Lime-cement concrete (LCC) is a non-structural concrete in which lime and cement are used as the main binders. However, although LCC has many applications in reducing the settlement of foundations and providing a support layer for shallow foundations, little research has been conducted to evaluate its behaviour in various moisture conditions. Previous researchers have studied the feasibility of using waste tires in conventional concrete to alleviate their negative environmental impacts. However, in field projects, rubber has not been widely used because its application leads to the strength reduction of concrete. In the case of LCC, attaining high strengths is not required and thus application of waste tire particles sounds reasonable. This research evaluated the impact of various rubber powder contents on the fresh, geotechnical and durability properties of LCC at different saturation degrees induced by the capillary action and groundwater level increment, which has not been studied before. The results of more than 320 tests showed that the application of tire powder increases workability and decreases the water absorption of LCC. Moreover, all 60-day cured specimens exposed to 100% saturation degree experienced a strength reduction of less than 10% by using rubber powder contents varying from 0 to 20%. Moreover, increasing the saturation degree from 0 to 100% decreased the average compressive strength by 13.5 and 22% for 60-day cured samples of two different mix designs. The results of this research confirm that LCC containing up to 10% rubber powder could be promisingly used underneath or close to the groundwater table without its strength and geotechnical properties being jeopardized due to rubber employment and/or exposure to ground moisture. The rapid growth in population and consequently in the vehicle numbers has led to the annual generation of approximately 1.5 billion tons of waste tires . The majThe use of scrap tire rubber as high-strain-capacity materials in road construction can improve the impact resistance, fatigue performance, and toughness of the base and subbase of roads . The addConcrete is considered the most widely used construction material in the world ,20,21,22To attain an adequate depth and provide an appropriate base for constructing a foundation, LC (in regions with higher temperature) and LCC could be employed for low-rise buildings up to about three stories a. For miLow moistures and high temperatures bring about better geotechnical properties for lime-based concrete  ,31,32. TA review of previous research studies indicated that even though numerous investigations were performed on the lime-stabilized soils, lime-based mortars, and lime-hemp concrete, few research studies were carried out on the lime-based concretes. In addition, although LCC has many applications in reducing the settlement of foundations in mid-rise buildings and providing a support layer for shallow foundations in low-rise buildings, little research has been conducted to evaluate their behaviour in various ground moisture conditions. This is while in many districts capillary suction or rise in the groundwater table is highly probable to reach LC and LCC, which eventually results in adverse impacts on the foundations and, consequently, on the structures. Additionally, no previous study has been conducted to evaluate the effects of waste tire powder on the fresh, geotechnical, and durability properties of LC and LCC.Hence, the current study aims to evaluate the effects of various RPCs, curing periods, and degrees of saturation on the workability, water absorption, compressive strength and many other geotechnical properties of two LCC mixes. It is clear that waste tires can be promisingly used in the field if the replacement of natural aggregates with rubber powder does not significantly jeopardize the fresh, mechanical and durability properties of LCC. However, getting advantage of this waste material can alleviate the concerns and adverse environmental impacts associated with waste tires’ disposal, particularly in some regions where vast amounts of waste tires are available.2, Al2O3, and Fe2O3, respectively, with a cumulative amount of 62.11%, which is lower than 70%  [terials) . Hence, terials) ,36.Hydrated lime , with a purity of over 70%, in compliance with the requirements of ASTM C977-18 , was purIn some previous research studies, it was reported that the water quality can also affect the mechanical properties of concrete and cementitious materials ,53,54,55As previously discussed, the objectives of this research study are to investigate the impacts of different rubber powder contents (RPCs) and different moisture conditions induced by the capillary phenomenon and rise in the groundwater table on the geotechnical properties of lime-cement concrete (LCC) with two different mix designs. Hence, the amounts of the materials, sample preparation process, curing condition, and curing time for all of the specimens, as well as all of the conducted tests, including characterizations and UCS tests, were quite the same as those utilized for LCC specimens in the authors’ previous studies ,21. HoweThe optimal content of clayey soil in lime-based concretes is suggested to be in the range of 20–30% of the dry weight of coarse-grained soil based on the National Lime Association and a number of recently published articles ,12,20,213 concrete [3 of concrete) in all samples of the concretes. Accordingly, two groups of specimens were prepared (Group A with 2% cement and 5% lime and Group B with 3% lime and 4% cement). Using a combination of lime and cement instead of using lime alone was based on the results obtained from previous research conducted by the authors [For the lime-based concrete projects, the amount of binders in field implementations varies from 150 to 200 kg/mconcrete . Regardi authors , which iThe fresh concrete was then poured into the cylindrical molds with 70 mm diameter and 140 mm length. After three days of curing, the samples were demolded, followed by measuring their height, diameter, and weight with accuracies of 0.1 mm and 0.01 g, respectively. Subsequently, samples were placed in plastic bags to prevent significant moisture loss during their curing process. The samples were cured in the laboratory environment with a temperature of 20 ± 1 °C and a natural humidity of about 26% for 14, 28, and 60 days. In order to make the results applicable for the field projects, it is better to simulate the real field condition ,67,68,69Workability tests are conducted to determine the fresh properties of concrete. The slump test was primarily designed and used to measure the workability of conventional concrete, and hence it may not be appropriate for other types of concretes such as lime-based concretes. However, it was reported that the flow table test could be a more practical test to evaluate the workability of lime-based mortars and concretes ,71. ThusTo study the water absorption of the samples, following ASTM C642 , the speThe geotechnical properties of tested specimens are presented in s). In other words, a secant modulus is used to study the resistance of lime-based concretes to deformation, which is measured by dividing 50% of the UCS to the corresponding axial strain [For unreinforced concretes where the material exhibits a non-linear behaviour or where the initial tangent modulus does not provide sufficient needed information, it is preferred to investigate secant modulus (El strain .D) of the specimens was determined, representing the deformation properties of the specimens which are calculated using Equation (2) [One of the crucial considerations for structural and non-structural concretes is ductility, which describes the capability of the concretes to have deformations and certain energy dissipation to avert abrupt brittle failure when they are subjected to extreme loads, earthquakes, and winds. Therefore, in this research, the deformability index (Ition (2) ,78.(2)IBulk modulus defines the elastic deformation of the concrete when it undergoes pressure on all axes; in other words, it measures the resistance of the samples to compression and is calculated through the following equation :(3)K=σ/ttlement .In order to investigate the elastic response of soil and concrete to stress and repeated loads, resilient modulus should be evaluated. It needs to be mentioned that numerous parameters, including soil type , loading condition, moisture content, density, etc., have considerable impacts on the resilient modulus ,82. ThomIn order to investigate the resistance of specimens to transverse deformation shear modulus of the samples was calculated. Since shear modulus is of particular importance for structural design and analysing the site response, disregarding this parameter may lead to severe damage and loss . Shear mxy + εyx .In this section, the effects of rubber powder content (RPC), curing time, two mix designs, and saturation degrees induced by the rise in the groundwater table were evaluated on the properties of lime-cement concrete (LCC) including its workability, water absorption, compressive strength, and geotechnical properties.From the results of flow table tests presented in The water absorption rate is often considered a good indication of the durability of concrete and cementitious materials. As observed in 3); second, the presence of large content of clay and soil, and third the water/binder ratio is much higher in lime-based concretes compared with OPC concrete to achieve required workability. It should be noted that the low amounts of binders in lime-based concretes often provide the required strength suggesting that using a higher amount of binder to gain higher strength values is not required nor economical. In addition, the brittleness index of concrete mostly increases with strength increase, which gives rise to crack propagation in case of settlement of sub-soil under the foundations.The UCS test results versus different RPC contents  at 14, 28 and 60 curing days at different degrees of saturation  for samples of Group A (2% cement + 5% lime) and Group B (4% cement + 3% lime) are demonstrated in In a previous study on the effects of saturation degrees and durations of curing on the compressive strength of lime concrete (LC), it was concluded that the mentioned parameters have considerable effects on the compressive strength of the samples ,30. Addi(1)Rubber powder has lower strength values compared with its matrix around. Hence, when the concrete is subjected to external forces, the cracks first appear in the contact zone of the concrete matrix, and then they gradually initiate propagation until the concrete crumbles. Such discrepancy in the performance makes rubber particles act like voids in concrete ,93,94,95(2)Rubber particles have a remarkably low modulus of elasticity compared with natural aggregates ,96,97,98(3)The hydrophobic nature of the rubber particles brings about imperfect adhesion and bonding between the cement paste and rubber particles which leads to further weakening of the mechanical performance of the entire concrete ,99,100.As previously discussed, higher RPCs, led to lower strength values. At a constant degree of saturation, the UCS reduction rate at different curing periods and various amounts of rubber powder was nearly constant. The UCS values of Group A samples at saturation degree of 0% and curing time of 14 days decreased by 5.96, 11.89, 18.98 and 25.84% by increasing the RPC from 0 to 5, 10, 15 and 20%, respectively. Similarly, for the same samples cured for 28 days, the percentages of reduction in compressive strength were 6.27, 11.70, 17.15, and 23.02%, respectively in comparison to the control sample. The same trend was observed for samples in Group B. Li et al.  also repThe results demonstrate that although increasing the RPC in LCC led to compressive strength reduction, LCC containing up to 10% rubber powder could be promisingly used underneath or close to the groundwater table without its strength and geotechnical properties being significantly jeopardized as a result of rubber employment and/or exposure to moisture. Using RPC up to 10% reduced the strength value by approximately 10% in many specimens. Moreover, all 60-day specimens exposed to 100% saturation degree had a strength reduction of less than 10% by using multiple contents of rubber powder varying from 5 to 20%. Additionally, strength reduction by using higher RPCs was comparatively lower in Group B of the samples than Group A, implying that using higher cement content and lower lime content mitigates the negative impact of rubber in LCC specimens.The compressive strength of specimens increased with increasing the curing period due to the hydration reactions. Nevertheless, insignificant increases in strength values were obtained after a curing period of 28 days, which was in line with the findings of previous studies ,24. In oAs shown in The stress–strain curves of 28 day-cured of the specimens from Groups A and B at different moisture conditions are demonstrated in Comparing the stress–strain curves of Groups A and B of the specimens shows that the failure strains for Group A of the specimens are lower than those of Group B specimens. This could be due to the fact that lime has a lower specific weight in comparison to cement. As mentioned before, the total percentage of binder in this study was a constant value of 7%, so that the volume of the binder when only 2% cement combined with 5% lime was used was higher than the binder volume when 4% cement combined with 3% lime was employed. Moreover, since the water content in all mix designs was a constant value of 24.04%, Group A experienced lower workability compared with Group B, which led to lower failure strains.Based on the results presented in As shown in As observed in The samples could resist the swelling and shrinkage of clayey soil in the mixtures because of cement contribution and its coexistence with lime. Such behaviour could be attributed to the filling of large volumes of the pores of sandy soil by the clayey soil along with the pozzolanic activities of lime and the cementation reactions from strong inter-particle bonding. Similar behaviour was observed in previous research studies where the introduction of cement to LC brought about a remarkable impact on the susceptibility of the LC to saturation and let the soil preserve its strength in the presence of moisture ,23,102.A direct relationship between secant modulus and bulk modulus is apparent from Equation (4). Hence, extending the duration of curing, decreasing RPC content, and lowering the saturation degree resulted in an increase in the bulk modulus of all the studied concretes. As shown in The correlation between resilient modulus and UCS values of the samples is linear and direct as confirmed with Equation (5). Thus, extending the duration of curing, increasing the RPC content, and lowering the saturation degree resulted in an increase in the resilient modulus of all the studied concretes. As presented in (1)Within a constant amount of binder, by increasing the lime content and decreasing the cement content, the UCS value decreased such that the UCS values of Group B samples were nearly two times those of Group A. Increasing the degree of saturation brought about a reduction in the UCS values at different curing times and various rubber powder contents. This could be attributed to the partial disintegration of the chemical bonds between lime and clayey soil. However, strength reduction due to the saturation increment was higher for samples from Group B compared with Group A; nevertheless, the ultimate UCS values of Group B samples, even in the condition of full saturation, were greatly higher than those obtained for the samples of Group A, implying their superb resistance in the presence of moisture.(2)LCC prepared with the mix design of Group B samples containing up to 10% rubber powder could be promisingly used in dry conditions and even underneath or close to the groundwater table with insignificant impact on the compressive strength and geotechnical properties because of rubber employment and/or exposure to moisture. Therefore, in some cities where vast amounts of waste tires are available, taking advantage of this waste material can not only provide reasonable resistance for LCC but can also alleviate the concerns and adverse environmental impacts associated with their disposal.(3)However, it should be noted that LCC samples with the mix designs of Group A are considered suitable to be cast in a totally dry land where there is a long distance between the bottom of the concrete and groundwater level or where the moisture from any direction cannot reach the concrete due to the capillary suction, etc. It is reported that the capillary action can take place and moisturize the clayey soils even up to 25 m above the groundwater level. Therefore, in the construction sites where the type of soil is predominantly clayey soil (such as Kerman city in Iran), the use of LCC prepared with the mix designs of Group A is not considered rational. Nevertheless, it is obvious that the capillary suction is considerably limited in coarse-grained soils so that they could be used where the type of soil beneath the foundation is a coarse-grained soil with high drainage capacity.(4)The performance of LCC (containing rubber powder) against multiple wet–dry and freeze–thaw cycles has not been studied in this study; thus, it is recommended for future research to investigate the durability of LCC containing rubber powder against wet–dry and freeze–thaw cycles. Moreover, the results of ongoing research conducted by the authors indicated the superb performance of fly ash and wood ash when they are used as cement or lime replacements in lime-based concretes exposed to different ground moisture conditions. Thus, it is also recommended to investigate the use of these by-products in such lime-based concretes containing rubber powder.Lime-cement concrete (LCC), as a non-structural concrete, has been broadly utilized in some warm regions to provide a support layer beneath the shallow foundations of low-rise buildings. However, fairly limited research has been conducted to evaluate the geotechnical and durability properties of LCC under different ground moisture conditions induced by the capillary action and rise in the groundwater table. On the other hand, several research studies were conducted on getting the advantage of waste tire rubber in conventional concretes. However, in field projects, rubber has not been widely used because its employment leads to strength reduction in concrete specimens. For structural concretes, achieving high strength values is of particular importance, but in the case of LCC, attaining high strengths is not required. Hence, in this research, the impact of various rubber powder contents (RPC), saturation degrees, curing times and two mix designs on the workability, geotechnical and durability properties of LCC were studied. The following main conclusions can be drawn:


Background: For measuring their impact in scientific research, the citation count of the publications is used in the bibliometric analysis, though still in the bibliometric analysis, there is no comprehensive summary of mild traumatic brain injury (mTBI) research. This article intends to provide the physicians and the neuroscientists with a reference guide to assess the most influential publications written on this subject through a macroscopic view of the research activities on mTBI.Methods: The database of the Web of Science was used to compile the 100 top-ranking publications on mTBI. The selected publications were evaluated on the basis of the several categorizations including the type of the publications, number of citations, country of origin, and year of publication.Results: Between 1946 and 2020, the 13,040 publications that were published were included in the database. The least cited publications received 274 citations, while the most cited received 1,748. Altogether, 71 publications were from the USA while 29 were from other countries. Among all the institutions, the University of Pittsburgh Medical Center led the list with six publications. Around 100 papers, mostly on the clinical studies in the categories of neurology and neurosciences, were published in 54 different journals.Conclusions: This study provides both a transverse section summary and historical retrospect for the clinical advances of mTBI, and the publications of important observations that contributed a significant impact on the treatment and prevention of mTBI had been identified. In the United States with the incidence of around 2.5 million emergency department visits per year, Mild traumatic brain injury (mTBI) is known to be the most common form of traumatic brain injury . With thCitation rate is an important index to quantify the quality of publications and research, although the number of citations for one article cannot completely reflect the level and academic quality of the research, indicating in its category, how celebrated that article has been , 3. BaseThree independent researchers on June 4, 2020 made use of the Web of Science (WOS), the most professional and authoritative citation indexing database, to recognize the 100 top-cited publications in the field of mTBI. The keywords “mTBI,” “mild TBI,” or “mild traumatic brain injury” were used to search the database. Publications specific to mTBI were identified. There were no restrictions on the article types. The 100 top-cited publications in the field of mTBI were identified and reviewed. As illustrated in After confirming the search scope, next comes the recognition of the 100 top-cited publications from the 13,040 publications, which were arranged in reverse chronological order. Then, screening of the relevant publications was done by three independent researchers. After reading the full text and abstract of each selected article, data collection was completed according to: years, journals, authors, countries (refer to corresponding authors' affiliations), institutions, study fields, publishers, article types, impact factors, and research methods. By logging into certain other search platforms like PubMed, Sciencedirect, Springerlink, and BioOne, publications without complete information and full text were obtained. In addition, we excluded publications (a) ranking below 150 and (b) about primary cerebroma such as pituitary adenomas, schwannomas, pineocytomas, and etc. according to the selection criteria. Contributions to the design and concept of the study were made by all the authors.n = 17), Australia (n = 5), Sweden (n = 4), Netherlands (n = 4), Germany (n = 4), UK (n = 3), and other countries . In the Annals of Emergency Medicine, the article in 2008 on a clinical policy research on evidence-based recommendations of select issues in the management of adult mild traumatic brain injury was the one with the least citations numbering 262 . These publications were published between 1946 and 2020. Distribution of the top-cited publications per year is shown in ountries . And theThe 100 top-cited publications were cited 277.6 times on average and the top 10 most-cited publications on mTBI are presented in n = 9), New England Journal of Medicine (n = 5), Neurology (n = 5), Journal of Neurotrauma (n = 5), Lancet Neurology (n = 4), and others (n = 72).Listed as the first authors, there were around 10 authors who had contributed more than two top-cited publications. Polderman K H, the author of four of the top 100 publications led the list. Nine other authors, with two of the top 100 publications each, followed. n = 6), followed by the Virginia Commonwealth University (n = 4). The remaining different institutions like the University of California Los Angeles, Columbia University, Cornell University Weill Medical College, Dartmouth-Hitchcock Medical Center, James A. Haley Veterans' Hospital, The Royal Children's Hospital (Melbourne), and The University of Texas, Galveston, USA all produced two publications, respectively , followed by review (n = 25), basic science research (n = 10), and Epidemiologic research (n = 8).The majority of the topics of the top 100 most-cited publications in the primary field study on mTBI were on neurology and neurosciences, followed by those on radiology, psychiatry, pediatrics, rehabilitation, internal and general medicine, and sport sciences, amongst others. A total of 23 categories  can be found and shown in There is no doubt that citation analysis can provide a large amount of information about journals, authors, institutions, and research directions. It can be used to identify landmark papers and influential journals, and help researchers and clinicians discover the basis, current status, and related progress of research. It not only provides a historical review for scientific research in the mTBI field, but also looks forward to its development trends and prospects , 12. InsThe major part of the most-cited publications in the mTBI field was from the United States as compared to that from any other country, which clearly indicated that the publications published from the United States were of high quality and standards over the past five decades. The most top-cited paper focused on the mTBI soldier returned from the Iraq war , which pThe worldwide productivity of published publications on mTBI were concentrated in Australia, Northern Europe, and Northern America, as was evident from the distribution map. JAMA-Journal of The American Medical Association published the most mTBI research worldwide, followed by the New England Journal of Medicine with the highest impact factor. In the United States, the author and research group of the highly cited papers mainly come from comprehensive universities, both the eastern and the west coast of the US. In Australia and Northern Europe, the top mTBI research group publications in the hospital and medicine center.For a long time, the clinical study predominated the mTBI research, from the 1990's, the review paper attracted more and more attention. Compared to other disease research fields, the proportion of basic science in mTBI was obviously lower , indicatThis bibliometric study also has some limitations. Firstly, the mTBI-related publications are being continually cited, the citation metrics might change since we completed the analyses. Secondly, self-reference bias should be should be taken into consideration. Nevertheless, given this research's breadth, richness, and abundant citations, we believe that it can still be invaluable in representing the overall tendency of important publications in the field of mTBI research.Improved recognition of the research in the field of traumatic brain injury and a cross-sectional summary of significant research earlier were enabled by the bibliometric analysis of the 100 top-cited publications. Definitely, it would reveal the trends of research requiring development and further investigations besides accelerating the progress of the studies on mTBI.The data used to support the findings of this study are available from the corresponding author upon request.XD and MC screened the articles. Data were extracted from each of the articles by JS, XD, and MC. NL, JS, and XD performed the analysis and drafted the manuscript. All authors contributed to the study conception and design, commented on previous versions of the manuscript, read, and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Known as an autoimmune glomerular disease, idiopathic membranous nephropathy (IMN) is considered to be associated with phospholipase A2 receptor (PLA2R) in terms of the main pathogenesis. The quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies by time-resolved fluoroimmunoassay (TRFIA) was determined, and the value of them, both in the clinical prediction of risk stratification in IMN, was observed in this study.  95 patients with IMN proved by renal biopsy were enrolled, who had tested positive for serum PLA2R antibodies by ELISA, and the quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies was achieved by TRFIA. All the patients were divided into low-, medium-, and high-risk groups, respectively, which were set as dependent variables, according to proteinuria and renal function. Random forest (RF) was used to estimate the value of serum PLA2R-IgG and PLA2R-IgG4 in predicting the risk stratification of progression in IMN.  Out-of-bag estimates of variable importance in RF were employed to evaluate the impact of each input variable on the final classification accuracy. The variable of albumin, PLA2R-IgG, and PLA2R-IgG4 had high values (>0.3) of 0.3156, 0.3981, and 0.7682, respectively, which meant that these three were more important for the risk stratification of progression in IMN. In order to further assess the contribution of PLA2R-IgG and PLA2R-IgG4 to the model, we built four different models and found that PLA2R-IgG4 played an important role in improving the predictive ability of the model.  In this study, we established a random forest model to evaluate the value of serum PLA2R-IgG4 antibodies in predicting risk stratification of IMN. Compared with PLA2R-IgG, PLA2R-IgG4 is a more efficient biomarker in predicting the risk of progression in IMN. Idiopathic membranous nephropathy (IMN), known as primary membrane nephropathy, is the most common cause of primary nephropathy syndrome in adults , 2, whicIn 2009, Beck et al.  found 70At present, the detection of sera anti-PLA2R antibodies normally applies indirect immunofluorescence assay (IIFA) and enzyme-linked immunosorbent assay (ELISA) . IIFA isIn this study, we determined the quantitative detection of anti-PLA2R-IgG and -IgG4 antibodies by TRFIA and observed the value of them both in the clinical prediction of different risk-stratified IMN.A total of 95 patients with IMN proved by renal biopsy, who had tested positive for serum PLA2R antibodies by ELISA, from the Affiliated Wuxi People's Hospital of Nanjing Medical University, were enrolled from January 2016 to December 2017. According to proteinuria <4 g/d, 4–8 g/d, and >8 g/d, with renal function taken into consideration, all the patients were divided into low-, medium-, and high-risk groups, respectively .Blood samples were collected before renal biopsy and before the immunosuppressive therapy, which were left standing to clot thoroughly before centrifuging at 3000 rpm/min for 4 min to obtain serum, and sera were then stored at −80°C for pending analysis. All renal tissue specimens were examined using light microscope, immunofluorescence, and electron microscope. Pathological grading was performed by Ehrenreich and Churg standards .1235 was purchased from Perkin Elmer (USA).Goat anti-human IgG antibodies were obtained from Jackson ImmunoResearch (USA), and mouse anti-human IgG4 antibodies were offered by Hytest (Finland). Europium labeling kits (1244-302) were purchased from Perkin Elmer (USA). The polystyrene microtiter plates were obtained from Nunc International (Denmark). The recombinant PLA2R antigen, series of standards of anti-human PLA2R-IgG and PLA2R-IgG4 were prepared in our laboratory as previously reported , 14. AllμL of standards or diluted sera were pipetted to the microtiter plates fixed with 5 μg/mL of rPLA2R. The working dilutions of serum samples were 1 : 200 and 1 : 20 in the anti-PLA2R-IgG and anti-PLA2R -IgG4 assays, respectively. The mixture was reacted with continuously shaking at 25°C for 1 h. After the unreacted substances were removed by washing for 3 times, the plates were pipetted with europium-labelled goat anti-human IgG or mouse anti-human IgG4 antibodies, shaken for 1 h at 25°C, and then rinsed for 6 times. Finally, 96-well plates were added with 200 μL of enhancement solution, agitated for 5 min, and measured in AutoDELFIA1235. The concentrations of serum samples of anti-PLA2R-IgG and anti-PLA2R-IgG4 were automatically calculated from the fluorescence of wells by AutoDELFIA1235. According to the previous work [Firstly, 100 ous work , 14, theThis work employed 38 features (variables) including pathological and clinical features to describe the patients' characters, which contained mean, standard deviation, and correlation coefficient of samples as shown in k-nearest neighbor (KNN) and support vector machines (SVM) classifiers, it has the following advantages: (1) it can assess the importance of variables when determining categories; (2) when building a forest, it can produce an unbiased estimate of the generalized error internally; (3) for unbalanced classification data sets, it can balance errors; (4) the learning process is fast.In machine learning, the random forest (RF)  is a clac denotes the number of classes. TPi denotes the number of true positive (TP) in subclass i. M and Mi denote the number of whole test samples and subclass test samples. ACCi denotes the accuracy in subclass i.The accuracy (ACC) is utilized to evaluate the performance of the RF model under 5-fold cross-validation (5-CV). The calculation method of ACC is as follows:To evaluate the impact of each input variable on the final classification accuracy. We employed out-of-bag estimates of variable importance in RF. The RF stored the increase in mean square error (MSE) averaged over all trees in the ensemble and divided by the standard deviation taken over the trees, for each variable. So, we could get the importance scores of all input variables. In general, the larger the score, the more important it is for the prediction model. In order to further evaluate the contribution of PLA2R-IgG and PLA2R-IgG4 to the model, we constructed four different models, which contain both PLA2R-IgG and PLA2R-IgG4 variables, PLA2R-IgG variable, PLA2R-IgG4 variable, and no PLA2R- IgG and PLA2R-IgG4 variables. The relevant information of the models is shown in The classification performance of the 4 models was verified by 5-fold cross-validation. And, the results are listed in t-test to evaluate the significant differences of average ACC between different models. The results were list in P value of model 3 and model 4 was 0.0022. This means that the PLA2R-IgG4 feature had a more significant performance improvement compared to the ordinary model (without PLA2R-IgG and PLA2R-IgG4).In this study, we employed It is widely recognized that IMN is an autoimmune glomerular disease in which autoantibodies combine with antigens on glomerular podocytes and deposit in glomerular capillary walls . With th−18 mol/L), wide monitoring range, and less susceptibility to matrix interference [Among all the PLA2R-IgG antibodies, PLA2R-IgG4 antibodies are predominant , 18. Lacrference . Our prerference . TherefoP value < 0.05). Compared with model 4, model 3 also had significant difference . It was obvious that PLA2R-IgG4 played an important role in improving the predictive ability of the model.In recent years, machine learning methods have been widely used in medicine –22 and bIn this study, we evaluated the value of serum PLA2R-IgG4 antibodies in predicting risk stratification of IMN by establishing a random forest model. Compared with PLA2R-IgG, PLA2R-IgG4 is a more efficient biomarker in predicting the risk of progression in IMN. The study results are satisfactory, while disadvantages remain (1) there is lack of analysis about the value of serum PLA2R-IgG4 in the prediction of treatment effect; (2) the sample size needs to be further expanded to minimize the prediction bias. In the next work, we will expand the sample size and survey the predictive effect of serum PLA2R-IgG4 in the therapeutic regimen and prognosis of IMN.


Medical images are important in diagnosing disease and treatment planning. Computer algorithms that describe anatomical structures that highlight regions of interest and remove unnecessary information are collectively known as medical image segmentation algorithms. The quality of these algorithms will directly affect the performance of the following processing steps. There are many studies about the algorithms of medical image segmentation and their applications, but none involved a bibliometric of medical image segmentation.This bibliometric work investigated the academic publication trends in medical image segmentation technology. These data were collected from the Web of Science (WoS) Core Collection and the Scopus. In the quantitative analysis stage, important visual maps were produced to show publication trends from five different perspectives including annual publications, countries, top authors, publication sources, and keywords. In the qualitative analysis stage, the frequently used methods and research trends in the medical image segmentation field were analyzed from 49 publications with the top annual citation rates.The analysis results showed that the number of publications had increased rapidly by year. The top related countries include the Chinese mainland, the United States, and India. Most of these publications were conference papers, besides there are also some top journals. The research hotspot in this field was deep learning‐based medical image segmentation algorithms based on keyword analysis. These publications were divided into three categories: reviews, segmentation algorithm publications, and other relevant publications. Among these three categories, segmentation algorithm publications occupied the vast majority, and deep learning neural network‐based algorithm was the research hotspots and frontiers.Through this bibliometric research work, the research hotspot in the medical image segmentation field is uncovered and can point to future research in the field. It can be expected that more researchers will focus their work on deep learning neural network‐based medical image segmentation. In the second section, the research methodology, the data sources, and bibliometric tools are described. In the third section, quantitative analysis has been implemented from five perspectives including annual publication, countries, authors, sources, and keywords. In the fourth section, qualitative analysis has been implemented to top annual citation rates publications. In the last section, the conclusion of this study is presented.2Using bibliometric combined with qualitative analysis, the publication trends in the medical image segmentation field were evaluated. Two well‐known academic databases, the WoS Core Collection and Scopus, were used to collect relevant publications. The WoS database is an internationally recognized database that can reflect high‐level scientific research. It enjoys a good reputation in the world of science, technology, and education with “Science citation index Expanded” (SCIE), “Social Science Citation Index” (SSCI), and other citation index databases, besides journal citation reports (JCR) and essential science indicators (ESI). It is the world's largest academic database, covering over 15 000 scientific, technical, and medical journals. WoS core collection includes SCIE, SSCI, Arts and Humanities Citation Index (A&HCI), and Emerging Source Citation Index (ESCI). Scopus covers the world's most extensive scientific and medical publications in abstracts, references, and indexes, which collects publications from many famous journals.The data collection and filtering process are shown in Figure 3Up to January 11th, 2021, a total number of 1914 publications related to medical image segmentation have been collected. In this section, a quantitative analysis of these publications will be conducted from five perspectives: annual publications analysis, countries and languages analysis, top authors analysis, sources analysis, and keywords analysis.3.1Figure The number of publications has grown at an average annual rate of 18.7% over the past 30 years. Stripping out the impact of the earlier years of a low number of publications, the average annual growth rate over the past decade has been 13.6%. Compared with all publications included in the Scopus database, the number of published articles has increased from 881 500 in 1990 to 2 712 413 in 2020, with an average annual growth rate of only 3.8%, and an average annual growth rate of 4.3% in the past decade. This indicates that the number of publications growth speed of the medical image segmentation research field is significantly higher than that in overall scientific research.The citations of these 1914 publications are analyzed as a whole. These publications were cited a total number of 29 669 times, among which 27 752 times were cited by others, accounting for 93.5%. The number of self‐citation was 1917 times, accounting for 6.5%. The general view is that a high other‐citation rate indicates the high quality of the article. Therefore, the subsequent citation analysis in this article excludes self‐citation and only analyzes other citation data.The average article citations per year are shown in Figure 3.2In our analysis set of 1914 publications, corresponding authors are distributed in 54 countries or regions, as shown in Figure Figure Figure The publications from Austrian or German authors have more than 100 average article citations, which is much higher than any other country or region in terms of citation intensity. The average article citations of the major participating countries or regions are listed in Table Table 3.3In our analysis set of 1914 publications, there were a total of 4357 related authors appearing in the author list. Figure Figure 3.4Figure 3.5Review articles collect information from tons of original research articles. The topic and keywords have lots of overlap. It affects the statistical data. Therefore, a total of 17 publications, which type was review, were removed from the analysis data set, and the keyword analysis was conducted on the remaining 1897 publications. Table A Word cloud can visually illustrate the situation of keywords and highlight the keywords with a high frequency of occurrence. To grasp the most prominent keywords in the medical image segmentation field quickly and intuitively, word clouds are generated for the extracted author keywords. Figure Figure The most frequent author's keywords are listed in Table Figure Three‐field plots were used to analyze publications in the medical image segmentation field, which not only focuses on the most frequent author's keywords, the top authors, and the top publication sources but also illustrates the relationship among them, as shown in Figures 4Up to January 11th, 2021, there were a total of 1914 publications in the medical image segmentation field in the Scopus database. To filter the most valuable high‐quality publications from this data set, all of them were sorted in descending order of annual citation rates, which is defined as the total number of citations divided by the number of years after publication. The publications whose annual citation rates were no less than 10 were filtered, and the results number was 49, accounting for 2.6% of the total number of publications. The annual citation rates of these publications ranged from 289.0 to 10.0. Qualitative analysis of the content of these top annual citation rates publications can help researchers to identify the most concerning research topics in the medical image segmentation field.The taxonomy method was applied to classify these 49 high annual citation rates publications into three categories and several subcategories, as shown in Figure 4.1There were 11 reviews among these 49 high annual citation rates publications in the medical image segmentation field, which occupied 22.4% of all high annual citation rates publications. This proportion is significantly higher than that of all reviews in the total publications, which was less than 1%. While the total number of reviews was 17, which indicated that more than 60% of these reviews on medical image segmentation had high annual citation rates. Therefore, reviews are classified into the first and most important category in this taxonomy. Qualitative analysis of these high annual citation rates reviews, which were published in different periods according to the time sequence, can help researchers to extract the most important information from the massive medical image segmentation publications and to grasp the research trend in this field from a macro perspective. In this subsection, these high annual citation rates reviews in the medical image segmentation field were analyzed according to the time of publication.The research of medical image segmentation was started in the 1990s, and it was not until 2000 that a high annual citation rates review in this field was published, while the peak of review publication appeared around 2010. In 2000, Pham et al. reviewed medical image segmentation methods and divided them into eight categories, which are “thresholding, regional growth, classifiers, clustering, Markov random field (MRF) models, artificial neural networks, deformable models, and atlas guided approaches.k‐nearest neighbor(k‐nn) and maximum likelihood; clustering methods, which include k‐means, Fuzzy C‐mean, and expectation maximization; and hybrid methods, graph cut (GCs).”With the prosperity of medical image segmentation research and a large number of research results published in this century, the number of reviews of medical image segmentation has increased gradually. In 2010, under the background of CT and MRI, Sharma and Aggarwal discussed automated medical image segmentation techniques and ranked them according to the applicability, suitability, performance, and computational cost, which are gray level and region‐based techniques, textural features‐based techniques, and neural network‐based algorithms.During this period, there are also some reviews of specific kinds of medical image segmentation methods that emerged. In 2008, He et al. conducted a comparative study on the application of eight different snake deformable contour methods and level set methods in medical image segmentation.With the boom of artificial intelligence, deep learning, and neural network technology research in recent years, more and more deep learning and neural network‐based medical image segmentation research results have been published. In 2019, based on summarizing these works, Hesamian et al. reviewed the main training techniques of medical image segmentation neural networks and analyzed the advantages and disadvantages of them.4.2The high annual citation rates publications on medical image segmentation algorithms are reviewed in this subsection. These publications are further classified according to different types of algorithms including traditional medical image segmentation algorithms, and deep learning neural network‐based medical image segmentation algorithms. There are a total of 33 publications in this category, accounting for 67.3% of the total number of high annual citation rates publications, covering a period from 1994 up to now. Qualitative analysis of these publications can help researchers to delve into the research details in this field on a microlevel.4.2.1There were only two publications in the last century on traditional medical image segmentation algorithms with high annual citation rates including the geometric snake modelIn the recent decade, although the research hotspot and frontier of medical image segmentation have changed to deep learning neural network‐based algorithms, there are still some traditional medical image segmentation algorithms that have been proposed. In 2012, Chen et al. proposed a 3D abdominal 3D organ segmentation method based on the combination of active appearance model (AAM), live wire (LW), and GCs.4.2.2In the recent 5 years, with the emergence of artificial intelligence technology, deep learning and convolutional neural network (CNN)‐based medical image segmentation algorithms have also been developed greatly. Although the high annual citation rates publications in this field only began in the last 5 years since 2016, the publication number was as high as 18, accounting for more than 50% of the publications on medical image segmentation algorithms, and the growth trend is accelerating. These publications were analyzed in chronological order in the following section.In 2016, Milletari et al. proposed a “convolutional neural network (VNET)‐based volumetric medical image segmentation,” which can segment prostate tissue fastly and accurately in MRI images.As well as 2016, there were two deep learning and CNN‐based medical image segmentation publications that received a high annual citation rates in the year 2017. Combining the fully convolutional networks (FCNs) and the fully convolutional residual networks (FC‐ResNets), Drozdzal et al. proposed a “simple and powerful pipeline for medical image segmentation.In 2018, the number of high annual citation rates publications for deep learning and CNN‐based medical image segmentation algorithms began to increase dramatically, and a total of seven publications entered the high annual citation rates list. Zongwei et al. proposed a nested U‐net architecture named Unet++ for medical image segmentation, which is a deeply supervised encoder‐decoder network in essence.In 2019, there was some reduction of high annual citation rates publications for deep learning and CNN‐based medical image segmentation algorithms, and a total of five articles entered the high annual citation rates list this year. Gu et al. proposed a “context encoder network for 2D medical image segmentation,” named CE‐Net, which was applied to several different tasks.In 2020, there is not any publication received more than 10 times citation. This may be due to the fact that the manuscripts that cited recent publications have not yet been published. Manuscripts usually take 3–6 months or more to be published.4.2.3HereSegmentation accuracy is the most important index to evaluate a medical image segmentation algorithm and should be the primary concern of relevant researchers. The analysis in SectionA and B represent the predicted region and the ground truth region, respectively.The dice value is between 0 and 1. The value is closer to 1, the segmentation accuracy is higher. It should be pointed out that, under the same algorithm, the dice values of different types of medical images or different tasks are often quite different. Although it is meaningful to compare the dice values given directly in these publications, it is more meaningful to analyze the differences under the same segmentation task. Among them, the U‐net4.3Apart from the categories identified in sections 5This bibliometric is first limited by the number of academic databases searched, especially not including non‐English databases, although the selected databases are reliable and comprise broadly representative collections. Second, the rapid progress in the field of medical image segmentation technology limits the timeliness of the bibliometric. Third, we emphasize that research activities in this field do not necessarily reflect the practical application or impact of these research findings in this field. The results of these studies only reflect current research trends in academia, which is the purpose of this bibliometric.6In this work, quantitative and qualitative analysis was conducted on publications in the medical image segmentation field get from the Scopus database as of January 11th, 2021. In the quantitative analysis stage, a total of 1914 publications were analyzed from five perspectives: annual publications, countries, top authors, publication sources, and keywords. The results showed that the number of publications in the medical image segmentation field increased rapidly by year, and the citation rate also increased as a whole. Most of the authors were from the Chinese mainland, the United States, and India, and there was a lot of cooperation between the Chinese mainland and the United States. Most of the top 10 most relevant authors were from the Chinese mainland, but none of them were high‐impact authors. More than half of the 1914 publications were conference papers, and “IEEE Transactions on Medical Imaging,” “Medical Image Analysis,” and “IEEE Access” were the top three journals. The keywords analysis showed that deep learning is the research hotspot in this field in recent years. In the qualitative analysis stage, 49 publications with no less than 10 annual citation rates were analyzed. The taxonomy method was applied to classify these publications into three categories including reviews, segmentation algorithms, and other relevant publications. Among these three categories, segmentation algorithms accounted for the vast majority, among which deep learning neural networks‐based algorithms were the research hotspots and frontiers. This article has a significant meaning for understanding medical image segmentation and following the direction of further research in this field. It can be expected that more and more researchers will work on the deep learning neural network‐based medical image segmentation, which may lead to more and more publications.Bin Zhang: Literature search and data analysis, writing original draft preparation, and obtain funding support.Bahbibi Rahmatullah: Supervision and revised the manuscript.Shir Li Wang: Supervision and revised the manuscript.Guangnan Zhang: Writing review and editing, obtain funding support.Huan Wang: Writing review and editing, obtain funding support.Nader Ale Ebrahim: provides the methodology and revised the manuscript.The authors declare that they have no conflict of interest.


In the space of four decades, Brazil has faced two serious pandemics: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Coronavirus disease 2019 (COVID-19). The country’s response to HIV/AIDS was coordinated by several stakeholders and recognised the importance of scientific evidence in guiding decision-making, and a network offering monitoring and antiretroviral treatment was provided through coordinated efforts by the country’s universal health system. Conversely, the lack of a centrally coordinated strategy and misalignment between government ministries regarding the COVID-19 pandemic response, together with the denial of scientific evidence, promotion of ineffective treatments and insufficient vaccination efforts, have all led to the uncontrolled spread of infection, the near-total collapse of the health system and excess deaths. In 1982, Brazil reported its first cases of acquired immunodeficiency syndrome (AIDS) as the country was emerging from a military dictatorship (1964-1985). In 1986, the Ministry of Health (MoH) established the National STD/AIDS Program, which involved extensive stakeholder participation.HIV/AIDS and Coronavirus disease 2019 (COVID-19) are diseases with distinct epidemiological, biological and clinical profiles. However, when faced with both infections, the scientific community responded promptly by identifying and sequencing causal agents, developing diagnostic tests, characterising each disease, setting up clinical trials to evaluate potential treatments and providing clinical facilities to care for infected individuals. Concerning COVID-19, effective vaccines were quickly developed using innovative technologies. Considering its experience acquired during the AIDS pandemic, the extensive reach of SUS and the presence of a robust national immunisation program (PNI) capable of vaccinating millions per day, Brazil had all the necessary tools to effectively respond to the COVID-19 pandemic. Unfortunately, despite activating the national Emergency Health Operations Centre in January 2020, prior to diagnosing the first domestic case,Many factors can help explain Brazil’s antithetic response to COVID-19 in comparison to HIV/AIDS. Disparities among Brazilians throughout the continental-sised country demanded coordinated efforts in both cases. For example, the alignment between the MoH and the Ministry of Foreign Affairs enabled Brazil to have a prominent position in international forums and to express leadership in negotiations to expand universal access to antiretrovirals. In contrast, since the beginning of the COVID-19 pandemic, there has been disarticulation regarding the acquisition of inputs, such as diagnostic kits and masks, between these same ministries. The lack of appropriate strategies has also hampered the acquisition of raw materials essential to vaccine production, as well as to vaccines themselves. In addition, misguided and often negligent decisions were also taken due to deficient coordination between the MoH and the Ministry of Economy, Finance and Planning, resulting in inadequate financial support to facilitate adherence to social distancing measures.It is important to note the autonomy of the MoH and the National AIDS Program with regard to ideological preferences or outside influence from private groups, which permitted the establishment of bold price negotiations in the purchasing of antiretrovirals, as well as the establishment of progressive health campaigns aimed at AIDS prevention. On the contrary, the government’s response to the current COVID-19 epidemic has been characterised by an absence of autonomy, as technical and expert committees have been marginalised at the expense of feeble solutions and ineffective treatments.Brazil also played an essential role to the approval to the use of compulsory licensing of drugs during pandemics, such as HIV/AIDS, as a basic human right.Denying the severity of COVID-19 and issuing recommendations for ineffective treatments has facilitated non-adherence to preventive measures.The restrictions imposed by EC95 weakened SUS and evaporated financial support necessary to spur scientific and technological development. All this is also in contrast to the AIDS epidemic measures.,,All of these aspects may have potentially increased morbidity and mortality, especially among the most vulnerable populations,The HIV/AIDS epidemic in Brazil prompted clear political decision-making and the establishment of strong partnerships among several stakeholders, including government leaders, civil society, universities, researchers and health professionals. Collaboration was also very clear and effective between ministries. As already mentioned, a good example was the alignment of the MoH and Foreign Affairs which facilitated the prominent position in various international fora, especially World Health Oraganization/Joint United Nations Programme on HIV/AIDS (WHO/UNAIDS), in defense of human rights, against discrimination and for a worldwide expansion of access to antiretrovirals. To effectively combat COVID-19, the lessons previously learned from the Brazilian experience with HIV/AIDS must be applied to counteract isolationism, boost international solidarity and cooperation, adequately finance science and quality public health services, confront anti-science rhetoric and anti-vaccine movements and prioritise egalitarian access to technological progress.


Background: Neurodegenerative diseases are disorders in which nerve cells start to lose function due to different causes. Like many other illnesses, they are considered to be highly prevalent in the 22 Arabic-speaking countries known to constitute the Arab world. The two most prevalent neurodegenerative disorders are Alzheimer's disease and Parkinson's disease.Aim: The aim of this paper is to assess the amount of research dedicated to neurodegenerative diseases by the Arab countries during a 15-year period, between 2005 and 2019.Methods: The number of publications by each Arab country as well as some non-Arab speaking countries was retrieved from PubMed. Publications in top 10 neuroscience journals were also tracked using the same method with each journal’s name included. The numbers were then normalized with respect to the average population and average gross domestic product (GDP) in each country to eliminate bias.Results: Arab countries were shown to contribute only 1,311 (0.774%) of the 169,330 articles published worldwide on neurodegenerative disorders. These 1,311 also constitute only 0.660% of the 198,869 Arab publications during the indicated period. Saudi Arabia had the highest contribution to these numbers with more than one-quarter the number of publications on neurodegenerative disorders. Approximately one-third of all neurodegenerative disease-related articles were associated with Alzheimer's disease, whereas one-fifth were related to Parkinson's disease. For the top 10 neuroscience journals, only a minimal contribution by Arab countries was noted.Conclusion: Although an increase in the number of articles by the Arab world was noted from 2013 onward, the contribution of the Arab countries on the subject to the number of publications still seems to be insufficient. The Arab world consists of 22 Arabic-speaking countries, concentrated mainly in the Middle East and North Africa. As in any part of the world, the various Arab countries differ significantly with respect to incomes, where some are considered high-income countries and others low-income. Although the amount of research conducted by the Arab world has increased remarkably during the last few years, Arab countries still seem to provide a deficient contribution to the total research conducted worldwide . MoreoveNeurodegenerative disorders are diseases where nerve cells start to lose function and consequently die, and proteins accumulate in the brain and other peripheral organs . They arStudies on Arab countries proved neurodegenerative diseases to be prevalent regionally, ranging between 1.1-2.3% in the ≥ 50 years population and 13.5-18.5% in the ≥ 80 years population , which eKeeping in mind the high incidence of neurodegenerative disorders and their risk factors, in addition to the low quantity of research on these disorders in the Arab world, we performed a bibliometric analysis of these countries’ contribution to such research. Therefore, this paper aims to assess the number of publications concerning neurodegenerative diseases between 2005 and 2019 from the 22 Arab countries, focusing mainly on the two most prevalent disorders: Alzheimer's disease and Parkinson's disease.Database and search strategy A screening was done for neurodegenerative-related publications for a period of 15 years (2005-2019) from all 22 Arab countries, constituting Algeria, Bahrain, Comoros, Djibouti, Egypt, Iraq, Jordan, Kuwait, Lebanon, Libya, Mauritania, Morocco, Oman, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, United Arab Emirates, and Yemen.Using Boolean operators AND, OR, and NOT, we searched PubMed for “neurodegenerative diseases”, “Alzheimer’s disease”, and “Parkinson’s disease”; the Medical Subject Headings (MeSH) for “name of Arab country required” affiliation, and the Mesh Dates "2005 - 2019". Cities in the United States (US) called Lebanon were excluded, and in Palestine, we used West Bank and Gaza.Countries with the highest research productivity related to neuroscience were also searched, including the US, the United Kingdom (UK), Germany, Japan, Canada, Italy, France, China, Netherlands, and Australia .The same methods were used to track publications in the top 10 neuroscience journals, searching for the journal’s name in addition to the procedures stated above.Inclusion and exclusion criteriaAll types of articles were included, as long as they had an author from the targeted country, and the article was published between 2005 and 2019.Interpretation and comparisonThe average population and gross domestic product (GDP) were acquired for each country between 2005 and 2019 using data from the 2019 World Population Prospects and the 2019 World Bank report on GDP respectively -11. For Data were analyzed using IBM SPSS Statistics for Windows, version 22.0, released 2013  where linear regression was used to relate the number of publications to both the average population and the average GDP.Table A significant increase in the number of publications began in 2013 and, thus, in the last seven years, 933 articles were published accounting for 80%, 90%, and 84% of the total articles related to neurodegenerative diseases, Alzheimer’s disease, and Parkinson's disease, respectively. .Figure 2 = 0.396).Figure Neurodegenerative studies related to Alzheimer’s disease represented 422 out of 1,311 (32.891%) or approximately one-third of the total Arab neurodegenerative studies. Similar to the results regarding total neurodegenerative diseases, Saudi Arabia had the highest number of publications (130), followed by Egypt (103), together contributing to more than one-half of the Arab publications in this field.Neurodegenerative studies related to Parkinson’s disease comprised 253 out of 1311 (19.298%), or approximately one-fifth or 422 out of the total of 1311 Arab neurodegenerative studies. Egypt had the highest number of publications (68), followed by Saudi Arabia (42).Table Neurology published the majority of Arab studies, i.e. 73 publications.Table In this bibliometric analysis, we assessed the neurodegenerative disease research productivity in all 22 Arab countries over a 15-year period, ranging from 2005 till 2019. As our results indicated, Saudi Arabia followed by Egypt published the greatest number of neurodegenerative diseases-related articles during this timeframe. In similar analytic studies, Saudi Arabia and Egypt have also ranked the highest in the number of Arab world publications on tobacco use . Saudi ANevertheless, it was essential to normalize this by using some parameters like population size and GDP. Among the two indicators used, we found GDP to be more representative in comparing the Arab countries' neurodegeneration research activity, with a strongly positive correlation. Egypt was ranked first among the 22 Arab countries in number of publications per GDP. Population size, however, which showed that Qatar had the highest number of neurodegenerative diseases publications per million persons, had a weaker correlation.We can therefore say that GDP, or the number of publications per billion dollars, is the most reliable marker for neurodegenerative diseases publications in the Arab world. Similarly, GDP has been found to be the most reliable indicator for stroke publications  and for Our results revealed that the number of neurodegeneration-related publications in Arab countries has been on the rise in the past seven years. One cannot, however, overlook the fact that the total number of neurodegenerative publications in the Arab world account for only 0.77% of the research done worldwide on this subject in the past 15 years. In fact, several studies have addressed the problem of shortage of medical research in Arab countries, proving that they are still lagging behind in biomedical publications, average citation frequency, and top journal publishing activity ,1. A bibThis inadequacy of medical publications in Arab countries can be traced to various factors including limited research facilities, inadequate academic advancements, and the absence of interest in research programs and funding opportunities . The lacFurthermore, in our analysis, it was evident that Alzheimer’s disease-related publications made up one-third of the total neurodegenerative disease studies in the Arab world. This might be justified by the importance of this inevitably progressive disease that has a major negative impact on the life of the patient’s family . AnotherWhen comparing the number of neurodegenerative-related publications in countries with the highest research activity in this field to the combined Arab countries, a huge difference is present between the 10th country Netherland, which is around four times the sum of Arab publications. This difference becomes surprisingly enormous when compared to the 1st country USA, which is around 40 times the sum of Arab publications.Regarding the quality of Arab papers in the field of neurodegenerative diseases, they were shown to be of low quality, since only 21 papers were published in top-ranked neuroscience journals, comprising no more than 2% of published neurodegenerative-related studies.LimitationsThe major limitation of this study was that only the PubMed database was searched, as the tracked number of publications might not be accurate. Furthermore, this study lacks publications written in languages other than English, such as French, which is widely used in some Arab regions, including Algeria, Comoros, Djibouti, Mauritania, Morocco, and Tunisia. Moreover, inaccuracy of data tracking may have occurred due to searching for the indexed and not the published date.To our knowledge, this is the first bibliometric analysis to assess research activity related to neurodegenerative diseases in the Arab world. Despite showing an increase in research productivity in the last few years, numbers remain far behind top-ranked countries in neuroscience research productivity. The low quality of research and strong correlation to GDP highlight the importance of collaboration between high- and low-income countries to establish new institutions that can come up with high-quality research.


Introduction The COVID-19 pandemic brought about seismic change for dentistry including the direction to provide remote advice and prescribe analgesia and antimicrobials. The possibilities for care have widened, but the impact of both restrictions and remobilisation on antibiotic prescribing is not known.Aims To report the impact of COVID-19 restrictions and remobilisation on dental antibiotic prescriptions and explore dentists' intentions and attitudes towards antibiotic prescribing.Design and setting Public Health Scotland national prescribing and claims data are reported alongside an online survey of Scottish general and public health service dentists including closed and open-ended questions.Results Antibiotic prescribing rose by 49% following the suspension of routine dental care, to a peak of 34,993 antibiotics (July 2020). The data also show that since the remobilisation of NHS dental care, antibiotic prescribing remains raised at levels around 28% higher than pre-pandemic. The survey highlights dentists' frustrations and concerns about this increased use of antibiotics. Most dentists intend to reduce their prescribing; however, significant challenges to this being realised were raised.Conclusions The previous success within dentistry to protect against the development of antimicrobial resistance has suffered a knock-back during the pandemic. A renewed focus on reducing unnecessary antibiotics within dentistry is required but, crucially, needs to be approached sensitively alongside the current backdrop of challenges within the service.Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1038/s41415-021-3621-8 für autorisierte Leser zusätzliche Dateien abrufbar. Highlights the increased antibiotic prescribing that resulted during the COVID-19 pandemic using routine national prescribing and claims data.Highlights that antibiotic use remains at a higher level despite the remobilisation of NHS dentistry.Details the results of a national survey of Scottish general and public dentists reporting ongoing challenges.Reports that dentists are aware they are prescribing at higher levels, are frustrated and concerned by this, and wish to reduce this but are facing challenges to do so.Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1038/s41415-021-3621-8 für autorisierte Leser zusätzliche Dateien abrufbar. There is emerging evidence to suggest that the pandemic has had an impact on antibiotic prescribing. A recent study4 highlighted that in the early months of the pandemic in England (April-July 2020), dental antibiotic prescribing was 25% higher compared with the same months in 2019.The efforts to control antimicrobial resistance through reducing the unnecessary exposure to antibiotics have seen some success in recent years. Total antibiotic use in Scotland decreased by 7.6% from 2015-2019, and over the same time period, the use in primary care decreased by 9.1% to the lowest figure since 1993.5 and NHS England announced the suspension and deferment of all routine, non-urgent dental care on 25 March 2020.6 During the suspension of routine dental care, Scottish practices were instructed to operate on an 'advice, analgesia, anti-microbial' basis with the rationale stated as 'where an extraction is not indicated an anti-microbial will provide relief until the tooth can be opened and drained by an urgent dental care team'.5 Patients with dental care concerns were remotely triaged by practices and those with an urgent need that could not wait were directed to the designated urgent dental care centre for the area. In England, the Office of the Chief Dental Officer (CDO) produced similar advice: dentists should not provide routine care; should offer telephone triage and advice, giving prescriptions where necessary; and should refer patients requiring active emergency treatment to regional urgent care centres. These arrangements stayed in place during the three-phase remobilisation of NHS dental services, with a return to emergency-only General Dental Services care in Scotland from 22 June 2020, routine non-aerosol generating procedures (AGPs) returning from 13 July 2020 and AGPs for urgent dental care only returning from 17 August 2020.7 The full range of NHS dental treatments (including AGPs for routine care) could not be provided until November 2020.8 On 21 June 2021, the CDO for Scotland wrote to the profession in response to recommendations raised by the Scottish Antibiotic Prescribing Group to emphasise that the first-line management of acute dental conditions should revert to clinical management rather than antibiotic prescribing.9The early months of the COVID-19 pandemic brought severe curtailment to the delivery of dental care within the UK. In Scotland, the Chief Dental Officer (CDO) wrote to all practices announcing the suspension of routine dental care on 23 March 2020It is not currently known what the impact of COVID-19 and the remobilisation of NHS dentistry has had on the levels of antibiotic prescribing, nor is it known whether the increased dental antibiotic prescribing figures seen in England is reflected in the data for the rest of the UK. Furthermore, the prescribing data only provide part of the picture and there is a need to hear from dentists themselves about the experiences and feelings that lie behind the antibiotic prescribing figures. This paper reports on an exploration of the Scottish data to report the impact of COVID-19 and remobilisation on dental antibiotic prescriptions, and the results of a national questionnaire of General Dental Services and Public Dental Services dentists in Scotland exploring dentists' intentions and attitudes towards antibiotic prescribing.We used Prescribing Information System for Scotland (PRISMS) data to obtain overall NHS antibiotic prescriptions and Management Information Dental Accounting System (MIDAS) data to obtain the total number of NHS claims. Both databases are held by Public Health Scotland. Data in PRISMS are identified by list number, which is a unique identifier of a dentist in a given dental practice. Antibiotic prescription data comprise all antibiotic items  prescribed by primary care dentists in Scotland and dispensed in community pharmacy. We calculated percentages of change between pre-pandemic levels of antibiotic prescription (January 2019) and post-pandemic levels by using a standard proportion calculation; that is, (prescriptions [post-pandemic] minus prescriptions [pre-pandemic] divided by prescriptions [pre-pandemic]). Claims data comprise course of treatment claims and non-course of treatment claims; for example, patient registrations. Data were included from January 2019 to May 2021. Prescribing rates were calculated as the total national number of antibiotic items prescribed by primary care dentists in Scotland per month divided by the total national number of claims in Scotland in the same month and multiplied by 100. They are presented with descriptive statistics - average (mean), standard deviation (SD) and range (minimum-maximum).Ethical review of the survey was completed by University of Aberdeen Research Governance on 30 September 2020 which classed this project as service evaluation. The project was registered with the Quality Improvement and Assurance Team (Project ID 5196) on 7 December 2020.10,11 The questionnaire was piloted with six dentists  who provided feedback to improve clarity of questions and to ensure response options were appropriate for both General Dental Services (GDS) and Public Dental Services (PDS) respondents. Within the questionnaire, the term 'lockdown' was defined as the period of March 2020 when routine dental care was suspended.The questionnaire included both open- and closed-ended questions. Items in the questionnaire were developed based on previous qualitative research exploring dental antibiotic prescribing.E-mails inviting dentists to complete the survey were sent via the NHS Education for Scotland Portal on 8 December 2020. One reminder e-mail was sent on 7 January 2021.www.openepi.com/).To achieve a precision of 5% with over 95% power to estimate the proportion of dentists that have 1) increased their prescribing during the pandemic or 2) intend to decrease their prescribing in the future, we required 300 responses. This assumes a population of 4,500 dentists in Scotland and an expected prevalence of 80% or above for each outcome. This calculation was done using OpenEpi, version 3, open source calculator  highlight the proportion of patients being treated who were prescribed antibiotics. The average monthly rate of antibiotic prescriptions per 100 claims pre-pandemic (January 2019-March 2020) was 5.4 antibiotics per 100 claims . This increased markedly to an average monthly rate of 148.7 antibiotics per 100 claims  during the period of most intense restrictions to service (April-August 2020). Rates then reduced to 17.7 antibiotics per 100 claims  during the remobilisation period (September-November 2020). However, data for the period December 2020-May 2021 highlight that prescribing rates have not reduced to pre-pandemic levels, with an average of 17.3 antibiotics per 100 claims .Responses were obtained from 311 dentists, of whom 278 (89%) were from GDS and 32 (10%) were working in PDS (one respondent did not declare). All health boards within Scotland except Shetland returned at least one response (see online supplementary information) and the distribution of dentists across health boards in our sample is similar to the distribution of GDS dentists in Scotland. The majority of respondents provided NHS dental services for the whole, main or equal proportion of their practice time (n = 267), with 44 providing whole or mostly private provision. (participant 191); 'we should never have prevented dental services' (participant 246); 'practices should never have been told to close and extractions should have continued throughout the pandemic. I am still unaware of any evidence to show this would have been unsafe' (participant 307).Frustration was expressed in the open responses about the restrictions, guidance and policies brought into effect during the pandemic: 'there was no good reason for practices to be closed'Harms caused by the impact of the restrictions on treatments were raised, including 'a loss of satisfaction and trust in dental care for these patients' (participant 143); 'the huge backlog of patients, the extreme reduction in capacity within the GDS [...] severe deterioration in the nation's dental health and an uptick in patients attending emergency departments and their GPs due to completely unavoidable lack of access to their dentist. Complaints are going to skyrocket' (participant 190).Deterioration to patients' dental health was mentioned as a concern alongside frustration about being prevented from effectively helping patients in need: 'it was wrong [prescribing antibiotics for pulpits] and felt wrong, it was a bad time not being able to help people in pain' (participant 246).Comments also suggested a loss of trust in regulatory bodies and in guidance, and a loss of professional autonomy: 'we are health professionals who have been treated like little children. I feel strongly about this. A wholly negative experience' (participant 209).Links were made by respondents between the changes to delivery of dental care and an increased use of antibiotics: 'first we are to reduce prescribing and then we are prevented from looking after our patients and asked to hand them out like sweeties' (participant 209); 'antibiotics should never have been used as a substitute for treatment [...] it should not have been forced upon us during lockdown' (participant 219). Respondents commented on their feelings that antibiotic prescribing had increased during COVID-19: 'I was shocked by the amount of antibiotics I prescribed over lockdown. All necessary because I couldn't see the patients face-to-face to treat them properly' (participant 100).The vast majority of respondents reported they had increased their antibiotic prescription slightly or greatly during the suspension of face-to-face care in March 2020  and the emergency-only GDS care in June 2020  compared to pre-COVID, as shown in Comments were also made about prescribing antibiotics counter to clinical assessment of need during COVID-19 to permit patients to access urgent treatment: 'urgent dental care centres during lockdown were declining patients if they haven't taken at least one course of antibiotics. You can understand how ridiculous this looks to patients' and dentists' eyes' (participant 272). This happened even when their clinical judgement was that it would not be of benefit: 'we were given no option but to Px [prescribe] ABs [antibiotics] even when we knew it would do no good' (participant 314). These comments are reflected in the quantitative responses where 84% (n = 262) of respondents were unsure, disagreed, or strongly disagreed that prescribing antibiotics when no other treatment is possible will effectively solve or manage the patient's condition. Most respondents  agreed or strongly agreed that prescribing antibiotics when no other treatment is possible goes against their views of best practice .Table 1 Reports were also shared of prescribing antibiotics as a means of providing some level of care when nothing else was possible: 'Antibiotics were often prescribed in lockdown when the symptoms were not indicative that antibiotics would have any effect just because "you had to do something"' (participant 57).There were strong feelings expressed such as: 'I felt terrible giving patients antibiotics that I knew were unlikely to help' (participant 311); 'the way antibiotics was [sic] prescribed by the hubs (and some GDPs) during lockdown was verging on criminal' (participant 287); and 'patients were having 5+ courses of antibiotics as no access to dentistry. Totally disgraceful' (participant 294).Further quantitative responses related to attitudes to prescribing antibiotics are presented in Some of the respondents reflected that antibiotic prescribing was already returning to a reduced pre-COVID-19 level: 'during lockdown was difficult [...] prescribing them [antibiotics] for 3 months when I knew this was not the ideal treatment was counter productive and I am very happy not to be in that situation anymore' (participant 49); 'Luckily being able to carry out treatments has ensured a decrease in prescribing already' (participant 279).However, for others, the picture has not yet changed and antibiotic prescribing remains at a higher level: 'I think we can't expect antibiotic prescription to reduce until we are working with less restrictions' (participant 275); 'how can we reduce the antibiotic prescribing with only enough PPE and time to see 5 AGPs a day if patients are in pain?' (participant 84). As well as the restrictions on AGP appointments, PPE and time, references were also made to the impact of the backlog and increased waiting lists, and the lack of dentists with face-fitted masks.When asked to quantitatively rate their intentions and expectations about antibiotic prescribing, the vast majority of respondents (80%) intend to decrease their prescriptions and 80% expect antibiotic prescribing to reduce in dentistry overall.Concerns were expressed by respondents that patients will have greater expectations for antibiotics post-COVID-19: 'Many patients are now happier to have antibiotics over treatment and expect things to be as they were in lockdown' (participant 183); 'Over the last number of years I feel the profession on the whole has been trying to reduce antibiotic prescriptions and instead using local measures to deal with the cause of the infection. We have been slowly changing public perception that antibiotics aren't always necessary or indicated and they're slowly accepting this. During COVID we have done the exact opposite of this and have only been prescribing antibiotics in a lot of cases and have undone years of hard work. I feel this has set us back a lot in terms of patient expectation' (participant 329). Furthermore, 42% (n = 132) of respondents agreed that prescribing antibiotics when no other treatment is possible preserves a good patient/dentist relationship. Around the same proportion  agreed that not providing antibiotics is likely to cause conflict .Comments also described the role of patients in terms of directly requesting antibiotics and refusing treatments so that antibiotics are the only route left: 'when a patient doesn't want a tooth out but they can't have rct [root canal treatment] for a weeks [sic] what other option is there?' (participant 316); 'patients think antibiotics are the golden nugget that will fix their pain and don't understand it will only temporarily take down the infection. Pts [patients] think Abs [antibiotics] will solve all their emergency issues and ask blatantly for them. Patients have boxes of Abs [antibiotics] lying in drawers at home [...] It's an absolute wild west out there when it comes to antibiotics' (participant 255).The vast majority of participants  agreed or strongly agreed that responsible use of antibiotics is important within dentistry . Only a 4 This study also provides further insight that higher levels of prescribing persist even with the remobilisation of NHS treatment (June to November 2020). Dentists report feeling compelled to 'do something' for patients and that prescribing antibiotics satisfied this need to provide some level of care during the COVID-19 restrictions when treatment options were so limited.This paper combines data from mixed sources to provide a unique insight into how the pandemic has impacted dentists' prescribing behaviour, perceptions and experiences. The data reported in this study from the national routine prescribing datasets show that dental antibiotic prescribing rose significantly in Scotland during the COVID-19 pandemic, echoing the picture reported during the early months of the pandemic in England.12 around the anticipated backlog of treatments and patients needing care suggests that there is a clear need to help support practices to manage this alongside the remobilisation of care. Furthermore, there has, as yet, been no real change in how dentists can deliver care with social distancing measures, PPE and fallow time restrictions remaining in place.Dentists are aware that they are prescribing antibiotics at higher levels and report feeling frustrated about prescribing antibiotics against their clinical judgement. They expressed concerns about the future impact of this increased antibiotic prescribing and most respondents reported an intention to reduce their antibiotic prescribing in the future. However, significant challenges were reported to reducing prescribing in the context of ongoing restrictions to the numbers of patients that can be seen and the large backlog of patients needing attention. The anxiety shared in this study, and others,12 highlighting that dentists would struggle with not providing a service to patients during the pandemic, seeing this as an integral part of their identity as a healthcare professional. Dentists in this study reported that prescribing antibiotics satisfied this 'need to do something', despite the fact antibiotics are unlikely to resolve much dental pain. This strong sense of duty to act may also be, in part, driven by concerns about the medico-legal consequences of withholding care. The potential legal consequences of not providing care when patients are clearly in need and may come to harm if not treated is a concern for UK dentists.13Dentists expressed feeling a strong sense of duty to act rather than leave patients in pain waiting with no treatment. This resonates with previous work,14 We would encourage the global dental community to reflect on lessons learned from this approach and come together to prepare for the next pandemic.Furthermore, going from the established guidance on management of acute dental problems to the advice, analgesia, antimicrobial (AAA) approach during the pandemic may also raise medico-legal concerns. Indeed, most dentists in this study agreed that prescribing antibiotics just because no other treatment is available goes against best practice. The move to AAA during the restrictions to dental services was not only applied within the UK but formed part of World Health Organisation global guidance.There are some strengths and limitations of this study to note. The data in this paper reflect the picture of antibiotic prescribing in Scotland only and generalisability beyond this context is uncertain. However, the use of routinely collected datasets to provide granular antibiotic prescribing data is a major strength which would not be possible in all countries. The claims data that have been used to calculate the proportions of patients being seen who received antibiotics may result in a degree of over-estimation of prescribing rates per claims, as submissions of claims may have been disrupted during the pandemic. Although the prescribing rates per claims figures should be interpreted with caution, the clear increase and sustained rise observed in the total number of antibiotic items comes at a time when the number of patients being seen was dramatically reduced.15 demonstrates the pandemic-related mental health burden within dentistry, with 27% of survey respondents reporting significant depressive symptoms and 55% reporting emotional exhaustion. The pressures and mental health impacts being faced within dentistry are likely to be a persisting challenge going forward, and renewed focus on mental health awareness and support within dentistry is apparent in recent initiatives.16,17The results reported in this paper suggest that a renewed focus on optimisation and reduction of antibiotic prescribing is warranted within dentistry but, crucially, this needs to be framed sensitively in what continues to be challenging times for dentistry. Alongside the frustrations expressed about the restrictions to service, loss of professional autonomy and loss of trust in regulatory bodies reported in this study, there is also the mental health impact which makes sensitive framing so critical. Recent research11 but also raising concerns about the potential for greater future demand following the widespread use of antibiotics during the pandemic. However, recent research18 examining Twitter communications about dental health and care during the pandemic suggested that the overuse of antibiotics and antimicrobial resistance was a concern to the general public too. These findings suggest that initiatives that target dentist-patient treatment discussions and decision-making may be indicated.The dentists in this study also highlighted the influential role patients can play in antibiotic prescribing, resonating with previous work19 highlights the increasing impact dentistry has within primary care antibiotic prescribing. In the six months before the pandemic restrictions of March 2020, on average, 7% of the total primary care antibiotic prescribing was within dentistry; however, in the six months from April-September 2020, this had increased to 12%. This represents an increase from dentists prescribing 1 in every 14 antibiotics in primary care to prescribing 1 in every 9 antibiotics. This further supports a renewed focus on antibiotic optimisation within dentistry and there are successful evidence-based initiatives that have been shown to help. Providing dentists with personalised prescribing feedback reports, alongside a short actionable message based on behaviour change theory, successfully reduced antibiotic prescribing rates.20 A novel initiative to examine whether the addition of in-practice training support to these feedback reports is currently underway to see if this brings about further reductions in antibiotic prescribing.21 The in-practice training support element may help dental practices to find a way to move forward with reducing dental antibiotic prescriptions in the current and future post-COVID-19 dental care landscape.Most dentists in this study felt that reducing antibiotic prescribing is very important and recent exploration of the Public Health Scotland prescribing in the community datasetsThe previous success within dentistry to protect against the development of antimicrobial resistance has suffered a knock-back during the pandemic. Antibiotic prescribing rose significantly in dentistry during the COVID-19 pandemic and prescribing continues at a higher level than pre-pandemic. A renewed focus on reducing unnecessary antibiotics is required but dentists report ongoing challenges that may stymie prescribing levels falling. Efforts to help support reducing dental prescribing need renewed focus alongside careful tailoring and sensitive framing for what continues to be a difficult new landscape for dentistry.Supplementary Table 1 (PDF 727KB)