Besides, the experimental group had evidently lower systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd), and mean blood flow velocity (Vm) and evidently higher pulsatility index (PI) (p < 0.05). The levels of S100 and NSE in the experimental group increased significantly, and the level of BNDF decreased significantly (p < 0.05). In patients with hypertensive cerebrovascular disease, the level of ADPN declines; the levels of hs-CRP and sICAM-1 rise; the incidence rate of cerebrovascular complications is elevated; and there are changes in the blood lipid, cerebrovascular hemodynamic, and neurological indexes, thereby further promoting the occurrence and development of hypertensive cerebrovascular disease.The study is aimed at studying the association between the levels of serum adiponectin (ADPN), high-sensitivity C-reactive protein (hs-CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) and hypertensive cerebrovascular complications. 50 patients with hypertensive cerebrovascular disease treated in Gansu Provincial Hospital from December 2016 to December 2018 were selected as the experimental group, and 50 normal people who underwent physical examination were selected as the control group. The blood pressure, heart rate, and the complications were recorded, and the serum blood lipid indexes were detected. Moreover, the content of serum ADPN, hs-CRP, and sICAM-1; the neurological indexes; brain-derived neurotrophic factor (BNDF); and neurone-specific enolase (NSE) were also determined using ELISA. The content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCR) in the experimental group was significantly higher than that in control group ( Cardiovascular disease has become an important cause of death and disability with age. The deaths caused by cardiovascular disease account for more than 20% in the elderly in Western Europe and North America. Cardiovascular disease may be a more horrible disease than death for the elderly. Hypertension is a major risk factor for stroke, and the incidence rate of atherosclerosis cerebral infarction in patients with hypertension is about 4 times than that in patients with normal blood pressure . The corAdiponectin (ADPN) is a kind of recently discovered adipocytokine produced and secreted by adipose tissues . StudiesIn the present study, patients with hypertensive cerebrovascular disease and normal people receiving physical examination were collected as experimental subjects. Then, venous blood was drawn to detect the serum routine biochemical indexes of hepatic and renal function, blood pressure and heart rate were measured in each group, and blood lipid indexes were detected. Moreover, the content of serum ADPN, hs-CRP, and sICAM-1 was determined using enzyme-linked immunosorbent assay (ELISA); the hemodynamic indexes were detected; and the neurological indexes of serum brain-derived neurotrophic factor (BNDF) and neurone-specific enolase (NSE) were also determined using ELISA, hoping to provide theoretical and experimental basis for the prevention and treatment of hypertensive cerebrovascular disease.A total of 50 patients with hypertensive cerebrovascular disease treated in Gansu Provincial Hospital from December 2016 to December 2018 were selected as the experimental group. In addition, 50 people with normal physical examination were selected as the control group, and they all signed the informed consent form. Inclusion criteria are as follows: subjects meeting the diagnostic criteria for hypertension in the Hypertension Prevention and Treatment Guideline, those who volunteered to participate in the study and signed the informed consent, and those receiving no treatment previously. Exclusion criteria are as follows: diabetic patients, those with secondary infection + severe hepatic and renal dysfunction, or those with acute myocardial infarction. All clinical specimens in this experiment were obtained upon the agreement of the Ethics Committee of Gansu Provincial Hospital and family members. The clinical research protocol was approved by the Ethics Committee of Gansu Provincial Hospital. The specific clinical data of the patients were collected at the time of admission, including age, gender, weight, physical condition, and hypertension classification , and theSerum biochemical indexes of hepatic and renal function will be affected by many diseases, and hypertensive cerebrovascular disease is no exception. Five mL of venous blood was drawn from the arm and placed in an EP tube containing an anticoagulant, followed by centrifugation at 2000 g for 15 min at room temperature. The supernatant was collected to detect the hepatic and renal function indexes BUN, SCR, AST, and ALT, so as to provide an important theoretical reference for early treatment.The left ventricles of patients were auscultated using a stethoscope in a quiet state, and the heartbeats per minute were recorded 3 times. After the cuff of the sphygmomanometer was wrapped around the patient's arm, the rubber ball was squeezed to gradually elevate the mercury column until no pulse of the brachial artery was heard by the stethoscope, at which moment the value in the sphygmomanometer was the systolic blood pressure. Then, the cuff was slowly deflated, and the value in the sphygmomanometer was the diastolic blood pressure at the moment when the sound turned from strong to weak. In the experimental group, the patients were grouped based on the expressions of serum ADPN, hs-CRP, and sICAM-1, and the cerebrovascular complications were recorded, mainly including cerebral hemorrhage, stroke, and cerebral infarction. The specific diagnostic criteria are as follows: a history of hypertension, heart disease, etc.; acute onset of all or local brain damage; and corresponding lesions or related diseases detected by CT. In the experimental group, ADPN < 2 mg/L, hs − CRP < 4 mg/L, and sICAM − 1 < 500 ng/mL indicated the low expression, otherwise the high expression –19.In patients with hypertension, the biochemical indexes of blood lipids will be changed, so their changes can be detected to indicate the occurrence and development of disease. Five mL of fasting peripheral venous blood was drawn in the morning and placed in the EP tube containing anticoagulant EDTA, followed by centrifugation at 3500 g for 10 min at room temperature. The supernatant was collected to detect the blood lipid indexes TG, TC, LDL, and HDL, so as to provide an important theoretical reference for early treatment.In the morning, 5 mL of peripheral venous blood was drawn on an empty stomach in each group, placed in an EP tube containing anticoagulant EDTA, and centrifuged at 3000 g for 10 min at room temperature. The supernatant was collected to detect the changes in content of serum ADPN, hs-CRP, and sICAM-1 according to the instructions of the ELISA kits (Nanjing Jiancheng Bioengineering Institute). Then, the absorbance of indexes in each group was measured using a microplate reader. The correlation of ADPN, hs-CRP, and sICAM-1 with the incidence rate of cerebrovascular complications was analyzed using the Pearson method.The systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd), mean blood flow velocity (Vm), and pulsatility index (PI) of each blood vessel were observed and recorded using the MEDENG CBA CV-300 cerebrovascular hemodynamic analyzer (probe frequency: 2 MHz) according to the manufacturer's instructions.In each group, 5 mL of fasting peripheral venous blood was drawn in the morning and placed in the EP tube containing anticoagulant EDTA, followed by centrifugation at 3000 g for 10 min at room temperature. The supernatant was collected according to the instructions of the ELISA kit (Nanjing Jiancheng Bioengineering Institute), and changes of serum S100, NSE, and BNDF were detected. Then, the absorbance of indexes in each group was measured using the microplate reader.p < 0.05 suggested that the difference was statistically significant. The bar graph was plotted using GraphPad Prism 5.0.All raw data obtained in the experiments were statistically analyzed using SPSS 21.0 software, and multiple comparisons were performed. The experimental results were expressed as mean ± standard deviation (p < 0.05), indicating the changes in liver and kidney metabolic functions in patients with hypertensive cerebrovascular disease, which can provide a basis for early prediction of disease.As shown in p < 0.05), suggesting the significant changes in blood pressure and heart rate of patients with hypertensive cerebrovascular disease.As shown in p < 0.05), while the content of HDL obviously declined compared with those in the control group (p < 0.05)  , suggestp < 0.05), while that of hs-CRP and sICAM-1 was evidently increased , while the BNDF level was significantly decreased (p < 0.05)  .In the experimental group, the patients were grouped based on the expressions of serum ADPN, hs-CRP, and sICAM-1, and the cerebrovascular complications were recorded. As shown in p < 0.05) and evidently higher PI (p < 0.05)  .p < 0.05), while hs-CRP and sICAM-1 were positively correlated with the incidence rate of cerebrovascular complications (p < 0.05)  .Hypertension is the most important risk factor for cerebral hemorrhage and cerebral infarction, as well as a major risk factor for cerebral hemorrhage. More than 75% of patients with hypertension and more than 80% of patients with cerebral hemorrhage are aged 50-70 years old. Cerebrovascular changes in hypertension, mainly including the increase in the arterial wall thickness, accompanied by the increased media/lumen ratio , are cloADPN synthesized in adipose tissues possesses the antiatherosclerosis, anti-inflammatory, and insulin-sensitizing effects . LindstrIn conclusion, a series of experiments in this study confirm that there are changes in the hepatic and renal function, blood lipids, and hemodynamics in patients with hypertensive cerebrovascular complications, further promoting the development of disease. Such effects can be further verified through animal experiments in the future. This study provides a theoretical basis for the pathogenesis, prevention, and treatment of hypertensive cerebrovascular complications, as well as new ideas for further research.


URIWW has collected water quality data on Rhode Island lakes and reservoirs for over 25 yr. The LAGOS-NE and URIWW datasets allowed for comparison of water quality trends at regional and sub-regional scales, respectively. We assessed regional (LAGOS-NE) and sub-regional (URIWW) trends with yearly median anomalies calculated on a per-station basis. Sub-regionally, temperature and chlorophyll a increased from 1993 to 2016. Total nitrogen, total phosphorus, and the nitrogen:phosphorus ratio (N:P) were stable. At the regional scale, the LAGOS-NE dataset showed similar trends to prior studies of the LAGOS-NE with chlorophyll a, total nitrogen, and N:P all stable over time. Total phosphorus did show a very slight increase. In short, algal biomass, as measured by chlorophyll a in Rhode Island lakes and reservoirs increased, despite stability in total nitrogen, total phosphorus, and the nitrogen to phosphorus ratio. Additionally, we demonstrated both the value of long-term monitoring programs, like URIWW, for identifying trends in environmental condition, and the utility of site-specific anomalies for analyzing for long-term water quality trends.Addressing anthropogenic impacts on aquatic ecosystems is a focus of lake management. Controlling phosphorus and nitrogen can mitigate these impacts, but determining management effectiveness requires long-term datasets. Recent analysis of the LAke multi-scaled GeOSpatial and temporal database for the Northeast (LAGOS-NE) United States found stable water quality in the northeastern and midwestern United States; however, sub-regional trends may be obscured. We used the University of Rhode Island’s Watershed Watch Volunteer Monitoring Program (URIWW) dataset to determine if there were sub-regional (i.e., 3000 km Thus, long-term data are needed to identify trends at local, regional, and national scales.Aquatic ecosystems have been altered as the result of human activities modifying nutrient cycling on a global scale . Becausea  provide data that allow for continental-scale water quality analysis. These data allow for analyses that can be useful for managing water resources by developing water quality criteria for N, P, and chlorophyll a . Studyina . Broad-sa . These ta . Despitea .2 and 1,000,000 km2 respectively, have investigated spatial and temporal water quality trends and have demonstrated that drivers explaining changes spatially may not explain changes temporally. These differences may be due to complex interactions occurring at the different scales through time (2) trends  trends . Similar regions , 2018. F regions . Given wIn this study, we focus on the state of Rhode Island for several reasons. Rhode Island has the second highest population density in the country, yet still has a mix of land use/land cover with developed areas making up ~21% of the state, forested areas ~37%, wetlands ~11%, and agriculture ~3%. The remainder of the land area is made up other land-use/land-cover classes. Given these facts, Rhode Island lakes occur across a gradient of land use/land cover and face a suite of human pressures that most lakes in the nation are also facing with nutrients and pathogens being of particular concern in the state . Lastly,a, and lake temperature? Second, are water quality trends in Rhode Island similar to regional trends in the northeastern United States? Another objective of this paper was to apply existing methods for examining long-term climate records , total phosphorus (TP), total nitrogen-to-total phosphorus ratio (TN:TP), chlorophyll ds e.g.,  to water.4306765 .The study area for this analysis includes lakes and reservoirs in the state of Rhode Island where data were collected by the University of Rhode Island’s Watershed Watch program  which ala and in deep lake (>5 m) dissolved oxygen. Water samples are collected three times per season (May through October) to be analyzed for nutrients and bacteria.The URIWW program began in 1988, monitoring 14 lakes, and has now grown to include over 250 monitoring locations on over 120 waterbodies, including rivers/streams and estuaries, with more than 400 trained volunteers. URIWW now provides more than 90% of Rhode Island’s lake baseline data and is an integral part of the state’s environmental data collection strategy. Data quality assurance and control is treated with paramount importance; volunteers are trained both in the classroom and in the field, regular quality checks occur, and volunteers are provided with all the necessary equipment and supplies, along with scheduled collection dates. For freshwater lakes and reservoirs, weekly Secchi depth and water temperature are recorded, along with bi-weekly chlorophyll a. In particular, we selected URIWW lakes and reservoirs  that matched the following criteria: (1) were sampled between 1993 and 2016; (2) were sampled in May–October; (3) had at least one sampling event per year in May through June, at least one sampling event per year in July through August, and at least one sampling event per year in September through October; (4) had at least one sampling event from 1993 to 2004 and 2005 to 2016; and (5) were sampled at a depth of 2 m or less. As not all sites have data for all selected years, we further filtered the data to select sites that had at least 10 yr of data for a given parameter within the 1993–2016 time frame. The final dataset used in our analysis included 60 lakes and reservoirs. Of these sites, our filtered dataset had 58 sites measured for temperature, 58 sites measured for chlorophyll a, 54 sites measured for TN, and 55 sites measured for TP. Of the 60 sampling sites, 51 had data for all five parameters. The N:P ratio was calculated by dividing the mass concentrations of total nitrogen and total phosphorus and then converting to a molar ratio by multiplying by 2.21 .For this analysis, we were interested in trends in lake temperature, TN, TP, TN:TP, and chlorophyll https://web.uri.edu/watershedwatch/uri-watershed-watch-monitoring-manuals/ and https://web.uri.edu/watershedwatch/uri-watershed-watch-quality-assurance-projectplans-qapps/, respectively. These methods, approved by both the state of Rhode Island and the U.S. Environmental Protection Agency, have remained fairly consistent, although over the nearly 30 yr changes did occur. When new methods were introduced, comparisons between old and new methods were conducted and in all cases no statistically significant differences were found with the new methods. Furthermore, the new methods did at times improve the limits of detection; however, this impacted a very small number (<1%) of measurements in this study. We did run our analyses , Vermont, New Hampshire, and Maine . We repe samples . At the We use data, also from LAGOS-NE, on landscape composition, maximum lake depth, and lake area . We use https://github.com/USEPA/ri_wq_trends/ and are archived at https://doi.org/10.5281/zenodo.4306765 . The slope of this line provides information on the average yearly change of that parameter over the time period studied.Testing for a regression slope being different than zero can be used to test for monotonic trends in water quality data . We usedP value cut-offs to assesses significance  relative frequency of high and low years in the beginning and end of the time frame are used to identify an increasing or decreasing pattern, and (3) the magnitude of the slope is used to infer an ecologically relevant change. Using all of this information, we determine that a trend exists if it meets at least 2 of the 3 criteria, a weak trend exists if it meets one of the criteria, and no trend exists if it meets none of the criteria.Traditionally, trends would be determined by assessing significance but recent guidelines suggest not using arbitrary ificance . Our intWe recognize that ecologically relevant change is system-dependent and no single value will be universally appropriate. We are using several values for this particular assessment, but other values could also be justified. There are various ways to identify important temperature changes in lakes and reservoirs. A policy-based approach could examine agreements that attempt to limit temperature increases, such as the Paris Agreement, which aims to limit increases over the next century to 2°C, which would be 0.02°C per year or, the state of Rhode Island criteria for temperature increase is 2.2°C or 0.022°C per year over a century , UN 2015For changes in chlorophyll, total phosphorus, and total nitrogen, we define an ecologically meaningful trend as one that would result in any oligotrophic lake changing to a mesotrophic state over the course of a century. We use the values defined by the trophic state limits in An ecologically meaningful trend for TN:TP could be one that would suggest a switch from nitrogen limitation to phosphorus limitation over a century. To identify this, we use information from experimental manipulations of nitrogen in lakes that identify those lakes as being nitrogen limited . In DownLakes and reservoirs in Rhode Island tended to be smaller and shallower, on average, than lakes included in the complete LAGOS-NE region . Also, Ra of 3.5 μg/L , and the majority of years with median temperature greater than the long-term median are occurring in the second half of the time period . The slope of 0.12 μg/L is greater than our threshold of 0.035 μg/L and the above-average years have mostly occurred in the most recent years  but the years greater than the median are distributed evenly throughout time. Also, a slope of 1.3 μg/L per year is lower than our threshold value of 3.5 μg/L suggesting little support for a meaningful ecological change over time , and years that are over the median do not show any pattern (P = 0.61) suggesting little evidence for a change in the concentrations of TN relative to the concentrations of TP . However, at the more localized scale of the state of Rhode Island, there is a clear increasing trend in chlorophyll a.Our sub-regional analysis indicates that increases in primary production, as measured by chlorophyll a show increasing trends from 1993 to 2016 in Rhode Island lakes and reservoirs  were sparse. There is no ecological or statistical trend in the years with consistently available data. The general picture in Rhode Island appears to be no increase in nitrogen, no trend in phosphorus, and little to no change in the TN:TP ratio . We intea may still occur. Additionally, our analysis points to the fact that chlorophyll a and algal biomass is driven by processes operating at different scales. For instance, nutrient management is largely a local to watershed scale effort, but may also be regional as atmospheric nitrogen deposition can be a significant source of nitrogen , whereas the site-specific anomalies correctly show no trend as each site did not change over time  although other data could possibly be used to estimate the long-term medians. In short, site-specific anomalies do require relatively large datasets and decisions on appropriate levels of aggregation, as with any analysis using aggregation, must be made carefully.Lastly, this analysis is only possible because of the availability of sound, long-term data on water quality in Rhode Island. Without the URIWW data and the commitment and participation of more than 2500 volunteers over the years, our analyses would have been impossible. Going forward, it is important to appreciate the role that volunteer monitoring and community science programs can play in capturing and better understanding long-term environmental trends.


Background: Antisocial behaviours make social interactions difficult among students. Moral emotions, online empathy, and anger management are social and emotional variables related to prosocial and antisocial behaviours and health problems. This research aims to assess the impact of Cooperative Project-Based Learning intervention on these three variables for Primary Education students. Additionally, the relations of these variables with key competencies, such as social and emotional competencies and literacy competence, were studied. Method: This research is made up of two studies, descriptive and quasi-experimental, during regular school hours. The descriptive study was carried out with a sample of 516 primary school students and aimed to assess the development of the three variables, taking into account personal and ethnic-cultural factors. The quasi-experimental study, with pre-test and post-test data, had the participation of 145 students to study the incidence of these variables after Cooperative Project-Based Learning intervention in Primary Education. Results: The results show the relation among the cited variables and the positive impact of the intervention on moral emotions and anger management in the experimental group compared to the control group. Experimental group girls presented higher scores in moral emotions than control group girls. Conclusion: These results open new research lines in relation to the intervention as a programme to prevent the appearance of antisocial behaviours and health problems at school. Positive social relationships can be altered by the appearance of antisocial behaviours, such as aggression, violence, or truancy, among others, which transgress moral and social norms . AntisocThe appearance of antisocial behaviours is also associated with a low level of empathy . EmpathyProsocial behaviours happen face-to-face, but they also happen when students interact online through social networking sites, online video games, e-mail, chats, or text messages. The adolescent population could misuse both the Internet and online social networks ,21, whicAttention control, such as anger management, is a regulating mechanism that is also important to ensure adequate social interaction and avoid antisocial behaviours . ProsociSchools must promote different dimensions of learning, including cognitive, social, emotional, and moral competencies, in their goal of promoting a comprehensive education . A EuropAn intervention based on Project-Based Learning, as a didactic method, could allow students to enhance key competencies, especially social, emotional, and moral competencies. This method promotes active participation in the learning process through social interactions and knowledge exchange . This tyCooperative Project-Based Learning, as a combined method, could also be an effective way to develop moral emotions, online empathy, and anger management in students in Grades Four, Five, and Six of Primary Education. For this reason, the main objective of the study is to analyse the impact of a specific intervention to enhance moral emotions, online empathy, and anger management. Before the analysis of the interventions’ impact, the three variables will also be analysed, taking into account personal factors such as age, sex, or ethnic-cultural group. Moreover, these personal factors will be analysed through their relationship with each other and with other variables, such as social and emotional competencies, empathy, and literacy competence, which have been described in an earlier study .Two different samples have participated in this research according to the two studies: descriptive and quasi-experimental see . Both saM = 9.17, SD = 0.53), 137 5th graders , and 153 6th graders . The students’ age range was 8 to 12 years old . The sample was divided into two groups, according to their ethnic-cultural group. The majority group consisted of 429 (83.1%) students, and the minority group consisted of 87 students (16.9%). The ethnic-cultural minority group included the gipsy ethnic group and immigrants: 24 (4.7%) students self-identified as members of the gipsy ethnic group (13 with both parents identifying as gipsy and 11 with at least one gipsy parent), and 63 students were immigrants (12.2% of the sample), including those who do not have Spanish nationality or children who, even though they have the Spanish nationality, have at least one of their parents with a foreign nationality. The rest of the students, not included in the minority group, were part of the majority group. The ethnic-cultural component is very similar to the average in the entire region of Andalusia, where there are approximately half a million people of the gipsy ethnic group (6.2%) and where the immigrant population represents 13.5% of the entire population [The descriptive study has a sample of 516 students (50.4% boys and 49.5% girls) from six Primary Education schools in Spain, from Grades 4, 5, and 6. The students were distributed as follows: 226 4th graders , enrolled in two lines of Grade 4, 5, and 6 during the 2017/2018 academic year. The control group consisted of 71 children (48.6% boys and 51.4% girls), and the experimental group consisted of 74 children (46.5% boys and 53.5% girls). In the same schools, the control group  included those in Grades 4 (n = 24), 5 (n = 21) and 6 (n = 26), and the experimental group  also included those in Grades 4 (n = 27), 5 (n = 21) and 6 (n = 26).The quasi-experimental study sample consisted of 145 children (47.6% boys and 52.41% girls), with an age range of 8 to 12 years  was completed for all research participants. At the end of that academic year, the questionnaire was given to both groups again, post-test (Time 2). At the beginning of the academic year, the researchers analysed the lesson plan of both groups. Additionally, the researchers were in contact with the teachers during the whole academic year, supervising the lesson plan in both groups. The intervention was carried out only in the experimental group by the regular teachers in the classroom, during regular lessons. The teachers of the experimental group received a three-hour training session for the adequate implementation of the intervention. The teachers were in permanent contact with the researchers during the intervention to facilitate a common experience in the different groups. In the control group, the intervention was not implemented, and students followed textbook activities according to the grade. The control group did not develop any cooperative activity or project-based methods during the academic year.In both studies, the students completed the questionnaires individually, as one more class activity, during school hours. Data collection was always carried out by a member of the research team, in the presence of the teachers who were responsible for each group. Teachers did not have access to individual questionnaires at any time. The researchers obtained the necessary authorisations, and the participants were informed of the objective of the research, the process, and the expected duration. Ethical Standards of American Psychological Association’s Ethics Code and the Ethical Committee of University of Córdoba  were followed for the study.The teachers of the experimental group students carried out an intervention of Cooperative Project-Based Learning  during tkamishibai . In a periodical inter-class activity, these groups of students tell the stories to groups of students of lower grades. When a group finishes creating a story, they begin creating another. At the end of the academic year, all of these stories created by the different groups were compiled into a book.The cooperative project has as its main objective to create several stories that teach prosocial values: respect, forgiveness, friendship, generosity, tolerance, effort, and peace. Creating a story is sequenced in four activities. The first activity consists of describing characters; in the second activity, the students have to describe a place; in the third activity, they have to make up the story using the characters and the place from the previous activities; and, finally, in the fourth activity, they have to divide the story into scenes, and they could learn and teach the values using a The students of the experimental group were grouped in cooperative base groups of 3–4 students. Each cooperative base group includes four roles: spokesperson, evaluator, evaluators’ assistant (when there were four members in the group), and material manager. These roles rotated when project activity was changed. Individually, each student has to propose a personal objective before each of the activities that made up the project. At the end of the activity, each student carries out a self-reflection exercise to achieve this objective. These reflective objectives deal with attitudes and behaviours that the students had with the rest of the partners in the cooperative base group during the interaction of the activities.The control group students maintained the usual curriculum and did not carry out any similar intervention activities.Moral Emotions Scale, Online Empathy Questionnaire, Anger Management Questionnaire, Social and Emotional Competencies Questionnaire, Basic Empathy Scale, and Literacy Proficiency Test.Information has been collected through an instrument composed of seven parts: personal data , The Moral Emotions Scale [ns Scale  is made The Online Empathy Questionnaire [Basic Empathy Scale [empathy through electronic devices. The instrument is made up of seven items that are Likert type answers from 1 to 5, where 1 is “Totally disagree” and 5 is “Totally agree”. This scale has two factors: online affective empathy and online cognitive empathy. The reliability of this research was high, in both the descriptive study (α = 0.80 and Ω = 0.80) and the quasi-experimental study, pre-test (α = 0.83 and Ω = 0.83), and post-test (α = 0.73 and Ω = 0.73).ionnaire  is an inhy Scale , and is The Anger Management Questionnaire is made up of four Likert type response items from 1 to 5, where 1 is “Totally disagree” and 5 is “Totally agree”. Confirmatory factor analysis was performed with the sample of 516 children and shows that the data obtained good scores in the different fit indices . The reliability of the instrument is adequate (α = 0.76 and Ω = 0.76) for the descriptive study sample and for the quasi-experimental study sample, pre-test (α = 0.72 and Ω = 0.73), and post-test (α = 0.77 and Ω = 0.78).The Social and Emotional Competencies Questionnaire (SEC-Q) [social and emotional competencies: self-awareness (four items), self-management and motivation (three items), social awareness and prosocial behaviour (six items), and decision-making (three items). The items are presented with Likert type responses from 1 to 5, where 1 is “Totally disagree” and 5 is “Totally agree”. The instrument has a high reliability in the descriptive (α = 0.80 and Ω = 0.86) and in the quasi-experimental study, pre-test (α = 0.82 and Ω = 0.82), and post-test (α = 0.85 and Ω = 0.85). (SEC-Q)  is compoThe Basic Empathy Scale (BES) [affective empathy (11 items) and cognitive empathy (nine items). The items are presented on a Likert scale where 1 is “Totally disagree”, and 5 is “Totally agree”. The reliability is high in the descriptive study sample (α = 0.83 and Ω = 0.82); quasi-experimental study, pre-test (α = 0.83 and Ω = 0.84), and post-test (α = 0.81 and Ω = 0.82).le (BES) , validatle (BES) , consistThe Literacy Proficiency Test [listening, reading, and writing. The listening part begins with the teacher reading a story, and the children answer various questions about the story. In the reading part, children answer written questions about a text that they had previously read. In the third part of the test—writing—students write a story based on an image. These tests are evaluated using two scales: the first scale measured comprehension (listening and reading), and the second scale measured expression (writing). Both scales were divided into six levels, including A1 (the most basic/introductory level), A2, B1, B2, C1, and C2 (mastery of proficiency level) based on the criteria from [writing A1 level is “He/she vaguely describes tangible realities that know or see using words”, and C2 level is “He/she rebuilds information and arguments from various sources, and presents them in a coherent and originally summarised way”. This instrument has been used by other researchers with the same samples [ncy Test  is basedncy Test  and asseria from . For exa samples ,50. The The psychometric properties of the questionnaires were checked. The reliability coefficient was analysed through Cronbach’s alpha and McDonald’s Omega, using Factor 10.5.2. In the case of the Anger Management Scale, due to no previous use of the scales in Primary Education children, confirmatory factor analyses were performed with EQS 6.2, which were adjusted to the robust maximum likelihood method and polychoric correlations (Satorra–Bentler chi-square). The data analyses were carried out using SPSS 25, and the effect size was estimated with the Campbell Collaboration calculator.t-test, and Levene’s test was performed to identify the homogeneity of the variances. The groups were compared with Cohen’s d with 95% CI, to show the strength of the relationships of moral emotions, online empathy, and anger management.Descriptive and comparative analyses were carried out with the first sample. The means of the variables with two groups were compared using the Student’s moral emotions, online empathy, and anger management) and age, social and emotional competencies, empathy, and literacy competence to find out possible relationships. The prediction of literacy competence and its factors, as dependent variables, were analysed using a cross-sectional linear regression  and with a longitudinal linear regression (predictor variables at time 1 and literacy competence and its factors at time 2).Correlations were calculated between the main study variables . The difference in moral emotions . According to sex, no significant differences were found in moral emotions . The scores of the students of the ethnic-cultural majority group did not show significant differences from the students of the ethnic-cultural minority group .Age did not show a significant correlation with online empathy , including its two factors; online empathy affective  and online empathy cognitive . Scores for online empathy  and their online affective empathy factor  showed no significant differences between boys and girls. However, scores for the online cognitive empathy factor showed significant differences between girls and boys . The scores of the students of the ethnic-cultural majority group did not show significant differences from the students of the ethnic-cultural minority group  and its factors: online affective empathy  and online cognitive empathy .Age did not show a significant correlation with Anger management  had a significant and negative correlation with age. No significant differences were found between boys and girls in anger management . The scores of the students of the ethnic-cultural majority group did not show significant differences from the students of the ethnic-cultural minority group .Moral emotions, online empathy, including its online affective empathy and online cognitive empathy factors, and anger management correlated positively and significantly. The correlations also show that moral emotions and anger management are significantly and positively related to social and emotional competencies, including all of its factors, and to empathy. Moral emotions correlated significantly with both factors: online affective empathy and online cognitive empathy. However, anger management only correlated significantly and positively with online cognitive empathy. Online empathy and its two factors correlated significantly and positively with empathy and its two factors, and with social and emotional competencies and some of its factors. Moral emotions, online empathy, and anger management did not significantly correlate with literacy competence . Four statistically significant cross-sectional models were estimated , listening , reading , and writing . Personal variables  and self-awareness were predictors in four models. Besides these variables, affective empathy was a predictor of literacy competence, and social-awareness and prosocial behaviour were predictors of listening.In the descriptive study, a first linear regression was performed to investigate the independent relationships between the predictors and ated see : literacliteracy competence were studied through a second linear regression, which was performed with moral emotions, online empathy, anger management, social and emotional competencies, empathy, and personal variables . Four statistically significant longitudinal models were estimated , listening , reading , and writing . Intervention group was a predictor in all four models. Besides this variable, age and self-awareness were predictors of literacy competence, listening, and reading.Longitudinal predictors of ated see : literacmoral emotions  and anger management  increased significantly after intervention in the experimental group compared to the control group. Online empathy  and its online affective empathy factor  showed a slight decrease in the scores of both groups, but these were not significant. Online cognitive empathy  showed an increase in the scores of the control and experimental groups, but there are also no significant differences.No significant differences between pre-test control and experimental groups were found in three variables see . Howevermoral emotions , online empathy , nor in their factors; online affective empathy  and online cognitive empathy ; and anger management .No significant differences at pre-test between control and experimental groups were found in three variables in boys see  or girlsonline empathy scores , including their factors online affective empathy  and online cognitive empathy , and anger management . However, the scores of the girls in the experimental group show significant differences with respect to the scores of the girls in the control group in moral emotions .As in the boys’ scores, there were no significant differences among the girls in both groups in the Moral emotions, online empathy, and anger management are important variables in the social , emotionMoral emotions have diverse relations with personal characteristics. Moral emotions were not correlated with age. This result would be in line with another study , which dThere was no relation between online empathy and age. Significant correlation between age and face-to-face empathy were found in 14–25 year olds , and chiAnger management has shown a significant and negative correlation with age, but no significant differences between boys and girls. Boys were more aggressive than girls, and older students were more aggressive than younger ones . The IntA previous study , with thThe results of the current research show that the use of Cooperative Project-Based Learning has produced benefits in the moral emotions and anger management of the experimental group by including prosocial values in the literacy area. In the same way, this happened in another study  with socThe intervention shows more unexpected results, such as that girls in the experimental group showed significant differences in the scores of moral emotions compared with the girls in the control group, while the boys in the experimental group did not show significant differences from the scores of the boys in the control group in any of the variables. A quasi-experimental study  also fouThe descriptive study shows the development of moral emotions, online empathy, and anger management in Primary Education, detailing analyses by sex and age. This study also showed the existing correlation with social and emotional competencies, including face-to-face empathy. The quasi-experimental study showed the positive impact of a Cooperative Project-Based Learning intervention on moral emotions and anger management when elements of social, emotional, and moral learning are introduced into literacy plan lessons.Schools must contribute to the total development of students. For this reason, the Council of Europe  advises The present study yields hopeful findings for improving the education of Primary Education students. The sample size is a limitation, which does not allow wide generalisation of the conclusions. Therefore, it is necessary to continue more studies on Primary Education, with more participants involved in other educational stages, to expand the knowledge of the study variables. The findings open new lines of research.The first line of research would be to analyse the possible causes of personal differences—as well as among different variables—and effects of new proposals that affect social, emotional, and moral development. The differences by sex were shown in the descriptive part of the study. New research is needed to verify didactic and organisational innovations that also allow enhancing the development of the social, emotional, and moral aspects in boys in pursuit of gender equality. Roseth  suggestsThe second research line would provide more information on the relationship between moral emotions, online empathy, anger management, and antisocial behaviours at school. A study carried out in middle schools  indicate


Besides, patients with seronegative HT had lower somatic anxiety than patients with HT who tested positive . Besides, no statistically significant difference was found between patients with HT and controls with regard to somatic anxiety. The present study suggests the relevance of alexithymia in patients suffering from HT, which may be intertwined with a possible state of underreported depression that is mainly expressed through physical complaints. Promoting the capability to describe and communicate feelings could contribute to psychological elaboration and coping with the disease and, consequently, to the improvement of self-management and perceived HRQoL.Emotion-processing impairment represents a risk factor for the development of somatic illness, affecting negatively both health-related quality of life (HRQoL) and disease management in several chronic diseases. The present pilot study aims at (i) investigating the associations between alexithymia and depression, anxiety, and HRQoL in patients with Hashimoto’s thyroiditis (HT); (ii) examining the association between these three psychological conditions together with HRQoL, and thyroid autoantibodies status as well as thyroid echotexture in patients with HT; and (iii) comparing the intensity of all these clinical psychological features in patients with HT versus controls. Twenty-one patients with serologically or ultrasonographically verified HT and 16 controls with non-toxic goiter or postsurgical hypothyroidism were recruited for this study. Serum thyrotropin (TSH) and free thyroxine, as well as thyroid autoantibodies (thyroglobulin antibodies and thyroid peroxidase antibodies), were assayed. Alexithymia, depression, anxiety, and HRQoL were assessed with Toronto Alexithymia Scale; Beck Depression Inventory, second edition; Hamilton Anxiety Rating Scale; and Health Survey Short-Form 36, respectively. A negative relationship between the difficulty to describe feelings and the cognitive component of depression was found ( Increasing interest exists regarding the crucial role of psychological factors predicting somatic diseases and influencing the management of chronic illness . Indeed,In this regard, the conceptual construct of alexithymia—defined as the inability to identify and describe feelings, accompanied by an externally oriented thinking—is of primary importance , becauseAmong the most frequent endocrinologic pathologies, it is known that hypothyroidism, which is characterized by failure of the thyroid to produce adequate amounts of thyroid hormones, affects approximately 5% of the adult population . HypothyTo the best of our knowledge, only three studies focused on the relationship between alexithymia and thyroid diseases, one of them including women in the postpartum setting  and two The present cross-sectional, pilot study aims at (i) investigating the associations between alexithymia and depression, anxiety, and HRQoL in patients with HT; (ii) examining the association between these three psychological conditions and HRQoL, and both thyroid autoantibodies status and thyroid echotexture in patients with HT; and (iii) comparing the intensity of such psychological conditions and HRQoL scores in patients with HT versus controls.Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria  and thyroid peroxidase antibodies (TPOAb)], whereas the second consisted of ultrasonographic evidence of hypoechoic and inhomogeneous echotexture of the thyroid. All patients with HT were on replacement therapy with levothyroxine. Patients with nodular goiter or with levothyroxine-replaced postsurgical hypothyroidism were enrolled as controls. All patients with nodular goiter were euthyroid , tested negative for both TgAb and TPOAb, and had normal thyroid echogenicity at ultrasound, whereas all patients who had been thyroidectomized were necessarily on levothyroxine. Patients who were thyroidectomized for thyroid nodules, whose serum TgAb and TPOAb were both negative prior to surgery, and whose thyroid histology demonstrated benignity of the nodule and histological absence of lymphocytic thyroiditis were eligible as controls. Exclusion criteria for both HT patients and controls were age <18 years; neuropsychiatric disturbances according to the criteria ; and seronfirmed . FinallyBlood was drawn in the morning (8–9 AM) after an overnight fasting a few days prior to the visit. Serum TSH, thyroxine (FT4), and thyroid autoantibodies were assayed by an immunometric method in patients with HT and controls and evaluated by a physician. Demographics  and body mass index (BMI) were collected during the visit.DSM-5—Research Version   .The Italian version of the Toronto Alexithymia Scale (TAS-20)  was usedThe Beck Depression Inventory, second edition (BDI-II), was administered to measure depressive symptoms. It consists of 21 items scored on a four-point Likert scale from 0 (not present) to 3 (severe) , allowinThe Hamilton Anxiety Rating Scale (HAM-A) was employed to measure anxiety symptoms. It consists of 14 items scored on a five-point Likert scale from 0 (not present) to 4 (severe) , allowint scores with a general population mean of 50 and a standard deviation (SD) of 10, with highest values indicating better perceived HRQoL. In the present study, the reliability (Cronbach’s α) of the measure was 0.71 and 0.79 for PCS and MCS, respectively   was usedectively .2 test or the Fisher exact test, as appropriate. The independent-samples Mann–Whitney U test was conducted to compare patients with HT versus controls. Spearman ρ was run to examine the correlations between TAS-20 scores and BDI-II, HAM-A, SF-36 PCS, and SF-36 MCS scores, and between these scores and thyroid autoantibodies status and thyroid echotexture in patients with HT. As the multiple comparisons that we run could inflate type I error , we further considered the effect size [and relative confidence intervals (CIs)] of the observed relationships, using the following cutoffs: r values of 0.1, 0.3, and 0.5 to test the strength of associations . Categorical variables were analyzed by the χciations . FinallyThe study was approved by the Ethical Committee of the University Hospital “G. Martino,” Messina, Italy, protocol identifying number 80/19, 16/09/2019. This study complies with the 1964 Helsinki Declaration and its later amendments. All participants were adequately informed about the scientific purpose of the study and gave their informed written consent. All data were analyzed anonymously.p = 0.055]. Age and BMI were similar in the two groups . Finally, most of participants had secondary or higher education level, with no difference between HT patients and controls .Women outnumbered men both in HT patients and in controls with a greater preponderance in the first group  ] .U = 15.50, p = 0.013, r = -0.68)   . As expe= -0.59) , with TP= -0.59) .No significant difference was found in scores obtained from the psychodiagnostic evaluation between patients with HT and controls .Although autoimmune thyroid diseases are considered risk factors for both depression and anxiety , the relIn our study, we found an overall prevalence of frank or possible alexithymia in 89.2% of cases, supporting the hypothesis that patients with HT and controls  may be affected by difficulty in identifying and describing feelings to a significant extent, thus focusing on external events rather than on inner experiences . Mean BDAnother interesting finding was the positive correlation between somatic anxiety and thyroid autoantibodies status in patients with HT, assessed through TgAb and TPOAb levels that provide serological evidence of autoimmune thyroiditis. This appears in line with a previous study showing that thyroid autoimmunity may be a high risk factor for anxiety disorders, as psychopathological disturbances and the autoimmune reaction are hypothesized to be rooted in the same aberrancy in the immunoendocrine system . From a Finally, no significant difference was found between patients with HT and controls in all the assessed psychological factors . In this regard, we should hypothesize that the small size of both groups may have prevented to reach statistical significance. Another limitation of the present pilot study is its cross-sectional design, which can limit generalizability of our findings. Consequently, no causal relationships can be inferred about the found association between the participants’ psychological status and thyroid autoantibodies. Finally, the use of self-report measures could represent another limitation, despite the gold-standard clinical psychological interview, which conferred a specific objectivity to the performed surveys.Future larger, longitudinal studies could provide more robust evidence, which is what we aim at performing in perspective research, considering also variables such as disease duration and thyroid-specific HRQoL questionnaires in order to provide more accurate disease-specific information , 2018. AOur study shows that the majority of patients with thyroid diseases—including both those with HT and controls—are alexithymic or potentially alexithymic and that patients with HT may harbor a possible underreporting of depression. Hence, potential benefits may derive from clinical psychological interventions in these patients. Promoting the capability to describe and communicate feelings could contribute to psychological elaboration and coping with thyroid diseases and, consequently, to the improvement of self-management and perceived HRQoL.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study was approved by the Ethical Committee of the University Hospital “G. Martino,” Messina, Italy, protocol identifying number 80/19, 16/09/2019. This study complies with the 1964 Helsinki Declaration and its later amendments. All participants were adequately informed about the scientific purpose of the study and gave their informed written consent. All data were analyzed anonymously.GM made significant contributions to the design of the research study, drafting of the manuscript, interpretation of the data, and revision of the manuscript. AC performed the statistical analysis, provided the interpretation of data, and gave significant contribution to the draft part of the manuscript. CV, UF-R, and TW provided substantial contribution in the drafting part of the manuscript and revised it critically. MQ and SB critically revised the manuscript. RV provided significant contribution in participants’ recruitment, drafting part, and revision of the manuscript. All authors gave their final approval of the manuscript to be submitted.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Objective: Neuropathic pain (NP) associated with depression or anxiety is highly prevalent in clinical practice. Publications about NP associated with depression or anxiety increased exponentially from 2000 to 2020. However, studies that applied the bibliometric method in analyzing global scientific research about NP associated with depression or anxiety are rare. This work used the bibliometric method to analyze the publications on NP associated with depression or anxiety between 2000 and 2020.Method: Publications from 2000 and 2020 were identified from the Thomson Reuters Web of Science (WoS) database. We employed CiteSpace V to conduct the bibliometric study.Results: A total of 915 articles or reviews were obtained from the WoS database. The number of publications has increased over the last two decades. The USA was the most productive among countries or regions in the field. According to the burst key words, neuroinflammation, hippocampus, safety, and modulation were the hot global research issues in the domain.Conclusion: Publications about NP associated with depression or anxiety have remarkably increased from 2000 to 2020. These historical opinions about NP associated with depression or anxiety could be an important practical basis for further research into potential development trends. Neuropathic pain (NP) is associated with various conditions involved in a lesion or disease of the somatosensory nervous system . The 915 studies were cited 28,689 times . The number of citations also increased from 11 in 2000 to 4,290 in 2020. A statistically significant change occurred in the percentage of citations from 2000 to 2020  with time.Each review or article was labeled with at least one subject category in the WoS database. Sixty-seven subject categories were dedicated to the 915 publications about anxiety or depression and NP. The top 15 subject categories in terms of the number of publications are shown in In Sixty-three countries or regions were involved in the 915 articles on NP associated with anxiety or depression. In total, 1,513 institutions published studies on NP and anxiety or depression . The topThe 915 articles on NP with anxiety or depression were written by 4,541 authors. In terms of the number of publications, the top three most productive authors were Rice ASC (16 publications), Wang J (13 publications), and Maione S (11 publications). Rice ASC had the highest H-index (14). The connections between these productive authors are represented in Q value implies the significance of community structure, that is, a Q > 0.3 corresponds to a significant community structure. The Q value for this work was 0.7671. “Cytokines” was the largest cluster (#0), followed by “randomized” (#1), “diabetic neuropathy” (#2), and “sensorial phenotype” (#3).The analysis of references is an important factor in a bibliometric study. The results in According to the strongest citation bursts, the top 33 keywords from 2000 included NP and amitriptyline, and those from 2002 included postherpetic neuralgia . The keyThe top 10 publications on NP and anxiety or depression are listed in The current study provides a bibliometric analysis of publications on NP associated with depression or anxiety from 2000 to 2020. It revealed that NP associated with depression or anxiety has been widely researched within the last two decades. Anxiety and depression occur frequently among patients with NP. Moreover, the quality of life and well-being of patients with chronic NP are more affected than those of patients with chronic non-NP, which is not caused by damaged or irritated nerves  had less than 30 annual publications. The second time period (2007–2015) had a steady increase in annual publications. The third time period (2016) showed a downward trend in the number of publications (61), but the output was still higher than the average in the first time period. The fourth time period was between 2017 and 2020. The year 2019 was the turning point because it was the first year when over 100 studies were published. Thus, studies on NP associated with depression or anxiety have received increasing attention in the last 20 years.The percentage of publications increased gradually for every three-year period, and the period from 2006 to 2008 had the maximum number of citations . The 2003–2005 period had the maximum citations per paper (84.97), and 2006–2008 had the largest H-index (47) and number of publications (300). This growth in publication number does not suggest a corresponding improvement in the quality of articles because the data extraction process obtained only the number of articles in the field and could not demonstrate the quality of articles. Overall, the high values for citations only indicated that these publications received increased attention in the area.The USA had the greatest number of publications (262), followed by China (172), England (92), Canada (67), and Germany (62). Among the top 10 countries, six were from Europe, two came from North America, and two were from Asia . Among tA total of 1,513 institutions or universities supported the research on NP associated with depression or anxiety. In terms of the source of publications, two institutions or universities were from North America, two were from Europe, one was from England, and one was from Australia. Therefore, institutions or universities were not important relative to the cooperation of countries.The results represented the worldwide research on NP combined with depression or anxiety from 2000 to 2020. The three main conclusions about NP associated with depression or anxiety in terms of categories  were as follows. First, the top categories about NP associated with depression or anxiety include neurosciences, clinical neurology, anesthesiology, pharmacology pharmacy, medicine general internal, medicine research experimental, and psychiatry. Therefore, given the top subject categories about NP in these fields, future researchers could explore NP in the neuromodulation and neuroimmunology fields.Second, the burst keywords in the beginning of 2000 were NP, amitriptyline, and postherpetic neuralgia. However, the burst keywords became neuroinflammation, hippocampus, safety, and modulation by the end of 2020. This change indicates that research on NP associated with depression or anxiety increasingly shifted from phenomenon to mechanism. Moreover, the top keywords with the strongest citation began in 2000 and included NP and amitriptyline. By the end of 2020, the top keywords were “postherpetic neuralgia” (2002–2009), “gabapentin” (2005–2012), and “double-blind” (2004–2011). The research frontiers can be indicated by an in-depth analysis of these keywords . Thus, some publications from other databases, such as PubMed and EBSCO, were possibly missed. However, given the essential number of publications included in this analysis, a large part of research on NP associated with depression or anxiety was most likely included. In addition, only the articles published in the English language were considered, a feature which may have induced some bias in the analysis. Furthermore, the use of clinical terms, such as depression and anxiety in the literature, is concerning. Thus, future researchers could consider conducting clinical studies to differentiate temporary sad mood and chronic clinical depression in the field. Moreover, psychiatry-related articles commonly appeared in neurology or neurosurgery journals; thus, future scientists could consider publishing articles or reviews in journals in psychiatry fields. The last limitation is that In this study, the bibliometric analysis provided information regarding emerging trends about publications on NP associated with depression or anxiety from 2000 to 2020. The results may be useful as a basis for helping patients with NP associated with depression or anxiety and as a foundation for further research in the field. Although this work has some limitations, it exposed the research trends on NP associated with depression or anxiety. The number of publications remarkably increased from 2000 to 2020, and the publication output increased from eight studies or reviews in 2000 to 106 studies or reviews in 2020. Additionally, future researchers can explore NP associated with depression or anxiety in the neuromodulation and neuroimmunology fields and determine the sequela and interventions of NP. Furthermore, future researchers can conclude the characteristic symptoms of NP associated with depression or anxiety. Meanwhile, future researchers could consider publishing articles or reviews on NP in psychiatry journals. Therefore, this work provides a comprehensive insight into NP associated with depression or anxiety and also provides information for researchers regarding potential collaboration with other institutions, authors, research topics, and trends.K-L-ML and Y-MC: conceptualization and methodology. Y-MC: software, formal analysis, investigation, and data curation. K-L-ML: validation. H-YH and Y-MC: resources. K-L-ML and H-YH: writing—original draft preparation and writing—review and editing. H-YH: visualization, supervision, and project administration. H-YH and X-QW: funding acquisition. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Wireless capsule endoscopy (WCE) is considered to be a powerful instrument for the diagnosis of intestine diseases. Convolution neural network (CNN) is a type of artificial intelligence that has the potential to assist the detection of WCE images. We aimed to perform a systematic review of the current research progress to the CNN application in WCE.I2 was used for the evaluation of heterogeneity.A search in PubMed, SinoMed, and Web of Science was conducted to collect all original publications about CNN implementation in WCE. Assessment of the risk of bias was performed by Quality Assessment of Diagnostic Accuracy Studies-2 risk list. Pooled sensitivity and specificity were calculated by an exact binominal rendition of the bivariate mixed-effects regression model. 16 articles with 23 independent studies were included. CNN application to WCE was divided into detection on erosion/ulcer, gastrointestinal bleeding (GI bleeding), and polyps/cancer. The pooled sensitivity of CNN for erosion/ulcer is 0.96 , for GI bleeding is 0.97 (95% CI 0.93–0.99), and for polyps/cancer is 0.97 (95% CI 0.82–0.99). The corresponding specificity of CNN for erosion/ulcer is 0.97 (95% CI 0.93–0.99), for GI bleeding is 1.00 (95% CI 0.99–1.00), and for polyps/cancer is 0.98 (95% CI 0.92–0.99).Based on our meta-analysis, CNN-dependent diagnosis of erosion/ulcer, GI bleeding, and polyps/cancer approached a high-level performance because of its high sensitivity and specificity. Therefore, future perspective, CNN has the potential to become an important assistant for the diagnosis of WCE.The online version contains supplementary material available at 10.1007/s00464-021-08689-3. Wireless capsule endoscopy (WCE) is a powerful medical instrument for the screening and diagnosis of intestine diseases . Accordi“Deep learning” is an advanced form of machine learning, which is classified and fed back through multi-layer feature extraction . The mosIn the field of endoscopy, the CNN model under supervised learning is the most widely used artificial intelligence (AI) method and is growing mature. The application of it can be divided into two groups: Computer-aided examination and diagnosis , which iThus, deep learning has the potential to automatically detect diseases and shorten WCE reading time. In this study, we constructed a systematic review and meta-analysis to assess the application and performance of CNN for WCE.We conducted this review in accordance with the Preferred Reporting Items for systematic reviews and meta-analysis (PRISMA2020) . The GraWe systematically searched studies that assessed the accuracy of CNN for the diagnosis of gastrointestinal diseases by the use of WCE via PubMed, SinoMed, and Web of Science.The search formula and corresponding search results of each database can be achieved in Supplementary Tables 2 and 3. We searched the databases between Jan 1, 2016, and March 15, 2021. We also searched the reference list of each primary study identified and previous systematic reviews.Two reviewers (KQ and JL) independently screened the titles and abstracts to determine whether the studies met inclusion criteria. Inclusion was based on titles and abstracts, as well as the full-text article.Only those studies which are associated with both WCE and CNN can be selected. Primary studies that only use normal endoscopy or did not include the usage of CNN are excluded from our research.Furthermore, the studies had to provide sufficient information to construct the 2 × 2 contingency table . Calculation methods of accuracy, specificity, and sensitivity are shown below.We only included publications written in English. Animal experiments, reviews, correspondences, case reports, expert opinions, and editorials were excluded. Disagreements in the inclusion process were resolved by a third reviewer.To evaluate the risk of bias, two reviewers independently applied the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) risk checklist  for the Data from all included studies were collected into a standardized data extraction sheet, which included the year of publication, study design, application of pathology, type of database, algorithm, capsule brand, training set, validation set, and test set. The investigator also recorded the number of true and false positives and negatives. We contacted the corresponding authors if necessary information was needed.If a study provides multiple contingency tables related to diagnostic accuracy due to different algorithms, we assume that these contingency tables are independent of each other. We extract the contingency table with the highest overall accuracy into our study for analysis.A subgroup analysis of the three most frequent types of lesions was performed to evaluate the quality of CNN in WCE image diagnosis, which are respectively erosion/ulcer, GI bleeding, and polyps/cancer. We tabulated true positives, false negatives, false positives, and true negatives of each research, which were used to calculate sensitivity and specificity and a corresponding CI.To synthesis data, an exact binominal rendition of the bivariate mixed-effects regression model developed by van Houwelingen  was usedThe original receiver operating curve scale was used to back-transform these quantities to obtain summary sensitivity, specificity, and diagnostic odds ratios. We then used the derived logit estimates of sensitivity, specificity, and respective variances to construct a hierarchical summary receiver operating curve for CNN with summary operating points for sensitivity and specificity on the curves and a 95% confidence contour ellipsoid. Additionally, the Fagan nomogram was used for the diagnosis of CNN.I2 was used to assess heterogeneity, I2 values > 50% were considered with significant heterogeneity. Study-level covariates can be used in meta-regression to combine results from multiple studies with attention to between-study variation [ariation . To inveariation .MIDAS module for STATA (version 15) was used for the meta-regression and bivariate summary receiver operating curve analysis. Graphs were produced with the MIDAS module and the QUADAS for Revman (version 5.4).The five GRADE considerations  are used to assess the certainty of evidence in our research . We asseThe database search of us retrieved 178 articles from PubMed, SinoMed, and Web of Science. First of all, 87 repeated articles were excluded. After title and abstract screening, 59 articles were excluded; finally, 16 articles were excluded after the full-text screening, leaving 16 articles with 23 independent studies for inclusion  , GI bleeding (seven studies), and polyps/cancer (seven studies). –40In total, 69,991,447 WCE images in which there are 15,291,964 lesion WCE images were included. All of those studies are retrospective studies. 13 of them use private databases of images while 3 applied online databases.Most of the studies used CNN for automatic detection, only one of them applied handwork and CNN joint applied. Pillcam and Ankon technology are the two widest used brands of WCE. All the research reported a relatively high accuracy, which is up to 80%, while most of those studies’ sensitivity and specificity are around 90%.For the detection of ulcers and erosions, Sen Wang et al.  used 49,The summary of studies that applied CNN techniques for WCE image analysis was listed in Table According to the QUADAS-2 tool, eight of the 23 studies scored a high risk of bias in patient selection, because they did not clearly state the standard of the included images and patients, and we are not sure whether the patients’ sample is a continuous cohort over a period of time. However, all of those studies scored a low risk in index test, reference standard, and flow and timing, which guarantees a low risk of bias. The summary of the quality assessment is presented in Fig. The detection of erosion/ulcer, GI bleeding, and polyps/cancer respectively contains nine, seven, and seven independent studies. Figure The Fagan images used to describe the post-test probability are shown in Fig. p < 0.1), which were showed in the Deeks’ funnel plot asymmetry test in Supplementary Fig. 2. Substantial heterogeneity exists among the studies . Results summary of data analysis were displayed in Table Supplementary Fig. 1 presents the bivariate summary receiver operating characteristic (SROC) curves. All subgroups analysis of GI diseases scored a high risk of bias , which will hinder the observation of mucosa and affect the correct diagnosis and analysis of WCE . ReinierAt present, the research of CNN in capsule gastroscopy diagnosis is still limited in the clinical research stage. All the studies are retrospective and most of them only focus on one or two kinds of diseases rather than comprehensive diagnosis. In addition, most of the research data are from single-center, and the clinical research based on multi-center has not been published yet, which will become the direction of our future efforts.There are some limitations in our study: Firstly, the risk of bias for erosion/ulcers and polyps/cancer is relatively high. It is possibly because the number of cases of lesions like polyps or ulcer is less than that of GI bleeding, while their diagnosis of AI is much more complex, which results in fewer samples of erosion/ulcers, polyps/cancer, and leads to the differences in the data sets used for training and validation in different centers. Secondly, high heterogeneity exists among the studies included in this review, which may be due to the differences of algorithms in some studies, as well as the distinct strictness of experts in different centers for positive judgment of lesions. These limitations result in the low test-accuracy in the certainty assessment of GRADE consideration and may harm the accuracy and applicability of this review.In conclusion, our research indicates that CNN has a considerable performance in WCE image diagnosis, and its quality in accuracy, sensitivity, and specificity has reached a relatively high level. With the development of algorithms and computer hardware, the accuracy of CNN will grow higher, and it will become an important tool to help doctors diagnose and play an irreplaceable role in future clinical applications. Besides, research on big data and multi-center will also be the trend of the process of AI application on WCE. Much more data and samples from various patients as training sets are more likely to improve the accuracy and reduce the risk of bias, to achieve the necessary conditions for this technology to be used in routine clinical practice.Supplementary file1 (JPG 127 kb)Supplementary file2 (JPG 101 kb)Supplementary file3 (DOCX 47 kb)Below is the link to the electronic supplementary material.


Age and sex modified the relationships between MVPA and clinical outcomes. MVPA is associated with various beneficial outcomes across the amount of MVPA. PA plans should be tailored for individual adults with CKD.The health benefits of physical activity (PA) are well known. However, the association between an adequate amount of moderate–vigorous PA (MVPA) and clinical outcomes has limited evidence in chronic kidney disease (CKD). We assessed PA using a self-administered questionnaire. The amount of MVPA was categorized into four groups: none, low, moderate, and high . We analyzed the association between the amount of MVPA and clinical outcomes. Among a total of 1909 adults with CKD, adults with MVPA showed various beneficial outcomes compared to those with no MVPA in a Kaplan–Meier curve followed over a median of 5.9 years. In multivariable-adjusted Cox proportional hazard models, a low and a moderate amount of MVPA was associated with a lower risk of all-cause death. A moderate amount of MVPA was associated with a lower risk of cardiovascular events. A high amount of MVPA was associated with a lower risk of end-stage kidney disease in ESKD in 1324 adults with eGFR <60 mL/min/1.73 m The health benefits of physical activity (PA) are well established. It is associated with primary prevention and better clinical outcomes in chronic diseases, including cardiovascular disease (CVD), diabetes, hypertension, cancer, depression, and osteoporosis ,2. PA ofCKD is a public health problem that amplifies the risks of mortality, cardiovascular events (CVEs), and progression to end-stage kidney disease (ESKD). Adults with CKD have reduced physical function and are not as aerobically fit as the general population. A meta-analysis of clinical trials of regular exercise training in adults with CKD demonstrated that regular exercise training improved aerobic capacity, muscle function, cardiovascular function, and health-related quality of life . A recenAlthough MVPA is beneficial for various chronic diseases, adults with CKD have fatigue, weakness, reduced exercise capacity, and multiple comorbidities, which make it difficult to engage in large amounts of MVPA . Moreovehttp://www.clinicaltrials.gov, accessed on 5 June 2019)  (C statistic index = 0.911).The associations between the amount of MVPA and clinical outcomes are shown in MVPA predicted the risk of all-cause death (C statistic index = 0.609) better than it predicted the risk of CVE and ESKD based on Harrell’s C-statistics . MVPA had a closer association with the risk of all-cause death than the risk of CVE and ESKD.p for interaction = 0.014) and among females than among males (p for interaction = 0.005). The association between the amount of MVPA and the risk of CVE was not different according to age and gender groups. The association between MVPA and mortality was more prominent among younger and females. Thus, age and sex modified the relationship between MVPA and mortality.When subgroups on the basis of age, sex, and eGFR stage were conducted, we observed modifications of the association between the amount of MVPA and clinical outcomes in nondialysis CKD patients . The ass2 .In a total of 1909 adults with CKD, the HRs for all-cause death and CVE in adults with MVPA were 0.51 (95% CI: 0.33–0.77) and 0.83 (95% CI: 0.59–1.15). The risk reduction of all-cause death was more prominent than that of CVE. The risk reduction of ESKD was not significant in a total of 1909 adults with CKD, but the high amount of MVPA was associated with reduced risk of ESKD in 1324 adults with eGFR < 60 mL/min/1.73 mIn the KNOW-CKD study, the factors associated with the amount of MVPA were sex, age, diabetes, and eGFR stage. The lower risk of all-cause death and CVE occurred in adults with a moderate amount of MVPA. Moreover, even a low amount of MVPA was associated with a lower risk of death, and a high amount of MVPA was associated with a lower risk of ESKD. The risk of clinical outcome varied in subgroups divided by age and sex. Our study suggests that the beneficial effects of MVPA differ with type of outcome, patient’s age, sex. Therefore, planning individualized MVPA would be better for adults with CKD.PA and exercise are principal interventions in the prevention and treatment of chronic diseases, including CVD, type 2 diabetes, cancer, lung disease, osteoporosis, and neuropsychiatric diseases . The FITAdults with CKD have weakness, loss of muscle mass, and poor physical performance. A large amount of MVPA could increase the risk of musculoskeletal and cardiovascular complications in CKD. A recent review described that quantifying the lowest and the highest levels of exercise that confer health benefits is important in exercise prescriptions . Overall2. A possible explanation is that MVPA may have various beneficial pathways for mental, physical, metabolic, and inflammatory function across the amount of MVPA in CKD.An observational study of the National Health and Nutrition Examination Survey (NHANES) data of 15,368 adults with CKD showed that physical inactivity was more common among those with CKD, and physical inactivity was associated with increased mortality . AnotherThe American Medical Association and the American College of Sports Medicine established an initiative that exercise is medicine . The WHOThis study has some limitations. First, causal relationships between MVPA and each clinical outcome are difficult to demonstrate due to the observational cohort study design. Reverse causality is possible for the associations. Second, although IPAQ is a widely used questionnaire, there is a lack of validation in CKD. The IPAQ has undergone validity assessment in young to middle-aged participants in the general population. Third, a single self-reported health questionnaire and IPAQ at the baseline were used in our assessments, which could have led to recall bias. MVPA often changes over time in response to individual depression, work, and lifestyle. Fourth, participation in MVPA was influenced by facility accessibility, weather, and other socioeconomic factors. Fifth, we measured the MVPA time of both leisure and occupational activities. Much existing evidence of health benefits relates to leisure-time PA ,26, and 2. Age and sex modified the relationship between the amount of MVPA and clinical outcomes.CKD adults with MVPA showed various beneficial outcomes compared to those with no MVPA across the amount of MVPA. A low and a moderate amount of MVPA (0–14.9 MET-hours/week) was associated with a lower risk of all-cause death. A moderate amount of MVPA (7.5–14.9 MET-hours/week) was associated with a lower risk of CVE. A high amount of MVPA (15.0–29.9 MET-hours/week) was associated with a lower risk of ESKD in adults with eGFR < 60 mL/min/1.73 mOur findings showed that adults with MVPA are associated with reduced risk of poor clinical outcomes across the amount of MVPA in CKD. Future studies could focus on the benefits of PA on clinical outcomes using FITT principles and consider differences in subgroups in a large population with CKD. PA should be tailored for each patient in accordance with lifestyle, social factors, and personal goals of outcomes .


Conclusion: Diabetogenic lifestyle behaviours increased in the general Austrian population in recent years, which was especially true for people with DM regarding PA.Background: Not smoking, performing >150 min of aerobic physical activity (PA) and muscle strengthening exercises/week, and consuming >5 portions of fruit and vegetables/day are lifestyle recommendations for both the general population and people with diabetes mellitus (DM). Methods: A total of 15,771 and 15,461 persons from the Austrian Health Interview Surveys 2014 and 2019, respectively, including 4.9% and 6.0% of people with DM, were analysed in terms of their smoking, PA, and nutritional behaviours. Logistic regression models were performed for the lifestyle factors, adjusted for socio-demographic and health-related factors. Adjusted interactions between the survey year and DM on the lifestyle factors were computed. Results: The proportions of smokers were 23.9% and 20.2%, of people complying with the PA recommendations were 24.9% and 21.4%, and with fruit and vegetables recommendations were 7.1% and 5.5%, respectively, with significantly lower proportions of smokers and persons complying with the PA recommendations among people with DM. The fully adjusted odds ratios  for people with DM were 1.09 (0.94–1.26), 1.44 (1.23–1.69), and 0.90 (0.71–1.13) for smoking, not complying with PA recommendations, and not complying with fruit and vegetables recommendations, respectively. The proportion of people complying with PA recommendations decreased to a greater extent ( Lifestyle measures are key interventions in the management of diabetes mellitus (DM), both to control the disease and to mitigate the risk of progression or exacerbation ,2. ThereAdditionally, circumstances change over time, as do lifestyle factors. Unforeseen, traumatic or positive events have additional impacts on lifestyle choices, such as eating habits, thereby influencing the adherence to recommendations . AdditioIt was, therefore, the aim of this study to analyse these indicators of health behaviour in patients with DM in comparison to the general population and to observe whether these health behaviours changed over time. Furthermore, the study explored whether the changes over time occurred in equal measures in people with DM as in persons without the disease. These results will help to inform whether changes in health promotion and public health programmes need to be considered in the prevention and management of DM.The Austrian Health Interview Surveys (ATHIS) for the years 2014 ,24 and 2The ATHIS 2014 was carried out via computer-assisted telephone interviewing (CATI) between October 2013 and June 2015. The cross-sample size drawn from the national central population register was 38,768 subjects. Out of this, the data for 15,771 subjects were eligible for inclusion in the analysis, representing a response rate of 40.7%. In addition to the CATI questions, paper questionnaires were sent out to the respondents for specific topics, including the questions about PA, which had to be returned through regular post. The response rate for this part of the survey was 93% .The ATHIS 2019 was carried out via computer-assisted personal interviewing (CAPI) and a web-based questionnaire between October 2018 and September 2019. The cross-sample size drawn from the national central population register was 30,608 subjects. Out of this, the data for 15,461 subjects were eligible for inclusion in the analysis , representing a response rate of 50.5%. Similar to ATHIS 2014, ATHIS 2019 also included a self-administered questionnaire for specific topics, including the questions about PA. This self-administered part was carried out by the participants on an electronic device of their choice . Only a minority (1.5%) of the participants preferred a paper–pencil version of the self-administered questionnaire, the answers to which were digitalised upon receipt .Smoking status: Daily cigarette smoking was indicated in the ATHIS 2014, if subjects answered “Yes, daily” to the question “Do you smoke?” and answered with “Cigarettes” to the question “Which of the following tobacco products do you use most frequently?”. In the ATHIS 2019, daily cigarette smoking was indicated, if the subjects answered “Yes” to the question “Do you smoke cigarettes daily?”. Physical activity: In evaluating the amount of PA, the 8-item PA Questionnaire of the EHIS (EHIS-PAQ) was used [was used . Compliawas used  was calcwas used , the indNutrition: Regarding nutrition, the respondents were asked how often per week they were eating fruits and vegetables, respectively, and if they answered with “Daily or more times per day”, they were asked to indicate, how many portions of fruits and vegetables, respectively, they were eating per day. The respondents were told that one portion was approximately a handful of fruit or vegetable, as a general rule. Since guidelines recommend the consumption of ≥5 portions of fruit or vegetables per day, with an emphasis on vegetable consumption [sumption , we calcsumption  and the sumption .Diabetes mellitus: Regarding DM, subjects were asked whether they had DM as a diagnosed chronic disease in the past 12 months. No distinction between the different types of DM was made, as this is not mandatory in the EHIS and the ATHIS follows the EHIS format.Socio-demographic and health-related variables: Participants’ sex  and age were recorded. Age was used in three categories . The relationship status was represented as either ‘in a relationship’ (including being married) or ‘not in a relationship’. Education was defined in three levels: primary education (compulsory education up to age 15); secondary education ; tertiary education (university). Furthermore, country of birth was documented into three categories: Austria; EU or EFTA states ; non-EU and non-EFTA states. The presence of a chronic disease was assessed with the question “Do you have a chronic disease or a chronic health problem?”. Finally, the body mass index (BMI) was calculated with the reported data for body weight and body height and categorised as underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), or obese (≥30 kg/m2).All analyses were carried out using IBM SPSS Statistics 22 . The sample was weighted using the geographical region, age in 5 year groups, sex, family status, migration background, and educational level, as the weighting factors. Bivariate analyses were performed by means of cross-tabulations and group differences were assessed with Pearson’s Chi-squared tests.Before including all variables into the multivariate model, the correlation of the variables with each other was tested by applying Pearson’s correlation coefficient in order to avoid problems of multicollinearity. The variables with the highest correlation were ‘presence of DM’ and ‘presence of any chronic diseases’, with a correlation coefficient of 0.236. There is no international standard for correct cut-off points for detecting multicollinearity , even thp-value for the interaction between the year and the presence of DM is presented. Finally, we calculated binary logistic regression analyses with the respective health behaviour as the dependent variable, and all socio-demographic and health-related variables as the independent variables. The estimates of the logistic regression models with all mutually adjusted socio-demographic and health-related variables on the likelihood of having an unfavourable health behaviour are presented as ORs and 95%  CIs.In order to test for the interaction between the year of evaluation and the presence of DM on the likelihood of the respective health behaviours, binary logistic regression analyses were carried out. In these analyses, the dependent variables were the different health behaviours, and we adjusted for the year of the survey, the presence of DM, and all socio-demographic and health-related variables. The The characteristics of the samples from both surveys are depicted in People with DM smoked significantly less often compared with persons without DM. The proportions of daily smokers decreased from 2014 to 2019, both in patients with DM and in those without the disease. Additionally, people with DM were even less likely to meet the PA recommendations, which also was a significant result. The proportion of people complying with the recommendations decreased from 2014 to 2019; however, according to the significant interaction, differences were observed between patients with DM and people without DM. Regarding compliance with the aerobic and total PA recommendations, a stronger decrease was observed in patients with DM compared to persons without DM. Furthermore, there were also significant differences in the proportions of people with DM and those without DM who ate at least two portions of fruit per day (in both surveys) and who ate at least 3 portions of vegetables per day (in the survey 2014). The proportions of subjects who ate the recommended amount of fruit or vegetables decreased from 2014 to 2019, both in persons with and without DM .As shown in As shown in The overall international trends toward unhealthy weight, little PA, and insufficient fruit and vegetable intake are mirrored in this Austrian cohort, and the situation has clearly deteriorated over time. These developments in themselves are already cause for much concern, as higher weight, a lack of PA , and unhSocial determinants of health are another important factor in tackling lifestyle changes. Austrian data follow other countries in that women eat healthier than men but are less physically active, and that migrants from outside the EU tend to have worse health outcomes than people born in Austria or the EU. Investments in multi-faceted and targeted programmes covering all settings pay dividends, as they considerably contribute to the prevention of DM and reduce mortality risks in people with DM, as mentioned above ,7. MoreoThe analysis also highlights that adults with DM are even less compliant with the recommended lifestyle adjustments than the general population. As non-compliance with recommended lifestyle choices can lead to the progression of DM, the development of co-morbidities, or preventable exacerbations ,39,41, tThe data and development over time in conjunction with the international evidence show that in order to reverse these trends, renewed efforts need to concentrate on bringing everything together in multi-faceted programmes that address all aspects of a healthy lifestyle, taking into account the necessity of easy applicability in everyday life and cutting across different settings. These approaches need to coordinate and align efforts from public health agencies with those in primary care and short-term inpatient programmes. They should include comprehensive approaches that take into account family and workplace situations and encourage not only obvious recommendations around PA and nutrition, but that also look at mental health, functional and critical healthy literacy  , and socA good example is the Finnish implementation programme for the prevention of type 2 DM (FIN-D2D), which combines integrated care guidelines with national incentives such as taxation to promote healthy food choices, short-term intervention programmes, and a comprehensive follow-up and support system in primary care . In sociThe strengths of the study include the large and representative sample sizes of the two surveys and the fact that the Austrian Central Population Register was used to draw the samples, which represents the entire Austrian population. In contrast to studies from clinical settings, the population-based design of our study permitted the combined analysis of healthy subjects with people with DM. The limitations of the study include the slightly different methods used (CATI in 2014 vs. CAPI in 2019), which could have yielded an underestimation of unfavourable health behaviour in 2014, since unfavourable behaviour is usually reported more honestly and more often in personal interviews compared to telephone interviews ,51. AddiPeople with DM show less favourable lifestyle behaviours compared to the general population, although unhealthy lifestyle behaviours have increased overall. This illustrates again that even though the prevention and management of DM has been widely studied over the past decades, with numerous guidelines and disease management programmes existing, long-term success remains elusive and limited. The reasons are manifold, although it is clear that well-defined measures and recommendations by themselves are not enough to enable people to sustainably change their lifestyles. As with all health promotion and prevention measures, it is necessary to co-design care plans together with the population and to support them over their life course, not only through clinical interventions, but more importantly by providing healthy environments that promote healthy choices.