We investigated the impact of a sports activities program on metabolic syndrome (MetS) components and pre-MetS among adolescents. Blood samples, blood pressure, weight, height, body mass index, waist circumference, body fat percentage, frequency of food consumption, daily time in moderate-to-vigorous physical activity (MVPA), and sedentary behavior (SB) of 92 male adolescents aged 14–18 years (16.07 ± 0.93) were evaluated. From this initial sample, 36 participants (39.1%) were diagnosed with pre-MetS or MetS and were invited to participate in the intervention program. Twelve individuals diagnosed with pre-MetS or MetS agreed to participate in a recreational sports activities program lasting 14 weeks. The pre- and post-sport program comparison showed a reduction in total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL), and an increase in HDL and MVPA time in the intervention group. Sports activities accounted for 42% of the MVPA daily recommendation, and at the end of the intervention period, only seven subjects maintained a positive diagnosis for pre-MetS or MetS. This study showed that recreational sports activities had a significant impact on the lipid profile. The increase in the prevalence of obesity and hypertension among children and adolescents is considered a public health problem with severe epidemiological and economic implications , and it MetS is often defined as the clustering of three or more risk factors. It can include adiposity, hyperglycemia, hypertension, hypertriglyceridemia, and lower high-density lipoprotein (HDL) . The MetUsing the adult criteria, the significant rates of this disorder in the pediatric population indicate the need for early diagnosis to avoid future complications in general health ,8. Thus,Pre-MetS and MetS are significantly and negatively associated with reduced physical activity and increased time spent in sedentary behavior (SB) . PhysicaConsidering the focus on lifestyle changes, multidisciplinary interventions  directed to adolescents have been conducted to reduce obesity and its comorbidities, including MetS ,16,17,18The sample consisted of students recruited from a full-time federal institution of technical education from the county of Rio Pomba, Minas Gerais, Brazil; according to the following inclusive criteria: to be a male resident high school student, living on the campus of the school; between 14 and 18 years of age. Of the approximately 500 students enrolled in the first, second, and third years of high school, 109 were considered eligible; however, 17 students did not perform the necessary assessments for the study. Thus, the MetS components were evaluated in a sample composed of 92 individuals. From this number, 36 were diagnosed with pre-MetS or MetS and were invited to participate in the activities program, with the final acceptance of 12 students. In this second phase, the exclusion criteria included the use of medications to control blood pressure, fasting glucose, or lipid metabolism, other previously diagnosed chronic diseases besides MetS, permanent or temporary physical disability, and caloric restriction diet.The research project was submitted and approved by the Human Research Ethics Board from the Federal University of Viçosa (Off. Ref. No. 177.176/2013/CEPH), following the Resolution 466/12 of the National Health Council and following the Declaration of Helsinki. All the participants were volunteers and signed the informed assent form, while parents of the participants under the age of 18 signed the informed parental consent.The study’s first phase is related to a pre-MetS and MetS cross-sectional baseline screening, while the second phase consisted of a longitudinal quasi-experimental study with the participation of 12 students (10 with pre-MetS and 2 with MetS) in a 14 week recreational sports program.In the first phase, all 92 students were evaluated for body composition, maturation status, eating habits, resting vitals, physical activity, SB, and MetS components, before the beginning of the program. Of the initial 92 students, the 12 participants in the intervention program also had their resting heart rate monitored to estimate the maximal heart rate. During the 13th week of the intervention, participants enrolled in the second phase had their physical activity and SB evaluated again, while the other evaluations were performed in the 14th week.® .After fasting for 12–14 h, morning blood samples were collected in the healthcare sector of the institution, by qualified and trained professionals, designated by the accredited laboratory to conduct the analyzes. We collected 5 mL of blood from the cubital vein and then centrifuged it at 3400 rpm for five minutes to separate serum from other blood components. The levels of fasting glucose, total cholesterol, HDL, and triglycerides were determined through enzymatic colorimetric assay method, while insulin level was analyzed using the electrochemiluminescence method. The equipment used for the blood tests was the biochemical analyzer Awareness TechnologyMetS and the cutoff points used for each of its components were defined according to De Ferranti et al. , which cInsulin resistance was evaluated by homeostatic model assessment (HOMA-IR), according to the equation proposed by Matthews et al. , and low®  and height to the nearest 0.1 cm using a portable stadiometer Sanny® . The body mass index (BMI) was calculated from the kg/m2 ratio, and the cutoff points proposed by the World Health Organization (WHO) were used to classify weight status [Anthropometric measures (height and weight) and skinfolds were performed according to procedures standardized by the International Society for the Advancement of Kinanthropometry . All meat status .® . Subsequently, the waist-to-height ratio was calculated.Waist circumference was obtained from two distinct anatomical points, including the measurement in the region of the smallest waist circumference (SWC) , as well® . The value of 20% as an indicator of body fat excess was used as recommended by Going et al. [Body fat percentage was estimated by the Slaughter et al.  equationg et al. .The maturational stage was obtained through the peak height velocity using the equation and the classification suggested by Mirwald et al. , which c®, São Paulo, Brazil), a stethoscope Premium®  and suitable cuff size for adolescents. Blood pressure was measured three times, after a period of 5–10 min at rest; and at least 1 min between measurements. Blood pressure was considered the average value from the last two measurements, according to the protocol proposed by the Guidelines for the Prevention of Atherosclerosis in Childhood and Adolescence . The meaBefore the beginning of the intervention activities, each participant had their resting heart rate evaluated. The student was taken to the evaluation room and asked to remain at rest, in the lying position, for 10 min. The lowest heart rate recorded in this period was used as the resting heart rate. The maximal heart rate was estimated using the Tanaka et al.  formula.The participant’s eating habits were assessed using a Food Frequency Questionnaire, adapted from a regional model, with the addition of types of food provided by the institutional refectory. The items included in the questionnaire were: bread, pasta, cereal, tuber, vegetables, fruits, meat, sausage, egg, sugar, sweets, snacks, oils, fats, and seasonings. Participants were instructed to fill out the number of times per week and per day in which they consumed a particular food group. As all the participants were resident students, most of the food consumption made for them was prepared by the school cafeteria. Then, to facilitate the completion of the questionnaire, we provided a spreadsheet with the average number of times per week each food group was served. Two nutritionists reviewed the forms as they were completed for accuracy. ® . Participants received the accelerometer and were instructed to wear it at the waist, toward the midline of the thigh, on the right side of the body, near the iliac crest. The accelerometer was worn for seven consecutive days and removed only during aquatic activities  and during sleep time. The data collection was considered valid for participants who recorded at least 10 h of daily use, in at least 4 weekdays and 1 weekend day [®, Florida, USA). The activity intensity classification was based on the cutoff points proposed by Puyau et al. [Physical activity and SB were assessed using a triaxial accelerometer Actigraphkend day . The accu et al. , which sTotal daily energy expenditure was estimated from the proposed equation of the National Academy of Sciences Institute of Medicine Food and Nutrition Board for boys aged 3–18 years . To calcParticipants were asked to attend intervention sessions regularly. Interventions were constituted of popular recreational sports in Brazil, including volleyball, basketball, soccer, and futsal modalities, practiced 4 days a week, lasting 1 h each. Futsal modality was offered in two weekly sessions. Volleyball and basketball were provided during the same session for similar durations of two times per week. Every 15 days, the volleyball/basketball session was replaced by a five-a-side soccer game.® with the Global Positioning System  to determine the intensity reached during intervention activities. The average session intensity was identified using the heart rate reserve method, calculated from the difference between resting heart rate and maximal heart rate, according to the following formula: heart rate reserve % = ((AHR − resting heart rate)/heart rate reserve) * 100; in which AHR means the average heart rate during the intervention session.Participants wore heart rate monitors GarminThe program lasted 14 weeks for a total of 56 sessions, and adolescents were asked to attend at least 70% of the total session number (29 sessions). A physical education teacher performed the intervention and was responsible for the sports practice organization, division of teams, sports rules adaptation when necessary, and activity time control. p < 0.05.The variables were checked for normality of distribution using Kolmogorov–Smirnov and Shapiro–Wilk tests for the first and second phases of the study, respectively. The linear regression model was applied to evaluate the association among adiposity, metabolic, hemodynamic, and anthropometric variables. Log transformations were used to normalize non-parametric data of triglycerides, HOMA-IR, and insulin. According to the data distribution, Student’s t-test or Mann–Whitney test was applied for independent samples. Moreover, in agreement with the distribution, paired Student t-test or Wilcoxon was used to evaluating possible differences in pre- and post-intervention variables. The effect size for the comparison tests was calculated using a specific formula. All statistics were performed using SPSS 20.0 , and significance was set at p = 0.004), BMI (p = 0.021), MWC (p = 0.030), and SWC (p = 0.025). Similarly, significantly higher values were found for systolic blood pressure (p = 0.005), diastolic blood pressure (p = 0.002), insulin (p = 0.049), HOMA-IR (p = 0.000), triglycerides (p = 0.000), and non-HDL (p = 0.000) in the pre-MetS and MetS groups (p = 0.004)  and 4.3% (n = 4), respectively. The individuals characterized with the pre-MetS or MetS were mostly (72.2%) in post-pubertal maturation stage, 27.8% were classified as pubescent, and no individual was classified as pre-pubertal. S groups . No sign= 0.004) .p < 0.001) (p < 0.05) after 14 weeks of the sports program. Besides that, the variables age and HDL demonstrated statistically significant increases (p < 0.05) when comparing the two study moments.On average participants attended 32.6 intervention sessions . < 0.001) . Howeverp = 0.016) and the total daily energy expenditure (p = 0.010). Although not significant, there was a trend in increasing MVPA during weekdays (p = 0.07). No significant differences were found in the other variables, including SB  and resting heart rate (62 bpm) average. The average heart rate during the intervention session was 134 ± 11.2 bpm. According to the heart rate values, the participants remained, on average, 25 min (≈42%) of the activity duration (60 min) within the moderate-to-vigorous intensity, with a mean of heart rate 157 ± 3.8 bpm. This time is considered an adequate amount of time in MVPA, considering the recommendation that 50% of physical education classes (approximately 30 min) should be performed at that intensity . In the The definition of an internationally accepted criterion for MetS diagnosis in children and adolescents is a current debate by many researchers ,38,39. Tp < 0.05). These results illustrate the metabolic impact of this condition and also suggest negative changes in lipid and glycolytic metabolism during adolescence. However, no significant differences in fasting glucose were identified between groups (with or without pre-MetS or MetS), since this variable typically exhibits a late response compared to the other MetS components [Our study diagnosed 4.3% of the total sample (n = 4) with MetS using the adult criteria, a prevalence similar to other studies involving adolescents ,41. Howemponents . SimilarThe literature has been cohesive in treating anthropometric variables as metabolic predictors and cardiovascular disease risk factors in Brazilian children and adolescents ,42. Our p < 0.05) in several risk factors, including total cholesterol, LDL, non-HDL cholesterol; as well as increase in protective factors such as HDL, daily MVPA, and total daily energy expenditure  . This hiThe intervention program was not intended to establish an intensity range to be maintained by adolescents. Despite that, the degree of involvement with the sports activities promoted voluntary, significant time in moderate to vigorous intensity. Approximately 42% (25 min) of the daily recommendation of MVPA was obtained during this intervention. Therefore, the physical activity ludic aspect should be contemplated in future intervention programs, especially in the school environment, to promote the adoption and maintenance of an active lifestyle by adolescents .We believe that the results achieved by this study should be interpreted as the exclusive result of the physical activity promotion since no statistically significant differences were found in the frequency of food consumption. This fact was already expected due to the standardization of food provided in a boarding school environment, where most meals reported by the adolescents were those offered by the institution.The main limitations of this study were the male participation restriction and the small number of participants in the intervention phase. However, the originality of the study stands out because, to the best of our knowledge, no intervention studies based on the promotion of recreational sports activities with Brazilian adolescents were found in the literature. As sports activities are inherent to the everyday life of schoolchildren, this increases the ecological validity of our findings. This type of group intervention should be considered as a viable, easy-to-perform, low-cost, and extremely motivational alternative for this particular population; when compared to interventions restricted to aerobic and resistance exercises program performed in closed and controlled environments. Lastly, it is suggested that future intervention studies focused on sports activities should extend the duration longer than 14 weeks and include female adolescents. We also suggested that interventions should be tailored according to the needs of this population.This study suggests a high prevalence of pre-MetS or MetS among adolescents. The new pre-MetS classification was meaningful in identifying those adolescents at risk for developing MetS and should be incorporated in this population. Following the intervention, reductions in risk factors for MetS were observed, mainly in the lipid measures. The intervention reinforces that recreational sports activities contributed to increasing time spent in MVPA. Besides that, it highlight that effects are essential as preventive action and non-pharmacological therapeutic procedures for adolescents at risk of developing chronic non-communicable diseases to improve their metabolic profile. Positive lifestyle changes by means of increasing MVPA and reducing SB are the bases for MetS prevention in this population.


The hippocampus and hippocampal subfields have been found to be diversely affected in Alzheimer’s Disease (AD) and early stages of Alzheimer’s disease by neuroimaging studies. However, our knowledge is still lacking about the trajectories of the hippocampus and hippocampal subfields atrophy with the progression of Alzheimer’s disease.To identify which subfields of the hippocampus differ in the trajectories of Alzheimer’s disease by magnetic resonance imaging (MRI) and to determine whether individual differences on memory could be explained by structural volumes of hippocampal subfields.Four groups of participants including 41 AD patients, 43 amnestic mild cognitive impairment (aMCI) patients, 35 subjective cognitive decline (SCD) patients and 42 normal controls (NC) received their structural MRI brain scans. Structural MR images were processed by the FreeSurfer 6.0 image analysis suite to extract the hippocampus and its subfields. Furthermore, we investigated relationships between hippocampal subfield volumes and memory test variables  and the regression model analyses were controlled for age, gender, education and eTIV.CA1, subiculum, presubiculum, molecular layer and fimbria showed the trend toward significant volume reduction among four groups with the progression of Alzheimer’s disease. Volume of left subiculum was most strongly and actively correlated with performance across AVLT measures.The trend changes in the hippocampus subfields and further illustrates that SCD is the preclinical stage of AD earlier than aMCI. Future studies should aim to associate the atrophy of the hippocampal subfields in SCD with possible conversion to aMCI or AD with longitudinal design. The pathophysiological process of Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, which is thought to have begun many years before the diagnosis. With the disease progression, as the preclinical AD, subjective cognitive decline (SCD) have worse cognition than normal controls (NC), while objective examination shows that they have not yet reached the level of amnestic mild cognitive impairment (aMCI) or AD dementia . The maiThe hippocampus is composed of several subfields with different histological characteristics, rather than a homogeneous structure. Hippocampal atrophy is the most significant structural biomarker of AD imaging . DiffereWe hypothesized that there may be 1) a change in the hippocampal subfields at different stages of AD in accordance to the trajectory of Alzheimer’s disease and 2) a relationship between hippocampal subfield volume and memory status . The purWe prepared 161 right-handed Chinese Han participants including 35 SCD patients, 43 aMCI patients and 41 AD patients, and 42 NC subjects from our databank . The cognitive functions of all the subjects were assessed by experienced neurologists. Including the Clinical Dementia Rating Scale (CDR) , the ChiThe normal controls did not present cognitive decline complaints and their performance in MMSE, MoCA and AVLT were in normal range. The patients with SCD were diagnosed based on the criteria proposed by SCD-I in 2014 , includiThe study approved by the medical research ethics committee and the institutional review board of Xuanwu Hospital, Capital Medical University, Beijing, China. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.3.The 3T magnetic resonance imaging system  was used for image acquisition at the Department of Radiology, XuanWu Hospital, Capital Medical University. T1-weighted MRI scans were acquired at the sagittal plane by using a magnetization prepared rapid acquisition gradient echo sequence with the following parameters: TR = 1900 ms, TE = 2.2 ms, FA = 9°, inversion time (TI) = 900 ms, matrix = 256 × 256, slices = 176, thickness = 1.0 mm and Voxel size = 1 × 1 × 1 mmhttp://freesurfer.net/)  .3) of 10 normal subjects. By maximizing the posterior probability of a segmentation, the left and right hippocampi were automatically segmented into twelve subfields: hippocampal tail, parasubiculum, presubiculum, subiculum, CA1, CA3, CA4, hippocampus–amygdala transition area (HATA), granule cell layer of dentate gyrus (GC-DG), molecular layer, fimbria, and hippocampal fissure. In this manuscript, the method for automated segmentation is standard. Additionally, the method for segmentation is validated to be accurate by First, the entire hippocampal formation was segmented using the routine volumetric FreeSurfer pipeline. Briefly, T1-weighted MR images were corrected for within-subject head motion; then, non-brain tissues were removed using a hybrid watershed/surface deformation algorithm . The resP < 0.05) were further explored using Bonferroni post hoc analysis. In the post hoc analysis, the differences between the individual experimental group and the control group were assessed. The left and right hemisphere measurements were analyzed, respectively. In addition, covariance analysis was used to analyze the volume differences in individual hippocampal subfield with age, sex, years of education and eTIV as covariates. Furthermore, we investigated relationships between hippocampal subfield volumes and memory test variables  through the regression model analyses controlled for age, gender, education and eTIV.Statistical analysis was carried out using Statistical Package for Social Sciences software . All the statistical tests were two-tailed. Categorization of demographic variables was assessed using Chi-square test. Continuous demographic variables were evaluated through ANOVA. In this study, the estimated total intracranial volume (eTIV) was used as a covariate to control head size. Statistically significant differences based on ANOVA (P > 0.05 for each group comparison). Comparing SCD and NC groups, there were no significant differences in MoCA, MMSE, immediate recall part of AVLT, the recognition part of AVLT, while significant difference (P = 0.012) in the delayed recall part of AVLT. The patients with AD and aMCI had significant lower scores in MoCA, MMSE, and AVLT compared with the healthy control participants (P < 0.005).The demographic characteristics of the normal control, the patients of SCD, the patients of aMCI and the patients of AD are shown in We tested differences in whole hippocampal volume and all subfields among four groups using ANCOVA with age, years of education, and eTIV as covariates. P < 0.2 were used in subsequent stepwise linear regressions. This was performed to avoid too many independent variables. In the regression model, variables were removed when P > 0.05. In a first step, all potential risk factors  were correlated with AVLT scores and only variables correlated with AVLT score at In this study, we investigated the volumetric difference of hippocampus and hippocampal subregions among AD, aMCI, SCD, and NC subjects. There were also trends in some hippocampal subregions with the trajectories of Alzheimer’s disease in addition to the volumetric differences between the four groups. Furthermore, we studied AVLT and typical hippocampal subfields related with memory. It also shown trends with the trajectories of Alzheimer’s disease.In our study, we found that the differences of hippocampus and hippocampal subfields with age, years of education, and eTIV as covariates. The effect of the size of the brain in different subjects was excluded. Our study showed that the difference in volumes was in the left whole hippocampus as that of previous studies . We furtThe functions of the hippocampal subfield were different, which were related to memory, executive function, attention deficits and so on . The anaThere are limitations in our study. Firstly, the main limitation is the lack of high risk group but asymptomatic control group besides the four groups . In future design, we will collect the high risk but asymptomatic control group. Furthermore, this study was based on cross-sectional data, longitudinal follow-up studies of the same cohort are conducted to identify early imaging markers for disease transformation and prediction. Finally, we only studied hippocampal subregion volume by structural MRI. The combination of the multimodal imaging  could be used in our future research.Our findings show that the trend changes in the hippocampus subfield and further illustrate that SCD is the preclinical stage of AD earlier than aMCI. The susceptibility of hippocampal subfield to AD pathological damage is different, so the volume of hippocampal subfield is better than the total volume of hippocampus in identifying early AD. It can better review the trajectory of AD, understand the mechanism, and identify sensitive biological indicators at different stages of AD.All datasets generated for this study are included in the manuscript and/or the supplementary files.WZ contributed to the main body of the manuscript. YH and SL conceptualized, designed, supervised the study and approved the final version of the manuscript. CY and MH contributed to study design and data collection. XW contributed to data analysis and manuscript preparation. All the authors interpreted the data, provided important feedback, and revised the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Childhood autism spectrum disorder (ASD) can easily be misdiagnosed, due to the nonspecific social and communicational deficits associated with the disorder. The present study attempted to profile the mental development and visual attention toward emotion among preschool children with mild or moderate ASD who were attending mainstream kindergartens. A total of 21 children (17 boys and 4 girls) diagnosed with mild or moderate ASD selected from 5,178 kindergarteners from the Xi’an city were recruited. Another group of 21 typically developing (TD) children who were matched with age, gender, and class served as controls. All children were assessed using the Griffiths Mental Development Scales–Chinese (GDS-C), and their social visual attention was assessed during watching 20 ecologically valid film scenes by using eye tracking technique. The results showed that ASD children had lower mental development scores in the Locomotor, Personal-Social, Language, Performance, and Practical Reasoning subscales than the TD peers. Moreover, deficits in recognizing emotions from facial expressions based on naturalistic scene stimuli with voice were found for ASD children. The deficits were significantly correlated with their ability in social interaction and development quotient in ASD group. ASD children showed atypical eye-gaze pattern when compared to TD children during facial emotion expression task. Children with ASD had reduced visual attention to facial emotion expression, especially for the eye region. The findings confirmed the deficits of ASD children in real life multimodal of emotion recognition, and their atypical eye-gaze pattern for emotion recognition. Parents and teachers of children with mild or moderate ASD should make informed educational decisions according to their level of mental development. In addition, eye tracking technique might clinically help provide evidence diagnosing children with mild or moderate ASD. Autism spectrum disorder (ASD) is a neurodevelopmental disorder which is characterized by pervasive social communication and social interaction deficits, as well as restricted interests and/or repetitive behavior . A numbeIntellectual disability is a common deficit associated with ASD, and it is considered an important predictor of intervention –6. ExamiIn addition to mental development, difficulty in understanding others’ emotional and mental states is considered as a core characteristic of ASD, and it is recognized as part of their social communicative impairments . CognitiSeeing the importance of the ability to understand other’s emotion expression in social interaction and communication, the majority of research on emotion recognition among ASD children focused on examination of facial expression during social interaction. However, many of them reported inconsistent findings . The incIn addition to the heterogeneity of ASD, the type of experimental stimuli also played a determining role in studying emotion recognition in ASD children. Although there have been extensive research examining emotion recognition through facial expression in children with ASD, most relied on static photographs of different facial expressions as visual stimuli –27, but Atypical visual processing underlies poor eye contact, and joint attention during social interaction is considered another core characteristic in individuals with ASD . Eye conAs discussed above, the current study aimed to assess the profile of intelligence and the ability of facial emotion recognition in children with mild or moderate ASD in urban kindergartens of Xi’an, China. GDS-C and eye tracking were used to describe the intelligence profile and eye movement during emotion recognition, and to correlate intelligence with eye movement characteristics, as an attempt to provide theoretical basis for educational decision for children with mild or moderate ASD. Findings could also contribute to a more effective diagnosis for children with mild-to-moderate ASD using eye movement technique in the clinical setting.Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria . All TD children had no psychiatric diagnoses or special educational needs, and none had a family member diagnosed with ASD, as reported by their parents. The CARS was also used to identify the TD children who have normal social and behavioral ability. The basic characteristics of participants were illustrated in The study was carried out in 12 urban kindergartens of Xi’an city from December 2017 to January 2018. Thirty-six children were diagnosed with ASD among a total of 5,178 kindergarten children by practicing pediatricians who were experienced in children developmental behavior based on the The intelligence profile of each participant was assessed using the GDS-C (3–8 years), administered by a certificated developmental pediatrician. The Griffiths’ test consists of six subscales, including Locomotor subscale , Personal-Social subscale , Language subscale (receptive and expressive language), Eye–Hand Coordination subscale (fine movements including drawing and writing), Performance subscale , and Practical Reasoning scales . The combination of all six subscale scores was assigned as the General Quotient (GQ).Percentile rank (PR) was calculated for all neurodevelopmental scores in order to compare the intelligence level within the same age. Neurodevelopmental outcome was classified as normal (PR ≥ 15), mildly delayed (2.5 ≤ PR < 15), or severely delayed (PR < 2.5).Both ASD and TD participants were assessed using GDS-C and CARS by two developmental behavior pediatricians, and every assessment was under the supervision of an MD/PhD professor in kindergartens. The CARS and parents’ report content scoring in Griffiths test were based on information gathered from teachers as well as from field observations.Twenty short film scenes  were selected from CASIA Chinese Natural Emotional Audio-Visual Database (CHEAVD) . This da™. Fixation detection was performed through the SMI BeGaze™ using Dispersion-Threshold (DT) algorithm. Eye-gaze data was recorded online with the software of Experiment Center 2.0 and analyzed offline with SMI BeGaze analysis software.To collect and quantify the eye-gaze data, a contactless eye-tracker SensoMotoric Instruments (SMI) RED 250  was used. The eye-tracker system is composed of an eye tracker hardware, a 22-inch monitor with a resolution of 1280 × 1024 pixels, and a stimuli presentation and control computer. The sampling rate was set at 120 Hz with an accuracy of 0.4°. The freedom of head movement was 40 cm × 20 cm at 70 cm distance. The experiment was prepared and presented in SMI Experiment CenterParticipants were tested individually in a quiet and well-lit room in the childcare center, which had no external light stimulus. Before the start of the testing session, participants were trained to get familiar with positive and negative emotions. Typical questions, such as how do you feel when eating your favorite food/when your pet ills, were asked to test if participants understand the two emotions. Besides, pictures and videos that describe various emotions were played by a tablet (Samsung ST800), and participants were instructed to choose a card, each of which correspond to a different emotion. Participants were praised for correct responses. The purpose of this training is to familiarize the participants with the emotions.After completing the training session, participants were adjusted to sit 60–80 cm from the eye-tracking monitor. The experimenter first calibrated the participant’s eye movements with the built-in five-point SMI calibration procedure, in which the participant had to track a moving dot across the screen with their eyes. Recalibration was required if the calibration results were poor. After calibration, each participant passively watched the video stimuli and was told to concentrate on the speech and actions of the actor/actress. Videos could be played for multiple times if the participant could not understand what was shown in it. After watching the videos, participants were asked to choose a card, which corresponds to the emotion of the actor/actress. The cards were shuffled while the participant watched the videos to prevent them from choosing the same one without consideration. The testing session included 20 videos, which were played randomly.To avoid possible effect of gender, multicharacters model, the scenes expressed by only woman characters were chosen to further analysis, and thus 10 scenes were used in eye gaze analysis. In addition, to quantify visual gaze patterns, three areas of interest (AOIs)  were selected for further analysis see Figure 2The eye region included, in the horizontal direction, the area ranging from the leftmost corner of the left eye to the rightmost corner of the right eye, and in the vertical direction, the area between the lower side of the eyebrow and the middle nose. The mouth region included, in the horizontal direction, the area between the upmost lip to the bottommost lip, and in the vertical direction, the area ranging from the leftmost lip corner to the rightmost lip corner. The face region included the face except the rest of the eyes and mouth. When identifying emotions, the key regions included the eyes, mouth, and face (excluding the eyes and mouth), which constitute the overall AOI. In addition, the visual fixation of body gesture of protagonist compared to face was also analyzed.In percent study, three eye-tracking parameters were calculated. The first parameter was the fixation duration time (FDT), defined as the total time of fixation lasting more than 100 ms, reflected the time taken by the participants to think. The second parameter was fixation count (FC), which evaluated the length of fixation lasting more than 100 ms, reflected the absolute attention played by the participants during the process of the experiment. The third parameter was the proportion of AOIs in the overall videos (PA), which was considered as the proportion of FDT and FC in AOI in the whole videos, reflected the degree of dispersion of the subject while watching. The minimum fixation duration was chosen as eye-tracking data of 100 ms . Since tt-tests were used to evaluate possible group difference in GQ, subscales scores of GDS-C, and accuracies of emotion recognition. A two-way repeated-measures ANOVA (two groups × two emotions) was conducted to compare the different patterns of eye-gaze model between children with ASD and TD children. Two-way repeated-measures Multivariate analysis of variance (MANOVA) were used to compare the different eye-gaze patterns in the three AOIs of the face. Pearson correlation analysis was used to evaluate the correlation among Griffiths Scale, eye movement modes, and the ability of emotion recognition. All statistical analyses were performed using SPSS Version 17.0 (IBM Corp). An alpha level of p = .05 was used to determine for significant results.Matched case–control design was used in the study, in which each ASD-TD children pair was matched by age (within 6 months) and gender, and both were originated from the same class. As GQ and subscales scores of GDS-C and accuracies of emotion recognition are independent and normally distributed with homogeneous variance, paired-sample t-tests revealed that there was a significant difference in the GQ score, which is 65.78 ± 13.78 for the ASD group and 76.70 ± 12.30 for the TD group . On the subscale scores, except for Eye-Hand Coordination subscale, there were statistically significant differences between two groups in the Locomotor, Personal-Social, Language, Performance, and Practical Reasoning subscales and GQ. The subscales and GQ scores of the GDS-C are summarized in The paired sample By comparing the structural mode of each subscale (3–8 years) scores between the two groups, we found statistical differences in the following areas including physical strength, gross body coordination, gross visual motor coordination, social skills for communication, receptive language, basic conception, semantic reasoning, expressive language, imitation, social reasoning, sequence reasoning, and conception. The other structural mode scores between the two groups didn’t have statistical differences. The detailed statistical difference structural mode of each subscale scores between ASD group and TD group are shown in t = −2.52, p = 0.021) and sadness emotion . Among which, the performance of happiness emotion was significantly better than those of sadness emotion in children with ASD . The children with ASD were seemingly easier to distinguish happiness than sadness emotion. In addition, to evaluate whether severity of the social deficits measured by the Griffiths Development Scales (GDS) was related to accuracy to recognize emotions, Pearson correlations were calculated between the scores of Developmental Quotient, Personal-Social subscale, and the mean identification accuracy on each emotion. Significant relationships were found only in the ASD group between accuracy and the GDS Developmental Quotient in total emotion and sadness emotion , indicating that children with high Developmental Quotient T-scores  made less emotion recognition errors. In addition, the significant correlations were found between Personal-Social subscale score and accuracy on total emotion  and sadness emotion .To examine whether groups were different in accuracy of emotion recognition, accuracy variable was generated by averaging the identification accuracy across all scenes within each emotion. The details of identification accuracy in multimodal emotion perception were described in p = 0.57], group , and effect interaction . These results implied that there were similar attention to whole video in children with ASD and TD when they watched the experiment scenes.The total numbers of FC and the total FDTs spent on the whole video screen in ASD group and TD group were shown in p < 0.01], but there was no significant difference for emotion  and interaction effect .The duration of fixation time on face region in ASD group  was overall significantly less compared to the duration of fixation time in the TD group .The two-way ANOVA (Group* Emotion) on ratio of face and body on FT also found similar results. There was an overall main effect for group , but there was no significant difference for emotion  and interaction effect .The number of FCs on face region in ASD group  was overall significantly less compared to the duration of fixation time in the TD group . In addition, as illustrated in However, when we divided the scenes into face area and body area, the two-way ANOVA (Group* Emotion) on FDT ratio of face and body yielded an overall main effect for group . The duration of fixation time in ASD group  was overall significantly less compared to the duration of fixation time in the TD group . Meanwhile, the main effect of region was significant , and was also significant effect for emotion , which was driven by significant interaction between effect and AOI . However, there was no significant interaction effect on the three-way interaction between group, AOI, and emotion  and interaction between emotion and group .The MANOVA yielded a significant main effect for group . We then explored the simple effects of group (adjusting for multiple comparisons using Bonferroni) in each emotion separately. The results showed that for both emotion expressions, the fixation times spent on eye region were significantly decreased in ASD group compared to TD group. In order to explore the sample emotion effect, we compared the pairs of emotions in each group and found that both ASD and TD children had more FDT on negative emotion than positive emotion in the eye region [F  = 14.11, p < 0.01).For eye region, significant effects were identified for group [F (2.238) = 42.174, p < 0.01), and post hoc comparisons revealed both ASD and TD children had more FDT on negative emotion than positive emotion in the face region. As illustrated in For face region, the significant effect of emotion was found (p < 0.05). As illustrated in p < 0.01), and emotion  = 5.620, p < 0.01), which was driven by significant region*emotion interaction  = 4.406, p < 0.05). But no significant of interaction effect on the three-way interaction between group, AOI and emotion  = 1.902, p = 0.115), interaction between AOIs and group, and interaction between emotion and group  = 0.005, p = 0.944). Then, the repeated-measures ANOVAs were performed to examine group differences and interactions for each region. The Huynh-Feldt correction was used to adjust for sphericity violations when necessary.Similar to FDT, the MANOVA yielded a significant main effect for group:  = 5.800, p < 0.05, and face, F  = 5.800, p < 0.05) and emotion  = 5.620, p <0.05, and face, F  = 5.620, p <0.05).As evidence in Fig.6, pairwise t-test revealed ASD children had less FCs on eyes and face region than TD children in each emotion condition. Both ASD and TD children had more FCs on negative emotion than positive emotion in the face region.For mouth region, no group and emotion differences were found. For other region, significant effects were identified for group  = 5.800, p = 0.001), the percentage of FCs on whole face region . These correlations indicated that looking longer and more attention at the face region was related to more accurate detections of emotion. However, there were no significant correlations were found in AOIs.To examine whether eye gaze pattern was related to accuracy of recognize emotions, Pearson correlations were calculated between accuracy of emotion recognition and the percentage of FDT and FCs on the whole face region and each AOIs. In the ASD group, significant relationships was found between accuracy of recognize emotions and the percentage of FDT on whole face region  in sadness emotion. The percentage of FDT and FCs on whole face region were both moderately positively associated with Personal-Social subscale score . However, no significant correlations were found in AOIs.To examine whether eye gaze pattern was related to the severity of development deficits in children with ASD, Pearson correlations were calculated between GQ, Personal-Social subscale score and the percentage of FDT and FCs on the whole face region and each AOIs. The percentage of FDT and FCs on whole face region were both moderately positively associated with GQ , The Province Natural Foundation of Shaanxi (2009JM4030), The Province Science and Technology Research Projects of Shaanxi (2013SF2-09), Shenzhen Speech Rehabilitation Technology Laboratory and Health and Health Services Research Fund (HHSRF), Shenzhen Fundamental Research Program JCYJ20170413161611534, JCYJ20160429184226930, and KQJSCX20170731163308665.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.


To investigate the influence of overweight and obesity on general performance and mortality in seniors.Cross-sectional multidisciplinary study on ageing of the Polish population.Community-dwelling individuals aged 65 years or older, selected using three-stage stratified, proportional draw.4944 Polish Caucasian seniors, aged 65 years or older recruited between October 2007 and October 2010.All study subjects underwent measurement of body mass index (BMI), waist circumference (WC), and arm circumference (AC). The physical and cognitive performance was evaluated using the Katz Activities of Daily Living (ADL) score and Mini-Mental State Examination (MMSE), respectively. Morbidity data were obtained from a medical questionnaire. Mortality data were obtained from the Population Register of Poland between October 2015 and October 2018.Increasing age was associated with a decreased prevalence of obesity . Higher BMI, WC and AC values were associated with higher ADL and MMSE scores . On multivariate analysis, all three body measurements in women remained independent predictors of the ADL score  and MMSE score . In men, physical functioning was associated with AC (p=0.003), and cognitive status was associated with AC (p<0.001) and BMI (p=0.013). There was no association between general obesity, abdominal obesity, or AC with several aging-related adverse conditions. Kaplan-Meier survival curves showed that overweight and obesity were associated with the lowest mortality. On multivariate analysis, BMI and AC values remained independent predictors of mortality. In successfully aging individuals, neither BMI, WC, nor AC remained such predictors.Overweight and obesity in Caucasian seniors are not associated with deterioration of physical and cognitive function or with increased mortality.Supplementary material is available for this article at 10.1007/s12603-019-1257-z and is accessible for authorized users. Obesity is a major public health problem. Over the last four decades, the global prevalence has increased from 3.2% to 10.8% in men and from 6.4% to 14.9% in women, with the upward trend persisting , 6. ThisObesity, through its metabolic and endocrine effects, significantly increases the incidence of many conditions, including type 2 diabetes, cardiovascular disease, and cancer . It alsoAnother public health problem that must be urgently addressed is the aging of the population. According to the estimation of the World Health Organization, in the middle of the twenty-first century, almost all European and North American countries will have more than 30% of citizens 60 years of age or older . The pheTo reduce the burden imposed by aging and aging-related disease on health care systems and to improve quality of seniors’ life, it is necessary to undertake actions ensuring not only longer, but also healthier lives. One of the first steps in this undertaking is an appreciation of how basic measurements of body mass and composition are associated with physical and cognitive performance, morbidity, and mortality in seniors and oldest-old individuals.The study was conducted as a part of the PolSenior project — a multicenter study focused on elderly subjects, implemented between October 2007 and October 2010. The project was coordinated by the International Institute of Molecular and Cell Biology (IIMCB) in Warsaw, Poland. The Study Scientific Board formulated the final study protocol, elaborated survey questions, selected laboratory parameters for analysis, prepared instructions for nurse trainers, monitored study flow, controlled the work of the Central Laboratory and regulated of access to the Central Database. Independently, an International Scientific Committee composed of experts in the field of geriatrics, gerontology and epidemiology was created to oversee the design and conduct of the study.The study was composed of four parts performed by nurses: (i) questionnaire survey; (ii) comprehensive geriatric assessment, including selected scales and tests; (iii) blood pressure and anthropometric measurements; (iv) blood and urine sample collection. Additionally, a detailed medical examination by geriatricians was performed in those participants who have accepted the proposal of further geriatric assessment.The 466 interviewers were recruited by the PBS DGA company, an agency with expertise in research projects for private and public sectors. They were active nurses who worked within local communities and were trained for the purpose of the PolSenior project. The interviewer visited each study participant three times in order to complete the medical and socioeconomic questionnaire and to collect blood and urine samples , 22.http://polsenior.iimcb.gov.pl/en.The detailed information about the PolSenior project is available online at Initially, the PolSenior program was planned to include 5,950 participants divided into six age groups of equal size and gender distribution , and a reference group consisting of subjects who were about to enter old age (55–59 years old). The responders were randomly recruited in bundles in a stratified, proportional three-stages draw. In the first stage local administrative units, including urban, rural, and urban-rural municipalities were identified. Towns and cities were divided into five groups, depending on size . In the second stage, streets in urban municipalities, and villages in rural municipalities were drawn. In the third stage of the draw, using the national database run by the Ministry of Internal Affairs and Administration, respondents were selected based on the Universal Electronic System for Registration of the Population (PESEL) . Out of Study participants were stratified according to age and sex. In younger seniors [65–79 years], survival in women [A] was independent of BMI [p=0.82]. In younger senior men [B], older senior women [C], and senior men  survival was associated with BMI [all p<0.001]. The BMI categories were: <18.5 kg/m2 [malnutrition], 18.5 to 24.9 kg/m2 [normal body weight], 25.0 to 29.9 kg/m2 [overweight], 30 to 34.9 kg/m2 [moderate obesity], 35.0 to 39.9 kg/m2 [severe obesity], and ≥40 kg/m2 [morbid obesity].4,944 Caucasian seniors  out of 4,979 participants of the PolSenior program aged ≥65 years were included in the present study. The remaining 35 individuals were not included due to the lack of body measurements. All anthropometric measurements and questionnaire data were obtained between October 2007 and October 2010. The physical examination included calculation of body mass index  and measurement of waist circumference  and arm circumference .For the purposes of the current study, aging-associated adverse conditions included cardiovascular disease , type 2 diabetes mellitus, chronic kidney disease (estimated glomerular filtration rate <60 mL/min), chronic obstructive pulmonary disease, cancer (skin cancers other than melanoma were not accounted for), a Mini-Mental State Examination (MMSE) score less than 24, and a Katz Activities of Daily Living (ADL) score less than 5. Survival data were obtained from the Population Register of Poland 8 years after recruitment into the study (from October 2015 and October 2018). At the moment of access to the register, 2392 individuals had died. The total number of person-years of observation was 261 594.Cognitive function was assessed using the MMSE preceded by a rough assessment of the participant’s hearing and vision . The stuStatistical analyses were performed using Statistica software, version 10  and the R program . Due to the skewed distribution of values for BMI, WC, and AC, variables were calculated as the median . The significance of the relation between analyzed factors was tested using nonparametric Kruskal-Wallis one-way analysis of variance (ANOVA) and rank-based nonparametric analysis of covariance (ANCOVA) for multifactorial analyses. We used Spearman’s rank correlation coefficient (rho) as a measure of correlation between parameters. A Kaplan-Meier plot was used to present survival curves, which were compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate survival analyses, with age as one of the covariates. Proportional-hazards assumption was tested using Schoenfeld residuals. For all statistical analyses, the level of significance was set at 0.05.The study was approved by the Bioethics Commission of the Medical University of Silesia in Katowice. Each respondent or his/her legal guardian signed informed consent and was assigned a unique identification number to ensure confidentiality of personal data. The data were anonymously stored in a Central Database.2 or greater as the definition of obesity, we found that 31.66% of study participants were obese and that there were more obese women than men . In addition, using a WC measurement of 80 cm or greater in women and 94 cm or greater in men as the cutoff for defining abdominal obesity, we found that 80.6% of all study participants had a WC measurement above the cutoff. Women were more commonly affected than men . We found that the percentage of obese individuals decreased with age in the entire cohort . In men, a BMI 30 kg/m2 or higher was associated with a lower incidence of cancer (p=0.03).There was no association between general obesity, abdominal obesity, or AC with several aging-related adverse conditions. However, obesity and abdominal obesity were associated with the incidence of some diseases. In both men and women, a BMI 30 kg/mAbdominal obesity was associated with a higher frequency of diabetes (p<0.001) in both men and women (both p<0.001) and of cardiovascular disease (p<0.001) in both men and women . Abdominal obesity was associated with a lower frequency of cancer in men (p=0.04).Increasing quartiles of AC were associated with an increasing frequency of cardiovascular disease in women (p=0.006), increasing frequency of dementia and diabetes in both sexes together and separately , and a decreasing frequency of cancer in men (p=0.006) and kidney insufficiency in women (p=0.002).2 was associated with the lowest mortality, while underweight (BMI <18.5 kg/m2) was associated with the highest mortality (p<0.001). In women, however, there was no such association  were associated with the highest mortality . Other independent predictors of mortality in women were age and the number of aging-related diseases. In men, BMI remained an independent predictor of mortality, with the lowest hazard ratio seen with a BMI of 30 to 34.9 kg/m2 . In addition, age, number of aging-related diseases, and smoking status also remained independent predictors of mortality.Multivariate analysis for age, sex, number of aging-associated diseases, smoking status and BMI or WC or AC, we used normal BMI values as a reference. In women, BMI remained an independent predictor of mortality, with the lowest hazard ratio (Hr) seen with a BMI of 35.0 to 39.9 kg/mWhen WC values were divided into a reference group without abdominal obesity and a group with abdominal obesity, age and the number of aging-related diseases were independent predictors of mortality in both sexes, and smoking status was an additional independent predictor in men. Abdominal obesity was not an independent predictor of mortality.The reference value for AC measurement was established as the first quartile. Increasing quartiles were independent predictors of decreasing mortality in both sexes . In addition, age and the number of aging-associated diseases were predictors of mortality in both sexes, while smoking status was an independent predictor only in men.Finally, we evaluated mortality in successfully aging seniors in relation to BMI, WC, or AC adjusted for age, sex, and smoking status. We found that in women, only age remained an independent predictor of mortality. In men, the independent predictors were age and smoking status.In young and middle-aged individuals, excess weight is among the major risk factors for the development of cardiometabolic and other diseases and for early death , 10. YetIn the entire cohort, not preselected according to the health and functional status, being aged 80 years or greater with overweight or obesity is associated with the best survival, even when age, number of aging-related adverse conditions, and smoking status are taken into account. This result suggests that, during aging complicated by such conditions, a higher body mass can exert a protective effect. It remains to be elucidated which of these conditions, if any, are less detrimental in the presence of obesity or whether a protective effect of obesity relies on general effects. Underweight is associated with the worst survival, and this condition can result from the terminal phase of cancer. In our study group, however, a current cancer diagnosis had no significant effect on mortality in underweight individuals compared with the other weight groups combined (data not shown). Thus, it is possible that underweight reflected inadequate nutrition and frailty or the presence of other life-threatening conditions , 32.In successfully aging seniors, we observed no positive or negative association of body measurements with mortality. This suggests that, in such individuals, overweight is not as detrimental as it is in younger humans, but neither it is protective. Some authors claim that the “obesity paradox” might, in fact, be a result of selection bias and methodological errors such as omitting important confounders in the analysis  , 34. In Presumably, the reasons why general and abdominal obesity are not detrimental in seniors, especially in the oldest-old, are numerous. We limit our discussion to the most likely candidates. First, although calorie restriction is the best-known effective method of extending lifespan and healthspan, there is a growing body of evidence indicating that diet composition is at least equally important , 36. TheSecond, not all obesity is associated with adipose tissue dysfunction, in which macrophage infiltration is seen, and excess inflammatory mediators and adipokines are produced. Individuals without this complication are known as “metabolically healthy obese” , 39.Third, in men and postmenopausal women, peripheral synthesis is the main source of estrogen, and adipose tissue is one of the sites of peripheral synthesis , 41. TheFinally, overweight and obese individuals are often taking medicine for cardiometabolic disease: the use of metformin, statins, and acetylsalicylic acid is more common than in their same-age non-overweight or non-obese counterparts. These medications slow the rate of aging and decrease the risk and severity of already existing disease, thus increasing the length of life , 44.Our study has some limitations. The first one regards the representativeness of the studied group. The project planned an equal number of respondents in each age group with equal gender distribution. This assumption allowed for a precise analysis of the examined factors in the oldest groups, which was a priority of the PolSenior study. Therefore, the structure of the studied population did not reflect the demographic structure of the senior population, as the oldest age groups were overrepresented.Similarly, the inclusion of equal numbers of men and women resulted in overrepresentation of men. Therefore, to achieve the representativeness of the studied group, the weighting adjustment method was applied . AnotherNext, other methods of assessing obesity, such as bioelectric impedance or dual-energy X-ray absorptiometry, are much better than BMI, WC, and AC because they allow for an estimation of body composition. However, in everyday practice, using a measuring tape and scale is fast, cost-free, and can be easily repeated during subsequent checkups. Therefore, to allow physicians to estimate body mass quickly, and to compare the results to the data of other reports, BMI and WC are typically used. However, BMI and WC measurements might be incorrect, especially in the oldest-old, due to spinal deformation . AnotherThe strength of this work relies on equally-sized 5-year age cohorts containing a similar number of women and men, allowing for a reliable analysis of the oldest study subjects and accurate comparison with other age groups and with the reports of other authors. We had access to detailed medical histories, current health status reports, and the results of the ADL and MMSE tests performed by trained nurses. We are confident that our analysis of the association of body mass with clinical data generated reliable results.In conclusion, our data show that overweight and obesity in Caucasian seniors are associated neither with a worsening of physical and cognitive function nor with increased mortality. Our data, and that of other authors suggest that senior individuals might function differently than young and middle-aged individuals. Therefore, consideration should be given to the creation of other body mass-related recommendations for seniors.Supplementary material, approximately 137 KB.


Few studies have suggested that patients with myocardial infarction (MI) may be at increased risk of cancer, but further large register-based studies are needed to evaluate this subject. The aim of this study was to assess the incident rates of cancer and death by history of MI, and whether an MI is independently associated with cancer in a large cohort study.All Danish residents aged 30–99 in 1996 without prior cancer or MI were included and were followed until 2012. Patients were grouped according to incident MI during follow-up. Incidence rates (IR) of cancer and death in individuals with and without MI and incidence rate ratios  of cancer associated with an MI were calculated.Of 2,871,168 individuals, 122,275 developed an MI during follow-up, 11,375 subsequently developed cancer  and 65,225 died . In the reference population, 372,397 developed cancer  and 753,767 died . Compared to the reference population, higher IRs of cancer and death were observed in all age groups  and time since an MI  in the MI population. MI was associated with an increased risk of overall cancer  after adjusting for age, sex and calendar year, also when additionally adjusting for chronic obstructive pulmonary disease, hypertension, dyslipidemia, diabetes and socioeconomic status , but not after further adjustment for the first 6 months post-MI .Patients after an MI have increased incidence of cancer, which may be explained by mutual risk, occult cancers and increased surveillance. Focus on risk factor management to reduce cancer and MI is warranted.The online version of this article (10.1186/s12872-018-0932-z) contains supplementary material, which is available to authorized users. Ischemic heart disease and cancer are the two primary causes of death worldwide. Denmark is the only country in Europe where cancer has surpassed cardiovascular disease as the primary cause of death in both women and men , 2. Due The association between cancer and MI is biologically plausible due to shared pathogenesis such as oxidative stress , 9 and sTo evaluate the association between an MI and cancer there are a number of caveats that need to be accounted for, which involves analyses of competing risk and surveillance bias. Due to high mortality rates after an MI, an independent association between an MI and cancer may, therefore, have been overlooked in previous studies, and the possible association calls for further investigations.Therefore, the aims of this study were to assess the incident rates of cancer and death by history of MI, as well as the association between an MI and new onset cancer in patients surviving a first-time MI compared with the reference population.All residents in Denmark receive a unique and permanent civil registration number at birth or immigration that enables linkage between nationwide registers at an individual level. Data for this study were obtained from four large Danish registries: The Danish Civil Registration System registry, the Danish National Patient Registry (NPR), the National Causes of Death Registry and the Danish National Prescription Registry. From the Danish Civil Registration System registry we obtained information on sex, date of birth and vital status (recorded within two weeks from the event), whereas causes of death were obtained from the National Causes of Death Registry and classified according to the International Classification of Diseases (ICD)-8 until 1993 and ICD-10 from 1994 and onwards. From the National Patient Registry we achieved information on all hospital admissions since 1977 with diagnoses coded according to the ICD system. Lastly, we obtained information on all claimed prescriptions in Denmark since 1995 from the Danish National Prescription Registry according to the Anatomical Therapeutic Chemical (ATC).Our study population comprised all individuals aged 30–99 years residing in Denmark on 1 January 1996. Patients with a first-time diagnosis of MI  or first-time cancer  prior to 1 January 1996 were excluded, as were individuals who had a first-time diagnosis of cancer and MI on the same day during follow-up. Patients were grouped according to incident MI during follow-up. Thus, the reference population comprised the total Danish population without prior MI or cancer in 01 January 1996, and the MI population comprised those individuals from the reference population who developed an MI during follow-up without prior cancer at the time of an MI. The ICD-8 diagnosis of an MI in the NPR has been validated in the Danish MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) study with a positive predictive value of 93.5% for definite or possible MI and a sensitivity of 92.8% for definite MI . The ICDThe following comorbidities were identified: hypertension, dyslipidemia, diabetes and chronic obstructive pulmonary disease . Hypertension was defined as combination treatment with at least two classes of antihypertensive drugs within 90 days, as previously validated . DiabeteSocioeconomic status was identified as educational attainment and categorized as follows: (1) Basic education ; (2) upper secondary ; (3) vocational; (4) short or medium length higher education ; (5) Master’s Degree or Ph.D. Degree; (6) unknown.The primary outcome was any incident cancer reported in the NPR or as cause of death (ICD-10 codes C00–96). From the NPR we also obtained information on the five most common types of cancer types according to the Association of Nordic Cancer Registries: Lung cancer including trachea and bronchus (C33–34), colorectal (C18–20), breast (C50), prostate (C61) and lower urinary tract cancer  (C66–68.0).The reference population was followed from 1 January 1996 until an MI event, death, cancer event, emigration, age 100 or 31 December 2012, whichever came first, and the MI population was followed from diagnosis of MI until death, cancer event, emigration, age 100 or 31 December 2012, whichever came first.We calculated crude incidence rates (IR) of cancer and death stratified by age groups  and time since a diagnosis of MI . We further examined the cumulative incidence of cancer according to history of an MI and age groups in which the competing risk of death was taken into account. We used a 0–1-2 outcome variable to determine those with no cancer diagnosis or date of death, those who received a cancer diagnosis or died from cancer, and those who died from other causes than cancer, respectively.We used time-dependent multivariable Poisson regression models to examine the incidence rate ratios (IRR) of cancer associated with an MI, as previously performed . Each inWe assessed the associations between MI and subsequent risk of cancer by two approaches. In the main analyses, we examined the association between MI and subsequent cancer risk according to time following MI . Secondly, we explored the IRRs of cancer associated with MI stratified by age compared with risk of cancer in the reference population . The same approach was used for the five selected types of cancers. All statistical analyses were conducted using SAS, version 9.4 .In accordance with our hypothesis, increased risk of cancer in MI patients could be confounded by shared risk factors or comorbidities that are markers of risk factors . We, theThe same analyses were performed without the first six months following an MI, as this period of time is most likely to be affected by surveillance bias.Following exclusion of individuals according to the pre-defined criteria, the final population comprised 2,871,168 individuals without prior MI or cancer, and 122,275 individuals subsequently developed an MI  of the MI patients developed first-time cancer and 65,225 (53.3%) died, whereas 372,397 (13.0%) individuals in the reference population developed cancer and 753,767 (26.3%) died , may explain the increased incidence of cancer after an MI. This is supported by the fact that the two smoke related cancers, lung and lower urinary tract cancer, seemed to be associated with MI before adjustment for comorbidities. Nonetheless, risk of lower urinary tract cancers remained significantly increased after full adjustment, which can likely be explained by unmeasured and residual confounding, e.g. history of tobacco. Based on our data, it is, however, difficult to explain the exact mechanism(s) why the association became insignificant after adjustment for comorbidities, but it may be speculated that environmental factors like tobacco and alcohol , unhealtThe strong associations between an MI and a new onset cancer in the first 6 months, especially the first month, even after adjustment for comorbidities compared to the remaining follow-up, indicate that our observations are likely explained by surveillance bias. Being in contact with the healthcare system increases the chance of early detection of cancer due to intensive clinical evaluation, a large number of tests and increased reporting of non-cardiac symptoms. Platelet inhibition may also induce bleeding in clinically silent cancers post MI, requiring further diagnostic testing. Another explanation to this association could be occult cancers during time of MI, as they provide a prothrombotic state  that mayOne could speculate that MI patients are more exposed to radiation through percutaneous coronary interventions and other procedures, which could affect our results. If so, we would have expected increasing risk of developing cancers in the chest, such as lung and breast cancer, in the years following MI. In this study, breast cancer showed a non-significantly increased risk of cancer only 10–17 years following MI. However, after the first year following an MI, a history of an MI was consistently associated with increased risk of lung and lower urinary tract cancers, suggesting that smoking may be the main explanation to this observation.The major strengths of this nationwide study include the diminished risk of selection bias, the minimal loss of follow-up ensured by the comprehensive Danish registries, and the large sample size of almost 3 million people with up to 17 years of follow-up, which gave us the unique possibility to study the risk of overall and subtypes of cancer in MI patients. Conversely, given the observational nature of this study, several important limitations need to be addressed.The primary limitation was the risk of unmeasured and residual confounding by variables not available to us from the administrative registries, namely smoking, alcohol consumption, body mass index, physical activity level, diet and metabolic abnormalities not requiring medication. Further studies are needed to discover the effect of these common risk factors on the risk of cancer in MI patients. Secondly, surveillance bias is likely to have affected our results, thus being in contact with the healthcare system increases the chance of diagnosing a cancer. Thirdly, our results rely on discharge diagnoses on cancer and MI from hospitals. Nonetheless, although minor misclassifications exist in the NPR, especially when the coding practice is unclear, the misclassifications are non-systematic and do not influence the overall validity of the NPR data , 30–32. This study suggests that the increased incidence of cancer among patients with myocardial infarction may be due mutual risk factors, occult cancers and increased surveillance rather than an independent association. Furthermore, death is still a larger clinical challenge at all ages, especially by cardiac death rather than cancer in the early years after the myocardial infarction. Cardiologists and general practitioners should be aware of signs and symptoms of cancer in myocardial infarction survivors, but focus on secondary prevention and management after MI to reduce mortality is warranted.Additional file 1:Figure S1A. Incidence rates of cancer and death stratified by age group 0-1 years post-MI in the reference and MI population. Figure S1B. Incidence of cancer and death stratified by age group 1-5 years post-MI in the reference and MI population. Figure S1C. Incidence of cancer and death stratified by age group 5-17 years post-MI in the reference and MI population. Figure S2. Cumulative incidence of cancer stratified by age group in the MI population. Figure S3. Cumulative incidence of death stratified by age group in the MI population. (DOCX 407 kb)Additional file 2:Table S1. One-year incidence rates of subtypes of cancer per 1,000 person-years according to age group. Table S2A. Incidence rate ratios of cancer associated with an MI adjusted for age, sex and calendar year according to time since MI. Table S2B. Incidence rate ratios of cancer associated with an MI adjusted for age, sex, calendar year, dyslipidemia, hypertension, diabetes, chronic obstructive pulmonary disease and socioeconomic status according to time since MI. Table S3A. Incidence rate ratios of overall cancer and selected subtypes of cancer stratified by age group and adjusted for sex and calendar year. Table S3B. Incidence rate ratios of overall cancer and selected subtypes of cancer stratified by age group and adjusted for sex, calendar year, dyslipidemia, hypertension, diabetes, chronic obstructive pulmonary disease and socioeconomic status. Table S3C. Incidence rate ratios of overall cancer and selected subtypes of cancer 6 months – 17 years post-MI stratified by age group and adjusted for sex, calendar year, dyslipidemia, hypertension, diabetes, chronic obstructive pulmonary disease and socioeconomic status. Table S4. Incidence rate ratios of overall cancer and selected subtypes of cancer stratified by gender. (DOCX 54 kb)


Unrestricted access to journal publications speeds research progress, productivity, and knowledge translation, which in turn develops and promotes the efficient dissemination of content. We describe access to the 500 most-cited emergency medicine (EM) articles (published between 2012 and 2016) in terms of publisher-based access (open access or subscription), alternate access routes (self-archived or author provided), and relative cost of access.Academia.edu, and the Unpaywall and Open Access Button browser plugins to locate self-archived copies. We contacted corresponding authors of the remaining inaccessible studies for a copy of each of their articles. We collected article processing and access costs from the journal publishers, and then calculated relative cost differences using the World Bank purchasing power parity index for the United States (U.S.), Germany, Turkey, China, Brazil, South Africa, and Australia. This allows costs to be understood relative to the economic context of the countries from which they originated.We used the Scopus database to identify the 500 most-cited EM articles published between 2012 and 2016. Access status was collected from the journal publisher. For studies not available via open access, we searched on Google, Google Scholar, Researchgate, We identified 500 articles for inclusion in the study. Of these, 167 (33%) were published in an open access format. Of the remaining 333 (67%), 204 (61%) were available elsewhere on the internet, 18 (4%) were provided by the authors, and 111 (22%) were accessible by subscription only. The mean article processing and access charges were $2,518.62 and $44.78, respectively. These costs were 2.24, 1.75, 2.28 and 1.56 times more expensive for South African, Chinese, Turkish, and Brazilian authors, respectively, than for U.S. authors .Despite the advantage of open access publication for knowledge translation, social responsibility, and increased citation, one in five of the 500 EM articles were accessible only via subscription. Access for scientists from upper-middle income countries was significantly hampered by cost. It is important to acknowledge the value this has for authors from low- and middle-income countries. Authors should also consider the citation advantage afforded by open access publishing when deciding where to publish. Access to key academic literature is vital for authors, scientists and clinicians, especially those working in low- and middle-income countries.6Unrestricted access to research improves research progress, productivity, and knowledge translation. These in turn develop and promote the efficient dissemination of content in an ever-expanding knowledge cycle.This was a retrospective, cross-sectional study using secondary, published data. We searched for articles via Scopus and SciVal  to identify the 500 most-cited EM articles published between 2012 and 2016. Scopus is the largest abstract and citation database of peer-reviewed literature. SciVal is a powerful data engine that can be used (amongst a vast number of other functions) to interrogate the Scopus database. We used it to perform an automated keyword search for EM articles, along with citation counts and journal, author and publisher details. Articles were then ranked using their citation count to allow selection of the sample.https://scholar.google.co.za/), Researchgate (https://www.researchgate.net/) and Academia (https://www.academia.edu/) to determine whether an archived copy existed. Unpaywall  and the Open Access Button (https://openaccessbutton.org/) browser plugins were also used for this purpose. We did not include a search of any of the shadow libraries (Libgen or Sci-Hub).Each of the included articles was manually checked to identify their open access status via the publisher’s websites. Where articles were not available open access from the publisher’s website (subscription-based articles), we used the article title to interrogate Google, Google Scholar  and asked to provide a copy of his or her article for a university research project. Corresponding authors were given 14 days to reply and were provided with full details of the study aims if they were requested. We collected article processing and access costs from each respective journal’s publisher. Publishers were contacted via email where cost information was not available on their public website.We used the World Bank’s purchasing power parity (PPP) index to calculate the relative journal article processing and access cost differences for selected countries. PPP is based on the hypothesis that similar items cost the same no matter where in the world it is purchased. For instance, a tall Starbucks caffé latte will not just cost $2.95 in the United States (U.S.), but anywhere in the world; the only difference would be the expression of $2.95 in a foreign currency (R40.90 in South Africa). In reality, however, parity doesn’t exist. The PPP index describes this deviation from parity and uses the U.S. dollars as its baseline. A tall Starbucks caffé latte in South Africa actually costs R27.00 ($1.95) and not R40.90 ($2.95). For an American tourist ordering a tall Starbucks caffé latte in South Africa, this will result in a 33% cost saving, but for a South African tourist in the U.S. this will result in a 50% cost increase. Although not directly applicable to publication cost, the PPP index offers a simplified, hypothetical comparison of the relative article processing and access cost between countries, as it does for other goods. For our analysis we included only the top publishing countries of each global publication region, as per Scopus .We employed Microsoft Excel  for data analysis. Article accessibility was presented descriptively. The PPP index was used to calculate the factor by which publication costs differed between the included publishing countries, relative to the U.S. dollar. These were compared using a paired t-test, with significance defined as a p-value of less than 0.05. To provide an understanding of the economic burden of scientific publishing for scientists and clinicians living in middle-income countries, we calculated an equivalent local cost of article processing and access for the four middle-income countries included  to the U.S. cost of publishing and access, by applying the PPP index in reverse. Essentially this calculation allowed us to describe a similar out-of-pocket expense for a researcher earning in one of these four countries and the U.S.The study protocol was reviewed and approved by both the Human Research Ethics committees of Stellenbosch University and the University of Cape Town, Cape Town, South Africa (largely due to involvement of an undergraduate researcher in the project).Critical Care and Resuscitation, levies no article processing cost for open access publishing. However, as a society journal, access is restricted to members of the society for the first three months following publication, after which it is made universally accessible. There were 471 (94.2%) articles with first authors from high-income countries and 25 (5%) from upper-middle income countries, with the remaining four (0.8%), split equally between articles with first authors from lower-middle and lower-income countries.We collected the 501 top-ranked EM articles by citation count. After excluding one article due to its retraction from circulation, we were left with 500 articles published over 29 journals. Of these journals, 22 (76%) were hybrid open access journals , six (21%) were open access-only journals, and one was a subscription-only journal. One journal, While two out of three of the top 500 cited EM articles were subscription based, only one in five were eventually found to need subscription for access. This figure broadly compares with the global open access rate, which is estimated at around 28% of peer-reviewed articles;3upper-middle income status.13The cost of access to non-open access articles was significantly prohibitive for the low- and middle-income countries included in our sample. It is notable that waivers and discounts would not apply to any of these countries, as they are specifically excluded by publishers due to their Upper-middle income countries aside, the African EM open-access study showed that the relative cost of access was much higher for low- and lower-middle income countries. Relative to the U.S., costs were 3.5 and 2.8 times more for Ghanaian and Tanzanian authors, respectively.9Apart from the social responsibility, publishing open access presents authors from high-income countries with an evidence-based opportunity to improve their citation counts (which is important for promotion and grant applications). Studies have shown that publishing open access improves discovery and citation of articles, offering a significant advantage.14Although applications like Unpaywall and Open Access Button make it easier to find archived publications, it is more complicated than locating an open access article directly through its publisher’s website. Archiving is also dependent on publisher regulations, which often prohibit archiving for up to 12 months, and restricts which versions of an article can be archived.Author responses to publication requests were less than half of what was observed in the African open access study. As the two cohorts differed substantially we did not explore this finding further. It is possible that the philanthropic nature of African authors played a role.There are a number of limitations to this study. It is likely that many, or all, of these papers would be accessible through the shadow library SciHub. Publishers are clear that SciHub’s business model contravenes copyright. However, research has shown that scientists are often willing to view SciHub use in less black-and-white terms.Our study only included articles from the Scopus database. A different database might have altered the findings of the study. However, Scopus does provide the largest abstract and citation database of peer-reviewed literature (including EM) globally, which explains our choice to use it. Finally, we only included articles from EM journals, which limits the list of top papers. Many top emergency care papers are published in leading non-EM journals with different access policies. This may also have affected the findings.In conclusion, this study showed that one in every five of the top 500 EM papers published in EM journals over a five-year period were not accessible without a subscription, and that access for scientists from low- and middle-income countries is significantly hampered by cost. It would be useful to view the uptake of open access over time to see if it is improving, as is happening in other specialties. Describing EM journals in terms of their accessibility  and then linking this to journal impact might help guide authors select more accessible journals. Authors, specifically those from high-income countries, should consider the citation advantage afforded by open access publishing when deciding where to publish. It is also important to acknowledge the value this has for authors from low- and middle-income countries.


Glioblastoma is the most common primary brain cancer in adults with an incidence of 3.4 per 100,000, making up about 15% of all brain tumors. Inconsistent results have been published in regard differences in survival between white and black glioblastoma patients. The objective of this to study the association between race and in Glioblastoma patients in the USA during 2010–2014.The National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) database were used to evaluate race/ethnicity ) and Hispanic) adults patients with first-time diagnosis of glioblastoma  from 2010–2014. The primary outcome was 3-year overall survival which was defined as months from diagnosis to death due to any cause and cancer, Kaplan-Meier (KM) and log-rank test were used to compare overall survival times across race groups. Cox proportional hazard models were used to determine the independent effect of race on 3-year survival. Age, gender, health insurance coverage, primary site, tumor size, extent of surgery and year of diagnosis were included in the adjusted model. The 3-year overall survival for API-non Hispanic (NH) patients decreased by 25% compared with White NH glioblastoma patients (hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.62–0.90)) after adjusting for age, gender, health insurance, primary site, tumor size, and extent of the surgery. Black NH  and Hispanic  exhibited similar mortality risks compared with White NH patients.Compared with White NH, API NH with glioblastoma have a better survival. The findings from this study can help increase the accuracy of the prognostic outlook for white, black and API patients with GBM. Glioblastoma (GBM) is the most common primary brain cancer in adults with an incidence of 3.4 per 100,000, making up about 15% of all brain tumors . DespiteRacial disparities in treatment and subsequent survival of brain tumors has been documented in several previous studies –15. HoweThe aim of this study was to investigate the association between race/ethnicity and survival in glioblastoma patients in the USA from 2010 to 2014.We conducted a secondary data analysis of the Surveillance Epidemiology and End Results (SEER) database. SEER is a cancer surveillance program of the National Cancer Institute’ s (NCI) that collects cancer incidence and survival data since 1973, including the Atlanta, Detroit, San Francisco-Oakland, Seatle-Puget Sound metropolitan areas and the states of Connecticut, Hawaii, Iowa, New Mexico, and Utah .The population of interest included adults 18 years-of-age or older, identified as White non-Hispanic (NH), Black NH, API NH, and Hispanics with a first-time diagnosis of glioblastoma . The period of this study was chosen as in 2009 a new drug, bevacizumab, was approved for use in GBM. Treatment of bevacizumab may improve general survival after 2009. Patients who were reported only on death certificate or at autopsy (n = 13) or with no information on race (n = 15) or defined as American Indian /AK Native (n = 16) were excluded. Also people with survival time zero were excluded (n = 12). The final population consisted of 3,473 patients.The primary outcome was overall survival (OS) which was defined as the time in months from diagnosis to death due to any cause and cancer. Patients who were alive at the date of the last contact were censored.The race and ethnicity categories were limited to non-Hispanic White, Black or API, and Hispanic due to the small numbers for other races. Confounding variables evaluated included age at diagnosis, gender, insurance status, primary site, tumor size, and extent of the surgery. Age in years was collapsed into dichotomous categories . Health insurance status was grouped into uninsured, any Medicaid and insured (combining SEER “Insured and Insured/No specifics” categories). Primary tumor sites were defined using ICD-O-3 topology codes into frontal, temporal, parietal, and occipital site (C711–C714 respectively). Tumor size was dichotomized using the tumor median size of 4.5 cm  and patients with unknown or not stated tumor size were included. Extent of the primary surgery was defined as “No Surgery”; “No Gross Total Resection” (No GTR) , biopsy, surgery NOS, partial resection NOS, and subtotal resection; and “Gross Total Resection” (GTR) . As the information used in this study was limited to the first course of treatment, such as radiation or chemotherapy status were not included in the analysis.All data accessed from SEER was de-identified (fully anonymized) and without any of the 18 direct identifiers according to the Health Insurance Portability and Accountability Act. The study population was characterized using descriptive statistics, these included examining frequency distributions of the categorical variables and assessing for missing data. Chi-square tests were used to compare categorical data . Analysis of variance was used for the age at diagnosis in years. Kaplan-Meier survival analysis was used to asses overall survival. The log-rank test was used to assess differences between survival curves across race/ethnicity. Univariate and Multivariate Cox Proportional hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the independent effect of race/ethnicity and overall 3-year survival rates were calculated. The correlation matrix of all potential confounders were examined to check for multicollinearity in the adjusted model. Multivariate analysis was performed using Cox proportional hazards model to determine the independent effect of race/ethnicity on 3-year overall survival, hazard ratios and their respective 95% confidence intervals were calculated. The proportional hazard assumptions were tested graphically. Age, gender, health insurance status, primary site, tumor size and extent of surgery were included in the adjusted model. All p values reported are two-tailed, and a p-value of <0.05 was considered as statistically significant. Statistical analysis was performed using STATA .Permission to use and access to the SEER database was obtained through the SEER website. Ethical approval was waived since the analysis was considered nonhuman subjects research by the Florida International University Health Sciences IRB.Among the glioblastoma patients identified, the majority were white (83.2%) and 5.9%, 5.4%, and 5.5% were black NH, API NH and Hispanic respectively. The unadjusted Cox regression model suggested no differences between Blacks NH , API NH  and Hispanic  showed a better 3-year overall survival for API NH patients compared to Whites NH, Black NH and Hispanics .This study found that API NH patients have a significantly better survival rate than White NH after controlling for age, gender, health insurance status, site, tumor size and extent of surgery. No significant differences in glioblastoma survival were observed among Black NH and Hispanic compared with White NH.Our findings revealed no difference in survival between black and white GBM patients are in line with most of the previous population-based studies –10. OnlyStudies including Asians are rare and revealed inconsistent results , 9, 10. The scant evidence in regard survival of Hispanic GBM patients is in disagreement with the results of our study , 9, 10. In agreement with previous studies, we found that age at diagnosis was associated with survival in GBM patients , 19. WheIt is not clear whether the difference in survival between races is to due differences in genetic factors, environmental exposures, or differences in treatment. However, it has been suggested that possible differences in the molecular and genetic makeup of tumors between races, which might account for some of the discrepancies seen in mortality . WienckeNaturally, our study had some limitations. The database of SEER did not collect information on comorbidities that could possibly influence mortality. Furthermore, we were unable to adjust our analysis on patients’ extent of radiation therapy, including dosage and type, as the SEER database did not include that information anymore. It has been shown that the SEER registry data, collected by routine methods, may not be an appropriate source for documenting rates of radiation therapy receipt by breast cancer patients or for investigating geographic variation in radiation therapy receipt . PreviouWe would like to point out that the population used in our research was large and representative of roughly one-fourth of the United States population. Patients with multiple different primary cancers, those who have had previous cancers, those with extracranial GBM, and those with different subtypes of GBM; giant cell GBM and gliosarcoma were excluded. By excluding these patients, we got a better idea of the association typically found in patients with GBM.In conclusion, our study identified the existence of a difference in survival in GBM patients based on race/ethnicity. API NH patients with glioblastoma have a better survival when compared to White NH patients, after controlling for age, gender, insurance status, site, tumor size and extent of surgery. Our findings expand on the topic of how race specifically affects a patient’s mortality, by using a population that is more generalizable to the typical GBM patient. Future prospective studies may investigate the cause of the differences in survival between API NH and other race/ethnicity groups. The association between EGFR and TP53 mutations and mortality, as well as the association between primary and secondary GBM and survival, may be studied independently of race, as this might be a key factor behind the differences we found. The findings from our study can help increase the accuracy of the prognostic outlook for white, black, Hispanic and API patients with GBM.