The concrete block and the thin CFRP sheet were considered independent solids connected at the interface surface. Glass fiber materials were modeled as beam elements with the same sections as the primary material. These were added in the corresponding direction . Details of the aggregates and the thin layer of resin or glass fiber mesh–CFRP sheet strip connector were not explicitly represented in the model and were implicitly considered in the contact between surfaces.The CFRP sheet was under a low level of stress compared to the ultimate capacity of the material. Therefore, the material composition was defined as linearly elastic. Generally speaking, the block of concrete was not damaged; only the contact zone with the different connection systems had cracks. As this zone was limited to the contact surface, it was treated separately. Hence, the concrete block was also defined as a homogeneous, linearly elastic material.Glass fiber fabrics are defined as elastic–plastic materials. The definition of the elastic branch is based on the provider’s properties, including a Young’s modulus of 72 GPa and a Poisson coefficient of 0.3. The plastic properties of the glass fiber materials were used to fit the models, and these were intended to include all the complex effects of the three-phase connection between the concrete, fabric, and CFRP sheet: sliding of the fibers, debonding of the fabric–CFRP sheet connection, and cracking of concrete around the fabric, for the cases including glass fiber meshes. The included parameters were the yielding stress of 180 MPa and consistent mass matrix formulation to obtain the shear modulus for the case of the straight mesh (A-SM), and a yielding stress of 25 MPa, transversal stiffness of 650 MPa, and slenderness compensation value of 0.9 for the definition of the plastic behavior of the A-IM cases. All these parameters were considered carefully as they are essential for the correct fitting of the experimental results presented later on.The Young’s modulus of the CFRP was experimentally obtained by testing the samples, while the Poisson’s coefficient was taken from Munoz et al. . The YouThe average concrete compressive strength was taken from The surface contact between CFRP and concrete is a complex system. Concrete cracks, and the block also generates friction with bonded aggregates. Moreover, the mesh introduces a complex tightening system that modifies the performance dramatically, as was observed in the experiment. Therefore, modeling the details of the interaction of these elements is beyond the scope of this work; additionally, there is no experimental evidence to sustain any assumption. Hence, to model this complex interface, we used a strategy of defining contacts. This approach simplifies the model but does not lose generality, and it is supported by the empirical observations. Hence, aggregates were not considered physically in the simulation, but they indirectly participate when adjusting contact properties to the experimental observations.Two models were used to represent the concrete–CFRP sheet interface; the first was a cohesive zone model  includiThe connection of the glass fiber mesh was defined as an embedded restraint in the concrete and CFRP sheet solid elements.The concrete was modeled by linear hexahedral elements of type C3D8R—an 8-node, brick-shaped, three-dimensional element with one point of integration to reduce the computational cost. According to the assumptions, the modeling of the concrete did not require precision. The CFRP sheet was modeled by linear wedge elements of type C3D6. This element type has 6 nodes and 2 integration points. The glass fiber mesh was modeled with B31 truss elements. The concrete, CFRP, and glass fiber mesh were meshed dependently with a maximum seed dimension of 15 mm. The Hex-Sweep technique was used. If a region is swept meshable, Abaqus/CAE can generate the swept mesh on a region that has been assigned the Hex.The resulting mesh can be observed in The boundary conditions were the same for both models. The bottom surface of the CFRP was simply supported. The shear load was indirectly imposed by a uniform displacement along the specimen’s longitudinal direction for all experimentally loaded faces. Finally, the CFRP face that was coplanar with the concrete face where the displacement was imposed was fixed.The analyses were carried out using a static general procedure, obtaining the shear load as the reaction associated with the imposed displacement for all time increments. The total time-period was assumed to be one second and the maximum number of increments was defined as 100.For the assumed approach of combining a frictional model to represent the CFR–concrete interaction together with embedding the mesh to model the CFRP–mesh–concrete response, there is a consistent relationship with the achieved results. The inclination of the mesh (A-IM) allowed us to consider the tensile response of the wires of the glass fiber fabric because of their relative orientation with respect to the load. A part of this load is axially resisted by the wires, which progressively develop a nonlinear response. This process allowed the load to continuously increase, although at progressively reduced stiffness up to failure. In contrast, the mesh only contributes to resisting the applied load through the shear mechanism for the A-SM cases. Hence, when the maximum shear strength is reached, all mesh capacity is lost, and only the frictional connection between the CFRP and concrete is available to resist the applied shear load. This theoretical analysis is translated in the experimental and numerical simulation results into the clear maximum peak of the force, followed by a force decrease, culminating in a constant residual shear strength due to the concrete–CFRP sheet frictional interaction.It should be noted that the obtained shear stiffness of the specimen is very similar in both cases (A-SM and A-IM), as is the slope after yielding. However, the yielding point is, in fact, influenced by the resisting mechanism of the embedded mesh, being lower for the combined axial-shear case (A-IM) than for the pure shear case (A-SM).The numerical results in terms of force reaction vs. displacement are compared to the average curve of the experimental results for each case. It was observed that the proposed numerical model accurately predicts the mechanical response of the experimental tests for both mesh orientations.No numerical values of the fitting quality are provided because the ad hoc definition of some of the variables of the numerical model would invalidate this quantification. The fitting quality can be observed through the comparison of the full force–displacement curves in The theoretical behavior inferred for both novel connection systems considering the embedding of a flexible glass fiber mesh can be seen in Although further research is necessary to accurately fit the defining properties of these models , the description of the qualitative response in Specimens without connectors (N) and those with only aggregate connections (A) presented the weakest shear resistance. The performance was fragile in all cases, with sudden failure. The post-critical response was related to merely friction between materials, not allowing significant energy dissipation. Both connections are considered unreliable for real works, disregarding even the classical connection approach of increasing the roughness via aggregate adhesion.Embedding a flexible structural glass fiber material as a connector between the CFRP sheet and the concrete increased the shear load-bearing capacity and enhanced the post-peak shear strength, changing the failure mode from sudden to progressive. Moreover, the system with the mesh connection could dissipate much more energy than that with the aggregate connection. The curve performance of the inclined mesh showed some similarities to a bolt connection.The numerical simulations combining a frictional model and the embedding of a fabric were capable of reproducing the experimental curves. Adjustment values must be taken with caution but are consistent with the results.The numerical model explains that the orientation of the fabric plays an important role in the structural response because of the possibility of combining two resisting strategies, axial and shear, when inclined with respect to the load direction.A real locking mechanism is a complex combination including concrete cracking, debonding of fibers and concrete, sliding of fibers, locking concrete in the grid gaps, friction between concrete and FRP, and breakage of fibers. The proposed strategy simplifies this complex combination of resisting mechanisms into only two equivalent interfaces: the frictional interface between concrete and FRP and the embedded beam elements between concrete, mesh, and FRP.The achieved level of load is less than that for a traditional bolt system but it has the advantage of not using steel connectors, and it involves a very simple manufacturing process for thinner slabs.In this research, an experimental study and numerical analysis of CFRP–concrete hybrid elements subjected to in-plane interface shear tests were carried out. The mechanical responses of different CFRP–concrete connection strategies, including a novel proposal based on embedding a fiber material, were analyzed and discussed. A simplified numerical model was fitted with the experimental results. The following concluding remarks can be made:


Compositing is an interesting strategy that has always been employed to introduce or enhance desired functionalities in material systems. In this paper, sponges containing polypropylene, lignin, and octavinyl-polyhedral oligomeric silsesquioxane (OV-POSS) were successfully prepared via an easy and elegant strategy called thermally induced phase separation (TIPS). To fully explore the behaviour of different components of prepared sponges, properties were characterized by a thermogravimetric analyser (TGA), differential scanning calorimetry (DSC), Fourier transform infrared measurement (FTIR), and scanning electron microscopy (SEM). Furthermore, wettability properties toward an organic liquid and oil were investigated. The FTIR analysis confirmed the chemical modification of the components. TGA and DSC measurements revealed thermal stability was much better with an increase in OV-POSS content. OV-POSS modified sponges exhibited ultra-hydrophobicity and high oleophilicity with water contact angles of more than 125°. The SEM revealed that POSS molecules acted as a support for reduced surface roughness. Moreover, OV-POSS-based blend sponges showed higher sorption capacities compared with other blend sponges without OV-POSS. The new blend sponges demonstrated a potential for use as sorbent engineering materials in water remediation. Industrial wastewater and oil spillage are considered as the main source of water pollution, which threatens human life and the marine system ,2,3,4,5.However, these methods had many disadvantages, such as that their application was limited, high-cost, poorly efficient, and had adverse effects on the environment. In this case, removing pollutants by low-cost and highly absorbent materials without generating by products that may cause further concern was the main target of material scientists for decades . DiffereA low-cost and efficient strategy to produce polymer-based monolith, the thermally induced phase separation (TIPS) method has been used as a typical facile process to fabricate sponges. TIPS method is based on dissolving a polymer in a solvent at an appropriate temperature, followed by cooling of the polymer solution. The phase separation happens in the cooling cycle. TIPS is a simple operation, energy-saving, and adaptable process ,17.Recently, we have reported a novel approach to fabricate low-cost and eco-friendly biomass-based porous materials using renewable lignin and polypropylene (PP) via TIPS used in water remediation .PP is a commonly used plastic in different industrial applications, especially in wastewater treatment as a sorbent, mainly due to the low cost, high oil sorption capacity, and relatively high efficiency ,20,21,22Furthermore, lignin is a natural organic polymer produced on a large scale from the paper and cellulose industries. At present, despite the various proposals for using lignin, only a small part (about 2%) of the 500 million tons produced annually is effectively utilized. Most of the lignin is burned or discharged into rivers, which threatens the environment ,24. LignOne of the limitations of fabrication lignin and polypropylene (PP) via TIPS method was increasing water wettability with increasing lignin content in the matrix of the sponge along with a slight decrease in thermal stability with an increased lignin content of more than 10 wt%. To solve the above drawbacks by increasing lignin amount in blend, we mixed it OV-POSS with different weight ratios to fabricate the final target product.In the past decades, the unique properties of OV-POSS received great attention for widespread application. OV-POSS can enhance fire retardation, has good mechanical properties and wettability. Where their particles form a rigid inorganic silica cage structure responsible for enhancing thermal stability . MoreoveFurthermore, OV-POSS contains a common nontoxic compatibilizer with the smallest, 1–3 nm, molecular silica ,37 that Herein, we propose a facile strategy of fabricating an environmentally friendly sponge that can be used to remove and recover, via thermally induced phase separation (TIPS), oil and organic liquid from water surfaces, using the three constituents—PP, lignin, and OV-POSS—. We then investigated the effect of OV-POSS nanoparticles with different levels (1 and 3 wt%), which were also used as compatibilizers, on the wettability and thermal properties of the blends.Polypropylene (PP) pellets, octavinyl-polyhedral oligomeric silsesquio ane OV-POSS, , lignin To fabricate the target sponges, the typical process was done as follows: The solution of PP was prepared by completely dissolving 2.8 g of PP pellets in a mixed solvent containing decalin (16 mL) and 1-butanol (24 mL), heating at a temperature of 115 °C until the polymer was completely dissolved to form a homogenous solution. Afterward, lignin and OV-POSS were added to the solution and gentle stirring followed for 1 h to obtain a uniform mixture. The solution was then cooled at room temperature for 2 h. It should be noticed that the phase separation finished in a short time. During the cooling stage, phase separation took place, forming a sponge. After that, the obtained sponge was immersed into acetone to remove the embedded solvent and subsequently dried under vacuum. The general procedure for the fabrication of the target sponge is illustrated in The molecular weight of PP was determined by polymer laboratory Gel permeation chromatography  at 150 °C, using 1,2,4-trichlorobenzene as a solvent, and the calibration was made with polystyrene standards.H NMR analysis was carried out to determine the chemical structure of the lignin, using a Bruker Avance 600 MHz spectrometer  at a frequency of 600 MHz at 25 °C. The lignin samples were dissolved with DMSO to enhance their solubility.−1. The spectra were generated in the range of 400–5000 cm−1 using attenuated total reflection (ATR) technique. The test was used in 64 scans with a 8 cm−1 resolution.The infrared spectra were obtained using an FTIR spectrometer . The spectra were recorded at the wavenumber range of 400–4000 cmThe thermal stability of PP, lignin, POSS, and obtained polypropylene/lignin blend monoliths were investigated using a thermogravimetric analyser . Sample masses of ~10 mg were heated at 30–700 °C at a heating rate of 10 °C/min under nitrogen flow (20 mL/min).DSC analyses were used to evaluate the effect of added lignin on the polypropylene thermal behaviour of the blend monoliths. The measurements were carried out using differential scanning calorimetry . Samples of ~3–5 mg in an aluminium container were carried out by heating/cooling at a rate of 10 °C/min under nitrogen atmosphere within a temperature range of 30–200 °C.The surface morphology of polypropylene/lignin sponges and their modifications with POSS were characterized using scanning electron microscopy . For SEM, samples were cut, fixed on double tape, and then plated with a thin film of gold before measurement.The contact angles and surface free energies were measured by an optical contact angle meter . In the testing process, double-sided tape attached the fibres to a glass slide, paved in the form of a plane . SurfaceThe sorption capacity Q (%) was calculated from the mass gain after the obtained samples were weighed and placed in a beaker containing a 5 mm layer of liquid (oil—organic solvents) floating on an 80 mm layer of water for a duration of 30 min to reach saturation. After that, the saturated materials were weighed again; the sorption capacity was calculated by Equation (1) , where WThe reusability of sorbent was estimated by repeated sorption and squeezing processes. The sorbent material was soaked into liquid, and the absorbed liquid within the sample was recovered by manual squeezing. The process was repeated for several cycles .The chemical structure of lignin was assessed by H NMR . The obt−1 that were attributed to the C–H stretching. The peaks at 1375, 1358 and 1330 cm−1 represent the syringyl group, the –CH3 bonding, and the C–O stretch, respectively [The Fourier transform infrared spectra (FTIR) method was used to describe the characteristics of functional groups present in the structure of the blend sponge with and without POSS . Polyproectively . The spe−1 corresponded to hydroxyl groups. This vibration of hydroxyl groups was visible also in PP10L and PP20L. On the other hand, with the addition of lignin to PP, a peak of aromatic skeletal vibrations was found at 1510 cm−1, which was more intense at higher lignin content. Anther essential structure in lignin was a weak shoulder at 1710 cm−1, which is associated with conjugated carbonyl stretching [Further, it was observed that the lignin peak at 3500 cmretching .−1 were observed, characteristic of the Si–O–Si stretching. The peak at 1603 cm−1 was associated with C=C stretching vibration of the vinyl group, besides peaks around 1410 cm−1 assigned to C=C stretching [−1 was related to Si–C stretching vibration [−1 (aromatic C=C stretching), 1513 cm−1 , and 1455 cm−1 (C–H deformation) were visible in all the composites [The FT-IR spectra of blend sponges with POSS are shown in retching . The peaibration . The pea−1. This indicated that lignin and POSS were successfully incorporated into the composites [It was observed the above peaks, representing bonds in POSS, appeared in all blend polymers after modification with POSS. The modification of the blended sponge with POSS is based on the interaction between the POSS molecule and the hydroxyl groups in lignin, which was proven by the disappearance of the peaks of hydroxyl groups in the range of 3400–3600 cmmposites ,53.Thermal gravity analysis (TGA) is a widely used tool to evaluate the thermal degradation behaviour of tested samples. The mass loss of the tested sponges was shown as a function of temperature on thermogravimetric (TG) and derivative of thermogravimetric (DTG) curves . The corThe thermal stability of POSS is shown in Moreover, it was observed that PP exhibited a one-step degradation process in the temperature range of 30 to 700 °C . MeanwhiPolypropylene started to degrade at 468.92 °C, the degradation continued until 497.65 °C with a remarkable char residue (1.40%) at 600 °C. Moreover, this behaviour was also observed in the thermal behaviour of composites blended with 10–20 wt% lignin. However, the results showed clearly that the addition of lignin at 10% would increase the onset of the temperature of the thermal degradation more than PP itself. In comparison, the thermal test analysis showed that a higher content of lignin in the blend matrix would reduce its thermal stability, as it was apparent on the tested sample PP20L, where the onset of the temperature of the thermal degradation was lower than the one of PP . At the The influence of POSS on the thermal behaviour of blends was also investigated. In the case of the work carried out under nitrogen atmosphere, it was notable the addition of POSS into the matrix of the sponge caused an increase in T5%, T10%, and T50% compared with a blended sponge without POSS . IncreasGenerally, there was an increase in the Tonset under the nitrogen atmosphere, which w attributed to possible cross-linking between blend chains and the POSS silicone core, and a thermally stable ceramic char surface layer was formed by POSS cage and acted as a thermal barrier for materials. The amounts of POSS present in the blends also affected the thermal stability due to significant enhancement with POSS. The increases in decomposition temperatures of PP10L-0.1P and PP20L-0.1P were 455.61 and 388.22 °C, whereas in the case of PP10L-0.3P and PP20L-0.3P, they were 463.78 and 399.50 °C, respectively.Further, all POSS used here improved the temperature of the maximum weight loss rate . AnotherC), are summarized in The DSC curves of polypropylene and its blends with and without POSS are shown in crystals .It was observed that neat PP had a melting enthalpysticizer . Howeversticizer .Surface topography is an important factor for studying the wettability of materials surfaces. The surface wettability of the samples is another interesting factor; it was studied by measuring the static contact angles between samples and water. The measured surface free energies are summarized in The blended sponges fabricated using the TIPS method can be considered as promising sorbents for oil spillage clean-up due to their 3D interconnected macroporous structures, hydrophobicity, and oleophilicity, resulting from mixing of lignin and POSS support micro/nanoscale structures, as discussed above. For further investigation of the absorption capacities of these blends of polypropylene/lignin with and without POSS for potential application in the clean-up of polluted oil spills, more experiments were set up using oils and organic solvents. The results are demonstrated in The synthesized sponges displayed good absorption capability for the various liquids and oils used. Their absorption capacity was evaluated as follows: A piece of the sponge was placed in contact with liquids dispersed on a water surface, as shown in Further, it was noticed that sponges modified with POSS exhibited higher sorption capacity due to the improved hydrophobicity, which ensured that water was completely rejected. It was also evident that there was a clear correlation between the volume of absorbed oil and the POSS content, which could be attributed to the increased lipophilic properties with an increase in POSS content. For example, sponges with 0.3% POSS absorbed oil more than sponges with 0.1% POSS . When thIn summary, we presented a facile method of fabrication eco-friendly blend sponges from PP, lignin, and POSS using an efficient way, namely, the thermally induced phase separation (TIPS). The influence of POSS on the surface wettability and thermal properties was deeply studied. The newly prepared sponges displayed high thermal stability with POSS compared with one without POSS. A DSC analysis showed that POSS had a significant influence on melting temperatures. SEM results indicated that the addition of POSS nanoparticles could enhance the dispersion and compatibility of the lignin in matrix systems by making the surface smoother.Meanwhile, POSS formed silicon bonds that protected the sponges from water penetration with water contact angles more than 125°, combined with improving oleophilicity, which significantly enhanced with increasing POSS content. The sorption tests for obtained sponges showed that POSS-based sponge absorbed oils and organic solvents more, and the sponge with POSS content exhibited higher sorption compared to the one without POSS. The experimental results of the sorption test also indicated that the blend sponge with an addition of 10% lignin and 0.3% POSS had the best performance. Hence, the proposed eco-friendly and inexpensive sponges with good thermal stability and wettability could be feasibly applied in water cleanup operations on an industrial scale.


IgG4-related disease involvement of the digestive tract is very rare. In few reported cases of isolated gastric/duodenal IgG4-related disease, none of which resulted in luminal obstruction.A 59 years old female presented with longstanding gastrointestinal symptoms. CT showed mural thickening of the proximal duodenum. Gastroscopy showed antral ulcer extending into the duodenum with outlet obstruction and biopsy showed acute on chronic duodenitis. Whipple’s procedure was performed and IgG4-related disease was diagnosed on final pathology. Symptoms were revolved on mycophenolate mofetil and prednisone with no recurrence.Our case is the only reported case with gastric outlet obstruction secondary to gastroduodenal IgG4-related disease. The diagnosis should be considered in the differential diagnosis of unexplained duodenal stricture, gastric outlet obstruction or gastrointestinal ulceration. IgG4-related disease usually responds to steroids but long-term response rates to steroid-sparing agents, especially in the subset of patients with luminal IgG4-related disease remains to be determined. IgG4-related disease (IgG4-RD) is a systemic inflammatory disorder characterized by abundant infiltration of IgG4-positive plasma cells in the affected organs . The livA 59 year old female with a past medical history of Guillain-Barré syndrome and previous gastric ulcer on multiple medications including naproxen 500 mg and omeprazole 20 mg daily presented with longstanding abdominal pain and progressive postprandial nausea, vomiting and weight loss over 6 months’ period. CT showed mural thickening of the proximal duodenum Fig. A. The paGross examination of the resected specimen revealed a large ulcerated mass (2.5 × 1.2 × 1.0 cm) involving stomach and duodenal wall Fig. A. There Postoperatively, the patient developed an anastomotic leak that was managed conservatively with antibiotics and drainage resulting in significant symptomatic improvement. MRCP did not show any pancreatic or biliary abnormalities.A few weeks later, she represented with abdominal pain, nausea and vomiting, with trivially elevated serum IgG4 at 0.965 g/L (0.039–0.864 g/L). CT scan revealed inflammatory changes at the anastomosis site with severe duodenal thickening  which is considered the chronic counterpart of Guillain–Barre syndrome –31. ThisAdditionally, preoperatively, the patient was discovered to have iron deficiency anemia. Colonoscopy was also performed which revealed patchy erythematous changes across the right colon up to the proximal transverse colon, with colonic biopsies showing chronic colitis with focal activity and ulceration. A diagnosis of inflammatory bowel disease (IBD) was suspected. However, following the Whipple resection and the subsequent diagnosis of IgG4-RD, we retrospectively performed IgG4 stain on the colonoscopic biopsy specimen which showed up to 21 IgG4 positive plasm cells per high power field. On one hand, given the context, colitis secondary to IgG4-RD is very plausible. On the other hand, IgG4-positive plasma cells are commonly seen in IBD, especially ulcerative colitis , 33. TheIgG-RD should be included in the differential diagnosis for unexplained duodenal stricture, gastric outlet obstruction and/or gastrointestinal ulceration. In order to diagnose or exclude IgG4-RD, a thorough assessment and correlation between the clinical and histopathological findings is crucial. Due to the disease’s insidious and multi-organ nature, obtaining a detailed history of the symptoms, organ involvement, chronicity and disease evolution, supported by radiological examination of the abdomen and the common organs affected by IgG4-RD is very helpful; but often not satisfactory to exclude the diagnosis. Because of its mimicry of many conditions, it is very difficult to rule out IgG4-RD without histopathological assessment with IgG4 staining. In gastrointestinal disease, where endoscopic biopsies are inconclusive or fail to rule out IgG4-RD, obtaining biopsies from another affected organ (e.g. Endoscopic ultrasound guided biopsies from the pancreas or lymph nodes) can be sought. Moreover, surgical resection should be the final resort to establish a tissue diagnosis, especially if malignancy has not been excluded.In conclusion, IgG4-RD involving the gastrointestinal tract is rare with cases reported in the literature presenting in variable ways. Our case is the only reported case with gastric outlet obstruction secondary to gastroduodenal IgG4-RD. This unique fibroinflammatory condition should be considered in the differential diagnosis of unexplained duodenal stricture, gastric outlet obstruction or gastrointestinal ulceration. IgG4-RD usually responds to steroids but long-term response rates to steroid-sparing agents, especially in the subset of patients with luminal IgG4-RD, remains to be determined.


The reasons for the inappropriate antimicrobial prescriptions were similar in the three areas evaluated: antimicrobial unnecessary and antimicrobial not recommended were the most frequent reasons for inappropriateness. Not participating in an antimicrobial stewardship program (ASP) was identified as a factor associated with inappropriate antimicrobial prescriptions in medical and surgical units, but not in Intensive Care Units (ICUs). ASPs may enhance the appropriateness of antimicrobial prescriptions especially in medical and surgical units. In ICUs, specific programs able to limit empirical therapies and encourage the collection of microbiological samples may be useful to set up targeted therapies and to design antimicrobial protocols.The objectives of the present study were to provide a snapshot analysis of antibiotic appropriateness in two hospitals in Southern Italy in three specific areas, surgical, medical and intensive care, and to evaluate the risk factors associated with inappropriateness in antimicrobial prescriptions. We conducted a multicentre observational study in two hospitals in the Campania region. We collected data of all patients admitted on the day of evaluation to antibiotic therapy or prophylaxis through a case report form. The primary outcome was to assess the inappropriateness of antibiotic prescribing, related to the spectrum, dose, route of administration and duration of treatment—in particular, to assess whether there was a difference in the adequacy of the prescriptive practice in the medical, surgical and intensive sectors. Prescriptive inappropriateness was more frequently observed in surgical units  than in medical units (53.8% of the 65 prescriptions,  Antibiotic resistance is a major public health problem and antimicrobial overuse is considered the principal driver in selecting for antimicrobial-resistant organisms, with a strong association between the rising rates of use and increasing rates of antimicrobial-resistant organisms ,2. ThereImproving antibiotic prescriptions in the hospital setting is of the utmost importance to preserve their effectiveness. Moreover, knowing the degree of inappropriateness in antimicrobial prescriptions and the factors associated may be useful in the design of strategies to reduce the development of multidrug-resistant microorganisms.The objectives of the present study were to provide a snapshot analysis of antibiotic appropriateness in two hospitals in Southern Italy in three specific areas, surgical, medical and intensive care, including both adult and paediatric patients, and to evaluate the risk factors associated with inappropriateness in antimicrobial prescriptions, such as the absence of an antimicrobial stewardship program in the unit. We chose to group the wards according to the area of interest  because the prescribing behaviour can significantly vary among physicians of different specialties. For example, an ethnographic study published a few years ago had demonstrated that, in medical wards, the antimicrobial prescribing activity was often considered the result of a collective decision-making process, involving different specialties, while in surgical units, it is more individualised and often relegated to junior physicians .This study was conducted in two hospitals in Naples and Caserta, in Southern Italy. The medical institution located in Naples includes 30 units for a total of 268 beds and does not have an emergency department; the community hospital in Caserta has 23 wards accounting for 486 active beds with an emergency department. All units of the two hospitals were included in the analysis; the list of wards, grouped according to the clinical area, is displayed in We conducted a prevalence study that was planned in accordance with the health directions of the two hospitals in order to analyse the antibiotic use and to evaluate the appropriateness of antibiotic prescribing; the assessment was performed through audits conducted in each facility, on 10–14 of February 2020 in Naples and 14–23 of November 2019 in Caserta. The infectious disease (ID) consultants involved received the same training on local and international guidelines on the main infectious syndromes and prepared a pre-formed case report form. The audits in each hospital were managed by ID consultants operating in the other centre.During the audits, the following data were collected: type of unit , number of patients admitted to the ward, number of patients receiving an empiric or targeted antimicrobial treatment and/or prophylaxis . For each antibiotic prescription, the team of ID specialists assessed the appropriateness in relation to the patient’s characteristics and the indication provided by national and international guidelines. All classes of antimicrobials for systemic use were included in the analysis. Topical antibiotics were excluded because they have a limited impact on the selection of resistance and were mostly unavailable in the formulary of both hospitals.For each patient undergoing antibiotic therapy, we collected the following data: type of acquisition of infection  criteria , healthcA therapy was defined as empirical when administered before the identification of the causative agent with the relative resistance profile, or targeted otherwise. The appropriateness of all prescriptions was evaluated in accordance with the international guidelines on the different clinical syndromes ,14,15,16For every antibiotic prescription considered inappropriate, the reason for inappropriateness was recorded; more than one reason could be reported for each prescription. The antibiotic was considered unnecessary when the patient’s clinical conditions did not show evidence of infection requiring an antimicrobial treatment. The therapy was considered inadequate or inactive when not able to cover the most likely causative agents, as indicated by the current guidelines , or when the agent displayed no activity against the pathogen involved (for targeted treatment).Antimicrobial therapy was considered not recommended when the antibiotic was active against the identified or presumed aetiologies but showed an excessively wide spectrum of activity. The duration of antimicrobial therapy was considered excessive when it exceeded the limit indicated by the international guidelines.The primary outcome was to assess the difference in the appropriateness of prescriptive practice in the medical, surgical and intensive care units.The secondary outcome was to identify the main drivers of prescriptive inappropriateness in order to implement strategies to optimise antibiotic prescribing in the three areas.All methods used in the study were in accordance with the international guidelines, with the standards on human experimentation of the Ethics Committee of the Azienda Ospedaliera Universitaria, University of Campania and with the Helsinki Declaration of 1975 and revised in 1983. Since the leadership of the University of Campania and Azienda Ospedaliera of Caserta formally approved the study and the data were collected during routine clinical activities, no approval was required by the local ethics committee.Continuous variables were summarised as mean and standard deviation, and categorical variables as absolute and relative frequencies. For continuous variables, the differences were evaluated by the Student t-test; categorical variables were compared by the chi-square test, using Fisher’s exact test when needed; odds ratios (OR) and their 95% confidence intervals were calculated for each comparison, as well as the chi-square test values. The sample size needed to obtain a statistical power of 80%, with a probability of type I error of 0.05 and an anticipated difference in the prevalence of inappropriate prescriptions of 20% between medical and surgical units and of 25% between surgical units and ICUs, was calculated.In the two hospitals, a total of 53 units were assessed; in particular, 19 medical, 25 surgical and 9 intensive care units (ICUs) were evaluated. The total number of patients assessed was 486: 210 in medical, 187 in surgical and 89 in ICUs . Of the In p = 0.0003) and ICUs  (In = 0.052) .As shown in p = 0.0006), and less frequently in the case of endocarditis or cardiovascular infections  and when microbiological specimens (hemocultures) were collected  (p = 0.04) as the independent predictor of prescriptive inappropriateness (= 0.048) . Multivaiateness .p = 0.001)  were inappropriate, higher than that observed among the 16 antimicrobial prescriptions recorded in ASP units  .p = 0.07); however, inappropriate prescriptions were recorded in the case of sepsis or septic shock  or bloodstream infections   . Multiva = 0.02) .Antibiotic resistance is rising to dangerously high levels all over the world. Overuse and misuse of antibiotics contribute to the acquisition and spread of infections due to antibiotic-resistant bacteria. Thus, knowing the degree of inappropriateness in antimicrobial prescriptions and the factors associated with the different hospital areas may be useful in the design of strategies to reduce inappropriateness in antimicrobial prescriptions and the development of multidrug-resistant microorganisms.In the present study, the level of inappropriate prescribing in the two hospitals evaluated in Southern Italy was high in all three areas (over 50%): medical, surgical and ICUs. The reasons for the inappropriate antimicrobial prescriptions, however, were similar in the three areas evaluated: antimicrobial unnecessary and antimicrobial not recommended were the most frequent reasons for inappropriateness. In the ICUs, the unnecessary use of antibiotics prevailed, probably because of the management of patients with more severe conditions, with symptoms similar to those of bacterial infections ,18.The highest rate (79.8%) of inappropriateness in antimicrobial prescriptions was observed in the surgical area, where the prescriptions of peri-operative prophylaxis obviously prevail. In fact, as already indicated in the literature, surgical prophylaxis often does not adhere to the guidelines, especially in terms of duration  or choicConsidering the factors associated with inappropriateness in antimicrobial prescriptions, the main factor in medical and surgical units was the absence of an antimicrobial stewardship program, so it would be useful to implement stewardship programs in all units of both centres. Hospital ASPs have shown a positive impact on antimicrobial consumption, antimicrobial appropriateness and the incidence of bloodstream infections due to multidrug-resistant microorganisms, with reduced length of hospitalisation and without an increase in mortality ,23,24,25The study shows some limitations, the most important of which is represented by the small sample size: all the data analysed were collected during a single week in each hospital, so a limited number of prescriptions have been included. This did not allow us in some cases to stratify the data according to all potentially relevant characteristics of patients, such as the disease severity or the source of infection. Furthermore, the cross-sectional design and the absence of pre-intervention data limited the possibility of fully evaluating the impact of the ongoing antimicrobial stewardship program on the appropriateness of prescriptions. Finally, we should consider that the definition of appropriateness is not universal and can significantly vary according to individual ethical considerations or concerns regarding the working context, such as the availability of rapid microbiological tests or local epidemiology of healthcare-associated infections . Indeed,In conclusion, the present paper suggests that an ASP may be useful especially in medical and surgical units with the aim of reducing the use of broad-spectrum antibiotics, favoring appropriateness in antimicrobial prescription and encouraging adherence to the guidelines of antibiotic prophylaxis in the surgical field. However, in ICUs, specific programs able to limit empirical therapies and encourage the collection of microbiological samples may be useful to set up targeted therapies and to design antimicrobial protocols according to the clinical presentation of the patients and the local epidemiological situation in infections by multidrug-resistant microorganisms.


However, with the increased quantity of perlite (from 45% to 60%), the concrete density reduction is not observed, as the expanded perlite demonstrates very low resistance to crushing. With the increased amount of perlite, the longer periods of mixing time for all the mix components are required to obtain the homogeneous and fluid concrete mix, what causes grounding down EP. Therefore, using larger quantities of this aggregate in RPC is not recommended. The lightweight RPC shows very good freeze-thaw resistance in the presence of de-icing salt . The above is explained by the compact microstructure of this concrete and the RPC mix location in open pores on the perlite aggregate surface, which consequently affects the strengthening of the aggregate-matrix contact without an interfacial transition zone (ITZ) visible. It has been demonstrated that pozzolanic activity of expanded perlite is much lower than the activity of silica fume and quartz powder, and its impact on increasing the RPC strength is minimal.This paper presents the test results of the lightweight concrete properties obtained by adding expanded perlite (EP) to an RPC mix in quantities from 30% to 60% by volume of the concrete mix. It has been shown that in these cases it is possible to obtain concrete containing 30% by volume with density of approximately 1900 kg/m PerlitePorosity of lightweight aggregate is associated with its density, which is the main parameter that determines its suitability for use in structural concretes . ExpandeExpanded perlite may be used in building materials as an additive to cement (in a form of powder) or as a lightweight aggregate in thermal insulating materials. Due to its high silica and aluminate content, EP may also be the main component of geopolymer materials ,10.Generally, it can be stated that the application of EP to the concrete mix instead of natural aggregates leads to the reduction of the hardened concrete strength as the perlite content in the concrete mix increases ,12,13,143, with the addition of pozzolan materials such as silica fume, fly ash, metakaolin, volcanic ashes, calcined clays, and shales [3 [Many authors conducted research on lightweight ultra hight performance concerts (LUHPC) ,23,24. Id shales . During d shales  proved td shales  demonstrhales [3 . Moreovehales [3 ,27 introIt is necessary to point out that numerical methods, applied to estimate the behavior of structure elements under loads, are very helpful to analyze the tensile strength of concrete or to predict areas and intensity of crack formations . However3 and the height compressive strength (ca. 280 MPa), by simply increasing the content of silica fumes in the RPC composition, without the use of lightweight aggregate, while applying the increased temperature (240 °C) during 24 h of concrete curing. The author also showed that the concretes cured in temperatures of 240 °C are characterized by lower density compared to the concretes cured in temperatures of 90 °C [The literature contains very few studies dedicated to the implementation of reactive powder concrete (RPC) in lightweight concretes technology. Sadrekarimi  obtainedof 90 °C .3 and the compressive strength of ca. 69 MPa when quartz was replaced with a lightweight volcanic aggregate (2400 kg/m3). Achieving higher compressive strength was possible with the application of lightweight aggregates, with the parallel application of steel micro fibers and pressure curing. However, such a treatment increased the RPC density to about 2400 kg/m3 with an increase of the compressive strength up to 176 MPa and a decrease of water absorption from 6.5% (for concrete cured in ambient conditions) down to 1.7% at the same time. Gökçe et al.  demonstrStudies ,33 appliThe research into lightweight reactive powder concrete with perlite was conducted by Al-Jumaily . The autIn this study, the influence of expanded perlite in quantities of 30%, 45%, and 60% by volume to the RPC mix, on the lightweight RPC properties was tested. Particular attention was paid to changes in density, compressive strength, and water absorption with the increase in quantity of EP in RPC. Microstructure analyses were also conducted, as well as investigation into the influence of pozzolanic activity of EP on the compressive strength of lightweight RPC.2/kg), with GGBFS content in amounts of ca. 60% by mass. Finely ground quartz sand, with maximum grain size < 800 μm, quartz powder, and waste silica, with the content of SiO2 > 90% by mass, were used. Theater to binder ratio equaled 0.2 and was obtained by the use of the polycarboxylate superplasticizer in the amount of 3.0% of the cement mass. The research of the chemical and physical properties  of the RPC mix composition are presented in this paper [For testing, the RPC mix was prepared with the blast furnace slag cement-CEM III/A 42.5 N,  primarily contains grain sizes >2 mm (52%). The aggregate used contained ca. 4% of powder with the particle size <0.063 mm. Increasing the quantity of expanded perlite (EP) in the RPC mix caused significant deterioration of its fluidity and required an increase in the amount of a superplasticizer from 3.0% to 5.0% by mass, at 60% of the EP content. The composition of tested mixes is presented in The tests of the physical properties of EP , were performed in accordance with PN-EN 13055:2016-07 standard—“Lightweight aggregates”.The consistence of the lightweight RPC mixes was tested by means of the flow table method, in accordance with PN-EN 1015-3:2000—“Methods of test for mortar for masonry—Part 3: Determination of consistence of fresh mor-tar (by flow table)”, by measuring the concrete flow diameter after 10, 30, and 60 min. 3 according to PN-EN 12390-7:2011—“Testing hardened concrete—Part 7: The density of hardened concrete”.The tests of concrete density were conducted on the samples sized 150 × 150 × 150 mm3. The samples were saturated with water and then dried to constant mass at the temperature of 50 °C. The test procedure is described in Polish standard PN-B 06250:1988 “Ordinary concrete”.The tests of water absorption were carried out for 28 days after the samples’ preparation. The sample size was 100 × 100 × 100 mm3. After mix preparation, and casting them in steel molds, the samples were demolded after 24 h and cured in water at a temperature of 20 ± 2 °C until the strength test . The procedure of flexural and compressive strength testing is described in PN-EN 196-1:2016-07—“Methods of testing cement—Part 1: The determination of strength”.To test strength, the prism samples were prepared sized 40 × 40 × 160 mmThe freeze-thaw resistance of lightweight RPC in the presence of de-icing salt was tested by means of Slab test , the classification of the concrete under its freeze-thaw resistance was based on a Swedish standard SS 13 72 44 “Concrete testing; Hardened concrete; Scaling at freezing—2005”.The microstructure of lightweight RPC was carried out with the use of the NOVA NANO SEM 200 scanning microscope  with the possibility of obtainment the EDS spectra in selected points.The test of the phase composition of EP and hardened lightweight RPC were conducted by means of powder X-ray diffraction within the angle range of 5° to 60° 2θ. The Philips X’PertSystem diffractometer  and CuKα radiation was used. The JCPDS-ICDD database was used to define the crystalline minerals based on known patterns .The results of the physical properties tests for expanded perlite are presented in Based on the results of the tests of the EP phase composition conducted by means of X-ray powder diffraction , it can It has been found that the addition of expanded perlite to RPC causes the loss of mix fluidity. Introduction of 30 vol.% of lightweight aggregate causes a reduction in the mix flow diameter from 220 mm to 175 mm. Application of larger quantities of EP (45% and 60%), despite the increased amount of superplasticizer in the concrete mix to 4.0% and 5.0% by mass, respectively, caused further significant loss of fluidity. The flow diameter of RPC mix with the application of 60 vol.% of expanded perlite was only 95 mm after 1 h, and at EP content of 45 vol.% it was 125 mm. The deterioration of concrete workability due to the introduction of expanded perlite was shown by the authors of papers ,39. ThisThere are also reports showing that the workability of concrete improves by adding EP ,13,42. AExpanded perlite is distributed evenly in the concrete mix, which is visible in macroscopic images of lightweight concrete samples containing 30%, 45%, and 60% of expanded perlite by volume after 28 days of curing . The hig3, whereas with the content of 45 vol.% and 60 vol.%, it is 1880 kg/m3 and 1870 kg/m3, respectively, and it differs slightly from the density of concrete containing 30 vol.% of EP.As expected, the addition of the expanded perlite to the RPC mix in quantities from 30 vol.% to 60 vol.% causes a reduction in the concrete density by approximately 13%, compared to the density of the RPC without lightweight aggregate . It was The reason for this phenomenon is the low crushing resistance of expanded perlite. Therefore, the lightweight aggregate, especially in higher dosage, requires a longer mixing time when being mixed with the RPC mix, in order to obtain the homogeneous and fluid concrete mix. Therefore, this proves that the application of this aggregate in larger quantities (45% and 60%) is not recommended to obtain the lightweight RPC with expanded perlite, as it does not allow us to obtain the concrete with a lower density.The reduction in concrete density may be achieved by the application of expanded perlite as a substitute to natural aggregate or sand, which has a specific gravity much lower than the specific weight of other ingredients of the RPC mix ,38,45. TThe RPC based on blast furnace slag cement CEM III/A 42.5 N used in this study achieves the compressive strength equal to 128.3 MPa after 28 days, and equal to 175.2 MPa after 365 days, and the flexural strength equal to 22.6 MPa after 28 days and 27.5 MPa after 365 days . A high The analysis of the strength test results for lightweight RPC containing 30 vol.% of expanded perlite showed that it was possible to obtain the concrete with a compressive strength > 65 MPa after 28 days and >70 MPa after 365 days of curing . The fleThe compressive and the flexural strength values for RPC with expanded perlite after 28 days is approximately 40% of the compressive strength value of the same concrete without the addition of the lightweight aggregate. We maintained the RPC strength at more or less the same level with various content of aggregate . The similar values between the compressive and the flexural strength of RPC containing 30 vol.%, 45 vol.%, and 60 vol.% of EP is due to the fact that the aggregate becomes finer during the longer mixing time which the components with the increased amount of perlite require to obtain the homogeneous and fluid concrete mix. This explains why the increased amounts of EP (45 vol.% and 60 vol.%) in RPC do not cause a reduction in the lightweight RPC density, which stays at the same level as RPC with 30 vol.% of EP. Expanded perlite shows a very low crushing resistance (0.66 MPa), compared to an aggregate with expanded clay (2.24 MPa) or an aggregate made of processed fly ash (3.83 MPa) . HoweverThe test results of the water absorption and the scaling mass of concrete samples subjected to freezing and de-icing salt are presented in the The water absorption of RPC equals only 3.3%. The received results show that water absorption of RPC with EP  slightlyThe results of freeze-thaw resistance of lightweight RPC in the presence of de-icing salt , showed The results of the microstructure tests of the lightweight RPC with expanded perlite in quantities of 30% and 60% by volume are presented in 2 ratio. It is undoubtedly the result of the blast furnace slag cement application containing approximately 60% of the ground granulated blast furnace slag (GGBFS). The CaO/SiO2 ratio in the C-S-H phase for pastes with GGBFS addition may amount to 1.2, whereas for pastes of Portland cement, this ratio is higher and may even amount to 1.9 [The concrete mix location in aggregate pores strengthens the bond between the aggregate and the RPC matrix. The bonding between the lightweight aggregate and the cement paste may be created by mechanical bonding, absorption of water and cement paste from the fresh concrete mix by the aggregate or, in some cases, the pozzolanic reactivity of the lightweight aggregates ,48. Due t to 1.9 .The analysis of the XRD patterns for the RPC specimens containing the expanded perlite in quantity of 30%  and 60% 2+, K+, N+, and OH− are adsorbed on the surface of the reactive aggregates [It is known that the finely ground expanded perlite added to cement shows pozzolanic properties when reacting with calcium ions and alkalis . As earlgregates . In casegregates .The tests of the expanded perlite particle size distribution conducted in this study  showed tThe tests of the expanded perlite pozzolanic activity conducted in this study demonstrated that the expanded perlite showed significantly lower pozzolanic activity compared to fly ash, silica fume, and even quartz powder . This isTaking the pozzolanic properties of the expanded perlite into account, tests were undertaken of with lightweight RPC containing 30% of perlite, with the addition of hydrated lime in 1% of the cement mass to the RPC mix. Data presented in 2 sample, the peaks characteristic for muscovite, one of the expanded perlite phases, disappear.The analysis of the XRD patterns for the concrete specimens containing the expanded perlite in the amount of 30 vol.%, with the addition of 1% of calcium hydroxide , showed It is well known that expanded perlite may be used, in powder form, as a mineral additive to cement, where the advantages of its pozzolanic properties may be utilized . HoweverThe results of consistency tests of RPC mix with EP showed that increasing the content of aggregate in an RPC mix causes significant workability loss . After 1A longer period of mixing time of an RPC mix which shows high viscosity , which iIt is notable that conducted analysis by the authors of this paper of the research presented in a previous paper , concernThe fact that ground EP shows pozzolanic properties  prompted2+) additionally introduced to the RPC mix.Yao et al.  demonstrThe pozzolanic properties of the expanded perlite are revealed to a greater extent when the ground perlite is added to the cement . Its addRPC with EP in quantity from 30% to 60% by volume are characterized by very low water absorption, ranging from 3.3% to 3.5%, which is not significantly different than the water absorption of RPC without a lightweight aggregate (3.3%). The above was explained by the very compact RPC microstructure, without visible larger pores . The C-SIntroduction of the expanded perlite-fraction 0/4 mm-to the RPC mix in quantities from 30% to 60% by volume causes a reduction in mix fluidity and homogeneity, which increases as a larger content of aggregate is applied in the mix. Maintaining the mix fluidity while using the larger amount of EP requires a larger quantity of a superplasticizer (to 5% by mass) and a longer time to mix ingredients.EP’s low resistance to crushing and required longer mixing time of the mix components causes grounding down the expanded perlite, which therefore has no influence on the decrease in the lightweight RPC density.3 to 1900 kg/m3. However, a further increase in EP content in RPC mix, from 30 to 60 vol.%, results in a lack of decrease in density and compressive strength of those lightweight concretes, which should have been expected with a significant increase in EP in the RPC. This is the result of the weak aggregate getting finer due to its very low resistance to crushing. The above test results indicate that application of larger amounts of EP (45 and 60 vol.%) is not recommended in order to obtain lightweight RPC. The addition of EP to RPC mix in the quantity of 30 vol.%, causes a decrease in the concrete density from 2200 kg/mThe water absorption of lightweight RPC with EP  is in the range of 3.3% to 3.5%, and is comparable to the water absorption of RPC without lightweight aggregate (3.3%). The low water absorption of lightweight concrete was explained by very compacted microstructures of hardened lightweight RPC.Expanded perlite in the form of aggregate shows pozzolanic properties. Its pozzolanic activity, however, is much lower than the activity of silica fume and quartz powder, the ingredients of the RPC mix. It has been demonstrated that EP in the RPC mix reacts with calcium hydroxide, but the pozzolanic activity it shows has a marginal impact on the increase of the lightweight RPC strength.


Antibiotic prescription rates were lower at the community primary care unit and higher when the physician was a resident or a family doctor. The deployment of an electronic clinical pathway reduced the rate of unnecessary antibiotic prescriptions. The effect was greater at 6 weeks post-implementation. However, discrepancy of patients’ baseline characteristics may have skewed the findings.Outpatient antibiotics are most frequently prescribed for upper respiratory tract infection (URI); however, most such prescriptions are inappropriate. We aimed to determine the effect of an electronic clinical pathway on the rates of overall and rational prescription of antibiotics in patients with URI. A pilot quasi-experimental study was conducted in a university hospital and two of its nearby primary care units (PCU) in northeast Thailand from June to September 2020. Clinical pathway pop-up windows were inserted into the hospital’s computer-based prescription system. Care providers were required to check the appropriate boxes before they were able to prescribe amoxicillin or co-amoxiclav. We examined a total of 675 visits to the outpatient department due to URI at three points in time: pre-intervention, immediately post-intervention, and 6 weeks post-intervention. Patients in the latter group tended to be younger and visits were more likely to be general practitioner-related and to the student PCU than in the other two groups. In addition, the rate of antibiotic prescription was significantly lower at 6 weeks after intervention than at either of the other time periods (32.0% vs 53.8% pre-intervention and 46.2% immediately post-intervention;  The spread of multidrug-resistant (MDR) bacteria is one of the most urgent global crises we currently face. In the United States, MDR bacteria is associated with approximately 100,000 in-hospital deaths annually and results in an economic burden of about USD 8 billion . One reaIn primary care settings, antibiotics are most frequently used to treat upper respiratory tract infection (URI). Such cases account for 75% of all antibiotic use in Ireland and 77% in Thailand ,5. AlthoThe use of a clinical pathway has been shown to reduce antibiotic use in URI ,13,14. HData from 675 outpatient department (OPD) visits due to URI were collected at three points during the study period: pre-intervention, immediately post-intervention, and 6 weeks post-intervention. The clinical pathway pop-up windows were added to the hospital’s electronic prescription process on 15 July 2020. Baseline data were collected for patients, including age, sex, medical conditions, symptoms, duration of illness, and recurrent URI history, as well as for the examining physician, including age, specialization, and location . The patp < 0.001; p < 0.001). However, when using cases with antibiotic prescription as a denominator, the rate of rational antibiotic prescription was highest immediately post-intervention (52.8%), differing significantly from those pre-intervention (21.3%) and 6 weeks after intervention . Mean duration of prescribed antibiotic treatment was similar in all three groups. After implementation of the clinical pathway, prescriptions shifted toward amoxicillin and away from co-amoxiclav. In the pre-intervention group, co-amoxiclav accounted for 48.8% of antibiotic prescriptions and amoxicillin only 40.5%. However, immediately post-intervention and at 6 weeks, the prescription rate of amoxiclav dropped to 34.0% and 23.6%, respectively, and that of amoxicillin increased to 54.4% and 68.0%.The rate of antibiotic prescription was significantly lower 6 weeks after intervention than at the other time periods  and higher when the physician was a resident or family doctor, with adjusted odds ratios of 1.66  and 10.05 , respectively.Statistically significant variables according to univariate analysis were included in subsequent multivariate analysis. After adjustment for physician’s age, specialization, and practice setting, the clinical pathway was still significantly associated with fewer antibiotic prescriptions with an adjusted odds ratio of 0.62  and 10.50 , respectively. The physician being a resident was associated with lower rates . These results were similar to those of Jenkin et al., who reported an 11.2% relative reduction in antibiotic prescription for non-pneumonia respiratory infection and a 14.4% relative reduction in broad-spectrum antibiotic use during the intervention period . In addiWe found that patients with exudative tonsillitis, cervical lymph node tenderness, purulent nasal discharge, or facial tenderness, on physical examination, had higher odds ratios of antibiotic prescription than those without, comparable to the findings of a previous study . Fever, In this study, factors associated with rational antibiotic use were quite similar to those associated with overall antibiotic use mentioned above. Clinical pathway use improved the rate of rational antibiotic prescription both immediately post-intervention and 6 weeks after. This may have been because the interactive pop-up windows provided the researchers with more clinical data to judge whether antibiotic prescriptions were rational or not. One factor associated with irrational prescription was greater physician age. This is similar to previous findings. Aspinall et al., for example, reported that providers ≥30 years of age prescribed more antibiotics for nonbacterial acute respiratory tract infections with an odds ratio of 2.6 and 95% confidence interval of 1.1 to 6.3 . ZoutmanThere were some limitations to this study. First, baseline characteristics in the three groups differed. This was especially true at 6 weeks post-intervention. Both patients and physicians in this group tended to be younger and visits were more likely to be GP-related and to the student PCU. Because the study site is a university hospital, we had planned to enroll all patients after the beginning of the semester in order to include more students. However, a series of COVID-19 outbreaks led to the new semester being postponed. This meant that the patients seen during the pre-intervention and immediate post-intervention periods were mostly university personnel, who were older and more likely to visit a premium clinic. This may have skewed the findings, as the setting being a premium clinic was associated with antibiotic prescription in the univariate but not multivariate model. Patients seeking antibiotics can also affect physicians’ decisions , but thiThis was a pilot quasi-experimental study conducted in a 1400-bed university hospital and two of its nearby PCUs in northeast Thailand: PCU KKU123 (student PCU) and PCU Samliam (community PCU), from June to September 2020. We inserted clinical pathway pop-up windows  lasting for at least 3–4 consecutive days at the beginning of illness;Worsening of symptoms or signs  following a typical viral URI that lasted 5–6 days and that were initially improving.For patients with ICD-10 CM codes J00 or J01, antibiotic prescription was considered rational if clinical presentation met at least one of the following criteria :SymptomsFor patients with ICD-10 CM codes J02 or J03, antibiotic prescription was considered rational if the patient had a cumulative modified Centor score ≥2 .Name of clinic at Srinagarind Hospital which opens after hours and provides care only by attendance. There are doctor’s fees and additional service charges in this clinic.Sample size calculation was based on the primary objective of the study. Based on a pilot study, the rate of antibiotic prescription in URI patients at Srinagarind Hospital prior to implementation was 32%. Assuming that the intervention would reduce the prescription rate to the national goal of below 20% , we detep-value < 0.05) were selected for multivariate logistic regression. All statistical analyses were performed using SPSS for Windows, version 26.0 (SPSS).Categorical variables were reported as number and percentage. Continuous variables were presented as mean with standard deviation (SD). Pearson’s chi-squared test was performed to compare the percentage of cases with the rates of overall and rational antibiotic prescription at pre-intervention, immediately post-intervention, and 6 weeks post-intervention. Fisher’s exact test was performed in cases where chi-square was not suitable. One-way analysis of variance (ANOVA) was used to compare the mean of each group. Associations were expressed as odds ratio (OR) and 95% confidence interval (95% CI). Factors possibly associated with antibiotic prescription and rational use were subjected to univariate analysis, and those that were statistically significant .Insertion of clinical pathway pop-up windows into a hospital computer-based prescription system reduced unnecessary antibiotic prescription and led to a shift from broad-spectrum to narrow-spectrum antibiotics. This effect was greater at 6 weeks after intervention. We also found that residents and family doctors were more likely to prescribe antibiotics than GPs, and that patients visiting a community PCU were less likely to receive antibiotics. Hospital administrators should be conscious of these factors and consider implementing the method described here in combination with other effective interventions in order to reduce antibiotic misuse and improve the quality of care.


Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL . The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD;  It has been 20 years since Immunoglobulin (Ig) G4-related disease (IgG4-RD) was first described in 2001 . HistoloPrevious studies have argued that patients with IgG4-RD might have an increased risk of malignancies including colorectal, lung, and pancreatic cancer as well as malignant lymphoma than the general population . In partMalignant lymphoma is classified into Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. In Japan, B cell lymphoma accounts for about 68% of all non-Hodgkin lymphoma. Of these, diffuse large B-cell lymphoma is the most common (33.3%), followed by marginal zone lymphoma (MZL) (9.58%) . Among aAmong molecules that could potentiate tumorigenesis, activation-induced cytidine deaminase (AID) is a member of the cytidine deaminase family enzymes that modify nucleotides causing various mutations. While AID plays a crucial role in B-cell tolerance, B-cell maturation, and antibody diversification by propelling somatic hypermutations in the Ig variable region to cause Ig class switching from IgM to other classes of Ig , AID expIn patients with IgG4-ROD, all biopsy specimens showed marked lymphoplasmacytic infiltration, scattered eosinophils, and reactive lymphoid follicles. There were no light-chain restrictions. All cases fulfilled the criteria of IgG4+/IgG+ cell ratio being more than 40% .In those with IgG4+ MZL, dense infiltration of medium-sized atypical lymphoid cells with a Ki-67 labeling index less than 10% were noted in all cases. These lymphoma cells were positive for CD20. Of note, abundant IgG4-positive cells with no light chain restriction and negative for CD20 were noted in all samples with the IgG4+/IgG+ cell ratio of more than 40% . Only scIn IgG4- MZL, similar histopathological findings to those of IgG4+ MZL were noted except for the paucity of IgG4-positive cells . Except This study examined the baseline demographics and histopathological characteristics of patients with IgG4-ROD, IgG4+ MZL, and IgG4- MZL, with additional focus on the extent of AID expression to clarify the pathogenesis of IgG4+ MZL. Ocular adnexa is the second most common site of extranodal marginal zone lymphomas (EMZLs) comprising 5–15% of non-Hodgkin lymphomas. While patients with EMZLs usually have indolent clinical courses, up to 50% of those with non-gastric EMZLs have been reported to experience disseminated diseases ,27. ThusWe previously reported that IgG4+ MZL of ocular adnexa might arise in a sequence of IgG4-ROD by immunohistochemical staining, quantification of IL-4, 5, 10, 13, TGFβ1, and FOXP3 using real-time polymerase chain reaction . HoweverThe other hypothesis is that AID overexpression may be a key finding propelling the oncogenesis. There has been growing evidence that AID overexpression has been noted to induce oncogenesis in some types of epithelial malignancies and oncogene translocation ,29,30. SOur study has a few limitations that need to be considered upon reviewing the result. First, the study was performed at a single Japanese university hospital, which reduces the generalizability of the results to patients with IgG4-ROD, IgG4+ MZL, and IgG4- MZL of ocular adnexa from other countries and facilities. In addition, given the disease’s rarity, we had difficulty collecting cases without missing data or specimens needed for the analysis. Thus, the small number of cases here needs to be noted. Secondly, given the scarcity of the orbital tissues available, we could not quantitatively measure the expression of AID messenger RNA and protein with PCR and Western blot, which warrants further investigations in the future. Additionally, given previous reports suggesting a possible role of follicular helper T cells and plasmacytoid dendritic cells in the pathogenesis of IgG4+ MZL, we would speculate the potential existence of these cells in MZL ,37, althFormalin -fixed paraffin-embedded orbital tissues from patients with IgG4-related ophthalmic disease (16 cases), ocular adnexal IgG4+ MZL (11 cases), and IgG4- MZL (12 cases) were examined .All samples used in this study were surgically biopsied orbital tissue specimens (tissue in the cavity where eyes are situated). The procedures were performed at Okayama University Hospital, Mitoyo General Hospital, and Okayama Medical Center on different days. The specimen was fixed immediately in 10% formaldehyde after biopsy and embedded in paraffin, from which serial 3-μm-thick sections were prepared and stained with hematoxylin and eosin. The sections were then immunohistochemically stained with an automated BOND-III Stainer . Primary polyclonal antibodies against AID , IgG , and IgG4 , CD20 , CD3 , CD5 , CD10 , CyclinD1 , Ki-67  were used. In accordance with the consensus statement on the pathological features of IgG4-RD , three dTo reduce the inter-rater bias, all cases were reviewed by two pathologists independently. Per the consensus statement for the pathological assessment of IgG4-RD ,3 and thAccording to previous reports ,3, we evp < 0.05.We analyzed the data using JMP version 15.1.0 . We used the Tukey–Kramer test to examine which pairwise comparisons are significant given the inequality of sample sizes between groups. The threshold for significance was defined as