The level of agreement between measurements was perfect (r > 0.9) for step length left and cadence and very large (r > 0.7) for step time left, gait cycle, and stride length. Regarding running at 10 km/h, bias and SEE analysis revealed significant differences for most of the variables except for stride time, rate and length, swing knee flexion for both legs, and thigh flexion left. The level of agreement between measurements was very large (r > 0.7) for stride time and rate, stride length, and vertical displacement. At 15 km/h, bias and SEE revealed significant differences for vertical displacement, landing knee flexion for both legs, stance knee flexion left, thigh flexion, and extension for both legs. The level of agreement between measurements in running at 15 km/h was almost perfect (r > 0.9) when comparing Qualisys and MotionMetrix parameters for stride time and rate, and stride length. The agreement between the two motion capture systems varied for different variables and speeds of locomotion, with some variables demonstrating high agreement while others showed poor agreement. Nonetheless, the findings presented here suggest that the MotionMetrix system is a promising option for sports practitioners and clinicians interested in measuring gait variables, particularly in the contexts examined in the study.Markerless motion capture systems (MCS) have been developed as an alternative solution to overcome the limitations of 3D MCS as they provide a more practical and efficient setup process given, among other factors, the lack of sensors attached to the body. However, this might affect the accuracy of the measures recorded. Thus, this study is aimed at evaluating the level of agreement between a markerless MSC  and an optoelectronic MCS . For such purpose, 24 healthy young adults were assessed for walking (at 5 km/h) and running (at 10 and 15 km/h) in a single session. The parameters obtained from MotionMetrix and Qualisys were tested in terms of level of agreement. When walking at 5 km/h, the MotionMetrix system significantly underestimated the stance and swing phases, as well as the load and pre-swing phases ( There are various technologies for analyzing gait and related parameters, including 3D motion capture systems (MCS), image processing, and wearable sensors ,2,3. MCSThe use of marker-based MCS has become widespread in both the research and diagnosis fields, but its application in places like patient homes, sports fields, and public spaces is limited by the need for very specific recording settings . Motion capture aims to measure the movement of the skeletal system. However, due to factors such as clothing, skin, and soft tissue movement, the retro-reflective markers placed on key bony landmarks like the lateral malleolus may move in relation to the underlying bones . VariousThe practicality and clinical adoption of marker-based motion capture is hindered by the considerable amount of time it takes to securely fix markers to participants. Even with a skilled researcher, this process can take between 20 to 30 min, not including the time needed to prepare the markers before data collection. Additionally, the presence of the markers on the participant’s body or clothing may make them aware of their presence, possibly affecting their natural movement.Markerless MCS share similarities with marker-based systems as they aim to accurately and reliably measure the 3D motion of human segments. Both systems aim for the representation of the skeletal system with a simplified biomechanical model. Nonetheless, Markerless systems do not require markers to be placed on the participant, instead using synchronized 2D video cameras to achieve a 3D reconstruction. Markerless MCS have been developed as an alternative solution to overcome the limitations of marker-based MCS ,6,7,8,9.One commercially available markerless system is the MotionMetrix software . The reliability of the system has been tested by evaluating the test-retest results of all variables during walking (at 5 km/h) and running (at 10 and 15 km/h), and the results suggest that the system may be useful in settings where more sophisticated systems (such as 3D MCS) are not accessible, taking into account the limitations of the software itself  . AdditioDespite its popularity among researchers and widespread use by clinicians and sports practitioners, there is still doubt about the accuracy and consistency of the MotionMetrix system compared to a recognized standard 3D MCS. Therefore, this study aims to evaluate the level of agreement between the MotionMetrix system and a 3D MCS  for walking (at 5 km/h) and running (at 10 and 15 km/h) in healthy adults. Twenty-four recreationally active young adults   were incSubjects were asked to avoid any strenuous physical activity for at least 48 h before the data collection and came to the laboratory only once. During the test, they wore their typical running clothes and shoes and went through a walking and running protocol on a treadmill  . Before The body height (m) and body mass (kg) of each subject were measured employing a stadiometer  and a bioimpedance scale , respectively.The MotionMetrix system was used in combination with two Kinect sensors  positioned on either side of the treadmill following a specific configuration see  as suggeEight Qualisys Oqus cameras  operating at 250 Hz and meticulously positioned to allow a full view of the treadmill  were empVisual 3D software  was used to process static and kinetic data. The motion data was processed using a low-pass filter with a cut-off frequency of 8 Hz to eliminate high-frequency noise. Joint angles were calculated using the x-y-z Cardan sequence, which represents flexion/extension, abduction/adduction, and axial rotation, without normalizing them to a static standing position. The laboratory frame was set up using the right-hand rule, with the positive y-direction facing forward, positive x-direction to the left, and positive z-direction upward. Variables of interest included the different phases of the gait cycle , stride rate and length, vertical displacement, spine angle, and landing, stance, and swing knee flexion (at 10 and 15 km/h).t-test pairwise mean comparison was performed to compare data obtained from MotionMetrix and Qualisys MCS. To assess the level of agreement between the two systems, Pearson’s product-moment correlation coefficient (r) was calculated between each variable. The correlation between measurements was interpreted using established criteria: <0.1 , 0.1–0.3 , 0.3–0.5 (moderate), 0.5–0.7 (large), 0.7–0.9 (very large), 0.9–1.0  ), using a “single measurement” type and “absolute agreement” definition for the ICC calculation. The benchmarks from Koo and Li [p < 0.05 was established.Descriptive data are presented as mean (±SD) and 95% confidence intervals (CI) The normal distribution of the data and equal distribution of variance were confirmed through the Shapiro–Wilk test and Levene’s test, respectively. A perfect) . Additioperfect)  and applo and Li  were useThe pairwise comparison between the data obtained from the MotionMetrix and 3D MCS revealed significant differences for most of the variables, although the systematic bias and SEE were low . p < 0.05). The systematic bias was relatively low (Bias ≤ −0.03 s) as well as the SEE (≤0.02 s).Specifically, the MotionMetrix system significantly underestimated the stance and swing phases, as well as the load and pre-swing phases , for the left step time and cadence, compared to Qualisys MCS, while walking at a speed of 5 km/h. Regarding the agreement of other variables, the text highlights that stride rate and length showed good agreement, with ICCs above 0.75, while gait cycle exhibited a moderate level of agreement, with ICCs exceeding 0.5. However, the other variables demonstrated poor agreement, with ICCs below 0.5. Concerning running at a speed of 10 km/h, both MCSs demonstrated good levels of agreement for stride time, stride rate, and knee flexion angles (stance and swing) on the left side. The agreement was also good for stride length. Conversely, the other variables had moderate to poor levels of agreement. At a faster running speed of 15 km/h, both MCSs demonstrated excellent levels of agreement for stride time, stride rate, stride length, and swing knee flexion on the left side. A good level of agreement was also observed for swing knee flexion on the right side, while moderate agreement was found for vertical displacement and knee flexion angles on the stance side. However, the ICCs for the other variables indicated poor levels of agreement.Assessing walking and running gait can be important for a variety of reasons, including diagnosing and monitoring certain conditions and injuries, evaluating the effectiveness of interventions, and tracking changes over time. However, the accuracy and reliability of gait measurements depend on the selection of appropriate variables and the quality of the measurement instruments used.p < 0.05) when compared to the gold standard system  during walking at 5 km/h. It is important to note that the MotionMetrix system utilized two Kinect cameras and software to evaluate walking and running gait in this study. Prior research has demonstrated that the Kinect cameras have underestimated step time and step length by 16% and 1.7%, respectively, during walking [p > 0.05, Bias = 0.00 s). Although significant differences were detected for step length when measured unilaterally, no significant differences were observed when measured as stride length , that is, one step after the other.Previous research has shown that the MotionMetrix system provides reliable measures for walking at 5 km/h of all parameters except for step width . Our stu walking . Our finp < 0.05) between MotionMetrix and Qualisys for thigh flexion in both legs , landing knee flexion , and step width (Bias = 0.03 m) at 10 km/h. At 15 km/h, the previous study found that MotionMetrix provided reliable values for all parameters except spine angle and step width, which exhibited CVs of 23.27% and 22.22%, respectively [Additionally, the aforementioned study investigated the test-retest reliability of MotionMetrix for analyzing running at 10 and 15 km/h . These aectively . In the When interpreting the findings here reported, readers must be aware of certain limitations. It is important to note that the treadmill protocol employed in this study aimed to minimize gait and running variability due to inexperience or fatigue ,20. PrevDespite the limitations exposed above, the study examined several variables that are commonly used to analyze gait patterns in walking and running, including step time, cadence, stride rate, stride length, and knee flexion angles. The study’s findings indicate that the MotionMetrix system is a reliable system for measuring these variables in both walking and running gait. These variables offer valuable information about the temporal and spatial aspects of gait, such as the duration of different phases, the frequency and distance of steps, and the angles of the joints involved in the movement. Accurate and reliable measurement of these variables can provide insights into the mechanics and efficiency of gait and help identify abnormalities or deviations from normal patterns. This information can guide the development of interventions, such as exercise programs or orthotics, to address gait impairments and improve functional outcomes. Therefore, considering these variables when assessing walking gait and running can provide valuable information for both research and clinical purposes, leading to a better understanding, diagnosis, and treatment of gait-related conditions and injuries.After comparing the measurements of gait and running variables provided by the MotionMetrix markerless software against a gold standard system , it is concluded that the agreement between the two motion capture systems varied for different variables and speeds of locomotion, with some variables demonstrating high agreement while others showed poor agreement. Nonetheless, the findings presented here suggest that the MotionMetrix system is a promising option for sports practitioners and clinicians interested in measuring gait variables, particularly in the contexts examined in the study. However, further research is needed to examine the agreement between different systems for other variables and in different contexts.


This study is a cross-sectional study, and the participants were recruited using both online platforms during the lockdown and through in-person interviews after the withdrawal of lockdown. After obtaining the proper consent from the participants, their sociodemographic variables, and KAP towards immunity boosting dietary behavior were assessed. Total 400 participants were included in this study and a non-probability sampling technique named purposive sampling has been followed for participants recruitment. Among the 400 participants, the majority of them (64.3%) were male, most of them (62.7%) were students, unmarried (69.5%), aged between 18–35 years (82.5%), had a bachelor’s degree (50.0%), and had a monthly family income between 10000–30000 BDT (35.5%). This study indicated that 82.8% of the populations had the correct knowledge, 71.3% had favorable attitudes, and 44% had good practices regarding immunity boosting diet during COVID-19. The majority (79.3%) of the participants had an idea about nutrition, most of them (78.5%) knew the nutrients needed to strengthen their immune system, almost all (98.5%) washed fruits and vegetables purchased from the market before eating them, 78% did not often purchase food online, and 53% often ate junk food. In a binary logistic regression, correct knowledge was significantly associated with the females, having HSC or bachelor’s degree, being in the occupation of business, laborer or others, and having a monthly family income between 50000–100000 or >100000. The favorable attitudes were significantly associated with having a master’s degree or above, and for government job holders. However, the good practices did not show any significant association with the sociodemographic factors in binary logistic regression. Moreover, the study found the presence of bad or unhealthy practices among the populations despite having correct knowledge and favorable attitudes. Thus, this study could identify the variables, such as gender differences, education, monthly family income, and occupation on which emphasis should be given during public health campaigns or training programs to improve the KAP regarding immunity boosting diet.During the increasing spread of COVID-19 occurrences in Chattogram Metropolitan Area (CMA) of Bangladesh, a series of measures were taken to control the transmission. These measures greatly influenced the knowledge, attitudes, and practices (KAP) of the population on their dietary behavior. However, there are no current studies demonstrating the KAP of the CMA citizens regarding their dietary habit that can boost the immunity. In this study, we appraised KAP in regard to immunity boosting dietary behavior from April 26, 2021 to November 17, 2021 during implementation of lockdown measures by the government of Bangladesh. Apart from the basic knowledge and attitudes toward immunity boosting dietary behavior, we have also aimed to assess the practices of the population by whether the nutrients, especially vitamin A, B In December 2019, a pneumonia-like outbreak in China’s Wuhan City of Hubei Province caused disquietude among researchers and medical professionals. Later, it came to light that this outbreak was caused by a newly identified coronavirus strain named SARS-CoV-2 . Buying 6, B9, B12, C, D, E, and trace minerals such as zinc, selenium, and iron increase the body’s capability to fight against viral infections [Among the various management approaches of COVID-19, healthy dietary behavior, nutrition, lifestyle and environment proved to significantly boost immunity and assisted in maintaining good health ,6. A divfections ,11. Relefections .The COVID-19 inducing home quarantine measures were suggested in multiple cities in various countries, including Chattogram of Bangladesh . The locIt is evident that in light of the current global pandemic situation, where people are in distress due to quarantine, it is important to perform substantive research into the influence of COVID-19 on the regular diet, and ways of combating COVID-19 with a diet that bolsters people’s immunity. Studying this will assist epidemiologists, public health researchers and dietitians in outlining their guidelines and dietary recommendations for future pandemics .Knowledge, attitudes, and practices can play vital role in shaping individuals’ dietary behaviors and their impact on immunity. A KAP study in Iran among Tehranian adolescents showed the role of healthy nutrition in preventing the non-communicable diseases . PreviouTherefore, the objective of this study is to determine the knowledge, attitudes, and practices regarding immunity boosting dietary behavior along with their occupational differences during COVID-19 among the citizens of CMA. The study was formulated and conducted through an online survey as well as through in-person interviews. Lifestyles during quarantine and the dietary behaviors were taken into consideration for better comparison and comprehension of the practices among the citizens of CMA, as well as to examine the possible risks of nutrient insufficiencies.This study has been carried out in accordance with the WMA Declaration of Helsinki–Ethical Principles for Medical Research Involving Human Subjects 1964. Formal ethical approval was granted by the Ethics Committee of the Chattogram Veterinary and Animal Sciences University, Bangladesh  EC/2019/126 (02), Date: 29 December 2019). The nature of this study was voluntary, and consent from each participant  was taken before inclusion in the study. The information of all the participants were kept anonymous, and confidentiality was properly maintained.A cross-sectional study was conducted among general public during the period of April 26, 2021 to November 17, 2021, and the data were collected online when the government of Bangladesh implemented lockdown strategy. Data were also collected through offline interviews after the withdrawal of lockdown. We have collected data through a non-probability sampling technique named purposive sampling. Half of our samples was collected online and the remaining half of the samples were collected through in-person interviews. Initially, a pre-structured questionnaire was developed using Google Forms in English language while providing the Bengali translation in the parenthesis. We pretested the questionnaire before final administration to the study population. The web-link of the questionnaires were then distributed to the participants through various social media platforms . The investigators’ idea for collecting the data through online platforms was to maintain social distance amid the confinement situation of Bangladesh. However, when the situation of COVID-19 improved and the lockdown was withdrawn, the investigators went into the field and collected data through in-person interviews from several regions of Chattogram, Bangladesh to include all categories of people in the survey. The in-person interview was conducted in the native language, Bengali. Cochran’s sample size formula for large populations has been used for the calculation of sample size [0 = Sample size; Z = Z-score = 1.96 for 95% level of confidence; p = Estimated proportion of the attribute that is present in the population = 50% (or 0.5); q = 1-p = 0.5; e = Margin of error = 5%.Here, nData needed to be collected from minimum 385 individuals, which is the calculated sample size based on the above formula. In this study, the investigators collected data from 400 potential respondents. The criteria for including in our study were being a resident of Chattogram metropolitan area, above 18 years of age and voluntarily participation. The geographic location of the participants can be found in the A pre-structured and self-reporting questionnaire was distributed that contained consent of participation, and questions regarding sociodemographic characteristics, knowledge, attitudes, and practices.Sociodemographic information of the participants such as gender, age, marital status, education level, occupation, monthly family income, employment status, and presence of children or elderly person in the family were collected for the study. Age group was classified into three classes: 18–35 years, 36–55 years, and >55 years. Monthly family income of the participants was categorized into five classes: <10000 Bangladeshi Taka (BDT), 10000–30000 BDT, 30000–50000 BDT, 50000–100000 BDT and >100000 BDT.To comprehend the degree of knowledge, attitudes, and practices of the participants along with their occupation differences, the questionnaire contains a total of 17 questions . The knowledge and attitudes questions were developed based on the objectives of the study and our target populations as we have already determined the key area of KAP that we want to investigate. On the other hand, the practices questions were generated based on the idea of immunity-boosting nutrients for SARS-CoV-2 that were either substantiated through scientific studies or hypothesized for having potential benefits .Special emphasis was given during validation of questions related to knowledge, attitudes and practices. After completing the preliminary draft of the questionnaire, it was ratified and approved by two different actions. Initially, it was verified by an expert member where the expert opinion was considered. Finally, a statistical test was employed to measure the consistency of questions in the questionnaire. Cronbach’s alpha test for measuring the internal consistency of KAP questions was used. This statistic is a measure of reliability that is commonly used for demonstrating whether the tests and scales which were adopted in the research are fit for the desired purpose. The acceptable range of Cronbach’s alpha coefficient for its reliability is 0.45–0.98 . In our Yes”, and “No” . The correct answer (Yes) was then denoted by 1, and the incorrect answer (No) was denoted by 0. The total score for this category was calculated by summarizing the raw values of 3 individual questions. Therefore, the value for knowledge had a range between 0–3, and an overall higher score was the indication of “correct” knowledge. The cut off value for “correct” knowledge was ≥2.The knowledge section contained 3 questions and each of them had a probable response of “Yes”, and “No” . The correct answer (Yes/No) was then denoted by 1, and the incorrect answer (Yes/No) was denoted by 0. After summarizing the raw values of the 4 individual questions, the total score for attitude ranged between 0–4, and an overall higher score was the indication of “favorable” attitude. The cut off value for “favorable” attitude was ≥3.The attitude section contained 4 questions and each question had a probable response of “Always”, “Often (4–5 days/week)”, “Sometimes (2–3 days/week)”, “Seldom (1 day/week)”, and “Never” ?). The desirable response (Always/ Often/ Sometimes) was then coded by 1, and the undesirable response (Seldom/ Never) was coded by 0. The summaries of the raw values for 10 practice questions ranged between 0–10, and an overall greater value was the indication of “good” practice. The cut off score for “good” practice was ≥9.The practice section contained 10 questions and all of them had a possible response of “Finally, sensitivity analysis has been conducted by raising/lowering the cutoff score of KAP by one unit to highlight the robustness of the results . When thKnowledge, Attitudes and Practices were used as dependent qualitative variables, while sociodemographic variables named Age, Gender, Marital status, Education, Occupation, Monthly family income, Are you employed during this quarantine, and Is there any child or elderly person in your family were used as independent qualitative variables. Also, while using Knowledge as dependent variable, Attitudes and Practices were used as independent variables. Similarly, Knowledge and Practices were used as independent variables while using Attitudes as dependent variable, and Knowledge and Attitudes were used as independent variables while using Practices as dependent variable. Thus, the relationships between knowledge, attitudes, and practices could also be assessed (Table 6).The statistical analysis of the data was performed by using Microsoft Excel 2021, IBM SPSS Statistics 26.0 , and R for Windows v4.1.2 . Initially, Microsoft Excel has been used to edit, sort and code the raw data. After that, the edited excel file was imported in SPSS where descriptive statistics  and first order analysis (chi-square test) were conducted. Fisher’s exact test was selected instead of chi-square test when more than 20% cells had expected frequencies less than 5, and it was conducted on R for Windows. Then, binary logistic regression analysis was conducted on SPSS with 95% confidence interval for determining the significant association between dependent and independent qualitative variables. In the binary logistic regression, The final analysis included 400 responders in total, of which 64.3% were male and the rest were female (35.8%), and the majority of them (82.5%) were between the ages of 18–35 years. More than half of the respondents were unmarried (69.5%). Most of them were students (62.7%), half of them had a bachelor’s level of education (50.0%), 35.5% of the responders’ family income was between 10,000 and 30,000 BDT per month, 50% of them were unemployed during the quarantine, and more than half of them had no children or elderly people in their family .In the overall assessment, 331 out 400 individuals had correct knowledge, 285 out of 400 had favorable attitude, and 176 out of 400 had good practices .The distribution of responses from participants is shown for each knowledge question in p = 0.463). The group having an HSC level of education had 23.168 times more correct knowledge than the group of responders having SSC level of education  (see Table 6).The respondents who were between 36–55 years were 0.699 times more likely to have correct knowledge on immunity boosting dietary behaviors than the respondents aging between 18 to 35 years  to the item of the attitude section regarding "Do you often eat at restaurants?" . The proportion of those with more positive attitudes was substantially more likely to be (i) those who are employed , (ii) the older group (age > 35 years) , (iii) responders who are married (n = 102)  (see Table 5).The findings indicated that 66.7% of respondents (n = 110) whose age was between 18–35 years old had a favorable attitude . Married respondents had 1.852 times more favorable attitudes than those who are unmarried . More favorable attitudes were seen in the responders who had government jobs, which is 6.048 times more than the students  (see Table 6).Finally, in terms of characteristics associated with more favorable attitudes toward immunity boosting dietary behavior, we found being older (aged 36–55 years) vs younger (aged 18–20 years) significantly differed . The response rate of "Sometimes (2–3 days/week)" was significantly higher in responders with private jobs  to the item of practice section regarding "How often do you eat food that contains Vit-D  or expose yourself under sunlight?". Similarly, the "often (4–5 days/week)" response rate is significantly higher in Others   see .p value = 0.656) (see Table 6). The proportion of good practice was much higher in (i) Government job responder group , (ii) females , (iii) responder group having education up to Master’s degree or above , (iv) responders with higher family income   see .p value = 0.127), sex , having higher education (HSC) vs SSC . The findings show that responders with government jobs have 2.401 times more good practice towards immunity boosting dietary behavior than students . There is also an increase in good practice with the increase in family income   see .Coronavirus is currently a global danger that affects practically all countries. Individuals on their own are learning about COVID-19 through numerous means such as social media, television, print media and newspapers. Furthermore, the government is carrying out steps that they deem to be of the highest significance. The purpose of this study was to assess the degree of knowledge, attitudes, and practices of immunity-boosting dietary behavior as a COVID-19 preventative intervention among the residents of Chattogram Metropolitan Area (CMA), Bangladesh along with their occupational differences. The findings indicate a significant number of sociodemographic characteristics that are associated with KAP, and could be beneficial for developing preventive health education programs for emerging infectious illnesses. Our study found that approximately 79 in every 100 (79.3%) participants had adequate knowledge about nutrition.age, gender, marital status, education, occupation, monthly family income, are you employed during this quarantine, and is there any child or elderly person in your family. Also, knowledge of the population showed significant association with their attitudes and practices. However, in case of attitudes, the significant relationship was with age, marital status, Education, occupation and the knowledge. Finally, the practices of the participants had significant association with their age, marital status, education, occupation, are you employed during this quarantine, and their knowledge. In binary logistic regression  reported of using herbal foods or products to reduce their risk of COVID-19 infection. About 71% of them drank hot tea ; while 56.5 percent used ginger, black seed, honey, and clove combined; and 32.8 percent, 30 percent, and 28.8 percent of them used ginger, black seed, honey, and clove, respectively in individual. These plants were consumed either alone or in conjunction with tea or hot water. Being female, young 18–29 years), married, and fearful of the pandemic were all factors connected with using herbal foods/products. Participants with a graduate degree were also more likely than those with a secondary degree or below to use preventative herbal foods/products [ years, mIn a study on Jordanian adolescents, over half of the teens reported eating vitamin-C rich foods believing it enhances their defense against coronavirus . AlthougThis study has some limitations. Firstly, it was a cross-sectional study, hence causal inferences could have not been made. Secondly, online reporting of the questionnaire may have several biases, although half of the study population was added through in-person interviews. Specifically, the online-based participants were mostly students, hence most of our participants were aged between 18–35 years old. There were also chances of response bias during online reporting. Thirdly, during the in-person interviews, most females declined to take part in the study, which resulted in a larger number of males in the study. Also, there could be presence of social desirability bias/reporting bias as people may not say what they truly believe but rather what they ought to do. Fourthly, the samples of the study were collected only from the populated or major sites of CMA, thus it caused exclusion of some smaller areas. Moreover, the use of purposive sampling may have unintentionally caused some selection bias or interviewer bias. Finally, we have used limited numbers of questions for measuring the degree of knowledge, attitudes, and practices, specifically three questions for knowledge and four questions for attitudes as we wanted to focus more on the practices category that included ten questions. Thus, the questionnaire itself has some limitations. Lastly, this KAP study regarding immunity-boosting diet did not construct the multi-dimensional measures.The findings suggest that during the lockdown period when higher transmission of COVID-19 was occurring, the populations of CMA showed substantive differences in their knowledge, attitudes, and practices regarding their dietary behavior. The findings of this study also indicate the necessity of effectual and tailored educational programs for ameliorating correct knowledge, favorable attitudes, and good practices regarding immunity-boosting dietary behavior during and even after COVID-19 among the populations. However, the result showed the presence of bad or unhealthy practices among the populations despite having correct knowledge and favorable attitudes, thus emphasis on this category should be given while making public health campaigns or training programs. Moreover, other population characteristics, such as gender differences, education, monthly family income, occupation etc. should be kept in consideration during these programs.S1 Data(XLSX)Click here for additional data file.


People with hemophilia (PWH), especially severe hemophilia, often experience bleeding episodes, which occur mostly at major joints. Intramural hematoma of the gastrointestinal (GI) tract is a rare, potentially life-threatening clinical bleeding manifestation in PWH. Prompt identification and timely administration of clotting factor concentrates are of utmost importance for effective management and optimal patient outcomes. In this report, we present the case of a 48-year-old male with severe hemophilia A. The patient developed a spontaneous intramural hematoma of the jejunum, leading to signs of acute abdomen, bloody stool, and paralytic ileus. Conservative management with factor VIII (FVIII) infusion was successfully administered. However, within a span of three months, the patient suffered from a recurrent episode of intramural hematoma, which was again effectively treated with conservative therapy. Subsequently, prophylactic FVIII therapy was administered to the patient, resulting in the absence of recurrence for over three years. Inspired by this case, we conducted a comprehensive review of the relevant literature and gathered data from 79 reported cases of intramural hematoma that were documented between the years 1956 and 2022. We classified these cases based on the site affected within the gastrointestinal (GI) tract (spread across five different locations) and proceeded to conduct a simple pooling analysis on the data collected, which subsequently revealed that the overall mortality rate of intramural hematoma in people with hemophilia (PWH) was found to be 12.2%, while children have a higher mortality rate (23.3%) than adults (4.9%). We hope this case report and literature review increase awareness of this rare bleeding manifestation in PWH, the effectiveness of conservative treatment, and the possibility of prophylaxis against recurrence. Hemophilia A and B are hereditary bleeding disorders characterized by deficiencies in coagulation factor VIII (FVIII) and factor IX (FIX), respectively ,2. IndivGastrointestinal (GI) bleeding, characterized by bleeding into the lumen of the GI tract, is a frequent complication among people with hemophilia (PWH), with a reported incidence ranging from 10% to 25% ,5. HowevThe first case of intramural intestinal hematoma was reported by McLouchlan in 1838, and it took an additional 100 years for Liverud to provide the first radiological description of this condition ,8. IntraHowever, nontraumatic or spontaneous intramural hematoma may occur in patients with impaired coagulation, in which anticoagulant therapy represents the primary cause in most cases. Additionally, spontaneous intramural hematoma is also observed in individuals with other bleeding disorders, such as idiopathic thrombocytopenic purpura and von Willebrand disease. Pancreatic diseases, liver failure, leukemia, lymphoma, and vasculitis are among the other risk factors for intramural hematoma ,10,11.In this report, we first present the case of a 48-year-old male with severe hemophilia A. The patient experienced a spontaneous intramural hematoma of the jejunum, which resulted in acute abdomen, bloody stool, and paralytic ileus. Despite being considered for surgical intervention twice, conservative management utilizing factor VIII (FVIII) infusion was successfully administered, and the patient’s condition demonstrated a favorable outcome. However, within three months, recurrent episodes of intramural hematoma occurred, prompting repeat use of FVIII infusion, which ultimately led to a full recovery. Following this, prophylactic FVIII therapy was given to the patient, resulting in the absence of any hematoma recurrence for over three years.Further, we conducted a comprehensive review of 79 reported cases of intramural hematoma in patients diagnosed with hemophilia A or hemophilia B. The analysis of these cases was based on the specific location of the hematoma within the gastrointestinal (GI) tract, leading to the identification of five distinct groups. In order to provide insights into the clinical presentation, diagnosis, management, and outcomes of these hematoma cases, a simple pooling analysis was conducted with a particular emphasis on delineating differences between the various sites within the GI tract where hematomas occurred. Notably, our findings led us to recommend conservative treatment as the primary therapeutic option over surgical intervention.A 48-year-old male who suffers from severe hemophilia A with a FVIII activity of less than 1%. He had been receiving on-demand therapy with FVIII infusion for over 40 years and has been under follow-up care at our hospital for 15 years. FVIII inhibitor had never been detected. He suffers from severe arthropathy affecting the right hip, left knee, and both ankles. Additionally, he has a history of hepatitis C virus (HCV) infection, which was treated successfully under anti-HCV therapy without virus detection for more than 15 years.3/µL. His prothrombin time/international normalized ratio (PT/INR) was normal at 1.14 but activated partial thromboplastin time (aPTT) was prolonged at 146.3 s (control: 32–45 s). Under the suspicion of acute abdomen, a computed tomography (CT) of the abdomen was performed, revealing bowel wall thickening in a wide segment of the jejunum, consistent with an intramural hematoma and an intussusception-like lesion in the jejunal region. Further, there was ascites with hyperdense layering noted in the perisplenic and subphrenic areas and the cul-de-sac, consistent with hemoperitoneum  with neutrophil predominance, an elevated C-reactive protein (CRP) level of 5.09 mg/dL, and a normal hemoglobin (Hb) level (Hb: 14.9 g/dL). Platelet count was normal at 398 × 10ritoneum .Following hospitalization, the patient was placed on bowel rest and administered regular infusions of rFVIII-Fc . A pharmacokinetic study of Eloctate calculated a half-life of 24.75 h from medical records and the Web-Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS-Hemo) online system [3/µL. Although the PT/INR was normal at 1.04, the aPTT was prolonged at >180.0 s (control: 32–45 s). An abdominal CT revealed segmental wall thickening at the midjejunum, compatible with intramural hematoma, causing partial obstruction of the bowel, dilatation of the proximal jejunum and stomach, indicating mechanical ileus. The involved segments of the hematoma differed from those in the previous episode  with neutrophil predominance and an elevated CRP level of 6.19 mg/dL. The patient’s Hb level was 15.0 g/dL, and his platelet count was 418 × 10 episode .After admission, conservative treatment with rFVIII-Fc in the form of Eloctate was administered at a dose of 2500 IU q12h  in order to maintain FVIII trough levels at around 80%. An enteroscopy was carried out during this hospitalization in order to exclude the presence of a jejunal tumor, which yielded negative tumor findings. Nevertheless, the procedure revealed segmental reddishness and swelling of the jejunum with lumen narrowing, compatible with intramural hematoma. Gradual reductions in abdominal pain levels were observed, and a repeated CT scan on the fifth day of hospitalization also indicated the resolution of hematoma and the absence of any evidence of small bowel obstruction. After a period of 9 days of hospitalization, the patient’s condition stabilized, and he was subsequently discharged without any complications. He received prophylactic treatment at home with Eloctate at a dose of 4500 IU once per week  in order to maintain FVIII trough levels at around 2–4%. No recurrences of intramural hematoma were recorded during the three-year period following the patient’s discharge (up to the point at which this report was written).To enhance our understanding of intramural hematoma of the GI tract in PWH, we conducted a literature search on PubMed, Google Scholar and Embase, utilizing the keywords “hemophilia” or “haemophilia”, and “intramural hematoma” or “intramural hemorrhage.” Inclusion criteria were individuals with hemophilia A and hemophilia B, and exclusion criteria were studies without full text or patient details. In the end, we extracted 69 articles, which described a total of 79 cases, including our own, from 1956 until October 2022. The selection process is illustrated in Data were gathered on several factors, including age, sex, hemophilia subtype, titers of clotting factor inhibitors, whether prophylactic treatment was administered prior to the bleeding event, and any relevant trauma history. Clinical features of complications such as nausea or vomiting (possible signs of ileus or GI obstruction), tarry or bloody stool or hematemesis (possible signs of bleeding into the lumen of the GI tract), hemoperitoneum (possible sign of bleeding out of the serosa of the GI tract), and intussusception were recorded if reported in the research. However, if a paper did not report these symptoms, the patients were assumed not to have them. Laboratory data, including Hb levels and leukocyte counts, were also collected. Clinical management, classified as either operative or conservative therapy, was examined. The primary outcome was either recovery (symptoms subsided or hematoma resolved) or mortality.p-value of less than 0.05 was considered significant. All statistical analyses were performed using the SAS 2.12.0 software from the Free Software Foundation in Boston, MA, USA.A simple pooling analysis was conducted, and statistical relationships among the above-mentioned parameters were analyzed using Pearson’s chi-square test or Fisher’s exact test for categorical data, while Wilcoxon rank-sum test was used for continuous data. A Nonetheless, caution must be exercised when interpreting these results, as several limitations need to be considered. The primary constraint pertains to the fact that the investigation encompassed articles published from 1956 to 2022, spanning a duration of 66 years, wherein the diagnostic instruments and medical interventions underwent considerable fluctuations. A second notable limitation is the inability to examine the regimen and utilization of factor replacement therapy in surgery and conservative management due to the shortage of relevant data. Nevertheless, it is important to consider that the brands, regimen, and dosing frequency for clotting factor concentrates (CFCs) infusion may substantially impact clinical outcomes. The third limitation concerns clinical parameters that were not included in the literature, potentially confounding the statistical findings. For instance, if the paper failed to report a particular symptom or complication, we labeled it as “symptom negative” or “complication negative”, which may have led to an over or underestimation of clinical outcomes. Fourth, the possibility of excluding pertinent literature cannot be ruled out. Despite meticulous scrutiny of the literary sources in the three designated databases, the elimination of studies without complete text and comprehensive patient information may have resulted in the absence of valuable data. It should be noted that most of the literature incorporated in this study was composed in English, increasing the possibility of overlooking relevant literature in other languages.Notwithstanding, our collection of 79 cases from 69 papers, with no artificial selection bias, should provide some degree of representation across various ages. For instance, approximately 30% of the 79 cases involved inhibitor patients with intramural hematoma, which corresponds to the prevalence of inhibitor patients in PWH. Consequently, our findings and analysis should reflect the real-world setting to some extent.Among the 79 cases extracted from 69 papers, data on sex was available for 72 cases, 72 of which were men, and none were women. Age information was given for 76 cases, where 31 of them were children under the age of 18 and 45 were adults. Hemophilia A was present in 62 cases, hemophilia B in 4 cases, and 13 cases were of an unknown hemophilia type. Of the 62 patients with hemophilia A, 23 had severe hemophilia, 7 had moderate hemophilia, 5 had mild hemophilia, and 27 had an unknown severity of hemophilia.In our research, the recorded ratio of cases of hemophilia A to hemophilia B was 62:4 (31:2). However, the prevalence of hemophilia A and B is estimated to be approximately 1/10,000 and 1/50,000, respectively, resulting in a ratio of approximately 5:1. Our review of the data indicates that intramural hematoma occurs more frequently in patients with hemophilia A than in those with hemophilia B. To the best of our knowledge, this finding has not been previously reported. Although the bleeding phenotypes of hemophilia A and hemophilia B have been thought of as highly similar, some authors have argued that the bleeding tendency of hemophilia B may be less severe than that of hemophilia A and thus that hemophilia B has superior long-term outcomes ,14,15. TInhibitor formation is the most serious complication of CFCs replacement therapy for PWH. The inhibitor prevalence in people with hemophilia A has been reported to be 24–44.5% ,18. In op = 0.00595 **) and bleeding through the serosa of the bowel into the peritoneum (p = 0.0039 **) than those without inhibitors. However, there was no significant difference in operation and mortality rates between patients with and without inhibitors.Patients with inhibitors, regardless of their titer levels, were significantly more likely to experience bleeding into the gastrointestinal (GI) lumen than those without inhibitors .The clinical symptoms of gastrointestinal (GI) obstruction, such as nausea and vomiting, were frequently observed in patients with intramural hematoma and were associated with the site of involvement. Specifically, patients with hematoma involving the upper GI tract, including the stomach , duodenum , and small intestine , were more likely to experience these symptoms compared to those with colonic involvement . This association was found to be statistically significant (p = 0.0281 *).Bleeding into the lumen was more commonly observed in patients with involvement of the small intestine , colon , or esophagus , and less frequently observed in those with involvement of the duodenum  or stomach . This association was also statistically significant (p = 0.2901). However, hemoperitoneum or perforation into the peritoneal space was associated with operation, with cases presenting with hemoperitoneum  being more likely to require operation compared to those without hemoperitoneum  (p < 0.0001 ***). The patients with hemoperitoneum (bleeding out of serosa of the GI tract) seemed to have higher mortality than those without hemoperitoneum, but the associated did not achieve significance (p = 0.1087).On the other hand, neither hemoperitoneum nor perforation of the serosa of the GI tract showed a significant association with the site of involvement (p = 0.0076 **), with the highest mortality rates observed in cases involving the duodenum. However, selection bias may have occurred because four of the nine deaths were reported in the same paper, in which only cases with duodenum involvement were reported, and all were pediatric patients [p = 0.0006 ***), with the duodenum  and colon  being more commonly involved in children and the small intestine  being the most involved site in adults.Mortality was found to differ significantly with the site of involvement (patients . Additiop = 0.0334 *). In addition, children are more likely to have a history of traumatic events, with a prevalence of 47.4% in children versus 3.4% in adults (p = 0.0004 ***). The comparison of the clinical data between children and adults is presented in According to the relevant data for both children and adults, children exhibit a higher prevalence of anemia (defined as a hemoglobin level of less than 11 g/dL), compared to adults, with a prevalence of 81% in children versus 52.8% in adults (p = 0.0074 **), with children displaying lower median Hb levels of 8.1 g/dL compared to adults at a median of 10.7 g/dL. Moreover, unfavorable outcomes were more prevalent in children, with a markedly increased mortality rate of 23.3% (7 out of 30 cases) compared to adults at a rate of 4.9% (2 out of 41 cases) (p = 0.0305 *).Furthermore, when comparing continuous Hb levels to the presence versus absence of categorical anemia, the results demonstrate even greater statistical significance .Operations were conducted on a total of 24 patients, out of which only 22 patients reported their prognosis. For the remaining 52 patients, all cases reported their prognosis and were treated with conservative management using clotting factor concentrates infusion (CFCs). The mortality rate was 22.7% (5 cases) among the 22 cases that underwent operations, whereas only 7.7% (4 cases) of the 52 patients treated with conservative management died. However, this difference in mortality rates was not statistically significant  of cases, occurring exclusively in the colon (4 cases) and small intestine (6 cases). There was no significant difference in incidence between children and adults, with four cases in children and six cases in adults. Three symptoms were common in cases of intussusception, namely, abdominal pain , vomiting (9 cases), and bloody stool (5 cases), accompanied by palpable tender masses (5 cases) and paralytic ileus (4 cases).In terms of management, six cases were treated conservatively, resulting in successful self-reduction within a week ,25. The Intramural hematoma of the gastrointestinal (GI) tract is a rare condition in PWH, despite their bleeding tendency. Bleeding into the walls of the esophagus, stomach, small intestine, or colon has been reported ,6,26,27.The most common pathological mechanism of intramural hematoma should be the tearing or rupture of terminal arterial vessels leaving the mesentery to penetrate the muscularis of the intestinal wall ,7,33. AsThe most frequently reported clinical manifestation among the cases was abdominal pain, which was mentioned in 61 cases (77.2%). Signs of gastrointestinal obstruction, such as nausea, vomiting, or decreased appetite, were also commonly observed (43 cases). Other clinical manifestations included constipation (7 cases), hematemesis (6 cases), tarry or bloody stool (21 cases), and diarrhea (4 cases). Physical examination revealed abdominal distention in 22 cases, palpable mass in 11 cases, and hypoactive bowel sounds in 10 cases. Hemodynamic instability was identified in cases with severe blood loss. Signs of peritoneal irritation were suggestive of severe conditions, such as bowel wall necrosis, perforation, or hemoperitoneum . In caseLaboratory investigations failed to provide specific diagnostic information regarding intramural hematoma in the patients under study. In 36 cases, reduced levels of Hb were observed, indicative of blood loss. Leukocytosis with a left shift and elevated CRP levels were also present in some cases, which might be associated with hemoperitoneum, more severe intramural hematoma, or even perforation into the lumen or out of the serosa of the GI tract. Elevated amylase and lipase levels are indicators of associated obstructive pancreatitis, especially in cases affecting the duodenum ,32. GlasAmong imaging studies, plain abdominal radiography is nonspecific and may reveal only evidence of GI obstruction if present ,20,34. AIntussusception is rare in adults, with only 2–3 cases per million per year . ApproxiWhile intussusception is typically treated through surgery, our research indicates that for these PWH, intussusception can be a transient condition that can be resolved through CFC infusion treatment, thereby rendering surgical intervention unnecessary ,28,39 unRapid and accurate diagnosis, along with timely management, are crucial for PWH with intramural hematoma ,33. ConsAlthough perforation into the peritoneal space or hemoperitoneum is typically viewed as requiring immediate surgical intervention, Janic et al. and Benjamin et al. have reported cases of successful nonsurgical management, implying that conservative therapy is a suitable option for PWH with mild hemoperitoneum ,42. In cIntriguingly, literature reviews of cases where individuals experienced an anticoagulant overdose and developed intramural hematoma have yielded similar results. The researchers inferred that the majority of such instances can be managed conservatively without the need for surgery .Regarding the issue of recurrence, Katsumi et al. reported the case of a 17-year-old patient with severe hemophilia A . This paIn contrast, our patient, a 48-year-old with no inhibitors, experienced one recurrent episode, and subsequently received prophylactic therapy once weekly, and showed no recurrent episodes for the following three years. Given the potentially life-threatening nature of intramural hematoma for PWH, prophylactic therapy with CFCs is crucial for reducing the risk of recurrence after one or more episodes. Prophylactic therapy with regular CFC infusion is effective in significantly reducing the likelihood of spontaneous bleeding events in PWH by reducing disease severity through maintenance of trough factor levels of >1% ,45,46.However, complete blocking of recurrent intramural hematoma in PWH with prophylactic therapy is not guaranteed. For example, Prieto et al. reported a 22-year-old patient with severe hemophilia A, who received prophylaxis using FVIII 40 IU/kg three times per week from the age of 19 years and still experienced spontaneous intramural hematoma of the jejunum [To provide further information, this report showcases all 79 cases of intramural hematoma of the GI tract, along with details pertaining to age, diagnosis, location, symptoms, management, and outcomes. These details are organized according to the specific sites involved: Small intestine in Intramural hematoma of the GI tract is rare among PWH. The presenting symptoms can vary depending on the site of involvement, ranging from mild abdominal pain to severe ileus and even large bloody stools, hemoperitoneum with unstable hemodynamics, and significant hematemesis. The recommended diagnostic choice is abdominal CT without contrast. The overall mortality rate is found to be 12.2%, while children have a higher mortality rate (23.3%) than adults (4.9%). Early conservative therapy with CFCs infusion should be the first-line therapeutic option, and surgical intervention should be reserved for complicated cases. Prophylaxis with regular CFCs infusion to prevent the recurrence of intramural hematoma may be an effective and practicable strategy but does not guarantee complete freedom from recurrence. We believe that our case report with a literature review will be clinically helpful for physicians to manage better the rare risky intramural hematoma in PWH.


In this study, weused four amorphous poly-alpha-olefin (APAO)grades to improve the toughness of drawn polypropylene (PP) tapes.The samples containing different amounts of APAOs were drawn in aheat chamber of a tensile testing machine. The APAOs reduced the workof drawing and increased the melting enthalpy of the drawn specimens,as they facilitated the movement of the PP molecules. The APAO withthe highest molecular weight and with a low level of crystallinityincreased both the tensile strength and the strain-at-break of thespecimens, so we also produced drawn tapes from that PP/APAO blendon a continuous-operation stretching line. The continuously drawntapes also showed improved toughness. Its versatility is ensured by its low price, easy processability,low density, and excellent chemical resistance. PP, however, has onlymodest mechanical properties. This problem can be overcome with reinforcement.The most common reinforcements are short glass fibers, which makesit possible to use PP for industrial applications.8 Such orientation can be achieved in different processes, such asgel-spinning, melt-spinning, and solid-state drawing. During gel-spinning,orientation is achieved in a polymer solution, and it is usually appliedfor polymers with very high molecular weight, as such polymers thatcannot be melted due to the immense amount of secondary bonds betweentheir huge molecules.9 Thus, gel-spinningis mostly used to produce high-end fibers with exceptional strengthand modulus,9 but it also gained importancein producing nanofibers.10 During melt-spinning,fibers are formed in the melt state. Melt-spinning has been used toproduce synthetic fibers for the textile industry using a wide rangeof polymers.9Molecular orientation is a uniquestate of the polymer materialswhen the chain molecules reside more-or-less parallel to each other,which dramatically—often by two orders of magnitude—increasesthe polymer’s strength in the direction of the orientation.13 During the drawing process, the internal stressescaused by the drawing forces drive the polymer molecules to move parallelnext to each other. In semicrystalline polymers, however, the crystallineand the amorphous phases behave differently during drawing. The crystallinephase, which originally forms spherulites or lamellae, goes througha complex process called micronecking, first described by Peterlin,14 and forms long fibrils.16 The moleculesof the amorphous phase, which originally did not show any definedarrangement whatsoever, are settled in a more-or-less parallel mannerdue to the increased molecular mobility.17 There are also tie molecules, however, that go through both theamorphous and the crystalline phases. As these molecules are alsopart of the crystalline phases, they are constrained, and they becometaut tie molecules during drawing.18In the case of solid-statedrawing, a preexisting polymer structure—fiberor tape—is drawn at an elevated temperature. In industrialprocessing, the tapes to be drawn are usually produced with sheetfilm extrusion or film blowing, with the former being the predominantmethod; as in the case of sheet film extrusion, the initial parametersof the film can be controlled more precisely with different coolingmethods . Biaxially orientedfilms, however, can only be produced by film blowing. An elevatedtemperature is needed during the drawing process, which should notexceed the melting temperature of the particular polymer grade, toprovide enough mobility to the molecules. The most important quantityin solid-state drawing is the draw ratio (λ), i.e., the ratioof the length of drawn and undrawn fibers or tapes. In the case ofPP tapes, usually a draw ratio between λ = 12 and λ =15 is applied in industrial production to achieve the most beneficialproperties.19 showed that in the case of drawn PP tapes, crystalline orientationreaches its peak at around the draw ratio of λ = 9, and at higherdraw ratios, only the orientation of the amorphous phase increases.19 Since then, several studies have showed theorientation of the crystalline phase is finished around the draw ratioof λ = 920 The degree of orientation isusually measured with wide angle X-ray diffraction. This method, however,only provides the orientation of the crystalline phase, but combinedwith other methods , the orientation of the amorphous phase also can be obtained.The degree of orientation is usually described by the Hermans orientationfunction, which is a dimensionless number, and it can vary between−0.5 and 1. If the orientation function is 1, that means atheoretically perfect orientation , while the valueof −0.5 means that they are all perpendicular to it. In thecase of completely random orientation, the orientation function is0. The amorphous orientation increases the tensile modulus much morethan the tensile strength; thus, above the draw ratio of approximatelyλ = 9, the maximum strain of the drawn tapes is reduced whiletheir strength is only moderately increased.20 This behavior can hinder the application of drawn PP tapes in manyindustrial segments where toughness is also important besides theincreased strength of the drawn tapes.21 This problemcould be overcome with the use of blends of PP and amorphous poly-alpha-olefins(APAOs) to produce drawn tapes.22In this model, the orientation of the amorphous and the crystallinephases can be differentiated. Yamada et al.23 APAOshave an unlimited solubility in PP, however, due to their atacticnature, their molecules can only reside in the amorphous phase ofthe PP.24 Chen et al.25 investigated the properties of iPP/aPP blends, and they found thata small amount of aPP increased the crystallinity of the blend, butthe overall crystallinity decreased with increasing aPP content. Thenormalized crystallinity of the PP phase, however, increased withincreasing aPP content. They concluded that this phenomenon was causedbecause the tiny molecules of aPP acted like a diluent, and they increasedthe mobility of iPP molecules and reduced the entanglements betweenthem.25 In this study, our goal is to exploit thisproperty of APAOs—which are very similar to aPP—to increasethe maximal strain of drawn PP tapes without the cost of reducingtensile strength.Amorphous APAOs are similar to atactic PP (aPP), as they mostlyconsist of propylene repeating units residing in an atactic manner,but, contrary to the aPP, APAOs are not a byproduct of isotactic PP(iPP) production; they are produced on purpose to be used as meltadhesives or sealants. This makes it possible for the producers totailor-make their properties, i.e., molecular weight, viscosity, meltingtemperature, etc. In the APAOs, propylene is sometimes copolymerizedwith larger alpha-olefins , and they usuallycontain plasticizers .2We used the TipplenH681F  highly isotactic PP homopolymer as the matrix material, witha melt flow index of 1.7 g/10 min (measured at 230 °C with 2.16kg). The APAOs used were propene-rich melt adhesives, and they aremarketed under the tradename of Vestoplast 708, Vestoplast 750, Vestoplast792, Vestoplast 888 . Hereinafter, these materials will be referredto as VP708, VP750, VP792, and VP888, respectively. Their propertiesare shown in The PP matrix and the APAOs were mixed in an LTE 26-44co-rotatingtwin-screw extruder .The revolution of the screw of the extruder was 90 1/min, and therevolution of the screw of the volumetric dosing unit was 12 1/min.The zone temperatures of the extruder were 160, 170, 175, 180, 180,180, 185, and 190 °C from hopper to die, and the temperatureof the die was 190 °C. The extruded filaments were granulatedwith an LZ-120/VS pelletizer . We prepared PP/APAO blends containing 5, 10, and 15 wt% of VP708, VP750, VP792, and VP888. The plain PP reference was alsoextruded to provide the same thermal history.Sheet films wereprepared from the blends with a 25–30Csingle-screw extruder and an LCR300 sheet-film line . For tensile drawing, 0.5 mm thick filmswere produced. In that case, the revolution of the screw was 90 1/min,and the take-up speed was 0.6 m/min. We produced 0.2 mm thick filmsfor the drawing line, with a screw revolution of 120 1/min and atake-up speed of 1.8 m/min. In both cases, the zone temperatures ofthe extruder were 170, 180, 190, 195, and 200 °C from hopperto die, the die temperature was 200 °C, and the first roll ofthe sheet-film line was tempered to 85 °C. The revolution ofthe winder was set according to the diameter of the roll (between6 and 11 1/min).Dumbbell specimens were punched out from thesheet films 1. The diThe specimens were drawnin the heating chamber of a Z250 tensiletesting machine . The machine was equippedwith wedge grips and a 20 kN load cell. The drawing temperature was130 °C, and the drawing speed was 600 mm/min. We stored the specimensin the heating chamber for at least 10 min before drawing to set theirtemperature and left at least 2 min between closing the chamber doorand the start of the drawing to maintain a constant temperature of130 °C in the chamber. The specimens containing 10 wt % APAOwere drawn to the draw ratio of λ = 5, 8, 9, 10, 12, 15, and22, while the specimens containing 5 and 15 wt % APAO were drawn tothe draw ratio of λ = 10. Force–strain curves duringthe drawing were recorded with the built-in software of the tensiletesting machine.The work of drawing was determined by calculatingthe area underthe force–elongation curves recorded during the drawing process.We expressed the work of drawing in terms of the area of the cross-sectionof the specimens (the work of drawing was divided with the area ofthe specimens) to make the results comparable. Note that as the cross-sectioncould not be continuously measured during the drawing process, thework of drawing was normalized to the initial cross-section of thespecimens, similar to the method frequently used in the evaluationof tensile tests. This way, although the drawing curves do not representthe real stress in the specimens upon drawing, the curves became comparableto each other.We also produced drawn tapes from the 0.2 mmthick films usinga custom-made drawing line 2 to modeXc is thecrystallinity of the sample (%), ΔHm is the melting enthalpy of the sample (J/g), and ΔHm0 is the melting enthalpy of a theoreticallyinfinite PP crystallite (207 J/g1).Differential scanning calorimetry (DSC) was performedon the sampleson a Q2000 DSC device with one heating ramp in the temperature range between 0 and 200 °C,with a heating rate of 10 °C/min in a 50 mL/min nitrogen atmosphere.The crystalline melting temperature was determined as the peak ofthe first heating curve, and crystalline melting enthalpy was determinedas the area under the melting peak with respect to the baseline. Thecrystallinity of the samples was determined with the following equation:Tensile tests were conducted with a Z005 tensile testing machine. In the case of the drawn tapes, we cutout a 100 mm long sample from the middle of the tape, and the tensiletests were performed on these specimens with a measuring length of40 mm. For undrawn samples, we used the specimens specified in 33.120Typical drawing curvesof the PP/APAO blends are presented in Below the draw ratio of λ = 9, the curvesof the blends withthe APAO content of 5 and 10 wt % coincide with the curves of thepure PP, only the curves of the blends with 15 wt % APAO content differfrom the others. Above λ = 9, however, a larger difference canbe observed between the curves. This can be attributed to the factthat at λ = 9, the orientation of the crystalline phase completes,and above that, only the orientation of the amorphous phase continues.As APAOs—due to their mostly atactic nature—are almostcompletely amorphous, their molecules only can be present in the amorphousregions of the PP. Thus, in the region of the amorphous orientation,the effect of APAOs is more considerable.The relationship betweenthe draw ratio and the specific work ofdrawing is linear 4. APAOs A small melting peak can be detectedon the DSC curves of the drawntapes between 150 and 154 °C. The size of this peak increasedwith increasing draw ratio. This peak can be attributed to the meltingof the imperfect fibrils produced by the intense drawing. A few instabilitiesalso can be seen on the DSC curves between 155 and 165 °C, especiallyin the case of tapes with higher draw ratios. This can be attributedto the increased relaxation phenomenon occurring in the highly drawntapes at elevated temperatures. Relaxation decreases the molecularorientation of the tapes and reduces the length of the drawn tapes.This phenomenon could change the contact surface between the samplesand the sample holder thus causing small fluctuations in the heatflow.25 On the other hand, both VP708 and VP888 facilitated the crystalgrowth of PP, as the specific melting enthalpy  was more than 1 for each blend.This effect was also noticeable in the case of the undrawn samples,as relative crystallinity was 1.07 and 1.08 in the case of PP/VP708and PP/VP888, respectively. The second heating cycle showed similarresults , however, also increasedthe tensile strength between the draw ratios of λ = 8 and λ= 10. This effect of Vestoplast 888 was also experienced when thePP/APAO blend was drawn on a drawing line, which modeled the continuousoperation of industrial-scale drawing.Based on the results,APAOs seem promising additives to simultaneouslyimprove the tensile strength and strain-at-break of drawn PP tapes.As those properties usually contradict each other, the PP/APAO blendscan obtain great industrial importance, especially, as the reducedwork of drawing can make the industrial-scale production of such tapesmore economically feasible.


Land Cover (LC) maps offer vital knowledge for various studies, ranging from sustainable development to climate change. The China Central-Asia West-Asia Economic Corridor region, as a core component of the Belt and Road initiative program, has been experiencing some of the most severe LC change tragedies, such as the Aral Sea crisis and Lake Urmia shrinkage, in recent decades. Therefore, there is a high demand for producing a fine-resolution, spatially-explicit, and long-term LC dataset for this region. However, except China, such dataset for the rest of the region  is currently lacking. Here, we constructed a historical set of six 30-m resolution LC maps between 1993 and 2018 at 5-year time intervals for the seven countries where nearly 200,000 Landsat scenes were classified into nine LC types within Google Earth Engine cloud computing platform. The generated LC maps displayed high accuracies. This publicly available dataset has the potential to be broadly applied in environmental policy and management. Understanding LC types and their changes over time at different spatial scales, from regional to global, is of paramount importance for multiple disciplines, such as environmental risk assessment, global warming, and sustainability4. Remote Sensing (RS) data, with its varying spatiotemporal resolutions, has become an essential tool for monitoring LC changes6. Despite the tremendous efforts that have been conducted in the LC change mapping field, accurate knowledge on historical LC changes over large areas is still limited8.Land Cover (LC) changes influence most natural and physical processes on Earth, such as the hydrological cycle, ecological balance, and ecosystem services9. Over the last decades, the Corridor has been impacted by some of the world’s worst LC change tragedies9. The Aral Sea crisis and Lake Urmia shrinkage are two main examples in this regard. More specifically, the Aral Sea in Central Asia has lost over 80 percent of its surface over the past few decades10, and Lake Urmia in Iran has similarly shrunk in surface area by 80 percent between 2005 and 201511. Given that those kinds of severe LC changes can threaten lives of millions of humans and species14 the precise long-term LC dataset along the Corridor is therefore essential for understanding the main causes of such changes.A key part of the Belt and Road Initiative (BRI) program, the China-Central Asia-West Asia Economic Corridor (here after referred to as the Corridor) encompasses eight countries  that mostly are situated in arid and semi-arid climates15, GlC200016, and MODIS17 datasets have been generated by the RS community. However, the existing LC products have limited applicability for a variety of long-term LC change monitoring applications due to their narrow temporal coverage, relatively low accuracies, and inconsistencies in the classification systems among different global LC products9. For example, although the Globland30 dataset is indeed a valuable product, theses dataset is only available at decadal intervals . It is also impractical to use this LC dataset as a benchmark for long-term LC change monitoring aim due to its unknown accuracy for 2000 and relatively low accuracy in certain regions, such as Central Asia where Sun et al.18, indicated a low Overall Accuracy (OA) of 46 percent. Similarly, Naboureh et al.19, claimed that Globland30 had a relatively low OA of 62.3 percent for Turkey. Thus, it is impractical to study historical LC changes using the available LC products.A number of high to coarse resolutions global LC products, such as FROM-GLC20 and the advent of Earth science data cloud computing and analysis tools, such as Google Earth Engine (GEE), have facilitated the production of various types of LC products19. As a result, several valuable LC datasets for various regions of the world have been generated. For instance, Calderón-Loor et al.7, generated a set of seven 30-m resolution LC maps covering the period of 1985–2015 at five-year intervals. In another attempt, Pekel et al.21, generated annual global surface water area dataset from 1984 to 2016. However, our team’s review9 revealed that a long-term LC dataset is still lacking for the majority of the Corridor, including Kyrgyzstan, Turkmenistan, Tajikistan, Uzbekistan, Iran, and Turkey. To the best of our knowledge, the only exception is China, where Yang and Huang5 created the first 30-m annual LC dataset spanning the period between 1990 and 2019, based on the GEE platform and Landsat data.Addressing this deficiency, the Landsat archive’s free sharing policy in 2008This paper presents a set of six 30-m resolution LC maps for seven countries from the Corridor, excluding China, namely Kyrgyzstan, Turkmenistan, Tajikistan, Uzbekistan, Iran, and Turkey Fig. . To geneThis study offers a set of six 30-m LC maps for the seven countries from the Corridor between 1993 and 2018. The entire procedure was carried out on the GEE cloud processing platform  and two West-Asian countries (Turkey and Iran), with a total area of about 6,435,208 km9. In this study, all the available surface reflectance Landsat data between 1st January 1991 and 31st December 2020, were acquired within the GEE cloud processing platform, as there were not adequate Landsat scenes covering the entire study area during 1984–1990  have been offering 30-m Earth observation data, which is widely known as an ideal source for LC mapping over large areas990 Fig. . A total990 Fig. . To miti25 data. Using the nearest neighbour interpolation method, all auxiliary variables were resampled to 30-m pixels in accordance with the Landsat pixel grid. Finally, a mean function was applied to all cloud-free stacks at each time step to generate a single mosaic image for classifying each LC map.Six bands from Landsat data, including Short-wave infrared 1, Short-wave infrared 2, Near-infrared, Green, Blue, and Red were utilized in this work. Moreover, using the Random Forest (RF) variable selection technique, eight spectral indices were calculated among various spectral indices to contribute in LC mapping 28, and JRC global surface water21, were used to obtain reference sample datasets for nine LC classes at five different time-steps  developed by our teamet al.19, the samples were first collected using Google Earth  and Landsat images. Then, their annual NDVI time series were extracted from Landsat images. Finally, the true label was determined for an LC class if the NDVI values of the given sample was stable over each time step.In order to ensure an adequate number of samples and a diverse representation of each LC class (random sampling technique), the visual interpretation technique was used when the collected samples by HRSG method was insufficient. The study aimed to have at least 30,000 training samples at each time step to achieve acceptable accuracy according to the conducted initial experiments. Therefore, samples were obtained using Landsat images, annual NDVI time series, and the Google Earth images. More specifically, following Naboureh et al.29, Their dataset includes a total of 8,196 samples collected between 2015 and 2018, as well as 213 samples from 2011 and 26 samples from 2008. We double checked these samples, and stable samples were added to the generated dataset for 2013 and 2018. Overall, the final dataset for each time interval includes over 50,000 pixel points  distributed across all sub-areas. This not only improved the model’s ability to generalize in diverse regions but also lowered the risk of discontinuous classification results across climatic zone boundaries.We conducted initial experiments to eliminate the possibility of discontinuous classification results near climatic zone boundaries, as reported by Shafizadeh-Moghadam 30. RF has become a popular choice for large-scale LC classification due its ability to handle complex and high-dimensional data31. An investigation, which focused on six different landscapes in the Corridor, found that RF had the best performance among several well-known supervised classification algorithms32. In addition, our research19 revealed that using an adaptive RF-based classification method can effectively address the impact of climate variations on LC classification accuracy. Consequently, to create LC maps for the years 1993, 2003, 2008, 2013, and 2018, this study utilized an adaptive RF classification scheme. The study region was separated into 25 sub-areas  products for a more comprehensive performance evaluation. To this end, the GlobLand30 version 2020 and Dynamic World version 2018 (time filter = between 1st January 2018 and 31st December 2018) products have been used in the comparison task. It should be noted that we focused on Turkey as testbed in this section. The reason for the selection of Turkey was twofold: Turkey encompasses different climate zones and elevation ranges, and, most importantly, there were available independent validation samples with a total of almost 6000 data points. It is worth mentioning that although the selected LC products share almost the same classification system, based on the classification system of this research , and User Accuracy (UA). In general, we used minimum 15,000 validation samples at each time interval for assessing the produced LC maps. We also used a visual interpretation technique to ensure the generated LC maps are noise free, particularly across climate zone boundaries, where sudden fluctuations can be noticed if the distribution of training reference samples is poor. Additionally, taking the year 2018 as an example, we compared the generated LC map in this study against GlobLand30 (30-m resolution) and Dynamic World34. This dataset consists of six land cover maps  for the Corridor region, which spans seven countries including Turkey, Iran, Kyrgyzstan, Kazakhstan, Tajikistan, Turkmenistan, and Uzbekistan. These LC maps include nine LC classes To evaluate the generated map, we used visual interpretation, statistical accuracy assessment, and inter-comparison with existing LC products for a fair and comprehensive evaluation of the produced LC maps.34 for the years 1993, 1998, 2003, 2008, 2013, and 2018 are noise-free and offer reasonable depictions of all nine LC types  against GlobLand30 and Dynamic World Products. To this end, because GlobLand30 is not accessible for 2018, the 2020 version of GlobLand30 product was used in this study. Moreover, the mean image (1st January 2018 to 31st December 2018) of Dynamic World in 2018 were obtained from GEE platform. As can be seen in Fig. We also applied a quantitative comparison between the results of the present work with the two LC products selecting Turkey as the experiment site. It was observed that the generated LC map in this study in 2018 achieving OA = 92% outperformed Dynamic World (OA = 70%) and Globland30 (OA = 60%) products. Except for water class  in Dynamic World, snow  and cropland  classes in Globland30, the obtained PA and UA values for all nine LC classes of the generated LC map in this study were higher than the other two LC products (Fig. 34 is not error-free and the users should consider possible error/noise when interpreting the LC maps, but the generated LC dataset is reasonable.We implemented an adaptive supervised classification scheme to accurately discriminate nine LC classes for a large-scale study. As shown in Fig. 35 over the last few decades, affecting the lives of nearly two billion people, this dataset can serve as a useful tool for analysing the dynamic of surface water changes in the study area (Fig. Accurate knowledge on LC types and their changes over time is critical for different research fields, such as ecological protection, environmental management, and sustainable development. LC datasets with high spatial and temporal resolution are critical for monitoring changes in land use, identifying patterns of deforestation and urbanization, and evaluating the impact of human activities on natural ecosystems. The generated LC dataset in this study with a 30-m resolution is the first of its kind for one of the BRI’s Corridor. This dataset provides a comprehensive picture of LC dynamic for seven countries in the region since 1993. The dataset has been meticulously validated to ensure its accuracy and reliability. This dataset can be included as part of the digital BRI program, which seeks to promote the use of science and technology for sustainable development of the BRI region. This dataset has multiple applications; for example, given the remarkable shrinkages in surface water area in the Corridor region


Vascular endothelial growth factors  have important roles in the development and function of the peripheral nervous system. Studies have confirmed that VEGFs, especially VEGF-A  may be associated with the diabetic peripheral neuropathy (DPN) process. However, different studies have shown inconsistent levels of VEGFs in DPN patients. Therefore, we conducted this meta-analysis to evaluate the relationship between cycling levels of VEGFs and DPN.This study searched 7 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM), to find the target researches. The random effects model was used to calculate the overall effect.p<0.00001) and healthy people . In addition, increased circulating VEGF levels were not associated with an increased risk of DPN .14 studies with 1983 participants were included, among which 13 studies were about VEGF and 1 was VEGF-B, so only the effects of VEGF were pooled. The result showed that there were obviously increased VEGF levels in DPN patients compared with diabetic patients without DPN (SMD:2.12, Compared with healthy people and diabetic patients without DPN, VEGF content in the peripheral blood of DPN patients is increased, but current evidence does not support the correlation between VEGF levels and the risk of DPN. This suggests that VEGF may play a role in the pathogenesis and repairment of DPN. The WHODespite the great harm and large number of patients, the pathogenesis of DPN has not been clearly explained. The occurrence of DPN is related to many pathogenic factors, including microvascular dysfunction, accumulation of advanced glycation end products(AGEs), inflammation, oxidative stress and autoimmunity . DPN hasAn important family of growth factors is vascular endothelial growth factor (VEGF) family, whose expression is mainly regulated by hypoxia-inducible factor (HIF) during hypoxia and are important participants in the angiogenesis process . VEGF faAs an important angiogenesis and neuroprotective factor, the changes in the VEGF family in diabetic complications have attracted wide attention. However, the changes of VEGF, the most famous molecule of the VEGF family, in the peripheral circulation of DPN patients are still contradictory, and different studies have shown different trends. It has been reported that VEGF levels in the peripheral blood of DPN patients are significantly higher than those of diabetic patients without DPN and healthy people, but some studies have reached different conclusions , 16. Due2This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for systematic reviews of observational studies. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), Number CRD42023389678.2.1Two investigators (Rui Ding and Shicong Zhu) independently conducted a systematic search on the databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM) through December 30, 2022, with language restrictions to Chinese and English. MeSH and free-text words are used for searching, with appropriate modifications for different databases. The search terms were used as follows:  AND . More detailed search terms and procedure are in Support Material.2.2(1) cohort, cross-sectional, or case-control studies; (2) the controls were diabetic patients without DPN or healthy controls; (3) providing mean values of VEGFs levels, or odds ratio (OR) with 95% confidence interval (95% CI) or sufficient data to calculate these levels; (4) studies in Chinese or English were considered for inclusion; If two studies used the same study population during the same period, we included only the study with larger sample size and longer follow-up.2.3(1) studies without available data for meta-analysis were excluded; (2) reported data were on only one group of subjects; (4) obviously irrelevant studies, articles without full text, conference abstracts, comments, reviews, case-only studies, and studies based on animal models or cell lines were excluded.2.4The risk of bias was evaluated using the Newcastle Ottawa scale (NOS) for case–control studies and an adapted form of the Newcastle Ottawa scale for cross-sectional studies , 18. The2.5I2 index and Cochran’s Q statistics were used for heterogeneity assessment. If pQ-text< 0.1 and I2>50%, it indicates that there is statistical heterogeneity. A sensitivity analysis to test the robustness of pooled estimates by excluding every single study was also performed. In addition, we planned a priori subgroup analysis based on: study location, study design, sample size, sample type, disease type and ages. Publication bias was assessed using funnel plot, Egger’s test and Begg’s test performed by Stata 15.0 software. If publication bias exists, we would use the trim and fill method to add several possible missing studies and recalculate the pooled estimates. Statistical significance was considered as p < 0.05.All meta-analyses were performed using RevMan software (version 5.3). Data will be analyzed using a random or fixed effects model (depending on which is appropriate). Continuous variables, presented as mean ± standard deviation, with SMD and 95%CI for effective measures. The pooled OR with 95% CI was calculated for the assessment of the association between VEGFs levels and DPN risk. The 33.1Of 1488 records  were initially identified from the online databases. After removing 367 duplicates, studies that did not meet the inclusion criteria were excluded by reading the title and abstract. After an initial review, 35 studies will be read in full text to determine whether they meet the inclusion criteria. Finally, 14 studies –32 were Those 14 studies involved a total of 1983 participants, including 807 DPN patients, 808 diabetic patients without DPN and 368 healthy people. Among the 14 studies, 13 studies , 25–32 r3.2p<0.00001, Heterogeneity: Tau² = 1.77; Chi² =389.47, P < 0.00001; I² = 97%, Eggerp=0.004), the funnel plot is shown in 13 studies compared VEGF levels in the blood of DPN patients and diabetic patients without DPN (N-DPN), but 1 study did not specify the data type , so we pooled the analysis of VEGF levels in the 12 studies. 1 study divided DPN patients into three grades and separately reported the VEGF content in each grade, so we combined the data of the three levels. The random effects model was adopted to pool the data due to apparent heterogeneity. As shown in 3.3p<0.00001, Heterogeneity: Tau² = 3.51; Chi² =304.85, P < 0.00001; I² = 97%, Eggerp=0.000, which indicates the existence of publication bias . At the same time, subgroup analysis also found that different study designs and sample sizes may also affect the level of VEGF. When the number of participants ≥200, VEGF in the peripheral blood of DPN patients did not significantly increase , and the same result was also found in the pooled effect of two case-control studies . Unfortunately, the above subgroup analysis fails to account for the high heterogeneity of the study. Some possible causes of heterogeneity such as disease course, diagnostic criteria, gender, and detection methods could not be further discussed in subgroup analysis due to the incomplete and inconsistent research reports.P = 0.39), sample type (p=0.05), age(p=0.26) and study design (P = 0.66).Our subgroup analysis of 9 studies with healthy people as controls found that different types of diabetes also affected the results of the pooled analysis, when the subjects included or only included type 1 diabetes patients, the increase of VEGF level became less significant . Simultaneously, subgroup analysis showed that there was no significant difference in subgroup according to location . This reminds us to pay attention to the role of diabetic types. Microvascular reactivity does not appear to be the same between type 1 diabetes and type 2 diabetes. VEGF has a strong ability to promote vascular permeability , but thiin vivo but mainly originate from higher artificial ex vivo release from platelets (Though our subgroup analysis does not find any difference this time, the content of VEGF in serum and plasma may indeed differ. Hanefeld et al.  found thlatelets . A recenlatelets . In addilatelets . Last buDPN is the most common diabetic microvascular complication. Long-term chronic hyperglycemia leads to neuronal damage and reduced nerve blood flow, in the meantime, ischemia and hypoxia caused by neurovascular defects can also lead to structural and functional changes in nerve tissue , 42. VEGIn diabetes mellitus, excessive or defective angiogenesis occurs. Excessive angiogenesis is often seen in diabetic retinopathy, while insufficient angiogenesis often impedes healing of diabetic foot ulcers. Abnormal angiogenesis in DPN has been specifically observed in some studies. Compared with healthy animals, functional blood vessels of the sciatic nerve in DPN animals have smaller density and shorter diameter, the content of VEGF, Ang-1 and other pro-angiogenesis regulatory factors in the sciatic nerve is lower , 51. ThuThe limitations of our study should be acknowledged. First, no eligible prospective cohort studies were found in our search, thus no causal relationship could be explored. Second, only one study focused exclusively on type 1 diabetes, so a more detailed analysis of diabetes types was not possible. Third, the OR values involved in this study were all unadjusted, so more adjusted OR is needed to refine the conclusion. Fourth, most of the included studies were rated as medium in quality. In view of the fact that high-quality studies can provide more effective information for analysis, more excellent trials should be added in the future. Finally, high heterogeneity and publication bias reminds us to treat the results of this study with caution.5In conclusion, the circulating VEGF levels in DPN patients were significantly higher than that in diabetic patients without DPN and healthy controls. This meta-analysis did not find a connection between the level of VEGF in peripheral blood and the risk of DPN. Due to the limitations of this study, more high-quality studies, especially cohort studies, are needed in the future to further clarify the relationship between DPN and VEGF. In addition, although our studies have proved that VEGF plays an important role in the pathogenesis and treatment of DPN, it still needs careful consideration as a biomarker and therapeutic approach.RD collected, analyzed, designed this study, and wrote the main manuscript as the first author. SZ and XZ extracted data and performed the statistical analysis. RD and SZ retrieved the literature and conducted a research quality assessment. RY supervised the work. All authors contributed to the article and approved the final manuscript.